CAD

Материал из hpluswiki
Перейти к навигации Перейти к поиску

CAD protein [Includes: Glutamine-dependent carbamoyl-phosphate synthase (EC 6.3.5.5); Aspartate carbamoyltransferase (EC 2.1.3.2); Dihydroorotase (EC 3.5.2.3)]

Publications[править]

Serum soluble Klotho is inversely related to coronary artery calcification assessed by intravascular ultrasound in patients with stable coronary artery disease.

Although the Klotho gene is recognized as an aging-suppressor gene, the clinical significance of its soluble product, soluble Klotho, in coronary artery disease (CAD) has not been completely determined. The relationship between soluble Klotho and coronary artery calcification (CAC) was investigated in patients with stable CAD. CAC in culprit lesions was analyzed in 75 non-dialysis patients with stable CAD who were scheduled for percutaneous coronary intervention (PCI) following intravascular ultrasound (IVUS). The main outcome measure was the calcium index (CalcIndex), a volumetric IVUS-derived measure of total calcification per culprit lesion. A low CalcIndex was defined as a first-quartile calcium index (<0.042). Patients were divided into two groups according to the median serum Klotho value: low Klotho (n = 37, ≤460 pg/mL) and high Klotho (n = 38, >460 pg/mL). The CalcIndex was significantly lower in patients with high than with low Klotho. Patients with high Klotho had a significantly higher prevalence of a low CalcIndex than those with low Klotho. The number of angiographic moderate-severe CACs in whole coronary arteries was significantly decreased in patients with high Klotho compared to low Klotho. Serum Klotho levels correlated significantly and inversely with the CalcIndex. This relationship was pronounced in patients with estimated glomerular filtration rate <60 mL/min/1.73 m . Logistic regression analysis showed that high Klotho was associated with a low CalcIndex independent of classical coronary risk factors and markers of mineral metabolism. High serum soluble Klotho levels are associated with a low degree of CAC in non-dialysis, stable CAD patients treated by PCI.


Keywords

  • Aging
  • Coronary artery calcification
  • Intravascular ultrasound
  • Klotho


Shear bond strengths of aged and non-aged CAD/CAM materials after different surface treatments.

To assess shear bond strengths (SBS) of resin composites on aged and non-aged prosthetic materials with various surface treatments. Cerasmart (CE), Vita Enamic (VE), Vita Mark II (VM), and IPS e.max CAD (EC) blocks were sliced, and rectangular-shaped specimens (14 × 12 × 1.5 mm; N = 352) were obtained. Half of the specimens were aged (5000 thermal cycles) for each material. Non-aged and aged specimens were divided into 4 groups according to the surface treatments (control, air abrasion, etching, and laser irradiation; n = 11) and processed for scanning electron microscopy (SEM). The repair procedure was performed after the surface treatments. SBS values and failure types were determined. Obtained data were statistically analyzed ([i]P[/i]≤.05). The material type, surface treatment type, and their interactions were found significant with regard to SBS ([i]P[/i]<.001). Aging also had a significant effect on prosthetic material-resin composite bonding ([i]P[/i]<.001). SBS values of non-aged specimens ranged from 12.16 to 17.91 MPa, while SBS values of aged specimens ranged from 9.46 to 15.61 MPa. Non-aged VM in combination with acid etching presented the highest score while the control group of aged CE showed the lowest. Etching was more effective in achieving durable SBS for VM and EC. Laser irradiation could be considered as an alternative surface treatment method to air abrasion for all tested materials. Aging had significant effect on SBS values generated between tested materials and resin composite.


Keywords

  • Bond strength
  • Computer-aided design and computer-aided manufacturing (CAD/CAM)
  • Laser
  • Repair
  • Surface treatment
  • Thermal aging


Prediction of Early Postoperative Major Cardiac Events and In-Hospital Mortality in Elderly Hip Fracture Patients: The Role of Different Types of Preoperative Cardiac Abnormalities on Echocardiography Report.

Transthoracic echocardiography (TTE) is a common cardiac screening test before hip fracture surgery. However, the general TTE test delays surgery, so it would be meaningful if we could simplify the TTE by only assessing cardiac abnormality specifically. Therefore, we aimed to establish the most clinically relevant abnormality by comparing the predictive value of each major cardiac abnormality in postoperative cardiac complications and mortality in elderly hip fracture patients. From January 2014 to January 2019, the medical records of all surgically treated elderly patients (>65 years) with hip fracture were analyzed. The major TTE abnormalities were defined as left ventricular hypertrophy, systolic pulmonary arterial pressure >25 mm Hg, moderate-severe valve abnormality, left ventricular ejection fraction (LVEF) <50%, and pericardial effusion. The outcomes were postoperative cardiac complications and in-hospital mortality. There were 354 patients involved finally. Postoperative cardiac complications were encountered in 7.6% (n=27) of patients. The mortality rate was 2.8% (n=10). History of coronary artery disease (CAD) (OR: 3.281, 95% CI: 1.332-8.079, p=0.010) and presence of aortic stenosis (AS) (OR:5.656, 95% CI: 1.869-17.117, p=0.002) were independent predictors of postoperative cardiac complications. In addition, age (OR: 1.264, 95% CI: 1.047-1.527, p=0.015), history of CAD (OR: 19.290, 95% CI: 2.002-185.885, p=0.010), presence of AS (OR:7.164, 95% CI: 1.988-51.413, p=0.040) and LVEF <50% (OR:8.803, 95% CI: 1.115-69.472, p=0.039) were independent predictors of mortality. However, the rest of preoperative TTE abnormalities were not associated with postoperative cardiac complications or mortality. Among the TTE abnormalities presented by elderly patients with hip fracture, moderate-severe AS was the predictor of postoperative cardiac complications. Moreover, moderate-severe AS and LVEF <50% were the predictors of in-hospital mortality. Therefore, we could simplify the TTE process by assessing aortic valve and LVEF specifically on focused echocardiography, which could avoid surgery delay.

MeSH Terms

  • Aged
  • Aortic Valve Stenosis
  • Cardiovascular Diseases
  • Comorbidity
  • Echocardiography
  • Female
  • Fracture Fixation
  • Hip Fractures
  • Hospital Mortality
  • Humans
  • Male
  • Postoperative Complications
  • Prognosis
  • Risk Factors

Keywords

  • aging
  • echocardiographic abnormality
  • hip fracture surgery
  • mortality
  • postoperative cardiac complications


Pathogenesis of chronic heart failure: cardiovascular aging, risk factors, comorbidities, and disease modifiers.

Chronic heart failure (HF) is rare in the young and common in the elderly in the Western world. HF in the young is usually due to specific causes, predominantly or exclusively affecting the heart (adult congenital heart disease, different types of cardiomyopathies, myocarditis, or cardiotoxicity). In contrast, the mechanisms underlying HF development in the elderly have not been completely delineated. We propose that in most elderly patients, HF, regardless of the left ventricular ejection fraction (LVEF), is the consequence of the acceleration of cardiovascular aging by specific risk factors (usually hypertension, obesity, type 2 diabetes mellitus [T2DM], coronary artery disease [[[CAD]]], and valvular heart disease [VHD]), most affecting both the heart and the vasculature. These risk factors act individually or more commonly in groups, directly or indirectly (hypertension, obesity, and T2DM may lead to HF through an intervening myocardial infarction). The eventual HF phenotype and outcomes in the elderly are additionally dependent on the presence and/or development of comorbidities (atrial fibrillation, anemia, depression, kidney disease, pulmonary disease, sleep disordered breathing, other) and disease modifiers (race, sex, genes, other). The clinical implications of this paradigm are that aggressive treatment of hypertension, obesity, T2DM (preferably with metformin and sodium-glucose cotransporter-2 inhibitors), CAD, and VHD on top of measures that retard cardiovascular aging are the steadfast underpinning for HF prevention in the elderly, which represent the vast majority of HF patients.


Keywords

  • Cardiovascular aging
  • Comorbidities
  • Disease modifiers
  • Heart failure
  • Risk factors


Impact of age on clinical outcomes of antihypertensive therapy in patients with hypertension and coronary artery disease: A sub-analysis of the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Artery Disease.

This study aimed to determine whether different systolic blood pressure (SBP) measurements achieved with antihypertensive therapy impact clinical outcomes by age in patients with hypertension and coronary artery disease (CAD). This post hoc analysis from the Heart Institute of Japan Candesartan Randomized Trial for Evaluation in Coronary Heart Disease (HIJ-CREATE) trial included 2048 patients with hypertension and angiographically documented CAD. Participants were divided into three groups based on age at enrollment: middle-aged (<60 years, n = 570), pre-elderly (≥60-<70 years, n = 730), and elderly (≥70 years, n = 748). Among the 2,048 patients, 1695 (82.7%) underwent percutaneous coronary intervention. The primary end point was the time to first occurrence of a major adverse cardiac event (MACE). During a median follow-up of 4.2 years, the MACE rate was 19.8%, 28.1%, and 31.1% in the middle-aged, pre-elderly, and elderly groups, respectively. Achieved BP was defined as the mean BP during scheduled visits. Patients with higher achieved SBP had a higher occurrence of MACE in all age groups. An unadjusted quadratic proportional hazard model was used to evaluate the relationship between achieved BP during follow-up and risk for MACE. In each age group, participants were divided into quartiles based on the achieved BP during follow-up. The relationship between achieved SBP and the incidence of MACE did not follow a J-shaped curve in any age group. In conclusion, in the contemporary era of aggressive coronary revascularization, a lower SBP target may be appropriate even in elderly patients with hypertension and CAD.


Keywords

  • aging
  • blood pressure target
  • coronary artery disease
  • hypertension
  • prognosis


Impact of the early-life skin microbiota on the development of canine atopic dermatitis in a high-risk breed birth cohort.

Canine atopic dermatitis (CAD) is a prevalent inflammatory skin disease of dogs worldwide. Certain breeds such as the West Highland White Terriers (WHWT) are predisposed to suffer from CAD. Microbial dysbiosis is known to play a significant role in the pathogenesis of the disease, which is similar to its human counterpart, atopic dermatitis (AD). To date, no large cohort-study has been conducted in a predisposed dog breed to study the impact of the early-life microbiota on the development of CAD, as well as the possible implication of factors such as hygiene and access to the outdoors. In this study skin samples of 143 WHWT, including 109 puppies up to three weeks old and 34 parent dogs, from 17 breeders, were subjected to 16S rRNA gene and ITS2 amplicon sequencing to disclose the bacterial and fungal oral and skin microbiota, respectively. The oral samples served as a control group to confirm differences between haired and mucosal surfaces. The cutaneous microbiota differed between sample sites and age of the dogs. The season of sampling, geographical origin as well as hygiene status of the household and the access to the outdoors shaped the skin microbiota of the puppies significantly. However, we found that the individual early-life microbiota did not predispose for the later development of CAD.

MeSH Terms

  • Aging
  • Animals
  • Bacteria
  • DNA, Intergenic
  • Dermatitis, Atopic
  • Dog Diseases
  • Dogs
  • Female
  • Fungi
  • Male
  • Microbiota
  • Mouth
  • Pruritus
  • RNA, Ribosomal, 16S
  • Skin


[Polymorbidity in elderly patients needing myocardial revascularization (a review article).]

In the present review, the main attention is focused on the problem of polymorbidity and age-related conditions in elderly patients with CAD who need myocardial revascularization. In addition to a high risk of mortality, elderly patients with polymorbidity are characterized reduced functional activity, cognitive impairment, low quality of life and frequent seeking medical help. There is evidence of the presence of common mechanisms that affect the aging process and the development of a number of associated diseases associated with age. Accordingly, the study of polymorbidity will allow us to develop strategies for the prevention it and understand the aging process and significantly reduce the risks of surgical intervention. In this regard, there is a necessity for research aimed at studying the causal relationship between coronary artery disease and polymorbidity in elderly patients with an additional assessment of functional and cognitive status for the development of specific prognostic tools and treatment strategies.

MeSH Terms

  • Aged
  • Cognitive Dysfunction
  • Coronary Artery Disease
  • Humans
  • Myocardial Revascularization
  • Quality of Life
  • Risk

Keywords

  • aging
  • elderly
  • ischemic heart disease
  • myocardial revascularization
  • polymorbidity


Fracture force of CAD/CAM resin composite crowns after in vitro aging.

The aim of this in vitro study was to investigate the influence of material, preparation, and pre-treatment on the aging and fracture force of CAD/CAM resin composite molar crowns. CAD/CAM molar crowns (n = 80) were milled from four resin composites (Block HC, Shofu; Lava Ultimate, 3 M; Grandio Blocs, Voco; and Tetric CAD, Ivoclar Vivadent, with/without sandblasting). Extracted human teeth were prepared with optimal preparation (height 6-8 mm, angle 6-8°) or worst-case preparation (height 3.5-4 mm, angle 10-15°). Both groups were prepared with a 1-mm deep cervical circular shoulder. Crowns were adhesively bonded after corresponding tooth treatment required for the individual adhesive systems (Table 1). Specimens were aged for 90 days in water storage (37 °C) and subsequently subjected to thermal cycling and mechanical loading (TCML 3000 × 5 °C/3000 × 55 °C, 2 min each cycle, H20 distilled; 1.2 × 10 cycles à 50 N, 1.6 Hz). De-bonding and fracture force was determined. one-way-ANOVA; post hoc Bonferroni, α = 0.05. Four crowns of Lava Ultimate with worst-case preparation de-bonded during TCML. Individual crowns without sandblasting treatment (3x Tetric CAD with optimal preparation; 1x Tetric CAD with worst-case preparation) de-bonded during water storage. One crown of Grandio Blocs with optimal preparation showed a small chipping during TCML. All other crowns survived TCML and water storage without failure. Fracture forces differed between 1272 ± 211 N (Lava Ultimate) and 3061 ± 521 N (Tetric CAD). All Grandio Blocs and Tetric CAD crowns revealed significantly (p ≤ 0.023) higher fracture forces than Block HC or Lava Ultimate crowns. No significantly different (p > 0.05) fracture forces were found between optimal or worst-case preparation/fit groups. De-bonding during water storage and TCML was dependent on material and crown pre-treatment. Therefore, surface roughening seems strongly required. Fracture forces were not influenced by preparation but by the type of material. Clinical success and de-bonding of CAD/CAM resin composite crowns is strongly influenced by the type of material and its pre-treatment.

MeSH Terms

  • Ceramics
  • Composite Resins
  • Computer-Aided Design
  • Crowns
  • Dental Porcelain
  • Dental Restoration Failure
  • Dental Stress Analysis
  • Humans
  • Materials Testing

Keywords

  • Aging
  • CAD/CAM
  • CAD/CAM bloc
  • Dental material
  • Fit
  • Preparation
  • Resin composite
  • Resin-based material
  • Storage
  • TCML


Clinical performance of chairside monolithic lithium disilicate glass-ceramic CAD-CAM crowns.

To evaluate the clinical performance and the effect of various patient and provider-related factors on the longevity of chairside monolithic posterior lithium disilicate glass-ceramic (LDGC) computer-aided design (CAD)-computer-aided manufacturing (CAM) crowns provided by predoctoral students. A sample of posterior LDGC CAD-CAM crowns was evaluated. Crown preparations were milled chairside using the CEREC Omnicam system and cemented with Rely-X Unicem or Calibra Universal resin cements. Clinical assessment of the crowns and supporting periodontal structures was performed using the modified California Dental Association (CDA) criteria. Intraoral photographs as well as radiographs were taken for further assessment by two evaluators. Kaplan-Meier survival analysis was performed. A total of 40 crowns were inserted in 32 patients and evaluated for 4 years. Three complications were observed (two-technical and one-biological). No chipping or fracture of crowns was observed. No significant association was found between age, sex, periodontal condition, tooth type, tooth vitality, cement type, and longevity. The 4-year cumulative survival and success rates were 95.0 and 92.3%, respectively. Chairside LDGC CAD-CAM crowns exhibited a high survival rate after 4 years in function and were shown to be a viable and reliable treatment option for posterior teeth. The high survival rate of chairside CAD-CAM crowns observed in this study suggests the likelihood of predictable performance in the predoctoral setup.

MeSH Terms

  • Ceramics
  • Computer-Aided Design
  • Crowns
  • Dental Porcelain
  • Dental Prosthesis Design
  • Humans
  • Materials Testing

Keywords

  • CAD-CAM
  • chairside
  • dental crowns
  • lithium disilicate
  • longevity
  • survival


Acute resveratrol supplementation in coronary artery disease: towards patient stratification.

[i]Objective:[/i] Resveratrol (RV) is a polyphenol with antioxidant, anti-inflammatory and cardio-protective properties. Our objective was to investigate whether acute supplementation with high doses of RV would improve flow-mediated dilation (FMD) and oxygen consumption (VO ) kinetics in older coronary artery disease (CAD) patients. [i]Design:[/i] We employed a placebo-controlled, single-blind, crossover design in which ten participants (aged 66.6 ± 7.8 years) received either RV or placebo (330 mg, 3× day ) during three consecutive days plus additional 330 mg in the morning of the fourth day with a seven-day wash-out period in-between. On the fourth day, FMD of the brachial artery and VO on-kinetics were determined. [i]Results:[/i] RV improved FMD in patients who had undergone coronary artery bypass grafting (CABG; -1.4 [i]vs[/i]. 5.0%; [i]p =[/i] .004), but not in those who had undergone percutaneous coronary intervention (PCI; 4.2 [i]vs[/i]. -0.2%; NS). [i]Conclusion:[/i] Acute high dose supplementation with RV improved FMD in patients after CABG surgery but impaired FMD in patients who underwent PCI. The revascularization method-related differential effects of RV may be due to its direct effects on endothelial-dependent dilator responses. Our findings have important implications for personalized treatment and stratification of older CAD patients.

MeSH Terms

  • Aged
  • Biomarkers
  • Brachial Artery
  • Cardiac Rehabilitation
  • Coronary Artery Bypass
  • Coronary Artery Disease
  • Cross-Over Studies
  • Exercise Therapy
  • Female
  • Humans
  • Kinetics
  • Male
  • Middle Aged
  • Oxygen
  • Oxygen Consumption
  • Percutaneous Coronary Intervention
  • Resveratrol
  • Single-Blind Method
  • Treatment Outcome
  • Vasodilation

Keywords

  • Antioxidant
  • aging
  • endothelial dysfunction
  • oxygen uptake


Cellular response to moderate chromatin architectural defects promotes longevity.

Changes in chromatin organization occur during aging. Overexpression of histones partially alleviates these changes and promotes longevity. We report that deletion of the histone H3-H4 minor locus [i]HHT1-HHF1[/i] extended the replicative life span of [i]Saccharomyces cerevisiae[/i]. This longevity effect was mediated through TOR signaling inhibition. We present evidence for evolutionarily conserved transcriptional and phenotypic responses to defects in chromatin structure, collectively termed the chromatin architectural defect (CAD) response. Promoters of the CAD response genes were sensitive to histone dosage, with [i]HHT1-HHF1[/i] deletion, nucleosome occupancy was reduced at these promoters allowing transcriptional activation induced by stress response transcription factors Msn2 and Gis1, both of which were required for the life-span extension of [i]hht1-hhf1[/i]Δ. Therefore, we conclude that the CAD response induced by moderate chromatin defects promotes longevity.

MeSH Terms

  • Chromatin
  • Gene Deletion
  • Gene Dosage
  • Gene Expression Profiling
  • Gene Expression Regulation, Fungal
  • Genes, Fungal
  • Histones
  • Longevity
  • Models, Biological
  • Mutation
  • Saccharomyces cerevisiae
  • Signal Transduction
  • Stress, Physiological


Myocyte enhancer factor 2A delays vascular endothelial cell senescence by activating the PI3K/p-Akt/SIRT1 pathway.

Myocyte enhancer factor 2A (MEF2A) dysfunction is closely related to the occurrence of senile diseases such as cardiocerebrovascular diseases, but the underlying molecular mechanism is unclear. Here, we studied the effects of MEF2A on the senescent phenotype of vascular endothelial cells (VEC) and downstream signaling pathway, and the association between plasma MEF2A levels and coronary artery disease (CAD). Results showed that MEF2A silencing promoted cell senescence and down-regulated PI3K/p-AKT/Sirtuin 1 (SIRT1) expression. MEF2A overexpression delayed cell senescence and up-regulated PI3K/p-AKT/SIRT1. Hydrogen peroxide (H O ) treatment induced cellular senescence and down-regulated the expression of MEF2A and PI3K/p-AKT/SIRT1. MEF2A overexpression inhibited cellular senescence and the down-regulation of PI3K/p-AKT/SIRT1 induced by H O . Further study revealed that MEF2A directly up-regulated the expression of PIK3CA and PIK3CG through MEF2 binding sites in the promoter region. Pearson correlation and logistic regression analysis showed that the plasma level of MEF2A was negatively correlated with CAD, and with age in the controls. These results suggested that MEF2A can directly up-regulate PI3K gene expression, and one of the molecular mechanisms of delaying effect of MEF2A on VEC cell senescence was SIRT1-expression activation through the PI3K/p-Akt pathway. Moreover, the plasma MEF2A levels may be a potential biomarker for CAD risk prediction.

MeSH Terms

  • Aged
  • Cellular Senescence
  • Coronary Artery Disease
  • Down-Regulation
  • Endothelial Cells
  • Female
  • Humans
  • Hydrogen Peroxide
  • MEF2 Transcription Factors
  • Male
  • Middle Aged
  • Phosphatidylinositol 3-Kinases
  • Phosphorylation
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction
  • Sirtuin 1

Keywords

  • Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA)
  • Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit gamma (PIK3CG)
  • Sirtuin 1 (SIRT1)
  • myocyte enhancer factor 2A
  • senescence


Altering of optical and mechanical properties in high-translucent CAD-CAM resin composites during aging.

This study was aimed to monitor the alteration of the optical and mechanical properties of high-translucent CAD-CAM resin composites (HTRCs) during aging. Corrections for the measured transmitted irradiance are proposed. Individual sets (n = 6) of plane-parallel test specimens (0.5-, 2- and 4-mm) of seven HTRCs were prepared. The optical properties (absorbance, transmittance, reflectance, linear absorption coefficient, and transmitted irradiance) were assessed by regular spectrometric testing methodologies and were corrected to account for light reflection. Several edge chipping resistance parameters (edge force at different edge distances, edge chip resistance), as well as mechanical parameters obtained from depth-sensing indentation (Vickers hardness, indentation modulus, creep, elastic and plastic indentation work), were considered. Aging involved storage for two weeks in artificial saliva at 37 °C, followed by thermal aging (10,000 thermocycles, 5 °C-55 °C) and storage in alcohol/water solution, employing non-aged specimens as a reference. Filler size and shape were analyzed by scanning electron microscopy. Reflectance varied from 11% to 27% and was altered during aging. Linear absorption coefficients of 0.281 mm to 0.369 mm were obtained for non-aged specimens, with very low changes during aging. A difference between the true and measured irradiance was identified to decrease exponentially with the specimen's thickness. The impact of HTRC was stronger than the impact of aging. Reflectance determined by spectrometric analysis was identified as a possible criterion to estimate surface degradation during aging. Corrections for thin and translucent specimens are needed when determining transmitted irradiance through restorations. Depth-sensing indentation was evidenced as the most discriminatory testing methodology for aging, but the results do not correlate with the edge chipping resistance parameters.

MeSH Terms

  • Composite Resins
  • Computer-Aided Design
  • Dental Materials
  • Hardness
  • Materials Testing
  • Saliva, Artificial
  • Surface Properties

Keywords

  • Aging
  • CAD-CAM resin based composites
  • Edge chipping resistance parameters
  • Micromechanical properties
  • Optical properties


Age-Related Improvements in Peak Cardiorespiratory Fitness among Coronary Heart Disease Patients Following Cardiac Rehabilitation.

While cardiorespiratory fitness (VO₂peak) can be improved with exercise and training, it is unclear whether older age is associated with an attenuated VO₂peak improvement among patients with coronary artery disease (CAD) who complete a cardiac rehabilitation (CR) program. A retrospective review of patient demographics and VO₂peak data from January 2012 to December 2017 was performed. CAD patients were included if they had successfully completed the supervised 6-month CR program (>75% of exercise prescription) and two VO₂peak assessments (respiratory exchange ratio (RER) >1.0). Among all patients, there was an improvement in VO₂peak from 21.1 ± 6.3 mL/kg/min to 26.5 ± 7.9 mL/kg/min ( 26% ΔVO₂peak). Patients in the younger age category (age category 1: 30⁻39 years old) tended to have a greater percent of relative VO₂peak improvement when compared to all other age categories (e.g., adults 50 years of age and older). In the regression analysis, VO₂peak improvement was associated with younger age ([i]β[/i] = -0.286, [i]p[/i] < 0.0001), after adjustment for the baseline VO₂peak ([i]β[/i] = -0.456, [i]p[/i] < 0.0001), final prescribed exercise speed at CR program completion ([i]β[/i] = 0.254, [i]p[/i] < 0.0001), body mass index ([i]β[/i] = -0.172, [i]p[/i] < 0.0001), and male sex ([i]β[/i] = 0.153, [i]p[/i] < 0.0001). Nonetheless, the study findings indicate that older adults who complete CR may be able to obtain clinically relevant improvements in VO₂peak of greater than 20%, and therefore, should be referred for CR.


Keywords

  • aerobic exercise
  • aging
  • cardiovascular disease
  • exercise testing


Revisiting Intermittent Therapy in Metastatic Prostate Cancer: Can Less Be More in the "New World Order"?

Androgen deprivation therapy (ADT) is the standard of care for men with metastatic hormone-sensitive prostate cancer (HSPC) and a potential treatment option in those with prostate-specific antigen relapse after local therapy. Based on promising biological and preclinical data, several clinical trials compared the efficacy of intermittent androgen deprivation (IAD) versus continuous androgen deprivation (CAD) with the objective of delaying disease progression and improving survival and quality of life (QoL). The objective of this review is to revisit the concept of IAD in the "new world order" and reconsider whether it has a potential clinical role in an era where we have seen unprecedented progress in the management of patients with metastatic HSPC. MEDLINE, Embase, and the Cochrane Library databases were searched for randomized controlled trials comparing IAD and CAD therapies. References of retrieved articles were also searched. Articles with at least 100 randomized patients, which were published in 2008 or later and had data on overall survival or QoL outcomes, were included. The evidence to date cannot exclude inferiority of IAD compared with CAD with respect to survival outcomes. The hazard ratios in metastatic disease indicate less favorable survival with IAD. No superiority trial conclusively favored IAD or CAD. Two trials demonstrated noninferiority of IAD, although the noninferiority margins (NIMs) are clinically concerning. Another trial could not exclude noninferiority. A modest but temporary QoL and symptom benefit generally favoring IAD was observed. IAD has not conclusively demonstrated an impact on disease progression or survival, and has only modest effects on QoL and symptoms measured in the short term. As such, it is not the standard of care, particularly in the era where we have seen unprecedented survival impact with combination ADT docetaxel or abiraterone prednisone. IAD may need to be reassessed in the context of current therapies, ideally driven by biological rationale, with the goal of minimizing physical and financial toxicities with appropriately designed informative clinical trials. In this report, we looked at two hormone therapy approaches for prostate cancer that is still sensitive to castration: one with treatment breaks and one without. Patients may tolerate therapy with breaks more easily, but this effect is not sustained and is not associated with better longevity. The best longevity is seen in patients who receive newer hormone therapies or chemotherapy in addition to continuous hormone therapy. Whether these newer therapies would be as effective if given intermittently is an important but unanswered question.

MeSH Terms

  • Androgen Antagonists
  • Castration
  • Clinical Trials, Phase III as Topic
  • Disease Progression
  • Disease-Free Survival
  • Humans
  • Longevity
  • Male
  • Neoplasm Recurrence, Local
  • Prostate-Specific Antigen
  • Prostatic Neoplasms
  • Quality of Life
  • Randomized Controlled Trials as Topic
  • Time Factors
  • Treatment Outcome

Keywords

  • Intermittent androgen deprivation
  • Prostate cancer


Effect of UV aging on translucency of currently used esthetic CAD-CAM materials.

To evaluate the relative translucency parameter (RTP) values of computer-aided design (CAD)-computer-aided manufacturing (CAM) materials after UV aging. 70 specimens (n = 10) of Bruxzir Anterior (BA); E.max Cad (EC); Lava Ultimate (LU); Cerasmart (CE); Vita Enamic (VE); Vita Suprinity (VS); Vita Mark II (VM) were prepared (1 mm ± 0.01 mm). Color measurements were performed using a spectrofotometer (VITA Easyshade). RTP values of the specimens before (RTP ) and after UV aging (RTP ) were evaluated. Statistical analyses were done with repeated measurements of two-way-ANOVA with Bonferroni test (P < 0.05). Evaluating RTP and RTP values; significant differences were found (P < 0.05). There were no significant difference between the RTP values of CE and VS (P = 0.779); EC and VM (P = 0.952); VM and LU (P = 0.995); EP and LU (P = 0.653). Evaluating RTP values; VE and BA were found significantly different from the others (P < 0.05). For all evaluated groups TP values decreased after UV aging (P < 0.05). The most RTP reduction was observed for LU; while VM and EC were less affected. Glass ceramic VE showed the highest RTP and zirconia-based BA was the most opaque restorative CAD-CAM material. UV aging caused the CAD-CAM materials get more opaque. In cases where translucency is needed chosing VE would give better esthetic results; while zirconia-based BA should be used if more opaque restoration is needed. Clinicians should be aware of that restorations get more opaque after usage.

MeSH Terms

  • Ceramics
  • Computer-Aided Design
  • Dental Materials
  • Dental Porcelain
  • Esthetics, Dental
  • Materials Testing
  • Surface Properties

Keywords

  • CAD-CAM
  • UV aging
  • ceramic
  • translucency
  • zirconia


An economic analysis of salmonella detection in fresh produce, poultry, and eggs using whole genome sequencing technology in Canada.

The study estimates the annual costs of nontyphoidal Salmonellosis (referred to as Salmonellosis from hereon) from fresh produce, poultry and eggs in Canada. It also estimates the economic benefits from introduction of Whole Genome Sequencing (WGS) in detection of Salmonellosis clusters and outbreaks. Monetary and non-monetary costs from Salmonellosis are estimated. Monetary costs are divided into direct healthcare, indirect, federal and producer costs. Probability models are used to account for uncertainty in the cost-of-illness estimates. Two types of non-monetary costs have been estimated: Disability-adjusted Live Years and Quality-adjusted Life Years. These estimates are then used to calculate the economic impact of WGS on detection of Salmonellosis. The estimated incidence of illnesses is 47,082 annually, which represents a cost of $287.78 million (total cases) and $166.28 million (reported cases) from the traditional technology. The total net benefit from introduction of WGS is estimated to range from $5.21 million-$90.25 million. All monetary values are in CAD unless stated otherwise. WGS will help in reducing the economic burden from Salmonellosis. These estimates help will aid policy related decision making.

MeSH Terms

  • Animals
  • Canada
  • Cost Savings
  • Cost of Illness
  • Cost-Benefit Analysis
  • DNA, Bacterial
  • Eggs
  • Food Microbiology
  • Fruit
  • Health Care Costs
  • Humans
  • Incidence
  • Life Expectancy
  • Poultry
  • Predictive Value of Tests
  • Quality-Adjusted Life Years
  • Salmonella
  • Salmonella Food Poisoning
  • Vegetables
  • Whole Exome Sequencing

Keywords

  • Canada
  • Cost-benefit
  • Economic analysis
  • Salmonella
  • Salmonellosis
  • Whole genome sequencing


Age, Sex, and Cardiovascular Risk Attributable to Lipoprotein Cholesterol Among Chinese Individuals with Coronary Artery Disease: A Case-Control Study.

To understand age- and gender-related differences and secular trends in coronary artery disease (CAD) lipid profiles and the characteristic of dyslipidemia in western China. An age-matched case-control study, including 2400 patients and 1200 controls was performed. All blood lipid tests evaluated from January 2012 to January 2015 at First Affiliated Hospital of Xinjiang Medical University were analyzed. Details of the gender and age of the patients were available. Trends were calculated using linear regression and Mantel-Haenszel X analyses. We determined the associations among total cholesterol (TC), triglycerides (TGs), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-1 (apoA-1), apolipoprotein B (apoB), nonhigh-density lipoprotein cholesterol (non-HDL-C), and high-density lipoprotein cholesterol (HDL-C) with CAD for different ages and gender. Except for patients who were <40 years old, the plasma levels of TC, TG, LDL-C, non-HDL-C, apoB, and apoB/apoA-1 were higher in the cases than in controls, and the average levels of these markers decreased significantly as age increased. In contrast, the levels of apoA-1 and HDL-C were significantly higher in the controls than in the patients, and the levels of these markers significantly increased as age increased. Women had higher levels of TC, LDL-C, non-HDL-C, and apoB and a higher value of the apoB/apoA-1 ratio compared to men. The decrease in the average levels of these markers with age was significantly lower in women compared to men. Logistic regression was used to compute the odds ratio of CAD for a one standard deviation change in each lipid marker. Most notably, the apoB/apoA-1 ratio could be a strong risk factor for CAD, and increasing values of the ratio showed a curved line for the graph of the relationship between the ratio and risk. Our results confirmed that serum lipid levels in patients with CAD varied by age and gender. The apoB/apoA-1 ratio remains a strong risk factor for CAD.

MeSH Terms

  • Age Factors
  • Aged
  • Apolipoprotein A-I
  • Apolipoprotein B-100
  • Case-Control Studies
  • China
  • Cholesterol
  • Cholesterol, HDL
  • Cholesterol, LDL
  • Coronary Artery Disease
  • Female
  • Humans
  • Life Style
  • Linear Models
  • Lipoproteins
  • Male
  • Middle Aged
  • Odds Ratio
  • Retrospective Studies
  • Risk Factors
  • Sex Factors
  • Treatment Outcome
  • Triglycerides

Keywords

  • aging
  • coronary heart disease
  • dyslipidemia
  • gender


Novel biomolecules of ageing, sex differences and potential underlying mechanisms of telomere shortening in coronary artery disease.

Telomere length (TL), growth differentiate factor (GDF)11, insulin growth factor (IGF)1, sirtuin (SIRT)1 and inflammatory processes have been related to ageing and age-related diseases, like coronary artery disease (CAD). We aimed to investigate the associations between leukocyte TLs (LTLs), chronological age, sex and comorbidities in CAD patients. Any covariations between LTL, GDF11, IGF1, SIRT-1 and pro-inflammatory cytokines were further assessed. In 300 patients with stable CAD (age 36-81 years, 20% females), DNA and RNA were isolated from whole blood for PCR analysis and relative quantification of LTLs and gene-expression of GDF11, IGF1,SIRT1, IL-12, IL-18 and IFNƴ, respectively. Serum was prepared for the analyses of circulating IL-18, IL-12, IL-6 and TNFα. Patients with previous myocardial infarction (MI) presented with 20% shorter LTLs vs. patients without (p = 0.019) indicating LTLs to be of importance for CAD severity. The observation however, was only observed in men (p = 0.009, n = 115), in which the upper LTL quartile associated with 64% lower frequency of previous MI compared to quartile 1-3 (p = 0.005, adjusted). LTLs were not differently distributed according to sex or comorbidities such as hypertension, diabetes type 2 and metabolic syndrome. LTLs and GDF11 were inversely correlated to age (r = -0.17; p = 0.007 and r = -0.16; p = 0.010, respectively), however, separated in gender, LTL only in women (r = -0.37) and GDF11 only in men (r = -0.19) (p = 0.006, both). GDF11 and SIRT1 were strongly inter-correlated (r = 0.56, p ≤ 0.001), suggesting common upstream regulators. LTLs were moderately correlated to GDF11 and SIRT1 in overweight women (BMI ≥ 25 kg/m ) (r = 0.41; p = 0.027 and 0.43; p = 0.020, respectively), which may reflect common life-style influences on LTLs and these markers. In all women, we observed further that the highest LTL quartile associated with higher GDF11 and SIRT expression and lower circulating levels of IL-12, IL-18 and TNFα, as compared to quartile 1, which may indicate lifestyle influences on female LTLs. In men, the highest LTL quartile associated with lower IFNƴ expression and lower circulating TNFα. Overall, the results indicate an association between chronic low-grade inflammation and LTLs. Shorter LTLs in CAD patients with previously suffered MI may indicate telomere attrition as part of its pathophysiology in men. The inverse association between LTLs and age exclusively in women underpins the previously reported decline in attrition rate in men with increasing age. As elevated GDF11 and SIRT1 along with attenuated pro-inflammatory cytokines seem to positively affect LTL in women, we hypothesize a potential sex-dimorphism in LTL regulation, which may implicate sex- adjusted health-preventive therapies.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Bone Morphogenetic Proteins
  • Coronary Artery Disease
  • Cross-Sectional Studies
  • Female
  • Genetic Markers
  • Growth Differentiation Factors
  • Humans
  • Leukocytes
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Norway
  • Sex Characteristics
  • Sirtuin 1
  • Telomere
  • Telomere Shortening

Keywords

  • Coronary artery disease
  • GDF11
  • IGF1
  • Inflammatory cytokines
  • SIRT1
  • Telomere lengths


Age-dependent association of pulse wave velocity with coronary artery disease and myocardial aging in high-risk patients.

Progressive arterial stiffening, as a marker of arterial aging, may reach a plateau in elderly patients and may thus lose its clinical utility. This phenomenon may be more prominent in high-risk patients. We aimed to investigate if carotid-to-femoral pulse wave velocity (cf-PWV) is related to coronary artery disease (CAD) and diastolic dysfunction in elderly high-risk patients as compared to a control group of younger individuals. One-hundred and ninety-two high-risk stable patients who underwent coronary artery angiography and assessment of cf-PWV were consecutively recruited. Indices of diastolic dysfunction were also measured by echocardiography, including the volume of the left atrium and the ratio of early transmitral peak velocity (E) to the mitral annular early diastolic velocity (E'). Increased cf-PWV was associated with the presence of CAD [odds ratio (OR) 1.34, P = 0.02], number of diseased coronary vessels (OR 1.17, P = 0.029) and CAD severity (P = 0.023) as assessed by Gensini score, in patients less than 65 years old after adjustment for traditional risk factors. Moreover, cf-PWV correlated with E/E' (P = 0.019) and increased the odds by 16% (OR 1.16, P = 0.048) for more severe diastolic dysfunction in patients aged below 65 years old. None of these outcomes correlated with cf-PWV in the elderly. In high cardiovascular risk patients, an age-dependent association of cf-PWV with CAD and diastolic dysfunction was evinced. In contrast to younger patients, these results suggest that measuring arterial stiffness in elderly high-risk patients may lack clinical value.

MeSH Terms

  • Age Factors
  • Aged
  • Aging
  • Case-Control Studies
  • Coronary Angiography
  • Coronary Artery Disease
  • Cross-Sectional Studies
  • Diastole
  • Echocardiography
  • Female
  • Greece
  • Humans
  • Male
  • Middle Aged
  • Peripheral Arterial Disease
  • Predictive Value of Tests
  • Prognosis
  • Pulse Wave Analysis
  • Risk Assessment
  • Risk Factors
  • Vascular Stiffness
  • Ventricular Dysfunction, Left
  • Ventricular Function, Left


The Effect of Residential Aged Care Size, Ownership Model, and Multichain Affiliation on Resident Comfort and Symptom Management at the End of Life.

In most resource-rich countries, a large and growing proportion of older adults with complex needs will die while in a residential aged care (RAC) facility. This study describes the impact of facility size (small/large), ownership model (profit/nonprofit) and provider (independent/chain) on resident comfort, and symptom management as reported by RAC staff. This retrospective "after-death" study collected decedent resident data from a subsample of 51 hospital-level RAC facilities in New Zealand. Symptom Management at the End-of-Life in Dementia and Comfort Assessment in Dying at End of life with Dementia (SM-EOLD and CAD-EOLD, respectively) scales were used by RAC staff who were closely associated with 217 deceased residents. Data collection occurred from January 2016 to February 2017. Results indicated that residents of large, nonprofit facilities experienced greater comfort at the end of life (CAD-EOLD) as indicated by a higher mean score of 37.21 (SD = 4.85, 95% CI = 34.4, 40.0) than residents of small for-profit facilities who recorded a lower mean score of 31.56 (SD = 6.20, 95% CI = 29.6, 33.4). There was also evidence of better symptom management for residents of chain facilities, with a higher mean score for symptom management (SM-EOLD total score) recorded for residents of chain facilities (mean = 28.07, SD = 7.64, 95% CI = 26.47, 29.66) than the mean score for independent facilities (mean = 23.93, SD = 8.72, 95% CI = 21.65, 26.20). Findings suggest that there are differences in the quality of end-of-life care given in RAC based on size, ownership model, and chain affiliation.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Death
  • Female
  • Homes for the Aged
  • Humans
  • Male
  • Nursing Homes
  • Ownership
  • Patient Satisfaction
  • Quality of Health Care
  • Terminal Care

Keywords

  • Residential aged care
  • aging
  • chain affiliation
  • end of life
  • older people
  • ownership model
  • palliative


Cardiovascular disease in nonagenarians: Prevalence and utilization of preventive therapies.

Nonagenarians are a fast growing segment of industrialized countries' populations. Despite a greater risk of cardiovascular disease, there are limited data about their use of preventive therapies and factors guiding decisions regarding their prescription. The aim of this study was to evaluate the prevalence of cardiovascular diseases and the patterns of use of cardiovascular treatments in subjects ≥90 years old. Population-based, cross-sectional study, in all nonagenarians residing in the Community of Madrid (Spain). Data were obtained from their electronic clinical records in primary care. Data were available from 59,423 subjects (mean age 93.3 years, 74.2% female, 13.5% with dementia). Prevalence of cardiovascular disease was 24.1% (10.9% with coronary artery disease (CAD), 13.1% with cerebrovascular disease (CVD) and 2.7% with peripheral artery disease(PAD)). In primary prevention, the use of statins and antiplatelet agents was 21.9% and 26.7%, respectively. Of subjects with vascular disease 27.7% were receiving a combined preventive strategy (use of antithrombotics, plus statins, plus blood pressure below 140/90 mmHg). Factors favourably associated with a combined preventive strategy were: female sex (odds ratio (OR) 1.29; 95% confidence interval (CI): 1.11-1.49), being independent versus totally dependent (OR 1.94; 95% CI: 1.43-2.65), diabetes (OR 1.42; 95% CI: 1.20-1.68), and negatively, age (OR 0.87; 95% CI: 0.85-0.90), CVD versus CAD (OR 0.41; 95% CI: 0.35-0.47), PAD versus CAD (OR 0.23; 95% CI: 0.18-0.30), dementia (OR 0.61; 95% CI: 0.49-0.76) and nursing home residency (OR 0.73; 95% CI: 0.57-0.93). Nonagenarians have a great burden of cardiovascular diseases and receive a great number of preventive therapies, even in primary prevention, despite their unproven efficacy at these ages.

MeSH Terms

  • Age Distribution
  • Aged, 80 and over
  • Cardiovascular Diseases
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Practice Patterns, Physicians'
  • Prevalence
  • Primary Prevention
  • Risk Factors
  • Spain
  • Time Factors
  • Treatment Outcome

Keywords

  • Aging
  • cardiovascular preventive therapies
  • cerebrovascular disease
  • coronary artery disease
  • oldest old
  • peripheral artery disease


Potential associations of testosterone/estradiol ratio, leukocyte hTERT expression and PBMC telomerase activity with aging and the presence of coronary artery disease in men.

The present study aimed to examine associations of the testosterone/estradiol ratio, human leukocyte telomerase reverse transcriptase (hTERT) expression and telomerase activity of peripheral blood mononuclear cells (PBMCs) with aging and the presence of coronary artery disease (CAD). Telomeres in leukocytes are shorter in individuals with CAD than in healthy individuals of the same age. Levels of sex hormones are related to aging, and the ratio of testosterone to estradiol has been linked to CAD in men. Here we compared younger men (22 ± 2 yr, n = 26), middle-aged men (31 ± 5 yr, n = 35), older men without CAD (60 ± 10 yr, n = 30) and older men with CAD (63 ± 8 yr, n = 30) in terms of testosterone/estradiol ratio, leukocyte telomerase reverse transcriptase (hTERT) expression, activity of telomerase in peripheral blood mononuclear cells (PBMCs), and length of PBMC telomeres. Levels of hTERT mRNA of leukocyte and PBMC telomerase activity were significantly lower in older men than in younger or middle-aged men (p < 0.05). These two parameters, as well as testosterone/estradiol ratio, were significantly lower in older men with CAD than in all the other groups (p < 0.05). The sex hormone ratio correlated significantly with age, hTERT mRNA levels, PBMC telomerase activity and telomere length (p < 0.05). These results support the hypothesis that sex hormone balance is a biomarker of telomerase function, and that both of these parameters change as men age or develop CAD.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Coronary Artery Disease
  • Estradiol
  • Humans
  • Leukocytes
  • Leukocytes, Mononuclear
  • Male
  • Middle Aged
  • RNA, Messenger
  • Telomerase
  • Telomere Homeostasis
  • Testosterone
  • Young Adult

Keywords

  • Aging
  • CAD
  • PBMC telomerase
  • Sex hormone
  • hTERT


Assessment of cardiovascular risk and preparticipation screening protocols in masters athletes: the Masters Athlete Screening Study (MASS): a cross-sectional study.

Underlying coronary artery disease (CAD) is the primary cause of sudden cardiac death in masters athletes (>35 years). Preparticipation screening may detect cardiovascular disease; however, the optimal screening method is undefined in this population. The Physical Activity Readiness Questionnaire for Everyone (PAR-Q ) and the American Heart Association (AHA) Preparticipation Screening Questionnaire are often currently used; however, a more comprehensive risk assessment may be required. We sought to ascertain the cardiovascular risk and to assess the effectiveness of screening tools in masters athletes. This cross-sectional study performed preparticipation screening on masters athletes, which included an ECG, the AHA 14-element recommendations and Framingham Risk Score (FRS). If the preparticipation screening was abnormal, further evaluations were performed. The effectiveness of the screening tools was determined by their positive predictive value (PPV). 798 athletes were included in the preparticipation screening analysis (62.7% male, 54.6±9.5 years, range 35-81). The metabolic equivalent task hours per week was 80.8±44.0, and the average physical activity experience was 35.1±14.8 years. Sixty-four per cent underwent additional evaluations. Cardiovascular disease was detected in 11.4%, with CAD (7.9%) being the most common diagnosis. High FRS (>20%) was seen in 8.5% of the study population. Ten athletes were diagnosed with significant CAD; 90% were asymptomatic. A high FRS was most indicative of underlying CAD (PPV 38.2%). Masters athletes are not immune to elevated cardiovascular risk and cardiovascular disease. Comprehensive preparticipation screening including an ECG and FRS can detect cardiovascular disease. An exercise stress test should be considered in those with risk factors, regardless of fitness level.


Keywords

  • aging
  • athlete
  • cardiology prevention
  • cardiovascular
  • sports


Comparison of marginal fit between CAD-CAM and hot-press lithium disilicate crowns.

Hot-pressing and computer-aided design and computer-aided manufacturing (CAD-CAM) are major techniques for the fabrication of lithium disilicate crowns. They exhibit different accuracies regarding marginal fit, an important factor in restoration survival. However, studies comparing the marginal fit of different fabrication methods are lacking. The purpose of this in vitro study was to compare the marginal discrepancy (MD) and absolute marginal discrepancy (AMD) of lithium disilicate crowns produced by the hot-press and CAD-CAM techniques. Thirty typodont teeth were divided into 2 groups. Fifteen teeth were scanned with the CEREC Omnicam intraoral scanner, and crowns were fabricated with the CEREC MC XL chairside CAD-CAM milling unit from IPS e.max CAD blocks. Fifteen typodont teeth were sent to a dental laboratory, and lithium disilicate crowns were fabricated from IPS e.max press ingots using the hot-press technique. The 30 crowns were cemented and then sectioned with a precision saw. The MD and AMD were measured for each crown with a light microscope. One-way ANOVA was conducted to analyze significant differences in crown marginal fit between the fabrication systems (α=.05). For the CAD-CAM technique, the mean values of the AMD measurements were 115 μm, and for the hot-press technique, 130 μm. The MD measurements were 87 μm for the CAD-CAM technique and 90 μm for the hot-press technique. One-way ANOVA revealed no significant differences between the fabrication methods regarding marginal fit (P>.05). No significant differences were found between the fabrication methods tested. Both the CAD-CAM and hot-press techniques for producing monolithic lithium disilicate crowns produced MD values of less than 120 μm, within the clinically acceptable range.

MeSH Terms

  • Ceramics
  • Computer-Aided Design
  • Crowns
  • Dental Casting Technique
  • Dental Impression Technique
  • Dental Marginal Adaptation
  • Dental Porcelain
  • Dental Prosthesis Design
  • Dental Restoration, Permanent
  • Humans
  • In Vitro Techniques
  • Longevity
  • Maxilla
  • Molar
  • Pressure
  • Surface Properties


Prognostic value of age adjusted segment involvement score as measured by coronary computed tomography: a potential marker of vascular age.

Extent of coronary atherosclerotic disease (CAD) burden on coronary computed tomography angiography (CCTA) as measured by segment involvement score (SIS) has a prognostic value. We sought to investigate the incremental prognostic value of 'age adjusted SIS' (aSIS), which may be a marker of premature atherosclerosis and vascular age. Consecutive patients were prospectively enrolled into the CONFIRM (Coronary CT Angiography EvaluatioN For Clinical Outcomes: An InteRnational Multicentre) multinational observational study. Patients were followed for the outcome of all-cause death. aSIS was calculated on CCTA for each patient, and its incremental prognostic value was evaluated. A total of 22,211 patients [mean age 58.5 ± 12.7 years, 55.8% male) with a median follow-up of 27.3 months (IQR 17.8, 35.4)] were identified. After adjustment for clinical factors and presence of obstructive CAD, higher aSIS was associated with increased death on multivariable analysis, with hazard ratio (HR) 2.40 (1.83-3.16, p < 0.001), C-statistic 0.723 (0.700-0.756), net reclassification improvement (NRI) 0.36 (0.26-0.47, p < 0.001), and relative integrated discrimination improvement (IDI) 0.33 (p = 0.009). aSIS had HR 3.48 (2.33-5.18, p < 0.001) for mortality in those without obstructive CAD, compared to HR 1.79 (1.25-2.58, p = 0.02) in those with obstructive CAD. In conclusion, aSIS has an incremental prognostic value to traditional risk factors and obstructive CAD, and may enhance CCTA risk stratification.

MeSH Terms

  • Age Factors
  • Aged
  • Aging
  • Computed Tomography Angiography
  • Coronary Angiography
  • Coronary Artery Disease
  • Coronary Vessels
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic
  • Predictive Value of Tests
  • Prognosis
  • Prospective Studies
  • Registries
  • Risk Factors
  • Time Factors

Keywords

  • Atherosclerosis
  • Computed tomography
  • Coronary
  • Prognosis


Vitamin D levels correlate with lymphocyte subsets in elderly patients with age-related diseases.

Hypovitaminosis D is associated with age-related illnesses, including hypertension, cardiovascular disease (CRVD), cerebrovascular disease (CAD) and type 2 diabetes mellitus (T2DM). In our retrospective observational study, blood samples of elderly healthy controls (n = 461) and patients with age-related diseases (n = 8,621) were subjected to flow-cytometry in order to determine correlations between age-related diseases and cluster of differentiation 4 (CD4), CD8, CD3, and CD19 lymphocyte markers, as well as serum levels of 25-hydroxyvitamin D (25(OH)D ) and 25-hydroxyvitamin D (25(OH)D ). More than 70% of the patients in each disease group had total vitamin D < 20 ng/mL (P < 0.001). In CRVD patients, CD3 and CD19 correlated (P < 0.05) with 25(OH)D . In CAD patients, CD8, CD4, CD19 and CD4/CD8 correlated (P < 0.05) with 25(OH)D , and CD8 correlated (P < 0.05) with 25(OH)D . In T2DM and hypertension patients, CD8, CD3, CD19 and CD4/CD8 correlated with 25(OH)D . Progressive trends (P < 0.05) towards increased CD8 and CD4/CD8 were observed in vitamin-D-deficient T2DM and hypertension patients. Significant differences (P < 0.05) in CD8 were observed in vitamin-D-deficient CAD patients, whereas significant differences (P < 0.05) in CD8 and CD19 were observed in CRVD patients. Higher CD8 and CD4/CD8 in 25(OH)D-deficient T2DM and hypertension patients suggested a Th1 lymphocyte profile induction. Increases in CD8-positive lymphocytes suggested a similar, less pronounced effect in vitamin-D-deficient CRVD and CAD patients.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Biomarkers
  • Cardiovascular Diseases
  • Case-Control Studies
  • Cerebrovascular Disorders
  • Diabetes Mellitus, Type 2
  • Female
  • Humans
  • Hypertension
  • Lymphocyte Subsets
  • Male
  • Retrospective Studies
  • Vitamin D
  • Vitamin D Deficiency
  • Vitamins


Effect of metabolic syndrome and aging on Ca dysfunction in coronary smooth muscle and coronary artery disease severity in Ossabaw miniature swine.

Metabolic syndrome (MetS) and aging are prevalent risk factors for coronary artery disease (CAD) and contribute to the etiology of CAD, including dysregulation of Ca handling mechanisms in coronary smooth muscle (CSM). The current study tested the hypothesis that CAD severity and CSM Ca dysregulation were different in MetS-induced CAD compared to aging-induced CAD. Young (2.5 ± 0.2 years) and old (8.8 ± 1.2 years) Ossabaw miniature swine were fed an atherogenic diet for 11 months to induce MetS and were compared to lean age-matched controls. The metabolic profile was confirmed by body weight, plasma cholesterol and triglycerides, and intravenous glucose tolerance test. CAD was measured with intravascular ultrasound and histology. Intracellular Ca ([Ca ] ) was assessed with fura-2 imaging. CAD severity was similar between MetS young and lean old swine, with MetS old swine exhibiting the most severe CAD. Compared to CSM [Ca ] handling in lean young, the MetS young and lean old swine exhibited increased sarcoplasmic reticulum Ca store release, increased Ca influx through voltage-gated Ca channels, and attenuated sarco-endoplasmic reticulum Ca ATPase activity. MetS old and MetS young swine had similar Ca dysregulation. Ca dysregulation, mainly the SR Ca store, in CSM is more pronounced in lean old swine, which is indicative of mild, proliferative CAD. MetS old and MetS young swine exhibit Ca dysfunction that is typical of late, severe disease. The more advanced, complex plaques in MetS old swine suggest that the "aging milieu" potentiates effects of Ca handling dysfunction in CAD.

MeSH Terms

  • Aging
  • Animals
  • Arteries
  • Atherosclerosis
  • Calcium
  • Calcium Channels
  • Coronary Artery Disease
  • Disease Models, Animal
  • Female
  • Male
  • Metabolic Syndrome
  • Myocytes, Smooth Muscle
  • Sarcoplasmic Reticulum Calcium-Transporting ATPases
  • Swine
  • Swine, Miniature
  • Ultrasonography, Interventional

Keywords

  • Atherosclerosis
  • Intravascular ultrasound
  • Metabolism
  • Obesity
  • Sarco-endoplasmic reticulum Ca(2 ) ATPase


Definitions and clinical impact of revascularization completeness.

The completeness of revascularization in patients with multivessel coronary artery disease (CAD) remains an unanswered question. Despite 20 years of investigation there are still major doubts in this topic, reaching as far as to the lack of a standardized definition. The employment of different definition and the multiplicity of confounding variables that in general favor patients who receive a complete revascularization (CR) are the reason of difficult comparisons between studies. The complexity of coronary anatomy diseases and the clinical features play important role in the revascularization strategy. However, the clinical impact of CR is different in particular clinical subsets, such as diabetes, ST-segment elevation myocardial infarction, cardiogenic shock, ischemic heart failure. The CR is a desirable objective, but it is not mandatory and sometimes a reasonable incomplete revascularization (IR) offers comparable results. Clinical variables, including patient's age, life expectancy, the severity of symptoms at presentation, comorbidities (particularly diabetes mellitus), left ventricular function and myocardial viability, as well as coronary anatomy should be considered in the decision making whether to attempt CR or to follow a reasonable IR strategy, for both percutaneous coronary intervention and coronary artery bypass graft surgery, in patients with multivessel CAD.

MeSH Terms

  • Age Factors
  • Coronary Artery Bypass
  • Coronary Artery Disease
  • Decision Making
  • Humans
  • Life Expectancy
  • Myocardial Revascularization
  • Percutaneous Coronary Intervention
  • Risk Factors
  • Severity of Illness Index


MicroRNA-216a induces endothelial senescence and inflammation via Smad3/IκBα pathway.

Vascular endothelial senescence contributes to atherosclerosis and coronary artery disease (CAD), but the mechanisms are yet to be clarified. We identified that microRNA-216a (miR-216a) significantly increased in senescent endothelial cells. The replicative senescence model of human umbilical vein endothelial cells (HUVECs) was established to explore the role of miR-216a in endothelial ageing and dysfunction. Luciferase assay indicated that Smad3 was a direct target of miR-216a. Stable expression of miR-216a induced a premature senescence-like phenotype in HUVECs with an impairment in proliferation and migration and led to an increased adhesion to monocytes by inhibiting Smad3 expression and thereafter modulating the degradation of NF-κB inhibitor alpha (IκBα) and activation of adhesion molecules. Conversely, inhibition of endogenous miR-216a in senescent HUVECs rescued Smad3 and IκBα expression and inhibited monocytes attachment. Plasma miR-216a was significantly higher in old CAD patients (>50 years) and associated with increased 31% risk for CAD (odds ratio 1.31, 95% confidence interval 1.03-1.66; P = .03) compared with the matched healthy controls (>50 years). Taken together, our data suggested that miR-216a promotes endothelial senescence and inflammation as an endogenous inhibitor of Smad3/IκBα pathway, which might serve as a novel target for ageing-related atherosclerotic diseases.

MeSH Terms

  • Aged
  • Base Sequence
  • Cell Adhesion
  • Cell Movement
  • Cell Proliferation
  • Cellular Senescence
  • Coronary Artery Disease
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Inflammation
  • MicroRNAs
  • Monocytes
  • NF-KappaB Inhibitor alpha
  • Phenotype
  • Signal Transduction
  • Smad3 Protein
  • Up-Regulation

Keywords

  • Smad3
  • atherosclerosis
  • endothelial senescence
  • inflammation
  • microRNA-216a


Heart Rate Fragmentation: A Symbolic Dynamical Approach.

We recently introduced the concept of heart rate fragmentation along with a set of metrics for its quantification. The term was coined to refer to an increase in the percentage of changes in heart rate acceleration sign, a dynamical marker of a type of anomalous variability. The effort was motivated by the observation that fragmentation, which is consistent with the breakdown of the neuroautonomic-electrophysiologic control system of the sino-atrial node, could confound traditional short-term analysis of heart rate variability. The objectives of this study were to: (1) introduce a symbolic dynamical approach to the problem of quantifying heart rate fragmentation; (2) evaluate how the distribution of the different dynamical patterns ("words") varied with the participants' age in a group of healthy subjects and patients with coronary artery disease (CAD); and (3) quantify the differences in the fragmentation patterns between the two sample populations. The symbolic dynamical method employed here was based on a ternary map of the increment NN interval time series and on the analysis of the relative frequency of symbolic sequences (words) with a pre-defined set of features. We analyzed annotated, open-access Holter databases of healthy subjects and patients with CAD, provided by the University of Rochester Telemetric and Holter ECG Warehouse (THEW). The degree of fragmentation was significantly higher in older individuals than in their younger counterparts. However, the fragmentation patterns were different in the two sample populations. In healthy subjects, older age was significantly associated with a higher percentage of transitions from acceleration/deceleration to zero acceleration and [i]vice versa[/i] (termed "soft" inflection points). In patients with CAD, older age was also significantly associated with higher percentages of frank reversals in heart rate acceleration (transitions from acceleration to deceleration and [i]vice versa[/i], termed "hard" inflection points). Compared to healthy subjects, patients with CAD had significantly higher percentages of soft and hard inflection points, an increased percentage of words with a high degree of fragmentation and a decreased percentage of words with a lower degree of fragmentation. The symbolic dynamical method employed here was useful to probe the newly recognized property of heart rate fragmentation. The findings from these cross-sectional studies confirm that CAD and older age are associated with higher levels of heart rate fragmentation. Furthermore, fragmentation with healthy aging appears to be phenotypically different from fragmentation in the context of CAD.


Keywords

  • aging
  • coronary artery disease
  • fragmentation
  • heart rate variability
  • symbolic dynamics
  • vagal tone


Diabetes Care Disparities in Long-standing Type 1 Diabetes in Canada and the U.S.: A Cross-sectional Comparison.

To assess national differences in diabetes care and quality of life (QOL) between individuals with long-standing type 1 diabetes (≥50 years) in Canada and the U.S. Cross-sectional data from identical surveys administered in the Canadian Study of Longevity in Diabetes and the Joslin Medalist Study, collected in 2013-2016 and 2005-2011, respectively, were compared. Laboratory values and ophthalmic examination were completed by clinical care physicians for Canadians and the Joslin Clinic for Americans. Univariate comparisons and multivariable regression for HbA , QOL, insulin pump use, and coronary artery disease (CAD) were performed. Nephropathy, CAD, and peripheral arterial disease (PAD) were self-reported; neuropathy was defined by a Michigan Neuropathy Screening Instrument (Questionnaire component) score ≥3, and proliferative retinopathy was documented from ophthalmic examination. QOL was self-reported on an ordinal scale. Three hundred sixty-one Canadians and 668 Americans had similar ages (mean 65.78 years [SD 8.67] vs. 66.38 years [7.66], [i]P[/i] = 0.27) and durations of diabetes (median 53.00 years [interquartile range 51.00, 58.00] vs. 53.00 years [51.00, 57.00], [i]P[/i] = 0.51). Canadians had higher HbA (mean 7.53% [SD 1.03] [59 mmol/mol] vs. 7.22% [0.98] [55 mmol/mol], [i]P[/i] < 0.0001), lower QOL (36.9% vs. 48.7% with "excellent" QOL, [i]P[/i] = 0.0002), and less CAD (29.7% vs. 41.2%, [i]P[/i] = 0.0003) and insulin pump use (43.3% vs. 55.6%, [i]P[/i] = 0.0002). Other complication rates were similar. Residual differences for Canadians compared with Americans remained after adjustment for age, sex, CAD, PAD, education, and relevant a priori selected variables: 0.28% higher HbA ([i]P[/i] = 0.0004); and odds ratios of 0.68 (95% CI 0.51, 0.90), 0.46 (0.31, 0.68), and 0.71 (0.52, 0.96) for higher QOL, CAD, and insulin pump use, respectively. Although Canadians and Americans have similar rates of complications other than CAD, further research is required to understand why Canadians have higher HbA levels, lower QOL, and less insulin pump use.

MeSH Terms

  • Aged
  • Body Mass Index
  • Canada
  • Coronary Artery Disease
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 1
  • Diabetic Retinopathy
  • Dose-Response Relationship, Drug
  • Female
  • Glycated Hemoglobin A
  • Healthcare Disparities
  • Humans
  • Insulin
  • Insulin Infusion Systems
  • Longevity
  • Male
  • Middle Aged
  • Peripheral Arterial Disease
  • Prevalence
  • Quality of Life
  • Surveys and Questionnaires
  • United States


The effects of aerobic and anaerobic exercises on circulating soluble-Klotho and IGF-I in young and elderly adults and in CAD patients.

Different studies support the notion that chronic aerobic exercises training can influence the circulating levels of soluble-Klotho (s-Klotho) and insulin-like growth factor 1 (IGF-I). The effects of s-Klotho include improving the quality of life, alleviating the negative impact of age on the body's work capacity, and possibly increasing longevity. This review provides an overview of the latest findings in this field of research in humans. The different modes of dynamic exercise and their impact on circulating levels of s-Klotho and IGF-I in young adult athletes, untrained young adults, trained healthy older adults, untrained healthy older adults, and coronary artery disease (CAD) patients are reviewed and discussed. Together these findings suggest that long-lasting (chronic) aerobic exercise training is probably one of the antiaging factors that counteract the aging and CAD process by increasing the circulating s-Klotho and lowering the IGF-I levels. However, following anaerobic exercise training the opposite occurs. The exact metabolic and physiological pathways involved in the activity of these well-trained young and master sportsmen should be further studied and elucidated. The purpose of this review was to provide a clarification regarding the roles of s-Klotho and intensities and durations of different exercise on human health.


Keywords

  • Aerobic exercise
  • aging
  • anaerobic exercise
  • coronary artery disease
  • elite athletes
  • epigenetic
  • master athletes


Association between coronary artery disease severity and overactive bladder in geriatric patients.

To investigate the association between overactive bladder (OAB) and coronary artery disease (CAD) as demonstrated on coronary angiography in patients > 65 years. The patients who were > 65 years completed an OAB-V8 form before undergoing coronary angiography at a tertiary care hospital. The presence of OAB was documented using the self-administered OAB-V8 questionnaire. Formal stratification of the coronary vessels plaque burden was assessed by calculation of a Gensini score for each patient. Body mass index (BMI) blood urea nitrogen (BUN), serum lipid profile, fasting plasma glucose, urinalysis, urine culture, uroflowmetry, and postvoiding residual urine volume were measured for each patient. A total of 308 patients were analysed. Before coronary angiography, the patients were divided into two groups according to the score on the OAB-V8 questionnaire. The OAB group (n: 153) comprised those with a score ≥ 8 and the non-OAB group (n: 155), those with a score < 8. The mean age of the patients was 75.08 ± 5.01 years in the OAB group and 68.73 ± 3.26 years in the non-OAB group (p < 0.001). The Gensini scores of the patients in the OAB and non-OAB groups were 22.48 ± 3.51 and 5.89 ± 2.72, respectively (p = 0.001). In multiple regression analysis, no significant difference was determined between the groups in terms of gender, fasting blood glucose level, presence of hypertension, smoking, BMI, and BUN, except LDL and cholesterol levels. In this preliminary investigation, the incidence of severe CAD was found to be higher in patients with OAB symptoms.

MeSH Terms

  • Aged, 80 and over
  • Coronary Artery Disease
  • Cross-Sectional Studies
  • Female
  • Humans
  • Male
  • Severity of Illness Index
  • Urinary Bladder, Overactive

Keywords

  • Coronary artery disease
  • Geriatrics
  • Overactive bladder


Genome-wide meta-analysis associates HLA-DQA1/DRB1 and LPA and lifestyle factors with human longevity.

Genomic analysis of longevity offers the potential to illuminate the biology of human aging. Here, using genome-wide association meta-analysis of 606,059 parents' survival, we discover two regions associated with longevity (HLA-DQA1/DRB1 and LPA). We also validate previous suggestions that APOE, CHRNA3/5, CDKN2A/B, SH2B3 and FOXO3A influence longevity. Next we show that giving up smoking, educational attainment, openness to new experience and high-density lipoprotein (HDL) cholesterol levels are most positively genetically correlated with lifespan while susceptibility to coronary artery disease (CAD), cigarettes smoked per day, lung cancer, insulin resistance and body fat are most negatively correlated. We suggest that the effect of education on lifespan is principally mediated through smoking while the effect of obesity appears to act via CAD. Using instrumental variables, we suggest that an increase of one body mass index unit reduces lifespan by 7 months while 1 year of education adds 11 months to expected lifespan.Variability in human longevity is genetically influenced. Using genetic data of parental lifespan, the authors identify associations at HLA-DQA/DRB1 and LPA and find that genetic variants that increase educational attainment have a positive effect on lifespan whereas increasing BMI negatively affects lifespan.

MeSH Terms

  • Alleles
  • Body Mass Index
  • Coronary Disease
  • Education
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • HLA-DQ alpha-Chains
  • HLA-DRB1 Chains
  • Humans
  • Insulin Resistance
  • Life Style
  • Lipoprotein(a)
  • Lipoproteins, HDL
  • Longevity
  • Lung Neoplasms
  • Obesity
  • Polymorphism, Single Nucleotide
  • Smoking
  • Socioeconomic Factors


Association Between Mental Health Burden and Coronary Artery Disease in U.S. Women Veterans Over 45: A National Cross-Sectional Study.

The women Veteran population accessing Veterans Health Administration (VA) care has grown rapidly. Women Veterans exhibit high rates of mental health conditions that increase coronary artery disease (CAD) risk; however, the relationship between specific conditions and increasing mental health burden to CAD in this population is unknown. Using VA National Patient Care Data for 2009, we identified women Veterans over 45 (N = 157,195). Logistic regression models examined different mental health diagnoses and increasing mental health burden (number of diagnostic clusters) as predictors of CAD. CAD prevalence was 4.16%, and 36% of women Veterans were current smokers. Depression exhibited the strongest association with CAD (odds ratio [OR] 1.60, 95% confidence interval [CI] [1.50-1.71]), similar to that of current smoking (OR 1.68 [1.58-1.78]). Controlling for demographic variables, smoking, diabetes, and obesity, each additional mental health diagnosis increased the odds of CAD by 44%. Women Veterans over age 45 accessing VA care exhibited a high degree of mental health burden, which is associated with elevated odds of CAD; those with depression alone had 60% higher odds of CAD. For women Veterans using VA, mental health diagnoses may act as CAD risk factors that are potentially modifiable. Novel interventions in primary care and mental health are needed to address heart disease in this growing and aging population.

MeSH Terms

  • Aged
  • Aging
  • Anxiety
  • Coronary Artery Disease
  • Cross-Sectional Studies
  • Depression
  • Female
  • Humans
  • Mental Health
  • Middle Aged
  • Prevalence
  • United States
  • United States Department of Veterans Affairs
  • Veterans
  • Veterans Health

Keywords

  • aging
  • anxiety
  • coronary artery disease
  • depression
  • women Veterans


Internal carotid artery dissection among younger and older patients with acute ischemic stroke.

Purpose/Aim of the study: Carotid artery dissection (CAD) is a known causative factor in the etiology of acute ischemic stroke in young patients. However, the significance of CAD in older patients with acute ischemic stroke is unclear with only a few prior clinical studies. In order to isolate the influence of CAD as an independent factor, we performed multivariate analyses of common covariables in acute ischemic stroke patients in northern Israel. Three hundred and forty-seven consecutive patients who suffered from acute ischemic stroke had initial CT angiography (CTA) ordered from the emergency room. We reviewed the CTAs for radiologic signs of CAD, and recorded patients' demographic and clinical data from the hospital's computerized information system. Eighteen of the 347 patients (5.19%) had CTA evidence of CAD, with no statistically significant differences based on age, gender or ethnicity. A statistically significant inverse association between hypertension and a lower rate of CAD was found before and after stepwise logistic regression, while hyperlipidemia showed a trend toward a similar inverse association that was borderline for statistical significance. Our study shows that CAD is an independent and significant causative factor for acute ischemic stroke. Therefore, diagnostic imaging is indicated to rule out CAD not only in young patients, but rather in all patients with acute ischemic stroke. The inverse correlation between common vascular risk factors (i.e. hypertension and hyperlipidemia) and CAD points to CAD as an independent nonatherosclerotic causative factor in the etiology of acute ischemic stroke.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Brain Ischemia
  • Carotid Artery, Internal, Dissection
  • Female
  • Humans
  • Hypertension
  • Male
  • Middle Aged
  • Regression Analysis
  • Retrospective Studies
  • Risk Factors
  • Stroke

Keywords

  • Carotid dissection
  • Israel
  • stroke


In Vitro versus In Vivo Phase Instability of Zirconia-Toughened Alumina Femoral Heads: A Critical Comparative Assessment.

A clear discrepancy between predicted in vitro and actual in vivo surface phase stability of BIOLOX [i]delta[/i] zirconia-toughened alumina (ZTA) femoral heads has been demonstrated by several independent research groups. Data from retrievals challenge the validity of the standard method currently utilized in evaluating surface stability and raise a series of important questions: (1) Why do in vitro hydrothermal aging treatments conspicuously fail to model actual results from the in vivo environment? (2) What is the preponderant microscopic phenomenon triggering the accelerated transformation in vivo? (3) Ultimately, what revisions of the current in vitro standard are needed in order to obtain consistent predictions of ZTA transformation kinetics in vivo? Reported in this paper is a new in toto method for visualizing the surface stability of femoral heads. It is based on CAD-assisted Raman spectroscopy to quantitatively assess the phase transformation observed in ZTA retrievals. Using a series of independent analytical probes, an evaluation of the microscopic mechanisms responsible for the polymorphic transformation is also provided. An outline is given of the possible ways in which the current hydrothermal simulation standard for artificial joints can be improved in an attempt to reduce the gap between in vitro simulation and reality.


Keywords

  • Raman spectroscopy
  • ZTA
  • femoral head
  • hydrothermal aging
  • in vitro
  • in vivo


Conflicting relationship between age-dependent disorders, valvular heart disease and coronary artery disease by covariance structure analysis: Possible contribution of natriuretic peptide.

It is conceivable that contemporary valvular heart disease (VHD) is affected largely by an age-dependent atherosclerotic process, which is similar to that observed in coronary artery disease (CAD). However, a comorbid condition of VHD and CAD has not been precisely examined. The first objective of this study was to examine a possible comorbid condition. Provided that there is no comorbidity, the second objective was to search for the possible reasons by using conventional risk factors and plasma B-type natriuretic peptide (BNP) because BNP has a potentiality to suppress atherosclerotic development. The study population consisted of 3,457 patients consecutively admitted to our institution. The possible comorbid condition of VHD and CAD and the factors that influence the comorbidity were examined by covariance structure analysis and multivariate analysis. The distribution of the patients with VHD and those with CAD in the histograms showed that the incidence of VHD and the severity of CAD rose with seniority in appearance. The real statistical analysis was planned by covariance structure analysis. The current path model revealed that aging was associated with VHD and CAD severity (P < 0.001 for each); however, as a notable result, there was an inverse association regarding the comorbid condition between VHD and CAD (Correlation coefficient [β]: -0.121, P < 0.001). As the second objective, to clarify the factors leading to this inverse association, the contribution of conventional risk factors, such as age, gender, hypertension, smoking, diabetes, obesity and dyslipidemia, to VHD and CAD were examined by multivariate analysis. However, these factors did not exert an opposing effect on VHD and CAD, and the inverse association defied explanation. Since different pathological mechanisms may contribute to the formation of VHD and CAD, a differentially proposed path model using plasma BNP revealed that an increase in plasma BNP being drawn by VHD suppressed the progression of CAD (β: -0.465, P < 0.001). The incidence of VHD and CAD showed a significant conflicting relationship. This result supported the likely presence of unknown diverse mechanisms on top of the common cascade of atherosclerosis. Among them, the continuous elevation of plasma BNP due to VHD might be one of the explicable factors suppressing the progression of CAD.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Atherosclerosis
  • Coronary Artery Disease
  • Female
  • Heart Valve Diseases
  • Humans
  • Incidence
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Natriuretic Peptides


Age-related modulation of angiogenesis-regulating factors in the swine meniscus.

An in-depth knowledge of the native meniscus morphology and biomechanics in its different areas is essential to develop an engineered tissue. Meniscus is characterized by a great regional variation in extracellular matrix components and in vascularization. Then, the aim of this work was to characterize the expression of factors involved in angiogenesis in different areas during meniscus maturation in pigs. The menisci were removed from the knee joints of neonatal, young and adult pigs, and they were divided into the inner, intermediate and outer areas. Vascular characterization and meniscal maturation were evaluated by immunohistochemistry and Western blot analysis. In particular, expression of the angiogenic factor Vascular Endothelial Growth Factor (VEGF) and the anti-angiogenic marker Endostatin (ENDO) was analysed, as well as the vascular endothelial cadherin (Ve-CAD). In addition, expression of Collagen II (COLL II) and SOX9 was examined, as markers of the fibro-cartilaginous differentiation. Expression of VEGF and Ve-CAD had a similar pattern in all animals, with a significant increase from the inner to the outer part of the meniscus. Pooling the zones, expression of both proteins was significantly higher in the neonatal meniscus than in young and adult menisci. Conversely, the young meniscus revealed a significantly higher expression of ENDO compared to the neonatal and adult ones. Analysis of tissue maturation markers showed an increase in COLL II and a decrease in SOX9 expression with age. These preliminary data highlight some of the changes that occur in the swine meniscus during growth, in particular the ensemble of regulatory factors involved in angiogenesis.

MeSH Terms

  • Age Factors
  • Aging
  • Animals
  • Animals, Newborn
  • Antigens, CD
  • Cadherins
  • Chondrocytes
  • Collagen Type II
  • Endostatins
  • Extracellular Matrix
  • Female
  • Gene Expression Regulation, Developmental
  • Joints
  • Menisci, Tibial
  • Neovascularization, Physiologic
  • SOX9 Transcription Factor
  • Swine
  • Vascular Endothelial Growth Factor A

Keywords

  • Meniscus
  • VEGF
  • endostatin
  • micro-vasculature
  • pig
  • tissue maturation


Central adiposity and the overweight risk paradox in aging: follow-up of 130,473 UK Biobank participants.

For older groups, being overweight [body mass index (BMI; in kg/m ): 25 to <30] is reportedly associated with a lower or similar risk of mortality than being normal weight (BMI: 18.5 to <25). However, this "risk paradox" is partly explained by smoking and disease-associated weight loss. This paradox may also arise from BMI failing to measure fat redistribution to a centralized position in later life. This study aimed to estimate associations between combined measurements of BMI and waist-to-hip ratio (WHR) with mortality and incident coronary artery disease (CAD). This study followed 130,473 UK Biobank participants aged 60-69 y (baseline 2006-2010) for ≤8.3 y ([i]n[/i] = 2974 deaths). Current smokers and individuals with recent or disease-associated (e.g., from dementia, heart failure, or cancer) weight loss were excluded, yielding a "healthier agers" group. Survival models were adjusted for age, sex, alcohol intake, smoking history, and educational attainment. Population and sex-specific lower and higher WHR tertiles were <0.91 and ≥0.96 for men and <0.79 and ≥0.85 for women, respectively. Ignoring WHR, the risk of mortality for overweight subjects was similar to that for normal-weight subjects (HR: 1.09; 95% CI: 0.99, 1.19; [i]P[/i] = 0.066). However, among normal-weight subjects, mortality increased for those with a higher WHR (HR: 1.33; 95% CI: 1.08, 1.65) compared with a lower WHR. Being overweight with a higher WHR was associated with substantial excess mortality (HR: 1.41; 95% CI: 1.25, 1.61) and greatly increased CAD incidence (sub-HR: 1.64; 95% CI: 1.39, 1.93) compared with being normal weight with a lower WHR. There was no interaction between physical activity and BMI plus WHR groups with respect to mortality. For healthier agers (i.e., nonsmokers without disease-associated weight loss), having central adiposity and a BMI corresponding to normal weight or overweight is associated with substantial excess mortality. The claimed BMI-defined overweight risk paradox may result in part from failing to account for central adiposity, rather than reflecting a protective physiologic effect of higher body-fat content in later life.

MeSH Terms

  • Adipose Tissue
  • Adiposity
  • Aged
  • Aging
  • Biological Specimen Banks
  • Body Mass Index
  • Coronary Artery Disease
  • Female
  • Humans
  • Male
  • Middle Aged
  • Obesity
  • Obesity, Abdominal
  • Overweight
  • Risk Factors
  • Smoking
  • United Kingdom
  • Waist-Hip Ratio

Keywords

  • UK Biobank
  • adiposity
  • aging
  • body mass index
  • coronary artery disease
  • mortality
  • older persons
  • overweight
  • waist-hip ratio


Heart Rate Fragmentation: A New Approach to the Analysis of Cardiac Interbeat Interval Dynamics.

Short-term heart rate variability (HRV) is most commonly attributed to physiologic vagal tone modulation. However, with aging and cardiovascular disease, the emergence of high short-term HRV, consistent with the breakdown of the neuroautonomic-electrophysiologic control system, may confound traditional HRV analysis. An apparent dynamical signature of such anomalous short-term HRV is frequent changes in heart rate acceleration sign, defined here as heart rate fragmentation. The aims were to: (1) introduce a set of metrics designed to probe the degree of sinus rhythm fragmentation; (2) test the hypothesis that the degree of fragmentation of heartbeat time series increases with the participants' age in a group of healthy subjects; (3) test the hypothesis that the heartbeat time series from patients with advanced coronary artery disease (CAD) are more fragmented than those from healthy subjects; and (4) compare the performance of the new fragmentation metrics with standard time and frequency domain measures of short-term HRV. We analyzed annotated, open-access Holter recordings (University of Rochester Holter Warehouse) from healthy subjects and patients with CAD using these newly introduced metrics of heart rate fragmentation, as well as standard time and frequency domain indices of short-term HRV, detrended fluctuation analysis and sample entropy. The degree of fragmentation of cardiac interbeat interval time series increased significantly as a function of age in the healthy population as well as in patients with CAD. Fragmentation was higher for the patients with CAD than the healthy subjects. Heart rate fragmentation metrics outperformed traditional short-term HRV indices, as well as two widely used nonlinear measures, sample entropy and detrended fluctuation analysis short-term exponent, in distinguishing healthy subjects and patients with CAD. The same level of discrimination was obtained from the analysis of normal-to-normal sinus (NN) and cardiac interbeat interval (RR) time series. The fragmentation framework and accompanying metrics introduced here constitute a new way of assessing short-term HRV under free-running conditions, one which appears to overcome salient limitations of traditional HRV analysis. Fragmentation of sinus rhythm cadence may provide new dynamical biomarkers for probing the integrity of the neuroautonomic-electrophysiologic network controlling the heartbeat in health and disease.


Keywords

  • aging
  • coronary artery disease
  • fragmentation index
  • heart rate variability
  • vagal tone


[Studying of the factors influencing biological age of long-livers of Almaty].

The article presents the results of a study of centenarians (25 patients older than 90 years) residents of Almaty, suffering from coronary artery disease (CAD) of different severity, for the purpose of definition of biological age of CAD and identify factors influencing aging process. Significant positive correlation between the thickness of an intragastric partition and indexes of chronological age, due biological age was defined. We assume that the hypertrophy of walls of a left ventricle (LV) is the main morphological indicator of an aging of cardiovascular system.

MeSH Terms

  • Age Factors
  • Aged, 80 and over
  • Aging
  • Coronary Artery Disease
  • Heart Ventricles
  • Humans
  • Hypertrophy
  • Kazakhstan

Keywords

  • biological age
  • chronological age
  • echocardiography
  • thickness of an interventricular partition


Management and risk factor control of coronary artery disease in elderly versus nonelderly: a multicenter registry.

Coronary artery disease (CAD) is a leading cause of death in elderly because aging is the important non-modifiable risk factors of atherosclerosis and also a predictor of poor outcomes. Underuse of guideline directed therapy may contribute to suboptimal risk factor control and worse outcomes in the elderly. We aimed to explore the management of CAD, risk factors control as well as goal attainment in elderly compared to nonelderly CAD patients. The CORE-Thailand is an ongoing multicenter, prospective, observational registry of patients with high atherosclerotic risk in Thailand. The data of 4120 CAD patients enrolled in this cohort was analyzed comparing between the elderly (age ≥ 65 years) [i]vs.[/i] nonelderly (age < 65 years). There were 2172 elderly and 1948 nonelderly patients. The elderly CAD patients had higher prevalence of hypertension, dyslipidemia, atrial fibrillation and chronic kidney disease. The proportion of patients who received coronary revascularization was not different between the elderly and nonelderly CAD patients. Antiplatelets were prescribed less in the elderly while statin was prescribed in the similar proportion. Goal attainments of risk factor control of glycemic control, low density lipoprotein cholesterol, and smoking cessation except the blood pressure goal were higher in the elderly CAD patients. The CORE-Thailand registry showed the equity in the treatment of CAD between elderly and non-elderly. Elderly CAD patients had higher rate of goal attainment in risk factor control except blood pressure goal. The effects of goal attainment on cardiovascular outcomes will be demonstrated from ongoing cohort.


Keywords

  • Aging
  • Coronary artery disease
  • Goal attainment
  • Inequity
  • The elderly


Identification of the main determinants of abdominal aorta size: a screening by Pocket Size Imaging Device.

Ultrasound exam as a screening test for abdominal aorta (AA) can visualize the aorta in 99% of patients and has a sensitivity and specificity approaching 100% in screening settings for aortic aneurysm. Pocket Size Imaging Device (PSID) has a potential value as a screening tool, because of its possible use in several clinical settings. Our aim was to assess the impact of demographics and cardiovascular (CV) risk factors on AA size by using PSID in an outpatient screening. Consecutive patients, referring for a CV assessment in a 6 months period, were screened. AA was visualized by subcostal view in longitudinal and transverse plans in order to determine the greatest anterior-posterior diameter. After excluding 5 patients with AA aneurysm, 508 outpatients were enrolled. All patients underwent a sequential assessment including clinical history with collection of CV risk factors, physical examination, PSID exam and standard Doppler echoc exam using a 2.5 transducer with harmonic capability, both by expert ultrasound operators, during the same morning. Standard echocardiography operators were blinded on PSID exam and viceversa. Diagnostic accuracy of AA size by PSID was tested successfully with standard echo machine in a subgroup (n = 102) (rho = 0.966, p < 0.0001). AA diameter was larger in men than in women and in ≥50 -years old subjects than in those <50 -years old (both p < 0.0001). AA was larger in patients with coronary artery disease (CAD) (p < 0.0001). By a multivariate model, male sex (p < 0.0001), age and body mass index (both p < 0.0001), CAD (p < 0.01) and heart rate (p = 0.018) were independent predictors of AA size (cumulative R  = 0.184, p < 0.0001). PSID is a reliable tool for the screening of determinants of AA size. AA diameter is greater in men and strongly influenced by aging and overweight. CAD may be also associated to increased AA diameter.

MeSH Terms

  • Aorta, Abdominal
  • Aortic Aneurysm, Abdominal
  • Echocardiography, Doppler
  • Equipment Design
  • Feasibility Studies
  • Female
  • Humans
  • Male
  • Middle Aged
  • Miniaturization
  • Reproducibility of Results

Keywords

  • Abdominal aorta
  • Aging
  • Cardiovascular risk factors
  • Coronary artery disease
  • Pocket size imaging device
  • Ultrasound


Transition in the mechanism of flow-mediated dilation with aging and development of coronary artery disease.

In microvessels of patients with coronary artery disease (CAD), flow-mediated dilation (FMD) is largely dependent upon the endothelium-derived hyperpolarizing factor H O . The goal of this study is to examine the influence of age and presence or absence of disease on the mechanism of FMD. Human coronary or adipose arterioles (~150 µm diameter) were prepared for videomicroscopy. The effect of inhibiting COX [indomethacin (Indo) or NOS (L-NAME), eliminating H O (polyethylene glycol-catalase (PEG-CAT)] or targeting a reduction in mitochondrial ROS with scavengers/inhibitors [Vitamin E ( Vitamin E); phenylboronic acid ( PBA)] was determined in children aged 0-18 years; young adults 19-55 years; older adults >55 years without CAD, and similarly aged adults with CAD. Indo eliminated FMD in children and reduced FMD in younger adults. This response was mediated mainly by PGI , as the prostacyclin-synthase-inhibitor trans-2-phenyl cyclopropylamine reduced FMD in children and young adults. L-NAME attenuated dilation in children and younger adults and eliminated FMD in older adults without CAD, but had no effect on vessels from those with CAD, where mitochondria-derived H O was the primary mediator. The magnitude of dilation was reduced in older compared to younger adults independent of CAD. Exogenous treatment with a sub-dilator dose of NO blocked FMD in vessels from subjects with CAD, while prolonged inhibition of NOS in young adults resulted in a phenotype similar to that observed in disease. The mediator of coronary arteriolar FMD evolves throughout life from prostacyclin in youth, to NO in adulthood. With the onset of CAD, NO-inhibitable release of H O emerges as the exclusive mediator of FMD. These findings have implications for use of pharmacological agents, such as nonsteroidal anti-inflammatory agents in children and the role of microvascular endothelium in cardiovascular health.

MeSH Terms

  • Adolescent
  • Adult
  • Aging
  • Blotting, Western
  • Child
  • Child, Preschool
  • Coronary Artery Disease
  • Coronary Vessels
  • Female
  • Humans
  • Immunohistochemistry
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Reactive Oxygen Species
  • Vasodilation
  • Young Adult

Keywords

  • Coronary artery disease
  • Flow-mediated dilation
  • Microvasculature
  • Vasodilation


Longevity-Associated FOXO3 Genotype and its Impact on Coronary Artery Disease Mortality in Japanese, Whites, and Blacks: A Prospective Study of Three American Populations.

We recently reported that protection against coronary artery disease (CAD) mortality is the major contributor to longer life associated with FOXO3 genotype. The present study examined this relation in more detail. We performed a 15-year observational study of 3,584 older American men of Japanese ancestry from the Kuakini Honolulu Heart Program cohort and 1,595 White and 1,067 Black elderly individuals from the Health Aging and Body Composition study. Multivariate Cox regression models demonstrated that carriage of the longevity-associated G allele of FOXO3 single nucleotide polymorphisms rs2802292 was a protective factor against CAD mortality in all three populations. In Japanese and Whites, but not in Blacks, the protective effect of the G allele was little changed in models adjusted for other major risk factors. Population-attributable risk (PAR) models found that the nonprotective TT genotype contributed 15%, 9%, and 3% to CAD mortality risk in Japanese, White, and Black Americans, respectively, and was one of the top three contributing factors to CAD mortality. In Japanese, this effect size was comparable with hypertension (15%), but in Whites and Blacks PAR for hypertension was higher (29% and 26%, respectively). G-allele carriers had lower plasma TNF-α than noncarriers, suggesting inflammation as a potential mediating factor for CAD mortality risk. FOXO3 genotype is an important risk factor for CAD mortality in older populations. More research is needed to identify potential mechanisms and targets for intervention.

MeSH Terms

  • African Americans
  • Aged
  • Aged, 80 and over
  • Asian Americans
  • Coronary Artery Disease
  • European Continental Ancestry Group
  • Forkhead Box Protein O3
  • Genotype
  • Humans
  • Japan
  • Longevity
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Prospective Studies
  • Risk Factors
  • United States

Keywords

  • Coronary artery disease
  • Genetic
  • Inflammation
  • Longevity
  • Mortality


Effects of aging and coronary artery disease on sympathetic neural recruitment strategies during end-inspiratory and end-expiratory apnea.

In response to acute physiological stress, the sympathetic nervous system modifies neural outflow through increased firing frequency of lower-threshold axons, recruitment of latent subpopulations of higher-threshold axons, and/or acute modifications of synaptic delays. Aging and coronary artery disease (CAD) often modify efferent muscle sympathetic nerve activity (MSNA). Therefore, we investigated whether CAD (n = 14; 61 ± 10 yr) and/or healthy aging without CAD (OH; n = 14; 59 ± 9 yr) modified these recruitment strategies that normally are observed in young healthy (YH; n = 14; 25 ± 3 yr) individuals. MSNA (microneurography) was measured at baseline and during maximal voluntary end-inspiratory (EI) and end-expiratory (EE) apneas. Action potential (AP) patterns were studied using a novel AP analysis technique. AP frequency increased in all groups during both EI- and EE-apnea (all P < 0.05). The mean AP content per integrated burst increased during EI- and EE-apnea in YH (EI: Δ6 ± 4 APs/burst; EE: Δ10 ± 6 APs/burst; both P < 0.01) and OH (EI: Δ3 ± 3 APs/burst; EE: Δ4 ± 5 APs/burst; both P < 0.01), but not in CAD (EI: Δ1 ± 3 APs/burst; EE: Δ2 ± 3 APs/burst; both P = NS). When APs were binned into "clusters" according to peak-to-peak amplitude, total clusters increased during EI- and EE-apnea in YH (EI: Δ5 ± 2; EE: Δ6 ± 4; both P < 0.01), during EI-apnea only in OH (EI: Δ1 ± 2; P < 0.01; EE: Δ1 ± 2; P = NS), and neither apnea in CAD (EI: Δ -2 ± 2; EE: Δ -1 ± 2; both P = NS). In all groups, the AP cluster size-latency profile was shifted downwards for every corresponding cluster during EI- and EE-apnea (all P < 0.01). As such, inherent dysregulation exists within the central features of apnea-related sympathetic outflow in aging and CAD.

MeSH Terms

  • Action Potentials
  • Adult
  • Age Factors
  • Aged
  • Aging
  • Apnea
  • Arterial Pressure
  • Blood Pressure
  • Breath Holding
  • Cardiac Output
  • Case-Control Studies
  • Coronary Artery Disease
  • Efferent Pathways
  • Exhalation
  • Female
  • Humans
  • Inhalation
  • Male
  • Middle Aged
  • Muscle, Skeletal
  • Plethysmography
  • Stroke Volume
  • Sympathetic Nervous System
  • Vascular Resistance
  • Young Adult

Keywords

  • aging
  • apnea
  • coronary artery disease
  • sympathetic nervous system
  • sympathetic neural recruitment patterns


Impact of Age on the Functional Significance of Intermediate Epicardial Artery Disease.

The functional significance of an intermediate coronary lesion is crucial for determining the treatment strategy, but age-related changes in cardiovascular function could affect the functional significance of an epicardial stenosis. The aim of this study was therefore to investigate the impact of age on fractional flow reserve (FFR) measurements in patients with intermediate coronary artery disease (CAD). Intracoronary pressure measurements and intravascular ultrasound (IVUS) were performed in 178 left anterior descending coronary arteries with intermediate stenosis. The morphological characteristics and FFR of 91 lesions in patients <65 years old were compared with those of 87 patients ≥65 years old. There was no difference in lesion location, diameter stenosis, minimum lumen area, plaque burden, or lesion length between the 2 age groups. Elderly patients had higher FFR (0.81±0.06 vs. 0.79±0.06, P=0.004) and lower ∆FFR, defined as the difference between resting Pd/Pa and FFR (0.13±0.05 vs. 0.15±0.05, P=0.014). Age, along with the location and degree of stenosis, was independently associated with FFR and ∆FFR (β=0.162, P=0.008; β=-0.131, P=0.043, respectively). Elderly patients with intermediate CAD are more likely to have higher FFR and lower ∆FFR, despite a similar degree of epicardial stenosis, compared with younger patients. (Circ J 2016; 80: 1583-1589).

MeSH Terms

  • Age Factors
  • Aged
  • Aging
  • Coronary Artery Disease
  • Female
  • Humans
  • Male
  • Middle Aged
  • Pericardium


N-carboxymethyllysine as a biomarker for coronary artery disease and age-related macular degeneration.

An association between coronary artery disease (CAD) and age-related macular degeneration (ARMD) has long been postulated, but exact mechanisms remain unclear. The global prevalence of CAD and ARMD increases and early biomarkers for early diagnosis of these diseases are necessary. The aim of this study was to investigate the plasma level of oxidative stress biomarker CML in patients with and without angiographic findings of atherosclerosis in the coronary arteries (CADath and CADath-, respectively) and to assess if there was an association of CAD with ARMD. The study enrolled 233 subjects. Based on cardiologic and ophthalmologic examinations, the patients were divided into four subgroups: CADath ARMD , CADath ARMD-, CADath-ARMD , and CADath-ARMD-. The enzyme-linked immunosorbent assay was used for the measurement of plasma CML levels. Serum lipid levels were determined by an automatic analyzer using conventional enzymatic methods. CADath patients had higher CML concentration compared to CADath- subjects (1.04±0.6 vs. 0.83±0.4ng/mL, P<0.001). The highest mean CML level (1.12±0.7ng/mL) was found in CADath ARMD patients. The mean plasma CML concentration was higher in subjects with any of the analyzed diseases compared to CADath-ARMD- subjects. A significant positive association of CADath (OR=2.50, 95% CI 1.60-3.90, P=0.0001), ARMD (OR=2.08, 95% CI 1.40-3.11, P=0.0001) and both analyzed diseases (OR=4.67, 95% CI 2.29-9.53, P=0.0001) with an increased level of plasma CML in a logistic regression model adjusting by age was identified. The level of CML, an oxidative stress biomarker, reflects the presence of atherosclerosis in coronary arteries and shows a possible link between ARMD and CADath via oxidative status.

MeSH Terms

  • Aged
  • Aging
  • Biomarkers
  • Body Mass Index
  • Case-Control Studies
  • Coronary Angiography
  • Coronary Artery Disease
  • Early Diagnosis
  • Enzyme-Linked Immunosorbent Assay
  • Female
  • Humans
  • Lipoproteins
  • Lysine
  • Macular Degeneration
  • Male
  • Middle Aged
  • Oxidative Stress
  • Prevalence
  • Risk Factors

Keywords

  • Age-related macular degeneration
  • Coronary artery disease
  • N-carboxymethyllysine


Selecting for neurogenic potential as an alternative for Alzheimer's disease drug discovery.

Neurons die in Alzheimer's disease (AD) and are not effectively replaced. An alternative approach to maintain nerve cell number is to identify compounds that stimulate the proliferation of endogenous neural stem cells in old individuals to replace lost neurons. However, unless a neurogenic drug is also neuroprotective, the replacement of lost neurons will not be sufficient to stop disease progression. The neuroprotective AD drug candidate J147 is shown to enhance memory, improve dendritic structure, and stimulate cell division in germinal regions of the brains of very old mice. Based on the potential neurogenic potential of J147, a neuronal stem cell screening assay was developed to optimize derivatives of J147 for human neurogenesis. The best derivative of J147, CAD-031, maintains the neuroprotective and memory enhancing properties of J147, yet is more active in the human neural stem cell assays. The combined properties of neuroprotection, neurogenesis, and memory enhancement in a single drug are more likely to be effective for the treatment of age-associated neurodegenerative disorders than any individual activity alone.

MeSH Terms

  • Alzheimer Disease
  • Amyloid beta-Protein Precursor
  • Animals
  • Cell Differentiation
  • Cells, Cultured
  • Curcumin
  • Disease Models, Animal
  • Drug Discovery
  • Embryonic Stem Cells
  • Female
  • Fibroblast Growth Factor 2
  • Gene Expression Regulation
  • Humans
  • Male
  • Memory Disorders
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Nerve Tissue Proteins
  • Neurons
  • Neuroprotective Agents
  • Presenilin-1

Keywords

  • Aging
  • Alzheimer's disease
  • J147
  • Memory enhancement
  • Neurodegenerative disease
  • Neurogenesis
  • Neuroprotection
  • Stem cells


The Prognostic Value of Percentage Total Plaque Score Adjusted to Age.

Total plaque score (TPS) on coronary computed tomography angiography (CCTA) has been validated as a surrogate measure of coronary artery disease (CAD) burden and is prognostic. We propose a novel measure, percentage TPS adjusted to age (%TPS/age), that may reflect vascular age and potentially more rapidly progressive atherosclerosis and evaluate its potential prognostic value. %TPS/age was calculated for consecutive patients prospectively enrolled into our institutional CCTA registry and evaluated for primary composite outcome of cardiac death, nonfatal myocardial infarction, and late revascularization. Of 1896 patients identified (mean age 57.7 ± 11.4 years, 50.1% male, median follow-up 18.6 months [interquartile range: 15.3, 32.4]), 552 (29%) had %TPS/age = 0 (no atherosclerosis), with 1 (0.2%) primary outcome observed (annual event rate [AER] = 0.1%). Two events (0.4%, AER = 0.3%) were observed in %TPS/age < 0.314 category, 22 (5.0%, AER = 2.2%) in %TPS/age 0.314 to 0.699 category, and 54 (12.0%, AER = 5.7%) in %TPS/age ≥ 0.700 category. After adjusting for clinical predictors and obstructive CAD, higher %TPS/age category was associated with hazard ratio 1.95 (1.31-2.88, P < .001) for primary outcome on multivariable analysis, Harrell-C-Statistic 0.87 (confidence interval 95%: 0.84-0.90), and net reclassification improvement of 0.71 ( P < .001). %TPS/Age has incremental prognostic value to traditional risk factors and CCTA measures of CAD and improves evaluation of burden of coronary atherosclerosis and clinical risk.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Computed Tomography Angiography
  • Coronary Angiography
  • Coronary Artery Disease
  • Female
  • Follow-Up Studies
  • Humans
  • Male
  • Middle Aged
  • Plaque, Atherosclerotic
  • Prognosis

Keywords

  • atherosclerosis
  • cardiac CT
  • prognosis
  • total plaque score
  • vascular age


WHO guidelines for a healthy diet and mortality from cardiovascular disease in European and American elderly: the CHANCES project.

Cardiovascular disease (CVD) represents a leading cause of mortality worldwide, especially in the elderly. Lowering the number of CVD deaths requires preventive strategies targeted on the elderly. The objective was to generate evidence on the association between WHO dietary recommendations and mortality from CVD, coronary artery disease (CAD), and stroke in the elderly aged ≥60 y. We analyzed data from 10 prospective cohort studies from Europe and the United States comprising a total sample of 281,874 men and women free from chronic diseases at baseline. Components of the Healthy Diet Indicator (HDI) included saturated fatty acids, polyunsaturated fatty acids, mono- and disaccharides, protein, cholesterol, dietary fiber, and fruit and vegetables. Cohort-specific HRs adjusted for sex, education, smoking, physical activity, and energy and alcohol intakes were pooled by using a random-effects model. During 3,322,768 person-years of follow-up, 12,492 people died of CVD. An increase of 10 HDI points (complete adherence to an additional WHO guideline) was, on average, not associated with CVD mortality (HR: 0.94; 95% CI: 0.86, 1.03), CAD mortality (HR: 0.99; 95% CI: 0.85, 1.14), or stroke mortality (HR: 0.95; 95% CI: 0.88, 1.03). However, after stratification of the data by geographic region, adherence to the HDI was associated with reduced CVD mortality in the southern European cohorts (HR: 0.87; 95% CI: 0.79, 0.96; I(2) = 0%) and in the US cohort (HR: 0.85; 95% CI: 0.83, 0.87; I(2) = not applicable). Overall, greater adherence to the WHO dietary guidelines was not significantly associated with CVD mortality, but the results varied across regions. Clear inverse associations were observed in elderly populations in southern Europe and the United States.

MeSH Terms

  • Aged
  • Cardiovascular Diseases
  • Cholesterol, Dietary
  • Chronic Disease
  • Diet
  • Dietary Carbohydrates
  • Dietary Fiber
  • Dietary Proteins
  • Ethnic Groups
  • Europe
  • Fatty Acids
  • Fatty Acids, Unsaturated
  • Female
  • Fruit
  • Humans
  • Male
  • Meta-Analysis as Topic
  • Middle Aged
  • Nutrition Assessment
  • Nutrition Policy
  • Patient Compliance
  • Prospective Studies
  • United States
  • Vegetables
  • World Health Organization

Keywords

  • CHANCES
  • aging
  • cardiovascular disease
  • cohort
  • meta-analysis


Major adverse cardiac events in elderly patients with coronary artery disease undergoing noncardiac surgery: A multicenter prospective study in China.

Major adverse cardiac events (MACEs) are important causes of perioperative morbidity and mortality for elderly patients undergoing non-cardiac surgery. Treatment and control rates for coronary artery disease (CAD) in Chinese patients are poorer than rates in western countries. However, no previous prospective study has focused on perioperative MACE in this population. Our aim was to ascertain the incidence and risk factors associated with MACEs in Chinese patients. Consecutive CAD patients, aged ≥60 years, who underwent non-cardiac surgery at five medical centers in China, were prospectively enrolled. Clinical variables, including electrocardiogram and troponin I levels, were evaluated to estimate MACEs. The main outcome was occurrence of at least one perioperative MACE from admittance to 30 days after surgery, defined as any of the following complications: cardiac death, nonfatal cardiac arrest, acute myocardial infarction (MI), congestive heart failure (CHF), and angina. MACE independent risk factors were based on the Andersen-Gill multiplicative intensity model. Of the 1422 patients recruited, 129 (9.1%) developed at least one MACE, and cardiac death occurred in 11 patients (0.8%). The independent risk factors contributing to postoperative MACE included age ≥75 years, female gender, history of MI, history of hypertension, high-risk surgery, intraoperative hypotension, and intraoperative hypoxemia. The incidence of MACE in Chinese elderly patients with CAD who underwent non-cardiac surgery was 9.1%. Seven independent risk factors for a perioperative MACE were identified. Preventing intraoperative hypoxemia and hypotension may reduce the occurrence of MACE in these high risk patients.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Angina Pectoris
  • China
  • Coronary Artery Disease
  • Elective Surgical Procedures
  • Electrocardiography
  • Female
  • Heart Failure
  • Humans
  • Incidence
  • Male
  • Morbidity
  • Postoperative Complications
  • Postoperative Period
  • Prospective Studies
  • Risk Factors
  • Treatment Outcome

Keywords

  • Aging
  • Coronary artery disease
  • Major adverse cardiac events (MACE)
  • Morbidity
  • Risk factors
  • Surgery


Disease complexity in acute coronary syndrome is related to the patient's immunological status.

Our aim was to investigate whether patients with acute coronary syndrome (ACS) display an overall T cell immunosenescence that could be contributing to worsening the stage of the disease. We compared the immunological status of 52 ACS patients, 21 controls with absence of coronary artery disease (CAD) (C1), and 50 healthy individuals (C2). We characterized leukocyte and T lymphocyte subpopulations by flow cytometry. CAD was classified according to SYNTAX score, number of diseased coronary vessels, previous episodes of ACS and left ventricular ejection fraction (LVEF). ACS patients showed an increased number of total leukocytes, neutrophils and monocytes (p < 0.001), but a decreased number of lymphocytes (p < 0.05). ACS patients had significantly higher levels of NK cells and CD8 T-cells (p < 0.05). ACS was associated with high differentiation in CD4 and CD8 T-lymphocytes. Frequencies of naïve, naïve CD31 , EM1, and pE1 subsets were significantly reduced in ACS patients (p < 0.05), while EM3, EM4 (in CD4 ), and E (in CD8 ) subsets were increased (p < 0.05). Aging of T-lymphocyte subpopulations was associated with a worse SYNTAX score (p < 0.05), and aging of CD4 T-lymphocytes with a larger number of affected vessels, larger number of previous ACS episodes and lower LVEF, in ACS patients (p > 0.05). Furthermore, the proliferation ability of CD4 and CD8 T-lymphocytes was significantly impaired in ACS patients (p < 0.05), although they had increased activation (p < 0.05). We conclude that ACS patients show a higher degree of T-lymphocyte immunosenescence than healthy controls, which could contribute to disease impairment through a compromised adaptive immune response.

MeSH Terms

  • Acute Coronary Syndrome
  • Adaptive Immunity
  • Aged
  • Analysis of Variance
  • Biomarkers
  • CD4-Positive T-Lymphocytes
  • Case-Control Studies
  • Coronary Angiography
  • Female
  • Humans
  • Immunosenescence
  • Killer Cells, Natural
  • Male
  • Middle Aged
  • Observer Variation
  • Prognosis
  • Reference Values
  • Severity of Illness Index
  • Statistics, Nonparametric
  • T-Lymphocytes, Regulatory

Keywords

  • Acute coronary syndrome
  • Differentiation
  • Immunosenescence
  • Inflammation
  • T-lymphocytes


Telomere length and outcomes in ischaemic heart failure: data from the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA).

Leucocyte telomere length is considered a marker of biological ageing and has been suggested to be shorter in patients with CAD and heart failure compared with healthy controls. The aim of this study was to determine whether telomere length is associated with clinical outcomes in patients with ischaemic heart failure and whether this association is superior to chronological age as defined by date of birth. We measured leucocyte telomere length in 3275 patients with chronic ischaemic systolic heart failure participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) study. The primary composite endpoint was cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, which occurred in 575 patients during follow-up. We observed a significant association of leucocyte telomere lengths with the primary endpoint (hazard ratio 1.10; 95% confidence interval 1.01-1.20; P=0.03). However, this observation was not superior to age as defined by date of birth. The neutral effect of rosuvastatin treatment on clinical outcomes was not modified by baseline telomere length. Biological age as defined by leucocyte telomere length was associated with clinical outcomes in patients with ischaemic heart failure, but this association did not add prognostic information above age as defined by date of birth.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Biomarkers
  • Double-Blind Method
  • Female
  • Heart Failure
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Leukocytes
  • Male
  • Myocardial Ischemia
  • Retrospective Studies
  • Rosuvastatin Calcium
  • Telomere

Keywords

  • Ageing
  • Healthy ageing
  • Heart failure
  • Leucocyte telomere length


Low serum tryptophan predicts higher mortality in cardiovascular disease.

The essential amino acid tryptophan is required for protein synthesis and formation of the neurotransmitter serotonin and may exert immunoregulatory functions. An accelerated tryptophan breakdown rate is associated with inflammation and immune activation. Serum concentrations of free tryptophan, neopterin and high-sensitivity C-reactive protein (hsCRP) were measured in 1196 patients with coronary artery disease (CAD) derived from the LUdwigshafen RIsk and Cardiovascular Health (LURIC) study. Tryptophan concentrations did not differ between patients with (mean ± SD: 40.1 ± 9.8 μM) or without (42.3 ± 23.9 μM; not significant, Welch's test) angiographic CAD, but patients with CAD had higher neopterin (9.1 ± 8.2 nM) and hsCRP (9.3 ± 18.5 mg/L) concentrations compared to patients without (neopterin: 7.6 ± 4.7 nM, hsCRP: 5.8 ± 7.6 mg/L; both P < 0.0001). There existed an inverse correlation between serum tryptophan and neopterin (Spearman's rank correlation: rs = -0.273) and hsCRP (rs = -0.163; both P < 0.0001) concentrations. Median observation time was 10.5 years, and 385 patients had died, including 244 patients due to cardiovascular and 132 due to noncardiovascular causes. After adjustments for cardiovascular risk factors and other possible confounders, the hazard ratio (with 95% CI) in the first tryptophan quartile of the study population was 1.51 (1.19-1.90; P = 0.0006) for total mortality, 1.41 (1.05-1.89; P = 0.0224) for cardiovascular and 1.79 (1.20-2.67; P = 0.0042) for noncardiovascular mortalities, respectively, thus indicating a significantly higher risk of death in patients with tryptophan concentrations < 34 μM. Low serum tryptophan in patients with CAD is associated with immune activation and indicates reduced life expectancy.

MeSH Terms

  • Adolescent
  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • C-Reactive Protein
  • Cardiovascular Diseases
  • Case-Control Studies
  • Female
  • Humans
  • Immunity
  • Indoleamine-Pyrrole 2,3,-Dioxygenase
  • Life Expectancy
  • Male
  • Middle Aged
  • Neopterin
  • Survival Analysis
  • Tryptophan
  • Young Adult

Keywords

  • C-reactive protein
  • Coronary artery disease
  • neopterin
  • tryptophan


Impact of age on mean platelet volume and its relationship with coronary artery disease: a single-centre cohort study.

Elderly patients represent a high risk category among subjects with atherosclerosis, due to the presence of comorbidities and suboptimal response to antiplatelet drugs. Mean platelet volume (MPV) has been indicated as a marker of platelet reactivity, with contrasting data on its role on coronary artery disease. Aim of the present study was to evaluate the impact of age on the MPV and its role on the extent of coronary artery disease (CAD). Our population is represented by a cohort of 3750 patients undergoing coronary angiography. Elderly were defined according to age ≥ 75 years. MPV was measured at admission. Significant coronary artery disease was defined as a stenosis >50% in at least 1 coronary vessel, while severe CAD was defined as left main and/or three-vessel disease. A total of 1170 out of 3750 (31.2%) patients were ≥ 75 years old. Advanced age was associated with female gender (p<0.001), hypertension (p<0.001), renal failure (p<0.001), previous myocardial infarction (p=0.03) coronary artery bypass grafting (p<0.001) indication to angiography (p<0.001), therapy with angiotension-receptor blockers, (p=0.003), nitrates, diuretics and calcium-antagonists (p<0.001), serum creatinine (p<0.001), fibrinogen (p<0.001) and C reactive protein (p=0.02), but inversely to percutaneous coronary interventions (p=0.02), dyslipidemia, family history of CAD and smoking (p<0.001, respectively), use of statins (p=0.02) and beta blockers (p=0.003), haemoglobin, total cholesterol and triglycerides (p<0.001, respectively), white blood cells (p=0.009) and platelet count (p=0.006). Elderly patients displayed a significantly larger platelet volume (p<0.001), with a direct linear relationship between age and the MPV (r=0.08, p<0.001), with age being confirmed as an independent predictor of larger MPV (≥10.85fl) at multivariate analysis (adjusted OR [95% CI]=1.18 [1.01-1.40], p=0.04). Among the elderly, MPV value above the median (≥10.85fl) was not associated with a higher prevalence of coronary artery disease (77.3 vs. 79.4%, p=0.39, adjusted OR [95% CI]=0.94 [0.66-1.33], p=0.71), or higher prevalence of severe CAD (35.2 vs. 32.4%, p=0.28, adjusted OR [95% CI]=1.34 [0.99-1.82], p=0.06). Advanced age was directly associated with larger mean platelet volume that, however, did not contribute to explain the higher prevalence and extent of coronary artery disease observed in elderly patients.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Aging
  • Cohort Studies
  • Coronary Angiography
  • Coronary Artery Disease
  • Female
  • Humans
  • Male
  • Mean Platelet Volume
  • Middle Aged
  • Platelet Count

Keywords

  • Ageing
  • Coronary angiography
  • Coronary artery disease
  • Platelet
  • Size


Benefits of exercise training and the correlation between aerobic capacity and functional outcomes and quality of life in elderly patients with coronary artery disease.

Cardiopulmonary exercise training is beneficial to people with coronary artery disease (CAD). Nevertheless, the correlation between aerobic capacity, and functional mobility and quality of life in elderly CAD patients is less addressed. The purpose of the current study is to investigate the beneficial effects of exercise training in elderly people with CAD, integrating exercise stress testing, functional mobility, handgrip strength, and health-related quality of life. Elderly people with CAD were enrolled from the outpatient clinic of a cardiac rehabilitation unit in a medical center. Participants were assigned to the exercise training group (N = 21) or the usual care group (N = 15). A total of 36 sessions of exercise training, completed in 12 weeks, was prescribed. Echocardiography, exercise stress testing, the 6-minute walking test, Timed Up and Go test, and handgrip strength testing were performed, and the Short-Form 36 questionnaire (SF-36) was administered at baseline and at 12-week follow-up. Peak oxygen consumption improved significantly after training. The heart rate recovery improved from 13.90/minute to 16.62/minute after exercise training. Functional mobility and handgrip strength also improved after training. Significant improvements were found in SF-36 physical function, social function, role limitation due to emotional problems, and mental health domains. A significant correlation between dynamic cardiopulmonary exercise testing parameters, the 6-minute walking test, Timed Up and Go test, handgrip strength, and SF-36 physical function and general health domains was also detected. Twelve-week, 36-session exercise training, including moderate-intensity cardiopulmonary exercise training, strengthening exercise, and balance training, is beneficial to elderly patients with CAD, and cardiopulmonary exercise testing parameters correlate well with balance and quality of life.

MeSH Terms

  • Aged
  • Coronary Artery Disease
  • Exercise
  • Female
  • Hand Strength
  • Heart Function Tests
  • Humans
  • Lung
  • Male
  • Physical Fitness
  • Quality of Life
  • Surveys and Questionnaires
  • Treatment Outcome

Keywords

  • Aerobic capacity
  • Coronary artery disease
  • Exercise
  • Geriatrics
  • Quality of life


Association of traditional risk factors with coronary artery disease in nonagenarians: the primary role of hypertension.

Previous studies have shown different relationships between traditional cardiovascular risk factors for coronary artery disease (CAD) in very elderly people. Although new associations with CAD have been reported, there is also evidence of the possibility of new therapeutic strategies for the treatment or prevention of CAD. This article retrospectively examines the possible association of traditional cardiovascular risk factors with CAD in very elderly people aged >90 years. This study represents the hypothesis that the elderly aged >90 years have a different cardiovascular profile with respect to CAD than patients <90 years old. Data on all patients aged >90 years who received a cardiac catheterization were collected from hospital charts from the Department of Internal Medicine, Saarland University Medical Center, Germany, within the study period of 2004-2013. The cardiovascular risk profiles were compared in patients aged >90 years with and without CAD after cardiac catheterization. One hundred and six out of 67,976 (0.2%, mean age 91.6±1.8 years, 40 female [37.7%]; 95% confidence interval [CI]: 0.1-0.2), and out of a total of 114 of the very elderly patients, were found to have CAD. From the results of this study, the author could establish only a causal relationship between hypertension and CAD in very elderly people (P=0.005). At best, this is just an association with a higher risk of CAD in this age group. Several studies with similar outcomes are needed to establish causality. This study could find no link between CAD and traditional risk factors, except for hypertension.

MeSH Terms

  • Aged, 80 and over
  • Blood Glucose
  • Body Mass Index
  • Cardiac Catheterization
  • Cardiovascular Diseases
  • Comorbidity
  • Coronary Artery Disease
  • Female
  • Germany
  • Humans
  • Hypertension
  • Lipids
  • Male
  • Mental Health
  • Retrospective Studies
  • Risk Factors
  • Smoking

Keywords

  • aging
  • diabetes
  • hypercholesterolemia
  • hyperlipidemia
  • hypertension
  • obesity


Regulatory/effector T-cell ratio is reduced in coronary artery disease.

The protective function of regulatory T cells (Treg) has been identified in experimental atherosclerosis, but the contribution of Treg to the pathogenesis of human coronary artery disease (CAD) remains poorly understood. We investigated Treg and regulatory T-cell/effector T-cell (Treg/Teff) ratio in peripheral blood samples from CAD patients using a new strategy for precise identification of Treg. METHODS AND RESULTS: Peripheral blood samples were collected from 73 stable CAD patients (55 middle-aged CAD patients and 18 old CAD patients) and 64 controls (47 middle-aged controls and 17 young controls). CD3( )CD4( )FoxP3( )T cells were divided into 3 fractions: CD45RA( )FoxP3(low)resting Treg(Fr1), CD45RA(-)FoxP3(high)activated Treg(Fr2), and CD45RA(-)FoxP3(low)non-Treg(Fr3). CAD patients had lower percentages of Fr1 and Fr2 and higher percentages of Fr3 and CD45RA(-)Foxp3(-)Teff(Fr4 5) within the CD3( )CD4( )T-cell population compared to age-matched controls. Treg/Teff ratio (Fr1 2/Fr3 4 5) in CAD patients was also markedly lower than in controls (middle-aged control, 0.17±0.09 vs. middle-aged CAD, 0.10±0.05; P<0.001). The percentage of CD4( )CD28(null)T cells within the CD4( )T-cell population was negatively correlated with Treg/Teff ratio, excluding CD4( )CD28(null)T cells <0.3% (r=-0.27, P<0.05). High-sensitivity C-reactive protein was also negatively correlated with Treg/Teff ratio (r=-0.22, P<0.05). CAD patients had reduced Treg and Treg/Teff ratio compared to healthy controls. The present findings may be helpful when developing immunotherapy for the prevention of CAD.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Angina Pectoris
  • Antigens, Differentiation, T-Lymphocyte
  • Atherosclerosis
  • Blood Glucose
  • Female
  • Humans
  • Lipids
  • Lymphocyte Activation
  • Lymphocyte Count
  • Male
  • Middle Aged
  • Myocardial Infarction
  • T-Lymphocyte Subsets
  • T-Lymphocytes, Regulatory


Acetylsalicylic acid, aging and coronary artery disease are associated with ABCA1 DNA methylation in men.

Previous studies have suggested that DNA methylation contributes to coronary artery disease (CAD) risk variability. DNA hypermethylation at the ATP-binding cassette transporter A1 (ABCA1) gene, an important modulator of high-density lipoprotein cholesterol and reverse cholesterol transport, has been previously associated with plasma lipid levels, aging and CAD, but the association with CAD has yet to be replicated. ABCA1 DNA methylation levels were measured in leucocytes of 88 men using bis-pyrosequencing. We first showed that DNA methylation at the ABCA1 gene promoter locus is associated with aging and CAD occurrence in men (P < 0.05). The latter association is stronger among older men with CAD (≥61 years old; n = 19), who showed at least 4.7% higher ABCA1 DNA methylation levels as compared to younger men with CAD (<61 years old; n = 19) or men without CAD (n = 50; P < 0.001). Higher ABCA1 DNA methylation levels in older men were also associated with higher total cholesterol (r = 0.34, P = 0.03), low-density lipoprotein cholesterol (r = 0.32, P = 0.04) and triglyceride levels (r = 0.26, P = 0.09). Furthermore, we showed that acetylsalicylic acid therapy is associated with 3.6% lower ABCA1 DNA methylation levels (P = 0.006), independent of aging and CAD status of patients. This study provides new evidence that the ABCA1 epigenetic profile is associated with CAD and aging, and highlights that epigenetic modifications might be a significant molecular mechanism involved in the pathophysiological processes associated with CAD. Acetylsalicylic acid treatment for CAD prevention might involve epigenetic mechanisms.


Keywords

  • ATP-binding cassette transporter A1
  • Aging
  • Cardiovascular disease
  • Epigenetics


Comparison of arterial stiffness parameters in patients with coronary artery disease and diabetes mellitus using Arteriograph.

Recently an expert consensus document advised to standardize user procedures and a new cut-off value for carotid-femoral pulse wave velocity in daily practice. Our aim was to observe aortic pulse wave velocity (PWVao) and augmentation index (AIXao) in two high cardiovascular risk groups: patients with verified coronary artery disease (CAD) or with type 2 diabetes mellitus (T2DM). We also aimed to determine the cut-off values for PWVao, AIXao in CAD and T2DM patients using oscillometric device (Arteriograph). We investigated 186 CAD and 152 T2DM patients. PWVao and AIXao increased significantly in the CAD group compared to the age-, gender-, blood pressure-, and heart rate-matched control group (10.2 /-2.3 vs. 9.3 /-1.5 m/s; p<0.001 and 34.9 /-14.6 vs. 31.9 /-12.8 %; p<0.05, respectively). When compared to the apparently healthy control subjects, T2DM patients had significantly elevated PWVao (9.7 /-1.7 vs. 9.3 /-1.5 m/s; p<0.05, respectively), however the AIXao did not differ significantly. The ROC-curves of CAD and healthy control subjects explored cut-off values of 10.2 m/s for PWVao and 33.23 % for AIXao. Our data provide supporting evidence about impaired arterial stiffness parameters in CAD and T2DM. Our findings encourage the implementation of arterial stiffness measurements by oscillometric method in daily clinical routine.

MeSH Terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Angiography
  • Blood Pressure
  • Coronary Artery Disease
  • Diabetes Mellitus, Type 2
  • Female
  • Heart Rate
  • Humans
  • Male
  • Middle Aged
  • Pulse Wave Analysis
  • Sex Characteristics
  • Vascular Stiffness


Chemerin levels as predictor of acute coronary events: a case-control study nested within the veterans affairs normative aging study.

Chemerin is a recently identified adipocytokine that has been positively correlated with the presence and severity of coronary artery disease (CAD). However, no studies have examined circulating chemerin levels as a predictor of acute coronary syndrome (ACS). The purpose of this study is to evaluate whether chemerin levels predict the onset of ACS. We studied 90 men whose serum had been collected at least 2 years before the development of ACS, and 162 controls matched with the cases in a 1:2 fashion for age and year of collection. The mean age of the cohort was 66.3±9.6 years (range 34-84 years). Serum chemerin levels were measured with a commercially available enzyme-linked immunosorbent assay. Age was positively associated with chemerin levels (r=0.39, p<0.001). Logistic regression analysis, adjusting for years since blood collection, demonstrated a null association between chemerin levels and the odds ratio for development of ACS (OR: 0.99, 95% CI [0.99-1.001]). This association remained null after adjusting for age (OR: 0.99 95% CI [0.99-1.001]). Although cross-sectional and case-control studies suggest a positive association between chemerin levels and CAD, we demonstrate that chemerin levels do not predict the development of ACS.

MeSH Terms

  • Acute Coronary Syndrome
  • Adult
  • Aged
  • Aged, 80 and over
  • Aging
  • Biomarkers
  • Case-Control Studies
  • Chemokines
  • Enzyme-Linked Immunosorbent Assay
  • Humans
  • Intercellular Signaling Peptides and Proteins
  • Logistic Models
  • Male
  • Middle Aged
  • Odds Ratio
  • Predictive Value of Tests
  • United States
  • Veterans

Keywords

  • Acute Coronary Events
  • Chemerin
  • Normative Aging Study


Adipose-derived mesenchymal stromal cells from aged patients with coronary artery disease keep mesenchymal stromal cell properties but exhibit characteristics of aging and have impaired angiogenic potential.

Tissue regeneration is impaired in aged individuals. Adipose-derived mesenchymal stromal cells (ADSCs), a promising source for cell therapy, were shown to secrete various angiogenic factors and improve vascularization of ischemic tissues. We analyzed how patient age affected the angiogenic properties of ADSCs. ADSCs were isolated from subcutaneous fat tissue of patients with coronary artery disease (CAD; n = 64, 43-77 years old) and without CAD (n = 31, 2-82 years old). ADSC phenotype characterized by flow cytometry was CD90( )/CD73( )/CD105( )/CD45(-)/CD31(-) for all samples, and these cells were capable of adipogenic and osteogenic differentiation. ADSCs from aged patients had shorter telomeres (quantitative reverse transcription polymerase chain reaction) and a tendency to attenuated telomerase activity. ADSC-conditioned media (ADSC-CM) stimulated capillary-like tube formation by endothelial cells (EA.hy926), and this effect significantly decreased with the age of patients both with and without CAD. Angiogenic factors (vascular endothelial growth factor, placental growth factor, hepatocyte growth factor, angiopoetin-1, and angiogenin) in ADSC-CM measured by enzyme-linked immunosorbent assay significantly decreased with patient age, whereas levels of antiangiogenic factors thrombospondin-1 and endostatin did not. Expression of angiogenic factors in ADSCs did not change with patient age (real-time polymerase chain reaction); however, gene expression of factors related to extracellular proteolysis (urokinase and its receptor, plasminogen activator inhibitor-1) and urokinase-type plasminogen activator receptor surface expression increased in ADSCs from aged patients with CAD. ADSCs from aged patients both with and without CAD acquire aging characteristics, and their angiogenic potential declines because of decreasing proangiogenic factor secretion. This could restrict the effectiveness of autologous cell therapy with ADSCs in aged patients.

MeSH Terms

  • Adipose Tissue
  • Adult
  • Aged
  • Aging
  • Angiopoietin-1
  • Cellular Senescence
  • Child
  • Child, Preschool
  • Coronary Artery Disease
  • Culture Media, Conditioned
  • Female
  • Hepatocyte Growth Factor
  • Humans
  • Hypertension
  • Male
  • Mesenchymal Stem Cells
  • Middle Aged
  • Neovascularization, Physiologic
  • Vascular Endothelial Growth Factor A

Keywords

  • Adipose-derived stromal cells
  • Aging
  • Cell therapy
  • Coronary artery disease
  • Therapeutic angiogenesis
  • Urokinase receptor


Perfusion characteristics of Moyamoya disease: an anatomically and clinically oriented analysis and comparison.

Moyamoya disease (MMD) is characterized by unique angiographic features of collateralization. However, a detailed quantification as well as comparative analysis with cerebrovascular atherosclerotic disease (CAD) and healthy controls have not been performed to date. We reviewed 67 patients with MMD undergoing Xenon-enhanced computed tomography, as well as 108 patients with CAD and 5 controls. In addition to cortical, central, and infratentorial regions of interest, particular emphasis was put on regions that are typically involved in MMD (pericallosal territory, basal ganglia). Cerebral blood flow (CBF), cerebrovascular reserve capacity (CVRC), and hemodynamic stress distribution were calculated. MMD is characterized by a significant, ubiquitous decrease in CVRC and a cortical but not pericallosal decrease in CBF when compared with controls. Baseline perfusion is maintained within the basal ganglia, and hemodynamic stress distribution confirmed a relative preservation of central regions of interest in MMD, indicative for its characteristic proximal collateralization pattern. In MMD and CAD, cortical and central CBF decreased significantly with age, whereas CVRC and hemodynamic stress distribution are relatively unaffected by age. No difference in CVRC of comparable regions of interest was seen between MMD and CAD, but stress distribution was significantly higher in MMD, illustrating the functionality of the characteristic rete mirabilis. Our data provide quantitative support for a territory-specific perfusion pattern that is unique for MMD, including central preservation of CBF compared with controls and patients with CAD. This correlates well with its characteristic feature of proximal collateralization. CVRC and hemodynamic stress distribution seem to be more robust parameters than CBF alone for assessment of disease severity.

MeSH Terms

  • Aging
  • Cerebral Angiography
  • Cerebrovascular Circulation
  • Humans
  • Image Processing, Computer-Assisted
  • Magnetic Resonance Angiography
  • Magnetic Resonance Imaging
  • Moyamoya Disease
  • Retrospective Studies
  • Tomography, X-Ray Computed
  • Xenon

Keywords

  • Moyamoya disease
  • Xenon
  • computed tomography
  • perfusion


Reduced Klotho is associated with the presence and severity of coronary artery disease.

Klotho is involved in vascular health. We aimed to analyse in a cross-sectional study the relationship between Klotho and human coronary artery disease (CAD). The study included 371 subjects who underwent coronary angiography and 70 patients who underwent elective cardiac surgery recruited between May 2008 and June 2009. The presence and severity (stenosis index) of CAD, cardiovascular risk factors, Klotho gene expression in the thoracic aorta, and serum soluble Klotho concentrations were evaluated. The soluble Klotho concentration was lower (p<0.001) in patients with significant CAD (n=233). The maximal stenosis observed in every epicardial artery and the stenosis severity index was significantly lower in patients within the higher soluble Klotho concentrations (p<0.0001). Multiple regression analysis showed that serum Klotho concentrations were inverse and significantly associated with CAD (adjusted R(2)=0.67, p<0.001). Multivariate logistic regression analysis showed that risk factors for significant CAD included age, diabetes, smoking and inflammation, whereas high serum Klotho values were associated with a lower risk for CAD. Lower mRNA expression level of Klotho was observed in 46 patients with significant CAD, as compared with subjects without CAD (p=0.01). Logistic regression analysis showed that high Klotho gene expression was independently associated with lower risk for CAD. Patients with significant CAD present lower soluble concentrations of Klotho, as well as reduced levels of Klotho gene expression in the vascular wall. Reduced serum Klotho concentrations and decreased vascular Klotho gene expression were associated with the presence and severity of CAD independently of established cardiovascular risk factors.

MeSH Terms

  • Aged
  • Aging
  • Coronary Angiography
  • Coronary Artery Disease
  • Coronary Vessels
  • Female
  • Gene Expression Regulation
  • Glucuronidase
  • Humans
  • Male
  • Middle Aged
  • Myocardial Revascularization
  • RNA
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Severity of Illness Index

Keywords Coronary Artery Disease


The rs1333049 polymorphism on locus 9p21.3 and extreme longevity in Spanish and Japanese cohorts.

The rs1333049 (G/C) polymorphism located on chromosome 9p21.3 is a candidate to influence extreme longevity owing to its association with age-related diseases, notably coronary artery disease (CAD). We compared allele/genotype distributions of rs1333049 in cases (centenarians) and controls (younger adults, without (healthy) or with CAD) in two independent cohorts: Spanish (centenarians: n = 152, 128 women, 100-111 years; healthy controls: n = 343, 212 women, age <50 years; CAD controls: n = 98, 32 women, age ≤65 years) and Japanese (centenarians: n = 742, 623 women, 100-115 years; healthy controls: n = 920, 511 women, < 60 years; CAD controls: n = 395, 45 women, age ≤65 years). The frequency of the "risk" C-allele tended to be lower in Spanish centenarians (47.0 %) than in their healthy (52.9 %, P = 0.088) or CAD controls (55.1 %, P = 0.078), and significant differences were found in genotype distributions (P = 0.034 and P = 0.045), with a higher frequency of the GG genotype in cases than in both healthy and CAD controls as well as a lower proportion of the CG genotype compared with healthy controls. In the Japanese cohort, the main finding was that the frequency of the C-allele did not differ between centenarians (46.4 %) and healthy controls (47.3 %, P = 0.602), but it was significantly lower in the former than in CAD controls (57.2 %, P < 0.001). Although more research is needed, the present and recent pioneer findings (Rejuvenation Res 13:23-26, 2010) suggest that the rs1333049 polymorphism could be among the genetic contributors to exceptional longevity in Southern European populations, albeit this association does not exist in the healthy (CAD-free) Japanese population.

MeSH Terms

  • Aged
  • Aged, 80 and over
  • Alleles
  • Chromosomes, Human, Pair 9
  • Coronary Disease
  • DNA
  • Female
  • Follow-Up Studies
  • Gene Frequency
  • Genetic Predisposition to Disease
  • Genotype
  • Humans
  • Japan
  • Longevity
  • Male
  • Middle Aged
  • Morbidity
  • Polymerase Chain Reaction
  • Polymorphism, Genetic
  • Retrospective Studies
  • Spain


Age-related impact of depressive symptoms on functional capacity measured with 6-minute walking test in coronary artery disease.

Patients affected by coronary artery disease (CAD) have a high prevalence of depressive disorders. It has been suggested that depressive symptoms significantly reduce exercise stress test performance in CAD patients, whereas their influence on functional capacity tests, such as the 6-minute walking test (6WT), has been less investigated. The aim of this study was to evaluate the correlation between depressive symptoms and 6WT in patients with CAD and the role of age on this relationship. We enrolled 148 CAD patients. Global functional capacity was measured with 6WT and the presence of depressive symptoms with the 30-item Geriatric Depression Scale (GDS). GDS score was analysed as a continuous variable or categorized as depression absent (score <10), probable (10-14), or present (≤15). A significant inverse correlation was observed between GDS score and distance walked at 6WT. Patients positive for depressive symptoms (probable or present) had a significantly worse performance compared to those with GDS score <10. In multivariable analysis adjusted for indexes of cardiovascular disease severity and comorbidity, the presence of depressive symptoms proved to be an independent predictor of distance walked at 6WT; the predictivity of depressive symptoms on 6WT was age dependent. Depressive symptoms negatively affect 6WT performance among older CAD subjects. Non-cardiovascular parameters, such as psycho-affective disorders, must be taken into account for the interpretation of 6WT performance in old age.

MeSH Terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • Coronary Artery Disease
  • Cross-Sectional Studies
  • Depressive Disorder
  • Exercise Test
  • Exercise Tolerance
  • Geriatric Assessment
  • Humans
  • Middle Aged
  • Multivariate Analysis
  • Predictive Value of Tests
  • Psychiatric Status Rating Scales
  • Risk Factors
  • Walking

Keywords

  • 6-minute walking test
  • Aging
  • coronary artery disease
  • depressive disorder


Removable dental prostheses and cardiovascular survival: a 15-year follow-up study.

In previous studies, increasing number of teeth predicted better survival and the acute needs for dental treatment predicted mortality. We sought to investigate whether restored dentitions by various removable dental prostheses impact cardiovascular (CVD) longevity. Kuopio Oral Health and Heart study was initiated as a cross-sectional investigation with 256 subjects with diagnosed coronary artery disease [[[CAD]]] and 250 age- and sex-matched controls without CAD in 1995-1996. The mean age of both groups was 61, 30% were females. We appended mortality follow-up records to the baseline data and formulated this 15-year follow-up study. We examined the relationship between various types of dental prostheses and cardiovascular mortality by proportional hazard regression analyses. We also explored their correlation to oral and systemic inflammatory markers such as asymptotic dental score and C-reactive protein. In a model adjusted for age, sex and smoking, groups having only natural teeth (NT), removable partial denture(s) [PD] and NT, a PD and a full denture [FD], and FD/FD or FD/NT demonstrated the following hazard ratios for mortality (95% confidence interval). NT both arches: 1.00 [reference]; PD and NT: 0.75 [0.22-2.56]; PD and FD: 1.99 [1.05-3.81]; and FD opposed by FD or NT: 1.71 [0.93-3.13], respectively [p for trend=0.05]. Although statistically not significant, those with PD and NT with mean a number of teeth [Nteeth] of 15.4 had better survival compared with those who had all NT [Nteeth=22.5]; while those who had FD and PD [Nteeth=6.5] had shorter longevity than those with FD/FD or FD/NT [Nteeth=3.5]. Although not all subgroups of dental prostheses reached significant relationship with CVD mortality, our study suggests that not only the number [quantity] of remaining teeth but their maintenance [quality] removing potential inflammatory foci, such as pericoronitis or retained root tips, may positively impact on cardiovascular survival.

MeSH Terms

  • Age Factors
  • C-Reactive Protein
  • Candidiasis, Oral
  • Case-Control Studies
  • Coronary Artery Disease
  • Cross-Sectional Studies
  • Dental Calculus
  • Dentition
  • Denture, Complete
  • Denture, Partial, Removable
  • Female
  • Finland
  • Follow-Up Studies
  • Humans
  • Hypertension
  • Inflammation Mediators
  • Longevity
  • Male
  • Middle Aged
  • Periodontal Diseases
  • Proportional Hazards Models
  • Prospective Studies
  • Sex Factors
  • Smoking
  • Streptococcal Infections

Keywords

  • Cardiovascular mortality
  • Dental prostheses
  • Inflammation
  • Number of teeth
  • Oral care


Endogenous sex steroid levels and cardiovascular disease in relation to the menopause: a systematic review.

Heart disease remains a major cause of death among women in the United States. This article focuses on physiologic endogenous estrogen levels with a systematic review of literature related to endogenous sex steroid levels and coronary artery disease (CAD) among postmenopausal women with natural or surgical menopause. There is adequate reason to seek evidence for associations of circulating estrogen levels and CAD. In the future, even if ovarian senescence-associated hormonal changes are confirmed to be associated with CAD in cohort studies of postmenopausal women, there may be other components explaining the gender differences in CAD patterns.

MeSH Terms

  • Aging
  • Androgens
  • Cardiovascular Diseases
  • Estradiol
  • Estrogen Replacement Therapy
  • Estrogens
  • Female
  • Hormone Replacement Therapy
  • Humans
  • Hyperlipidemias
  • Postmenopause
  • Risk Factors
  • Sex Hormone-Binding Globulin


Angiopoietin-like 2 promotes atherogenesis in mice.

Angiopoietin like-2 (angptl2), a proinflammatory protein, is overexpressed in endothelial cells (ECs) from patients with coronary artery disease (CAD). Whether angptl2 contributes to atherogenesis is unknown. We tested the hypothesis that angptl2 promotes inflammation and leukocyte adhesion onto ECs, thereby accelerating atherogenesis in preatherosclerotic dyslipidemic mice. In ECs freshly isolated from the aorta, basal expression of TNF-α and IL-6 mRNA was higher in 3-month-old severely dyslipidemic mice (LDLr(-/-); hApoB100( / ) [ATX]) than in control healthy wild-type (WT) mice (P<0.05) and was increased in both groups by exogenous angptl2 (100 nmol/L). Angptl2 stimulated the adhesion of leukocytes ex vivo on the native aortic endothelium of ATX, but not WT mice, in association with higher expression of ICAM-1 and P-selectin in ECs (P<0.05). Antibodies against these endothelial adhesion molecules prevented leukocyte adhesion. Intravenous administration of angptl2 for 1 month in preatherosclerotic 3-month-old ATX mice increased (P<0.05) total cholesterol and LDL-cholesterol levels, strongly induced (P<0.05) the expression of endothelial proinflammatory cytokines and adhesion molecules while accelerating atherosclerotic lesion formation by 10-fold (P<0.05). Plasma and aortic tissue levels of angptl2 increased (P<0.05) with age and were higher in 6- and 12-month-old ATX mice than in age-matched WT mice. Angptl2 accumulated to high levels in the atherosclerotic lesions (P<0.05). Finally, angptl2 was greatly expressed (P<0.05) in ECs cultured from CAD patients, and circulating angptl2 levels were 6-fold higher in CAD patients compared with age-matched healthy volunteers. Angptl2 contributes to the pathogenesis of atherosclerosis.

MeSH Terms

  • Angiopoietin-2
  • Animals
  • Atherosclerosis
  • Cell Adhesion
  • Endothelial Cells
  • Inflammation
  • Leukocytes
  • Male
  • Mice
  • Mice, Inbred C57BL

Keywords

  • CAD
  • adhesion molecules
  • aging
  • freshly isolated mouse endothelial cells
  • inflammation
  • mouse model of atherosclerosis