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The article discusses the most important age-dependent changes in the cardiovascular system. It mentions about the altered cellular function, cardiac shape, plasticity and valvular stiffening which contribute to reduced cardiovascular reserve, the impact of normal ageing on the increase in the late systolic pressure, and concludes that the heart and vessels undergo major changes with advancing age.

Whilst there is a small literature on the cardiovascular toxicity of opiates, there is no detailed antemortem data on non-cardiovascular patient populations. A cross-sectional and longitudinal naturalistic observational study was performed comparing methadone ( N = 71)-, buprenorphine ( N = 593)-, naltrexone ( N = 23)-treated patients with controls ( N = 576) on indices of arterial stiffness and vascular age by Pulse Wave Analysis in primary care, 2006-2011. Controls were younger 29.96 ± 0.45 (mean ± SEM) vs. 34.00 ± 0.34-39.22 ± 1.11 years (all P < 0.005) and had fewer smokers (15.9 % vs. 86.9 %-92.96 %, all P < 0.0001). The sex ratio was similar (69.6 vs. 67.7 % male, P = 0.46). These baseline differences were controlled for by multiple regression. Linear regression of vascular age, central augmentation pressure, central augmentation index and other measures against chronologic age showed significant protective effects by treatment group against the treatment standard of methadone, in both sexes in additive and interactive models (all P < 0.02). Interactive terms in treatment type remained significant including all conventional risk factors accounting for differing opiate exposures. The principal findings from multiple regression were confirmed in the time series analysis up to 5 years by repeated measures nonlinear regression. These studies show that the deleterious impact of chronic opiate pharmacotherapy on vascular age and arterial stiffness varies significantly by treatment type. [ABSTRACT FROM AUTHOR]

Epidemiological studies have shown that age is the chief risk factor for atherosclerotic cardiovascular diseases, but the molecular mechanisms that underlie the increase in risk conferred by aging remain unclear. Evidence suggests that the cardiovascular repair system is impaired with advancing age, thereby inducing age-associated cardiovascular dysfunction. Such impairment could be attributable to senescence of cardiovascular tissues at the cellular level as a result of telomere shortening, DNA damage, and genomic instability. In fact, the replicative ability of cardiovascular cells, particularly stem cells and/or progenitor cells, has been shown to decline with age. Recently, considerable progress has been made in understanding the pathogenesis of human progeroid syndromes that feature cardiovascular aging. Most of the genes responsible have a role in DNA metabolism, and mutated forms of these genes result in alterations of the response to DNA damage and in decreased cell proliferation, which might be common features of a phenotype of aging. Here we review the cardiovascular research on cellular senescence, stem cell aging, and progeroid syndromes and discuss the potential role of cellular senescence in the mechanisms underlying both normal aging and premature aging syndromes. [ABSTRACT FROM AUTHOR]

Background: Although generally assumed to be an adaptive response to increased blood pressure (BP), arterial stiffness is now recognized as an independent predictor of cardiovascular (CV) events [1]. Moreover it precedes hypertension in at least two mouse models [2-3]. Therefore, the present study aims to investigate the temporal development of aortic stiffening and peripheral blood pressure (BP) alterations in spontaneously ageing mice. Methods: A longitudinal cardiovascular characterization of spontaneously ageing C57Bl6 mice (2, 4, 6, 9, 12 and 24- month old) (male, n > 8) was performed. This includes in vivo analysis of peripheral BP (Coda) and aortic pulse wave velocity (aPWV, Vevo2100), combined with ex vivo aortic studies of isometric reactivity (organ baths) and aortic stiffness measurements (Peterson modulus, Ep) in the Rodent Oscillatory Tension set-up for Arterial Compliance (ROTSAC). Results: In vivo and ex vivo characterisation confirms that aortic stiffness precedes peripheral BP alterations in spontaneously ageing C57Bl6 mice, with significantly increased aPWV from 6 month of age (Figure A), whereas peripheral BP measurement only shows elevated pulse pressure in 24 month old mice (30% increase vs. all other ages, Figure B). Ex vivo investigation of the thoracic aorta further reveals that the aortic stiffening is both contraction-independent (Figure C) and dependent (Figure D), since older mice display increased contractions to phenylephrine (PE) (Figure E and F). Conclusion: Spontaneously ageing C57Bl6 mice present with significant aortic stiffness by 6-months of age, which is both contraction-dependent and independent in origin. Aortic stiffness thereby precedes the development of peripheral BP alterations by 18 months. [ABSTRACT FROM AUTHOR]

Objective: To characterise the comparative potency of optically pure (R)- and (S)-verapamil as regards negative dromotropic effects on atrioventricular (AV) node conduction and to compare the hemodynamic effects of single doses of the enantiomers in healthy volunteers. Methods: Eight healthy volunteers received a single oral dose of 120 mg (S)-verapamil, 480 mg (R)-verapamil, 240 mg racemic verapamil (rac-verapamil) or placebo on 4 separate occasions. Serum concentrations of (R)- and (S)-verapamil were measured up to 24 h. Cardiovascular effects were assessed by electrocardiography, measurement of blood pressure and transthoracic impedance cardiography (cardiac output and total peripheral resistance). The comparative potency of (R)- and (S)-verapamil with regard to prolongation of the PR interval in the surface ECG was estimated by use of the areas under the effect-time and serum concentration-time curves and linear regression analyses of per cent change in PR interval from baseline versus the logarithm of serum (R)- or (S)-verapamil concentration. Results: The PR interval was significantly prolonged after all verapamil treatments as compared with placebo. (S)-verapamil was 20.6–21.8 times more potent than (R)-verapamil with regard to negative dromotropic effects. (R)-verapamil caused a significantly greater maximum reduction in the mean arterial pressure (MAP) than placebo [15.9±6.8 versus 8.7±3.2 mmHg (mean±SD); 95% CI on the difference, 0.79–13.7 mmHg; p<0.05], whereas MAP was not affected by the other verapamil treatments. No significant changes were observed in heart rate, cardiac output and total peripheral resistance after any verapamil treatment as compared with placebo. Conclusions: (S)-verapamil was about 20 times more potent than (R)-verapamil with regard to negative dromotropic effects on AV node conduction. (R)-verapamil but not (S)-verapamil significantly reduced the MAP as compared with placebo. [ABSTRACT FROM AUTHOR]