Arterial and cardiac aging: Major shareholders in cardiovascular disease enterprises: Part I: Aging arteries: A "set up" for vascular disease

There is a growing body of evidence that increased large artery thickening and stiffness and endothelial dysfunction in apparently otherwise healthy older persons, along with the ensuing increase in systolic and pulse pressure that was formerly thought to be part of "normal" aging, precede clinical disease and predict a higher risk for developing clinical atherosclerosis, hypertension, and stroke (Table). Some of these vascular changes that occur with aging in normotensive humans, including endothelial dysfunction, have been observed in hypertensive patients at an earlier age and are more marked than in normotensive subjects. Such otherwise asymptomatic individuals might be considered to manifest unsuccessful vascular aging. When stated in this context, unsuccessful vascular aging becomes the risk factor for eventual clinical disease manifestations. Some epidemiologists will perceive the risk of unsuccessful vascular aging as synonymous with subclinical cardiovascular disease; however, evidence is mounting that subclinical vascular disease in older persons represents specific aspects of vascular aging and is not synonymous with low-grade atherosclerosis or hypertension. Rather, vascular aging and vascular disease are partners; each contributes specific components to what is presently referred to as "vascular disease." Thus, what clinical medicine and epidemiology now refer to as vascular disease should be regarded as the "vascular aging-vascular disease interaction." Aging blood vessels provide the milieu in which vascular diseases can flourish. If vascular aging is a risk factor for disease, then age-associated vascular changes represent a potential target for treatment and prevention. The vascular changes due to aging in persons who do not have a diagnosis of clinical cardiovascular disease have remained largely outside the bailiwick of clinical cardiology, however, and until recently have not been the focus of preventive measures. Lifestyle intervention or pharmacotherapy to retard the rate of progression of subclinical disease might be considered before the clinical disease becomes manifest. With respect to lifestyle, the risk factor of lack of vigorous exercise increases dramatically with age in otherwise healthy persons. It is noteworthy that pulse pressure, PWV, and carotid augmentation index are lower and baroreceptor reflex function is improved in older persons who are physically conditioned compared with sedentary persons. Exercise conditioning also improves endothelial function in older persons. In addition, there is evidence to indicate that diets low in sodium are associated with reduced arterial stiffening with aging. With respect to pharmacotherapy, angiotensin-converting enzyme inhibitors have been shown to retard vascular aging in rodents. Retardation or reduction in IM thickness in humans has been achieved by drug/diet intervention. It is thus far unproved if such treatment can "prevent" unsuccessful aging of the vasculature in individuals of younger-middle age who exhibit excessive subclinical evidence of unsuccessful aging.