A Vascular Theory of Aging

ADVANCING age is unequivocally the dominant risk factor for atherosclerosis and its major clinical consequences of ischemic heart disease and cerebrovascular disease (1–4). For example, the Framingham score for the risk of coronary heart disease allocates seven points to men with ages between 70 and 74 years compared with only three points for men with severe hypercholesterolemia and hypertension and two points for the presence of diabetes mellitus and smoking (5). Many possible explanations for the association between age and vascular disease have been proposed (3), but it is not mediated by any simple association between chronological age and duration of exposure to other established risk factors. In fact, many studies have found that in very elderly people, the association between hypertension, hyperlipidemia, and health outcomes is reversed (6–8). Advancing age is a pivotal and independent risk factor for cardiovascular disease. Given the increasing age of the population and our success in managing other vascular risk factors in middle age, it is clear that future gains in preventing cardiovascular disease require an increased understanding of vascular aging (9).