Aging and Atherosclerosis: Changing Considerations in Cardiovascular Disease Prevention as the Barrier to Immortality...

Of all the risk factors to cardiovascular disease (CVD), age is the most powerful: CVD incidence and prevalence rise progressively at all ages beyond young adulthood. This reflects the central role of time, and hence duration, in the atherogenic process. It also reflects age-related changes in physiology - notably alterations in body mass and composition favoring increased adiposity and in sex hormone secretion (combining adverse effects of androgens on lipoprotein lipid levels in males, lowering HDL, and of the decline in estrogens in postmenopausal females, raising LDL). The interactions among the passage of time, these physiological changes and perhaps aging per se, and pathological forces such as cigarette smoking, hypertension, and genetically determined dyslipoproteinemia conspire to accelerate the rate of atherogenesis. Thus clinical atherosclerosis and its complications rise exponentially with increasing age in the population at large. However, the relationship between dyslipoproteinemia and CVD risk in the individual patient actually declines with advancing age. This apparent paradox reflects confounding introduced by the advent of disease processes that cause wasting and inflammation such as cancer, infection, diabetes, trauma, and even CVD that actually lower lipid levels, frequently to the level of hypocholesterolemia. Thus, while with age the population-attributable risk of hypercholesterolemia (and/or low HDL) rises, the cholesterol-attributable risk in the individual falls. As a result the prescription of lipid-lowering therapy in elderly patients requires exquisite individualization: patients most likely to benefit are those with existing CVD (i.e., in secondary prevention) who nevertheless enjoy robust health and are highly motivated to comply with demanding regimens of diet and exercise plus drugs where needed to reach target LDL levels (less than 100 mg/dl). At the other extreme are those least likely to benefit: patients who are frail and failing from CVD or other wasting diseases of old age that present a more immediate threat to survival.