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Consequences of vascular aging: concepts for the clinician.

The incidence and prevalence of cardiovascular disease continue to rise with the increasing number and proportion of elderly individuals in the general population and particularly in the patient population with cardiovascular disease. An understanding of the physiologic changes associated with vascular aging is an important component of the treatment of older individuals because these changes alter the substrate upon which disease is superimposed and in so doing alter its presentation, severity and response to therapeutic interventions. Age-associated changes in vascular properties can be divided into two categories: those which increase central vascular stiffness, and those which decrease endothelial responsiveness. The former are due, in large part, to histologic changes including an increase in the collagen and a decrease in the elastin components. The changes in collagen content are believed to be particularly marked in diabetics because of an increase in glycosylated collagen cross links associated with the disease. Increased central vascular stiffness increases the velocity of the pulse wave from the aortic valve to the iliac bifurcation and also the velocity of the reflected wave. This results in an increase in systolic, a decrease in diastolic, and therefore an increase in pulse pressure. From a clinical standpoint, this marker of central vascular stiffness has emerged as one of the most important risk factors for the development of cardiovascular disease in the middle-aged and older population. Data from the Framingham study indicate, in fact, that pulse pressure is a more important discriminator of cardiovascular risk than systolic or diastolic blood pressure. Increased vascular stiffness is also responsible for isolated systolic hypertension in older individuals. Surveys indicate that over half of older individuals with hypertension have an increase in systolic pressure associated with a normal or low diastolic pressure. Two large clinical trials indicate that treatment of isolated systolic hypertension in older individuals decreases stroke, heart failure, and infarction or cardiovascular death, particularly in older diabetic patients. Increased vascular stiffness may also be responsible, in part, for the marked age-associated increase in mortality and morbidity following an infarction. Data from the GISSI-2 trial investigators, as well as other large infarction trials, demonstrate a logarithmic increase in in-hospital and 6-month mortality, as well as large increases in congestive heart failure and ventricular rupture as age increases from under 65 years to over 85 years. A report from the SAVE investigators indicates that increased vascular stiffness, indexed by pulse pressure, may be responsible, in part, for this age-associated rise in mortality. The third area where vascular stiffness may impact on cardiovascular disease is the development and progression of what is commonly termed diastolic heart failure in the elderly. Up to 40% of older individuals presenting with pulmonary edema may have a normal ejection fraction. Although symptoms are commonly attributed to a diastolic, relaxation abnormality, Hopkins data indicate that age-associated increases in both vascular and ventricular systolic stiffness may play an important role in many of these patients. In healthy individuals, interventions which decrease stiffness improve aerobic cardiovascular performance. Clinical trials are underway in patient populations as well. The second major change in vascular properties associated with physiologic aging Address: