Morbidity, mortality, and antihypertensive treatment effects by extent of atherosclerosis in older adults with isolated systolic hypertension

The Systolic Hypertension in the Elderly Program (SHEP) demonstrated a significant reduction in stroke and coronary event rates among participants randomly assigned to active blood pressure treatment. Selected participants were evaluated for peripheral atherosclerosis and followed up for cardiovascular events beyond the end of the SHEP trial. Antihypertensive treatment effects were evaluated based on the presence or absence of clinical or subclinical atherosclerosis. As an ancillary study to SHEP, 190 participants at the Pittsburgh center were evaluated for peripheral atherosclerosis, defined as either an internal carotid stenosis (by duplex scan) or lower extremity arterial disease (identified by ankle blood pressure). Participants were subsequently followed up for cardiovascular events. Estimates of 4-year mortality rates were 4.8% for participants with no atherosclerosis, 16.7% for those with subclinical atherosclerosis, and 23% among those with clinical evidence of atherosclerosis (P < .001). Fatal plus nonfatal cardiovascular event rates were 10.9%, 29.8%, and 58.3% for the three groups, respectively (P < .001). Differences remained significant after adjustment for age, sex, treatment assignment, smoking, and high-density lipoprotein cholesterol. Individuals assigned to placebo at the beginning of SHEP had higher cardiovascular event rates than individuals assigned to active treatment (P = .011), with the most striking difference 3 or more years after the end of the SHEP trial. When this analysis was stratified by the presence or absence of detectable atherosclerosis, the absolute treatment effect was largest among those with evidence of disease. Individuals with systolic hypertension and evidence of peripheral atherosclerosis are at high risk for cardiovascular events. Targeting this group for antihypertensive therapy would result in the prevention of a large number of cardiovascular events.