The coronary artery disease paradox

The first large scale, long and appropriately controlled clinical trial in hypertension, the Veterans Administration Study, was completed in 1970. Since then 16 additional such trials have been completed and have unequivocally demonstrated that pharmacologic therapy for hypertension reduces cardiovascular events. These trials, which have been performed in the U.S., Europe and Australia, showed active of hypertension treatment reduced stroke by more than 40% compared to placebo or community control. This degree of benefit is nearly precisely what a group of epidemiologic studies estimated as to the increased likelihood of stroke associated with the 5-6 mm Hg higher diastolic blood pressure (BP) measured in the control groups. For coronary artery disease (CAD), the reduction was only 16%, considerably less then the 24% predicted by those same epidemiologic surveys. The reason for this paradox (treatment of hypertension reduces stroke as expected but falls far short for CAD) is unclear and there are many possible explanations: 1) Though nearly 50,000 subjects have been enrolled in these trials, the average duration was less than five years and it may simply take longer to reduce coronary artery events. 2) The trials entered and treated patients based only on diastolic BP. Perhaps treatment and risk prediction based on systolic BP might have been more accurate. 3) The drugs used in the trials (diuretics and beta adrenoreceptor blockers in higher than the doses we currently recommend) may have adversely affected other risk factors (lipids, glucose tolerance) and so reduced the expected benefit. 4) And finally, the regimens used included some therapeutic strategies that may not have reduced BP for all 24 hours and put patients at risk of plaque rupture due to the rise of relatively acute rise in BP associated with awakening. These and other possible explanations for the CAD paradox will be discussed