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An explanation for the higher incidence of cardiovascular disease and heart failure in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) with doxazosin and the Vasodilator Heart Failure Trial (V-HeFT) with prazosin might be decreased expression of heat shock proteins. Heat shock proteins help to protect cells from ischemic injury by decreasing oxidation, suppressing cytokine action, refolding damaged proteins, and decreasing apoptosis. I hypothesize that alpha-adrenergic blockade decreases heat shock protein levels, thus making the heart and vascular system vulnerable to injury from pathologic processes such as ischemia, hypertension, oxidation or inflammation. Similarly, poor cardiovascular outcomes with calcium-channel blockers might be due to decreased expression of heat shock proteins.

Hypothesis to explain poor outcomes in the ALLHAT and V-HeFT trials: decreased expression of heat shock proteins.