Dehydroepiandrosterone and cardiac allograft vasculopathy

Background: Tissue culture, animal model, and epidemiologic studies suggest that dehydroepiandrosterone may inhibit atherosclerosis through its potent antiproliferative effects. Because cardiac allograft vasculopathy is predominantly a proliferative abnormality of intimal and medial smooth muscle cells, plasma levels of dehydroepiandrosterone may play an important role in the development of this disease. Methods: Sixty-one cardiac allograft recipients who survived for 1 year or more and had at least one annual follow-up cardiac catheterization were included in the study. Plasma levels of dehydroepiandrosterone, dehydroepiandrosterone sulfate, and free dehydroepiandrosterone (dehydroepiandrosterone not bound to sex hormone- binding globulin) were measured in all 61 subjects and compared with the presence or absence of cardiac allograft vasculopathy as defined by angiography. Results: Plasma levels of total and free dehydroepiandrosterone were lower in subjects in whom cardiac allograft vasculopathy developed (p = 0.005 and 0.003, respectively). Furthermore, the time to development of cardiac allograft vasculopathy was shorter in subjects with low levels of total and free dehydroepiandrosterone (p = 0.062 and 0.040, respectively). This relationship was maintained after adjusting for age, gender, cholesterol, prednisone use, and blood pressure. Conclusions: Low plasma levels of dehydroepiandrosterone may facilitate and high levels may retard the development of cardiac allograft vasculopathy.