Simvastatin treatment is associated with improvement in coronary endothelial function and decreased cytokine activation in patients after heart transplantation

OBJECTIVES This study was designed to assess the association between 3-hydr oxy-3-methylglutaryl coenzyme A (HMG-CoA)reductase inhibition, coronary end othelial function and cytokine activation in heart transplant recipients wi thout angiographically detectable disease. BACKGROUND Coronary endothelial dysfunction contributes to cardiac allograf t vasculopathy. The vasoprotective effects of statins in heart transplant r ecipients may include restoration of endothelial function and suppression o f allograft inflammatory activity. METHODS Heart transplant recipients (one to three years after heart transpl ant) were divided into three groups based on the total cholesterol levels: group 1 (n = 21), patients with a history of hypercholesterolemia adequatel y controlled with simvastatin; group 2 (n = 19), patients with hypercholest erolemia not adequately treated with simvastatin; and group 3 (n = 40), pat ients without hypercholesterolemia. Coronary vasomotor function and intimal thickness as well as coronary sinus and aortic cytokine concentrations (tu mor necrosis factor [TNF]-alpha, interleukin [IL]-6 and soluble IL-2 recept or) were investigated. In a prospective one-year follow-up study, changes i n coronary endothelial function and cytokine levels were compared between 1 1 hypercholesterolemic patients treated with simvastatin and 9 controls. RESULTS Epicardial and microvascular endothelial functions were better in g roups 1 and 3 than they were in group 2 (p < 0.01 and p < 0.05). Transcardi ac IL-6 and TNF-alpha gradients were significantly increased in groups 2 an d 3 compared with group 1 (IL-6: p < 0.05; TNF-alpha: p < 0.01). Plaque are as were significantly increased in groups 1 and 2 (p < 0.05 vs. group 3), w hereas lumen area was increased in group 2 compared with group 1 (p < 0.05) , demonstrating adaptive vascular remodeling. In patients treated with simv astatin, coronary endothelial function and cardiac cytokine activity signif icantly improved during the one-year follow-up. CONCLUSIONS Inhibition of allograft inflammatory activity and attenuation o f the coronary endothelial dysfunction observed in cardiac transplant recip ients during treatment with simvastatin may represent an important mechanis m by which HMG-CoA reductase inhibitors protect against the development of cardiac allograft vasculopathy. (C) 2001 by the American College of Cardiol ogy.