The risk of coronary artery disease after heart transplantation is increased in patients receiving low-dose cyclosporine, regardless of blood cyclosporine levels

Background: Coronary artery disease (CAD) of allografted hearts is the main cause of late mortality after cardiac transplant, but its etiology is still undetermined. Hypothesis: This study was undertaken to evaluate the relevance of several risk factors, including cyclosporine (CsA) dose and blood CsA levels, to the incidence of CAD.Methods: In 163 heart transplants performed between November 1985 and August 1994 at our Institution, CAD was diagnosed by coronary angiography or at postmortem examination. Patients in whom postmortem examination or coronary angiography was not performed, as well as those <15 years of age and those who died within 1 month of surgery, were excluded from the study. The following risk factors were analyzed: recipient age, gender, pretransplant diagnosis, donor age, number of human leukocyte antigen (HLA)-AB mismatches, cytomegalovirus serology, mean serum cholesterol and triglyceride levels, the number of treated acute rejections, mean weighted CsA dose (CsA dose(w)) and weighted blood CsA levels (blood CsA level(w)).Results: Coronary artery disease was diagnosed in 32 patients (19.6%). A low mean CsA dose(w) was the only significant predictor for CAD at multivariate analysis (p < 0.01); there was no correlation with blood CsA level(w). In the patients receiving a CsA dose(w) > 4 mg/kg/day, the 8.9 year probability of their remaining CAD free was 69% [confidence interval (CI) 50-87%] in comparison with 31% (CI 0-65%) in patients receiving a CsA dose(w) < 4 mg/kg/day.Conclusion: In our experience, a low CsA maintenance dose is the main risk factor for CAD, irrespective of blood CsA levels.