Immune and nonimmune predictors of cardiac allograft vasculopathy onset and severity: Multivariate risk factor analysis and role of immunosuppression

We studied 361 patients, to evaluate risk factors for cardiac allograft vasculopathy (CAV) onset and severity/diffusion in heart transplantation (HT). Rejection scores (RS) on endomyocardial biopsy were calculated (first year and whole follow-up). CAV onset was defined as any lesion seen at yearly angiography. A CAV severity/diffusion index was calculated for each patient summing up the scores of all lesions. Cox multivariate analysis included: donor age, sex, and weight; recipient sex, age, pre-HT diagnosis, hypertension, diabetes and hyperlipidemia post-HT; number of treated rejections and RS; and immunosuppressive dosage at 3, 6, and 12 months. CAV frequency was 2% at 1 year, 22% at 5 and 39% at 10 years. Risk factors for CAV onset were older donor age [p<0.0001, relative risk (RR)=9.9], male donor (p<0.001, RR=3.2), high RS for severe (greater than or equal to3A) grades (p<0.02, RR=2.01), high cyclosporine at 3 months (p<0.02, RR=1.9). Risk factors for CAV severity/diffusion were higher donor weight (p<0.01, RR=7.5), high prednisone dosage at 1 year (p<0.0001, RR=21.1), and coronary disease pre-HT (p<0.002, RR=9.7). High RS was an independent predictor for CAV onset, not severity/diffusion. This suggests an immune basis for CAV onset and nonimmune modulation for progression. High RS for severe grades may provide a predictor for patients at risk.