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 (> or = 3A) 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.
Caforio
Alida L P
AL
Department of Cardiology, University of Padua, Padua, Italy. alida.caforio@unipd.it
Tona
Francesco
F
Fortina
Anna Belloni
AB
Angelini
Annalisa
A
Piaserico
Stefano
S
Gambino
Antonio
A
Feltrin
Giuseppe
G
Ramondo
Angelo
A
Valente
Marialuisa
M
Iliceto
Sabino
S
Thiene
Gaetano
G
Gerosa
Gino
G
D000328:Adult; D017668:Age of Onset; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D001835:Body Weight; D017023:Coronary Angiography; D003327:Coronary Disease / Q000175:diagnosis* / Q000209:etiology / Q000473:pathology* / Q000517:prevention & control; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology*; D016572:Cyclosporine / Q000627:therapeutic use; D005260:Female; D006084:Graft Rejection / Q000188:drug therapy* / Q000276:immunology; D016027:Heart Transplantation; D006801:Humans; D007108:Immune Tolerance; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D011379:Prognosis; D012307:Risk Factors; D014184:Transplantation, Homologous
D000893:Anti-Inflammatory Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011241:Prednisone