Racial Disparities after Heart Transplant: Evidence from IMAGE

Abstract

Purpose The basis for increased mortality after heart transplant in non-Caucasians is poorly defined. We hypothesized that increased risk of adverse events is due to biological factors related to the alloimmune response. To test this hypothesis in the IMAGE study, we determined whether the event rate of the primary outcome (rejection with hemodynamic compromise, graft dysfunction, death, or retransplantation) varied by race in heart transplant recipients. We explored whether racial differences may be due to differences in levels of calcineurin inhibitors (CNI) or gene expression profile (GEP) scores. Methods and Materials We studied the event rate of the primary outcome, comparing racial groups in the IMAGE population, stratified by time post-transplant. We assessed whether differences in event rate varied as a function of CNI levels and GEP score. Logistic regression was used to compute the relative risk across racial groups and linear modeling was used to measure the dependence of GEP score and CNI on race. Results We found increased incidence of the primary endpoint in African Americans and other non-Caucasians, compared to Caucasians (18.3% and 22.2% vs. 8.5% respectively). African Americans had higher GEP score than Caucasians on CSA (p=0.01) despite similar levels. GEP score was higher, albeit tacrolimus blood level was lower, for other non-Caucasians than Caucasians. Conclusions Non-Caucasian heart transplant patients are 2.5-3 times more likely than Caucasians to experience rejection with hemodynamic compromise or death. Our data suggest that the increased risk of adverse outcomes may be due to the biology of the alloimmune response, which is less effectively abrogated by immunosuppression in non-Caucasians. Group Month post-tx Events/pt/yr Tac median trough CSA median trough GEP score mean (Tac) GEP score mean (CSA) Caucasian 7-12 0.09 8.8 167 28.8 26.1 13-36 0.07 8.2 144 30 30.1 >36 0.05 7.0 118 30 30 African American 7-12 0.27 9.3 141 30.5 32.2 13-36 0.18 8.4 120 29.8 32.2 >36 0.14 7.1 111 29.4 30.5 Other non-Caucasian 7-12 0.87 8.2 183 29.7 28.5 13-36 0.21 7.0 173 31.8 29.4 >36 0.07 5.7 122 29.6 28.0