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The Influence of Race and Common Genetic Variations on Outcomes After Pediatric Heart Transplantation
D J Green1, M M Brooks2, G J Burckart1
1Pediatric Clinical Pharmacology Staff, Office of Clinical Pharmacology, Office of Translational Sciences, Center for Drug Evaluation and Research, U.S. Food and Drug Administration, Silver Spring, MD.
Insights
Racial disparities persist in pediatric heart transplantation outcomes. Black children faced higher risks of death, graft loss, and rejection, even after accounting for clinical and genetic factors.
Area of Science:
- Pediatric Cardiology
- Transplantation Medicine
- Health Disparities Research
Background:
- Significant racial disparities exist in pediatric heart transplantation outcomes.
- Unfavorable outcomes, including death and graft loss, disproportionately affect Black children.
Purpose of the Study:
- To identify specific pediatric post-heart transplantation outcomes that differ by race.
- To investigate whether demographic, clinical, and genetic factors explain these racial differences.
Main Methods:
- Retrospective analysis of 80 Black and 450 non-Black pediatric heart transplant recipients (1993-2008).
- Genotyping for 20 candidate genes.
- Multivariate regression analysis adjusting for multiple variables.
Main Results:
- Black recipients had significantly higher unadjusted 5-year rates of death, graft loss, acute rejection with hemodynamic compromise, and late rejection.
- Black recipients were older at transplant, more likely to have cardiomyopathy and public insurance, and less likely to receive induction therapy.
- Even after adjusting for clinical and genetic factors, Black race remained a significant risk factor for adverse outcomes, explaining only 8-19% of the excess risk.
Conclusions:
- Racial differences in survival, graft loss, and rejection outcomes after pediatric heart transplantation are confirmed.
- These disparities are not fully explained by known recipient demographic, clinical, or genetic attributes.
Abstract:
Significant racial disparity remains in the incidence of unfavorable outcomes following heart transplantation. We sought to determine which pediatric posttransplantation outcomes differ by race and whether these can be explained by recipient demographic, clinical, and genetic attributes. Data were collected for 80 black and 450 nonblack pediatric recipients transplanted at 1 of 6 centers between 1993 and 2008. Genotyping was performed for 20 candidate genes. Average follow-up was 6.25 years. Unadjusted 5-year rates for death (p = 0.001), graft loss (p = 0.015), acute rejection with severe hemodynamic compromise (p = 0.001), late rejection (p = 0.005), and late rejection with hemodynamic compromise (p = 0.004) were significantly higher among blacks compared with nonblacks. Black recipients were more likely to be older at the time of transplantation (p < 0.001), suffer from cardiomyopathy (p = 0.004), and have public insurance (p < 0.001), and were less likely to undergo induction therapy (p = 0.0039). In multivariate regression models adjusting for age, sex, cardiac diagnosis, insurance status, and genetic variations, black race remained a significant risk factor for all the above outcomes. These clinical and genetic variables explained only 8-19% of the excess risk observed for black recipients. We have confirmed racial differences in survival, graft loss, and several rejection outcomes following heart transplantation in children, which could not be fully explained by differences in recipient attributes.
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