Ancestryverschillen in hartfalen en MACE bij volwassenen met aangeboren hartafwijkingen — All of Us

Most individuals born with congenital heart disease now survive to adulthood, producing a growing population at risk for major adverse cardiovascular events (MACE). Ancestry-based disparities are incompletely characterized and polygenic risk has not been related to outcomes. We analyzed 6,771 adult ACHD participants in All of Us (White n=5,065, Hispanic n=882, Black n=824) and computed five polygenic scores: one for coronary artery disease and four for heart failure trained on African, European, Hispanic or Latin American, and multi-ancestry data. MACE was present in 51.0% and differed by ancestry (Black 56.3%, White 50.7%, Hispanic 47.5%; P=0.001). Black participants developed heart failure 11 years earlier (median 54 vs. 65 years). The pooled disparity attenuated to the null after comorbidity adjustment, with chronic kidney disease accounting for 58.6% of the age- and sex-adjusted effect, but age-specific estimates opposed one another (adjusted OR 1.78 at 40, 0.66 at 80; interaction P<0.001); survivor selection may contribute at older ages. No score improved discrimination or explained the disparity (area under the curve change ≤0.0047). The African-ancestry score was associated with heart failure alone (OR 1.09 per SD, q=0.022); the European and multi-ancestry scores with heart failure, arrhythmia, and MACE alike. Performance did not track training-population ancestry. The coronary and African-ancestry scores ordered the same participants in opposite directions (r=-0.198), indicating between-group offsets reflect allele frequency rather than genomic risk. Black participants underwent fewer structural cardiac reinterventions (8.6% vs. 16.4%; adjusted OR 0.47, P<0.001) despite comparable adjusted ACE inhibitor or angiotensin receptor blocker prescription.