Abstract 18306: Race, Natriuretic Peptides, and Physiological Perturbations

Abstract

Listen

Translate article

Introduction: Racial differences in natriuretic peptide (NP) levels among young adults are uncharacterized. Race-based differences in NP response to physiological and pharmacological perturbations are unknown. Methods and Results: A population-level study in healthy young individuals (18-40 years) with NT-proBNP measurements from the 1999-2004 National Health and Nutrition Examination Survey cycles was conducted. In this study of 3055 individuals, Blacks [34.3% (29.3-38.9%)] had lower NT-proBNP levels compared with Whites. Healthy participants were recruited in 2018-23 in a mechanistic trial to assess the racial differences in NP response to standardized exercise and 6 weeks of metoprolol (started at 50 mg/day and doubled every 2 weeks). MR-proANP was measured pre- and post-exercise, before starting metoprolol and then every 2 weeks till study completion. Among 72 young adults [39 (54.2%) White, 37 (51.4%) females], the increase in MR-proANP levels was higher in Whites [49.0% (38.2-60.6%) compared with Blacks [35.9% (25.2-47.6%)] after exercise (p int : 0.004). With metoprolol, MR-proANP levels increased by 36.3% (23.3-50.8%) in Whites and 28.3% (15.0-43.0%) in Blacks (p int :0.42). To assess the mechanism of ANP increase, iPSC-CM (3 controls and 3 experiments) were treated with metoprolol to assess the change in NPPA expression. miR-425 (negative regulator of ANP) levels were measured at the abovementioned time points. The expression of NPPA in iPSC-CM did not change on treatment with metoprolol. With metoprolol, the relative expression of miR-425 reduced by ~10% at the end of 6 weeks. Conclusion: Using multiple lines of evidence, this study established that healthy young Blacks have lower NP levels and have a blunted NP response to exercise compared with Whites. ANP protein levels differed but no changes in ANP expression were noted with metoprolol. Further work is needed to elucidate pathways underlying miR-425 expression responsiveness with metoprolol.