Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension

Jason H. Karnes, Howard W. Wiener, Tae Hwi Schwantes-An, Balaji Natarajan, Andrew J. Sweatt, Abhishek Chaturvedi, Amit Arora, Ken Batai, Vineet Nair, Heidi E. Steiner, Jason B. Giles, Jeffrey Yu, Maryam Hosseini, Michael W. Pauciulo, Katie A. Lutz, Anna W. Coleman, Jeremy Feldman, Rebecca Vanderpool, Haiyang Tang, Joe G.N. GarciaJason X.J. Yuan, Rick Kittles, Vinicio de Jesus Perez, Roham T. Zamanian, Franz Rischard, Hemant K. Tiwari, William C. Nichols, Raymond L. Benza, Ankit A. Desai

Research output: Contribution to journalArticle

2 Scopus citations

Abstract

Rationale: Limited information is available on racial/ethnic differences in pulmonary arterial hypertension (PAH).Objectives: Determine effects of race/ethnicity and ancestry on mortality and disease outcomes in diverse patients with PAH.Methods: Patients with Group 1 PAH were included from two national registries with genome-wide data and two local cohorts, and further incorporated in a global meta-analysis. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated for transplant-free, all-cause mortality in Hispanic patients with non-Hispanic white (NHW) patients as the reference group. Odds ratios (ORs) for inpatient-specific mortality in patients with PAH were also calculated for race/ethnic groups from an additional National Inpatient Sample dataset not included in the meta-analysis.Measurements and Main Results: After covariate adjustment, self-reported Hispanic patients (n = 290) exhibited significantly reduced mortality versus NHW patients (n = 1,970) after global meta-analysis (HR, 0.60 [95% CI, 0.41-0.87]; P = 0.008). Although not significant, increasing Native American genetic ancestry appeared to account for part of the observed mortality benefit (HR, 0.48 [95% CI, 0.23-1.01]; P = 0.053) in the two national registries. Finally, in the National Inpatient Sample, an inpatient mortality benefit was also observed for Hispanic patients (n = 1,524) versus NHW patients (n = 8,829; OR, 0.65 [95% CI, 0.50-0.84]; P = 0.001). An inpatient mortality benefit was observed for Native American patients (n = 185; OR, 0.38 [95% CI, 0.15-0.93]; P = 0.034).Conclusions: This study demonstrates a reproducible survival benefit for Hispanic patients with Group 1 PAH in multiple clinical settings. Our results implicate contributions of genetic ancestry to differential survival in PAH.

Original languageEnglish (US)
Pages (from-to)1407-1415
Number of pages9
JournalAmerican journal of respiratory and critical care medicine
Volume201
Issue number11
DOIs
StatePublished - Jun 1 2020

Keywords

  • Hispanic American
  • Native American
  • health disparities
  • pulmonary arterial hypertension
  • survival

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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    Karnes, J. H., Wiener, H. W., Schwantes-An, T. H., Natarajan, B., Sweatt, A. J., Chaturvedi, A., Arora, A., Batai, K., Nair, V., Steiner, H. E., Giles, J. B., Yu, J., Hosseini, M., Pauciulo, M. W., Lutz, K. A., Coleman, A. W., Feldman, J., Vanderpool, R., Tang, H., ... Desai, A. A. (2020). Genetic Admixture and Survival in Diverse Populations with Pulmonary Arterial Hypertension. American journal of respiratory and critical care medicine, 201(11), 1407-1415. https://doi.org/10.1164/rccm.201907-1447OC