Proteomics, Human Environmental Exposure, and Cardiometabolic Risk

Andrew S Perry; Kai Zhang; Venkatesh L Murthy; Bina Choi; Shilin Zhao; Priya Gajjar; Laura A Colangelo; Lifang Hou; Mary B Rice; John Jeffrey Carr; April P Carson; Anne E Nigra; Ramachandran S Vasan; Robert E Gerszten; Sadiya S Khan; Ravi Kalhan; Matthew Nayor; Ravi V Shah

doi:10.1161/CIRCRESAHA.124.324559

Proteomics, Human Environmental Exposure, and Cardiometabolic Risk

Circ Res. 2024 Apr 25. doi: 10.1161/CIRCRESAHA.124.324559. Online ahead of print.

Authors

Andrew S Perry¹, Kai Zhang², Venkatesh L Murthy³, Bina Choi⁴, Shilin Zhao¹, Priya Gajjar⁵, Laura A Colangelo⁶, Lifang Hou⁶, Mary B Rice⁷, John Jeffrey Carr¹, April P Carson⁸, Anne E Nigra⁹, Ramachandran S Vasan¹⁰, Robert E Gerszten^{11

12}, Sadiya S Khan¹³, Ravi Kalhan¹⁴, Matthew Nayor¹⁵, Ravi V Shah¹

Affiliations

¹ Vanderbilt Translational and Clinical Cardiovascular Research Center, Vanderbilt University School of Medicine, Nashville, TN (A.S.P., S.Z., J.J.C., R.V.S.).
² Department of Environmental Health Sciences, School of Public Health, University at Albany, State University of New York, (K.Z.).
³ Department of Medicine, University of Michigan, Ann Arbor (V.L.M.).
⁴ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA (B.C.).
⁵ Cardiovascular Medicine Section, Department of Medicine, Boston University School of Medicine, MA. (P.G.).
⁶ Department of Preventive Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. (L.A.C., L.H.).
⁷ Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA (M.B.R.).
⁸ Department of Medicine, University of Mississippi Medical Center, Jackson (A.P.C.).
⁹ Department of Environmental Health Science, Columbia University Mailman School of Public Health, New York, NY (A.E.N.).
¹⁰ School of Public Health, School of Medicine, University of Texas San Antonio (R.S.V.).
¹¹ Broad Institute of Harvard and MIT, Cambridge, MA (R.E.G.).
¹² Cardiovascular Institute, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA (R.E.G.).
¹³ Division of Cardiology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. (S.S.K.).
¹⁴ Division of Pulmonary and Critical Care Medicine, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL. (R.K.).
¹⁵ Sections of Cardiovascular Medicine and Preventive Medicine and Epidemiology, Department of Medicine, Boston University School of Medicine, MA. (M.N.).

PMID: 38662804
DOI: 10.1161/CIRCRESAHA.124.324559

Abstract

Background: The biological mechanisms linking environmental exposures with cardiovascular disease pathobiology are incompletely understood. We sought to identify circulating proteomic signatures of environmental exposures and examine their associations with cardiometabolic and respiratory disease in observational cohort studies.

Methods: We tested the relations of >6500 circulating proteins with 29 environmental exposures across the built environment, green space, air pollution, temperature, and social vulnerability indicators in ≈3000 participants of the CARDIA study (Coronary Artery Risk Development in Young Adults) across 4 centers using penalized and ordinary linear regression. In >3500 participants from FHS (Framingham Heart Study) and JHS (Jackson Heart Study), we evaluated the prospective relations of proteomic signatures of the envirome with cardiovascular disease and mortality using Cox models.

Results: Proteomic signatures of the envirome identified novel/established cardiovascular disease-relevant pathways including DNA damage, fibrosis, inflammation, and mitochondrial function. The proteomic signatures of the envirome were broadly related to cardiometabolic disease and respiratory phenotypes (eg, body mass index, lipids, and left ventricular mass) in CARDIA, with replication in FHS/JHS. A proteomic signature of social vulnerability was associated with a composite of cardiovascular disease/mortality (1428 events; FHS: hazard ratio, 1.16 [95% CI, 1.08-1.24]; P=1.77×10^-5; JHS: hazard ratio, 1.25 [95% CI, 1.13-1.38]; P=6.38×10^-6; hazard ratioexpressed as per 1 SD increase in proteomic signature), robust to adjustment for known clinical risk factors.

Conclusions: Environmental exposures are related to an inflammatory-metabolic proteome, which identifies individuals with cardiometabolic disease and respiratory phenotypes and outcomes. Future work examining the dynamic impact of the environment on human cardiometabolic health is warranted.

Keywords: cardiovascular diseases; heart failure; hypertension; myocardial infarction; risk factors.