Proteomics, Human Environmental Exposure, and Cardiometabolic Risk.

Publisher: Lippincott Williams & Wilkins Country of Publication: United States NLM ID: 0047103 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1524-4571 (Electronic) Linking ISSN: 00097330 NLM ISO Abbreviation: Circ Res Subsets: MEDLINE

Publication: Baltimore, MD : Lippincott Williams & Wilkins
Original Publication: Baltimore, Md. Grune & Stratton.

Proteomics*/methods ; Environmental Exposure*/adverse effects ; Cardiovascular Diseases*/blood ; Cardiovascular Diseases*/etiology ; Cardiovascular Diseases*/epidemiology ; Cardiometabolic Risk Factors*; Humans ; Female ; Male ; Adult ; Middle Aged ; Prospective Studies ; Young Adult

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, 1.14-1.38]; P =6.38×10 ^-6 ; hazard ratio expressed 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.
Competing Interests: Disclosures R.V. Shah is supported in part by grants from the National Institutes of Health and the American Heart Association. In the past 12 months, R.V. Shah has served for a consultant for Amgen and Cytokinetics. R.V. Shah is a co-inventor on a patent for ex-RNAs signatures of cardiac remodeling and a pending patent on proteomic signatures of fitness and lung and liver diseases. V.L. Murthy has received grant support from Siemens Healthineers, NIDDK, NIA, NHLBI and AHA. V.L. Murthy has received other research support from NIVA Medical Imaging Solutions. V.L. Murthy owns stock in Eli Lilly, Johnson & Johnson, Merck, Bristo-Myers Squibb, Pfizer and stock options in Ionetix. V.L. Murthy has received research grants and speaking honoraria from Quart Medical. M. Nayor received speaking honoraria from Cytokinetics. M. Nayor is supported by the NIH and by a Career Investment Award from the Department of Medicine, Boston University School of Medicine. B. Choi is supported by the NIH and American Heart Association. M.B. Rice is supported by the NIH and reports fees from the Conservation Law Foundation. The remaining authors report no disclosures.

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R01 AG081244 United States AG NIA NIH HHS; R01 HL133870 United States HL NHLBI NIH HHS; N01HC25195 United States HL NHLBI NIH HHS; 75N92019D00031 United States HL NHLBI NIH HHS; R01 HL122477 United States HL NHLBI NIH HHS

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

Date Created: 20240425 Date Completed: 20240620 Latest Revision: 20240827

20240827

PMC11189739

10.1161/CIRCRESAHA.124.324559

38662804