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, 1.14-1.38]; 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.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 138-154 |
| Number of pages | 17 |
| Journal | Circulation research |
| Volume | 135 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jun 21 2024 |
Funding
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. This work was supported by the American Heart Association (20SFRN35120123). FHS (Framingham Heart Study) is supported by the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH; contracts N01-HC-25195, HHSN268201500001I, and 75N92019D00031). JHS (Jackson Heart Study) is supported and conducted in collaboration with the Jackson State University (HHSN268201800013I), the Tougaloo College (HHSN268201800014I), the Mississippi State Department of Health (HHSN268201800015I), and the University of Mississippi Medical Center (HHSN268201800010I, HHSN268201800011I, and HHSN268201800012I) contracts from the NHLBI and the National Institute on Minority Health and Health Disparities . The authors also wish to thank the staff and participants of JHS. Support for proteomic quantification in JHS was provided by a grant to R.E. Gerszten from the NHLBI (R01HL133870). CARDIA is conducted and supported by the NHLBI in collaboration with the University of Alabama at Birmingham (HHSN268201800005I and HHSN268201800007I), the Northwestern University (HHSN268201800003I), the University of Minnesota (HHSN268201800006I), and the Kaiser Foundation Research Institute (HHSN268201800004I). Support for quantification of the human envirome in CARDIA (Coronary Artery Risk Development in Young Adults) was provided in part by grants awarded to K. Zhang and L. Hou from the American Heart Association (19TPA34830085) and the National Institute of Aging (R01AG081244). Proteomics quantification was funded by the NHLBI (HL122477; P.I. Kalhan). This article has been reviewed by CARDIA for scientific content. The views expressed in this article are those of the authors and do not necessarily represent the views of the NHLBI; the NIH; or the US Department of Health and Human Services.
Keywords
- cardiovascular diseases
- environment
- heart failure
- hypertension
- myocardial infarction
- risk factors
ASJC Scopus subject areas
- Physiology
- Cardiology and Cardiovascular Medicine
