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, J. Jeffrey Carr, April P. Carson, Anne E. Nigra, Ramachandran S. Vasan, Robert E. Gerszten, Sadiya S. Khan, Ravi Kalhan, Matthew Nayor, Ravi V. Shah

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

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 languageEnglish (US)
Pages (from-to)138-154
Number of pages17
JournalCirculation research
Volume135
Issue number1
DOIs
StatePublished - Jun 21 2024
Externally publishedYes

Keywords

  • cardiovascular diseases
  • environment
  • heart failure
  • hypertension
  • myocardial infarction
  • risk factors

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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