Proteomic Profiling of Pulmonary Function and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities Study

Authors

Yura Lee
Astrid M Manuel
Ngoc Quynh H Nguyen
Christine Ladd-Acosta
Alanna C Morrison
Kari E North
Eric Boerwinkle
Amil M Shah
Zhongming Zhao
Stephanie J London
Bing Yu

Language

English

Publication Date

3-3-2026

Journal

Journal of the American Heart Association

DOI

10.1161/JAHA.125.043281

PMID

41717923

Abstract

Background: Pulmonary function is linked to cardiovascular disease risk; however, the underlying mechanisms remain unclear. We aimed to identify protein biomarkers associated with pulmonary function and examine their impact on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and all-cause mortality.

Methods: Data from White and Black Americans in the Atherosclerosis Risk in Communities study (visit 2: N=11 354, mean age=57 years; visit 5: N=3517, mean age=75 years), a prospective cohort, were analyzed. Linear regression assessed associations between protein levels and pulmonary function measures, including forced expiratory volume in 1 second and forced vital capacity. The impact of the identified proteins on incident chronic obstructive pulmonary disease, coronary heart disease, heart failure, and mortality was estimated using logistic regression and Cox proportional hazards models. Pathway enrichment and Mendelian randomization explored underlying biological functions and causal effects.

Results: Of 4766 proteins analyzed, 364 were cross-sectionally associated with forced expiratory volume in 1 second (and forced vital capacity (false discovery rate< 0.05). Ninety-four and 270 proteins had concordant positive and negative effects, respectively. Five pathways related to pulmonary and cardiac function were enriched. Of the 364 proteins, 112 were linked to all 4 outcomes, where 86 were associated with increased risk (odds ratio/hazard ratio [OR/HR], 1.05-1.42) and 26 with reduced risk (OR/HR, 0.69-0.96). Six proteins (STAT3 [signal transducer and activator of transcription 3], MIC-1 [growth differentiation factor 15], apoA-II [apolipoprotein A-II], TPST1 [protein-tyrosine sulfotransferase 1], integrin a1b1 [integrin alpha-I: beta-1 complex], and BLC [C-X-C motif chemokine 13]) showed potential inverse causal effects on with forced expiratory volume in 1 second and forced vital capacity, and integrin a1b1 demonstrated consistent inverse associations with chronic obstructive pulmonary disease, coronary heart disease, and heart failure risks.

Conclusions: Proteins associated with pulmonary function may influence CVD risk. Six proteins, including integrin a1b1, represent promising targets for future interventions.

Keywords

Humans, Male, Female, Aged, Middle Aged, Proteomics, United States, Pulmonary Disease, Chronic Obstructive, Prospective Studies, Forced Expiratory Volume, Vital Capacity, Lung, Biomarkers, Risk Assessment, Risk Factors, Heart Failure, Incidence, Coronary Disease, Cardiovascular Diseases, Black or African American, Cross-Sectional Studies, White, biomarker, forced expiratory volume in 1 second, forced vital capacity, proteomics, pulmonary function

Published Open-Access

yes

Recommended Citation

Lee, Yura; Manuel, Astrid M; Nguyen, Ngoc Quynh H; et al., "Proteomic Profiling of Pulmonary Function and Cardiovascular Disease Risk in the Atherosclerosis Risk in Communities Study" (2026). Faculty, Staff and Student Publications. 6308.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6308