Yimin Yang | Search PubMed

PubMed2026

Proteomic pathways mediating low socioeconomic status and cardiovascular events in older adults in CHS and ARIC.

BACKGROUND AND AIMS: Many studies have linked socioeconomic status (SES) and cardiovascular outcomes, yet the biologic mechanisms mediating these associations are only partially understood. The objective of this study was to identify molecular mediators of the association of low SES with coronary heart disease (CHD) and stroke. METHODS: This research was conducted in 2942 Black and White adults in the Cardiovascular Health Study (mean age 76.2 years) and 10,689 Black and White adults in the Atherosclerosis Risk in Communities Study (mean age 60.0 years). We used factor analysis to create a composite measure of low educational attainment, low-income, and blue-collar occupation. Approximately 5000 proteins were measured with an aptamer-based method, and CHD and stroke events were adjudicated. Results were stratified by race, which was conceptualized as a social factor. RESULTS: Low SES was associated with 44 and 262 proteins, in Black and White adults, respectively. No protein met the Bonferroni adjusted threshold for statistically significantly mediation among Black participants. Among White participants, 23 proteins mediated the association between SES adversity and CHD and 5 mediated the association between SES adversity and stroke. The strongest mediating associations for CHD included PTPRS, SCG3, and MMP12. The strongest mediating associations for stroke included NCAN, FAM20B, and APLP1. SPARCL1 and CDCP1 remained the strongest mediators of the association between SES adversity and CHD, after adjusting for potential confounders and traditional cardiovascular risk factors. CONCLUSION: We identified several biomarkers that characterize the biologic risk of SES adversity on CHD and stroke.

Aged↗

PubMed2026

Large-Scale Proteomic Profiling of Incident Heart Failure and Its Subtypes in Older Adults.

BACKGROUND: Heart failure (HF) and its main subtypes, heart failure with preserved ejection fraction (HFpEF) and heart failure with reduced ejection fraction (HFrEF), impose an enormous health burden on elders. Assessment of the circulating proteome to illuminate pathogenesis could open new opportunities for treatment. METHODS: We conducted a plasma proteomics screen of incident HF and its subtypes in 2 older population-based cohorts, the CHS (Cardiovascular Health Study) and the AGES-RS (Aging, Gene/Environment Susceptibility-Reykjavik Study). The 2 studies used SomaLogic platforms, with 4404 aptamers in common. Multivariable Cox models were fit to evaluate individual-protein associations with HF, HFpEF, and HFrEF separately in each cohort, and study-specific associations were combined by fixed-effects meta-analysis. Replication was performed in the ARIC (Atherosclerosis Risk in Communities) cohort. Two-sample Mendelian randomization of HF and its subtypes, along with colocalization analysis, was performed to support causal inference. RESULTS: Among 8599 participants, 1590 experienced incident HF (536 HFpEF, 471 HFrEF). There were 119 proteins associated with HF, 15 proteins with HFpEF, and 11 proteins with HFrEF, at Bonferroni-corrected significance. Among these, 9 have never previously been identified for cardiovascular diseases, and another 61 represent new associations with incident HF or its subtypes. Of these 70 proteins, 55 of the 66 available replicated externally. Mendelian randomization analysis revealed 7 proteins genetically associated with HF at nominal significance; 2 were separately associated with HFpEF, and another 2 with HFrEF. Seven of these 9 proteins (NPDC1 [neural proliferation differentiation and control protein 1], APOF [apolipoprotein F], LMAN2 [lectin, mannose-binding 2], ADIPOQ [adiponectin], CD14 [cluster of differentiation 14], ARHGAP1 [Rho GTPase-activating protein 1], C9 [complement 9]) showed new, possibly causal associations, although we did not detect evidence for colocalization. CONCLUSIONS: In this large-scale proteomic study involving 3 longitudinal cohorts of older adults, we identified and replicated 55 novel protein markers of HF or its subtypes, and 7 new, possibly causal proteins. These proteins may enhance risk prediction, improve understanding of pathobiology, and help prioritize targets for therapeutic development of these foremost disorders in elders.

Humans↗