# Proteomics of Cardiovascular Risk: The Multiethnic Study of Atherosclerosis

> **NIH NIH R01** · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · 2021 · $717,697

## Abstract

PROJECT SUMMARY
Atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF) remain the leading cause of mortality in
the U.S. Despite improved therapies, the incidence of first ASCVD and HF events is still unacceptably high.
Progress in preventing and managing these conditions will require a better understanding of their novel risk
factors and biological pathways. Protein levels can serve as potent, specific, and modifiable biomarkers for
ASCVD and HF risk, guide therapy and elucidate causal pathways. Large-scale proteomic technology has
become available to scan 4,993 distinct proteins simultaneously in just 0.15 ml of plasma, using modified
aptamers as binding reagents. The overarching goal of this proposal is to apply large-scale proteomics to
patients who are free of cardiovascular disease (CVD) to improve incident ASCVD and HF risk prediction and
increase understanding of the biological pathways and mechanisms underlying the development of these
diseases. We will conduct the proteomic investigation in MESA, a well-characterized, racially diverse cohort of
6814 persons without CVD at baseline, recruited between 2000 and 2002. Now >15 years out from the initial
study visit, >800 cardiovascular events have accumulated, providing an opportunity for ASCVD and HF risk
modeling. MESA was conceived with the primary goal to study “progression of subclinical to clinical CVD, with
coronary artery calcification (CAC) as a subclinical measure of ASCVD and cardiac MR (CMR) as a subclinical
measure of HF. Thus, in addition to modeling of ASCVD and HF clinical outcomes, we will devise proteomic
risk scores for the development of subclinical ASCVD and HF and for their conversion to clinical events. We
will conduct proteomic studies at three study visits that span 10 years, to delineate longitudinal proteomic risk
trajectories and create “live” mutable risk scores. Lastly, in an exploratory aim, we will leverage MESA’s near
equal representation of men and women and its racial diversity by testing for any heterogeneity of proteomic
risk scores and biological pathways associated with ASCVD and HF, according to sex and by race. Models for
ASCVD and HF risk will be developed within MESA and then externally validated in the Atherosclerosis Risk in
Communities (ARIC) cohort. In sum, our Aims are to assay the concentrations of 4,993 plasma proteins in
6,043 MESA participants at 3 study visits spanning 10 years to: 1) improve the risk prediction of incident
ASCVD and HF outcomes and earlier subclinical disease, 2) inform the biological pathways of incident ASCVD
and HF outcomes and subclinical disease, 3) inform sex and racial differences in the biology and propensity to
develop ASCVD and HF, and 4) validate key findings in the ARIC cohort.

## Key facts

- **NIH application ID:** 10279850
- **Project number:** 1R01HL159081-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
- **Principal Investigator:** Rajat Deo
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $717,697
- **Award type:** 1
- **Project period:** 2021-07-02 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10279850

## Citation

> US National Institutes of Health, RePORTER application 10279850, Proteomics of Cardiovascular Risk: The Multiethnic Study of Atherosclerosis (1R01HL159081-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10279850. Licensed CC0.

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