# Coronary plaque changes with statin and colchicine among people with high polygenic risk- a mechanistic pilot study

> **NIH NIH R01** · MASSACHUSETTS GENERAL HOSPITAL · 2024 · $816,786

## Abstract

Project Summary
Genome-wide polygenic score for coronary artery disease (CAD) identifies 20% of the population with more
than double the average risk. Those individuals are not identified by clinical risk factors or family history, yet
they derive the greatest relative and absolute benefit from LDL-cholesterol lowering therapy.
A key barrier to the use of polygenic score in clinic to prevent CAD is the lack of prospective implementation
studies that quantify and characterize coronary atherosclerosis in individuals with high polygenic risk and
reverse it using pharmacological interventions. LDL-cholesterol pathways account for only a small proportion of
risk, and other mechanisms such as inflammation are of interest. Low dose colchicine has been shown to
reduce the risk of cardiovascular evens in patients with stable coronary artery disease, but the exact
mechanism of how colchicine affects coronary plaque is unknown.
Our proposal addresses those gaps and leverages recent innovations in genomic medicine, biobank data, and
coronary imaging for plaque characterization, through a genomic medicine implementation study of returning
results to hospital biobank participants followed by a mechanistic clinical trial of rosuvastatin and colchicine
using biomarkers and coronary plaque phenotypes on noninvasive coronary CT angiography (CCTA).
We already identified a target population from our hospital biobank consisting of several thousand individuals
who have no known cardiovascular disease, are not on lipid lowering or anti-inflammatory therapy, and have a
high polygenic score defined as top 20% of the distribution. In AIM1, we will return a high polygenic risk score
result to 300 participants and assess baseline and one-year cardiovascular health compared to a matched
group from the MGH Primary Care Cohort. In AIM2, we will measure lipid and inflammatory biomarkers and
perform CCTA on the 300 participants to study coronary plaque volumes and high-risk features, and their
association with cardiovascular health and lipid and inflammatory biomarkers among individuals with high
polygenic risk. In AIM3, we will determine if combination therapy with statin and low dose colchicine –
compared with statin alone – favorably modulates progression and composition of coronary atherosclerosis in
individuals with high polygenic score in a mechanistic pilot study of 150 participants followed for one year. This
study will provide a framework for identification, disclosure, and reversal of subclinical coronary atherosclerosis
in individuals with high polygenic risk and inform the mechanism by which low dose colchicine reduces
cardiovascular events through longitudinal phenotyping of coronary plaque.

## Key facts

- **NIH application ID:** 10874668
- **Project number:** 5R01HL164629-02
- **Recipient organization:** MASSACHUSETTS GENERAL HOSPITAL
- **Principal Investigator:** Akl C Fahed
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $816,786
- **Award type:** 5
- **Project period:** 2023-07-01 → 2028-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10874668

## Citation

> US National Institutes of Health, RePORTER application 10874668, Coronary plaque changes with statin and colchicine among people with high polygenic risk- a mechanistic pilot study (5R01HL164629-02). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10874668. Licensed CC0.

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