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Updated: Jun 1, 2025

Coronary Progenitor Cells and Soluble Biomarkers in Cardiovascular Prognosis after Coronary Angioplasty
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Genomic Drivers of Coronary Artery Disease and Risk of Future Outcomes After Coronary Angiography

Kelvin Supriami1,2,3, Sarah M Urbut1,2,3, José R Tello-Ayala2,3,4

  • 1Department of Medicine, Harvard Medical School, Boston, Massachusetts.

JAMA Network Open
|January 21, 2025
PubMed

Insights

Genomic risk factors like familial hypercholesterolemia (FH) and high polygenic risk score (PRS) are linked to severe coronary artery disease (CAD) and adverse outcomes after angiography. Clonal hematopoiesis (CHIP) is associated with heart failure and mortality.

Area of Science:

  • Cardiovascular Genetics
  • Interventional Cardiology
  • Genomic Medicine

Background:

  • Understanding the impact of genetic factors on coronary artery disease (CAD) presentation and outcomes post-coronary angiography is crucial.
  • Genomic risk factors, including familial hypercholesterolemia (FH), high polygenic risk score (PRS), and clonal hematopoiesis of indeterminate potential (CHIP), play a role in CAD.
  • The specific angiographic characteristics and post-procedure risks associated with these genomic drivers require further elucidation.

Purpose of the Study:

  • To investigate the angiographic features of CAD in patients with FH, high PRS, and CHIP.
  • To evaluate the association between these genomic risk factors and outcomes following coronary angiography.
  • To determine if specific genetic predispositions influence the severity of CAD and subsequent clinical events.

Main Methods:

  • A retrospective cohort study was conducted using data from 3518 participants in the Mass General Brigham Biobank with available genomic information.
  • Participants who underwent coronary angiography between July 18, 2000, and August 1, 2023, were analyzed.
  • Genomic risk factors (FH variants, high CAD PRS, CHIP driver variations) were identified and correlated with angiographic findings and clinical outcomes.

Main Results:

  • Over 40% of participants (1509/3518) had at least one genomic driver of CAD (FH, high PRS, or CHIP).
  • Genomic drivers, particularly FH and high PRS, were associated with acute coronary syndromes presentation, and increased CAD presence, burden, and severity.
  • FH and high PRS carriers showed increased risks for repeat angiograms, revascularization, and in-stent restenosis. CHIP carriers had higher risks for heart failure and all-cause mortality.

Conclusions:

  • Germline genetic factors (monogenic and polygenic) are significantly associated with acute coronary syndromes, atherosclerosis severity, and adverse angiographic outcomes.
  • Clonal hematopoiesis of indeterminate potential (CHIP) is linked to increased risks of heart failure and mortality post-coronary angiography.
  • These findings highlight the importance of integrating genomic risk assessment into the management of patients undergoing coronary angiography.
Abstract

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