Genetic Factors Predict Post-Angiography Outcomes

TOPLINE:

The genomic drivers of coronary artery disease (CAD) are associated with the presentation of acute coronary syndromes and the severity and burden of angiographic CAD; these drivers also predict the risk for adverse outcomes after angiography.

METHODOLOGY:

• Researchers conducted a retrospective cohort study to examine the association of genomic drivers of CAD with the severity of the condition and future outcomes in patients who underwent coronary angiography.
• They included 3518 participants with genomic data (median age, 64 years; 70.1% men; 89.6% White individuals) from a hospital-based biobank who underwent their first coronary angiography between July 2000 and August 2023 and were followed through October 2023.
• Pathogenic variants of causal genes of familial hypercholesterolemia, a high CAD polygenic risk score, and clonal hematopoiesis of indeterminate potential (CHIP) were defined as genomic drivers of CAD.
• The presentation (acute or stable), severity (none, mild, moderate, or severe), and burden (measured using the modified Gensini score) of CAD were outcomes of interest.
• Angiographic outcomes included repeat angiogram, revascularization, and in-stent restenosis; clinical outcomes were incident heart failure and all-cause mortality.

TAKEAWAY:

• Patients with at least one genomic driver of CAD showed higher odds of having angiographic CAD, ranging from mild (adjusted odds ratio [aOR], 1.61; P = 4.09 × 10⁻⁴) to severe (aOR, 2.94; P = 8.57 × 10⁻³³), than did those without the condition and were more likely to present with acute coronary syndromes (aOR, 2.67; P = 7.57 × 10⁻²²).
• Carriers of familial hypercholesterolemia undergoing coronary angiography showed higher odds of having moderate to severe angiographic CAD than of having mild or no CAD (aOR, 3.01; P = .03). Each standard deviation increase in the polygenic risk score was correlated with a 12.51-point higher Gensini score (P −16).
• During 9.2 years of follow-up, familial hypercholesterolemia variants and a high polygenic risk score were associated with an increased risk for a repeat angiogram and revascularization; a high polygenic risk score also was associated with an increased risk for in-stent restenosis.
• CHIP carriers showed no significant association with angiographic outcomes but had increased risks for heart failure and mortality.

IN PRACTICE:

“While genomics has conventionally been perceived as most helpful in primary CAD prevention, recent evidence shows a strong ability to even predict risk of recurrent events after a CAD diagnosis. We observed that the germline genomic risk at the time of coronary angiography may be predictive of repeat angiogram, revascularization, and in-stent restenosis, even after adjusting for disease burden,” the authors of the study wrote. “Genomic risk information might be helpful in guiding secondary prevention strategies, even after CAD is diagnosed on coronary angiography, such as with more aggressive treatment goals for individuals at the highest risk of progression due to the underlying genomic profile,” they added.

SOURCE:

This study was led by Kelvin Supriami, MD, and Sarah M. Urbut, MD, PhD, of the Department of Medicine at Harvard Medical School, Boston. It was published online on January 21, 2025, in JAMA Network Open.

LIMITATIONS:

The small sample size for familial hypercholesterolemia carriers and a primarily White study population limited the generalizability of the findings. The ability of coronary angiography to fully assess the presence of plaques, biologic factors, and extent of the disease is limited. CHIP was identified within 10 years before coronary angiography, so patients who developed CHIP after enrollment in the biobank but before angiography might have been missed.

DISCLOSURES:

The authors of this study received support from multiple organizations including the Indonesian Endowment Fund for Education; National Human Genome Research Institute; National Science Foundation; National Heart, Lung, and Blood Institute; American Heart Association; and National Institutes of Health. Several authors reported having financial ties with institutions, academies, and companies outside the submitted work. 

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.