Key result
High polygenic risk score is linked to ~60% higher post-catheterization mortality vs. low score.
Why the study?
Polygenic risk scores for CAD can identify individuals at elevated risk, but their predictive value for all-cause mortality after coronary angiography beyond traditional risk factors and angiographic CAD was unclear.
Does a high polygenic risk score for CAD predict all-cause mortality in individuals undergoing coronary angiography?
Cohort (n=1,503)
Does a high polygenic risk score for CAD predict all-cause mortality in individuals undergoing coronary angiography?
Hazard Ratio: 1.6 (95% CI 1.2–2.2)
p-value: p=0.004
A genome-wide polygenic risk score for CAD improves risk stratification for all-cause mortality when added to traditional risk factors and coronary angiography, particularly identifying elevated risk in patients without angiographic CAD.
Genome-wide PRS for CAD was associated with mortality beyond angiographic disease; leaves open incremental value for clinical risk stratification.
BACKGROUND: Coronary artery disease (CAD) is influenced by genetic variation and traditional risk factors. Polygenic risk scores (PRS), which can be ascertained before the development of traditional risk factors, have been shown to identify individuals at elevated risk of CAD. Here, we demonstrate that a genome-wide PRS for CAD predicts all-cause mortality after accounting for not only traditional cardiovascular risk factors but also angiographic CAD itself. METHODS: Individuals who underwent coronary angiography and were enrolled in an institutional biobank were included; those with prior myocardial infarction or heart transplant were excluded. Using a pruning-and-thresholding approach, a genome-wide PRS comprised of 139 239 variants was calculated for 1503 participants who underwent coronary angiography and genotyping. Individuals were categorized into high PRS (hiPRS) and low-PRS control groups using the maximally selected rank statistic. Stratified analysis based on angiographic findings was also performed. The primary outcome was all-cause mortality following the index coronary angiogram. RESULTS: ) but did not differ by sex, body mass index, or traditional risk-factor profiles. Individuals with hiPRS were at significantly increased risk of all-cause mortality after cardiac catheterization, adjusting for traditional risk factors and angiographic extent of CAD (hazard ratio, 1.6; 95% CI, 1.2-2.2; P=0.004). The strongest increase in risk of all-cause mortality conferred by hiPRS was seen among individuals without angiographic CAD (hazard ratio, 2.4; 95% CI, 1.1-5.5; P=0.04). In the overall cohort, adding hiPRS to traditional risk assessment improved prediction of 5-year all-cause mortality (area under the receiver-operating curve 0.70; 95% CI, 0.66-0.75 versus 0.66; 95% CI, 0.61-0.70; P=0.001). CONCLUSIONS: A genome-wide PRS improves risk stratification when added to traditional risk factors and coronary angiography. Individuals without angiographic CAD but with hiPRS remain at significantly elevated risk of mortality.
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Levin et al. (2018) conducted a cohort in Coronary artery disease (n=1,503). High polygenic risk score (hiPRS) vs. Low polygenic risk score (low-PRS) was evaluated on All-cause mortality following the index coronary angiogram (HR 1.6, 95% CI 1.2-2.2, p=0.004). A high polygenic risk score significantly increased the risk of all-cause mortality after cardiac catheterization compared to a low score (HR 1.6; 95% CI 1.2-2.2; P=0.004).
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