Use of a polygenic risk score to enhance early detection of coronary atherosclerosis

Figures

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  Fig. 1. Presence, extent and severity of coronary plaque by genetic risk category. (A) Bar graph highlights the stepwise increase in CCTA-detected atherosclerosis and plaque severity across the genetic risk categories. Across the adult age spectrum, the prevalence of CCTA-detected atherosclerosis (B) and prevalence of extensive plaque (C) both increase by genetic risk category (P-trend < .001 for graded increase in presence, extent, and severity).

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  Fig. 2. Association between CAD-PRS categories and presence, extent, and severity of plaque. Relative risk regression models for presence, extent, and severity of plaque on CCTA were adjusted for age, sex, smoking status, history of dyslipidemia, history of hypertension, history of chronic kidney disease, history of diabetes, statin treatment, antihypertensive treatment, and principal components 1–5.

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  Fig. 3. Age-stratified analysis. Continuous modeling of relative risk using a spline function demonstrates a stronger effect of high CAD-PRS at younger ages, with attenuation of genetic risk with increasing age. A significant interaction between age and PRS group was observed (Wald test P = 0.017).

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  Fig. 4. Discrimination performance of sequential prediction models for coronary plaque. C-statistics are shown for sequentially adjusted models predicting (A) presence of plaque, (B) extent of plaque, and (C) severity of plaque. Models were evaluated with stepwise inclusion of covariates: age and sex (baseline model), addition of traditional cardiovascular risk factors, addition of the coronary artery disease polygenic risk score (CAD PRS), and the fully adjusted model including both risk factors and CAD PRS. Points represent C-statistics and error bars denote 95% confidence intervals; dotted lines indicate performance of the baseline model.

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  Fig. 5. Bar plot of cardiovascular event rates (composite of CV death, MI, and late coronary revascularization >90 days after CCTA) stratified by CCTA plaque severity (none, nonobstructive, obstructive) and CAD-PRS (low, intermediate, high) over a median follow-up of 6.3 years (P < .001 for global comparison). Event rates include only revascularizations occurring >90 days after CCTA to minimize inclusion of procedures related to the index study, differing from time-to-event analyses that include all revascularizations.