Key result
Each 1 SD increase in systolic blood pressure polygenic risk score was associated with a higher risk of incident cardiovascular events (HR 1.07; 95% CI 1.04-1.10).
Why the study?
To evaluate the relative contributions of traditional cardiovascular risk factors to adverse cardiovascular events across varying blood pressure genetic risk profiles.
Does a multiancestry genome-wide blood pressure polygenic risk score associate with adverse cardiovascular events, and how do modifiable risk factors affect this risk?
Cohort (n=21,897)
Does a multiancestry genome-wide blood pressure polygenic risk score associate with adverse cardiovascular events, and how do modifiable risk factors affect this risk?
Hazard Ratio: 1.07 (95% CI 1.04–1.1)
A multiancestry genome-wide blood pressure polygenic risk score is associated with adverse cardiovascular events, but adequate control of modifiable risk factors can significantly reduce this risk even in genetically predisposed individuals.
Supports multiancestry BP PRS for CV risk research; hypothesis-generating and should not yet alter practice.
BACKGROUND: Traditional cardiovascular risk factors and the underlying genetic risk of elevated blood pressure (BP) determine an individual's composite risk of developing adverse cardiovascular events. We sought to evaluate the relative contributions of the traditional cardiovascular risk factors to the development of adverse cardiovascular events in the context of varying BP genetic risk profiles. METHODS: Genome-wide polygenic risk score (PRS) was computed using multiancestry genome-wide association estimates among US adults who underwent whole-genome sequencing in the Trans-Omics for Precision program. Individuals were stratified into high, intermediate, and low genetic risk groups (>80th, 20-80th, and <20th centiles of systolic BP [SBP] PRS). Based on the ACC/AHA Pooled Cohort Equations, participants were stratified into low and high (10 year-atherosclerotic cardiovascular disease [CVD] risk: <10% or ≥10%) cardiovascular risk factor profile groups. The primary study outcome was incident cardiovascular event (composite of incident heart failure, incident stroke, and incident coronary heart disease). RESULTS: Among 21 897 US adults (median age: 56 years; 56.0% women; 35.8% non-White race/ethnicity), 1 SD increase in the SBP PRS, computed using 1.08 million variants, was associated with SBP (β: 4.39 [95% CI, 4.13-4.65]) and hypertension (odds ratio, 1.50 [95% CI, 1.46-1.55]), respectively. This association was robustly seen across racial/ethnic groups. Each SD increase in SBP PRS was associated with a higher risk of the incident CVD (multivariable-adjusted hazards ratio, 1.07 [95% CI, 1.04-1.10]) after controlling for ACC/AHA Pooled Cohort Equations risk scores. Among individuals with a high SBP PRS, low atherosclerotic CVD risk was associated with a 58% lower hazard for incident CVD (multivariable-adjusted hazards ratio, 0.42 [95% CI, 0.36-0.50]) compared to those with high atherosclerotic CVD risk. A similar pattern was noted in intermediate and low genetic risk groups. CONCLUSIONS: In a multiancestry cohort of >21 000 US adults, genome-wide SBP PRS was associated with BP traits and adverse cardiovascular events. Adequate control of modifiable cardiovascular risk factors may reduce the predisposition to adverse cardiovascular events among those with a high SBP PRS.
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Parcha et al. (2022) conducted a cohort in Cardiovascular disease (n=21,897). Systolic blood pressure polygenic risk score (SBP PRS) vs. Lower SBP PRS was evaluated on incident cardiovascular event (composite of incident heart failure, incident stroke, and incident coronary heart disease) (HR 1.07, 95% CI 1.04-1.10). Each 1 SD increase in systolic blood pressure polygenic risk score was associated with a higher risk of incident cardiovascular events (HR 1.07; 95% CI 1.04-1.10).
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