Polygenic Risk, Midlife Life’s Simple 7, and Lifetime Risk of Stroke

BACKGROUND: Recent genetic discoveries in stroke have unleashed the potential of using genetic information for risk predictionand health interventions aimed at disease prevention. We sought to estimate the lifetime risk of stroke (LTRS) by levels ofgenetic risk and to investigate whether optimal cardiovascular health can offset the negative impact of high genetic risk onlifetime risk of stroke. METHODS AND RESULTS: Study participants were 11 568 middle-agedadults (56% women, 23% Black adults), who were free ofstroke at baseline and were followed up for a median of 28 years. The remaining LTRS was estimated according to levels of geneticrisk based on a validated stroke polygenic risk score, and to levels of cardiovascular health based on the American HeartAssociation Life’s Simple 7 recommendations. At age 45, individuals with high, intermediate, and low polygenic risk score had aremaining LTRS of 23.2% (95% CI, 20.8%–25.5%),13.8% (95% CI, 11.7%–15.8%),and 9.6% (95% CI, 7.3%–11.8%),respectively.Those with both a high genetic risk and an inadequate Life’s Simple 7 experienced the highest LTRS: 24.8% (95% CI, 22.0%–27.6%).Across all polygenic risk score categories, those with an optimal Life’s Simple 7 had a ≈30% to 43% lower LTRS thanthose with an inadequate Life’s Simple 7. This corresponded to almost 6 additional years lived free of stroke. CONCLUSIONS: The LTRS varies by levels of polygenic risk and cardiovascular health. Maintaining an optimal cardiovascularhealth can partially offset a high genetic risk, emphasizing the importance of modifiable risk factors and illustrating the potentialof personalizing genetic risk information to motivate lifestyle changes for stroke prevention.