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 prediction and health interventions aimed at disease prevention. We sought to estimate the lifetime risk of stroke (LTRS) by levels of genetic risk and to investigate whether optimal cardiovascular health can offset the negative impact of high genetic risk on lifetime risk of stroke. Methods and Results Study participants were 11 568 middle-aged adults (56% women, 23% Black adults), who were free of stroke at baseline and were followed up for a median of 28 years. The remaining LTRS was estimated according to levels of genetic risk based on a validated stroke polygenic risk score, and to levels of cardiovascular health based on the American Heart Association Life's Simple 7 recommendations. At age 45, individuals with high, intermediate, and low polygenic risk score had a remaining 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 than those 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 cardiovascular health can partially offset a high genetic risk, emphasizing the importance of modifiable risk factors and illustrating the potential of personalizing genetic risk information to motivate lifestyle changes for stroke prevention.