TY - JOUR
T1 - Polygenic Risk, Midlife Life’s Simple 7, and Lifetime Risk of Stroke
AU - Thomas, Emy A.
AU - Enduru, Nitesh
AU - Tin, Adrienne
AU - Boerwinkle, Eric
AU - Griswold, Michael E.
AU - Mosley, Thomas H.
AU - Gottesman, Rebecca F.
AU - Fornage, Myriam
N1 - Funding Information:
The Atherosclerosis Risk in Communities study has been funded in whole or in part with federal funds from the National Heart, Lung, and Blood Institute, National Institutes of Health (NIH), Department of Health and Human Services, under contract nos. HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700004I, and HHSN268201700005I. Funding was also supported by R01HL087641, R01HL059367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. MF is supported in part by NIH grants U19-NS120384 and UH3-NS100605. RG is supported by the National Institute of Neurological Disorders and Stroke Intramural Research Program.
Publisher Copyright:
© 2022 The Authors.
PY - 2022/8/2
Y1 - 2022/8/2
N2 - 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.
AB - 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.
KW - epidemiology
KW - modifiable risk factors
KW - polygenic risk
KW - stroke
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U2 - 10.1161/JAHA.122.025703
DO - 10.1161/JAHA.122.025703
M3 - Article
C2 - 35862192
AN - SCOPUS:85135501759
SN - 2047-9980
VL - 11
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 15
M1 - e025703
ER -