Genetic Stroke Risk May Be Offset by Optimal Cardiovascular Health


Those with an optimal Life's Simple 7 score had roughly a 30% to 43% lower lifetime stroke risk than those with an inadequate Life's Simple 7 categorization, corresponding to almost 6 additional years of stroke-free life.

A version of this story originally appeared on our sister site, Practical Cardiology.

Myriam Fornage, PhD, professor of molecular medicine and human genetics, Institute of Molecular Medicine, The University of Texas Health Science Center at Houston

Myriam Fornage, PhD

Data from an analysis of more than 11,000 individuals of middle-age without a history of stroke suggest that optimized cardiovascular health—defined using the American Heart Association’s (AHA) Midlife Life's Simple 7—was associated with a reduction in the lifetime of stroke across various subgroups defined by varying levels of polygenic risk score.1

The AHA's Life's Simple 7 list—which was recently updated and renamed Life’s Essential 82—is based on modifiable risk factors including total cholesterol, blood pressure, blood glucose, physical activity, diet, smoking status, and body mass index (BMI). For each of these risk factors, participants were categorized into 3 groups: poor, intermediate, and ideal. Across all polygenic risk score categories, individuals with an optimal Life's Simple 7 had an approximately 30% to 43% lower lifetime stroke risk than those with an inadequate Life's Simple 7 categorization. This reduction corresponded to almost 6 additional years lived free of stroke.

“We know that well-managed, modifiable risk factors, especially treatment of hypertension, can noticeably lower an individual’s risk of stroke,” said senior investigator Myriam Fornage, PhD, professor of molecular medicine and human genetics, Institute of Molecular Medicine, The University of Texas Health Science Center at Houston, in a statement.3 “Our study confirmed that we may be able to mitigate the lifetime risk of stroke by modifying other risk factors, and that regardless of genetics—whether you have a high polygenic risk score or low polygenic risk score—maintaining good cardiovascular health decreases the lifetime risk of stroke. So, modifiable risk factors are crucial in preventing stroke.”

Fornage et al conducted this assessment with data from the Atherosclerosis Risk in Communities Study, funded by the NIH's National Institute for Neurological Disorders and Stroke. Their aim was to assess the role of cardiovascular health on the negative impact of high genetic risk of stroke in this middle-aged population. In total, investigators incldued 11,568 patients free from stroke at baseline (56% were women, and 23% were Black adults), with a median age of 54 (IQR, 49-59) years, median follow-up of 28 years (IQR, 19-30), mean BMI of 26.8 kg/m2 ( IQR, 24.0-30.3).

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The polygenic risk scores were calculated using 3 million single-nucleotide polymorphisms (SNPs) across the whole genome and participants were categorized as having low, intermediate, or high genetic risk based on the number of stroke-related SNPs. Of those more than 11,000 individuals, 2892 were classified as having high genetic risk, 5783 as having intermediate genetic risk, and 2893 as having low genetic risk. Those with a high genetic risk had a greater prevalence of parental history of stroke, hypertension, and diabetes, and had a higher body mass index and total plasma cholesterol level compared with those with intermediate and low genetic risk (P <.001).

Additionally, those with high, intermediate, and low genetic risk scores had a remaining lifetime stroke risk of 23.2% (95% CI, 20.8-25.5%), 13.8% (95% CI, 11.7-15.8%), and 9.6% (95% CI, 7.3-1.8%), respectively, at 45 years of age. Cardiovascular health scores, on the other hand, showed a remaining lifetime risk of stroke of 17.6% (95% CI, 15.6–19.6%), 13.4% (95% CI, 11.8–15.1%), and 9.8% (95% CI, 7.1–12.5%), respectively, for those with inadequate, average, and optimal Life’s Simple 7 scores at 45 years of age.

Individuals with both high genetic risk and inadequate Life's Simple 7 scores displayed a greater lifetime risk of stroke at 24.8% (95% CI, 22.0-27.6%), whereas those with high genetic risk but optimal cardiovascular health had a risk of 17.27% (95% CI, 10.88-23.66%). In contrast, the lowest lifetime risk of stroke was observed among those individuals with both low genetic risk and optimized cardiovascular health (7.48%; 95% CI, 3.09-11.87).

“This is the first step in using genetic information to identify people who may be at higher risk for stroke, and also in motivating people to make lifestyle changes for cardiovascular disease prevention,” Fornage said in a statement.3 “This type of study shows us the possibilities for the future. Polygenic risk scores are not used clinically at this point; however, this may be the first step towards achieving personalized risk information to be used in lifestyle and health change. Having optimal cardiovascular health is crucial in stroke prevention.”

1. Thomas EA, Enduru N, Tin A, et al. Polygenic Risk, Midlife Life's Simple 7, and Lifetime Risk of Stroke. JAHA. Published July 20, 2022. doi:10.1161/JAHA.122.025703
2. Lloyd-Jones DM, Allen NB, Anderson CAM, et al. Life’s Essential 8: Updating and Enhancing the American Heart Association’s Construct of Cardiovascular Health: A Presidential Advisory From the American Heart Association. Circulation. 2022;0:10. doi:10.1161/CIR.0000000000001078
3. Higher cardiovascular health may partially offset increased genetic risk for stroke. News release. AHA. July 20, 2022. Accessed July 22, 2022.
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