Optimized Cardiovascular Health Could Offset Genetic Stroke Risk by 30-40%

Myriam Fornage, PhD

New research from an analysis of the Atherosclerosis Risk in Communities (ARIC) Study suggests optimal cardiovascular health could help partially offset genetic risk in those with an increased genetic risk for stroke.

An analysis of data from more than 11,000 middle-aged adults free from stroke at baseline and followed for a median of 28 years, results of the study demonstrate optimal cardiovascular health, which was defined using the American Heart Association’s Midlife’s Simple 7, was associated with a reduction in lifetime risk of stroke across subgroups defined by varying levels of polygenic risk score.

“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 at the Institute of Molecular Medicine at The University of Texas Health Science Center at Houston, in a statement. “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.”

Funded by the National Institute for Neurological Disorders and Stroke, a division of the National Institutes of Health, the current study was conducted by Fornage and colleagues with the intent of exploring how cardiovascular health might offset the negative impact of high genetic risk on lifetime risk of stroke among middle-aged patients in the US. With this in mind, the study was designed as an analysis of data from the ARIC study. Using information provided by the ARIC study, investigators identified 11,568 patients free from stroke at baseline for inclusion in their analyses. These patients had a median age of 54 (IQR, 49-59) years, median follow-up of 28 (IQR, 19-30) years, mean BMI of 26.8 ( IQR, 24.0-30.3) kg/m2, 56% were women, and 23% were Black adults.

For the purpose of analysis, polygenic risk scores were calculated using 3,000,000 single-nucleotide polymorphisms across the whole genome and participants were categorized as having low, intermediate, or high genetic risk based on the number of stroke-related single-nucleotide polymorphisms. Cardiovascular health scores were calculated based on adherence to the principles outlined within the American Heart Association Life’s Simple 7, which was recently updated and renamed Life’s Essential 8.

Overall, 2892 were classified as having high genetic risk, 5783 were classified as having intermediate genetic risk, and 2893 were classified as having low genetic risk. Compared to participants with intermediate and 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 (P<0.001).

Upon analysis, individuals with high, intermediate, and low genetic risk score 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. For cardiovascular health scores, those with an inadequate, average, and optimal Life’s Simple 7 score had 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, at 45 years of age.

Further analysis suggested those with high genetic risk and inadequate cardiovascular health scores exhibited a greater lifetime risk of stroke at 24.8% (95% CI, 22.0-27.6%). In contrast, the lifetime risk of stroke among those with high genetic risk and optimal cardiovascular health was 17.27% (95% CI, 10.88-23.66%). Meanwhile, the lowest lifetime risk of stroke was observed among patients with low genetic risk and optimal cardiovascular health (7.48% [95% CI, 3.09-11.87]). Investigators noted results indicated those with optimal cardiovascular health had a 30-40% lower lifetime risk of stroke than those with inadequate cardiovascular health, which corresponded to about 6 additional stroke-free years.

“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 added. “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.”

This study, “Polygenic Risk, Midlife Life's Simple 7, and Lifetime Risk of Stroke,” was published in Journal of the American Heart Association.