Lifetime Risk for Stroke Varies by Levels of Polygenic Risk, Cardiovascular Health

Depending on race, the lifetime risk for stroke varies considerably, according to levels of polygenic risk and cardiovascular health. In fact, maintenance of optimal midlife cardiovascular health offsets the lifetime risk for stroke by 43% and lengthens the years lived free of stroke by 5 to 6 years. These are the findings of a study published in the Journal of the American Heart Association.

In the field of stroke, recent genetic discoveries have unleashed the potential of utilizing genetic information for risk prevention and health interventions targeted at disease prevention. This prompted researchers to assess the lifetime risk for stroke based on levels of genetic risk and to explore whether optimal cardiovascular health can counterbalance the negative impact of high genetic risk on lifetime risk for stroke.

A primary analysis was conducted among 11,568 middle-aged adults (56% women; 23% Black adults) from the prospective Atherosclerosis Risk in Communities (ARIC) study who were free of stroke at baseline and were followed for a median of 28 years. The remaining lifetime risk for stroke was estimated according to levels of genetic risk that were based on a validated stroke polygenic risk score and levels of cardiovascular health that were based on the American Heart Association Life’s Simple 7 (LS7) recommendations.

The study included patients hospitalized for stroke that had occurred by December 31, 2018. All strokes were classified as hemorrhagic stroke (subarachnoid and intracerebral hemorrhage) or ischemic stroke (thrombotic and embolic brain infarction), which were based on available data, including neuroimaging, review of medical records, and autopsy.

At age 45 years, individuals with high, intermediate, and low polygenic risk scores had a remaining 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%) lifetime risk for stroke, respectively.

Additionally, those with both a high genetic risk and an inadequate LS7 experienced the highest lifetime risk for stroke — that is, 24.8% (95% CI, 22.0%-27.6%). Across all of the polygenic risk score categories, participants with an optimal LS7 had an approximately 30%-43% lower lifetime risk for stroke than those with an inadequate LS7 — corresponding to nearly 6 additional years lived free of stroke.

The researchers acknowledged the study had several limitations. To begin, the performance of the stroke polygenic risk score used in the study remains suboptimal because of the lack of diversity and rather limited sample size of current genome-wide association studies for stroke and stroke subtypes. Further, the stroke polygenic risk score that was used in this study was defined according to genetic risk factors associated with stroke and stroke-related traits — some of which likely impacted LS7 status.

Improved polygenic risk scores for stroke are needed prior to the achievement of clinical utility, particularly among Black adults for whom the predictive strength of the current polygenic risk score is poor, according to the study findings. “Maintaining an optimal cardiovascular health can partially offset a high genetic risk, [thus] emphasizing the importance of modifiable risk factors and illustrating the potential of personalizing genetic risk information to motivate lifestyle [and vascular health] changes for stroke prevention,” the researchers concluded.

Disclosure: None of the study authors has declared affiliations with biotech, pharmaceutical, and/or device companies.