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 lifetime stroke risk (LTRS) by genetic risk levels and investigate whether optimal cardiovascular health can offset the negative impact of high genetic risk on lifetime stroke risk.
Methods and Results
Study participants were 11,568 middle-aged adults (56% women, 23% black adults), who did not have a stroke at baseline and were followed for a median of 28 years. Remaining lifetime stroke risk ( LTRS) was estimated based on genetic risk levels based on a validated polygenic stroke risk score, and based on cardiovascular health levels based on recommendations. American Heart Association ’s Life’s Simple 7 .
At age 45, people with high, intermediate, and low polygenic risk scores 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 high genetic risk and 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 corresponds to almost 6 additional years lived without stroke.
Conclusions
The LTRS varies depending on polygenic risk levels and cardiovascular health. Maintaining optimal cardiovascular health may partially offset 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.
Comments
People genetically at higher risk for stroke can reduce that risk by up to 43% by adopting a healthy cardiovascular lifestyle, according to new research led by UTHealth Houston , published today in the Journal of the American Heart Association .
The study included 11,568 adults ages 45 to 64 who did not have a stroke at baseline and were followed for a median of 28 years. Cardiovascular health levels were based on the American Heart Association’s Life’s Simple 7 recommendations, which include quitting smoking, eating better, being active, losing weight, controlling blood pressure, controlling cholesterol, and lowering blood sugar.
The lifetime risk of stroke was calculated according to what is called a polygenic stroke risk score, and people who had more genetic risk factors linked to stroke risk scored higher.
“Our study confirmed that modifying lifestyle risk factors, such as blood pressure control, can offset a genetic risk of stroke,” said Myriam Fornage, PhD, senior author and professor of molecular medicine and genetics. human at the Institute of Molecular Medicine at UTHealth Houston.
"We can use genetic information to determine who is at higher risk and encourage them to adopt a healthy cardiovascular lifestyle, such as following the AHA’s Life’s Simple 7, to reduce that risk and live a longer, healthier life." Fornage is the Laurence and Johanna Favrot Distinguished Professor of Cardiology at UTHealth Houston McGovern Medical School.
Each year, 795,000 people in the U.S. suffer a stroke, according to the Centers for Disease Control and Prevention.
That’s equivalent to someone having a stroke every 40 seconds and someone dying from a stroke every 3.5 minutes.
Stroke is a leading cause of serious long-term disability, reducing mobility in more than half of stroke survivors aged 65 years and older. But stroke also occurs in younger adults: In 2014, 38% of people hospitalized for stroke were under 65 years old.
People in the study who scored highest in genetic risk for stroke and lowest in cardiovascular health had the highest lifetime risk of stroke at 25%. Regardless of the level of genetic risk for stroke, those who had practiced optimal cardiovascular health reduced that risk by 30% to 45%. That added up to almost six more years of stroke-free life.
Overall, people with low adherence to Life’s Simple 7 had the most strokes (56.8%), while people with high adherence had 71 strokes (6.2%).
A limitation of the article is that the polygenic risk score has not been widely validated, so its clinical utility is not optimal, particularly for people of diverse racial or ethnic backgrounds.
Clinical Perspective What’s new? Estimates of lifetime risk of stroke and years lived free of disease according to levels of polygenic risk and cardiovascular health (based on the American Heart Association’s Life’s Simple 7 (LS7) recommendations) in white men and women. and blacks have not been previously reported. . Depending on race, lifetime stroke risk varies substantially depending on polygenic risk levels and cardiovascular health. Maintaining optimal cardiovascular health in midlife offsets the lifetime risk of stroke by 30% to 43% and prolongs stroke-free years by 5 to 6 years. What are the clinical implications? Reporting the impact of cardiovascular health and polygenic risk on the long-term absolute odds of stroke (lifetime risk of stroke) can be more easily interpreted by both clinicians and patients. The benefit of maintaining optimal cardiovascular health on lifetime stroke risk at all levels of genetic risk emphasizes the importance of modifiable risk factors in prevention efforts to reduce stroke risk for all. . Improved polygenic risk scores for stroke are needed before clinical utility can be achieved, especially in black adults for whom the predictive strength of the current score is poor. |
UTHealth Houston co-authors were Nitesh Enduru, MPH; graduate research assistant at UTHealth Houston School of Biomedical Informatics; and Eric Boerwinkle, PhD, dean of the UTHealth School of Public Health. Other collaborators included Adrienne Tin, PhD; Michael E. Griswold, PhD; and Thomas H. Mosley, PhD, of the University of Mississippi in Jackson, Mississippi; and Rebecca F. Gottesman, MD, PhD, of the National Institute of Neurological Disorders and Stroke (NINDS). The paper’s first author was Emy A. Thomas, formerly of UTHealth Houston.
Fornage and Boerwinkle are also members of the University of Texas MD Anderson Cancer Center at UTHealth Houston Graduate School of Biomedical Sciences.
The study was funded by NINDS (including grants U19-NS120384 and UH3-NS100605), part of the National Institutes of Health.
