Healthy Lifestyle Trumps Genes for Stroke Risk

I met all 4 of the healthy lifestyle factors and still had a stroke. 

Healthy Lifestyle Trumps Genes for Stroke Risk

Fewer strokes with good exercise and diet habits, despite high genetic risk

• by Kate Kneisel, Contributing Writer, MedPage Today October 26, 2018

Action Points

• Genetic and lifestyle factors were independently associated with risk of incident stroke.
• Note that the study suggests that adhering to a healthy lifestyle could attenuate the effect of genetics on stroke risk.

Individuals following a healthy lifestyle had lower stroke risk regardless of genetic risk factors compared to those with unhealthier habits such as smoking and poor diet, according to results of a prospective study of men and women in the UK Biobank database in Great Britain.
The population-based assessment of the independent effects of genetic and lifestyle factors found that the risk of stroke was 35% higher among those at high genetic risk compared with those at low genetic risk (hazard ratio 1.35, 95% CI1.21-1.50), according to Loes C.A. Rutten-Jacobs, German Center for Neurodegenerative diseases, Bonn, Germany, and colleagues.
Importantly, regardless of a person's level of genetic risk, having an unfavorable lifestyle that included 0 or 1 of 4 healthy lifestyle factors based on American Heart Association guidelines -- no current smoking, healthy diet, body mass index <30, and moderate physical activity two or more times weekly -- was associated with a 66% increased risk of stroke compared with having a favorable lifestyle that includes three or four healthy lifestyle factors (HR 1.66, CI 1.45-1.89), the group reported online in The BMJ.
Rutten-Jacobs and colleagues emphasized that while no firm conclusions can be drawn about cause and effect from an observational study, "it might be hypothesized that adhering to a healthy lifestyle could attenuate the effect of genetics on stroke risk. A previous study in coronary artery disease (CAD)... found a statistically significant interplay between genetic and lifestyle risk factors in CAD risk."
A high genetic risk combined with an unfavorable lifestyle profile was associated with a more than twofold increase in risk of stroke compared with a low genetic risk and a favorable lifestyle. Of lifestyle factors, the effect of smoking was strongest -- about twice as strong as effects of the other individual lifestyle scores.
Asked for his perspective, Gregg C. Fonarow, MD, of the David Geffen School of Medicine at UCLA in Los Angeles, said the findings reflect a significant body of research, which has linked both genetic and lifestyle factors with the risk of stroke.
"Importantly, irrespective of the level of underlying genetic risk, a healthy lifestyle was associated with lower stroke risk," Fonarow, who was not involved in the study, told MedPage Today via email. "Both men and women have higher risk of stroke with unhealthy lifestyles in this study; however the relative and absolute risks were higher in men compared to women."
Indeed, men with an unfavorable lifestyle had a higher relative risk of stroke than did women with an unfavorable lifestyle (82% versus 36% increased risk, respectively).
"These same lifestyle interventions [i.e. not smoking, regular physical activity, healthy diet, and avoiding diabetes] have been shown to be associated with lower risk of heart disease, thus supporting benefits in terms of both long-term heart and brain health," Fonarow added. "Additional studies in more diverse individuals in terms of race/ethnicity and region of the world may provide additional insights."
The group developed a weighted genetic risk score based on 90 stroke-related gene variants in 306,473 white men and women in the UK Biobank database and tested its association with incident stroke, and whether adherence to a healthy lifestyle influenced this association. Participants were 40 to 73 years old and had no history of stroke or heart attack.
Genetic risk was divided into thirds, and lifestyle was recorded as "favorable" (three or four healthy lifestyle factors), "intermediate" (two healthy lifestyle factors), or "unfavorable" (no or one healthy lifestyle factor).
During a median follow-up of 7.1 years, 2,077 incident strokes were noted, the group reported. "The association between genetic risk and incident stroke was unchanged after adjustment for lifestyle, and the association of lifestyle with incident stroke was essentially unchanged after adjustment for the genetic risk score."
Rutten-Jacobs and colleagues calculated hazard ratios for stroke in participants classified as having low or high genetic risk, associated with the following risk factors:

• Current smoking: 2.35 (95% CI 1.84-3.01) low risk; 1.87 (95% CI 1.48-2.37) high risk
• BMI ≥30: 1.43 (95% CI 1.20-1.71) low risk; 1.19 (95% CI 1.02-1.40) high risk
• Lack of regular moderate physical activity: 1.09 (95% CI 0.92-1.28) low risk; 1.09 (95% CI 0.94-1.26) high risk
• Unhealthy diet: 1.10 (95% CI 0.93-1.30) low risk; 1.21 (95% CI 1.05-1.40) high risk

These findings "highlight the potential of lifestyle measures to reduce risk of stroke across entire populations, even in those at high genetic risk of stroke," noted Rutten-Jacobs and co-authors.
The group acknowledged several limitations, such as the narrow range of lifestyle factors, and that the study population included only people of European descent, which limits the findings' generalizability.

This work was in part supported by the British Heart Foundation. HSM has been paid for delivering educational presentations for AstraZeneca.
LCAR-J was supported by a British Heart Foundation; CLS receives salary from UK Biobank and the Scottish funding Council; MD received funding from the European Union's Horizon 2020 research and innovation programme; HSM is supported by a National Institute for Health Research (NIHR) senior investigator award, and the Cambridge Universities NIHR Comprehensive Biomedical Research Centre.

• Reviewed by Robert Jasmer, MD Associate Clinical Professor of Medicine, University of California, San Francisco and Dorothy Caputo, MA, BSN, RN, Nurse Planner

last updated 10.29.2018

• Primary Source

  The BMJ

  Source Reference: Loes CA Rutten-Jacobs LCA et al "Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants" BMJ 2018;363:k4168