Grace Y. Kuo, MD, MS, BA

Jain P, Suemoto C, Rexrode K, Manson J, Robins J, Hernan M, et al. Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke. Stroke. 2020.

We are fortunate enough to be in an era in which we have multiple validated treatments for stroke care. However, with the decrease in overall stroke incidence and mortality, we are beginning to see a gender disparity in the disease of stroke. More women, particularly in the elderly populations, suffer from stroke than men. Although it may be due to longer life expectancy for women, it is still important to look for strategies to decrease this disparity. Prospective studies have found an inverse association between healthy lifestyles and strokes. However, as the natural history of the chronic conditions that lead to strokes occurs over decades, the actual effects of lifestyle interventions for primary prevention are difficult to study in randomized trials.

The article “Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke” is an attempt to understand the effects of dietary and non-dietary modifications on stroke risk by using longitudinal observational data in a hypothetical analysis to estimate the possible risk reduction of the interventions. Data was obtained from the Nurse’s Health Study (NHS), a database that was started in 1976 with 121,701 participants. In 1984, the participants were sent a food frequency questionnaire (FFQ), which was used as a basis for dietary pattern. Based on this survey, 59,727 participants were deemed eligible, after exclusion criteria of having pre-existing cardiovascular events (stroke, MI, angina, history of CABG) and cancer. Incomplete surveys or surveys with implausible responses were also excluded from analysis. 1986, the first follow-up year, was set as the baseline year to allow for adjustment for pre-baseline confounders. Every two years thereafter, participants were sent follow-up questionnaires. Participants were followed until their first diagnosis of stroke, death or June 2012.

Interventions were categorized into non-dietary interventions: smoking cessation, average of at least 30 minutes of exercise per day, and decrease of BMI by 5% if BMI > 25kg/m2 at initial survey; and dietary interventions: eat at least 3 servings of fish per week, eat at least 1 serving of nuts per day, eat at least 2 servings of whole grains per day, eat at least 5 servings of fruits and vegetables per day, eat less than 3 servings of unprocessed red meat per day, eat zero servings of processed red meat per day, and drink 5-15 grams of alcohol per week. The dietary and non-dietary interventions were also evaluated as a collective, respectively. Data analysis was performed using the parametric g-formula, an analytic tool that has previously been described and used to investigate effect of hypothetical lifestyle strategies on coronary heart disease, diabetes, and respiratory disease. The validity of the parametric assumptions was confirmed by comparing the model’s estimated values of the outcomes under no intervention to the natural observed means of the study.

The average age of study patients was 52 years old, mean BMI was 24.5 kg/m2. 95% were white, 21% were smokers and 54% were post-menopausal. During the study period, 9,998 participants died of causes other than stroke. 10,393 were lost to follow up. The total occurrence of stroke during the study was 2,349 (observed risk of 4.45%); within the total strokes, 1,251 were ischemic, 351 were hemorrhagic, and 747 were of unknown subtype. Data analysis of no intervention estimated an overall 26-year stroke risk of 4.7% (95% CI 4.5-4.9).

The study model estimated that after the collective non-dietary interventions of smoking cessation, exercise, and BMI reduction, the 26-year stroke risk was predicted to be 3.5% (95% CI 2.6%-4.3%). Individually, each intervention has a smaller but still existing estimated risk reduction. Collective dietary intervention was estimated to have a 26-year stroke risk of 3.6% (95% CI 2.7%-4.5%). This effect was mainly supported by the isolated interventions of increased fish and nuts intake, and decreased unprocessed red meat intake.

Lastly, a subgroup analysis showed that the difference between estimated risk and observed risk was even greater when looking at the subgroup of women with high baseline risk of stroke. In this population, observed stroke risk was 6.6%, estimated 26-year stroke risk under the joint non-dietary interventions was 4.8% (95% CI 3.1%-7.0%), and under the joint dietary interventions, was 4.7% (95% CI 3.2%-6.6%).

Overall, lifestyle modifications applied to middle-aged women without cardiovascular disease and cancer were estimated to reduce 26-year stroke risk by up to 25%, according to the study model. It’s important to note that analysis by stroke subtype showed that this risk reduction was mainly carried by the the 36% risk reduction of ischemic strokes. When evaluating the risk of hemorrhagic strokes, the estimated stroke risk was not significantly different than the predicted stroke risk if no intervention took place in the model, nor was it significantly different from the observed risk of hemorrhagic strokes.

Primary prevention randomized trials in lifestyle modifications and stroke risk reduction are difficult to conduct due to needing a large study population and a long follow-up period. The hypothetical predictions of this study are useful as a framework to better understand the likely scope of efficacy. The dietary strategies were based on food items and servings, thus making interpretation and transitional practice more natural. On the other hand, the study population of nurses is likely to be more educated than the general public. Assuming that many or most of the study population continues to hold their occupation throughout the study period, steady income of a certain earning status may also be a characteristic of the study population that is unique. Nonetheless, the results of this study support the importance of both dietary and non-dietary lifestyle strategies to reduce stroke risk in middle aged women over a longitudinal period. This knowledge reinforces the need for a widespread health education regarding appropriate healthy dietary and lifestyle choices to help with primary prevention of stroke in the female population.