Women's Health Initiative Strong and Healthy Pragmatic Physical Activity Intervention Trial for Cardiovascular Disease Prevention: Design and Baseline Characteristics

Abstract

Background: National guidelines promote physical activity to prevent cardiovascular disease (CVD), yet no randomized controlled trial has tested whether physical activity reduces CVD.

Methods: The Women's Health Initiative (WHI) Strong and Healthy (WHISH) pragmatic trial used a randomized consent design to assign women for whom cardiovascular outcomes were available through WHI data collection (N = 18 985) or linkage to the Centers for Medicare and Medicaid Services (N30 346), to a physical activity intervention or "usual activity" comparison, stratified by ages 68-99 years (in tertiles), U.S. geographic region, and outcomes data source. Women assigned to the intervention could "opt out" after receiving initial physical activity materials. Intervention materials applied evidence-based behavioral science principles to promote current national recommendations for older Americans. The intervention was adapted to participant input regarding preferences, resources, barriers, and motivational drivers and was targeted for 3 categories of women at lower, middle, or higher levels of self-reported physical functioning and physical activity. Physical activity was assessed in both arms through annual questionnaires. The primary outcome is major cardiovascular events, specifically myocardial infarction, stroke, or CVD death; primary safety outcomes are hip fracture and non-CVD death. The trial is monitored annually by an independent Data Safety and Monitoring Board. Final analyses will be based on intention to treat in all randomized participants, regardless of intervention engagement.

Results: The 49 331 randomized participants had a mean baseline age of 79.7 years; 84.3% were White, 9.2% Black, 3.3% Hispanic, 1.9% Asian/Pacific Islander, 0.3% Native American, and 1% were of unknown race/ethnicity. The mean baseline RAND-36 physical function score was 71.6 (± 25.2 SD). There were no differences between Intervention (N = 24 657) and Control (N = 24 674) at baseline for age, race/ethnicity, current smoking (2.5%), use of blood pressure or lipid-lowering medications, body mass index, physical function, physical activity, or prior CVD (10.1%).

Conclusion: The WHISH trial is rigorously testing whether a physical activity intervention reduces major CV events in a large, diverse cohort of older women. Clinical Trials Registration Number: NCT02425345.

Keywords: Cardiovascular; Falls; Physical activity; Physical function.

Figure 1.

Randomized consent study design (based on Zelen, N Engl J Med 1979) (9)

Figure 2.

WHISH Trial Consort Diagram.

Figure 3.

Estimated power for the WHISH primary endpoint as a function of the observed effect size of physical activity.