Abstract Body (Do not enter title and authors here): Abstract
Background: Despite evidence linking physical activity (PA) to improved cardiovascular outcomes, its impact on cardiovascular-kidney-metabolic syndrome (CKM) progression among women of reproductive age is unclear. The limited integration of data on gender-specific risk factors and behavioral patterns further exacerbates this.

Objective: This study aims to assess the relationship between PA and the development of CKM in women of reproductive age using data from a population-based cohort.

Methods: Using data from the National Institutes of Health All of Us Research Program, we categorized CKM stages as follows: stage 0 (no risk factors), stage 1 (excess/dysfunctional adiposity or prediabetes), stages 2-3 (metabolic risk factors, moderated-to-high risk kidney disease, or subclinical cardiovascular disease [CVD]), and stage 4 (clinical CVD; with stage 4b indicating kidney failure). PA was measured using Fitbit data or self-reported surveys and quantified as sedentary mins/week and moderate-to-vigorous PA (MVPA) metabolic equivalent task (MET)-mins/week. Associations between quintiles of PA measures and CKM stages were evaluated using multinomial logistic regression models, adjusting for demographics, socioeconomic status, health history, lifestyle factors and healthcare access.

Results: Among 4,550 women of reproductive age, mean age was 36 (±5) years, 78% were White, and 49% had CKM syndrome. Mean (SD) of age entering stages 1, 2, 3, 4, and 4b were 28 (±6), 32 (±6), 35 (±5), 35 (±5), and 35 (±4) years, respectively (Figure 1). Mean (SD) sedentary mins/week and MVPA MET-mins/week were 4,466 (2,060) and 1,368 (1,412). Mean sedentary time was 4,466±2,060 minutes/week, and MVPA was 1,368±1,412 MET-minutes/week. Compared to the lowest quintile, women in higher quintiles of sedentary time (>4,446 vs. ≤3,000 minutes/week) showed reduced odds of CKM stages 2-3, while higher MVPA (>1,194 vs. ≤402 MET-minutes/week) was associated with lower odds of CKM stages 2-3 (Figure 2). Women with moderate MVPA levels (730-1,920 vs. ≤402 MET-minutes/week) demonstrated lower odds of stage 4 CKM syndrome.

Conclusion: Among women of reproductive age, higher levels of physical activity than currently recommended were associated with reduced odds of developing advanced CKM stages. This suggests an opportunity to re-evaluate the existing physical activity guidelines for optimal CKM in this population, and the need for gender-specific recommendations to prevent early-onset CKM.