Residential green space, walkability, and cardiometabolic biomarkers in midlife women: a longitudinal cohort study.

Background. Cardiovascular disease remains the leading cause of death among U.S. women. Green spaces and neighborhood features may influence cardiometabolic health by modulating environmental stressors and physical activity. Few longitudinal studies have examined green space, walkability, and cardio-inflammatory biomarkers, particularly in midlife women during the menopausal transition-a period of elevated cardiovascular risk. Methods. We analyzed longitudinal data from the multi-ethnic, multi-site U.S. Study of Women's Health Across the Nation (1999-2017) to examine associations between residential green space, walkability index, and cardio-inflammatory biomarkers across multiple clinical visits. Green space exposure was assessed using the National Land Cover Database (NLCD), with supplemental measures from the Normalized Difference Vegetation Index (NDVI). Exposures, categorized into tertiles, were weighted by 12 month geocoded residential history. Linear mixed-effects models estimated associations with systemic inflammatory, fibrinolytic, and lipid biomarkers, adjusting for socioeconomic, lifestyle, and environmental factors. Interaction analyses tested effect modification, with subgroup effects estimated. Results. Medium residential NLCD greenness in 1000 m buffer was associated with an 11.5% lower (95% Confidence Interval: -18.4, -3.9%) high-sensitivity C-reactive protein (hs-CRP), along with lower fibrinogen and tissue-plasminogen activator antigen levels compared to low greenness tertile, suggesting anti-inflammatory and anticoagulant effects. Higher NDVI greenness showed a similar negative association with hs-CRP (-10.2%, 95% CI: -18.6, -1.1%). Compared to low walkability tertile, medium walkability group was linked to higher low-density lipoprotein and total cholesterol. Effect modification analyses indicating lower hs-CRP, higher high-density lipoprotein (HDL), and lower triglycerides, suggested potential biological interactions between green space and women who transitioned to post-menopausal period. Conclusion. Findings support green space's role in reducing systemic inflammation while highlighting the complex interplay of walkability, air pollution, and urban factors. Greenness and walkability capture distinct built environmental aspects, underscoring the need for green infrastructure to mitigate gentrification, reduce pollution, and support cardiovascular health.