Joint patterns of physical activity and sedentary behaviour and risks of all-cause and cardiovascular mortality in postmenopausal women: prospective cohorts from the UK, the US, and China

Background Menopause is a critical cardiometabolic transition characterised by declining oestrogen, which increases risk of central obesity, dyslipidaemia, insulin resistance, and cardiovascular disease (CVD). Lifestyle-based prevention strategies for postmenopausal women remain insufficiently defined, particularly regarding the optimal combination of physical activity (PA) and sedentary behaviour (SED) across ethnicities. Objectives To investigate the independent and joint associations of moderate-to-vigorous PA (MVPA), light PA (LPA), and SED with all-cause and cardiovascular mortality in postmenopausal women across three multi-ethnic prospective cohorts, and to explore underlying metabolic mediation pathways. Methods Data were analysed from UK Biobank (UKB, primary; n=34,364), NHANES 2007–2023 (US; n=4,992), and CHNS 1997–2015 (China; n=1,329). UKB used wrist accelerometers (7-day); NHANES/CHNS used validated questionnaires. Cox models assessed per-SD associations of MVPA, LPA, and SED with mortality. Restricted cubic splines characterised dose-response relationships. Isotemporal substitution modelled reallocation of 1 h/day SED to LPA or MVPA. Mediation analyses examined pathways through central obesity (Body Roundness Index [BRI], waist-to-height ratio [WtHR]), lipids, glycaemic markers, blood pressure, and inflammation. Additive interactions between PA, SED, and central obesity were evaluated. Results Per-SD higher MVPA was associated with ~15% lower all-cause mortality (HR≈0.85, p<0.001); LPA showed comparable benefit. Per-SD higher SED increased mortality by ~15%. MVPA showed an L-shaped dose-response (plateau beyond ~4 h/week); SED risk rose markedly above ~11.2 h/day. Replacing 1 h/day SED with MVPA reduced all-cause mortality by ~18%; LPA substitution by ~16%. In high-risk subgroups (central obesity, prolonged SED, low MVPA), LPA substitution yielded greater gains (~17% lower all-cause; ~21% lower cardiovascular mortality). Central obesity (BRI, WtHR) was the dominant mediator (up to 19%), followed by HbA1c, TyG, HDL-C, blood pressure, and CRP. Synergistic additive interactions were found between insufficient MVPA and central obesity (AP=0.31, p<0.001), and between prolonged SED and central obesity (AP=0.24, p=0.02). Conclusions In postmenopausal women across three ethnicities, higher MVPA and LPA and lower SED independently reduced all-cause and cardiovascular mortality. A stepwise strategy—first replacing SED with sustainable LPA, then gradually adding MVPA—is the most practical approach, especially in women with central obesity. Central obesity and HDL-C are key mediating targets for lifestyle intervention in this high-risk population.figure 1figure 2