Cardiometabolic multimorbidity (CMM) represents an escalating challenge in public health, with its early determinants not yet comprehensively elucidated. Estimated cardiorespiratory fitness (eCRF), a straightforward and non-invasive indicator of physical fitness, has not been thoroughly investigated in relation to its association with the incidence of CMM. This prospective cohort study comprised 4,620 participants aged 45 years and older, who were free of CMM at baseline, as part of the China Health and Retirement Longitudinal Study (CHARLS). eCRF was calculated using validated sex-specific algorithms that incorporated variables such as age, body mass index (BMI), waist circumference, resting heart rate, physical activity levels, and smoking status. CMM was characterized by the presence of at least two cardiometabolic diseases, including heart disease, stroke, or diabetes. To assess the association between eCRF and the incidence of CMM, Cox proportional hazards models were employed to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), with adjustments made for sociodemographic factors, lifestyle behaviors, and clinical biomarkers. Additionally, restricted cubic splines were utilized to explore dose-response relationships, and subgroup analyses were conducted to identify potential effect modifiers. Over a maximum follow-up of nine years, 433 incident cases of CMM were recorded. An increase of one standard deviation (SD) in eCRF was associated with a 39% lower risk of CMM (HR = 0.61, 95% CI: 0.52–0.73) in the fully adjusted model. Participants in the highest eCRF quartile exhibited a 65% lower risk compared to those in the lowest quartile (HR = 0.35, 95% CI: 0.22–0.55; P for trend < 0.001). A linear dose-response relationship was confirmed through restricted cubic spline analysis ( P for non-linearity = 0.54). The inverse association was consistently observed across various sensitivity analyses. A significant interaction was identified with hypertension status ( P for interaction = 0.02), indicating a more pronounced inverse association among non-hypertension individuals. Higher eCRF was associated with a lower risk of incident CMM in a linear dose-response relationship among middle-aged and older Chinese adults.
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