What is the clinical evidence from this study?

Study design: Cohort. Population: Cardiometabolic multimorbidity (CMM) (n=2661). Intervention: Depression and no vigorous physical activity (VPA) vs. No depression and engaging in VPA. Primary outcome: Incident cardiometabolic multimorbidity (CMM) (HR 1.93, 95% CI 1.52-2.44).

What does this research mean for the field?

Coexisting depression and lack of vigorous physical activity significantly increase the risk of incident cardiometabolic multimorbidity compared to being physically active without depression. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

This research investigates how depression and physical activity together influence the development of cardiometabolic multimorbidity in older adults.

April 22, 2026Open Access

Joint association of depression and physical activity with incident cardiometabolic multimorbidity (CMM) among middle-aged and older adults in China

Key Result

Coexisting depression and lack of vigorous physical activity significantly increased the risk of incident cardiometabolic multimorbidity (HR 1.93) compared to individuals without depression who were physically active.

Key Points

This research investigates how depression and physical activity together influence the development of cardiometabolic multimorbidity in older adults.
Conducted a prospective cohort study with 2,661 adults aged ≥ 45 years without cardiometabolic multimorbidity at baseline.
Followed participants for an average of 9 years to identify new cases of cardiometabolic multimorbidity.
Utilized Cox proportional hazards models to estimate hazard ratios for joint effects of depression and vigorous physical activity.
Participants with depression and no vigorous physical activity had the highest risk of developing cardiometabolic multimorbidity (HR 1.93).
Those with depression but engaging in vigorous physical activity also had increased risk (HR 1.84).
There was a clear dose-response relationship showing higher risks with greater exposure to both factors.

Study Design

Type

Cohort (n=2,661)

Multicenter

Yes

Structured PICO

Does the joint presence of depression and lack of vigorous physical activity increase the risk of incident cardiometabolic multimorbidity in middle-aged and older adults?

Population

2,661 adults aged ≥ 45 years without cardiometabolic multimorbidity (CMM) at baseline, from the China Health and Retirement Longitudinal Study (CHARLS).

Intervention

Joint exposure to depression (assessed via CESD-10 score ≥10) and lack of vigorous physical activity (VPA).

Comparator

Participants without depression who engaged in vigorous physical activity (VPA).

Outcome

Incident cardiometabolic multimorbidity (CMM), defined as the coexistence of ≥ 2 physician-diagnosed conditions (hypertension, diabetes mellitus, cardiovascular disease, and stroke) during follow-up.composite

The joint presence of depression and physical inactivity significantly increases the risk of developing cardiometabolic multimorbidity in middle-aged and older adults, highlighting the need for integrated mental health and lifestyle interventions.

Main Result

Effect estimate: HR 1.93 (95% CI 1.52-2.44)

Absolute Event Rate: 42.6% vs 17.5%

Limitations

Depression and physical activity were assessed using self-reported measures, which may introduce misclassification
Exposures were measured only at baseline and may not capture changes over time
Residual confounding, including the potential influence of medications, cannot be entirely excluded
The study population consisted of middle-aged and older Chinese adults, which may limit generalizability to other populations

Abstract

Abstract Depression and physical inactivity are both associated with cardiometabolic disorders; however, their joint effects on the development of CMM, defined as the coexistence of ≥ 2 cardiometabolic conditions, remain unclear. We aimed to investigate the combined association of depression and vigorous physical activity (VPA) with incident CMM and to examine whether this association differed across metabolic status. This prospective cohort study included 2,661 adults aged ≥ 45 years without CMM at baseline (2011) from the China Health and Retirement Longitudinal Study. Participants were followed through 2020 (median follow-up: 9 years), during which 797 incident CMM cases were identified. Depression and VPA were jointly categorized into four groups. Cox proportional hazards models with multiple imputation were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Estimated glucose disposal rate (eGDR) was evaluated as a potential effect modifier using stratified analyses and interaction tests. Sensitivity analyses were performed using alternative metabolic indicators, including the triglyceride–glucose (TyG) index, waist-to-height ratio (WHtR), and cardiometabolic index (CMI). Compared with participants without depression who engaged in VPA (reference), those with both depression and no VPA had the highest risk of CMM (HR 1.93, 95% CI 1.52–2.44), followed by those with depression but engaging in VPA (HR 1.84, 95% CI 1.41–2.39) and those without depression but no VPA (HR 1.52, 95% CI 1.22–1.89). The associations were consistent across metabolic strata defined by eGDR. No evidence of interaction was observed between depression and VPA (P for interaction > 0.05). A dose–response relationship was observed across joint exposure categories (P for trend < 0.001). Sensitivity analyses yielded similar results. Depression and lack of VPA jointly increase the risk of CMM in middle-aged and older adults. Engagement in VPA may partially mitigate the elevated cardiometabolic risk associated with depression. These findings highlight the importance of integrated mental health and lifestyle interventions for preventing CMM.

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