Handgrip strength stratifies the association of depressive symptoms with 9-year mortality in the Mexican Health and Aging Study

Background: We examined whether coexisting low handgrip strength (HGS) and depressive symptoms identifies a higher-risk profile and whether baseline HGS modifies the association between depressive symptoms and 9-year all-cause mortality. Methods: A secondary analysis of adults aged ≥50 years from the 2012 objective-measures sub-sample of the Mexican Health and Aging Study (MHAS/ENASEM), with vital status through 2021. HGS was measured during the standardized health visit and classified into sex-specific tertiles. Depressive symptoms were defined as ≥5 positive responses on the validated 9-item MHAS instrument. We fitted adjusted Cox models using a four-category joint classification and a specification including HGS tertiles, depressive symptoms, and their interaction; stratified models were used when proportional hazards diagnostics indicated departures. Results: The analytic cohort included 1748 participants and 335 deaths. In the stratified four-category model, compared with participants with neither condition, mortality was higher in the low-HGS-only group (HR 1.76, 95% CI 1.31–2.36) and in the group with both low HGS and depressive symptoms (HR 1.78, 95% CI 1.28–2.47), whereas the depressive-symptoms-only group was not clearly associated with mortality (HR 1.31, 95% CI 0.93–1.84). In the interaction model, T3 versus T1 was associated with lower mortality (HR 0.32, 95% CI 0.20–0.51), and the depressive symptoms×T3 term was consistent with heterogeneity across strength levels (HR 2.34, 95% CI 1.20–4.55). Conclusions: Low HGS was the strongest baseline marker of higher 9-year mortality. The association between depressive symptoms and mortality varied across strength levels and was most evident in the highest HGS tertile.