Abstract
BackgroundLow handgrip strength (HGS) predicts cardiovascular disease (CVD) risk, potentially via insulin resistance (IR). The triglyceride-glucose (TyG) index and its combinations with adiposity measures (TyG-BMI, TyG-WC, TyG-WHtR) enhance CVD prediction, but the prognostic value in low HGS populations is unknown.MethodsThis UK Biobank prospective cohort study analyzed 18,341 participants with low HGS (mean age 59.2 years, 61.2% female). Multivariable Cox models assessed associations between TyG-related indices and incident CVD, coronary heart disease (CHD) and stroke. Subgroup and mediation analyses identified effect modifiers and pathways; sensitivity analyses validated result robustness.ResultsOver 13.4 median years, 2,666 CVD cases occurred. Per 1-SD increase, TyG, TyG-BMI, TyG-WC and TyG-WHtR were significantly associated with higher CVD incidence (adjusted HRs: 1.08, 1.13, 1.15, 1.15 respectively; all p < 0.001). TyG-related indices showed significant interaction effects for CVD/CHD across subgroups including age, disease status and medication use. Mediation analyses indicated dyslipidemia, inflammation and IR mediated the associations.ConclusionsElevated TyG-related indices independently predict increased CVD and CHD incidence in individuals with low HGS, offering value for early risk identification and the development of preventive strategies.