Strength-related multimorbidity and grip strength as joint predictors of cardiovascular mortality in the UK biobank

Abstract Background Multimorbidity is a major and increasing public health challenge. However, how muscle strength interacts with clusters of long-term conditions (LTCs) to influence cardiovascular risk remains poorly understood. Emerging evidence suggests that LTCs linked to muscle weakness may drive disproportionate mortality through shared inflammatory, metabolic and vascular pathways. Aim To investigate the associations of Strength-Related Multimorbidity (SRM) and grip strength with cardiovascular mortality, and to examine their combined effects in the UK Biobank cohort. Methods This analysis included 213,937 adults (mean age: 55.8 ± 8.1 years; 49.3% women). SRM was defined as ≥2 of five LTCs most strongly associated with weak muscle strength (rheumatoid arthritis, gout, type 2 diabetes, coronary heart disease, and stroke). Grip strength was measured using a hydraulic dynamometer and categorised as strong (27 kg men; 16 kg women), weak (20–27 kg men; 12–16 kg women), or very weak (20 kg men; 12 kg women). Cox proportional hazards models estimated hazard ratios (HRs) for cardiovascular mortality, adjusting for age, sex, smoking, alcohol intake, socioeconomic status, ethnicity and sedentary time. Additive and multiplicative interactions between SRM and grip strength were evaluated. Results Over a mean follow-up of 11.7 years, 5,528 cardiovascular deaths occurred. SRM prevalence was 4.2% (n=10,048). Compared with individuals without SRM, those with SRM had a markedly higher CVD mortality risk (HR 4.26, 95% CI 3.96–4.58). The combination of SRM and weak grip strength further amplified risk (HR 6.26, 95% CI 5.42–7.24). A significant additive interaction was observed. Participants with both SRM and very weak grip strength reached an equivalent CVD mortality risk 18.5 years earlier than those with neither SRM nor weak muscle strength. Conclusion Strength-Related Multimorbidity and low muscle strength interact synergistically to substantially increase cardiovascular mortality risk. Incorporating muscle strength assessment into multimorbidity management may enable earlier risk stratification and inform targeted prevention strategies to preserve physical function and reduce premature cardiovascular mortality.