Association of a novel triglyceride-glucose and non-HDL-to-HDL cholesterol ratio (TyG-NHHR) index with cardiometabolic multimorbidity: a dual-cohort prospective study in Chinese and European adults

Cardiometabolic multimorbidity (CMM), defined as the coexistence of two or more cardiometabolic diseases, represents a growing challenge for population health and health systems worldwide. Insulin resistance and atherogenic dyslipidemia are key metabolic disturbances underlying CMM, yet their joint contribution to CMM development remains incompletely understood. A composite index integrating the triglyceride–glucose (TyG) index and the non–HDL-cholesterol–to–HDL-cholesterol ratio (NHHR), termed TyG-NHHR, was developed to examine its association with incident CMM in two population-based cohorts. Prospective data from the China Health and Retirement Longitudinal Study (2011–2018) and the English Longitudinal Study of Ageing (2008–2014) were analysed. After excluding participants with prevalent CMM or missing data, 9,297 adults aged 45 years and older were included. TyG-NHHR was calculated as TyG multiplied by NHHR. Incident CMM was defined as the new onset of at least two cardiometabolic conditions (heart disease, stroke, hypertension, or diabetes) during follow-up. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs), adjusting for sociodemographic characteristics, lifestyle factors, body mass index, and medication use. Baseline, cumulative, and trajectory patterns of TyG-NHHR were examined, with dose–response relationships assessed using restricted cubic splines. Joint effect and bidirectional mediation analyses were conducted to explore interrelationships between TyG and NHHR. During a median follow-up of 7 years, 1,851 participants (19.9%) developed CMM. Higher TyG-NHHR levels were consistently associated with increased CMM risk. Each standard deviation increase in baseline TyG-NHHR was associated with a 13% higher risk of CMM (HR 1.13, 95% CI 1.09–1.17). Participants in the highest quartile had a substantially elevated risk compared with those in the lowest quartile (HR 1.56, 95% CI 1.33–1.83), with stronger associations observed for cumulative exposure and persistently high trajectories. A linear dose–response relationship was identified. Joint-effect analysis indicated overlapping metabolic pathways between TyG and NHHR. Mediation analysis indicated that insulin resistance accounted for a substantial proportion of the association between atherogenic dyslipidemia and CMM, whereas the reverse pathway was limited. Findings were consistent across subgroups and sensitivity analyses. TyG-NHHR is a simple, routinely derived metabolic index associated with the risk of developing cardiometabolic multimorbidity in middle-aged and older adults across diverse populations. Integrated metabolic indicators such as TyG-NHHR may support early identification of individuals at elevated risk of CMM and inform population-level prevention strategies, particularly in resource-limited settings.