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.

backgroundCardiometabolic 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.

methodsProspective 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.

resultsDuring 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.

conclusionsTyG-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.