Associations of eight insulin resistance-related indices and genetic risk with incident cardiometabolic multimorbidity among participants with hypertension: a large prospective cohort study
Authors' conclusion
Higher levels of IR-related indices, especially TyG-WHtR, were associated with an elevated risk of incident CMM in individuals with hypertension, particularly among those with high genetic risk. Inflammatory, hepatic, and renal biomarker abnormalities were related to the associations. IR-related indices, particularly TyG-WHtR, may provide useful information for risk stratification of CMM among individuals with hypertension.
Study context
- Population
- Hypertensive patients free of pre-existing coronary heart disease, stroke or T2D, UK Biobank28,455 cardiometabolic multimorbidity (CMM) events
- Participants
- 129,853 patients
- Exposure
- Highest vs lowest tertiles of 8 insulin resistance (IR)-related indices
- Outcome
- Incident cardiometabolic multimorbidity (CMM)
- Follow-up
- Median 13 years
Methodological detailsobservational, UK Biobank
- Observational
- UK Biobank
Main finding
As reported in the abstract
Incident CMM
Estimate (95% CI)
Highest tertilevs Lowest tertile
multivariable-adjusted HR, TyG index 1.78(1.73–1.83)
Highest tertilevs Lowest tertile
multivariable-adjusted HR, TyG-BMI 2.10(2.04–2.17)
Highest tertilevs Lowest tertile
multivariable-adjusted HR, TyG-WC 2.29(2.21–2.37)
Highest tertilevs Lowest tertile
multivariable-adjusted HR, TyG-WHtR 2.23(2.16–2.30)
Highest tertilevs Lowest tertile
multivariable-adjusted HR, TyG-WWI 2.08(2.02–2.15)
Highest tertilevs Lowest tertile
multivariable-adjusted HR, TyG-BRI 2.17(2.10–2.24)
Highest tertilevs Lowest tertile
multivariable-adjusted HR, TyG-ABSI 1.90(1.84–1.97)
Highest tertilevs Lowest tertile
multivariable-adjusted HR, TG-HDL-C 1.73(1.68–1.79)
- Per SD increment: higher CMM risk
- 18%-48%
Observational data: associations, not effects.
Further findings
Incremental predictive value
- All indices improved incremental predictive value; TyG-waist-to-height ratio (TyG-WHtR) strongest
Joint and interaction effects with genetic risk
- High IR-related indices plus high genetic risk had the highest CMM risk, with additive interactions
- High genetic risk appeared to strengthen associations, with evidence of multiplicative interactions
Exploratory biomarker analyses
- Systemic inflammation and liver and renal function biomarkers might statistically account for part of the associations
Original publication
Associations of eight insulin resistance-related indices and genetic risk with incident cardiometabolic multimorbidity among participants with hypertension: a large prospective cohort study. Cardiovasc Diabetol. Published 30 March 2026. doi:10.
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