Associations of mental health symptoms and triglyceride-glucose index with incident cardiovascular disease: a cohort study from the UK Biobank.

Authors

Tianci Yao, Ying Zhu, Hongyu Yan, Qinmei Ke

Published in

Frontiers in endocrinology. Volume 17. Pages 1874050. Epub Jun 24, 2026.

Abstract

Mental health symptoms often coexist with insulin resistance (IR), and they are independently associated with incident cardiovascular disease (CVD). However, it remains unclear whether mitigating IR can reduce the risk of incident CVD in populations with mental health symptoms.
This study included 250,716 adults from the UK Biobank free of prevalent CVD at baseline. IR was reflected by the triglyceride-glucose (TyG) index. Mental health symptoms were assessed by the 4-item Patient Health Questionnaire (PHQ-4) scores, categorized as no symptoms (0), mild symptoms (1), and clear symptoms (≥ 2). We used Cox proportional hazards models to assess the independent and joint associations of TyG and PHQ-4 with incident CVD and myocardial infarction (MI). The multiplicative and additive interactions were assessed between TyG tertiles and PHQ-4 status.
During a median follow-up of 13.6 years, 22,867 incident CVD and 7,649 incident MI cases were recorded. Compared to participants with PHQ-4 = 0, those with PHQ-4 ≥ 2 had higher risks of incident CVD (hazard ratio [HR], 1.35; 95% confidence interval [CI], 1.31-1.39) and MI (1.30, 1.23-1.37), and the proportions mediated by TyG were 5.3% (4.5%-6.3%) and 9.3% (7.4%-12.5%), respectively, whereas no significant mediation effect was observed in participants with PHQ-4 = 1. Significant multiplicative (HR for interaction, 1.11; 95%CI, 1.02-1.19) and additive interactions (relative excess risk due to interaction [RERI], 0.25; 95%CI, 0.15-0.35) were found between TyG tertile 3 and PHQ-4 ≥ 2 on incident CVD, and additive interaction (RERI, 0.33; 95%CI, 0.14-0.52) was seen on incident MI. Those with PHQ-4 ≥ 2 and TyG tertile 3 had the highest risks of incident CVD (1.80, 1.71-1.90) and incident MI (2.17, 1.97-2.38).
Clear mental health symptoms (PHQ-4 score ≥ 2) were associated with higher risk of incident CVD, with IR reflected by TyG index partially and modestly mediating the association, suggesting that targeting IR may help attenuate cardiovascular risk among populations with clear mental health symptoms. Our findings support integrated interventions to reduce the burden of CVD, particularly in individuals with clear mental health symptoms who are more vulnerable to IR.

PMID:
42422430
Bibliographic data and abstract were imported from PubMed on 09 Jul 2026.

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