Background: Cardiovascular disease (CVD) is the leading cause of premature mortality in bipolar disorder (BD). While lithium is a first-line mood stabilizer, its long-term cardiovascular safety profile remains debated, with conflicting evidence regarding potential toxicity versus protective effects. This study aimed to evaluate the association between lithium use and incident CVD risk in claims-based cohort of patients with BD.
Methods: We conducted a claims-based longitudinal cohort study using the Beijing Medical Claim Data for Employees (BMCDE) database from 2010 to 2017. Patients newly diagnosed with BD were categorized into lithium and non‑lithium user groups. Inverse probability weighting (IPW) was applied to control for baseline confounding. Weighted Cox proportional hazards models were used to estimate hazard ratios (HRs) for incident CVDs, including ischemic heart disease (IHD) and stroke.
Results: The study included 2945 patients (mean age 44.5 years) with a mean follow-up of 3 years. Lithium use was associated with a significantly lower risk of overall CVD (HR = 0.38; 95% CI 0.18-0.78) and specifically IHD (HR = 0.20; 95% CI 0.06-0.67). No significant association was found for stroke (HR = 0.69; 95% CI 0.27-1.75). Subgroup analyses revealed that this lower risk was most pronounced among older individuals, males, and those with pre-existing cardiovascular risk factors.
Conclusions: Lithium use is associated with a reduced risk of incident CVDs, particularly IHD, in patients with BD. These findings suggest that lithium may confer dual psychiatric and somatic benefits, supporting its continued utility in high-risk populations.
Keywords: Bipolar disorder; Cardiovascular disease; Ischemic heart disease; Lithium; Older age bipolar disorder.
Copyright © 2026. Published by Elsevier B.V.