Association between lithium and arterial atherosclerosis in physically healthy bipolar disorder

Patients with bipolar disorder (BD) have an elevated risk of cardiovascular disease, primarily driven by atherosclerosis. This study aimed to identify clinical and medication-related features associated with accelerated atherosclerosis in medicated BD patients.

One hundred ten physically healthy patients with bipolar I disorder aged 20-60 years and 107 normal controls (NCs) underwent measurement of carotid intima-media thickness (CIMT) using high-resolution ultrasonography. BD patients were divided into normal and elevated CIMT groups using threshold defined by the American Society of Echocardiography. Clinical data were obtained through structured interviews and medical record review.

Patients with BD exhibited significantly greater mean CIMT than NCs. BD patients with serum lithium levels ≤0.6 mEq/L had significantly higher odds of greater CIMT (95% confidence interval for odds ratio: 1.16-7.09). Multivariable logistic regression showed that longer illness duration and higher lithium level were significantly associated with normal CIMT. After controlling for age and BMI, lower lithium level, shorter illness duration, and higher triglyceride level remained independently associated with greater CIMT, accounting for 34.3% of the variance. Among current lithium-treated patients, only BMI was independently associated with CIMT (β = 0.249, p = 0.038).

Among treatment-seeking adults with BD, higher serum lithium levels were associated with lower and normal CIMT, while illness chronicity showed the opposite trend. The present findings support a potential anti-atherosclerotic role of lithium therapy and underscore the importance of weight management in reducing cardiovascular risk in the BD population-even among those on lithium.