Lithium’s Cardiac Safety Reassessed

Cardiovascular disease kills more bipolar patients than suicide does, and lithium may cut that risk in half

STUDY: Xu N et al, Journal of Affective Disorders 2026

STUDY TYPE: Claims-based longitudinal cohort study

FUNDING: Independent

Background

Cardiovascular disease is the top cause of early death in bipolar disorder, yet lithium’s effect on the heart has been murky. Lab studies point to benefits like less inflammation and better blood vessel function, but toxic lithium levels can cause arrhythmias, so the net effect in real patients wasn’t clear.

The Study

• 2,945 adults newly diagnosed with bipolar disorder in a Beijing insurance database, average age 45.
• Compared those started on lithium (1,129) against those who weren’t (1,816), using statistical weighting to balance the groups.
• Followed for an average of 3 years, tracking new cardiovascular disease, ischemic heart disease, and stroke.

Lithium users had a lower rate of any cardiovascular disease (hazard ratio 0.38) and an even bigger drop in ischemic heart disease (hazard ratio 0.20). Stroke risk didn’t differ between groups.

The benefit showed up most clearly in patients over 50, men, and those who already had heart risk factors like hypertension or diabetes. Patients who stayed with lithium (took it at least 80% of the time) got the protection; those who didn’t take it consistently showed no significant benefit.

These benefits held up compared to untreated bipolar, and compared to treatment with antipsychotics (studies in depression show greater cardiovascular mortality with antipsychotics).

Limitations

Without randomization, causation isn’t clear, and lifestyle factors like smoking, diet, and exercise weren’t controlled for. Lithium blood levels weren’t measured, and patients were classified by their starting treatment, not what they were actually taking years later. Stroke and heart failure numbers were small, which limits confidence in those specific results.

Practice Implications

1. This builds on growing evidence of cardiovascular benefits with lithium, including less atherosclerosis, lower stroke risk, enhanced cardiac remodeling, as well as lower overall mortality rates.
2. With lithium, t-wave flattening and inversion on ECG can occur but is benign.  (usually benign). More serious arrhythmias are rare and usually involve slowing or blocking of conduction: AV block, bundle branch block, sick sinus syndrome, and ventricular extrasystoles.