Patients with bipolar disorder are more likely to experience major adverse cardiac events (MACE), according to the results of a study published in Psychosomatic Medicine.

Researchers analyzed data from the Rochester Epidemiology Project (REP) provided by clinicians in Olmsted County, Minnesota, of individuals older than 30 years who sought primary care between 1998 and 2003. They excluded patients with known history of coronary artery disease, stroke, atrial fibrillation, or heart failure. Individuals with higher probability of having bipolar disorder were identified through billing codes, cross-matching with the Mayo Clinic Bipolar Biobank Study and a previous cohort study, and identifying patients prescribed mood stabilizers or who had inpatient hospitalizations for bipolar disorder.

The investigators found that the group with bipolar disorder was younger (47.7±10.9 vs 49.8±13.3 years; P =.001) compared with a reference group. Individuals with bipolar disorder were also more likely to have higher body mass index (BMI), hypertension, diabetes, chronic kidney disease, current smoking, alcohol use disorder (AUD), and substance use disorders (SUD). They had lower diastolic blood pressure values and high-density lipoprotein (HDL) cholesterol levels.

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Over the median follow-up of 16.5 years, 5636 MACE events occurred. Event-free survival rates were 0.81 for individuals with bipolar disorder (n=288) and 0.86 for individuals in the reference group (n=35,326; log-rank P =.018).

The hazard ratio for MACE was higher for all risk factors, AUD, bipolar disorder, and major depressive disorder (MDD). An inverse relationship was reported for MACE and HDL.

After adjusting for age and sex, the investigators reported an association between bipolar disorder and MACE (HR 1.93; 95% CI, 1.43-2.52; P <.001). That association remained significant after adjusting for smoking, diabetes, hypertension, HDL, BMI, age, and sex (HR 1.66; 95% CI, 1.17-2.28; P = .005), as well as adjusting for AUD, SUD, and MDD (HR 1.56; 95% CI, 1.09-2.14; P =.010).

The association persisted in analysis excluding violent deaths (Model 3 HR 1.58; 95% CI, 1.12-2.23; P =.009) and deaths unrelated to cardiovascular mortality, as well as adjusting for the Charlson Comorbidity Index (Model 4 HR 1.77; 95% CI: 1.37-2.28; P <.001).

The researchers said that adjustments to the American College of Cardiology/American Heart Association’s atherosclerotic cardiovascular disease risk estimator may be necessary to take the impact of bipolar disorder into consideration.

“Our findings also underscore the importance of the future development of medical and lifestyle interventions to more effectively address the burden of [cardiovascular disease] in patients with [bipolar disorder],” the investigators said. “Such interventions may need to be tailored to the unique challenges presented in [bipolar disorder] and will require interdisciplinary collaborations between psychiatry, psychology, cardiology, physical medicine and rehabilitation, case management, occupational and physical therapy, and likely several other disciplines.”

A limitation of the study is the inability to adjust for the impact of medications, which could adversely affect risk factors for cardiovascular risk factors and lead to adverse cardiovascular events.

Disclosure: One study author declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Foroughi M, Medina Inojosa JR, Lopez-Jimenez F, et al. Association of bipolar disorder with major adverse cardiovascular events: a population-based historical cohort study. Psychosomatic Medicine. Published online October 4, 2021. doi:10.1097/PSY.0000000000001017

This article originally appeared on Psychiatry Advisor