case vignette

“Mr. Kennedy” is a 34-year-old white male with a history of bipolar I disorder. In his latest episode, he was depressed with psychotic features. The onset of his mood disorder was at the age of 21. He is currently taking clozapine 125 mg BID and valproic acid 1500 mg at bedtime. He is morbidly obese (BMI = 50) and has hypertension and hyperlipidemia. He has a problem with fast blood sugar but does not meet the criteria for diabetes.

At the outpatient visit, Mr. Kennedy and his psychiatrist decided to discontinue valproic acid due to elevated liver function tests. Mr. Kennedy tapered off his valproic acid dose over a four-month period. After 1 year, his weight had decreased by 26 pounds (approximately 8% of his total body weight) and his BMI had decreased to 45, but there were no changes in his psychiatric symptoms. In his four years since discontinuing valproate, Mr. Kennedy’s weight has dropped an additional 22 pounds, bringing his BMI to 42. Three weeks after his recent outpatient visit, his mother called to tell the psychiatrist that Mr. Kennedy had died from what appeared to be a myocardial infarction.

Bipolar disorder is associated with increased cardiovascular comorbidity and mortality, and reduced life expectancy.^1-5 Most previous studies were conducted in Europe and North America, with more limited evidence in Asian populations. In patients with bipolar disorder, heart failure may be the leading cause of excessive sudden cardiac death in patients over 50 years of age.⁶ Another small study found evidence of unfavorable cardiac structural measurements in patients with bipolar disorder.⁷

current research

Lee and friends⁸ We hypothesized that Asian patients with bipolar disorder would have significantly increased cardiometabolic disease, including hospitalization for heart failure (hHF) and early all-cause mortality. Through a national population-based cohort study conducted in the South, researchers investigated ischemic stroke, ischemic heart disease (IHD), We compared the risks of combined cardiometabolic disease and all-cause mortality. South Korea.

The researchers analyzed data from the Korea National Health Insurance Corporation (KNHIS), an anonymized public database covering all South Korean residents from 2002 to 2018. A representative sample cohort of all individuals diagnosed with bipolar disorder for the first time between 2003 and 2107 was drawn. Groups representing 20% ​​of the total sample were selected by stratified random sampling with proportional distribution within age, gender, place of residence, and household income strata.

Inclusion criteria were a primary diagnosis of F30-31 and at least one claim for psychiatric medication. Individuals with a record of psychotic disorder codes (F20-29) were excluded. For comparison, a representative 20% sample cohort of healthy controls who had never been diagnosed with a major mental illness (depression, bipolar disorder, or psychotic disorder) was used for bipolar disorder patients. were selected using the same sampling method.

Exclusion criteria for both groups were: death within 90 days of baseline, treatment for cardiometabolic disease or coronary artery disease, and transient cerebral ischemia before or within 3 months of baseline. were hospitalized for a seizure and/or were under 18 years of age.

The study cohort consisted of 11,329 participants with bipolar disorder and one-on-one matched controls. Outcomes were ischemic stroke, IHD, hHF, cardiometabolic disease complex, and all-cause mortality during follow-up. The cohort was followed from baseline until death, development of outcomes, or December 31, 2018, whichever came first. We used Kaplan-Meier curves and compared the cumulative incidence of outcomes between bipolar disorder patients and healthy controls using the log-rank test. Multivariate Cox regression analysis was used to calculate hazard ratios (HR) and 95% confidence intervals (CI) for outcomes in bipolar disorder patients and controls.

The average follow-up period for the cohort was approximately 11 years. The cumulative incidence of all outcomes was significantly higher in patients with bipolar disorder than in controls. The incidence rates per 1000 person-years for patients with bipolar disorder were 0.94 for ischemic stroke, 9.5 for IHD, 0.95 for hHF, 85.1 for combined cardiometabolic disease, and 5.5 for all-cause mortality. Hazards for all outcomes were significantly higher in patients with bipolar disorder: ischemic stroke HR=2.0, 95% CI 1.4-2.7, IHD HR=1.6, 95% CI 1.4-1.7, hHF HR=2.5, 95% CI 1.8-3.6, cardiometabolic composite HR=1.94, 95% CI 1.86-2.02, all-cause mortality HR=2.2, 95% CI 1.9-2.5.

In subgroup analyzes by age, the association between bipolar disorder and all outcomes except ischemic stroke was more pronounced in younger people. In subgroup analyzes by gender, the association between bipolar disorder and all outcomes except her hHF was more pronounced in women. In sensitivity analyses, the pattern of findings did not change regardless of prior treatment with mood stabilizers or whether the initial diagnosis was depression or bipolar disorder.

Research conclusion

In a population-based national cohort of low-risk individuals without baseline hypertension, dyslipidemia, diabetes, or other cardiometabolic or vascular disease, bipolar disorder was associated with ischemic stroke, IHD, hHF, and complex cardiometabolic disease. was associated with an increased risk of -Causing death during follow-up. In subgroup analyses, these associations were more pronounced in younger individuals and women.

Strengths of the study include the use of a large, representative national dataset with rigorous matching. Study limitations include the focus on Korean adults with low baseline cardiovascular risk, which limits generalizability to other populations. Observational nature of the study design. and the lack of specific information regarding the cause of death.

conclusion

Bipolar disorder was associated with an increased risk of cardiometabolic disease and early death from all causes, especially in young people and women. The findings suggest that regular screening and preventive measures for cardiovascular disease are warranted for bipolar disorder patients of all ages. Potentially relevant interventions include patient education, lifestyle modifications, and cardioprotective pharmacological treatments.

Dr. Miller He is a professor in the Department of Psychiatry and Health Behavior at Augusta University in Georgia. He is on the editorial board and heads the schizophrenia section. Psychiatry Times®. The authors report receiving research support from Augusta University, National Institute of Mental Health, and Stanley Medical Research Institute.

References

1. Vieta E, Berk M, Schulze TG, et al. Bipolar disorder. Nat Rev Disprimer. 2018;4:18008.

2. Hayes JF, Miles J, Walters K, et al. A systematic review and meta-analysis of early mortality in bipolar affective disorder. Acta Psychiatrist Scando. 2015;131(6):417-425.

3. Westman J, Hällgren J, Wahlbeck K, et al. Cardiovascular mortality in bipolar disorder: a population-based cohort study in Sweden. BMJ Open. 2013;3(4):e002373.

4. Callaghan RC, Khizar A. Incidence of cardiovascular disease in patients with bipolar disorder: a population-based longitudinal study in Ontario, Canada. J Affect Disorder. 2010;122(1-2):118-123.

5. Foroughi M, Medina Inojosa JR, Lopez-Jimenez F, et al. Association between bipolar disorder and major adverse cardiovascular events: A population-based historical cohort study. Psychosom Med. 2022;84(1):97-103.

6. Chen PH, Tsai SY, Pan CH, et al. Incidence and risk factors for sudden cardiac death in bipolar disorder over the lifespan. J Affect Disorder. 2020;274:210-217.

7. Chen PH, Chen SJ, Xiao CY, et al. Echocardiography of cardiac structure and function in middle-aged and older patients with bipolar disorder. J Affect Disorder. 2022;296:428-433.

8. Lee YB, Kim H, Lee J et al. Bipolar disorder and the risk of cardiometabolic disease, heart failure, and all-cause mortality: a population-based matched cohort study in South Korea. science officer. 2024;14(1):1932.