OBJECTIVE: This study aimed to assess the association of bipolar disorder (BD) with risk of major adverse cardiac events (MACEs) after adjusting for established cardiovascular disease (CVD) risk factors. METHODS: We conducted a population-based historical cohort study using the Rochester Epidemiology Project. Patients older than 30 years with a clinical encounter from 1998 to 2000 with no prior MACE, atrial fibrillation, or heart failure were followed up through March 1, 2016. BD diagnosis was validated by chart review. Cox proportional hazards regression models were adjusted for established CVD risk factors, alcohol use disorder, other substance use disorders (SUDs), and major depressive disorder (MDD). RESULTS: The cohort included 288 individuals with BD (0.81%) and 35,326 individuals without BD as the reference group (Ref). Median (interquartile range) follow-up was 16.5 (14.6-17.5) years. A total of 5636 MACE events occurred (BD, 59; Ref, 5577). Survival analysis showed an association between BD and MACE (median event-free-survival rates: BD, 0.80; Ref, 0.86; log-rank p = .018). Multivariate regression adjusting for age and sex also yielded an association between BD and MACE (hazard ratio [HR] = 1.93; 95% confidence interval [CI] = 1.43-2.52; p < .001). The association remained significant after further adjusting for smoking, diabetes mellitus, hypertension, high-density lipoprotein cholesterol, and body mass index (HR = 1.66; 95% CI = 1.17-2.28; p = .006), and for alcohol use disorder, SUD, and MDD (HR = 1.56; 95% CI = 1.09-2.14; p = .010). CONCLUSIONS: In this study, BD was associated with an increased risk of MACE, which persisted after adjusting for established CVD risk factors, SUDs, and MDD. These results suggest that BD is an independent risk factor for major clinical cardiac disease outcomes.

Center of Biomedical Research and Innovation Universidad de los Andes Santiago Chile

Department of Medicine Northwell Health Lenox Hill Hospital New York New York

Department of Psychiatry and Behavioral Sciences SUNY Downstate Health Sciences University Brooklyn New York

Department of Psychiatry Faculty of Medicine Universidad de los Andes

Division of Epidemiology Department of Health Sciences Research and Department of Neurology Mayo Clinic Rochester Minnesota

Division of Preventive Cardiology Department of Cardiovascular Medicine Mayo Clinic Rochester Minnesota

From the Department of Psychiatry and Psychology Mayo Clinic Rochester Minnesota

International Clinical Research Center St Anne's University Hospital Brno Czech Republic

Mental Health Service Clínica Universidad de los Andes Santiago Chile

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$a Foroughi, Moein $u From the Department of Psychiatry and Psychology (Foroughi, Suarez, Prieto, Frye, Morgan), Mayo Clinic, Rochester, Minnesota; Department of Psychiatry and Behavioral Sciences (Foroughi), SUNY Downstate Health Sciences University, Brooklyn, New York; Division of Preventive Cardiology, Department of Cardiovascular Medicine (Medina Inojosa, Lopez-Jimenez, Saeidifard), Mayo Clinic, Rochester, Minnesota; Department of Medicine (Saeidifard), Northwell Health-Lenox Hill Hospital, New York, New York; International Clinical Research Center (Stokin), St. Anne's University Hospital, Brno, Czech Republic; Department of Psychiatry, Faculty of Medicine (Prieto), Universidad de los Andes; Mental Health Service (Prieto), Clínica Universidad de los Andes, Santiago, Chile; Division of Epidemiology, Department of Health Sciences Research and Department of Neurology (Rocca), Mayo Clinic, Rochester, Minnesota; and Center of Biomedical Research and Innovation (Prieto), Universidad de los Andes, Santiago. Chile

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$a Association of Bipolar Disorder With Major Adverse Cardiovascular Events: A Population-Based Historical Cohort Study / $c M. Foroughi, JR. Medina Inojosa, F. Lopez-Jimenez, F. Saeidifard, L. Suarez, GB. Stokin, ML. Prieto, WA. Rocca, MA. Frye, RJ. Morgan

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$a OBJECTIVE: This study aimed to assess the association of bipolar disorder (BD) with risk of major adverse cardiac events (MACEs) after adjusting for established cardiovascular disease (CVD) risk factors. METHODS: We conducted a population-based historical cohort study using the Rochester Epidemiology Project. Patients older than 30 years with a clinical encounter from 1998 to 2000 with no prior MACE, atrial fibrillation, or heart failure were followed up through March 1, 2016. BD diagnosis was validated by chart review. Cox proportional hazards regression models were adjusted for established CVD risk factors, alcohol use disorder, other substance use disorders (SUDs), and major depressive disorder (MDD). RESULTS: The cohort included 288 individuals with BD (0.81%) and 35,326 individuals without BD as the reference group (Ref). Median (interquartile range) follow-up was 16.5 (14.6-17.5) years. A total of 5636 MACE events occurred (BD, 59; Ref, 5577). Survival analysis showed an association between BD and MACE (median event-free-survival rates: BD, 0.80; Ref, 0.86; log-rank p = .018). Multivariate regression adjusting for age and sex also yielded an association between BD and MACE (hazard ratio [HR] = 1.93; 95% confidence interval [CI] = 1.43-2.52; p < .001). The association remained significant after further adjusting for smoking, diabetes mellitus, hypertension, high-density lipoprotein cholesterol, and body mass index (HR = 1.66; 95% CI = 1.17-2.28; p = .006), and for alcohol use disorder, SUD, and MDD (HR = 1.56; 95% CI = 1.09-2.14; p = .010). CONCLUSIONS: In this study, BD was associated with an increased risk of MACE, which persisted after adjusting for established CVD risk factors, SUDs, and MDD. These results suggest that BD is an independent risk factor for major clinical cardiac disease outcomes.

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