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Manic/Hypomanic Symptom Burden and Cardiovascular Mortality in Bipolar Disorder

From the Department of Psychiatry (J.G.F., W.H.C.), Roy J. and Lucille A. Carver College of Medicine, University of Iowa Hospitals and Clinics, Iowa City, Iowa; Department of Psychiatry and Human Behavior (D.A.S.), The Warren Alpert Medical School of Brown University, Providence, Rhode Island; Department of Psychiatry (J.E.), Columbia University College of Physicians and Surgeons, New York, New York; New York State Psychiatric Institute (J.E.), New York, New York; Department of Psychiatry (A.C.L., C.L.), Weill Medical College of Cornell University, New York, New York; Department of Psychiatry (J.P.R.), Washington University School of Medicine, St. Louis, Missouri.

Address correspondence and reprint requests to Jess G. Fiedorowicz, 200 Hawkins Drive W278GH, Iowa City, IA 52242. E-mail: jess-fiedorowicz{at}uiowa.edu

Objectives: To compare the risk for cardiovascular mortality between bipolar I and bipolar II subtypes and determine correlates of cardiovascular mortality. Bipolar disorder conveys an increased risk of cardiovascular mortality.

Methods: Participants with major affective disorders were recruited for the National Institute of Mental Health Collaborative Depression Study and followed prospectively for up to 25 years. A total of 435 participants met the diagnostic criteria for bipolar I (n = 288) or bipolar II (n = 147) disorder based on Research Diagnostic Criteria at intake and measures of psychiatric symptoms during follow-up. Diagnostic subtypes were contrasted by cardiovascular mortality risk using Cox proportional hazards regression. Affective symptom burden (the proportion of time with clinically significant manic/hypomanic or depressive symptoms) and treatment exposure were additionally included in the models.

Results: Thirty-three participants died from cardiovascular causes. Participants with bipolar I disorder had more than double the cardiovascular mortality risk of those with bipolar II disorder, after controlling for age and gender (hazard ratio = 2.35, 95% Confidence Interval = 1.04-5.33; p = .04). The observed difference in cardiovascular mortality between these subtypes was at least partially confounded by the burden of clinically significant manic/hypomanic symptoms which predicted cardiovascular mortality independent of diagnosis, treatment exposure, age, gender, and cardiovascular risk factors at intake. Selective serotonin uptake inhibitors seemed protective although they were introduced late in follow-up. Depressive symptom burden was not related to cardiovascular mortality.

Conclusions: Participants with bipolar I disorder may face a greater risk of cardiovascular mortality than those with bipolar II disorder. This difference in cardiovascular mortality risk may reflect manic/hypomanic symptom burden.

Key Words: adult • bipolar disorder • cardiovascular mortality • mania • prospective cohort study • risk factors

Abbreviations: CDS = collaborative depression study; DSM-IV = Diagnostic and Statistical Manual of Mental Disorders, 4th Edition; RDC = Research Diagnostic Criteria; PSR = Psychiatric Status Rating.