There has been considerable interest in the elevated risk of cardiovascular disease associated with serious mental illness. Although the contemporary literature has paid much attention to major depression and schizophrenia, focus on the risk of cardiovascular mortality for patients with bipolar disorder has been more limited, despite some interest in the historical literature.
Methods
We reviewed the historical and contemporary literature related to cardiovascular morbidity and mortality in bipolar disorder.
Results
In studies that specifically assess cardiovascular mortality, bipolar disorder has been associated with a near doubling of risk when compared with general population estimates. This may be explained by the elevated burden of cardiovascular risk factors found in this population. These findings predate modern treatments for bipolar disorder, which may further influence cardiovascular risk.
Conclusions
Given the substantial risk of cardiovascular disease, rigorous assessment of cardiovascular risk is warranted for patients with bipolar disorder. Modifiable risk factors should be treated when identified. Further research is warranted to study mechanisms by which this elevated risk for cardiovascular disease are mediated and to identify systems for effective delivery of integrated medical and psychiatric care for individuals with bipolar disorder.
KraepelinE.Manic-depressive insanity and paranoia. Edinburgh, Scotland: E and Livingstone S; 1921.
2.
BellLV.On a form of disease resembling some advanced stages of mania and fever, but so contradistinguished from any ordinarily described combination of symptoms, as to render it probable that it may be overlooked and hitherto unrecorded malady. American Journal of Insanity. 1849;6:97–127.
3.
RayI.On undescribed forms of acute maniacal disease. American Journal of Insanity. 1853;10:95–111.
4.
DerbyIM.Manic-depressive “exhaustion” deaths: an analysis of “exhaustion” case histories. Psychiatr Q. 1933;7:436–449.
5.
AdlandML.Review, case studies, therapy, and interpretation of the acute exhaustive psychoses. Psychiatr Q. 1947;21:38–69.
6.
SlaterE.Zur Erbpathoogie des manisch-depressiven Irreseins. Die Eltern und Kinder von ManischDepressiven. [Hereditary pathology of manic-depressive illness. Parents and offspring of manic-depressives]. Gesamte Z Neurol Psychiatr.1938;163:1–47.
7.
BumkeO.Handbuch der Geisteskrankheiten.Berlin, Germany: Julius Springer Verlag; 1928.
8.
AlstromCH.Mortality in mental hospitals. Acta Psy-chiatr Neurol. 1942;17:1–42.
9.
OdegardO.Mortality in Norwegian mental hospitals 1926-1941. Acta Genet Stat Med.1951;2:141–173.
10.
MalzbergB.Rates of discharge and rates of mortality among first admissions to the New York civil state hospitals. Ment Hyg. 1952;36:104–120.
11.
MalzbergB.Rates of discharge and rates of mortality among first admissions to the New York civil state hospitals. II. Ment Hyg. 1952;36:618–638.
12.
MalzbergBM.Rates of discharge and rates of mortality among first admissions to the New York Civil State Hospitals. III. Ment Hyg. 1953;37:619–654.
13.
BabigianHM, OdoroffCL.The mortality experience of a population with psychiatric illness. Am J Psychiatry. 1969;126:470–480.
14.
MerikangasKR, KalaydjianA.Magnitude and impact of comorbidity of mental disorders from epidemiologic surveys. Curr Opin Psychiatry. 2007;20:353–358.
15.
BerksonJ.Limitations of the application of fourfold tables to hospital data. Biometrics Bulletin. 1946;2:47–53.
16.
TsuangMT, WoolsonRF, FlemingJA.Causes of death in schizophrenia and manic-depression. Br J Psychiatry. 1980;136:239–242.
17.
WeekeA, JuelK, VaethM.Cardiovascular death and manic-depressive psychosis. J Affect Disord. 1987;13:287–292.
18.
WeekeA, VaethM.Excess mortality of bipolar and unipolar manic-depressive patients. J Affect Disord. 1986;11:227–234.
19.
SharmaR, MarkarHR.Mortality in affective disorder. J Affect Disord. 1994;31:91–96.
20.
AngstF, StassenHH, ClaytonPJ, . Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord. 2002;68:167–181.
21.
LaursenTM, Munk-OlsenT, NordentoftM, . Increased mortality among patients admitted with major psychiatric disorders: a register-based study comparing mortality in unipolar depressive disorder, bipolar affective disorder, schizoaffective disorder, and schizophrenia. J Clin Psychiatry. 2007;68:899–907.
22.
OsbyU, BrandtL, CorreiaN, . Excess mortality in bipolar and unipolar disorder in Sweden. Arch Gen Psychiatry. 2001;58:844–850.
23.
PerrisC, d'EliaG.A study of bipolar (manic-depressive) and unipolar recurrent depressive psychoses. Mortality X., suicide and life-cycles. Acta Psychiatr Scand Suppl.1966;194:172–189.
24.
SimsA, PriorP.The pattern of mortality in severe neuroses. Br J Psychiatry. 1978;133:299–305.
25.
KallnerG, LindeliusR, PettersonU, . Mortality in 497 patients with affective disorders attending a lithium clinic or after having left it. Pharmacopsychiatry. 2000;33:8–13.
26.
Müller-OerlinghausenB, WolfT, AhrensB, . Mortality during initial and during later lithium treatment. A collaborative study by the International Group for the Study of Lithium-treated Patients. Acta Psychiatr Scand. 1994;90:295–297.
27.
ZilberN, SchufmanN, LernerY.Mortality among psychiatric patients—the groups at risk. Acta Psychiatr Scand. 1989;79:248–256.
TsaiSY, LeeCH, KuoCJ, . A retrospective analysis of risk and protective factors for natural death in bipolar disorder. J Clin Psychiatry. 2005;66:1586–1591.
30.
CraigTJ, YeQ, BrometEJ.Mortality among firstadmission patients with psychosis. Compr Psychiatry. 2006;47:246–251.
31.
BlackDW, WarrackG, WinokurG.The Iowa recordlinkage study. III. Excess mortality among patients with ‘functional’ disorders. Arch Gen Psychiatry. 1985;42:82–88.
32.
MeloniD, MiccinesiG, BenciniA, . Mortality among discharged psychiatric patients in Florence, Italy. Psychiatr Serv. 2006;57:1474–1481.
33.
RorsmanB.Mortality among psychiatric patients. Acta Psychiatr Scand. 1974;50:354–375.
34.
MartinRL, CloningerCR, GuzeSB, . Mortality in a follow-up of 500 psychiatric outpatients. II. Causespecific mortality. Arch Gen Psychiatry. 1985;42:58–66.
35.
MartinRL.Methodological and conceptual problems in the study of mortality in psychiatry. Psychiatr Dev. 1985;3:317–333.
SachsG, BowdenC, CalabreseJR, . Effects of lamotrigine and lithium on body weight during maintenance treatment of bipolar I disorder. Bipolar Disord. 2006;8:175–181.
38.
HermidaOG, FontelaT, GhiglioneM, . Effect of lithium on plasma glucose, insulin and glucagon in normal and streptozotocin-diabetic rats: role of glucagon in the hyperglycaemic response. Br J Pharmacol. 1994;111:861–865.
39.
DinesenH, GramL, AndersenT, . Weight gain during treatment with valproate. Acta Neurol Scand. 1984;70:65–69.
40.
PylvänenV, KnipM, PakarinenA, . Serum insulin and leptin levels in valproate-associated obesity. Epilepsia. 2002;43:514–517.
41.
HuangTL, ChenJF.Serum lipid profiles and schizophrenia: effects of conventional or atypical antipsychotic drugs in Taiwan. Schizophr Res. 2005;80:55–59.
42.
HendersonDC, CaglieroE, GrayC, . Clozapine, diabetes mellitus, weight gain, and lipid abnormalities: a five-year naturalistic study. Am J Psychiatry. 2000;157:975–981.
43.
SpivakB, LamschteinC, TalmonY, . The impact of clozapine treatment on serum lipids in chronic schizophrenic patients. Clin Neuropharmacol. 1999;22:98–101.
44.
GaulinBD, MarkowitzJS, CaleyCF, . Clozapine-associated elevation in serum triglycerides. Am J Psychiatry. 1999;156:1270–1272.
GuoJJ, KeckPEJr, Corey-LislePK, . Risk of diabetes mellitus associated with atypical antipsychotic use among patients with bipolar disorder: a retrospective, population-based, case-control study. J Clin Psychiatry. 2006;67:1055–1061.
47.
LambertBL, ChouCH, ChangKY, . Antipsychotic exposure and type 2 diabetes among patients with schizophrenia: a matched case-control study of California Medicaid claims. Pharmacoepidemiol Drug Saf. 2005;14:417–425.
48.
OllendorfDA, JoyceAT, RuckerM.Rate of newonset diabetes among patients treated with atypical or conventional antipsychotic medications for schizophrenia. MedGenMed. 2004;6:5.
49.
SernyakMJ, GulanskiB, RosenheckR.Undiagnosed hyperglycemia in patients treated with atypical antipsychotics. J Clin Psychiatry. 2005;66:1463–1467.
50.
CarlsonC, HornbuckleK, DelisleF, . Diabetes mellitus and antipsychotic treatment in the United Kingdom. Eur Neuropsychopharmacol. 2006;16:366–375.
51.
GianfrancescoF, WhiteR, WangRH, . Antipsychotic-induced type 2 diabetes: evidence from a large health plan database. J Clin Psychopharmacol. 2003;23:328–335.
52.
SimpsonGM.Atypical antipsychotics and the burden of disease. Am J Manag Care. 2005;11:(suppl)S235–S241.
53.
VolavkaJ, CzoborP, SheitmanB, . Clozapine, olanzapine, risperidone, and haloperidol in the treatment of patients with chronic schizophrenia and schizoaffective disorder. Am J Psychiatry. 2002;159:255–262.
54.
ZipurskyRB, GuH, GreenAI, . Course and predictors of weight gain in people with first-episode psychosis treated with olanzapine or haloperidol. Br J Psychiatry. 2005;187:537–543.
55.
KilbourneAM, RofeyDL, McCarthyJF, . Nutrition and exercise behavior among patients with bipolar disorder. Bipolar Disord. 2007;9:443–452.
56.
LasserK, BoydJW, WoolhandlerS, . Smoking and mental illness: a population-based prevalence study. JAMA. 2000;284:2606–2610.
57.
McElroySL, FryeMA, SuppesT, . Correlates of overweight and obesity in 644 patients with bipolar disorder. J Clin Psychiatry. 2002;63:207–213.
58.
FagioliniA, FrankE, ScottJA, . Metabolic syndrome in bipolar disorder: findings from the Bipolar Disorder Center for Pennsylvanians. Bipolar Disord. 2005;7:424–430.
59.
ShahA, ShenN, El-MallakhRS.Weight gain occurs after onset of bipolar illness in overweight bipolar patients. Ann Clin Psychiatry. 2006;18:239–241.
60.
BirkenaesAB, OpjordsmoenS, BrunborgC, . The level of cardiovascular risk factors in bipolar disorder equals that of schizophrenia: a comparative study. J Clin Psychiatry. 2007;68:917–923.
61.
FiedorowiczJG, PalagummiNM, Forman-HoffmanVL, . Elevated prevalence of obesity, metabolic syndrome, and cardiovascular risk factors in bipolar disorder. Ann Clin Psychiatry. 2008;20:131–137.
62.
KilbourneAM, CorneliusJR, HanX, . Burden of general medical conditions among individuals with bipolar disorder. Bipolar Disord. 2004;6:368–373.
JohannessenL, StrudsholmU, FoldagerL, . Increased risk of hypertension in patients with bipolar disorder and patients with anxiety compared to background population and patients with schizophrenia. J Affect Disord. 2006;95:13–17.
65.
RaphaelT, ParsonsJP.Blood sugar studies in dementia praecox and manic-depressive insanity. Arch Neurol Psychiatry. 1921;5:687–709.
66.
KasaninJ.The blood sugar curve in mental disease: II. The schizophrenia (dementia praecox) groups. Arch Neurol Psychiatry. 1926;16:414–419.
67.
CassidyF, AhearnE, CarrollBJ.Elevated frequency of diabetes mellitus in hospitalized manic-depressive patients. Am J Psychiatry. 1999;156:1417–1420.
68.
BrandrupE, RandrupA.A controlled investigation of plasma lipids in manic-depressives. Br J Psychiatry. 1967;113:987–992.
69.
CardenasJ, FryeMA, MarusakSL, . Modal subcomponents of metabolic syndrome in patients with bipolar disorder. J Affect Disord. 2008;106:91–97.
70.
Garcia-PortillaMP, SaizPA, BenabarreA, . The prevalence of metabolic syndrome in patients with bipolar disorder. J Affect Disord. 2008;106:197–201.
71.
van WinkelR, De HertM, Van EyckD, . Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder. Bipolar Disord. 2008;10:342–348.
72.
De HertM, van WinkelR, Van EyckD, . Prevalence of diabetes, metabolic syndrome and metabolic abnormalities in schizophrenia over the course of the illness: a cross-sectional study. Clin Pract Epidemol Ment Health. 2006;2:14.
73.
TeixeiraPJ, RochaFL.The prevalence of metabolic syndrome among psychiatric inpatients in Brazil. Rev Bras Psiquiatr. 2007;29:330–336.
74.
YumruM, SavasHA, KurtE, . Atypical antipsychotics related metabolic syndrome in bipolar patients. J Affect Disord. 2007;98:247–252.
75.
KilbourneAM, PostEP, BauerMS, . Therapeutic drug and cardiovascular disease risk monitoring in patients with bipolar disorder. J Affect Disord. 2007;102:145–151.
76.
KreyenbuhlJ, DickersonFB, MedoffDR, . Extent and management of cardiovascular risk factors in patients with type 2 diabetes and serious mental illness. J Nerv Ment Dis. 2006;194:404–410.
