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Cardiovascular risk factors in outpatients with bipolar disorder: a report from the Brazilian Research Network in Bipolar Disorder

Abstract

Objective:

Bipolar disorder (BD) is associated with significant morbidity and mortality due to comorbid general medical conditions, particularly cardiovascular disease. This study is the first report of the Brazilian Research Network in Bipolar Disorder (BRN-BD) that aims to evaluate the prevalence and clinical correlates of cardiovascular risk factors among Brazilian patients with BD.

Methods:

A cross-sectional study of 159 patients with DSM-IV BD, 18 years or older, consecutively recruited from the Bipolar Research Program (PROMAN) in São Paulo and the Bipolar Disorder Program (PROTAHBI) in Porto Alegre. Clinical, demographic, anthropometric, and metabolic variables were systematically assessed.

Results:

High rates of smoking (27%), physical inactivity (64.9%), alcohol use disorders (20.8%), elevated fasting glucose (26.4%), diabetes (13.2%), hypertension (38.4%), hypertriglyceridemia (25.8%), low HDL-cholesterol (27.7%), general (38.4%) and abdominal obesity (59.1%) were found in the sample. Male patients were more likely to have alcohol use disorders, diabetes, and hypertriglyceridemia, whereas female patients showed higher prevalence of abdominal obesity. Variables such as medication use pattern, alcohol use disorder, and physical activity were associated with selected cardiovascular risk factors in the multivariable analysis.

Conclusion:

This report of the BRN-BD provides new data regarding prevalence rates and associated cardiovascular risk factors in Brazilian outpatients with BD. There is a need for increasing both awareness and recognition about metabolic and cardiovascular diseases in this patient population.

Bipolar disorder; cardiovascular risk factors; comorbidity


Introduction

Bipolar disorder (BD) is a chronic and disabling illness associated with significant morbidity and mortality.11. Kupfer DJ. The increasing medical burden in bipolar disorder. JAMA. 2005;293:2528-30. Patients with BD are subject to premature death from all causes when compared to the general population22. Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord. 2002;68:167-81. and usually have several comorbid general medical conditions associated with worse outcomes and higher burden of disease.33. Krishnan KR. Psychiatric and medical comorbidities of bipolar disorder. Psychosom Med. 2005;67:1-8.

4. Thompson WK, Kupfer DJ, Fagiolini A, Scott JA, Frank E. Prevalence and clinical correlates of medical comorbidities in patients with bipolar I disorder: analysis of acute-phase data from a randomized controlled trial. J Clin Psychiatry. 2006;67:783-8.
-55. Guo JJ, Keck PE Jr, Li H, Jang R, Kelton CM. Treatment costs and health care utilization for patients with bipolar disorder in a large managed care population. Value Health. 2008;11:416-23.

Increased rates of obesity,66. McElroy SL, Frye MA, Suppes T, Dhavale D, Keck PE Jr, Leverich GS, et al. Correlates of overweight and obesity in 644 patients with bipolar disorder. J Clin Psychiatry. 2002;63:207-13.,77. Fagiolini A, Kupfer DJ, Houck PR, Novick DM, Frank E. Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry. 2003;160:112-7. diabetes,88. McIntyre RS, Soczynska JK, Beyer JL, Woldeyohannes HO, Law CW, Miranda A, et al. Medical comorbidity in bipolar disorder: re-prioritizing unmet needs. Curr Opin Psychiatry. 2007;20:406-16. hypertension,99. McIntyre RS, Konarski JZ, Misener VL, Kennedy SH. Bipolar disorder and diabetes mellitus: epidemiology, etiology, and treatment implications. Ann Clin Psychiatry. 2005;17:83-93. dyslipidemia,1010. Kilbourne AM, Cornelius JR, Han X, Pincus HA, Shad M, Salloum I, et al. Burden of general medical conditions among individuals with bipolar disorder. Bipolar Disord. 2004;6:368-73. and metabolic syndrome1111. Taylor V, MacQueen G. Associations between bipolar disorder and metabolic syndrome: a review. J Clin Psychiatry. 2006;67:1034-41.

12. Teixeira PJ, Rocha FL. The prevalence of metabolic syndrome among psychiatric inpatients in Brazil. Rev Bras Psiquiatr. 2007;29:330-6.
-1313. De Almeida KM, De Macedo-Soares MB, Issler CK, Amaral JA, Caetano SC, Dias RS, et al. Obesity and metabolic syndrome in Brazilian patients with bipolar disorder. Acta Neuropsychiatr. 2009;21:84-8. have been reported in recent clinical and epidemiological studies.1414. Goldstein BI, Fagiolini A, Houck P, Kupfer DJ. Cardiovascular disease and hypertension among adults with bipolar I disorder in the United States. Bipolar Disord. 2009;11:657-62.,1515. Goldstein BI, Liu SM, Zivkovic N, Schaffer A, Chien LC, Blanco C. The burden of obesity among adults with bipolar disorder in the United States. Bipolar Disord. 2011;13:387-95. In addition to being exposed to the weight gain effects of the pharmacological treatment, BD patients are more likely to have sedentary lifestyles and poor dietary habits,1616. Kilbourne AM, Rofey DL, McCarthy JF, Post EP, Welsh D, Blow FC. Nutrition and exercise behavior among patients with bipolar disorder. Bipolar Disord. 2007;9:443-52. which are well-established cardiovascular risk factors.1717. Morriss R, Mohammed FA. Metabolism, lifestyle and bipolar affective disorder. J Psychopharmacol. 2005;19:94-101.

Most of the abovementioned data come from developed countries, which have somewhat distinct realities from the developing world. In Brazil, together with an increase in the absolute prevalence of obesity and metabolic syndrome, the trend is shifting toward the lower income population.1818. Monteiro CA, Conde WL, Popkin BM. Income-specific trends in obesity in Brazil: 1975-2003. Am J Public Health. 2007;97:1808-12. This is of particular interest for the field of BD since most patients are treated by the public health system and prescription patterns may be different from the rest of the world, particularly regarding the use of atypical antipsychotics.1919. Kapczinski F, Gentil V. CANMAT guidelines for bipolar disorder: a commentary from South America. Bipolar Disord. 2005;7:87-8.

Despite being a leader in psychiatric research among developing countries,2020. Dainesi SM, Elkis H. Current clinical research environment: focus on psychiatry. Rev Bras Psiquiatr. 2007;29:283-90. one of the shortcomings that may constrain the progress of clinical research in Brazil is the relatively limited number of patients enrolled in most studies, and a natural step to overcome this limitation is to establish research networks.2121. Miguel EC, Ferrão YA, Rosário MC, Mathis MA, Torres AR, Fontenelle LF, et al. The Brazilian research consortium on obsessive-compulsive spectrum disorders: recruitment, assessment instruments, methods for the development of multicenter collaborative studies and preliminary results. Rev Bras Psiquiatr. 2008;30:185-96. In 2005, the Brazilian Association for Bipolar Disorder (ABTB) created the Brazilian Research Network in Bipolar Disorder (BRN-BD) as a means to promote the integration of BD research centers and to develop collaborative studies. The BRN-BD comprises BD urban university-affiliated treatment and research centers of São Paulo, Porto Alegre, Salvador, and Fortaleza, and some studies from this initiative have already been published.2222. Quarantini LC, Miranda-Scippa A, Nery-Fernandes F, Andrade-Nascimento M, Galvão-de-Almeida A, Guimarães JL, et al. The impact of comorbid posttraumatic stress disorder on bipolar disorder patients. J Affect Disord. 2010;123:71-6.

23. Andrade-Nascimento M, Miranda-Scippa Â, Nery-Fernandes F, Kapczinski F, Quarantini LC. The identification of unipolar mania subtype based on anxiety comorbidity. J Affect Disord. 2011;132:356-9.

24. Brietzke E, Moreira CL, Duarte SV, Nery FG, Kapczinski F, Miranda Scippa A, et al. Impact of comorbid migraine on the clinical course of bipolar disorder. Compr Psychiatry. 2012;53:809-12.
-2525. Seixas C, Miranda-Scippa A, Nery-Fernandes F, Andrade-Nascimento M, Quarantini LC, Kapczinski F, et al. Prevalence and clinical impact of eating disorders in bipolar patients. Rev Bras Psiquiatr. 2012;34:66-70.

In this context, the present study is a report of the BRN-BD that aims to evaluate the prevalence and clinical correlates of cardiovascular risk factors among patients with BD from two research centers in São Paulo (PROMAN) and Porto Alegre (PROTAHBI), Brazil.

Methods

Subjects

The study is a cross-sectional analysis of outpatients with BD, 18 years or older, consecutively recruited from the Bipolar Research Program (PROMAN) at the University of São Paulo Medical School, São Paulo, Brazil, and the Bipolar Disorder Program (PROTAHBI) at the Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil. Because these institutions are tertiary treatment facilities, patients are usually referred from primary care units and secondary hospitals for specialized treatment. As part of the research protocols of both sites, BD and comorbid conditions are diagnosed with the Structured Clinical Interview for DSM-IV¯ Axis I Disorders (SCID-I). Exclusion criteria were schizophrenia or other psychotic disorders, schizoaffective disorders, and organic mental disorders. The study was approved by the Institutional Review Boards (FMUSP 1326/06 and GPPG-HCPA 06-245) of both research sites, and all participants gave written informed consent before entering the study.

Clinical and laboratory data

Patient assessment was similar in both institutions. Clinical, demographic, anthropometrical, and metabolic measures were assessed at the first visit. These included height and weight, body mass index (BMI), waist circumference, and blood pressure (measured twice at different times during the interview with calibrated manual sphygmomanometers at a seated position after at least a 5-minute rest). All patients were wearing light clothes and no shoes, and there was no need of fasting for anthropometric evaluation. Mood symptoms were assessed with the 17-item Hamilton Depression Rating Scale (HAM-D) and the Young Mania Rating Scale (YMRS). Patients were requested to have a fasting blood sample drawn the next day to evaluate fasting serum glucose, high-density cholesterol (HDL), and triglycerides levels. Patients from the PROTAHBI site also had total cholesterol data available. A second study visit was scheduled to provide test results and counseling. Those patients who needed to be treated were referred for treatment.

Determination of cardiovascular risk factors

Cardiovascular risk factors were diagnosed according to recent Brazilian guidelines for diabetes, hypertension, and dyslipidemia.2626. Sociedade Brasileira de Endocrinologia e Metabologia. Diabetes mellitus: classificação e diagnóstico [Internet]. 2004 Jun 04 [cited 2013 May 21]. http://www.projetodiretrizes.org.br/4_volume/06-diabetes-c.pdf
http://www.projetodiretrizes.org.br/4_vo...

27. V Diretrizes brasileiras de hipertensão arterial. Arq Bras Cardiol. 2007;89:e24-79.
-2828. IV Diretriz brasileira sobre dislipidemias e prevenção da aterosclerose: Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2007;88:2-19. High glucose was defined as fasting glucose ≥ 100 mg/dL; high total cholesterol as fasting total cholesterol ≥ 240 mg/dL; low HDL cholesterol as fasting HDL cholesterol < 40 mg/dL (men) or < 50 mg/dL (women); diabetes as fasting glucose ≥ 126 mg/dL or previous diagnosis of diabetes and current use of hypoglycemic medication; hypertriglyceridemia as fasting triglycerides ≥ 200 mg/dL; hypertension as blood pressure ≥ 140/90 mmHg or previous diagnosis of arterial hypertension and current use of antihypertensive drugs; overweight as BMI between 25-29.9 kg/m2; obesity as BMI ≥ 30; abdominal obesity as waist circumference ≥ 102 cm (men) and ≥ 88 cm (women); physical inactivity as self-report of no regular exercise; and smoking as self-report of current use of cigarettes, cigars or pipes.

Statistical analysis

Differences between patients from the two research sites as well as differences in clinical variables associated with each cardiovascular risk factor were compared using chi-squared tests for dichotomous variables, whereas Student's t tests or Mann-Whitney tests were used for parametric and non-parametric continuous data. Multilevel logistic regression analyses were used in order to control for confounding factors associated with cardiovascular risk factors. Age, gender, and research site were included in the first level, whereas other related variables such as smoking, physical activity, alcohol use disorders, and medication use (lithium, valproate, other anticonvulsants, antidepressants, typical and atypical antipsychotics) were included in the second level. All tests were two-tailed.

Results

A total of 159 outpatients were enrolled in the study, 84 from the PROMAN site and 75 from the PROTAHBI site. Demographic and clinical characteristics of the sample are shown in Table 1. Patients from the PROMAN site were more likely to be younger (p = 0.031), single (p = 0.018), and have more years of formal education (p < 0.001). There were significant differences in prescription patterns between the sites, such as more use of atypical antipsychotics (p = 0.001), antidepressants (p = 0.002), and lamotrigine (p = 0.005) at the PROMAN site, whereas we found more use of lithium (p = 0.001) and valproate (p = 0.013) at the PROTAHBI site. Patients from the PROTAHBI site also had more depressive (p = 0.001) and manic (p = 0.001) symptoms.

Table 1
Sociodemographic and clinical variables of bipolar disorder outpatients

The prevalence of the selected cardiovascular risk factors is presented in Table 2. In addition to the high rates of the different risk factors, we found significant gender differences. Male patients were more likely to have alcohol use disorders (p = 0.001), diabetes (p = 0.037), and hypertriglyceridemia (p < 0.001); female patients showed increased rates of abdominal obesity (p = 0.007).

Table 2
Prevalence of cardiovascular risk factors in bipolar disorder outpatients

In the multilevel logistic regression - after controlling for site, age, and gender -, valproate (odds ratio [OR] = 2.11; confidence interval [CI] = 1.03-4.35) was associated with obesity. Older age (OR = 1.09; CI = 1.03-1.15) and male gender (OR = 5.15; CI = 1.45-18.29) remained associated with diabetes; recruitment from the PROTAHBI site (OR = 2.18; CI = 1.04-4.60) and older age (OR = 1.09; CI = 1.05-1.13) were positively associated with hypertension, whereas physical activity (OR = 0.35; CI = 0.14-0.87) and lithium use (OR = 0.18; CI = 0.07-0.46) were negatively associated with this disease. Recruitment from the PROTAHBI site (OR = 2.34; CI = 1.09-5.03) was positively associated with reduced HDL-cholesterol, while alcohol use disorder (OR = 0.30; CI = 0.09-0.99) was negatively associated with this cardiovascular risk factor; and male gender (OR = 4.09; CI = 1.92-8.70) remained associated with hypertriglyceridemia.

Discussion

Our study investigated the prevalence and clinical correlates of well-established cardiovascular risk factors in two samples of outpatients with BD. In line with previous studies, we found elevated prevalence rates of obesity, smoking, physical inactivity, diabetes, hypertension, and dyslipidemia in Brazilian BD outpatients. We also found statistically significant gender differences regarding alcohol use disorders, diabetes, hypertriglyceridemia, and abdominal obesity.

BD is associated with substantial morbidity and increased rates of all-cause mortality,2929. Tsai SY, Lee CH, Kuo CJ, Chen CC. A retrospective analysis of risk and protective factors for natural death in bipolar disorder. J Clin Psychiatry. 2005;66:1586-91.,3030. Laursen TM, Munk-Olsen T, Nordentoft M, Mortensen PB. 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. and there has been increasing awareness and recognition about the contribution of cardiovascular risk factors to the medical burden of this illness.3131. Suppes T, McElroy SL, Hirschfeld R. Awareness of metabolic concerns and perceived impact of pharmacotherapy in patients with bipolar disorder: a survey of 500 US psychiatrists. Psychopharmacol Bull. 2007;40:22-37; quiz 38-40.,3232. Bauer M, Lecrubier Y, Suppes T. Awareness of metabolic concerns in patients with bipolar disorder: a survey of European psychiatrists. Eur Psychiatry. 2008;23:169-77. In addition to general medical conditions such as cardiovascular, endocrine, and metabolic diseases,88. McIntyre RS, Soczynska JK, Beyer JL, Woldeyohannes HO, Law CW, Miranda A, et al. Medical comorbidity in bipolar disorder: re-prioritizing unmet needs. Curr Opin Psychiatry. 2007;20:406-16.,3333. Carney CP, Jones LE. Medical comorbidity in women and men with bipolar disorders: a population-based controlled study. Psychosom Med. 2006;68:684-91. patients with BD usually have a wide range of modifiable cardiovascular risk factors such as obesity, smoking, physical inactivity, and poor eating habits.1717. Morriss R, Mohammed FA. Metabolism, lifestyle and bipolar affective disorder. J Psychopharmacol. 2005;19:94-101.

As expected and in line with recent studies from other countries, patients with BD had higher prevalence of the selected cardiovascular risk factors when compared with data regarding the Brazilian population, in which recent studies have shown rates of 5-10% for diabetes and around 30% for hypertension and high cholesterol.2626. Sociedade Brasileira de Endocrinologia e Metabologia. Diabetes mellitus: classificação e diagnóstico [Internet]. 2004 Jun 04 [cited 2013 May 21]. http://www.projetodiretrizes.org.br/4_volume/06-diabetes-c.pdf
http://www.projetodiretrizes.org.br/4_vo...

27. V Diretrizes brasileiras de hipertensão arterial. Arq Bras Cardiol. 2007;89:e24-79.
-2828. IV Diretriz brasileira sobre dislipidemias e prevenção da aterosclerose: Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2007;88:2-19. Previous findings on the prevalence of comorbid general medical conditions in BD have reported alarming high rates of cardiovascular risk factors such as obesity (20-32%),3434. McElroy SL, Kotwal R, Malhotra S, Nelson EB, Keck PE, Nemeroff CB. Are mood disorders and obesity related? A review for the mental health professional. J Clin Psychiatry. 2004;65:634-51. hypertension (34-60%),1010. Kilbourne AM, Cornelius JR, Han X, Pincus HA, Shad M, Salloum I, et al. Burden of general medical conditions among individuals with bipolar disorder. Bipolar Disord. 2004;6:368-73.,3535. Birkenaes AB, Opjordsmoen S, Brunborg C, Engh JA, Jonsdottir H, Ringen PA, et al. The level of cardiovascular risk factors in bipolar disorder equals that of schizophrenia: a comparative study. J Clin Psychiatry. 2007;68:917-23. diabetes (2-26%),99. McIntyre RS, Konarski JZ, Misener VL, Kennedy SH. Bipolar disorder and diabetes mellitus: epidemiology, etiology, and treatment implications. Ann Clin Psychiatry. 2005;17:83-93. and dyslipidemia (23-41%).88. McIntyre RS, Soczynska JK, Beyer JL, Woldeyohannes HO, Law CW, Miranda A, et al. Medical comorbidity in bipolar disorder: re-prioritizing unmet needs. Curr Opin Psychiatry. 2007;20:406-16. Furthermore, studies investigating the prevalence of the metabolic syndrome in BD patients have reported varying rates as low as 18-25.3% in Belgium3636. van Winkel R, De Hert M, Van Eyck D, Hanssens L, Wampers M, Scheen A, et al. Prevalence of diabetes and the metabolic syndrome in a sample of patients with bipolar disorder. Bipolar Disord. 2008;10:342-8. and Italy,3737. Salvi V, Albert U, Chiarle A, Soreca I, Bogetto F, Maina G. Metabolic syndrome in Italian patients with bipolar disorder. Gen Hosp Psychiatry. 2008;30:318-23. 33.9% in Taiwan,3838. Chang HH, Chou CH, Chen PS, Gean PW, Huang HC, Lin CY, et al. High prevalence of metabolic disturbances in patients with bipolar disorder in Taiwan. J Affect Disord. 2009;117:124-9. and as high as 40-49% in the United States.3939. Fagiolini A, Chengappa KN, Soreca I, Chang J. Bipolar disorder and the metabolic syndrome: causal factors, psychiatric outcomes and economic burden. CNS Drugs 2008;22:655-69.,4040. Cardenas J, Frye MA, Marusak SL, Levander EM, Chirichigno JW, Lewis S, et al. Modal subcomponents of metabolic syndrome in patients with bipolar disorder. J Affect Disord. 2008; 106:91-7. A recent report on cardiovascular risk factors in BD patients4141. Garcia-Portilla MP, Saiz PA, Bascaran MT, Martínez AS, Benabarre A, Sierra P, et al. Cardiovascular risk in patients with bipolar disorder. J Affect Disord. 2009;115:302-8. has also pointed out differences between prevalence rates not only among different countries, but also according to the cardiovascular risk estimation method used. In addition to these findings, our results underscore the relevance of considering regional differences when studying cardiovascular risk factors in psychiatric patients. Differences in lifestyle, socioeconomic level, and unequal access to psychotropic medication are probably related to the distinctive results between sites.1919. Kapczinski F, Gentil V. CANMAT guidelines for bipolar disorder: a commentary from South America. Bipolar Disord. 2005;7:87-8.

There may be a wide range of confounding factors when studying cardiovascular risk factors in patients with severe mental illnesses.4242. Newcomer JW. Medical risk in patients with bipolar disorder and schizophrenia. J Clin Psychiatry. 2006;67:25-30.,4343. Elkis H, Gama C, Suplicy H, Tambascia M, Bressan R, Lyra R, et al. [Brazilian Consensus on second-generation antipsychotics and metabolic disorders]. Rev Bras Psiquiatr. 2008;30:77-85. Despite individual variables such as age and gender, patients with BD are particularly at risk due to both disease and treatment-related factors.3939. Fagiolini A, Chengappa KN, Soreca I, Chang J. Bipolar disorder and the metabolic syndrome: causal factors, psychiatric outcomes and economic burden. CNS Drugs 2008;22:655-69. Clinical and biological features such as depression with atypical features, anxiety, hypercortisolism, disruption of the adipocytokine levels and pro-inflammatory states, increased oxidative stress and DNA damage,4444. Kapczinski F, Vieta E, Andreazza AC, Frey BN, Gomes FA, Tramontina J, et al. Allostatic load in bipolar disorder: implications for pathophysiology and treatment. Neurosci Biobehav Rev. 2008;32:675-92. as well as treatment with weight gaining medication and polipharmacy, are related to increased medical burden in BD.4545. Fagiolini A, Chengappa KN. Weight gain and metabolic issues of medicines used for bipolar disorder. Curr Psychiatry Rep. 2007;9:521-8. The interplay among these factors may have a cumulative effect on morbidity and mortality resulting from a hazardous combination of intrinsic and exogenous pathophysiological mediators.

In this context, differences in cardiovascular risk factors prevalence rates seen in our study may be explained not only by distinct genetic, lifestyle, and dietary backgrounds, but also by varying prescription patterns. In order to control for potential confounders (age, gender, and treatment site), we used multivariable analysis to explore other associated risk factors. Some variables such as medication use pattern, alcohol use disorder, and physical activity were associated with selected cardiovascular risk factors and may represent a possible target for intervention. The multivariable analysis approach is relevant in this study since most of the variables studied are highly correlated.4646. Yanovski SZ, Yanovski JA. Obesity. N Engl J Med. 2002;346:591-602.

Our results must be interpreted in the light of some of limitations. In addition to the relatively small size, our samples came from tertiary treatment settings, and most of the participants were difficult-to-treat patients, which may limit the generalization of our results to the whole spectrum of BD. Due to the cross-sectional nature of our study, we cannot offer mechanistic causal explanations, and longitudinal studies are necessary to further clarify the abovementioned associations.

Despite these limitations, this report of the BRN-BD provides a significant amount of new data regarding prevalence rates and associated cardiovascular risk factors in Brazilian outpatients with BD. This information may be useful for increasing both awareness and recognition of comorbid metabolic and cardiovascular diseases in this patient population, which may potentially lead to changes in clinical practice resulting in a reduction in the increased medical burden of BD.

Funding for this study was provided partly by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundo de Incentivo è Pesquisa - Hospital de Clínicas de Porto Alegre (FIPE-HCPA), Brazil.

References

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    Kupfer DJ. The increasing medical burden in bipolar disorder. JAMA. 2005;293:2528-30.
  • 2
    Angst F, Stassen HH, Clayton PJ, Angst J. Mortality of patients with mood disorders: follow-up over 34-38 years. J Affect Disord. 2002;68:167-81.
  • 3
    Krishnan KR. Psychiatric and medical comorbidities of bipolar disorder. Psychosom Med. 2005;67:1-8.
  • 4
    Thompson WK, Kupfer DJ, Fagiolini A, Scott JA, Frank E. Prevalence and clinical correlates of medical comorbidities in patients with bipolar I disorder: analysis of acute-phase data from a randomized controlled trial. J Clin Psychiatry. 2006;67:783-8.
  • 5
    Guo JJ, Keck PE Jr, Li H, Jang R, Kelton CM. Treatment costs and health care utilization for patients with bipolar disorder in a large managed care population. Value Health. 2008;11:416-23.
  • 6
    McElroy SL, Frye MA, Suppes T, Dhavale D, Keck PE Jr, Leverich GS, et al. Correlates of overweight and obesity in 644 patients with bipolar disorder. J Clin Psychiatry. 2002;63:207-13.
  • 7
    Fagiolini A, Kupfer DJ, Houck PR, Novick DM, Frank E. Obesity as a correlate of outcome in patients with bipolar I disorder. Am J Psychiatry. 2003;160:112-7.
  • 8
    McIntyre RS, Soczynska JK, Beyer JL, Woldeyohannes HO, Law CW, Miranda A, et al. Medical comorbidity in bipolar disorder: re-prioritizing unmet needs. Curr Opin Psychiatry. 2007;20:406-16.
  • 9
    McIntyre RS, Konarski JZ, Misener VL, Kennedy SH. Bipolar disorder and diabetes mellitus: epidemiology, etiology, and treatment implications. Ann Clin Psychiatry. 2005;17:83-93.
  • 10
    Kilbourne AM, Cornelius JR, Han X, Pincus HA, Shad M, Salloum I, et al. Burden of general medical conditions among individuals with bipolar disorder. Bipolar Disord. 2004;6:368-73.
  • 11
    Taylor V, MacQueen G. Associations between bipolar disorder and metabolic syndrome: a review. J Clin Psychiatry. 2006;67:1034-41.
  • 12
    Teixeira PJ, Rocha FL. The prevalence of metabolic syndrome among psychiatric inpatients in Brazil. Rev Bras Psiquiatr. 2007;29:330-6.
  • 13
    De Almeida KM, De Macedo-Soares MB, Issler CK, Amaral JA, Caetano SC, Dias RS, et al. Obesity and metabolic syndrome in Brazilian patients with bipolar disorder. Acta Neuropsychiatr. 2009;21:84-8.
  • 14
    Goldstein BI, Fagiolini A, Houck P, Kupfer DJ. Cardiovascular disease and hypertension among adults with bipolar I disorder in the United States. Bipolar Disord. 2009;11:657-62.
  • 15
    Goldstein BI, Liu SM, Zivkovic N, Schaffer A, Chien LC, Blanco C. The burden of obesity among adults with bipolar disorder in the United States. Bipolar Disord. 2011;13:387-95.
  • 16
    Kilbourne AM, Rofey DL, McCarthy JF, Post EP, Welsh D, Blow FC. Nutrition and exercise behavior among patients with bipolar disorder. Bipolar Disord. 2007;9:443-52.
  • 17
    Morriss R, Mohammed FA. Metabolism, lifestyle and bipolar affective disorder. J Psychopharmacol. 2005;19:94-101.
  • 18
    Monteiro CA, Conde WL, Popkin BM. Income-specific trends in obesity in Brazil: 1975-2003. Am J Public Health. 2007;97:1808-12.
  • 19
    Kapczinski F, Gentil V. CANMAT guidelines for bipolar disorder: a commentary from South America. Bipolar Disord. 2005;7:87-8.
  • 20
    Dainesi SM, Elkis H. Current clinical research environment: focus on psychiatry. Rev Bras Psiquiatr. 2007;29:283-90.
  • 21
    Miguel EC, Ferrão YA, Rosário MC, Mathis MA, Torres AR, Fontenelle LF, et al. The Brazilian research consortium on obsessive-compulsive spectrum disorders: recruitment, assessment instruments, methods for the development of multicenter collaborative studies and preliminary results. Rev Bras Psiquiatr. 2008;30:185-96.
  • 22
    Quarantini LC, Miranda-Scippa A, Nery-Fernandes F, Andrade-Nascimento M, Galvão-de-Almeida A, Guimarães JL, et al. The impact of comorbid posttraumatic stress disorder on bipolar disorder patients. J Affect Disord. 2010;123:71-6.
  • 23
    Andrade-Nascimento M, Miranda-Scippa Â, Nery-Fernandes F, Kapczinski F, Quarantini LC. The identification of unipolar mania subtype based on anxiety comorbidity. J Affect Disord. 2011;132:356-9.
  • 24
    Brietzke E, Moreira CL, Duarte SV, Nery FG, Kapczinski F, Miranda Scippa A, et al. Impact of comorbid migraine on the clinical course of bipolar disorder. Compr Psychiatry. 2012;53:809-12.
  • 25
    Seixas C, Miranda-Scippa A, Nery-Fernandes F, Andrade-Nascimento M, Quarantini LC, Kapczinski F, et al. Prevalence and clinical impact of eating disorders in bipolar patients. Rev Bras Psiquiatr. 2012;34:66-70.
  • 26
    Sociedade Brasileira de Endocrinologia e Metabologia. Diabetes mellitus: classificação e diagnóstico [Internet]. 2004 Jun 04 [cited 2013 May 21]. http://www.projetodiretrizes.org.br/4_volume/06-diabetes-c.pdf
    » http://www.projetodiretrizes.org.br/4_volume/06-diabetes-c.pdf
  • 27
    V Diretrizes brasileiras de hipertensão arterial. Arq Bras Cardiol. 2007;89:e24-79.
  • 28
    IV Diretriz brasileira sobre dislipidemias e prevenção da aterosclerose: Departamento de Aterosclerose da Sociedade Brasileira de Cardiologia. Arq Bras Cardiol. 2007;88:2-19.
  • 29
    Tsai SY, Lee CH, Kuo CJ, Chen CC. A retrospective analysis of risk and protective factors for natural death in bipolar disorder. J Clin Psychiatry. 2005;66:1586-91.
  • 30
    Laursen TM, Munk-Olsen T, Nordentoft M, Mortensen PB. 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.
  • 31
    Suppes T, McElroy SL, Hirschfeld R. Awareness of metabolic concerns and perceived impact of pharmacotherapy in patients with bipolar disorder: a survey of 500 US psychiatrists. Psychopharmacol Bull. 2007;40:22-37; quiz 38-40.
  • 32
    Bauer M, Lecrubier Y, Suppes T. Awareness of metabolic concerns in patients with bipolar disorder: a survey of European psychiatrists. Eur Psychiatry. 2008;23:169-77.
  • 33
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Publication Dates

  • Publication in this collection
    April-June 2013

History

  • Received
    19 Dec 2011
  • Accepted
    16 Apr 2012
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