Cardiovascular Mortality and Related Risk Factors among Persons with Schizophrenia: A Review of the Published Literature
Public Health Reviewsvolume 34, Article number: 11 (2012)
Although persons with schizophrenia (PWS) are entitled to health care and medical preventive and curative treatments in accordance with the same standards as other persons, they suffer from excess mortality compared with the general population. The main cause of natural premature death of PWS is attributed to cardiovascular disorders (CVD). We reviewed the studies of PWS, their risk factors and CVD mortality. In every study, PWS have increased risk of CVD mortality. Additionally, most but not all of the studies found increased CVD behavioral risk factors (i.e., smoking, sedentary life style/less physical activity, increased body mass index (BMI)) in PWS. In order to promote better health care to this population, we propose general recommendations to service users and their families, general and mental health professionals and policy makers. Severe mental illness such as schizophrenia should be addressed as a “risk equivalent” for CVD. Awareness of this association should be implemented in routine psychiatric and general medicine practice as well as at national levels for policy makers. Cardiovascular morbidity and mortality should be referred to as a measure of quality of care. Better communication between different physicians and other health care providers, who treat PWS, should be encouraged. This can be accompanied with technological advances (i.e., unified electronic medical record). Understanding of suggested treatment and adherence to recommendations in PWS may be improved by if relatives and friends accompany the patient in medical settings.
United Nations General Assembly. Universal Declaration of Human Rights. 217 A (III). UN General Assemby; 10 December 1948. Available from URL: http://www.unhcr.org/refworld/docid/3ae6b3712c.html (accessed 9 December 2012).
United Nations Office of the High Commission for Human Rights. Principles for the protection of persons with mental illness and the improvement of mental health care. Resolution 46/119. UN General Assemby; 17 December 1991. Available from URL: http://www.equalrightstrust.org/view-subdocument/index.htm?id=465 (accessed 8 July 2013).
Brown S. Excess mortality of schizophrenia. A meta-analysis. Br J Psychiatry. 1997;171:502–8.
Saha S, Chant D, McGrath J. A systematic review of mortality in schizophrenia: is the differential mortality gap worsening over time? Arch Gen Psychiatry. 2007;64:1123–31.
Hennekens CH, Hennekens AR, Hollar D, Casey DE. Schizophrenia and increased risks of cardiovascular disease. Am Heart J. 2005;150:1115–21.
Roger VL, Go AS, Lloyd-Jones DM, Benjamin EJ, Berry JD, et al. Heart disease and stroke statistics—2012 update: a report from the American Heart Association. Circulation. 2012;125:e2–220.
Evans A, Tolonen H, Hense HW, Ferrario M, Sans S, Kuulasmaa K; WHO MONICA Project. Trends in coronary risk factors in the WHO MONICA project. Int J Epidemiol. 2001;30:S35–40.
Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–52.
Greenland P, Knoll MD, Stamler J, Neaton JD, Dyer AR, et al. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA. 2003;290:891–7.
Khot UN, Khot MB, Bajzer CT, Sapp SK, Ohman EM, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA. 2003;290:898–904.
World Health Organization. Global health risks: mortality and burden of disease attributable to selected major risks. WHO: 2009. Available from URL: www.who.int/healthinfo/global_burden_disease/GlobalHealthRisks_report_full.pdf (accessed 8 July 2013).
Wu SI, Chen SC, Juang JJ, Fang CK, Liu SI, et al. Diagnostic procedures, revascularization, and inpatient mortality after acute myocardial infarction in patients with schizophrenia and bipolar disorder. Psychosom Med. 2013;75:52–9.
Ratliff JC, Palmese LB, Reutenauer EL, Srihari VH, Tek C. Obese schizophrenia spectrum patients have significantly higher 10-year general cardiovascular risk and vascular ages than obese individuals without severe mental illness. Psychosomatics. 2013;54:67–73.
Morden NE, Lai Z, Goodrich DE, MacKenzie T, McCarthy JF, et al. Eight-year trends of cardiometabolic morbidity and mortality in patients with schizophrenia. Gen Hosp Psychiatry. 2012;34:368–79.
Lahti M, Tiihonen J, Wildgust H, Beary M, Hodgson R, et al. Cardiovascular morbidity, mortality and pharmacotherapy in patients with schizophrenia. Psychol Med. 2012;12:1–11.
Laursen TM, Nordentoft M. Heart disease treatment and mortality in schizophrenia and bipolar disorder - changes in the Danish population between 1994 and 2006. J Psychiatr Res. 2011;45:29–35.
Kelly DL, McMahon RP, Liu F, Love RC, Wehring HJ, et al. Cardiovascular disease mortality in patients with chronic schizophrenia treated with clozapine: a retrospective cohort study. J Clin Psychiatry. 2010;71:304–11.
Brown S, Kim M, Mitchell C, Inskip H. Twenty-five year mortality of a community cohort with schizophrenia. Br J Psychiatry. 2010;196:116–21.
Kilbourne AM, Morden NE, Austin K, Ilgen M, McCarthy JF, et al. Excess heart-disease-related mortality in a national study of patients with mental disorders: identifying modifiable risk factors. Gen Hosp Psychiatry. 2009;31:555–63.
Tokuda Y, Obara H, Nakazato N, Stein GH. Acute care hospital mortality of schizophrenic patients. J Hosp Med. 2008;3:110–6.
Fors BM, Isacson D, Bingefors K, Widerlov B. Mortality among persons with schizophrenia in Sweden: an epidemiological study. Nord J Psychiatry. 2007;61:252–9.
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.
Vancampfort D, Probst M, Scheewe T, De Herdt A, Sweers K, et al. Relationships between physical fitness, physical activity, smoking and metabolic and mental health parameters in people with schizophrenia. Psychiatry Res. 2013;207:25–32.
Lee J, Nurjono M, Wong A, Salim A. Prevalence of metabolic syndrome among patients with schizophrenia in singapore. Ann Acad Med Singapore. 2012;41:457–62.
Kodesh A, Goldshtein I, Gelkopf M, Goren I, Chodick G, Shalev V. Epidemiology and comorbidity of severe mental illnesses in the community: findings from a computerized mental health registry in a large Israeli health organization. Soc Psychiatry Psychiatr Epidemiol. 2012;47:1775–82.
Schoepf D, Potluri R, Uppal H, Natalwala A, Narendran P, Heun R. Type-2 diabetes mellitus in schizophrenia: increased prevalence and major risk factor of excess mortality in a naturalistic 7-year follow-up. Eur Psychiatry. 2012;27:33–42.
Jin H, Folsom D, Sasaki A, Mudaliar S, Henry R, et al. Increased Framingham 10-year risk of coronary heart disease in middle-aged and older patients with psychotic symptoms. Schizophr Res. 2011;125:295–9.
Yazici MK, Anil Yagcioglu AE, Ertugrul A, Eni N, Karahan S, et al. The prevalence and clinical correlates of metabolic syndrome in patients with schizophrenia: findings from a cohort in Turkey. Eur Arch Psychiatry Clin Neurosci. 2011;261:69–78.
Chwastiak LA, Rosenheck RA, Kazis LE. Association of psychiatric illness and obesity, physical inactivity, and smoking among a national sample of veterans. Psychosomatics. 2011;52:230–6.
McClave AK, McKnight-Eily LR, Davis SP, Dube SR. Smoking characteristics of adults with selected lifetime mental illnesses: results from the 2007 National Health Interview Survey. Am J Public Health. 2010;100:2464–72.
Vinogradova Y, Coupland C, Hippisley-Cox J, Whyte S, Penny C. Effects of severe mental illness on survival of people with diabetes. Br J Psychiatry. 2010;197:272–7.
Ferreira L, Belo A, Abreu-Lima C. A case-control study of cardiovascular risk factors and cardiovascular risk among patients with schizophrenia in a country in the low cardiovascular risk region of Europe. Rev Port Cardiol. 2010;29:1481–93.
Saarni SE, Saarni SI, Fogelholm M, Heliovaara M, Perala J, et al. Body composition in psychotic disorders: a general population survey. Psychol Med. 2009;39:801–10.
Callaghan RC, Boire MD, Lazo RG, McKenzie K, Cohn T. Schizophrenia and the incidence of cardiovascular morbidity: a population-based longitudinal study in Ontario, Canada. Schizophr Res. 2009;115:325–32.
Weber NS, Cowan DN, Millikan AM, Niebuhr DW. Psychiatric and general medical conditions comorbid with schizophrenia in the National Hospital Discharge Survey. Psychiatr Serv. 2009;60:1059–67.
Birkenaes AB, Opjordsmoen S, Brunborg C, Engh JA, Jonsdottir H, 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.
Weiss AP, Henderson DC, Weilburg JB, Goff DC, Meigs JB, et al. Treatment of cardiac risk factors among patients with schizophrenia and diabetes. Psychiatr Serv. 2006;57:1145–52.
Martin Otano L, Barbadillo Izquierdo L, Galdeano Mondragon A, Alonso Pinedo M, Querejeta Ayerdi I. After six months of anti-psychotic treatment: is the improvement in mental health at the expense of physical health? Rev Psiquiatr Salud Ment. 2013;6:26–32. [In Spanish]
Strom BL, Eng SM, Faich G, Reynolds RF, D’Agostino RB, et al. Comparative mortality associated with ziprasidone and olanzapine in real-world use among 18,154 patients with schizophrenia: The Ziprasidone Observational Study of Cardiac Outcomes (ZODIAC). Am J Psychiatry. 2011;168:193–201.
Truyers C, Buntinx F, De Lepeleire J, De Hert M, Van Winkel R, et al. Incident somatic comorbidity after psychosis: results from a retrospective cohort study based on Flemish general practice data. BMC Fam Pract. 2011;12:132.
Woo YS, Kim W, Chae JH, Yoon BH, Bahk WM. Blood pressure changes during clozapine or olanzapine treatment in Korean schizophrenic patients. World J Biol Psychiatry. 2009;10:420–5.
Jerrell JM, McIntyre RS, Tripathi A. Incidence and costs of cardiometabolic conditions in patients with schizophrenia treated with antipsychotic medications. Clin Schizophr Relat Psychoses. 2010;4:161–8.
Tiihonen J, Lonnqvist J, Wahlbeck K, Klaukka T, Niskanen L, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet. 2009;374:620–7.
Newcomer JW, Campos JA, Marcus RN, Breder C, Berman RM, et al. A multicenter, randomized, double-blind study of the effects of aripiprazole in overweight subjects with schizophrenia or schizoaffective disorder switched from olanzapine. J Clin Psychiatry. 2008;69:1046–56.
Tirupati S, Chua LE. Obesity and metabolic syndrome in a psychiatric rehabilitation service. Aust N Z J Psychiatry. 2007;41:606–10.
Hagg S, Lindblom Y, Mjorndal T, Adolfsson R. High prevalence of the metabolic syndrome among a Swedish cohort of patients with schizophrenia. Int Clin Psychopharmacol. 2006;21:93–8.
Joukamaa M, Heliovaara M, Knekt P, Aromaa A, Raitasalo R, Lehtinen V. Schizophrenia, neuroleptic medication and mortality. Br J Psychiatry. 2006;188:122–7.
Lamberti JS, Olson D, Crilly JF, Olivares T, Williams GC, et al. Prevalence of the metabolic syndrome among patients receiving clozapine. Am J Psychiatry. 2006;163:1273–6.
Dohrenwend BP, Levav I, Shrout PE, Schwartz S, Naveh G, et al. Socioeconomic status and psychiatric disorders: the causation-selection issue. Science. 1992;255:946–52.
Werner S, Malaspina D, Rabinowitz J. Socioeconomic status at birth is associated with risk of schizophrenia: population-based multilevel study. Schizophr Bull. 2007;33:1373–8.
Os JV, Driessen G, Gunther N, Delespaul P. Neighbourhood variation in incidence of schizophrenia. Br J Psychiatry. 2000;176:243–8.
Kohn R, Dohrenwend BP, Mirotznik J. Epidemiological findings on selected psychiatric disorders in the general population. In: Dohrenwend BP, (editor). Adversity, Stress and Psychopathology. New York: Oxford University Press; 1998. p.235–84.
Boydell J, Os J, McKenzie K, Murray RM. The association of inequality with the incidence of schizophrenia. Soc Psychiat Epidemiol. 2004;39:597–9.
Clark AM, DesMeules M, Luo W, Duncan AS, Wielgosz A. Socioeconomic status and cardiovascular disease: risks and implications for care. Nat Rev Cardiology. 2009;6:712–22.
Kaplan GA, Keil JE. Socioeconomic factors and cardiovascular disease: a review of the literature. Circulation. 1993;88:1973–98.
Avendano M, Kunst AE, Huisman M, Lenthe FV, Bopp M, et al. Socioeconomic status and ischaemic heart disease mortality in 10 western European populations during the 1990s. Heart. 2006;92:461–7.
Gerber Y, Benyamini Y, Goldbourt U, Drory Y. Neighborhood socioeconomic context and long-term survival after myocardial infarction. Circulation. 2010;121:375–83.
Robbins JM, Vaccarino V, Zhang H, Kasl SV. Socioeconomic status and type 2 diabetes in African American and non-Hispanic white women and men: evidence from the Third National Health and Nutrition Examination Survey. Am J Public Health. 2001;91:76–83.
Jotkowitz AB, Rabinowitz G, Segal AR, Weitzman R, Epstein L, Porath A. Do patients with diabetes and low socioeconomic status receive less care and have worse outcomes? A national study. Am J Med. 2006;119:665–9.
Rabi D, Edwards A, Southern D, Svenson L, Sargious P, et al. Association of socio-economic status with diabetes prevalence and utilization of diabetes care services. BMC Health Serv Res. 2006;6:124.
Lee TC, Glynn RJ, Peña JM, Paynter NP, Conen D, et al. Socioeconomic status and incident type 2 diabetes mellitus: data from the Women’s Health Study. PLoS One. 2011;6:e27670.
Brummett BH, Babyak MA, Siegler IC, Shanahan M, Harris KM, et al. Systolic blood pressure, socioeconomic status, and biobehavioral risk factors in a nationally representative US young adult sample. Hypertension. 2011;58:161–6.
Colhoun HM, Hemingway H, Poulter NR. Socio-economic status and blood pressure: an overview analysis. J Hum Hypertens. 1998;12:91–110.
Qi V, Phillips S, Hopman W. Determinants of a healthy lifestyle and use of preventive screening in Canada. BMC Public Health. 2006;6:275.
Wang Y, Beydoun MA. The obesity epidemic in the United States—gender, age, socioeconomic, racial/ethnic, and geographic characteristics: a systematic review and meta-regression analysis. Epidemiol Rev. 2007;29:6–28.
Najman JM, Toloo G, Siskind V. Socioeconomic disadvantage and changes in health risk behaviours in Australia: 1989–90 to 2001. Bull World Health Organ. 2006;84:976–84.
Castelli WP. Epidemiology of coronary heart disease: the Framingham study. Am J Med. 1984;76:4–12.
Lynch J, Davey Smith G, Harper S, Bainbridge K. Explaining the social gradient in coronary heart disease: comparing relative and absolute risk approaches. J Epidemiol Community Health. 2006;60:436–41.
Allardyce J, Gilmour H, Atkinson J, Rapson T, Bishop J, McCreadie RG. Social fragmentation, deprivation and urbanicity: relation to first-admission rates for psychoses. Br J Psychiatry. 2005;187:401–6.
Lögdberg B, Nilsson LL, Levander MT, Levander S. Schizophrenia, neighbourhood, and crime. Acta Psychiatr Scand. 2004;110:92–7.
Curtis S, Copeland A, Fagg J, Congdon P, Almog M, Fitzpatrick J. The ecological relationship between deprivation, social isolation and rates of hospital admission for acute psychiatric care: a comparison of London and New York City. Health Place. 2006;12:19–37.
Stjärne MK, Ponce de Leon A, Hallqvist J. Contextual effects of social fragmentation and material deprivation on risk of myocardial infarction—results from the Stockholm Heart Epidemiology Program (SHEEP). Int J Epidemiol. 2004;33:732–41.
Oud M, Meyboom-de Jong B. Somatic diseases in patients with schizophrenia in general practice: their prevalence and health care. BMC Fam Pract. 2009;10:32.
Mitchell AJ, Malone D, Doebbeling CC. Quality of medical care for people with and without comorbid mental illness and substance misuse: systematic review of comparative studies. Br J Psychiatry. 2009;194:491–9.
Kilbourne AM, McCarthy JF, Post EP, Welsh D, Pincus HA, et al. Access to and satisfaction with care comparing patients with and without serious mental illness. Int J Psychiatry Med. 2006;36:383–99.
Mitchell AJ, Lawrence D. Revascularisation and mortality rates following acute coronary syndromes in people with severe mental illness: comparative meta-analysis. Br J Psychiatry. 2011;198:434–41.
Roberts L, Roalfe A, Wilson S, Lester H. Physical health care of patients with schizophrenia in primary care: a comparative study. Fam Pract. 2007;24:34–40.
Copeland LA, Zeber JE, Wang CP, Parchman ML, Lawrence VA, et al. Patterns of primary care and mortality among patients with schizophrenia or diabetes: a cluster analysis approach to the retrospective study of healthcare utilization. BMC Health Serv Res. 2009;9:127.
Nasrallah HA, Meyer JM, Goff DC, McEvoy JP, Davis SM, et al. Low rates of treatment for hypertension, dyslipidemia and diabetes in schizophrenia: data from the CATIE schizophrenia trial sample at baseline. Schizophr Res. 2006;86:15–22.
Kreyenbuhl J, Dickerson FB, Medoff DR, Brown CH, Goldberg RW, et al. Extent and management of cardiovascular risk factors in patients with type 2 diabetes and serious mental illness. J Nerv Ment Dis. 2006;194:404–10.
Goldman LS. Medical illness in patients with schizophrenia. J Clin Psychiatry. 1999;60 Suppl 21:10–5.
Fioravanti M, Carlone O, Vitale B, Cinti M, Clare L. A meta-analysis of cognitive deficits in adults with a diagnosis of schizophrenia. Neuropsychol Rev. 2005;15:73–95.
Reichenberg A, Weiser M, Rapp MA, Rabinowiz J, Caspi A, et al. Elaboration on premorbid intellectual performance in schizophrenia: premorbid intellectual decline and risk for schizophrenia. Arch Gen Psychiatry. 2005;62:1297–304.
Woodberry KA, Giuliano AJ, Seidman LJ. Premorbid IQ in schizophrenia: a meta-analytic review. Am J Psychiatry. 2008;165:579–87.
Elvevåg B, Goldberg TE. Cognitive impairment in schizophrenia is the core of the disorder. Crit Rev Neurobiol. 2000;14:1–21.
Savla GN, Vella L, Armstrong CC, Penn DL, Twamley EW. Deficits in domains of social cognition in schizophrenia: a meta-analysis of the empirical evidence. Schizophr Bull. 2012 Sep 4; epub ahead of print.
Nitzan U, Hirsch E, Walter G, Lurie I, Aviram S, Bloch Y. Comprehension and companionship in the emergency department as predictors of treatment adherence. Australas Psychiatry. 2012;20:112–6.
Arvaniti A, Samakouri M, Kalamara E, Bochtsou V, Bikos C, Livaditis M. Health service staff’s attitudes towards patients with mental illness. Soc Psychiat Epidemiol. 2009;44:658–65.
Thornicroft G, Rose D, Kassam A. Discrimination in health care against people with mental illness. Int Rev Psychiatry. 2007;19:113–22.
Jones S, Howard L, Thornicroft G. ‘Diagnostic overshadowing’: worse physical health care for people with mental illness. Acta Psychiatr Scand. 2008;118:169–71.
Morden NE, Mistler LA, Weeks WB, Bartels SJ. Health care for patients with serious mental illness: family medicine’s role. J Am Board Fam Med. 2009;22:187–95.
González-Torres M, Oraa R, Arístegui M, Fernández-Rivas A, Guimon J. Stigma and discrimination towards people with schizophrenia and their family members. Soc Psychiat Epidemiol. 2007;42:14–23.
De Hert M, Dekker JM, Wood D, Kahl KG, Holt RI, Moller HJ. Cardiovascular disease and diabetes in people with severe mental illness position statement from the European Psychiatric Association (EPA), supported by the European Association for the Study of Diabetes (EASD) and the European Society of Cardiology (ESC). Eur Psychiatry. 2009;24:412–24.
Newcomer JW, Hennekens CH. Severe mental illness and risk of cardiovascular disease. JAMA. 2007;298:1794–6.
Davidson M. Risk of cardiovascular disease and sudden death in schizophrenia. J Clin Psychiatry. 2002;63 Suppl 9:5–11.
Fleischhacker WW, Cetkovich-Bakmas M, De Hert M, Hennekens CH, Lambert M, et al. Comorbid somatic illnesses in patients with severe mental disorders: clinical, policy, and research challenges. J Clin Psychiatry. 2008;69:514–9.