Dr Julie Langan-Martin 2017

Cardiovascular morbidity and mortality in schizophrenia: implications for primary care

Julie Langan, Daniel J. Smith

Julie Langan, Clinical Lecturer in Psychiatry, Institute of Health and Wellbeing, University of Glasgow, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 0XH.
Daniel J. Smith*, Reader in Psychiatry, Institute of Health and Wellbeing, University of Glasgow, Gartnavel Royal Hospital, 1055 Great Western Road, Glasgow, G12 0XH. Telephone: 0141 211 3930
*Corresponding Author.  Email: daniel.smith@glasgow.ac.uk 
Julie Langan		Daniel Smith

People with schizophrenia have substantial premature mortality compared to individuals without schizophrenia. They also have a wide range of comorbid and multiple physical health conditions but are less likely than people without schizophrenia to have a primary care record of cardiovascular disease. This suggests a systematic under-recognition and under-treatment of cardiovascular disease. In combination with inequitable prescribing patterns, reduced screening and fewer preventative health interventions, this may contribute to the increased mortality seen in this vulnerable patient group. Here we examine the evidence for this pattern, report on recent trends and discuss possible explanations. We also discuss potential strategies for improving the long-term cardiometabolic care of patients with schizophrenia in both primary and secondary care settings.

Key Words:
Schizophrenia, cardiovascular morbidity, premature mortality, primary care
Key Messages:
People with schizophrenia die earlier than those without schizophrenia, most commonly from cardiovascular disease.  They have a wide range of multiple comorbid physical health problems compared to people without schizophrenia, even after controlling for the effects of age, gender and social deprivation. Despite this, they experience less screening, fewer preventative health interventions and inequitable prescribing patterns. 

In primary care, recorded rates of comorbid physical illness are lower than expected for a number of cardiovascular disorders, including atrial fibrillation, hypertension, coronary heart disease and peripheral vascular disease. This suggests a systematic under-recognition and under-treatment of cardiovascular disease of people with schizophrenia within primary care.

There is evidence too for inequalities in health care provision at a secondary care level.

These findings may contribute to the substantial cardiovascular-related morbidity and premature mortality observed in this patient group and requires a new integrated approach to the physical health-care of patients with schizophrenia. 

It is well recognised that individuals with schizophrenia have increased standardised mortality rates compared to the general population,,&. On average, men with schizophrenia die 20 years earlier and women die 15 years earlier than the general population5&6.  Although death due to suicide is a contributing factor, approximately two-thirds of this premature mortality is due to cardiovascular disease, smoking-related lung disease and type II diabetes,, &. At least 10% of patients prescribed long-term antipsychotic medications will develop type II diabetes (2-3 times the rate in the general population) and rates of smoking in schizophrenia are extraordinarily high (estimated at 70% compared to 20% in the general population).  However, despite higher rates of medical comorbidities, there is also evidence that patients with schizophrenia receive less screening and fewer preventative interventions than patients without schizophrenia. This ultimately leads to poorer recognition of physical illness and delayed or suboptimal treatment. 

Recent work also suggests that this mortality gap may be getting worse. In the United States the mortality gap has widened from 12.8 to 15.4 years over a 7 year period (2000 to 2007) and a retrospective linked analysis of hospital admissions in England has shown that one-year post-discharge standardised mortality ratios (SMR) for people with schizophrenia have increased from 1.6 (1.5 to 1.8) in 1999 to 2.2 (2.0 to 2.4) in 20061. In particular, there was an increase in standardised mortality ratios for circulatory disease (from 1.6 to 2.5), and respiratory disease (from 3.1 to 4.7). This increase in SMR over recent years has been replicated elsewhere by Saha et al6 and Hoye et al in Norway.  This health inequality – which some authors have called a scandal- should be a priority area for medical research and intervention at both a primary care and secondary care levels. 

A primary care perspective:
Physical-health comorbidities are very common in people with schizophrenia, even after adjusting for age, gender and deprivation. By assessing the primary care records of 1.8 million individuals in Scotland, we found that patients with schizophrenia were significantly less likely to have no recorded comorbidity (OR 0.61, 95% CI 0.58 to 0.64) and significantly more likely to have one comorbidity (OR 1.21, 95% CI 1.16 to 1.27), two comorbidities (OR 1.37, 95% CI 1.29 to 1.44) and three or more comorbidities (OR 1.19, 95% CI 1.12 to 1.27) (Table 1). These high rates of multimorbidity for schizophrenia reinforce the finding that multimorbidity, which was previously thought of as a problem limited to elderly populations, is also occurring to a significant level in those under 65 years, and especially for those with mental illness.& Furthermore, there is a strong and consistent association between socioeconomic deprivation and multimorbidity, with evidence of an onset of multimorbidity up to 15 years earlier in the most deprived areas compared to the most affluent areas16. This issue is very relevant because major mental illnesses are over-represented in more deprived communities.   

We also found that despite high rates of conditions such as viral hepatitis, constipation, Parkinson’s disease, diabetes, and respiratory disease in patients with schizophrenia, recorded rates of cardiovascular disorders (including atrial fibrillation, hypertension, congestive heart disease and peripheral vascular disease) were lower than for individuals without schizophrenia (Table 1). Other studies4& have identified lower than expected rates of hypertension and ischaemic heart disease in individuals with schizophrenia compared to controls.  These findings suggest that under-recognition of cardiovascular disease is a significant issue for this population.  

The cardiovascular treatment gap for schizophrenia:
Patients with major mental illness and comorbid physical problems may not receive the same level of assessment and treatment for their physical problems as patients without major mental illness11. The reasons for this are likely to be complex, multifactorial and are currently not fully understood. There are Quality and Outcome Frameworks for the physical health monitoring of individuals with major mental illness, including the recording of body mass index (BMI) (MH12), blood pressure (MH13), total to HDL cholesterol ratio (MH14) and blood glucose (MH15) . However, despite this, there appears to be consistently lower than expected screening and diagnosis of conditions associated with increased premature cardiovascular mortality. For example, an audit of individuals with severe mental illness in Hampshire found that documented evidence of blood pressure recording was found in only 32% of case notes, while glucose (16%), lipids (9%) and weight (2%) were assessed even less frequently. Other studies& have replicated these findings. Clearly, more needs to be done to optimise the early detection of these disease processes in order to attempt to address high cardiovascular morbidity and premature mortality in this patient group. 

Individuals with major mental illness and cardiovascular disease also experience inequitable prescribing.  A recent meta-analysis of prescribing data highlighted that individuals with severe mental illness had much lower than expected rates of prescribed medications for cardiovascular disease.  Additionally, there is evidence that traditional risk calculators for cardiovascular disease, such as Framingham, ASSIGN and QRISK, may not be valid for individuals with severe mental illness. This may be due to the reality that individuals with major mental illness are often younger, have higher blood pressure and are more likely to smoke than the general population. While there appear to be difficulties in accessing care at primary care level, there is also evidence that there are potential inequalities of medical care at the secondary care level too; with evidence that patients with schizophrenia who have heart disease have lower rates of hospitalization, fewer invasive cardiac procedures and higher mortality than the general population with heart disease.& 

The need for integrated care:
The challenge for primary care practitioners of adequately addressing the complexity of medical, psychiatric, substance misuse and social problems in the context of limited time and limited resources is substantial. Current healthcare systems throughout the world (including the UK) are predominately organised around a ‘single-disease’ approach to both physical and mental disorder. However, we know that most individuals with long-term conditions are likely to have more than one16.  We need models of care which allow a much more integrated approach to diagnosing, monitoring and treating the physical health problems of patients with mental illness, particularly in areas of high social and economic deprivation. The World Health Organisation (WHO) defines integrated care as the management and delivery of health care along a continuum of preventative and curative services, according to patient needs over time and across different levels of the health system. However, how best to deliver this form of integrated healthcare in a cost effective manner remains a challenge.  

On a more practical level, in the short- to medium-term, perhaps a greater awareness within the primary care team, the secondary care community mental health team and the wider secondary health care service about physical health monitoring and the need to screen for and manage cardiovascular disease in patients with major mental illness is required.  Psychiatrists should seek to improve the degree to which they engage with the physical health needs of their patients, for example with better assessment and monitoring, closer liaison with primary care colleagues, supporting and delivering exercise and smoking cessation programmes, improving antipsychotic prescribing skills and recognising the opportunities within early intervention services for addressing the long-term physical health needs of young people with major mental illness. GPs may need to develop better strategies for engaging individuals with major mental illness in order to improve attendance at screening and physical health checks. They could be more aware of elevated cardiovascular morbidity risk in this group of patients and perhaps be more proactive in attempting to modify cardiovascular risk factors at consultations.  A review of the existing cardiovascular risk algorithms should occur and consideration given to the development of an adapted risk algorithm specifically targeted for individuals with major mental illness.

Future research:
 Longer-term, the medical academic community should come together to design and test creative new interventions specifically for physical illness in mental health, in order to gather the evidence for new integrated innovations in service organisation and delivery.  Such interventions could be at several levels, from healthcare systems changes and large-scale integrated or collaborative care models, to focused interventions in high-risk groups, such as young adults with first episode psychosis living in deprived communities.

In conclusion, given the apparent widening of the mortality gap between those with major mental illness and those without, combined with a systematic under-recognition, under-diagnosis and under-treatment of cardiovascular risk factors, it is clear that psychiatrists, general practitioners, researchers and policy-makers urgently need to work together to develop and evaluate services which will improve the physical, psychological and social outcomes for patients with major mental illness.
Word Count 1,436

Table 1 Physical health comorbidities in patients with schizophrenia compared to controls. (Adapted with permission from Smith et al 201314)

Number (%)
Number (%)
Odds ratio* (95% CI)
No  physical co-morbidity
4,069 (42.1)
796,039 (56.3)
0.61 (0.58 to 0.64) (p<0.001)
One physical co-morbidity
2,363 (24.4)
290,950 (20.6)
1.21 (1.16 to  1.27) (p<0.001)
Two  physical co-morbidities
1,493 (15.4)
148,231 (10.5)
1.37 (1.29 to 1.44) (p<0.001)
Three or more Physical co-morbidities
1,752 (18.1)
179,481 (12.7)
1.19 (1.12 to 1.27) (p<0.001)
Individual Conditions

Peripheral vascular disease
167 (1.7)
23,073 (1.6)
0.83 (0.71 to 0.97) (p=0.02)
Coronary heart disease
579 (5.9)
80,888 (5.7)
0.75 (0.69 to 0.82) (p<0.001)
1,551 (16.0)
232,763 (16.5)
0.71 (0.67 to 0.76) (p<0.001)
Atrial fibrillation
137 (1.4)
23,839 (1.7)
0.62 (0.51 to 0.73) (p<0.001)

Acknowledgments and funding: 
We thank the Chief Scientist Office of the Scottish Government Health Directorates (Applied Research Programme Grant ARPG/07/1); the Scottish School of Primary Care, and the Primary Care Clinical Informatics Unit at the University of Aberdeen, which provided the data. The views in this publication are not necessarily the views of the University of Aberdeen, of University of Glasgow, their agents, or employees. We thank Katie Wilde and Fiona Chaloner of the University of Aberdeen, who did the initial data extraction and management.


Hoang U, Stewart R, Goldacre MJ. Mortality after hospital discharge for people with schizophrenia or bipolar disorder: retrospective study BMJ 2011; 343. d5422
 Wahlbeck K, Westman J, Nordentoft M, et al. Outcomes of Nordic mental health systems: life expectancy of patients with mental disorders. Br J Psychiatry 2011; 199:453–8.
 Laursen TM, Munk-Olsen T, Gasses C. Chronic somatic comorbidity and excess mortality due to natural causes in persons with schizophrenia or bipolar affective disorder. PLoS ONE 2011; 6: e24597
 Crump C, Winkleby MA, Sundquist K, et al. Comorbidities and mortality in persons with schizophrenia: a Swedish national cohort study. Am J Psychiatry 2013; 170:324–33.
 Tiihonen J, Lönnqvist J, Wahlbeck K, et al. 11-year follow-up of mortality in patients with schizophrenia: a population-based cohort study (FIN11 study). Lancet 2009; 374:620–27.
 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; 64:609–16.
 Laursen TM, Munk-Olsen T, Nordentoft M, et al. 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.
 Heila H, Haukka J, Suvisaari J, et al. Mortality among patients with schizophrenia and reduced psychiatric hospital care. Psychol Med 2005; 35:725–32.
 Ya-Mei Bai, Tung-Ping Su, Mu-Hong Chen, Tzeng-Ji Chen, Wen-Han Chang, Risk of developing diabetes mellitus and hyperlipidemia among patients with bipolar disorder, major depressive disorder, and schizophrenia: A 10-year nationwide population-based prospective cohort study, Journal of Affective Disorders, ISSN 0165-0327, 10.1016/j.jad.2013.02.019.
10 Myles, N., Newall, H.D., Curtis, J.Tobacco use before, at and after first-epsiode psychosis: a systematic meta-analysis. Journal of Clinical Psychiatry 2012; 73(4): 468-475.
 Mackell JA, Harrison DJ, McDonnell DD. Relationship between preventative physical health care and mental health in individuals with schizophrenia: a survey of caregivers. Ment Health Serv Res; 2005; 7: 225–228.
12 Morden, N.E., Lai, Z., Goodrich, D.E., Mackenzie, T., McCarthy, J.F., Austin, K., Welsh, D.E., Bartels, S., Kilbourne, A.M., Eight-year trends of cardiometabolic morbidity and mortality in patients with schizophrenia. Gen. Hosp. Psychiatry 2012; 34, 368–379.
 Hoye, A., Jacobsen, B.K., Hansen, V., Increasing mortality in schizophrenia: are women at particular risk? A follow-up of 1111 patients admitted during 1980–2006 in Northern Norway. Schizophr. Res.2011; 132, 228–232.
 Thornicroft G, Brohan E, Rose D, Sartorius N, Leese M: Global pattern of experienced and anticipated discrimination against people with schizophrenia: a cross-sectional survey. The Lancet 2009, 373(9661):408-415.
 Smith DJ, Langan J, McLean G, et al. Schizophrenia is associated with excess multiple physical-health comorbidities but low levels of recorded cardiovascular disease in primary care: cross-sectional study. BMJ Open 2013;3:e002808
 Barnett K, Mercer SW, Norbury M, Watt G, Wyke S, Guthrie B: Epidemiology of multimorbidity and implications for health care, research, and medical education: a cross-sectional study. The Lancet 2012; 380; 37-43
 Network NCMH: Liaison psychiatry – the way ahead. http://wwwnhsconfedorg/Publications/Documents/Liaison-psychiatry-the-way-aheadpdf 2012
 Carney CP, Jones L, Woolson RF. Medical comorbidity in women and men with schizophrenia. A population-based controlled study. J Gen Intern Med 2006; 21:1133–7.
 NHS Employers. Quality and Outcomes Framework guidance for GMS contract 2011/2012: Delivering investment in general practice. http://www.nhsemployers.org/Aboutus/Publications/Dcouments/QOF_guidance_GMS_contract_2011_12.pdf.2011. 
Holt RI, Abdelrahman T, Hirsch et al The prevalence of undiagnosed metabolic abnormalities in people with serious mental illness. J Psychopharmacology 2010; 24: 867-873
 Mai, Q., Holman, C.D., Sanfilippo, F.M., Emery, J.D., Preen, D.B., 2Mental illness related disparities in diabetes prevalence, quality of care and outcomes: a population-based longitudinal study. BMC Med.2011 9, 118
 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.
 Mitchell AJ, Lord O, Malone D. Differences in the prescribing of medication for physical disorders in individuals with v. Without mental illness: meta-analysis. Br J Psychiatry 2012; 201:435–43.
 Holt RI Cardiovascular disease and diabetes in people with severe mental illness: causes, consequences and pragmatic management PCCJ epublication ahead of print
 Laursen, T.M., 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.
 Mitchell, A.J., Lawrence, D., Revascularisation and mortality rates following acute coronary syndromes in people with severe mental illness: comparative metanalysis. Br. J. Psychiatry 2011. 198, 434–441.
 Integrated health services; What and Why?http://www.who.int/healthsystems/service_delivery_techbrief1.pdf