SMI and risk of CHD-review final

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					     Are people with severe mental illness at higher risk for
             developing cardiovascular disease?
                      A review of literature
             Dr Jharna Kumbang, Specialist Registrar in Public Health
                             Dr Alison Hill, Director
                      South East Public Health Observatory

                                   January 2008




EXECUTIVE SUMMARY
The NHS South Central PCTs are committed to reducing health inequalities
through cardiovascular risk reduction, identifying and managing those people
at high cardiovascular disease risk.       One population considered to be at
particular risk are those with severe mental illness. A literature review was
carried out to assess the risk of cardiovascular disease amongst cohorts of
people with severe mental illness.

People with severe mental illness are 2-3 fold higher risk of dying from
cardiovascular diseases compared to general population. The risk could be
explained by higher rates of smoking, obesity, lack of physical exercise and
antipsychotic medications.

    1. BACKGROUND
There are significant inequalities in health status across NHS South Central. The
Directors of Public Health in the PCTs in South Central aim to reduce health
inequalities by targeting in particular morbidity and mortality from cardiovascular
diseases (CVD). There is concern that the risk of CVD among people with severe
mental illness (SMI) has not been fully recognised. This review aimed to assess the
risk of cardiovascular diseases among people with severe mental illness (SMI).

We chose to review the risk through a literature review as routine data would not be
able to identify the long term risk of cardiovascular disease in this population,
whereas cohort studies using large health care databases are able to look over a
longer time period.




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   2. INTRODUCTION
The term ‘mental illness’ refers to a variety of illnesses with a range of symptoms and
experiences, which affect the functioning of the mind. The term severe mental illness
(SMI) is used to describe a diverse range of conditions as described below.

The term 'severe mental illness’ (SMI)1 brings together two complex concepts. The
first is defined in terms of five groups of disorders from the International Classification
of Diseases (ICD 10):
      schizophrenic and delusional disorders
      mood (affective) disorders, including depressive, manic and bipolar forms
      neuroses, including phobic, panic and obsessive–compulsive disorders
      behavioural disorders, including eating, sleeping and stress disorders
      Personality disorders of eight different kinds.

The second component of SMI places the ICD symptoms and disorders within the
context of a judgement of behaviour, course and potential vulnerability, for example:
    active self-injury, food refusal, suicidal behaviour
    threatening or injurious behaviours, drug abuse, severe personality disorder
    embarrassing, overactive or bizarre behaviours
    long-term 'negative' symptoms, such as slowness, self-neglect, social
       withdrawal
    Physical disability, learning disabilities, social disadvantage.

Risk factors for CVD such as lower level of physical activity, smoking, obesity and
weight gain (due to antipsychotic medication) have been linked to people with SMI.
The aim of this literature search is to find out whether people with SMI are at higher
risk of developing CVD.

   3. METHODS
This involved a literature search via Medline (1996 to date) using following key
words: severe mental illness, schizophrenia, depression, cardiovascular diseases
and excess risk.

    4. PREVALENCE OF SMI
It has been estimated that one in four people will suffer a mental health problem at
some point in their lives. Around one in every three people who see their GP will
have a significant mental component to their illness2 . It has been estimated that
about 6 per 1000 of the population have mental illness of a severity that warrants
long-term care3.

      5. RISK OF CARDIOVASCULAR DISEASE IN PEOPLE WITH SMI

PEOPLE WITH DIAGNOSIS OF SMI




1 Wing, J. K. (1994): Mental illness. In Health care needs assessment: the epidemiologically based needs assessment reviews (ed. A. Stevens
   and J. Raftery).Radcliffe Press, Oxford.


2 Singleton, N., Bumpstead, R., O’Brien, M., Lee, A. and Melzer, H. (2000):‘Psychiatric morbidity among adults living in private households’
   Office for National Statistics. London.
3 Charlwood P, Mason A, Goldacre M, Cleary R, Wilkinson E (eds). Health Outcome Indicators: Severe Mental Illness. Report of a working
group to the Department of Health. Oxford: National Centre for Health Outcomes Development, 1999..




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Various studies reported that higher mortality and morbidity from coronary heart
disease in people with SMI4,5,6,7. A recent (2007) retrospective cohort study by
Osborn et al based on United Kingdom's General Practice Research Database,
estimated the excess mortality and the contribution of antipsychotic medication,
smoking, and social deprivation. Two cohorts were compared: people with SMI
diagnoses and people without such diagnoses. A total of 46 136 people with SMI and
300 426 without SMI were selected for the study. Main finding were described below:

For coronary heart disease (CHD) mortality in people with SMI compared with
controls, the hazard ratios (HRs) were -
    3.22 (95% confidence interval (CI), 1.99-5.21) for people aged 18 to 49
        years old, indicating a more than three-fold higher risk of CHD mortality
        among people with SMI ( <50yrs) compared with people without SMI.
    1.86 (95% CI, 1.63-2.12) for those aged 50 to 75 years old, and
    1.05 (95% CI, 0.92-1.19) for those older than 75 years.

For stroke deaths, the hazard ratios were-

             2.53 (95% CI, 0.99-6.47) for those younger than 50 years, indicating a
              more than two-fold higher stroke death among people with SMI (<50yrs)
              compared to people without SMI.
             1.89 (95% CI, 1.50-2.38) for those aged 50 to 75 years old, and
             1.34 (95% CI, 1.17-1.54) for those older than 75 years.

Increased HRs for CHD mortality occurred irrespective of sex, SMI diagnosis,
smoking or prescription of antipsychotic medication during follow- up. This large
community sample demonstrated that people with SMI have an two to three
fold increase in risk of death from CHD and stroke that is not wholly explained
by antipsychotic medication, smoking, or social deprivation scores4.

Other studies show results consistent with these results. A population-based record-
linkage study of 210 129 users of mental health services in Western Australia during
1980-1998, observed that ischaemic heart disease (IHD) mortality rates was the
major cause of excess (IHD accounted for 16% of all excess deaths, compared with
8% of excess deaths due to suicide) mortality in psychiatric patients. Patients with
dementia experienced the highest excess mortality (SMR (95% CI) for male: 4.48
(3.09- 6.49) and for female: 2.88(2.56-3.23), followed by patients with other
psychoses (SMR (95%CI) for male 2.47 (2.15-2.85) and for female: 2.85(2.54 –
3.19)5. A study by Henson et al reported that people with severe mental illness (SMI)
have a two-fold risk of dying from CHD in comparison to the general population7 .

SCHIZOPHRENIA

Studies revealed that people with schizophrenia have higher rates of cardiovascular
disease, including myocardial infarction, than the general population8,9. Study by
Brown et al reported –

4 Osborn, D. P., Levy, G., Nazareth, I., et al (2007): Relative risk of cardiovascular and cancer mortality in people with severe mental illness
   from the United Kingdom's general practice research database. Archives of General Psychiatry, 64, 242 -249
5 Lawrence DM, Holman CD, Jablensky AV, Hobbs MS, Death rate from ischaemic heart disease in Western Australian psychiatric patients
   1980-1998. Br J Psychiatry; 2003 Jan; 182:31-6.
6 Phelan, M., Stradins, L. & Morrison, S. (2001) Physical health of people with severe mental illness. BMJ, 322, 443 -444
7 Hansen, V., Jacobsen, B. K. & Arnesen, E. (2001) Cause-specific mortality in psychiatric patients after deinstitutionalisation. British Journal of
   Psychiatry, 179, 438 –443
8 Tsuang MT, Perkins K, Simpson JC. Physical diseases in schizophrenia and affective disorder. J Clin Psychiatry 1983;44: 42-46




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            Significantly higher mortality from cardiovascular disease both in
             schizophrenic men (SMR (95%CI): 1.69(1.30-2.16) and women (SMR
             (95%CI):1.37(1.06-1.76)9 suggesting 70% higher death among men and
             nearly 40% higher death among women.

DEPRESSION

Depressive symptoms and clinical depression also have an unfavourable impact on
mortality in CHD patients10,11. A meta-analysis by Barth et al concluded that
depressive symptoms increase the risk of mortality in CHD patients-

            The risk of depressed patients dying in the 2 years after the initial
             assessment was two times higher than that of nondepressed patients (OR,
             2.24; 1.37–3.60). This negative prognostic effect also remained in the long-
             term (OR, 1.78; 1.12–2.83) and after adjustment for other risk factors (HR
             [adj], 1.76; 1.27–2.43).
            Within the first 6 months, depressive disorders were found to have no
             significant effect on mortality (OR, 2.07; CI, 0.82–5.26). However, after 2
             years, the risk was more than two times higher for CHD in patients with
             clinical depression (OR, 2.61; 1.53–4.47)11.

Even in normal CHD-free populations, long term studies demonstrated that
depression doubles the risk of subsequent acute coronary events12and increases
mortality risk13.

ANXIETY

Studies of patients with pre-existing CHD showed that anxiety, independently of
conventional risk factors, can be predictive of recurrent acute CHD events 14. A
prospective study of anxiety in normal populations showed that there was an
association between anxiety assessed at enlistment and subsequent CHD mortality
over many years, even when conventional risk factors were controlled for relative
risks were significant, 5-6 for sudden death and 2-3 for fatal acute myocardial
infarction (AMI)15.

PANIC DISORDER

A study by Gomez-Caminero et al examined the association between panic
disorder (PD) and coronary heart disease (CHD) in a large national managed care

9 Brown, S., Birtwistle, J., Roe, L., et al (1999) The unhealthy lifestyle of people with schizophrenia. Psychological Medicine, 29, 697 –701
10 van Melle JP, de Jonge P, Spijkerman TA, Tijssen JG, Ormel J, van Veldhuisen DJ, van den Brink RH, van den Berg MP: Prognostic
   association of depression following myocardial infarction with mortality and cardiovascular events: a meta-analysis. Psychosom Med 2004;
   66:814–822
11 Barth J, Schumacher M, Herrmann-Lingen C: Depression as a risk factor for mortality in patients with coronary heart disease: a meta-
   analysis. Psychosom Med 2004; 66:802–813.
12 Ford DE, Mead LA, Chang PP, et al. Depression is a risk factor for coronary artery disease in men: the precursors study. Arch Intern Med
   1998; 158: 1422-1426.
13 Simonsick EM, Wallace RB, Blazer DG, Berkman LF. Depressive symptomatology and hypertension-associated morbidity and mortality in
   older adults. Psychosom Med 1995; 57: 427-435.
14 Moser DK, Dracup K. Is anxiety early after myocardial infarction associated with subsequent ischemic and arrhythmic events? Psychosom
   Med 1996; 58: 395-401
15 Kawachi I, Gollditz G, Ascherio A, et al. Prospective study of phobic anxiety and risk of coronary heart disease in men. Circulation 1994; 89:
   1992-1997.




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database in the United Kingdom. This was a cohort study with a total of 39,920 PD
patients and an equal number of patients without PD. They reported that –

           Patients with PD were observed to have nearly a 2-fold increased risk for
            CHD (HR =1.87, 95% CI = 1.80 –1.91) after adjusting for confounders.
           Patients with a co-morbid diagnosis of depression were almost 3 times more
            likely to develop CHD (HR =2.60, 95% CI =2.30 –3.01)16.

Few other studies also showed that CHD mortality risk may be doubled in people
with the disorder17,18.

    6. WHAT ARE THE RISK FACTORS?
Risk factors for cardiovascular disease, among people with SMI included family
history, smoking, poor diet, high cholesterol, obesity, lack of exercise and
Psychotropic medication.

A cross-sectional screening by Osborn et al compared the main risk factors for CHD
in people with and without SMI in primary care, to investigate the role of socio-
economic variables, and to examine any association between antipsychotic
medication and CHD risk. They studied 75 of 182 general practice patients with SMI
and 150 of 313 such patients without SMI attended the interview. SMI was
associated with-

           Raised 10-year CHD risk scores (OR=1.8,95% CI 1.0-3.1);
           High density lipoprotein (HDL) cholesterol levels <1.0 mmol/l (OR=4.0,
            95% CI 1.5-10.7);
           Raised cholesterol/HDL-cholesterol ratios (OR=1.8,95% CI 1.0-3.2);
           Diabetes mellitus (OR=3.8,95% CI 1.1-13.3) and
           Smoking (OR=3.0, 95% CI 1.7-3.4).

These associations varied significantly with age. More patients with SMI than controls
exhibited raised 10-years CHD risk scores, except above the age of 60 years. They
concluded that excess risk factors for CHD are not wholly accounted for by
medication or socio-economic deprivation. The authors identified an urgent need for
CHD screening and for relevant interventions for smoking cessation and diabetes, as
well as advice on diet and exercise, in patients with SMI19.

Another study by the same authors in 2007 looked into evidence regarding coronary
heart disease (CHD) related lifestyle in people with severe mental illnesses (SMI).
They aimed to quantify adverse CHD knowledge, diet and exercise in a
representative primary care sample, and to determine whether socio-economic
deprivation explained any findings. This study compared CHD lifestyle and CHD
knowledge in 74 people with SMI and 148 without from seven general practices.
They measured CHD knowledge, dietary fibre, fats and exercise using validated
instruments and adjusted for socio-economic status. They found that people with
SMI:


16 Gomez-Caminero A, Blumentals WA, Russo LJ, Brown RR, Castilla-Puentes R:Does Panic Disorder Increase the Risk of Coronary Heart
   Disease? A Cohort Study of a National Managed Care Database. Psychosom. Med. 2005;67:688-691
17 Coryell W, Noyes R, House JD. Mortality among outpatients with anxiety disorder. Am J Psychiatry 1986; 143: 508-510.
18 Weissman MM, Markowitz JS, Ouellette R, et al. Panic disorder and cardiovascular/cerebrovascular problems: results from a community
   survey. Am J Psychiatry 1990; 147: 1504-1508.
19 Osborn, D. P. J., Nazareth, I. & King, M. B. (2006) Risk for coronary heart disease in people with severe mental illness: cross-sectional
   comparative study in primary care. British Journal of Psychiatry, 188, 271 -277




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           had lower levels of knowledge regarding risk factors : OR= 0.49 (95%
            CI: 0.27-0.88),
           were less likely to take exercise: OR=0.49 (0.27-0.86),
           ate a diet lower in fibre: OR =0.46 (0.26-0.82) or
           ate lower saturated fat diets: OR= 0.53 (0.30-0.94).

These results were stable irrespective of antipsychotic medication, socio-economic
status or type of statistical analysis. They concluded that high fat, low fibre diets, lack
of exercise and smoking are the likely causes of the majority of CHD in this high-risk
group, irrespective of medication and socio-economic deprivation20.

As described above patients with SMI, for example schizophrenia, were more likely
than the general population to have lifestyle risk factors for cardiovascular disease
and mortality21,22,23. This excess risk of CHD mortality and morbidity among people
with SMI could be due to smoking24. Smoking prevalence was significantly higher
among people with mental health problems than among the general population25. A
national study of psychiatric morbidity among 8000 people in the general UK
population, which found that people with neurotic disorders (e.g. depressive
episodes, phobias, obsessive compulsive disorder) were twice as likely to smoke as
those with no neurotic disorder. Having more than one neurotic disorder was
associated with heavier smoking26. In a study looked into cardiovascular risk in 102
people with schizophrenia living in the community, 70% of those surveyed were
smokers27.Other risk factors are lower level of physical activity28, obesity29 and
psychotropic medication. The risk of CHD may increase as a result of metabolic and
endocrine effects of antipsychotic, including weight gain30, dyslipidemia19       and
diabetes mellitus31 .

    7. CONCLUSION
People with severe mental illness (SMI) are at two to three fold increased risk of
dying from coronary heart disease in comparison to the general population. The risk
could be explained by higher rates of smoking, obesity, lack of physical exercise or
antipsychotic medications. The need for screening to detect these risk factors is
identified by most of the authors.




20 Osborn DP, Nazareth I, King MB (2007):Physical activity, dietary habits and Coronary Heart Disease risk factor knowledge amongst people
   with severe mental illness: a cross sectional comparative study in primary care. Soc Psychiatry Psychiatr Epidemiol. 2007 Oct;42(10):787-93.
21 Kendrick T, Cardiovascular and respiratory risk factors and symptoms among general practice patients with long-term mental illness. Br J
   Psychiatry 1996;169: 733-739
22 Brown S, Birtwistle J, Roe L, Thompson C: The unhealthy lifestyle of people with schizophrenia. Psychol Med 1999;29: 697-701
23 Smith S, Yeomans D, Bushe CJ, Eriksson C, Harrison T, Holmes R, Mynors-Wallis L, Onaway H, Sullivan G; A well-being programme in
   severe mental illness- Baseline findings in a UK cohort.Int J Clin Pract. 2007 Dec;61(12):1971-8
24 de Leon J, Diaz FJ: A meta-analysis of worldwide studies demonstrates an association between schizophrenia and tobacco smoking
   behaviors. Schizophr Res 2005, 76:135-157.
25 McNeill A (2001) Smoking and Mental Health: A Literature Review London: Action on Smoking and Health
26 Coultard M, Farrell M, Singleton N and Meltzer H, (2000) Tobacco, alcohol and drug use and mental health London: Stationery Office
27 McCreadie R, on behalf of the Scottish Schizophrenia Lifestyle Group (2003)‘Diet, smoking and cardiovascular risk in people with
   schizophrenia:Descriptive study’ British Journal of Psychiatry Vol. 183, pp534-539
28 Martinsen, E. W. (1990) Physical fitness, anxiety and depression. British Journal of Hospital Medicine, 43, 194-199
29 Wallace, B. & Tenant, C. (1998): Nutrition and obesity in the chronic mentally ill. Australian and New Zealand Journal of Psychiatry, 32, 82-85
30 Blackburn, G. L. (2000) Weight gain and antipsychotic medication. Journal of Clinical Psychiatry, 61 (suppl. 8), 36 –41
31 Haddad, P. M. (2004) Antipsychotics and diabetes: review of non-prospective data. British Journal of Psychiatry, 184 (suppl. 47), p80 –86.




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