Risk of Cardiovascular Disease in Schizophrenia: A Mini Review

 

Varshita Veerni Jaya Ratna*, Monika Vempadapu, Raj Kiran Kolakota, Vinodkumar Mugada

Department of Pharmacy Practice, Vignan Institute of Pharmaceutical Technology, Beside VSEZ, Duvvada, AP, India-530049

*Corresponding Author E-mail: varshitavjr.10@gmail.com

 

ABSTRACT:

Schizophrenia is one of the major causes of increased mortality from cardiovascular disease (CVD). There is a growing concern that this condition is not fully understood and efficiently addressed. The mortality is due to premature cardiovascular deaths rather than suicide. Most of the anti-psychotropic agents are orexigenic and they increase weight and promote dyslipidemia. Cardiac risk factors are undertreated among patients with schizophrenia, and they are less likely to receive cardiac revascularisation than those without a mental illness. Various factors which increase the cardiovascular risk are antipsychotic medications and lifestyle (e.g., smoking, general neglect of health, poor diet and decreased access to health care services) in schizophrenic patients. Publications were searched based on various search terms and the databases included are PUBMED; SCIENCE DIRECT and TRIP databases. Data extraction was carried out to record the following; author, year of publication, type of study, study participants, sample size, questionnaires, and assessment tools. The risk for cardiovascular-related deaths in people with schizophrenia is increased, but their underlying mechanisms are not fully known. Coordinated interventions, thorough monitoring, in different healthcare settings could probably reduce the risk. There is an urgent need to develop and implement effective programs to increase life expectancy in schizophrenia, and we argue that mental health workers should be more involved in this important task.

 

KEYWORDS: Schizophrenia, cardiovascular diseases, risk, prevalence.

 

 

INTRODUCTION:

Schizophrenia is defined as a psychiatric diagnosis that describes a neuropsychiatric abnormality and mental disorder characterized by abnormalities in the perception or expression of reality. It commonly manifests in the form of auditory hallucinations, paranoid or bizarre delusions, or disorganized speech and thinking with significant social or occupational dysfunction1. Cardiovascular disorder is the leading death cause worldwide. CVS is responsible for most of the deaths annually than any other disease since190055. It has also been proved that cardiovascular diseases are the most fre­quent cause of morbidity and mortality throughout the world. It has a major impact on life expectancy56 and significantly contributes to morbidity and mortality in middle aged population. It serves as the common cause of premature death and also contributes to deterioration of quality of life.

 

The cardiovascular diseases burden increased worldwide as well as in India2. Total 100 patients according to selection criteria were selected for present study of which 24 % were female patients and 76% were male patients. The common cardiovascular diseases found in this study were IHD, Hypertension, CCF, Angina pectoris, MI etc. IHD was the major cardiovascular disease found in most of study participant. To treat the IHD and to maintain good blood supply to heart antiplatelet aggregating drugs utilized most commonly and frequently51.

 

Schizophrenia is described as a chronic, debilitating, heterogeneous and multi-faceted disorder, with a prevalence of 1% worldwide 4,5 with a higher risk of cardiovascular morbidity and mortality. When compared to the general population more than two-thirds of schizophrenic patients die from CVD 6,7, with an increased incidence of total cardiovascular disease (CVD), stroke, coronary heart disease (CHD) and congestive heart failure, with pooled relative-risks ranging from 1.2 to 1.818. Schizophrenia is a chronic disease that afflicts approximately 1% of the population worldwide52. It usually afflicts people at a young age and, according to a report of the World Health Organization, it is among the seven most disabling diseases in the age group between 20 and 45, surpassing by far diabetes, HIV or cardiovascular diseases. Suicide rates of people with schizophrenia are high53. A number of reviews have shown that there is an excess mortality in people with schizophrenia, the overall mortality being twice as high as that in the general population, so that schizophrenia has been called a life-shortening disease2,3,54.

 

A recent meta-analysis provided detailed data on the incidence and prevalence of CVD and established that patients with SMI [severe mental illness] showed a 78% higher risk for developing CVD and a 53% higher risk for harboring factors related to CVD9. Schizophrenic patients have a shortened life expectancy when compared to the general population i.e., approximately 10–18 years, with cardiovascular disease (CVD) being the primary contributor. Reasons for the cardiovascular complications in schizophrenic patients are complex and combining effects of schizophrenia-related factors10, which are a genetic predisposition, negative psychopathology, unhealthy diet and sedentary lifestyle, poverty, suboptimal medical monitoring and care, and prior antipsychotics exposure and/or current antipsychotic treatment11,12. Various reasons ranging from genes to environment are responsible for the increased risk of cardiovascular diseases in schizophrenic patients which are responsible for their shortened life.

 

The schizophrenic patient is 40% less likely to receive treatment for their co morbidities13, even with an established diagnosis for cardiovascular complication, the revascularization rate was found to be 47% less than in general population. Schizophrenic population in British were prescribed with beta-blockers [82%], statins [51%]14, and 53% received follow-up with a cardiologist within 30 days of discharge. For preventing the progression of a risk factor to CAD, schizophrenic patients don’t receive adequate treatment and they are undertreated, receive poor treatment if they develop CAD, which is the leading cause of death in these vulnerable patients 15.

 

Risk factors such as smoking, sedentary and unhealthy lifestyle, metabolic syndrome and obesity are modifiable and reduction in them can reduce disease burden and increase longevity. Quality of life and reduction in CVD risk factors can be improved by exercise, physical fitness (PF) which is measured as peak oxygen uptake (VO2peak) plays an important role that physical activity in controlling CVD risk factors 16,17. Progression of atherosclerosis can be reduced in schizophrenic patients by providing omega-3 fatty acid18.

 

The risk of death was 1.56 times higher in schizophrenic patients due to acute coronary syndrome within 30 days of discharge. Patient noncompliance, unwillingness to seek help, physical discomfort while treating patients with mental illness and difficult-to-access health networks are various obstacles to adequate treatment of CAD-related co-morbidities in schizophrenia19.

 

METHODOLOGY:

Search strategy:

A literature search was conducted using PUBMED; SCIENCE DIRECT and TRIP databases from the year 2010 to 2018 for articles that examined for cardiovascular diseases risk in schizophrenia. To begin the search, a broad search strategy was used to identify relevant articles using combinations of the following search terms. There were 443 articles identified across all three databases. The search terms included were; schizophrenia; cardiovascular diseases; increased risk; risk-associated; prevalence

 

Eligibility criteria:

Peer-reviewed empirical and normative research articles published in English were included if they met any of the following criteria: -- schizophrenic patients, age [18-50], language [English], research articles, full-text articles.

 

Any of the following types of publication were excluded: – co-morbidities, letter to the editor, case reports, review articles, alcohol dependence or other substance dependence, newsletters, commentaries, presentations, animal studies, other psychological disorders.

 

Study selection:

A four-phase trial was conducted for the selection of study. In phase, the articles were excluded based on the inclusion criteria and duplications. In phase 2, the articles were excluded after the title and abstract screening. In phase 3, the articles were excluded after the full-text screening. In phase 4, the articles were excluded during data extraction.

 

DISCUSSION:

Schizophrenia is significantly associated with an increased risk of 53% of CVD, 71% of stroke, and 81% of CHF20. Persons with schizophrenia have a similar cardiovascular risk profile to age-matched and gender-matched controls. Among schizophrenia patients, there is an increased clinical and public health burden of CHD which is responsible for their reduced quality of life. Persons with schizophrenia showed a significantly greater risk (AHR=1.43, 95% CI, 1.22–1.69) for cardiovascular morbidity than the general population21. Patients with schizophrenia had an increased risk for CVD, stroke, and CHF and also total CVD events, as compared with the control22. The pathophysiological mechanisms responsible for increased CVD risk in schizophrenia is not well understood, but the co-morbid disorders such as diabetes, hypertension, and hyperlipidaemia23-26, are known to have a positive association with the incidence of CVD. However, even after the treatment for these co-morbid disorders, it was found that schizophrenia patients were still at a higher risk for CVD. Therefore, it can be explained that physical co-morbidities might not be the only contributor to the increased incidence of CVD in schizophrenia.

 

The study revealed that 56.7% of the patients with Schizophrenia had severe impairment and 43.3%of the patients with schizophrenia had moderate impairment in self care management. In the study, 30 patients with schizophrenia subjected to token economy intervention had shown significant improvement (p<0.001) in total self care management such as bathing and grooming, clothing and dressing, eating and feeding, neatness and maintenance activities and recreation/leisure activities58.

In schizophrenic patients the CHD risk was about 34% higher in male and 50% higher in female, which is similar to the recent findings of WHO which was reported that about a 29% increase in Framingham 10-year cardiac risk in men and a 30% increase in women are more likely to smoke than other individuals with severe mental illness27, even after controlling for institutionalization, socioeconomic status and medications28-30. Concerning sex differences in the incidence of schizophrenia, we found that the median male: female rate ratio was 1.4, which is consistent with another systematic review of sex difference in the incidence of schizophrenia31, it was found that pooled male: female rate ratio was 1.4 (95 percent confidence interval: 1.3, 1.6), determined using meta-analysis. The difference in the sex which was identified in the incidence rates is not reflected in prevalence estimates32. A recent prevalence study from Finland also confirmed the lack of sex difference in the lifetime prevalence of schizophrenia33. Specifically, patients who were not engaged in paid follow-up assessments were expected to have increased cardiovascular disorders as a result of poorer monitoring of risk. Till date, there is no cardiovascular risk engine which has been validated in schizophrenic patients. Blonde et al34 demonstrated the incidence of CHD (which is defined as a risk of developing one of the following: angina pectoris, myocardial infarction or coronary disease death) in each treatment for a cohort of 1,000 patients using the Framingham risk equation over a 10-year period35. Patients with schizophrenia have higher mortality rates and incidence of myocardial infarction when compared to patients without schizophrenia, but this is not associated with the drugs36.

 

Excessive morbidity in schizophrenia patients is caused due to unhealthy lifestyles including; smoking, poor diet, lack of exercise and obesity37,38. The factors which predispose CVD risk and affect the wellbeing of schizophrenic patients include inappropriate dietary habits; such as lower intake of fruit or fibre and physical inactivity, increasing age, obesity, cigarette smoking, diabetes mellitus, lipid abnormalities, hypertension, elevated serum homocysteine, markers of abnormal coagulation or inflammatory activity (C-reactive protein) and a family history of heart disease, active smoking is generally associated with increased risk of CVD, these patients are more prone to smoking39-40. Cardiovascular disease has a high prevalence in India. Circulating levels of C-Reactive protein (CRP) is found to be increased in cardiovascular disease which may be used as a marker for diagnosis purpose57.The estimated Framingham 10year CHD risk was increased by at least 50% in middle-aged and older patients with schizophrenia when compared to general population and 70% estimated increase in CHD risk was consistent from CATIE         study 41.

 

 

Early diagnosis of CVD in schizophrenia can be made by regular monitoring of carotid intima-media thickness, ankle-brachial index or Doppler echocardiography, other risk assessment tools such as schizophrenia specific CVD risk algorithm could be used for early diagnosis of CVD in schizophrenic patients42. Primary prevention of risk factors is associated with decreased incidence of CVD in schizophrenic patients and prevention strategies include encouraging healthy lifestyles, smoking cessation, appropriate diets and levels of activity, and integrating medical services, as well as screening and treatment43. Modifications in their sedentary lifestyles are crucial to reduce risk factors of CHD in the general population as well as among patients with schizophrenia who are at even higher risks which are exacerbated by number of barriers such as non-compliance with their antipsychotic drug regimens, which occurs in 50% of the patients with schizophrenia at some time during their illness 44.

 

The onset of cardiovascular events is higher in patients with schizophrenia and hence physician should be alert to both the higher risk and the earlier onset of some conditions 45 and the CVD risk score estimate indicates that only a small proportion of those with schizophrenia at risk of CVD aged 55 years and which underestimate risk in schizophrenia, particularly in men. The absolute risk increases rapidly with age; which leads to a lower identification of younger individuals who are at a higher risk and an increased identification of older individuals at low risk46. The above mentioned issue question the validity of the instruments in conditions such as schizophrenia, where mortality rates are observed at a very young age47 which can lead to under-prediction of CVD risk and a loss of opportunity for primary prevention interventions, which contributes to the high rates of mortality in individuals with schizophrenia48,49. Schizophrenic patients may need intensive and individual aid in changing their lifestyle factors, if suitable actions are not made, it is possible and most likely that the disparity in mortality outcomes will persist, as concluded by Lawrence et al 50.

 

 

Table 1: Studies reporting risk of cardiovascular disease in schizophrenia patients

S. No.

Author and year of publication

Study

population

Type of

research

Risk factor

Measured

Outcome

1.

Blonde L et al., 200831

Patients with schizophrenia

Cohort study

Incidence of CHD

Higher mortality and morbidity rates.

2.

Lawrence D et al., 201047

Schizophrenic patients changing their lifestyle factors

Intervention studies

Insufficient

health service for schizophrenic patients.

Increased mortality is seen in schizophrenic patients.

3.

Tsai K et al., 201217

Persons with schizophrenia

Case-control study

Cardiovascular risk profile.

Greater risk for cardiovascular morbidity than the general population.

4.

Cohn T et al., 200424

schizophrenic patients

Cohort study

10-year cardiac risk.

Increased cardiovascular risk despite the absence of co-morbidities.

5.

Perälä J et al., 200730

patients who were not engaged in paid follow-up assessments

Cohort study

poorer monitoring of risk.

Increased cardiovascular disorders.

 

 

CONCLUSION:

Based on the overall systematic review done, we conclude that the schizophrenic patients are at a higher risk of developing cardiovascular diseases than normal individuals when exposed to risk factors such as smoking, obesity, unhealthy diet, polypharmacy and non-compliance to antipsychotic medications. Schizophrenic patients with co-morbid disorders such as diabetes, hypertension, and hyperlipidaemia are at higher risk of developing cardiovascular diseases.

 

Management of these co-morbid disorders has still not decreased the risk of cardiovascular disorders. Prevention of cardiovascular diseases in the schizophrenic patients can be provided through monitoring of patients for any signs and symptoms of cardiovascular diseases. Thorough monitoring is required for early detection of cardiovascular disease and the implementation of behavioral and pharmacological interventions.

 

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Received on 10.10.2018            Modified on 25.01.2019

Accepted on 19.02.2019            © A&V Publications All right reserved

Asian J. Res. Pharm. Sci. 2019; 9(2):131-136.

DOI: 10.5958/2231-5659.2019.00019.5