MetS and Metabolic Abnormalities in Schizophrenia
MetS and Metabolic Abnormalities in Schizophrenia
Individuals with schizophrenia have high levels of medical comorbidity and cardiovascular risk factors. The presence of 3 or more specific factors is indicative of metabolic syndrome, which is a significant influence upon future morbidity and mortality. We aimed to clarify the prevalence and predictors of metabolic syndrome (MetS) in adults with schizophrenia and related disorders, accounting for subgroup differences. A PRISMA systematic search, appraisal, and meta-analysis were conducted of 126 analyses in 77 publications (n = 25 692). The overall rate of MetS was 32.5% (95% CI = 30.1%–35.0%), and there were only minor differences according to the different definitions of MetS, treatment setting (inpatient vs outpatient), by country of origin and no appreciable difference between males and females. Older age had a modest influence on the rate of MetS (adjusted R = .20; P < .0001), but the strongest influence was of illness duration (adjusted R = .35; P < .0001). At a study level, waist size was most useful in predicting high rate of MetS with a sensitivity of 79.4% and a specificity of 78.8%. Sensitivity and specificity of high blood pressure, high triglycerides, high glucose and low high-density lipoprotein, and age (>38 y) are shown in supplementary appendix 2 online. Regarding prescribed antipsychotic medication, highest rates were seen in those prescribed clozapine (51.9%) and lowest rates of MetS in those who were unmedicated (20.2%). Present findings strongly support the notion that patients with schizophrenia should be considered a high-risk group. Patients with schizophrenia should receive regular monitoring and adequate treatment of cardio-metabolic risk factors.
Increased rates of cardiovascular disease (CVD) and associated premature mortality have become a major concern in patients with schizophrenia. In order to help psychiatric clinicians to focus more on these CVD risks in patients with schizophrenia, the concept of MetS has found its way into the psychiatric literature. The metabolic syndrome (MetS) brings together a collection of abnormal clinical and metabolic findings that are predictive for CVD. These abnormal findings include visceral adiposity, insulin resistance, increased blood pressure, elevated triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels. The most common definitions for the MetS are the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program,10 and the adapted Adult Treatment Panel (ATP III-A) proposed by the American Heart Association11 which allows for a lower threshold for impaired fasting glucose of 100 mg/dl (Table 1). The International Diabetes Federation (IDF) stresses the importance of waist circumference as a mandatory feature.12 Recently, more stringent and ethnic/race specific criteria were defined with, eg, slightly modified criteria of waist circumference for Asians (90 cm for male and 80 cm for female).
In the general population, MetS is associated with a 4 times relative risk of developing diabetes and approximately a 2-fold risk of coronary heart disease, stroke, and premature mortality. As a result, MetS has been proposed as an alternative or an augmentation to the Framingham15 or systematic coronary risk evaluation16 calculations to assess the risk of CVD and death. Similar results for the MetS as a predictor of the risk of coronary heart disease have been found previously in schizophrenia.
In part, the development of the MetS is attributable to genetic risk, limited access to general somatic health care, and unhealthy lifestyle choices including physical inactivity, poor diet, and high rates of cigarette smoking. In the general population, genetic and geographical environmental differences might partially be responsible for the observation that estimated rates of MetS alter to different countries of origin. For example, adopting the ATP III definition, the age-adjusted rates are 18.4% for men and 14.4% for women in Europeans, 28.8% for men and 31.8% for women in South Asians, 15.5% for men and 23.4% for women in African-Caribbeans, while the rate was 15.7% in Taiwan and 23.7% in the United States, respectively. Although previous narrative reviews reported on differences in MetS rates between different countries, to the best of our knowledge, meta-analytic data comparing MetS rates across different countries in patients with schizophrenia are lacking. In the same way, it remains to be explored if MetS rates differ between different treatment settings, ie, in order to identify patients at risk psychiatric clinicians should know if patients in particular treatment settings are at higher risk or not.
In recent years, it has become apparent that in patients with schizophrenia particular antipsychotic agents (AP) can have a negative impact on some of the modifiable MetS risk factors. The differential effects of various AP on weight are well described, with clozapine and olanzapine associated with the highest weight gain. Previous systematic reviews on metabolic side effects of AP were of AP have only focussed upon metabolic changes after exposure following convenience testing. A recent meta-analysis suggested a typical weight gain of 3.8 kg in drug-naïve patients after starting antipsychotic treatment in the first 3 months of treatment. No data on differences in MetS rates between patients taking different APs are available.
In the same way, no systematic data on differences in MetS rates between patients with and without AP and between first-episode and chronic patients are available. Knowledge of all these differences would guide psychiatric clinicians in identifying patients at risk for CVD. Given this uncertainty, we conducted a systematic review and meta-analysis with an objective to clarify prevalence rate of MetS in schizophrenia and related disorders taking into account variations in country, setting, stage of illness, AP treatment, and illness duration. Our secondary aim was to clarify the prevalence rates of every individual MetS risk factor in those systematically monitored. A tertiary aim was to examine which individual MetS risk factors would be useful markers of the full MetS at the study level.
Abstract and Introduction
Abstract
Individuals with schizophrenia have high levels of medical comorbidity and cardiovascular risk factors. The presence of 3 or more specific factors is indicative of metabolic syndrome, which is a significant influence upon future morbidity and mortality. We aimed to clarify the prevalence and predictors of metabolic syndrome (MetS) in adults with schizophrenia and related disorders, accounting for subgroup differences. A PRISMA systematic search, appraisal, and meta-analysis were conducted of 126 analyses in 77 publications (n = 25 692). The overall rate of MetS was 32.5% (95% CI = 30.1%–35.0%), and there were only minor differences according to the different definitions of MetS, treatment setting (inpatient vs outpatient), by country of origin and no appreciable difference between males and females. Older age had a modest influence on the rate of MetS (adjusted R = .20; P < .0001), but the strongest influence was of illness duration (adjusted R = .35; P < .0001). At a study level, waist size was most useful in predicting high rate of MetS with a sensitivity of 79.4% and a specificity of 78.8%. Sensitivity and specificity of high blood pressure, high triglycerides, high glucose and low high-density lipoprotein, and age (>38 y) are shown in supplementary appendix 2 online. Regarding prescribed antipsychotic medication, highest rates were seen in those prescribed clozapine (51.9%) and lowest rates of MetS in those who were unmedicated (20.2%). Present findings strongly support the notion that patients with schizophrenia should be considered a high-risk group. Patients with schizophrenia should receive regular monitoring and adequate treatment of cardio-metabolic risk factors.
Introduction
Increased rates of cardiovascular disease (CVD) and associated premature mortality have become a major concern in patients with schizophrenia. In order to help psychiatric clinicians to focus more on these CVD risks in patients with schizophrenia, the concept of MetS has found its way into the psychiatric literature. The metabolic syndrome (MetS) brings together a collection of abnormal clinical and metabolic findings that are predictive for CVD. These abnormal findings include visceral adiposity, insulin resistance, increased blood pressure, elevated triglyceride levels, and low high-density lipoprotein (HDL) cholesterol levels. The most common definitions for the MetS are the Adult Treatment Panel III (ATP III) of the National Cholesterol Education Program,10 and the adapted Adult Treatment Panel (ATP III-A) proposed by the American Heart Association11 which allows for a lower threshold for impaired fasting glucose of 100 mg/dl (Table 1). The International Diabetes Federation (IDF) stresses the importance of waist circumference as a mandatory feature.12 Recently, more stringent and ethnic/race specific criteria were defined with, eg, slightly modified criteria of waist circumference for Asians (90 cm for male and 80 cm for female).
In the general population, MetS is associated with a 4 times relative risk of developing diabetes and approximately a 2-fold risk of coronary heart disease, stroke, and premature mortality. As a result, MetS has been proposed as an alternative or an augmentation to the Framingham15 or systematic coronary risk evaluation16 calculations to assess the risk of CVD and death. Similar results for the MetS as a predictor of the risk of coronary heart disease have been found previously in schizophrenia.
In part, the development of the MetS is attributable to genetic risk, limited access to general somatic health care, and unhealthy lifestyle choices including physical inactivity, poor diet, and high rates of cigarette smoking. In the general population, genetic and geographical environmental differences might partially be responsible for the observation that estimated rates of MetS alter to different countries of origin. For example, adopting the ATP III definition, the age-adjusted rates are 18.4% for men and 14.4% for women in Europeans, 28.8% for men and 31.8% for women in South Asians, 15.5% for men and 23.4% for women in African-Caribbeans, while the rate was 15.7% in Taiwan and 23.7% in the United States, respectively. Although previous narrative reviews reported on differences in MetS rates between different countries, to the best of our knowledge, meta-analytic data comparing MetS rates across different countries in patients with schizophrenia are lacking. In the same way, it remains to be explored if MetS rates differ between different treatment settings, ie, in order to identify patients at risk psychiatric clinicians should know if patients in particular treatment settings are at higher risk or not.
In recent years, it has become apparent that in patients with schizophrenia particular antipsychotic agents (AP) can have a negative impact on some of the modifiable MetS risk factors. The differential effects of various AP on weight are well described, with clozapine and olanzapine associated with the highest weight gain. Previous systematic reviews on metabolic side effects of AP were of AP have only focussed upon metabolic changes after exposure following convenience testing. A recent meta-analysis suggested a typical weight gain of 3.8 kg in drug-naïve patients after starting antipsychotic treatment in the first 3 months of treatment. No data on differences in MetS rates between patients taking different APs are available.
In the same way, no systematic data on differences in MetS rates between patients with and without AP and between first-episode and chronic patients are available. Knowledge of all these differences would guide psychiatric clinicians in identifying patients at risk for CVD. Given this uncertainty, we conducted a systematic review and meta-analysis with an objective to clarify prevalence rate of MetS in schizophrenia and related disorders taking into account variations in country, setting, stage of illness, AP treatment, and illness duration. Our secondary aim was to clarify the prevalence rates of every individual MetS risk factor in those systematically monitored. A tertiary aim was to examine which individual MetS risk factors would be useful markers of the full MetS at the study level.
