Cardiovascular risk in a first-episode psychosis sample: A ‘critical period’ for prevention?
Introduction
Individuals with serious mental illness (SMI) die, on average, 25 years earlier than their peers (Colton and Manderscheid, 2006, Parks et al., 2006). While 30–40% of this premature mortality is attributable to suicide and accidental injury, cardiovascular disease accounts for the majority of early death. The single most common cause of death in patients with schizophrenia is cardiovascular disease (Osby et al., 2000, Capasso et al., 2008, Tiihonen et al., 2009). Patients with schizophrenia, relative to peers without SMI, experience a 3-fold increase in cardiovascular mortality between the ages of 18 and 49 and almost a 2-fold increase in mortality between the ages of 50 and 75 years (Osborn et al., 2007). They have a greater incidence of myocardial infarction than demographically similar persons without schizophrenia (Brown et al., 2000, Enger et al., 2004).
The causes of this increased cardiovascular burden in patients with schizophrenia are likely multi-factorial. Modifiable risk factors for cardiovascular disease include smoking, obesity, diabetes, dyslipidemia, and hypertension (Yusuf et al., 2004). When compared to age- and gender-matched controls, persons with chronic psychosis have higher rates of nicotine dependence (70–80% vs 25–30%) (de Leon and Diaz, 2005), obesity (45–55% vs 31–39%) (De Hert et al., 2009, Meigs et al., 2003), diabetes (13% vs 3%) (Goff et al., 2005), dyslipidemia (25–69% vs 24–48%) (De Hert et al., 2009, Meigs et al., 2003) and hypertension (27% vs 17%) (Goff et al., 2005). The largest study comparing cardiovascular risk factors in chronic schizophrenia patients, drawn from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Schizophrenia Trial, with age-, gender-, and race-matched controls from the U.S. National Health and Nutrition Examination Survey (NHANES) showed that patients had significantly higher 10-year coronary heart disease risk. This was due to higher rates of smoking, diabetes, and hypertension. Also, the mean (SD) duration of antipsychotic use in the CATIE study was 14.4 (10.7) years (Lieberman et al., 2005) and long-term use of antipsychotic medications may play an important role in the increased risk for cardiovascular diseases (Goff et al., 2005, Newcomer, 2009). Antipsychotic medication use is associated with significant weight gain, dyslipidemia, and insulin resistance (Stahl et al., 2009).
In contrast to the consistent evidence across all measures of cardiovascular risk in chronic schizophrenia, studies of ‘first episode’ psychosis samples have been inconsistent. The first study comparing cardiovascular risk factors in drug-naïve first-episode schizophrenia patients with matched controls found that patients had significantly higher fasting plasma glucose levels. HDL cholesterol was not different, but total cholesterol was lower in patients (Ryan et al., 2003). These authors were unable to replicate these findings with a different sample, and, in a second study, reported that first-episode schizophrenia patients, their first degree relatives, and matched controls did not differ with respect to fasting plasma glucose levels (Spelman et al., 2007). Another study of drug-naïve first-episode psychosis patients compared to age, gender, and race matched controls showed that patients had a significantly higher prevalence of diabetes but lower frequencies of obesity and total and LDL cholesterol (Verma et al., 2009). A study of 38 first-episode psychosis patients compared to age, gender, and race matched controls did not find significant differences in fasting plasma glucose levels, glucose tolerance, body mass index, waist circumference and pulse pressure (Sengupta et al., 2008). Another study of antipsychotic-naïve, first-episode schizophrenia patients compared to healthy controls did not show significant differences in fasting glucose and insulin resistance (Arranz et al., 2004).
The use of specialized early intervention services (EI) to reduce long term psychosocial morbidity in psychotic disorders has been substantiated by several high quality studies (Marshall and Rathbone, 2006). The traditional focus of EI has been to deliver best available treatments during a putative ‘critical period’ for psychosocial development wherein intensive early intervention is hypothesized to achieve disproportionately positive results on long term outcomes. We propose an analogous formulation for reducing cardiovascular morbidity and mortality. The existence of EI clinics around the world, which are redefining care for early psychosis patients, presents an opportunity for the study and development of primary and secondary preventions of cardiovascular disease in schizophrenia.
Given the discrepancies in the reported prevalence of cardiovascular risk factors in early psychosis samples, the current study aimed to measure these risks again in a carefully characterized sample of patients referred to an early intervention clinic. Also, we used the best available risk calculator to formulate a 10 year risk estimate of developing coronary heart disease. We report a cross sectional comparison of these first-episode psychosis patients with age, gender, and race matched controls from the U. S. National Health and Nutrition Examination Survey (NHANES) (Centers for Disease Control and Prevention, 2005–2006).
Section snippets
Methods
Subjects for this analysis were drawn from an ongoing NIH-funded pragmatic randomized controlled trial titled Specialized Treatment Early in Psychosis (STEP). The broader goals of this trial are to determine the effectiveness and costs of a package of empirically supported treatments delivered within a U.S. community mental health center (Srihari et al., 2009). The subjects were consecutively enrolled in the study. The target sample of the NIH trial includes Connecticut residents between the
Results
The sample for this analysis was young (mean 22.5 years, SD 4.4), predominantly male (89%) early psychosis patients with a variety of preliminary diagnoses including schizophrenia (35%), schizophreniform disorder (32%), schizoaffective disorder (13%), and psychotic disorder not otherwise specified (20%). The sample was ethnically and racially diverse with 28 (50%) African-American, 10 (17%) Hispanic, 17 (31%) Caucasians. The majority were prescribed with risperidone (n = 26), and others were on
Discussion
The major finding of this study is that patients who are early in the course of a psychotic illness, do not yet significantly differ from their peers in terms of extant 10-year risk calculators for coronary heart disease. This contrasts with consistent reports of increased risk among patients later in the course of psychotic illnesses and supports the proposal that early intervention programs embrace a role in primary prevention of cardiovascular morbidity.
Two cardiovascular risk factors that
Role of funding source
The Specialized Treatment Early in Psychosis (STEP) Program is supported by The Donaghue Foundation Grant number DF07-014 and by the National Institute of Health (NIH), Grant number 1RC1MH088971-01. Both The Donaghue Foundation and the NIH had no further role in the study design, in the collection, analysis and interpretation of data; in the writing of the report; and in the decision to submit the paper for publication. Dr. Tek's work on this project is supported by the National Institute of
Contributors section
Drs. Phutane, Tek and Srihari designed the study, wrote the protocol, managed the literature search and analysis and wrote the manuscript. Drs. Chwastiak, Ratliff, Ozyuksel and Woods participated in the editing of the manuscript and the conduct of the analysis. All authors contributed to and have approved the final manuscript.
Conflict of interest
All authors declare that they have no conflicts of interest.
Acknowledgement
None.
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2015, Schizophrenia ResearchCitation Excerpt :However, compared with a European population-based study (Vishram et al., 2014), the prevalence of MetS in patients with FES found in our study is significantly higher (p = 0.04). Others have found similar rates of MetS in patients with FES and healthy controls (Fleischhacker et al., 2013; Phutane et al., 2011). In contrast to the EUFEST study (Fleischhacker et al., 2013), the majority of patients in our study were exposed to antipsychotic medication more than 6 weeks prior to inclusion.
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2015, The Lancet PsychiatryCitation Excerpt :These findings point to the significance of early intervention for prevention of weight gain in patients with a first episode of psychosis. A cross-sectional analysis56 shows that such individuals do not present with significantly higher cardiovascular risk than that of age-matched and race-matched controls. The first year of treatment with antipsychotic drugs thus seems to be a crucial period during which young people develop risk factors for cardiovascular disease.57