Metabolic syndrome, abdominal obesity and hyperuricemia in schizophrenia: Results from the FACE-SZ cohort

Abstract

Objective

Abdominal obesity was suggested to be a better predictor than Metabolic Syndrome (MetS) for cardiovascular mortality, however this is has not been extensively studied in schizophrenia. Hyperuricemia (HU) was also suggested to be both an independent risk factor for greater somatic comorbidity and a global metabolic stress marker in patients with schizophrenia.

The aim of this study was to estimate the prevalence of MetS, abdominal obesity and HU, to examine the association between metabolic parameters with HU in a cohort of French patients with schizophrenia or schizo-affective disorder (SZ), and to estimate the prevalence rates of treatment of cardio-vascular risk factors.

Method

240 SZ patients (age = 31.4 years, male gender 74.3%) were systematically included. Metabolic syndrome was defined according to the International Diabetes Federation and HU if serum uric acid level was above 360 μmol/L.

Results

MetS, abdominal obesity and HU were found respectively in 24.2%, 21.3% and 19.6% of patients. In terms of risk factors, multiple logistic regression showed that after taking into account the potential confounders, the risk for HU was higher in males (OR = 5.9, IC95 [1.7–21.4]) and in subjects with high waist circumference (OR = 3.1, IC95 [1.1–8.3]) or hypertriglyceridemia (OR = 4.9, IC95 [1.9–13]). No association with hypertension, low HDL cholesterol or high fasting glucose was observed. Only 10% of patients with hypertension received a specific treatment, 18% for high fasting glucose and 8% for dyslipidemia.

Conclusions

The prevalence of MetS, abdominal obesity and hyperuricemia is elevated in French patients with schizophrenia, all of which are considerably under-diagnosed and undertreated. HU is strongly associated with abdominal obesity but not with psychiatric symptomatology.

Introduction

MetS is defined by the presence of three or more of the following five criteria: increased waist circumference, hypertriglyceridemia, low HDL cholesterol level, high blood pressure, and high fasting glucose concentration (Alberti et al., 2006). High prevalence of metabolic syndrome (MetS) has been reported repeatedly in patients with schizophrenia (Mitchell et al., 2013b, Vancampfort et al., 2013), partly because of a sedentary lifestyle and lack of exercise, and partly because of the administration of second-generation antipsychotics (Mitchell et al., 2013a), especially olanzapine and clozapine, known to induce more metabolic disturbances than other antipsychotics (Ma et al., 2014, Mitchell et al., 2012).

In the general population, proposed criteria for identifying subjects with MetS have contributed greatly to preventive medicine, but the value of metabolic syndrome as a scientific concept remains controversial (Despres and Lemieux, 2006). The presence of metabolic syndrome alone cannot predict global cardiovascular disease risk. But abdominal obesity — the most prevalent manifestation of metabolic syndrome — is a marker of ‘dysfunctional adipose tissue’, and is of central importance in clinical diagnosis (Despres and Lemieux, 2006).

Epidemiological and clinical studies have confirmed a positive correlation between body weight and serum uric acid level in different non-psychiatric populations (Han et al., 2014, Lin et al., 2008, Shiraishi and Une, 2009). HU in obesity is mainly attributed to an impaired renal clearance of uric acid (Yamashita et al., 1986). Beyond the well-known risk of gout, hyperuricemia has been suggested to be an independent risk factor of MetS and other somatic comorbidities (including kidney disease, type II diabetes, sexual dysfunction, coronary heart disease, vascular disease, and ischemic stroke) (Aribas et al., 2014, Chen et al., 2009, Huang et al., 2012, Kim et al., 2009, Kim et al., 2010, Li et al., 2014, Reininghaus et al., 2014, Viazzi et al., 2011, Xu et al., 2013). HU was also identified as an independent risk factor for all-cause mortality (Liu et al., 2012, Niskanen et al., 2004, Park et al., 2011, Xu et al., 2013). Only one study assessed uric acid levels in patients with schizophrenia to date (Chiu et al., 2012). In this sample of 637 patients, high acid uric levels were associated with hypertriglyceridemia, low HLD cholesterol levels, hypertension and MetS (with an odds ratio of 9.28) in males, but not in females.

HU may not be only a marker of cardiovascular risk in schizophrenia, but also a marker of general oxidative stress. Circulating uric acid was described as one of the major antioxidants of the plasma that protects cells from oxidative damage (Ishizaka et al., 2014, Pingmuangkaew et al., 2015). Based on other oxidative markers than HU, a considerable body of research has identified a disturbed antioxidant defense in patients with first episode schizophrenia as well as in later stages of the disease (for review see (Yao et al., 2013)). A chronic sub-inflammation of the central nervous system may underline pathophysiological mechanisms in schizophrenia and activate anti-oxidative pathways. It is therefore unclear if higher uric acid level in schizophrenia may be considered as a biomarker of an anti-oxidative protective mechanism occurring in psychiatric illness or of the cardiometabolic disturbances via impaired renal clearance.

The primary objective of this study is to estimate the prevalence of MetS, abdominal obesity and hyperuricemia in a cohort of French patients with schizophrenia, to determine their correlations with socio-demographic, clinical, and treatment-related characteristics and to investigate the gap between optimal care and effective care in treated patients. The secondary objective is to examine the association between MetS, abdominal obesity, HU, and psychiatric clinical characteristics, including psychiatric treatments.