Elsevier

Schizophrenia Research

Volume 90, Issues 1–3, February 2007, Pages 162-173
Schizophrenia Research

Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: Results of the CLAMORS Study

https://doi.org/10.1016/j.schres.2006.09.025Get rights and content

Abstract

Aim

To assess the prevalence of Coronary Heart Disease (CHD) and Metabolic Syndrome (MS) in patients treated with antipsychotics.

Methods

Retrospective, cross-sectional, multicenter study in which 117 Spanish psychiatrists (the CLAMORS Study Collaborative Group) recruited consecutive outpatients meeting DSM-IV criteria for Schizophrenia, Schizophreniform or Schizoaffective Disorder, receiving antipsychotic treatment for at least 12 weeks. CHD risk was assessed by SCORE (10-year CV death) and Framingham (10-year all CHD events) function. MS was defined by at least 3 of the following components: waist circumference > 102 (men)/> 88 (women) cm; triglycerides 150 mg/dl; HDL-cholesterol < 40 mg/dl (men)/< 50 mg/dl (women); blood pressure ≥ 130/85; fasting glucose ≥ 110 mg/dl.

Results

1452 evaluable patients (863 men, 60.9%), aged 40.7 ± 12.2 years (mean ± SD) were included. MS was present in 24.6% [23.6% (men), 27.2% (women); p = 0.130)]. The overall 10-year risks were 0.9 ± 1.9 (SCORE) and 7.2 ± 7.6 (Framingham). 8% (95%CI: 6.5–9.5) and 22.1% (95%CI: 20.0–24.3) of patients showed a high/very high risk according to SCORE (≥ 3%) and Framingham (≥ 10%) function. Abdominal obesity and low HDL-cholesterol were more prevalent in women: 54.5% (95%CI: 50.2–58.9) versus 34.3% (95%CI: 31.0–37.7), and 46.1% (95%CI: 41.4) versus 28.5 (95%CI: 50.8), p < 0.001 in both cases. Hypertension and hypertriglyceridemia were more prevalent in men: 59.0% (95%CI: 55.7–62.3) versus 46.0% (95%CI: 41.8–50.2), and 40.7% (95%CI: 37.2–44.2) versus 32.4 (95%CI: 28.3–36.5), p < 0.01 in both cases.

Conclusions

CHD risk and MS prevalences among patients with schizophrenia treated with antipsychotics were in the same range as the Spanish general population 10 to 15 years older.

Introduction

Mortality due to any cause has been shown to be considerably greater among chronic patients with schizophrenia than in the general population in different settings (Brown et al., 2000, Babidge et al., 2001, Hiroeh et al., 2001, Morgan et al., 2003). The reasons for this excess mortality include patients' life style, increased suicidability, premature development of cardiovascular disease, and high prevalences of metabolic syndrome (MS) and carbohydrate and lipid metabolic disorders (Sernyak et al., 2002, Bobes et al., 2003, Wirshing, 2004, Enger et al., 2004, Lamberti et al., 2004, Cohn et al., 2004, Saari et al., 2005, Holt, 2005).

Obesity is increasingly prevalent, and has become a serious public health problem in developed countries. In the United States, it has been reported that one-third of the adult population is obese (Centers for Disease Control (CDC), 1997), while in Spain the figure is lower, around 15% (Aranceta et al., 2003). Obesity – particularly abdominal obesity – also appears to be a frequent concomitant condition in schizophrenic patients (Allison et al., 1999, Bobes et al., 2003, Wirshing, 2004). Potential factors associated with the development of obesity include the particular life style of patients with schizophrenia, unbalanced dietary habits and, recently, the effects of psychotropic medication — including both first and second generation antipsychotic drugs (Meyer, 2002, Wirshing and Meyer, 2003, Conley et al., 2005). The importance of these adverse effects is not limited to the fact that they constitute a source of treatment non-compliance (Bernstein, 1987, Fakhoury et al., 2001). Indeed, in the same way as in the general population, they pose an increased risk of developing medical problems related to obesity, such as type 2 diabetes (Lebovitz, 2001, Haupt and Newcomer, 2001) and particularly the development of MS (Newcomer, 2001, Newcomer, 2005, Heiskanen et al., 2003, Kato et al., 2003, Littrell et al., 2003, Straker et al., 2003, American Diabetes Association et al., 2004, Basu et al., 2004, Cohn et al., 2004, Kato et al., 2004, Marder et al., 2004, McEvoy et al., 2005, Birkenaes et al., 2006, De Hert et al., 2006, Suvisaari et al., 2006). Moreover, these conditions constitute cardiovascular risk factors (Mukherjee et al., 1996, Davidson, 2002, Meltzer et al., 2002, Citrome and Jaffe, 2003, Meyer et al., 2005).

However, despite growing interest in this comorbidity in patients receiving antipsychotic treatment, few data are available on its prevalence. In particular, prevalence of diabetes has been reported to be between 9% and 14% (Lindenmayer et al., 2003, Kabinoff et al., 2003), and that of dyslipidemia and arterial hypertension prevalences to be 43% and 30% respectively (Gupta et al., 2003). The CATIE clinical trial, which included patients receiving antipsychotic treatment matched for age, race, and gender with subjects from the NHANES study (McEvoy et al., 2005, Meyer et al., 2005, Goff et al., 2005a, Stroup et al., 2006), estimated the mean risk of serious fatal and nonfatal Coronary Heart Disease (CHD) within 10 years, according to the Framingham function, at 9.4% in males and 6.3% in females (Goff et al., 2005a). These figures are higher than those reported in the general population in the United States, 7.0% in males and 4.2% in females (Plan and Operation of the Third National Health and Nutrition Examination Survey, 1988–94). Moreover, the CATIE trial documented a high prevalence of MS (40.9%) (McEvoy et al., 2005). Few of these studies have provided data on CHD risk according to the Framingham function (Wilson et al., 1988), and on cardiovascular mortality (CVM) risk using the more recent SCORE function (Conroy et al., 2003).

This present cross-sectional, retrospective study (CLAMORS Study: Cardiovascular, Lipid and Metabolic Outcomes Research in Schizophrenia Study) was conceived with the aim of using appropriate methodology to evaluate the prevalence of cardiovascular risk factors (CVRFs), overall CHD risk and CVM risk, and the prevalence of MS in patients with schizophrenia, schizophreniform or schizoaffective disorder receiving treatment with the antipsychotics most commonly used in our setting.

Section snippets

Investigators and patients

Psychiatrists from all over Spain participated in the study. Selection of the investigators was initially based on quotas reflecting the population sizes in the different regions. The study was carried out between May 2004 and April 2005 in a psychiatry outpatient clinic setting, under the usual medical practice conditions and in accordance with the clinical practice of each investigator.

The study enrolled consecutive patients of both sexes, aged 18–74 years, with a diagnosis of schizophrenia,

Evaluable patients

After increasing the number of patients to be included per investigator, in order to attain the minimum sample size, 1704 patients were recruited by 117 psychiatrists from 91 different centers. Of these, 252 (14.8%) who failed to meet the study evaluability criteria were excluded. The main reason for exclusion (202 patients, 11.9%) was current antipsychotic treatment for less than 12 weeks (Fig. 1).

Patient characteristics

Table 1 shows the patients' main sociodemographic and general clinical characteristics. The

Discussion

The CLAMORS study corroborates the results of earlier studies published in the literature.

Table 5 shows a comparison of the prevalence of MS in the CLAMORS study and in previous studies of patients with schizophrenia in various health settings, and in populations without schizophrenia in Spain. In general, with the exception of the study by Saari et al. (2005) the prevalence of MS was found to be lower in the population with schizophrenia in Spain than in other countries. However, the

Acknowledgement

Pfizer España provided an unrestricted grant for this multicenter, cross-sectional study. Pfizer España contributed to and approved the study design and the final draft of the manuscript. A CRO was engaged by Pfizer España to conduct the study, including logistics, monitoring, data management, and statistical analysis. Pfizer España oversaw the entire process of the study.

Conflict of interest: Drs. Bobes, Arango, Aranda and Carmena have been consultants for Pfizer España. Ms Garcia-Garcia is an

References (71)

  • J.P. McEvoy et al.

    Prevalence of the metabolic syndrome in patients with schizophrenia: baseline results from the Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial and comparison with national estimates from NHANES III

    Schizophr. Res.

    (2005)
  • J.M. Meyer et al.

    The Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) schizophrenia trial: clinical comparison of subgroups with and without the metabolic syndrome

    Schizophr. Res.

    (2005)
  • M.G. Morgan et al.

    Prospective analysis of premature mortality in schizophrenia in relation to health service engagement: a 7.5-year study within an epidemiologically complete, homogeneous population in rural Ireland

    Psychiatry Res.

    (2003)
  • S. Mukherjee et al.

    Diabetes mellitus in schizophrenic patients

    Compr. Psychiatry

    (1996)
  • D.B. Allison et al.

    The distribution of body mass index among individuals with and without schizophrenia

    J. Clin. Psychiatry

    (1999)
  • E.E. Álvarez et al.

    Prevalence of the metabolic syndrome in the population of Canary Islands, Spain

    Med. Clin. (Barc)

    (2003)
  • American Diabetes Association et al.

    Consensus development conference on antipsychotic drugs and obesity and diabetes

    Diabetes Care

    (2004)
  • J.F. Ascaso et al.

    Grado de concordancia de los distintos criterios que definen el síndrome metabólico en el estudio DESIRE [abstract]

    Av. Diabetol.

    (2004)
  • N.C. Babidge et al.

    Mortality among homeless people with schizophrenia in Sydney, Australia: a 10-year follow-up

    Acta Psychiatr. Scand.

    (2001)
  • R. Basu et al.

    The prevalence of the metabolic syndrome in patients with schizoaffective disorder-bipolar subtype

    Bipolar Disord

    (2004)
  • M.C. Bautista et al.

    The Mediterranean diet: is it cardioprotective?

    Prog. Cardiovasc. Nurs.

    (2005)
  • J.G. Bernstein

    Induction of obesity by psychotropic drugs

    Ann. N.Y. Acad. Sci.

    (1987)
  • A.B. Birkenaes et al.

    Socio-demographic characteristics and cardiovascular risk factors in patients with severe mental disorders compared with the general population

    Schizophr. Res.

    (2006)
  • S. Brown et al.

    Causes of the excess mortality of schizophrenia

    Br. J. Psychiatry

    (2000)
  • F. Cañas et al.

    Cardiovascular risk factors in patients with schizophrenia in Spain: RICAVA Study

    Schizophr. Res.

    (2006)
  • Centers for Disease Control

    Update: prevalence of overweight among children, adolescents, and adults. United States, 1988–1994

    MMWR Morb. Mortal. Wkly. Rep.

    (1997)
  • L.L. Citrome et al.

    Relationship of atypical antipsychotics with development of diabetes mellitus

    Ann. Pharmacother.

    (2003)
  • M.M. Coca et al.

    Prevalencia de síndrome metabólico en la población de un centro de atención primaria urbano

    Aten. Prim.

    (2005)
  • T. Cohn et al.

    Characterizing coronary hearth disease risk in chronic schizophrenia: high prevalence of the metabolic symdrome

    Can. J. Psychiatry

    (2004)
  • R.M. Conroy et al.

    Estimation of tenyear risk of fatal cardiovascular disease in Europe: the SCORE project

    Eur. Heart J.

    (2003)
  • C.U. Correll et al.

    Metabolic syndrome and the risk of coronary heart disease in 367 patients treated with second-generation antipsychotic drugs

    J. Clin. Psychiatry

    (2006)
  • M. Davidson

    Risk of cardiovascular disease and sudden death in schizophrenia

    J. Clin. Psychiatry

    (2002)
  • C. Enger et al.

    Serious cardiovascular events and mortality among patients with schizophrenia

    J. Nerv. Ment. Dis.

    (2004)
  • Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults, 2001. Executive summary of...
  • W.K.H. Fakhoury et al.

    Prevalence and extent of distress of adverse effects of antipsychotics among callers to a United Kingdom National Mental Health Helpline

    Int. Clin. Psychopharmacol.

    (2001)
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    The CLAMORS Study Collaborative Group includes the following investigators: Albaiges L (Barcelona), Alday MO (Barcelona), Alonso M (Cantabria), Álvarez P (Valladolid), Álvarez S (Asturias), Alzate G (Navarra), Anguiano JB (Vizcaya), Antón C (Baleares), Aragues E (Vizcaya), Asensio F (Barcelona), Bardolet C (Baleares), Barragán J (Alicante), Bellido JA (Barcelona), Bordas R (Barcelona), Busto J (Badajoz), Cadevall J (Barcelona), Cañete J (Barcelona), Capllonch I (Baleares), Carmona C (Barcelona), Carrasco E (Murcia), Carrillo A (Madrid), Castillo C (Baleares), Chinea ER (Tenerife), Cleris M (Barcelona), De Dios C (Madrid), De Uña MA (Zaragoza), Díaz N (Barcelona), Doménech JR (Barcelona), Ducaju M (Madrid), Echeveste M (Vizcaya), Fernández A (Madrid), Fernández-Cuevas A (Madrid), Fernández-Villamor R (Sevilla), Figuerido JL (Álava), Fluvia J (Alicante), Franch JI (Valladolid), Galán F (Badajoz), García I (Madrid), García J (Zaragoza), García-Portilla MP (Asturias), Gil P (Vizcaya), Gómez-Trigo J (Madrid), González FA (Santa Cruz de Tenerife), González G (Vizcaya), González P (Lleida), González T (Madrid), González-Quirós M (Asturias), Graizer O (Madrid), Hernández C (Madrid), Hernández JL (Las Palmas de Gran Canaria), Iglesias C (Asturias), Irurita J (Las Palmas de Gran Canaria), Justo MI (Barcelona), Karim M (Álava), Larrazabal LM (Vizcaya), Lizarraga J (Vizcaya), Lojo FM (Murcia), López I (Baleares), López J (Baleares), López L (Murcia), Loro M (Segovia), Martín E (Madrid), Martín F (Burgos), Martínez A (Almería), Martínez de Morentín JJ (Navarra), Martínez JL (Madrid), Martínez JM (Zamora), Martínez M (Málaga), Martínez R (Barcelona), Medina G (Valladolid), Medina JL (Madrid), Megía P (Palencia), Mendezona JI (Vizcaya), Merino MJ (Asturias), Messays M (Barcelona), Misiego JM (Baleares), Mongil JM (Cádiz), Montejo AL (Salamanca), Montes JM (Madrid), More MA (Madrid), Moyano L (Córdoba), Natividad MC (Barcelona), Pacheco L (Vizcaya), Palao DJ (Barcelona), Palomo AL (Barcelona), Parramón G (Barcelona), Pascual G (Zaragoza), Pastor A (Valencia), Pastor FJ (Vizcaya), Peralta E (Almería), Pérez E (Alicante), Prieto N (Salamanca), Rodríguez E (Málaga), Rodríguez JC (Málaga), Roig A (Valencia), Rojano P (Madrid), Rubio T (Zaragoza), Ruiz FC (Palencia), Ruiz JM (Álava), Salesansky A (Las Palmas de Gran Canaria), Salgado MC (Madrid), San Narciso GI (Asturias), Sánchez JM (Cádiz), Sanz J (Vizcaya), Shabiaga P (Barcelona), Silveira JR (A Coruña), Sopelana PA (Madrid), Soto JA (Madrid), Sotomayor E. (Asturias), Teba F (Barcelona), Valdelomar M (Barcelona), Valle JR (Sevilla), Vicente FJ (Madrid), Villagran D (Cádiz), Villamor A (Álava).

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