Cardiovascular and metabolic risk in outpatients with schizophrenia treated with antipsychotics: Results of the CLAMORS Study
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
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- 1
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).