This study is, to the best of our knowledge, one of the first to provide nationally representative estimates of the prevalence and characteristics of physical disease in hospitalized patients with schizophrenia in Spain. Our results indicate that schizophrenia is associated with a substantial burden of physical comorbidities; that these comorbidities appear early in life; and that they have a severe impact on mortality. Also, in agreement with prior reports [3, 4, 19, 20], our data indicate that hospitalized schizophrenic individuals often have numerous physical diseases, and that several of these diseases are of known clinical severity and prognostic relevance, however, the study design do not allow us for making causal inferences.
As for the most prevalent ICD-9 groups, our data were in general agreement with international figures. Thus, the rates of endocrine, circulatory, respiratory, and digestive diseases in our population were comparable to those in other studies that analyzed whole populations or used administrative data [19, 21, 22]. Certain physical diseases (substance abuse, injury-poisoning, and infections such as AIDS) were much more frequent in young people [20, 23]. In contrast, circulatory and endocrine diseases were more common in patients over the age of 40 years.
Our data also identify gender-related differences in the physical diseases of patients with schizophrenia. Thus, compared with women, men had significantly higher rates of substance abuse (alcohol, drugs, and cigarette-smoking ), and a higher prevalence in certain diagnostic groups, such as chronic respiratory processes, digestive diseases, and infectious diseases [6, 23, 25]. Although men had a lower overall risk of circulatory disease, they suffered more from ischemic heart disease and myocardial infarction. On the other hand, women were more likely to have endocrine diseases, musculoskeletal and connective tissue diseases, neurological diseases, and neoplasms, possibly related to their older age [25–27].
The results of our study add to the existing controversy about differences in the rates of physical illnesses in patients with schizophrenia compared to the general population [1, 7]. Thus, a comparison of our data and official figures for the Spanish general population provided by the National Health Survey  suggests that subjects with schizophrenia have higher rates of substance abuse/dependency, diabetes mellitus, digestive diseases, neoplasms, and AIDS. On the other hand, we found no pronounced differences in the frequency of COPD and ischemic heart disease. These findings, though noteworthy in view of the high prevalence of related risk factors, such as diabetes and smoking, are comparable to results of previous studies. Thus, Carney and colleagues  found that whereas a somewhat higher percentage of persons with schizophrenia had ischemic heart disease than did controls from the general population (2.3% vs. 1.9%), the adjusted odds ratio was not significant. Regarding COPD, our data also agree with previous reports . However, it should be noted that diagnosis of early-stage COPD can be difficult  and the reported rate of COPD may be biased by a failure to perform diagnostic spirometry . In addition, a tendency to ignore a diagnosis of COPD in patients with schizophrenia has been reported .
Concerning mortality, this study highlights the impact of physical disease on the risk of death in people with schizophrenia. Our analysis indicates that the Charlson index score and the presence of certain physical diseases (e.g., respiratory, circulatory, tumoral, infectious, digestive, and injury-poisoning) significantly increase the risk of death during hospitalization. In addition, our data underscore that physical disease in schizophrenia was associated to disproportionately high mortality risks relative to the general population. These results, that agree with prior reports [2, 31–33], raise concerns about the consequences and causes of physical disorders in patients with schizophrenia and identify a compelling need for a specific approach aimed to detect physical comorbidities, especially those that are most common and closely related to mortality. In this regard, the high risk of mortality from respiratory diseases in our population suggests that a specific approach be used to monitor and control modifiable risk factors, such as smoking . Furthermore, as the prevalence and the type of physical comorbidity show significant differences between both genders, the preventive and therapeutic measures to reduce such a disease burden and associated mortality must, in addition, have a specific gender orientation.
Our study was observational, and thus we cannot definitely identify the influence of factors linked to lifestyle, adverse drug effects, or socio-economic level to explain the pattern of physical diseases in our population. Likewise, it is impossible for us to analyze the adequacy of healthcare received by the patients. Several authors have suggested that people with schizophrenia may receive inadequate medical treatment and experience inequalities and difficulties in accessing various medical procedures, even when free and universal healthcare is available, as in Spain, at the point of care [35, 36].
The results of this study extend previous work by providing a comprehensive overview of medical disorders associated with schizophrenia. In particular, our study has several strengths compared to previous reports: (a) we characterized physical diseases in a large population-based representative sample of patients with schizophrenia; and, (b) we included all diseases and objectively classified them according to the ICD-9 system. In addition, our data represent clinical practice patterns for professionals nationwide, allowing us to generalize the results. Furthermore, the use of the Charlson comorbidity index, which is widely used to predict hospitalization outcome, increases the validity of observations.
We must also acknowledge possible limitations of our work. This study is subject to the limitations inherent in retrospective studies using administrative databases. Data from these databases lack of many measures obtainable only from chart review or survey with the attendant potential for omitting important prognostic factors. Furthermore, these data do not allow causal inferences to be made. However, the use of such databases is well-established in psychiatric epidemiology and health services research and has been shown to furnish valuable information for assessing the need for preventive and therapeutic care and for service planning [37–39]. Additionally, the Spanish Ministry of Health  systematically performs assurance audits of the National Hospital Discharge Registry to verify coding adequacy. Moreover, we followed the guidelines for reporting observational studies, as outlined by the STROBE Initiative .
We also recognize that the presence of a control group would have resulted in more far-reaching results and a more precise determination of the risk and time of development of physical comorbidities in patients with schizophrenia. Currently, however, it was not possible for us to consider a sufficiently large control group representative of the patients studied. Nevertheless, given that, to our knowledge, this work constitutes the first study with this range of diagnosis and population size carried out in our country, we hope that our results will be the base of other studies with a stronger methodological design.
Finally, it is inarguable that hospitalized subjects will have a disease load and severity greater than the outpatient population. However, our results clearly show the distribution and prevalence of different physical diseases that can contribute to the deterioration of health, causing patients to be admitted into hospital and increasing their risk of death. As with several recent studies [36, 41], our results have implications for the design of preventive and therapeutic programs and services for people with schizophrenia that aim to reduce the prevalence and negative impacts of physical diseases in this population.