People with schizophrenia are known to be at higher risk of premature death; however, the contributions of modifiable risk factors to mortality risk in this population remain largely unknown. In our study, we report the lifetime prevalence of smoking to be 55% in people with schizophrenia. Our findings show that the risk of increased mortality from smoking is significant (HR = 2.1) and is first evident in the middle ages (35–54 y). We did not find an increased risk of mortality in people aged 19–34 years, likely because total mortality in this group was very low and cumulative and detrimental effects of smoking have not had sufficient time to accrue in younger people. Our risk estimates are similar to recent general population estimates as White26
reported that in the general population risk of cardiovascular death in smokers was about twice that of nonsmokers. Of further interest is the 12-fold risk of cardiac related mortality in the middle ages compared with nonsmokers. Overall, these data underscore the importance of planning for the assessment and treatment of cigarette smoking in people with this illness as they are at a significantly increased risk of mortality, particularly, cardiac mortality compared with people with schizophrenia who do not smoke cigarettes.
Our most puzzling finding was that in the older ages (55–69 y) mortality risk was lower for smokers unlike the pattern in the general population. A few reasons may explain this finding. First, our sample included a limited number of people in this age bracket (N
= 156), possibly due in part to the low average life span (61 y) in patients with schizophrenia. Second, older patients have many comorbid health problems that may confound any impact of smoking on total mortality.27
Lastly, in keeping with the sharply decreased average in people with schizophrenia compared with the general population, patients who smoke may have died prior to the age of 55 years from cardiovascular related mortality so that older surviving smokers in our sample may have been selected from those least likely to develop smoking-related complications.
Our results also suggest that the greater the number of cigarettes smoked daily, the greater the risk for mortality in persons with schizophrenia. We found that those aged 35–54 years who smoke greater than a pack per day had a 170% increased absolute mortality risk (HR = 2.7) as compared with nonsmokers. These findings are similar to general population data that suggest that disease risk is highest in those who smoke more than 20 cigarettes per day. Additionally, it is known that few systems of the body are unaffected by smoking.28
Smoking is undoubtedly a risk factor for cardiovascular disease and associated mortality (ischemic heart disease, cerebrovascular disease, atherosclerosis, aneurysm); however it is also associated in the general population with an increased risk for mortality from malignant neoplasm (lung, laryngeal, pharyngeal, digestive tract, colorectal, and oral)29,30
and respiratory diseases (pneumonia, chronic obstructive pulmonary disease).18
Thus, all-cause mortality was examined in our current study to include morbidities related to all body systems. Of particular note, cardiovascular disease was the most frequently occurring cause of death, and cardiac related mortality risk was greatly elevated compared with nonsmokers in this our sample. Cancer mortality in this sample (7 cases of cancer death among 664 smokers vs 4 cases among 594 nonsmokers) was too infrequent to ascertain whether smoking increased cancer death risk in this population.
The strengths of this study include the large sample size and specific clinical chart information regarding smoking and substance use. Other studies have relied upon Medical claim data,31
and unclear or combined diagnoses.31,33
The additional chart data we have gathered in this study are significantly richer than administrative data that have many limitations.34
First, diagnoses in administrative data are often inaccurate. Second, listed causes of death such as “cardiac arrest,” eg, may not always reflect the root cause of a problem because many conditions in addition to cardiovascular disease can lead to cardiac arrest. We were careful to include all underlying medical disorders and contributing factors listed on the death records to help determine if deaths listed as cardiac were due to primary or secondary cardiac cause. Third, administrative data may not accurately reflect true medical conditions. Previous studies have found that over 25% of medical record diagnoses do not match administrative data.35
This type of clinical data has many strengths over using administrative or Medicaid data by not being tied to claims. Another strength of this study is the follow-up period of 4–10 years.
Limitations of this study include the retrospective nature of the data gathering and the lack of pack years on all patients who are smokers. Also, the number of deaths for causes other than cardiac disease was too small to analyze for differences in cause-specific mortality. Additionally, patients were identified by having an inpatient hospitalization in state facilities, thus representing a group who likely received medical assistance, had more severe mental illness at the start of mortality follow-up, and who may have been more or less likely to receive adequate medical treatment. The initial sample was identified as being treated with SGAs between 1994 and 2000; however, antipsychotic treatment changed during their course of treatment and use of other concomitant medications or first-generation antipsychotics, as well as information on subsequent antipsychotic changes, were not recorded. All analyses were controlled for clozapine vs other antipsychotic treatment to account for antipsychotic treatment with a high weight gain liability; clozapine treatment was not associated with an increased risk of mortality. Other antipsychotics and concomitant medications may contribute to a differential mortality risk due to different side effect profiles, however, this analysis was unable to control for other treatments. Given the inclusion criteria, these subjects identified through inpatient hospitalization records may not be representative of patients treated entirely in the outpatient sector.
There has been increasing attention focused on the need to improve care for individuals with co-occurring mental illness and cigarette smoking or substance use disorders.36
This underserved population requires the development of evidence-based approaches to improve their lives. This study demonstrates that smoking should be a top priority in the treatment of people with schizophrenia as lives are considerably shortened with tobacco use.