© 2007 American Thoracic Society doi: 10.1164/rccm.200610-1565ED
C-reactive ProteinDoes It Predict Mortality?Royal Free and University College Medical School London, United Kingdom Chronic obstructive pulmonary disease (COPD) is a growing cause of mortality and morbidity and hence imposes an increasingly large burden on health services throughout the world. COPD is primarily an inflammatory disorder of the lungs. Measurement of airway inflammation can be difficult in clinical trials because patients cannot always provide a sputum sample even with induction. Exhaled breath condensate offers a more reliable method of sampling, but only a few markers can be detected. More recently, the extrapulmonary nature of COPD, with muscle wasting and weight loss, has been recognized. These clinical findings, coupled with the success of troponin as a marker in myocardial infarction, have focused research on systemic markers in the blood of patients with COPD. C-reactive protein (CRP) measured in serum can be sensitively and reliably determined on a routine basis at low cost. There is a large body of work that shows that systemic inflammation exists in stable COPD. In the setting of COPD, systemic inflammation has been associated with reduced lung function, diminished muscle strength, and 6-minute walking distances (1, 2). In this issue of the Journal (pp. 250–255), using data from the Copenhagen City Heart Study, Dahl and colleagues report that prospective measurements of serum CRP in both crude and confounder-adjusted analyses were predictive of hospitalization and death from COPD (3). These results agree with numerous prospective studies that show that CRP is a strong predictor of future mortality (4). However, these data do not permit the conclusion that CRP is an independent risk factor for mortality in COPD since, in the strictest statistical sense, such a statement requires that predictive variables in the regression model not be correlated with each other and that all potential confounders be included (5, 6). There are some reasons for caution in linking CRP and COPD outcome. First, CRP increases in response to a number of infectious and inflammatory conditions and therefore it is not specific to COPD. Second, it has been estimated that 40 to 50% of the variation in serum CRP levels is due to inherited characteristics (7). Third, although inhaled corticosteroids can dramatically lower CRP levels by up to 50% (8), the evidence that they reduce COPD mortality is much less clear cut and any benefits may be limited to reducing cardiovascular mortality (9). In patients with mild to moderate COPD, Man and colleagues have recently reported a positive trend between quintiles of CRP and increased cardiovascular, cerebrovascular, and cancer deaths, but not deaths from respiratory disease (10). These results fit with a number of studies that have shown that that an elevated CRP will predict mortality from cardiovascular causes in patients with other diseases, such as diabetes or renal disease (11, 12). However, it should be noted that the cardiologists have not yet fully endorsed the use of CRP in risk assessment, with the Centers for Disease Control and Prevention and the American Heart Association recommending its measurement only in adults at intermediate risk of heart disease. Similarly, the European Society of Cardiology guidelines on coronary heart disease note that the benefits of CRP measurement remain uncertain (13). In the study by Dahl and colleagues (3), were the COPD deaths from cardiovascular or respiratory causes? Only 57 of the 83 deaths had COPD as the major cause. Seven deaths were due to lung cancer, seven to cardiovascular disease, and 12 to a variety of other causes. Even those deaths listed as COPD could have been misdiagnosed, because dyspnea can occur with a myocardial infarction. The authors attempted to answer this question by looking at the prevalence of cardiovascular disease in the deceased, hospitalized, and no-event groups. They found no difference. However, with only 83 deaths and 185 hospitalizations, the study was possibly underpowered to distinguish all but the greatest differences. Patients with COPD will die of cardiovascular disease, but then so will people without COPD. This is because there are other important risk factors for cardiovascular disease: hypertension, diabetes, raised cholesterol and triglyceride levels, obesity, and smoking. Therefore, it may not be legitimate to attribute all cardiovascular deaths in patients with COPD to COPD itself. This said, patients with COPD may be undertreated for cardiovascular problems because the physician focuses on the more immediate lung issues. The Copenhagen City Heart Study is an outstanding epidemiologic study, and the record linkage with the Danish National Hospital Discharge Register and the Danish National Register of Causes of Death shows how data from various sources sometimes need to be combined to answer some of the more difficult research questions. Large observational studies are extremely useful in identifying the effects on health of diet, lifestyle, and the environment. Unfortunately, they cannot always demonstrate causality. The study by Dahl and colleagues will give impetus for further research on the role of CRP in COPD. FOOTNOTES Conflict of Interest Statement: G.C.D. does not have a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
Related articles in AJRCCM:
This article has been cited by other articles:
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
