Aricol republicat de Dr. Danut Isacoff
Authors: John E. Hokanson, PhD (John.Hokanson@UCDenver.edu) Department of Epidemiology, Colorado School of Public Health, University of Colorado Denver, 13001 East 17th Avenue
Clinical and epidemiologic observations have demonstrated an association between chronic obstructive pulmonary disease (COPD) and coronary heart disease (CHD). There is also strong evidence of increased mortality due to cardiovascular disease in COPD and individuals with both COPD and CHD have greater mortality rates than those with COPD or CHD alone. Despite a medical literature on the relationship between COPD and CHD
dating back more than 50 years understanding the nature of this relationship remains a challenge. To address this issue one must appreciate the characteristics of these common, complex, chronic diseases.
As early as 1946, Spain and Handler demonstrated an associationbetween pulmonary disease and CHD among autopsy
cases (1). This observation was extended to individual case reports using electrocardiograms (ECG) to determine coronary disease involvement (2). As noted by Drake, this observation might be expected given both disorders are associated with older age (2). Later, Thomas demonstrated a variety of different ECG abnormalities in patients with chronic pulmonary disease and again suggested the high prevalence of both disorders is related to older age and not that pulmonary disease predisposes one to coronary disease or visa versa (3).
These early studies highlight a number of issues that will haunt investigators in attempts to understand the relationship between COPD and CHD. First, these complex diseases are heterogeneous in nature. Second, these studies demonstrate the long latency period for these chronic diseases. Third, these studies highlight the need to consider confounding when examining the association between pulmonary disease and heart disease.
To address these issues it can be valuable to consider the natural history of these disease processes. Examining the underlying pathophysiologic abnormalities using biomarkers, sub-clinical pathology using non-invasive imagining, and clinical disease and it’s consequences, it can be possible to develop a meaningful understanding of the disease process.
The early studies relating pulmonary disease with CHD indicated a wide array of both lung and heart abnormalities (1, 3). Advances in non-invasive imaging have dramatically helped our understanding of the heterogeneity of these diseases. Using high resolution computed tomography (CT) two phenotypes of COPD; emphysema predominant and airway remodeling predominant can be identified (4). These two phenotypes apparently have distinct etiologic pathways. A recent publication indicated a genetic association (ADRB2) with airway remodeling (luminal area) but found no such association with emphysema (5). This suggests different pathophysiologic processes leading to these distinct COPD phenotypes. A similar situation is observed when assessing coronary function using imagining techniques. Unique risk factor and biomarker profiles suggest distinct pathophysiologic processes are associated with coronary function phenotypes determined by cardiac magnetic resonance imaging (MRI) (6). Thus, patterns identified by genetics, biomarkers, and sub-clinical imaging provide an important set of tools in dissecting heterogeneous diseases such as COPD and CHD. As suggested by the early studies (1, 3) chronic pulmonary disease and CHD are not always clinically evident. Both COPD and CHD have a long latency period in which pathophysiologic processes are at work prior to clinical symptoms. Autopsy studies indicate evidence of atherosclerotic plaque in young adults with no history of clinical disease (7). NHANES III data show that impaired pulmonary function was evident in undiagnosed individuals (8). Asymptomatic smokers have been shown to have some degree of both airway disease and emphysema by CT imaging (4). A number of studies have also demonstrated sub-clinical coronary disease in asymptomatic individuals that predict future coronary disease events, for example, the presence of calcified plaque by electron beam CT (9). Thus, it is difficult to determine the time course of the relevant physiologic processes but it also presents a challenge in actually determining
who does or does not have disease. The use of sub-clinical imaging techniques has dramatic change our ability to overcome issues of long latency periods in chronic diseases. Clearly age plays a major role in both COPD and CHD and potentially confounds the relationship between the two diseases.
The NHANES III data show the prevalence of COPD increases with age (10). The prevalence of cardiovascular disease also increases with increasing age (11). So is the observed association between COPD andCHDstrictly because both diseases increase with age? Multivariate statistical procedures allow for adjustment of age however these procedures rely on the appropriate modeling of the relationship (e.g. linear, quadratic, etc.). Thus, there is always the possibility of residual confounding particularly given the strong relationship of age with both COPD and CHD.
Smoking history is another potential confounding factor that needs to be considered in examining the association between COPD and CHD. Smoking history presents a particular challenge in the ability of measurement instruments to adequately estimate true smoking exposure. This leads to the possibility of misclassification and residual confounding related to smoking history. Despite these limitations, recent evidence supports a relationship between lung function and CHD after accounting for age, smoking history, and other potential confounders (12).
One possible solution to some of these dilemmas is to identify specific biomarkers that are related to the pathophysiologic process of interest. One such molecule that has been examined in this context is cardiac troponin I (cTn-I). Troponins are involved in the calcium dependent contractile apparatus of muscles. Elevated cTn-I is a marker of cardiac damage that can be used in the diagnosis of myocardial infarction (13). Several reports have indicated that cardiac troponins are elevated during acute exacerbations of COPD and in critically ill patients (14–16). A recent report demonstrated that elevated cTn-T is associated with mortality after COPD exacerbations (17). The manuscript by Fruchter and Yigia published herein (18) expanded these observations by showing that cTn-I elevations are associated with long-term mortality after COPD exacerbation. As mentioned by the authors, there are other possible explanations for the relationship between elevated cTn-I and mortality in COPD, however this study and others do support a potential
biological role for the observed association between COPD and CHD.
Biomarkers can aid in our understanding of underlying mechanisms of disease. Examining the full range of the disease process from genetic factors to the underlying pathophysiologic abnormality using biomarkers to sub-clinical pathology using non-invasive imaging to clinical disease, complications, and mortality will facilitate our understanding of common, complex, chronic diseases.
Articol preluat din COPD: Journal of Chronic Obstructive Pulmonary Disease, 2009; 6:149–151