The prevalence of clinically-relevant comorbid conditions in patients with physician-diagnosed COPD: a cross-sectional study using data from NHANES 1999–2008

Chronic Obstructive Pulmonary Disease (COPD) is the 4^th most common cause of death in the United States, with projections that it will move into 3^rd place by 2020. Currently, COPD is the attributable cause of death for more than 120,000 deaths per year. While deaths from stroke and heart disease decreased between 1970 and 2002, death rates for COPD nearly doubled [1]. COPD is also a leading cause of hospitalizations in older adults [2], as well as of other morbidity.

COPD does not simply contribute to mortality. It may contribute substantially to difficulties with activities of daily living and disrupt social functioning [3]. A study in 2003, for example, found the presence of either moderate or severe COPD to be associated with a higher odds ratio of functional limitations [4].

The majority of patients with COPD have more than just COPD - comorbidities in COPD are the rule, rather than the exception. A study of 200 COPD patients from a managed care organization, for example, found that 94% of patients had at least one other chronic medical condition [5]. This is significant because comorbidities in COPD are associated with poorer outcomes, both for COPD and the other conditions [6, 7]. Previous studies have shown an association between a variety of chronic conditions and COPD, including hypertension, diabetes, heart failure, coronary artery disease, and malignancy [6‐9].

Previous studies on comorbidities in COPD have typically focused on selected chronic medical conditions, such as heart failure and diabetes. These studies have largely failed to look comprehensively at many other high-priority conditions, such as arthritis and obesity, and important functional limitations, like cognitive impairment and limited mobility. Functional limitations can have a significant impact on the treatment of chronic conditions, as patients may have difficulty adhering to treatment regimens [10]. These conditions may also modify the effectiveness of COPD therapy, cause potentially dangerous therapeutic interactions, and make COPD therapies less feasible.

Despite these potential interactions and the complexities of clinical decision-making for people with COPD, little population–based data on the prevalence of comorbidities in COPD is available. To date, there have been no nationally-representative studies of the prevalence of comorbidities in COPD. Moreover, COPD clinical practice guidelines do not provide specific recommendations for older patients with multiple comorbid diseases [11]. Thus, in this study, we aim to describe the prevalence of clinically-relevant comorbid conditions that add to the complexity of clinical decision-making or self-management of COPD in a nationally-representative population of people with physician-diagnosed COPD. We also compare these prevalence estimates to those seen in subjects without COPD, to gain a better understanding of which conditions in particular are more common in people with COPD.

The prevalence of comorbid chronic disease among subjects with physician-diagnosed COPD was: congestive heart failure (12.1%), coronary heart disease (12.7%),hypertension (60.4%), hypercholesterolemia (47.6%), stroke (8.9%), diabetes (16.3%), osteoporosis (16.9%), arthritis (54.6%), cancer (16.5%), depression (20.6%), and anxiety (8.6%). Clinical factors potentially complicating the treatment of COPD were: dizziness or balance problems (41.1%), obesity (40.3%), urinary incontinence (34.9%), anemia (9.3%), low GFR (16.2%), use of >4 prescription medications (51.8%), and frailty (9.5%). Subjects with COPD were also found to have the following “health status” factors: memory problems (18.5%), mobility difficulty (55.6%), hearing impairment (12.1%), and visual impairment (14.0%). 96.4% of subjects with COPD had at leastone comorbidity.

Table 1 describes the basic demographic features of those with and without COPD. Those with COPD tended to be older and female.

Figures 1, 2 and 3 depict the prevalence rates of conditions in the three domains (diseases, clinical factors, and health status factors) in subjects with COPD. These figures provide a visual illustration of the high prevalence of comorbidities in patients with physician-diagnosed COPD; they do not statistically compare groups. The majority of the conditions are markedly more common in the ≥65 age group than in the younger age groups. While some conditions are more common in one gender than the other (depression, CHD, osteoporosis, and hearing impairment), others, such as polypharmacy, obesity, dizziness or balance problems, and memory problems are equally common among the two genders. Missing bars on the graph represent conditions for which the sample size was small in a given gender and age group.

Table 2 compares the prevalence rates of the conditions in subjects with COPD to those without COPD. Most of the conditions are significantly more prevalent in the subjects with COPD than in the subjects without COPD. While not shown in the table, some portion of these differences can be accounted for by differences in age and gender distribution in the COPD and non-COPD groups. While not shown here, we found little difference in the prevalence of comorbid conditions between COPD subjects with and without a history of smoking,

Table 3 compares the prevalence of conditions in subjects with COPD to those prevalence values found in previous publications. The table also notes the country of study, the sample size, and the sampling method. We found that, in most cases, the population-based prevalence of comorbid conditions is at least as high, if not higher, as the prevalence found in these less-generalizable COPD populations.

In this paper, we describe the prevalence of clinically-relevant comorbid conditions in a nationally-representative sample of people with physician-diagnosed COPD. We found that 96.4% of adults with physician-diagnosed COPD have at least one condition that may complicate the treatment of COPD. Most notably, 51.8% of people with COPD 45 and older are taking more than 4 medications (polypharmacy), 55.6% report mobility difficulty, 60.4% have hypertension, and 54.6% have arthritis.

These prevalence values are relatively consistent with those found in previous studies of comorbidities in COPD. However, there is a large range of previously reported prevalence values. For example, estimates of arthritis in COPD range from 22% [5] to 70% [23]. Neither of these studies, nor any other recent studies investigating comorbidity in COPD, have examined nationally-representative data. This both limits the applicability of these prevalence estimates and helps account for the large ranges in these estimates. In fact, several papers have cited lack of national representation or specific population bias as a weakness [5, 8, 24]. As such, our study both confirms the high prevalence of comorbidities in patients with COPD and provides specific prevalence values that are relevant on a national scale.

Another strength of our study is the range of clinically-relevant conditions assessed. While there is a lot of data on, for example, cardiovascular disease in COPD [8], there are few studies that look at the wide variety of medical conditions and functional limitations we have assessed. This is important partially because comorbidity has been found to be an important aspect of quality of life in COPD [25‐27], as well as an independent risk factor for hospitalization [28]. In addition, comorbidities increase the risk of hospitalization and mortality in patients with COPD [8], and significantly increase the costs of treating COPD [29]. These conditions are also highly relevant for clinical decision-making and self-management.

The classification of the conditions into disease, clinical factor, and health status factor domains highlights that a wide range of conditions relevant to the clinical management of people with COPD are quite prevalent, and that these relevant conditions extend beyond traditionally-defined diseases.

Physicians must be judicious when caring for patients with COPD. The high prevalence of comorbidity and polypharmacy means physicians must be cognizant of potential adverse drug events and nonadherence. People with COPD are often complex, and, thus, we will need to improve our ability to prioritize treatment recommendations based on relative benefits and harms and patient preferences. Current guidelines, and our evidence base, do not yet adequately inform this critical clinical decision-making [13].

Clinical practice guidelines generally do not address how to treat COPD in the context of comorbid conditions [11]. As such, these guidelines may be of little help when dealing with the majority of COPD patients [30, 31]. For example, β-blockers, which are indicated for cardiovascular disease, may worsen lung function in some patients with COPD; some studies, however, have shown that this is not a contraindication to the initiation of β-blockers [32]. Conversely, bronchodilators, which are believed to be beneficial for pulmonary function, may worsen tachyarrhythmias [9]. Guidance about these potential interactions, and the quality of evidence supporting any recommendations about them, would be very useful to clinicians. Our results can inform clinical practice guideline priority-setting processes to determine which comorbidities should be addressed in future COPD guidelines.

It is imperative that therapeutic trials be designed to reflect the true population of people with COPD. Many studies exclude patients with significant comorbid conditions [33]. Herland et al. found that only 17% of a group of COPD patients would be eligible for a “typical” clinical trial. 65.9% of COPD patients in this study were “excluded” due to significant comorbidities, including diabetes, depression, and ischemic heart disease [34]. These exclusions may be troublesome given the high prevalence of these diseases in people with COPD, and the potential for interactions between the diseases and their treatments. Our study highlights the need for future clinical trials to evaluate safety and effectiveness in COPD patients with multiple comorbidities.

There is evidence that treating COPD may benefit the course of comorbid conditions, and, visa-versa [35]. For example, several observational studies have shown improved outcomes in COPD patients treated with statins [36, 37], independent of whether patients have a comorbid diagnosis of ischemic heart disease [38]. While a randomized controlled trial has shown an improvement in exercise tolerance in COPD patients treated with statins [39], more prospective intervention trials are needed to look at the use of statins in COPD [40].

Given these potential complications of treatment and the interactions between comorbid conditions and COPD, some researchers have started to advocate for an integrated-care approach to the management of patients with COPD. Sonetti et al. in a recent review advocate for a chronic care model approach to COPD management, with an approach that includes automatic screening for common comorbidities [41, 42]. In order to truly move to such a system, however, it is necessary to have a good understanding of how best to treat COPD in the context of comorbid conditions. First steps to accomplishing this are (a) determining common “patterns” of co-existing conditions (b) including patients with comorbid conditions in clinical trials with appropriate analytic strategies to understand heterogeneity of treatment effect [43] (c) evaluating current treatment regimens in patients with different patterns of comorbid conditions and (d) continuing to study possible pathophysiologic connections between COPD and comorbidities. Further research should also continue to explore the effects comorbid conditions have on outcomes (health-related and other) in COPD.

Comorbid conditions are the rule, not the exception, in patients with physician-diagnosed COPD. While 96.4% of adults 45 and older with COPD have at least one condition that may complicate the treatment of COPD, few trials or practice guidelines take these conditions into consideration. Describing the nationally-representative prevalence of comorbid conditions in patients with physician-diagnosed COPD is the first step towards developing an evidence base, and clinical practice guidelines, that better represent the true population of patients with COPD.