This article is a 2-part series that highlights the persistent unmet needs connected with the early diagnosis and optimal management of adult patients with COPD. The first part focused on the primary care setting for healthcare delivery (add link to previous article) and this second part looks more closely at the negative aspects of COPD and our patients’ cardiovascular health.
The National Heart, Lung and Blood Institute (NHLI) estimates that 13 million U.S. adults have chronic obstructive pulmonary disease (COPD) and another 11 million are undiagnosed or developing COPD.1 It does not, however, include other obstructive diseases such as asthma. The global prevalence of physiologically-defined COPD in adults aged >40 years, is approximately 9-10%.2
As reported in the first part of this series, COPD is a disease that affects a small percentage of the population cared for by allopathic and osteopathic family physicians (FPs). However, 90% of COPD patients have one or more related diseases and more than half present with three or more additional chronic diseases. The morbidity seen in primary healthcare comes close to that reported in population-based studies.3 It is also well known that COPD tends to be underdiagnosed by FPs.3,4
The Halbert report found the COPD range to be 3-5% in the studies that used respiratory symptoms-based medical diagnosis as case definition.5 Comparing these data to the GOLD criteria as case definitions, FPs might be under-diagnosing 69% of their patient population with COPD. This is a high under-diagnosis ratio, and it has scarcely changed in the last ten years.4
COPD is not the only specific condition relegated to an aged population. Many other diseases or conditions are also present at a frequency that is higher than expected, such as: heart failure, arrhythmia, ischemic heart disease, anxiety/depression, obesity, thyroid disease, asthma, osteoporosis, generalized atherosclerosis and chronic liver disease. Interestingly, tobacco smoking-related inflammation is postulated as a possible cause of many of these diseases.6
Cardiovascular Disease Linkage
The most widely used marker of disease severity and progression is FEV(1). However, FEV(1) correlates poorly with both symptoms and other measures of disease progression and thus there is an urgent need for other biological markers to better characterize individuals with COPD. Fibrinogen is an acute phase plasma protein and has been reported having potential clinical utility as a COPD biomarker. There is strong evidence of an association between fibrinogen and the presence of COPD, the presence and frequency of exacerbations and mortality.7 However, while fibrinogen is associated with disease severity, it does not predict lung function decline, a measure used as a surrogate for disease activity. One potential mechanism of clinical application may lie with the fact that fibrinogen is reduced by p38 mitogen-activated protein kinase inhibitors in individuals with stable disease and by oral corticosteroids during exacerbations. Monitoring this protein could stratify individuals with COPD into those with high or low risk of future exacerbations and mortality.7
COPD patients who also present with cardiovascular diseases register more episodes of COPD exacerbation, more hospital admissions, a notable increase in cost of medical care and higher cardiovascular disease mortality.8,9 As reported by several authors, cardiovascular risk factors, such as hypertension, dyslipidemia, diabetes and obesity, are among the most prevalent diseases in COPD patients.10,11 This has been shown, however, to be due to the appropriate aging of patients, since, once age had been controlled for, prevalence did not prove very different to what might have been expected (Table 1). These findings indicate that, when studying the association between COPD and cardiovascular diseases, the confounding role of risk factors must be taken into account. Of parallel interest to clinicians is the fact that anxiety and depression are also frequent among patients with COPD. Among stable COPD patients, prevalence of depression ranged from 10% to 42% and prevalence of anxiety from 10% to 19%.12
A University of Nottingham report published in 2010 examined primary care records of more than a million members of the general population who were >35 years of age. Within this cross-sectional analysis, individuals with COPD were substantially more likely to have pre-existing cardiovascular and/or cardio-metabolic disease, had suffered a previous stroke and were also at high-risk for acute cardiovascular events.13
A Veterans Administration Medical System (VAMS) cohort study, using longitudinal administrative data to describe the prevalence and incidence of cardiovascular diseases among patients treated for COPD, revealed a steadily-increasing COPD prevalence from 1991 to 1999.14 The COPD cohort included all patients with a diagnosis of COPD admitted to a VAMS hospital (N = 70,679) or seen in an outpatient clinic (N = 314,209) in fiscal year 1998. Each patient with COPD was matched to a veteran of the same age and gender who did not have a COPD diagnosis, creating a non-COPD cohort for comparison. Among all hospitalized veterans, the prevalence of coronary artery disease, congestive heart failure and atrial fibrillation were also very high (33.6%, 24.4%, and 14.3%, respectively) and significantly higher than those seen among the matched non-COPD cohort (27.1%, 13.5%, and 10.4%; p < 0.001). Among COPD outpatients, increased complications were found in every cardiovascular disease category with rate ratios that were greater than observed among inpatients. The authors concluded that cardiovascular diseases are remarkably prevalent among veterans with COPD, and their incidence is likely to increase as the veteran population ages.
High-Sensitivity C-reactive Protein
C-reactive protein (hsCRP) is a good example of a circulating biomarker observed in patients with this disease. Recent studies have shown that it is particularly associated with some phenotypes of COPD, that it is linked with cardiovascular and other comorbidities, and that it has genetic determinants.15 The use of biomarker monitoring, such as hsCRP, may support a paradigm shift for primary care osteopathic and allopathic physicians, whereby treatment of COPD would no longer be limited to relief of bronchial obstruction, but rather, address the systemic inflammation that characterizes this disease.15,16
Another research group investigated the frequency of ischemic ECG changes and its relevance in relation to clinical outcome and predictors of impaired survival in patients with COPD.17 Clinical characteristics, pulmonary function, and comorbidities were assessed in 536 patients with COPD during baseline assessment of a comprehensive pulmonary rehabilitation program. Moreover, electrocardiograms at rest were obtained for all patients. All electrocardiograms were scored independently by two cardiologists using the Minnesota scoring system. Major or minor Q or QS pattern, ST junction and segment depression, T-wave items, or left bundle branch block were considered ischemic ECG changes. One hundred thirteen patients (21%) had ischemic ECG changes. Fourty-two of 293 patients (14%) without self-reported cardiovascular comorbidities had ischemic ECG changes. In addition, patients with ischemic ECG changes had higher dyspnea grades, worse exercise performance, more systemic inflammation, and higher scores on the Charlson Comorbidity Index, BODE and ADO indexes compared to patients without ischemic ECG changes, whereas forced expiratory volume in the first second was similar. The authors concluded that ischemic ECG changes are common in patients with COPD and are also associated with poor clinical outcome – irrespective of forced expiratory volume in the first second. These results suggest an important role for cardiovascular disease in impaired survival in these patients.17
Myocardial Infarction & Stroke
Feary and colleagues also investigated the association of COPD and specific cardiovascular diagnoses.13 They found that a diagnosis of COPD was associated with a statistically-significant 5-fold increase in the odds of having had a cardiovascular co-diagnosis and a 3-fold increase in having had a stroke, compared with patients without COPD. The association of COPD with either comorbidity was strongest in younger patients (aged 35-44 years) and, in the case of the association with cardiovascular disease, strongest in patients who had never smoked.
A population study from Denmark concluded that acute myocardial infarction (AMI) is the most important comorbidity in patients with COPD.18 These researchers went on to state that AMI is the one comorbidity diagnosis with the greatest potential for treatment and prevention to improve the overall prognosis of patients with COPD.
As part of a community-based health check in Takahata, Japan, investigators performed blood pressure measurements, phlebotomy, electrocardiograms and spirometry on patients 40 years of age and older. 19 The mean FEV(1)% predicted and FVC% predicted in patients with concomitant atrial fibrillation (AF) was significantly lower than in non-AF subjects. The prevalence of AF was higher in those subjects with airflow limitation or lung restriction than in those without. Furthermore, AF prevalence was higher in those subjects with severe airflow obstruction (FEV(1)% predicted < 50) than in those who had mild or moderate airflow obstruction (FEV(1)% predicted ≥ 50). From these data, they concluded that impaired pulmonary function is an independent risk factor for AF in the Japanese general population.
Care Integration Research
As pointed out by the Canadian team of Bourbeau and Saad, every patient with COPD has to become a partner and an active participant in his own care.20 Many systematic reviews of self-management have shown positive outcomes for patients with COPD. These studies have in common some self-management interventions, including an action plan, in the event of an exacerbation of a patient’s COPD. This plan is embedded in an integrated healthcare system and oftentimes coordinated by a case manager for educational sessions and regular communication.
Their report also highlights recently-published and controversial clinical trial data that bring into question certain elements of the effectiveness of self-management programs, especially in patients with high burden of disease and comorbidities. In the end, it may be more challenging to make the patient with severe COPD a successful partner without risk of the occurrence of serious adverse events.
Finally, they mention that healthcare delivery has to be well integrated and more coherent, which means delivery consisting of a strategic alliance between all levels of care and supported by interdisciplinary teams for patients with high-risk and complex COPD. Clinical practice has to be structured to address COPD throughout the disease spectrum, which includes integration of secondary versus primary care decisions, team work, partnership, self-management and continuity of care. The osteopathic family physician is positioned as the perfect manager of this continuum of care.
Assessment & Management
One of the aims of the COPD Assessment Test (CAT) is to aid communication between the physician and patient about the burden of COPD on the patient’s life.21 The CAT is a disease-specific instrument that aids physician assessment of COPD. However, CAT does not appear to improve detection of non-COPD symptoms and comorbidities.
Some 15 years after reports first highlighted the unmet needs of people with severe COPD, there has been a paucity of robust trial evidence about interventions that can address those patient needs. There is an urgent need to develop and evaluate holistic care interventions designed to improve quality-of-life (QoL) for people with severe COPD.22
On The Horizon
Worldwide, clinicians face the task of providing millions of patients with the best possible treatment and management of COPD. Currently, management primarily involves short-term goals targeting immediate patient benefit. Although there is considerable knowledge available to assist clinicians in minimizing the current impact of COPD on patients, relatively little is known about which dominant factors – exacerbations, mortality, comorbidities and the long-term consequences of COPD – will predict future risks.
One international group proposes a new paradigm to achieve optimal COPD care based on the concept that “here-and-now goals” should be integrated with goals to improve long-term outcomes and reduce future risks.23 While knowledge on risk factors for poorer outcomes in COPD is growing and some data exist on positive effects of pharmacological interventions, information on defining the benefits of all commonly used interventions for reducing the risk of various future disease outcomes is still scarce. Greater insight is needed into the relationships between the two pillars of optimal COPD care: best current control and future risk reduction. This broader approach to disease management should result in improved care for every patient with COPD now and into the future. Osteopathic and allopathic family medicine physicians are positioned to directly contribute to that broad approach.
The pathology of COPD comes with high health, social and economic impact. Patients with COPD also present with high comorbidity to offices, hospitals and clinics. As a consequence, stratification of patients with COPD should take into consideration the contributions comorbidity adds to the burden of illness in addition to the degree of obstruction. The clinical practice guidelines target isolated diseases and do not link the negative impact of comorbidities. Moreover, the healthcare delivery models based on disease management offer a poor response to the comorbidity issues and tend to fragment the delivery of patient care.24 In addition, emerging healthcare models based on tele-monitoring and self-management facilitate delivery of a 21st Century patient-centered medical home model for chronically-ill patients.25 There is a need for improving the diagnosis of COPD in family practices, and clinical practice guidelines need to be reviewed and rendered patient-centric rather than disease-oriented.26 Comorbidity poses an ongoing challenge for the care of patients with COPD, and therefore studies are needed that will help specify these different patient profiles.
Ken Korber is the education director for the American College of Osteopathic Family Physicians (ACOFP) and the COPD Alliance.
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