Elsevier

Translational Research

Volume 162, Issue 4, October 2013, Pages 237-251
Translational Research

In-Depth Review: Unraveling the Complexity of COPD
Review Article
Chronic obstructive pulmonary disease and cardiovascular disease

https://doi.org/10.1016/j.trsl.2013.05.001Get rights and content

Chronic obstructive pulmonary disease (COPD) is an inflammatory disease of the lung associated with progressive airflow limitation and punctuated by episodes of acute exacerbation. There is growing recognition that the inflammatory state associated with COPD is not confined to the lungs but also involves the systemic circulation and can impact nonpulmonary organs. Epidemiologic and mechanistic studies indicate that COPD is associated with a high frequency of coronary artery disease, congestive heart failure and cardiac arrhythmias, independent of shared risk factors. Possible pathways include complex interrelationships between chronic low-grade systemic inflammation and oxidative stress as well as shared risk factors such as age, cigarette smoking, and environmental pollutants. In this review, we provide an overview of the epidemiologic data linking COPD with cardiovascular disease, comment on the interrelationships among COPD, inflammation, and cardiovascular disease, and highlight diagnostic and therapeutic challenges.

Section snippets

Epidemiology

COPD is a common disease that affects 5%–10% of the population in the United States.6 The age-adjusted prevalence rate for CAD in the United States is 6%,7 and about 1.7% of the population has CHF.8 With the aging population and increasing longevity, it is not surprising that many of these chronic diseases coexist. However, a number of cardiovascular conditions have been reported to occur with a greater frequency in patients with COPD than in the general population, including atherosclerosis,

Pathophysiology of Cardiovascular Disease

Airflow obstruction and COPD are associated independently with cardiovascular mortality as well as an increased incidence of CAD, CHF, and arrhythmias, although the underlying mechanisms remain unclear and the presence of shared risk factors does not explain these observations completely. In addition to the common demographic and behavioral risks, it appears that multiple pathobiologic pathways may contribute to the development of both progressive COPD and CVD. It is important to note that the

Aging and senescence

Because both COPD and CAD have higher prevalence with advanced age, it is tempting to think of both as part of the aging process. The prevalence of COPD increases with increasing age and is about 6-fold higher in subjects older than 70 years compared with those 40 years old–49 years old.45 Similarly, the prevalence of CVD increases with age, and CAD is 17 times more prevalent in subjects older than 65 years than those 18 years–44 years.7 In the original Framingham cohort, the prevalence of CHF

Atherosclerosis and inflammation

The most important common pathophysiological process in CAD, CVA, and PVD is atherosclerosis, and it is now well established that atherosclerosis is an inflammatory condition.73 A detailed discussion of mechanisms of atherogenesis is outside the scope of this article; however, injury of the endothelium results in the initiation of a cascade of events in which multiple inflammatory and adhesion molecules, leukocytes, platelets, and macrophages interact with the endothelium to promote recruitment

Coronary ischemia

The most important risk factor for CHF in population studies is CAD, with a population-attributable risk of 61.6%.133 With accelerated atherosclerosis and CAD in COPD, it stands to reason that CAD might be the most plausible link to explain the high rates of CHF observed in patients with COPD. There is also emerging evidence that myocardial ischemia may contribute to diastolic dysfunction in COPD.134 In addition, activation of RAS might have a role in the pathogenesis of cardiac dysfunction in

Pathophysiology of Cardiac Arrhythmias

The mechanisms underlying cardiac arrhythmias in patients with COPD are likely multiple. Patients with COPD have hypoxemia, hypercarbia, and respiratory acidosis—all known precipitants of arrhythmias.41, 44 These tend to occur in later stages of the disease or during acute exacerbations. COPD is also associated with autonomic neuropathy, even in milder stages of the disease,143, 144 and its presence has been associated with a prolonged QTc interval and increased risk of ventricular arrhythmias.

Clinical Manifestations and Diagnosis

COPD and CHF share common symptoms such as dyspnea, cough, wheezing, and sometimes nocturnal cough and paroxysmal nocturnal dyspnea.29 Peripheral edema can be seen in both CHF and cor pulmonale resulting from lung disease, and exertional dyspnea is also a symptom of CAD. In a patient already diagnosed with one of these conditions, the symptoms of the other are frequently overlooked.20, 146 In most circumstances, differentiation of these 2 entities can be achieved if history and physical

Impact of CVD on COPD

The presence of CVD is a major risk factor for poor outcomes in COPD. The Tucson Epidemiologic Study of Airways Obstructive Disease showed that CVD causes more than half the mortality in COPD, including those with severe airflow obstruction.151 There is also evidence that the risk of acute vascular events is particularly high during acute exacerbations. Donaldson et al152 showed that the risk of risk of myocardial infarction 1 day–5 days after an exacerbation increased 2.3-fold, and subtle

Medication Interactions

β-Agonist and anticholinergic therapy is a vital part of the armamentarium of medications to treat COPD, and it has been debated whether these agents increase the risk of CVD events. A nested case-control study involving 6018 subjects with COPD from the Saskatchewan Cohort Study found that the rate of arrhythmia was elevated with the new use of ipratropium (RR, 2.4; 95% CI, 1.4–4.0) and of long-acting β-agonists (RR, 4.5; 95% CI, 1.4–14.4). The researchers did not find an elevated risk with

Acute Exacerbations

The pathophysiological pathways associated with stable COPD appear to be intensified during acute exacerbations. This is evidenced by higher levels of pulmonary and systemic inflammation, oxidative stress, and lung hyperinflation.195, 196, 197 These factors likely result in accentuation of the previously mentioned cardiovascular effects, with a greater risk of coronary insufficiency, plaque rupture, and heart failure. Donaldson et al152 showed that the risk of myocardial infarction 1 day–5 days

Future

Therapy for COPD with existing medications targeting the lung may not be enough to improve outcomes. Although it is possible that controlling pulmonary inflammation may have salutary effects on systemic inflammation and its consequences, there is also a need to target CVD. Prospective longitudinal and randomized controlled trials are needed urgently to compare outcomes with cardiovascular drugs in COPD. One such study, the Simvastatin Therapy for Moderate and Severe COPD (NCT01061671) is

Summary

COPD is associated with a high frequency of CAD, CHF, and arrhythmias, in excess of that seen in matched control subjects. This seems to stem from chronic, low-grade systemic inflammation; oxidative stress; and multiple other mechanisms, including shared risk factors. Drugs used for COPD can cause arrhythmias and may increase cardiovascular mortality. Additional studies are needed to obtain safety data in this high-risk population. On the other hand, multiple cardiovascular medications seem to

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    Conflict of Interest: M. T. Dransfield has served as a consultant to Boehringer Ingelheim, GlaxoSmithKline, and Ikaria, and his institution has received research support from the National Institutes of Health, Aeris, Astra Zeneca, Boehringer Ingelheim, Boston Scientific, Centocor, Forest, GlaxoSmithKline, Ikaria, Medimmune, Otsuka, and Pfizer. S. P. Bhatt has no conflicts of interest to declare pertinent to the content of this article. Both authors have read the journal's policy on disclosure of potential conflicts of interest.

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