Unraveling the Relationship Between COPD and Stroke

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Pulmonologists and neurologists should work together to improve care for patients with stroke.
Pulmonologists and neurologists should work together to improve care for patients with stroke.

Emerging evidence suggests that chronic obstructive pulmonary disease (COPD) could be a risk factor for stroke.1,2 COPD is the fourth leading cause of death worldwide, and up to 80% of patients with the disease have at least one comorbidity.2 Many of the commonalities between COPD and stroke portend poor outcomes for patients with both diseases: age, indoor and outdoor pollution exposure, tobacco smoke, asthma and airway hyper-reactivity, and lower socioeconomic status.2

One of the preventable confounders for COPD and stroke risk is smoking, which contributes to fatal events and stroke.2 Indeed, in a systematic review of 30 studies, Ann D. Morgan, MSc, of the National Heart and Lung Institute at the Imperial College London, and colleagues, found that COPD increased the prevalence and incidence of stroke. Even when the researchers adjusted for smoking, COPD was still a risk factor for stroke.1

In a recent interview with Pulmonology Advisor, coauthor Jennifer Quint, MD, clinical senior lecturer in respiratory epidemiology at the National Heart and Lung Institute in London, United Kingdom, explained, “Independently of COPD, smoking increases the risk of having a stroke. There is something about having COPD, too, though, that also increases the risk. This may be linked to inflammation that occurs as a result of having COPD.”

“Tobacco smoking is a risk factor both for ischemic stroke and COPD. Patients who are hospitalized for either condition should receive intensive tobacco cessation education and support both during the hospital and as they make the transition to their postdischarge residence,” neurologist Dawn M. Bravata, MD, of Indiana University School of Medicine and the Richard L. Roudebush VA Medical Center in Indianapolis, told Pulmonology Advisor.

Exacerbations and Comorbidities That Increase Stroke Risk

Current and former smokers with a 10-pack-year history were included in a cohort study of 16,485 patients with COPD (age range, 40-80 years) with cardiovascular disease (CVD) or multiple CVD risk factors to determine whether acute exacerbations of COPD (AECOPD) increased the risk for CV events.3 Kunisaki and colleagues found that when people with COPD needed additional antibiotics or corticosteroids, they were at higher risk of having a CV event, including CV death, myocardial infarction (MI), unstable angina, transient ischemic attack, or stroke 30 days after the exacerbation (hazard ratio, 3.8; 95% CI, 2.7-5.5). For those who required hospitalization, the risk more than doubled 30 days after AECOPD (hazard ratio, 9.9; 95% CI, 6.6-14.9).3

“We still do not know how to prevent these strokes, so we need more studies to determine what specific medications or changes in lifestyle/environment we should be recommending. For now, it makes sense to pursue a healthy lifestyle (exercise, smoking cessation, and a healthy diet) and management of general medical issues like blood pressure and cholesterol in patients with COPD,” advised lead author and pulmonologist Ken M. Kunisaki, MD, MS, associate professor of medicine at the University of Minnesota and medical director of the COPD case management program at the Minneapolis VA Health Care System.

To determine which patients with COPD have even an higher risk than the general population of those with COPD, Rothnie and colleagues categorized AECOPD by severity in a self-controlled case series study.4 The participants included 5860 adults with COPD who had a first MI (n=2850) or ischemic stroke (n=3010) and at least one AECOPD.4 As they theorized, the researchers found a dose-response relationship between the severity of the AECOPD and the risk for MI or stroke 91 days after the acute exacerbation.4

For patients who had a severe AECOPD, the incidence rate ratio (IRR) was 2.58 (95% CI, 2.26-2.95) for MI and 1.97 (95% CI, 1.66-2.33) for ischemic stroke.4 Patients with a moderate AECOPD had slightly lower risk for MI (IRR 1.58; 95% CI, 1.46-1.71) and ischemic stroke (IRR 1.45; 95% CI, 1.33-1.57).4

Which Stroke Subtypes Are More Prevalent With COPD?

Orea-Tejeda and colleagues conducted a case-control study of 162 patients with COPD and determined that right ventricular heart failure increased the risk for ischemic stroke (odds ratio, 3.03; 95% CI, 1.13-10.12; P =.044).5 While the researchers included only ischemic stroke in the study, coauthor Dulce González-Islas, PhD, from the Heart Failure and Respiratory Distress Clinic at the Instituto Nacional de Enfermedades Respiratorias “Ismael Cosío Villegas” in Mexico City, confirmed what she had observed in the COPD literature: “The information from several trials on stroke in patients with COPD are usually the ischemic (thrombotic) type.”

However, pulmonologist Dr Kunisaki offered another perspective: “A few studies looked at stroke subtypes in COPD and found that, compared [with] people without COPD, those with COPD had a higher risk for both ischemic strokes and hemorrhagic strokes. However, we cannot be very confident about stroke subtypes in COPD because there are not a lot of data about this.”

Oxygen Therapy for Comorbid Stroke and COPD

Clinicians and researchers are still attempting to demystify the associations between COPD and stroke, including hypoxia, systemic inflammation, hypercapnia, and oxidative stress.2 Whereas some studies extoll the benefits of oxygen therapy for COPD, others have suggested that hypoxia and hypercapnia or hypercapnia alone may offer neuroprotection to patients with stroke.2

Pulmonologist Dr Quint cautioned, “Some people with COPD are at risk of having increased carbon dioxide levels if they receive high doses of oxygen, so sometimes oxygen therapy has to be closely monitored in people with COPD. This is not the case in all people with COPD, though, and some patients can tolerate high doses of oxygen therapy.”

Interdisciplinary Collaboration Is Essential

A Veterans Health Administration study highlighted the critical need for interdisciplinary health teams to better manage patients after an ischemic stroke and after an MI (N=40,230).6 Bravata and colleagues found that more patients who had an MI (n=4169) received successful hypertension treatment compared with 2127 patients after stroke (77%; 95% CI, 0.75-0.78 vs 64%; 95% CI, 0.62-0.67; P <.0001, respectively). Although hypertension control should be the foundation of secondary stroke prevention, the researchers theorized that cardiologists may be more comfortable titrating hypertension medications compared with neurologists.6

Lead author Dr Bravata explained how pulmonologists and neurologists might improve care for patients with stroke: “The 2 specialties have a shared interest in the diagnosis and management of sleep apnea. The American Heart Association/American Stroke Association 2014 Stroke Prevention Guidelines7 recommend the diagnosis and treatment of sleep apnea among patients with cerebrovascular disease. Creating systems of care to provide for the rapid assessment and management of stroke and transient ischemic attack [in] patients with sleep apnea should be a focus of collaboration for pulmonologists and neurologists.”

Pulmonologist Dr Quint offered additional pearls: “We know people with COPD are less likely to receive beta-blockers because they have COPD, and yet guidelines for conditions such as heart failure or in people who have had a heart attack state they should receive them. We also need to be thinking about the patients we see as individuals, and not just focus on the condition we are treating.”

Summary & Clinical Applicability

COPD is a risk factor for CVD, but what is less understood is the relationship between COPD and stroke. Researchers are still unraveling the relationship between the 2 conditions and how treatment for COPD may mitigate stroke risk.

Limitations & Disclosures

None.

References

1. Morgan AD, Sharma C, Rothnie KJ, Potts J, Smeeth L, Quint JK. Chronic obstructive pulmonary disease and the risk of stroke. Ann Am Thorac Soc. 2017;14(5):754-765.

2. Corlateanu A, Covantev S, Mathioudakis AG, Botnaru V, Cazzola M, Siafakas N. Chronic obstructive pulmonary disease and stroke [published online May 10, 2018]. COPD. doi:10.1080/15412555.2018.1464551

3. Kunisaki KM, Dransfield MT, Anderson JA, et al. Exacerbations of chronic obstructive pulmonary disease and cardiac events: a post hoc cohort analysis from the SUMMIT randomized clinical trial. Am J Respir Crit Care Med. 2018;198(1):51-57.

4. Rothnie KJ, Connell O, Müllerová H, et al. Myocardial infarction and ischaemic stroke following exacerbations of chronic obstructive pulmonary disease [published online May 3, 2018]. Ann Am Thorac Soc. doi:10.1513/AnnalsATS.201710-815OC

5. Orea-Tejeda A, Bozada-Gutiérrez K, Pineda-Juárez J, et al. Right heart failure as a risk for stroke in patients with chronic obstructive pulmonary disease: a case-control study. Stroke Cerebrovasc Dis. 2017;26(12):2988-2993.

6. Bravata DM, Daggy J, Brosch J, et al. Comparison of risk factor control in the year after discharge for ischemic stroke versus acute myocardial infarction. Stroke. 2018;49(2):296-303.

7. Kernan WN, Ovbiagele B, Black HR, et al; for the American Heart Association Stroke Council, Council on Cardiovascular and Stroke Nursing, Council on Clinical Cardiology, and Council on Peripheral Vascular Disease. Guidelines for the prevention of stroke in patients with stroke and transient ischemic attack: a guideline for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014;45(7):2160-2236.

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