Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial

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Abstract

Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) are common, associated with acute inflammation, and may increase subsequent cardiovascular disease (CVD) risk.

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Inflammatory markers and the risk of coronary heart disease in men and women.

Jennifer K Pai, Tobias Pischon, Jing Ma … (2004)

Few studies have simultaneously investigated the role of soluble tumor necrosis factor alpha (TNF-alpha) receptors types 1 and 2 (sTNF-R1 and sTNF-R2), C-reactive protein, and interleukin-6 as predictors of cardiovascular events. The value of these inflammatory markers as independent predictors remains controversial. We examined plasma levels of sTNF-R1, sTNF-R2, interleukin-6, and C-reactive protein as markers of risk for coronary heart disease among women participating in the Nurses' Health Study and men participating in the Health Professionals Follow-up Study in nested case-control analyses. Among participants who provided a blood sample and who were free of cardiovascular disease at baseline, 239 women and 265 men had a nonfatal myocardial infarction or fatal coronary heart disease during eight years and six years of follow-up, respectively. Using risk-set sampling, we selected controls in a 2:1 ratio with matching for age, smoking status, and date of blood sampling. After adjustment for matching factors, high levels of interleukin-6 and C-reactive protein were significantly related to an increased risk of coronary heart disease in both sexes, whereas high levels of soluble TNF-alpha receptors were significant only among women. Further adjustment for lipid and nonlipid factors attenuated all associations; only C-reactive protein levels remained significant. The relative risk among all participants was 1.79 for those with C-reactive protein levels of at least 3.0 mg per liter, as compared with those with levels of less than 1.0 mg per liter (95 percent confidence interval, 1.27 to 2.51; P for trend <0.001). Additional adjustment for the presence or absence of diabetes and hypertension moderately attenuated the relative risk to 1.68 (95 percent confidence interval, 1.18 to 2.38; P for trend = 0.008). Elevated levels of inflammatory markers, particularly C-reactive protein, indicate an increased risk of coronary heart disease. Although plasma lipid levels were more strongly associated with an increased risk than were inflammatory markers, the level of C-reactive protein remained a significant contributor to the prediction of coronary heart disease. Copyright 2004 Massachusetts Medical Society.

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Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease.

Mette Kjaergaard Thomsen, Morten Dahl, Peter Lange … (2012)

Patients with chronic obstructive pulmonary disease (COPD) have evidence of systemic inflammation that may be implicated in the development of comorbidities. To test the hypothesis that elevated levels of three inflammatory biomarkers are associated with increased risk of comorbidities in COPD. We examined 8,656 patients with COPD from two large Danish population studies and during a median 5 years' follow-up recorded hospital admissions due to major comorbidities as endpoints. We measured baseline C-reactive protein (CRP), fibrinogen, and leukocyte count, and recorded admissions due to ischemic heart disease, myocardial infarction, heart failure, type II diabetes, lung cancer, pneumonia, pulmonary embolism, hip fracture, and depression for all participants. Multifactorially adjusted risk of ischemic heart disease was increased by a factor of 2.19 (95% confidence interval, 1.48-3.23) in individuals with three biomarkers elevated (CRP > 3 mg/L, fibrinogen > 14 μmol/L, and leukocyte count > 9 × 10(9)/L) versus individuals with all three biomarkers at or below these limits. Corresponding hazard ratios were 2.32 (1.34-4.04) for myocardial infarction, 2.63 (1.71-4.04) for heart failure, 3.54 (2.03-6.19) for diabetes, 4.00 (2.12-7.54) for lung cancer, and 2.71 (2.03-3.63) for pneumonia. There were no consistent differences in risk of pulmonary embolism, hip fracture, or depression as a function of these three biomarkers. Simultaneously elevated levels of CRP, fibrinogen, and leukocyte count are associated with a two- to fourfold increased risk of major comorbidities in COPD. These biomarkers may be an additional tool for clinicians to conduct stratified management of comorbidities in COPD.

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The Study to Understand Mortality and Morbidity in COPD (SUMMIT) study protocol.

Jorgen Vestbo, Julie Anderson, Robert D Brook … (2013)

Chronic obstructive pulmonary disease (COPD) often coexists with other chronic diseases and comorbidities that can markedly influence patients' health status and prognosis. This is particularly true for cardiovascular disease (CVD). However, there have been no trials assessing the effect of COPD medications on CVD in patients with both diseases. The "Study to Understand Mortality and Morbidity in COPD" (SUMMIT) aims at determining the impact of fluticasone furoate/vilanterol combination and the individual components on the survival of patients with moderate COPD and either a history of CVD or at increased risk for CVD. SUMMIT is a multicentre, randomised, double-blind, parallel-group, placebo-controlled trial of 16 000 patients with moderate COPD randomly assigned to once daily treatment with fluticasone furoate/vilanterol (100/25 μg), fluticasone furoate (100 μg), vilanterol (25 μg) or matched placebo; mortality is the primary end-point. The study is an event-driven trial powered by the comparison of furoate/vilanterol versus placebo. Secondary end-points are decline in forced expiratory volume in 1 s and effect on a composite cardiovascular end-point. This article describes the design of the SUMMIT study.

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Author and article information

Journal

Title: American Journal of Respiratory and Critical Care Medicine

Abbreviated Title: Am J Respir Crit Care Med

Publisher: American Thoracic Society

ISSN (Print): 1073-449X

ISSN (Electronic): 1535-4970

Publication date Created: July 2018

Publication date (Print): July 2018

Volume: 198

Issue: 1

Pages: 51-57

Affiliations

[1 ]Minneapolis Veterans Affairs Health Care System, Minneapolis, Minnesota

[2 ]University of Minnesota, Minneapolis, Minnesota

[3 ]Lung Health Center, University of Alabama at Birmingham, Birmingham, Alabama

[4 ]Birmingham Veterans Affairs Medical Center, Birmingham, Alabama

[5 ]GlaxoSmithKline, Stockley Park, United Kingdom

[6 ]University of Michigan, Ann Arbor, Michigan

[7 ]University of Liverpool, Liverpool, United Kingdom

[8 ]Brigham and Women’s Hospital, Boston, Massachusetts

[9 ]GlaxoSmithKline, Research Triangle Park, North Carolina

[10 ]Veramed Ltd., Twickenham, United Kingdom

[11 ]Weill Cornell Medical College of Cornell University, New York, New York

[12 ]University of Edinburgh, Edinburgh, United Kingdom; and

[13 ]University of Manchester, Manchester, United Kingdom

Article

DOI: 10.1164/rccm.201711-2239OC

PMC ID: 6913068

PubMed ID: 29442524

SO-VID: d9021b18-4afc-4869-8486-fa03576c9372

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Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial

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Most cited references 7

Inflammatory markers and the risk of coronary heart disease in men and women.

Inflammatory biomarkers and comorbidities in chronic obstructive pulmonary disease.

The Study to Understand Mortality and Morbidity in COPD (SUMMIT) study protocol.

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Affiliations

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History

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