Articles
Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis

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Summary

Background

Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disorder associated with increased comorbid prevalence of cardiovascular diseases. We aimed to quantify the magnitudes of association between overall and specific types of cardiovascular disease, major cardiovascular risk factors, and COPD.

Methods

We searched Cochrane, Medline, and Embase databases for studies published between Jan 1, 1980, and April 30, 2015, on the prevalence of cardiovascular disease and its risk factors in patients with COPD versus matched controls or random samples from the general public. We assessed associations with random-effects meta-analyses. We studied heterogeneity and biases with random-effects meta-regressions, jackknife sensitivity analyses, assessment of funnel plots, and Egger tests.

Findings

We identified 18 176 unique references and included 29 datasets in the meta-analyses. Compared with the non-COPD population, patients with COPD were more likely to be diagnosed with cardiovascular disease (odds ratio [OR] 2·46; 95% CI 2·02–3·00; p<0·0001), including a two to five times higher risk of ischaemic heart disease, cardiac dysrhythmia, heart failure, diseases of the pulmonary circulation, and diseases of the arteries. Additionally, patients with COPD reported hypertension more often (OR 1·33, 95% CI 1·13–1·56; p=0·0007), diabetes (1·36, 1·21–1·53; p<0·0001], and ever smoking (4·25, 3·23–5·60; p<0·0001). The associations between COPD and these cardiovascular disease types and cardiovascular disease risk factors were consistent and valid across studies. Enrolment period, age, quality of data, and COPD diagnosis partly explained the heterogeneity.

Interpretation

The coexistence of COPD, cardiovascular disease, and major risk factors for cardiovascular disease highlights the crucial need for the development of strategies to screen for and reduce cardiovascular risks associated with COPD.

Funding

Canadian Institutes of Health Research.

Introduction

Chronic obstructive pulmonary disease (COPD) is characterised by progressive and partially irreversible airflow limitation, abnormal inflammatory response in the airways, and systemic manifestations.1 As the third leading cause of death worldwide,2 COPD imposes substantial economic and human burdens to both individuals and societies.3, 4 Management of the disease is often complicated by the presence of comorbidities,5 which have been widely recognised as an important component of COPD.6 Cardiovascular comorbidities are one of the most frequent systemic manifestations that have the biggest effect in patients with COPD,1, 7 contributing substantially to disease progression, clinical outcomes, mortality, and resource use.8, 9, 10

Understanding the association between COPD and cardiovascular disease has important implications for disease management, such as targeted treatments and cautions about drug usage. Independent studies have shown a significantly increased risk of cardiovascular disease in patients with COPD, and this was summarised in a recent narrative review.11 However, no previous study has formally quantified the magnitude of the increased risk using quantitative evidence synthesis. Furthermore, the association between cardiovascular risk factors and COPD is not well understood.

With this in mind, we aimed to work out the magnitude of the association between cardiovascular disease and COPD, and between cardiovascular risk factors and COPD in patients with COPD compared with the general population by doing a meta-analysis of observational studies; and to assess the validity of association estimates and potential sources of heterogeneity with modern statistical approaches.

Section snippets

Search strategies

JT and WC independently searched the Cochrane Database of Systematic Reviews, Medline, and Embase databases to identify primary studies and reviews related to the prevalence of cardiovascular diseases in COPD published between Jan 1, 1980, and April 30, 2015 (appendix). The following search terms were used in combination: “chronic obstructive pulmonary disease”, “prevalence”, and “comorbidities”. A sensitive search strategy was developed that included both subject and keyword terms for Medline,

Results

Our literature search and review of reference lists initially identified 18 176 articles. 18 087 articles were subsequently excluded; figure 1 shows the reasons for exclusion. Our meta-analysis included 29 datasets from 27 unique studies.17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43 Of the studies included in the meta-analysis, Agarwal and colleages17 reported projected prevalence estimates instead of recorded prevalence. The studies

Discussion

To update and extend the qualitative review by Müllerova and colleagues,11 we quantified the magnitude of risk of cardiovascular disease and risk factor outcomes in COPD through a formal meta-analysis. We found a nearly 2·5 times increased risk of cardiovascular disease overall, a two to five times higher risk of major cardiovascular disease types (ischaemic heart disease, cardiac dysrhythmia, heart failure, diseases of the pulmonary circulation, and arterial diseases), roughly one-third higher

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    These authors contributed equally to this work

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