Chest
Volume 143, Issue 3, March 2013, Pages 798-807
Journal home page for Chest

Translating Basic Research into Clinical Practice
Cardiovascular Disease in COPD: Mechanisms

https://doi.org/10.1378/chest.12-0938Get rights and content

It is now well established that cardiovascular disease contributes significantly to both morbidity and mortality in COPD. Shared risk factors for cardiovascular disease and COPD, such as smoking, low socioeconomic class, and a sedentary lifestyle contribute to the natural history of each of these conditions. However, it is now apparent that alternative, novel mechanisms are involved in the pathogenesis of cardiovascular disease, and these may play an important role in driving the increased cardiovascular risk associated with COPD. In this article, we discuss the potential mechanisms that link COPD to an increased risk of cardiovascular disease.

Section snippets

Traditional Risk Factors

Smoking is the causative factor in the majority of individuals with COPD and is a causative factor in the development of coronary artery disease. It is, therefore, difficult to show in a COPD population that the increased risk of cardiovascular disease is due to COPD alone because COPD and smoking are inextricably linked. It is also very difficult to correct for cigarette smoke exposure statistically in studies. It seems likely, then, that cigarette smoke plays an important role in the

Systemic Inflammation

It is well recognized that COPD is associated with not only pulmonary but also systemic inflammation. In a systematic review of 14 original studies, Gan and coworkers7 demonstrated that levels of systemic inflammatory markers, including blood leukocyte count, C-reactive protein (CRP), IL-6, and fibrinogen, were elevated in patients with COPD compared with smoking control subjects. This systemic inflammation increases with disease severity8 and is associated with increased mortality.9 It has

Future Directions

Research examining the mechanisms of cardiovascular disease in COPD is at an early stage. Although COPD is associated with a number of measures of cardiovascular risk and associated with mediators of cardiovascular disease, atherosclerosis, and thrombosis, it is still unclear whether these markers play a specific role in the pathogenesis or are epiphenomena. Although we are closer to uncovering the causative mechanisms for cardiovascular disease in COPD, more work is required to elucidate these.

Conclusion

A number of putative mechanisms have been proposed that link coronary heart disease and COPD (Fig 1). Further elucidation of these mechanisms should provide novel targets for treatment of both the lung and the cardiovascular manifestations of COPD.

Acknowledgments

Financial/nonfinancial disclosures: The authors have reported to CHEST the following conflicts of interest: Prof MacNee has acted in an advisory capacity for GlaxoSmithKline plc; Pfizer, Inc; Novartis AG; and Almirall, SA. He has received payment from GlaxoSmithKline plc and Pfizer, Inc, for research programs and clinical activities and has received payments from Boehringer Ingelheim GmbH, GlaxoSmithKline plc, AstraZeneca, Novartis AG, and Janssen Pharmaceuticals, Inc, to travel to meetings and

References (119)

  • MC Corretti et al.

    Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force

    J Am Coll Cardiol

    (2002)
  • C Vlachopoulos et al.

    Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis

    J Am Coll Cardiol

    (2010)
  • CE Bolton et al.

    Aortic calcification, arterial stiffness and bone mineral density in patients with COPD

    Artery Res

    (2011)
  • N Yokohori et al.

    Increased levels of cell death and proliferation in alveolar wall cells in patients with pulmonary emphysema

    Chest

    (2004)
  • SW Brouilette et al.

    Telomere length, risk of coronary heart disease, and statin treatment in the West of Scotland Primary Prevention Study: a nested case-control study

    Lancet

    (2007)
  • DW Mapel et al.

    Trends and cardiovascular co-morbidities of COPD patients in the Veterans Administration Medical System, 1991-1999

    COPD

    (2005)
  • DD Sin et al.

    Chronic obstructive pulmonary disease as a risk factor for cardiovascular morbidity and mortality

    Proc Am Thorac Soc

    (2005)
  • NR Anthonisen et al.

    Hospitalizations and mortality in the Lung Health Study

    Am J Respir Crit Care Med

    (2002)
  • H Iwamoto et al.

    Airflow limitation in smokers is associated with subclinical atherosclerosis

    Am J Respir Crit Care Med

    (2009)
  • DM Mannino et al.

    Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD

    Eur Respir J

    (2008)
  • WQ Gan et al.

    Association between chronic obstructive pulmonary disease and systemic inflammation: a systematic review and a meta-analysis

    Thorax

    (2004)
  • JP de Torres et al.

    C-reactive protein levels and clinically important predictive outcomes in stable COPD patients

    Eur Respir J

    (2006)
  • M Dahl et al.

    C-reactive protein as a predictor of prognosis in chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2007)
  • A Agustí

    Systemic effects of chronic obstructive pulmonary disease: what we know and what we don't know (but should)

    Proc Am Thorac Soc

    (2007)
  • A Agustí et al.

    Persistent systemic inflammation is associated with poor clinical outcomes in COPD: a novel phenotype

    PLoS ONE

    (2012)
  • BR Celli et al.

    Inflammatory biomarkers improve clinical prediction of mortality in chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2012)
  • JR Hurst et al.

    Use of plasma biomarkers at exacerbation of chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2006)
  • PM Ridker et al.

    Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events

    N Engl J Med

    (2002)
  • DD Sin et al.

    Serum PARC/CCL-18 concentrations and health outcomes in chronic obstructive pulmonary disease

    Am J Respir Crit Care Med

    (2011)
  • AO Kraaijeveld et al.

    CC chemokine ligand-5 (CCL5/RANTES) and CC chemokine ligand-18 (CCL18/PARC) are specific markers of refractory unstable angina pectoris and are transiently raised during severe ischemic symptoms

    Circulation

    (2007)
  • PM Ridker et al.

    Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein

    N Engl J Med

    (2008)
  • PM Ridker et al.

    C-reactive protein levels and outcomes after statin therapy

    N Engl J Med

    (2005)
  • PS Sever et al.

    Evaluation of C-reactive protein prior to and on-treatment as a predictor of benefit from atorvastatin: observations from the Anglo-Scandinavian Cardiac Outcomes Trial

    Eur Heart J

    (2012)
  • JR Hurst et al.

    Mechanism of statin-associated mortality reduction in COPD

    Chest

    (2007)
  • JA Aviña-Zubieta et al.

    Risk of cardiovascular mortality in patients with rheumatoid arthritis: a meta-analysis of observational studies

    Arthritis Rheum

    (2008)
  • MJL Peters et al.

    EULAR evidence-based recommendations for cardiovascular risk management in patients with rheumatoid arthritis and other forms of inflammatory arthritis

    Ann Rheum Dis

    (2010)
  • PH Brekke et al.

    Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation

    Eur Respir J

    (2008)
  • AD Høiseth et al.

    Elevated high-sensitivity cardiac troponin T is associated with increased mortality after acute exacerbation of chronic obstructive pulmonary disease

    Thorax

    (2011)
  • P Libby et al.

    Pathophysiology of coronary artery disease

    Circulation

    (2005)
  • S Verma et al.

    Endothelin antagonism and interleukin-6 inhibition attenuate the proatherogenic effects of C-reactive protein

    Circulation

    (2002)
  • ET Yeh et al.

    C-reactive protein: linking inflammation to cardiovascular complications

    Circulation

    (2001)
  • M Torzewski et al.

    C-reactive protein in the arterial intima: role of C-reactive protein receptor-dependent monocyte recruitment in atherogenesis

    Arterioscler Thromb Vasc Biol

    (2000)
  • SK Venugopal et al.

    Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells

    Circulation

    (2002)
  • S Devaraj et al.

    C-reactive protein increases plasminogen activator inhibitor-1 expression and activity in human aortic endothelial cells: implications for the metabolic syndrome and atherothrombosis

    Circulation

    (2003)
  • G Luc et al.

    C-reactive protein, interleukin-6, and fibrinogen as predictors of coronary heart disease: the PRIME Study

    Arterioscler Thromb Vasc Biol

    (2003)
  • SM Boekholdt et al.

    IL-8 plasma concentrations and the risk of future coronary artery disease in apparently healthy men and women: the EPIC-Norfolk prospective population study

    Arterioscler Thromb Vasc Biol

    (2004)
  • PM Ridker et al.

    Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men

    Circulation

    (2000)
  • JM Coulson et al.

    Excessive aortic inflammation in chronic obstructive pulmonary disease: an 18F-FDG PET pilot study

    J Nucl Med

    (2010)
  • C Alessandri et al.

    Hypercoagulability state in patients with chronic obstructive pulmonary disease

    Thromb Haemost

    (1994)
  • J-I Ashitani et al.

    Elevated plasma procoagulant and fibrinolytic markers in patients with chronic obstructive pulmonary disease

    Intern Med

    (2002)
  • Cited by (0)

    Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.

    View full text