Cardiovascular Diseases in COPD: From Diagnosis and Prevalence to Therapy

Chronic obstructive pulmonary disease (COPD) is considered one of the leading causes of mortality. Cardiovascular comorbidities are diagnosed often in COPD patients, not only because of the common risk factors these two diseases share, but also because of the systemic inflammation which characterizes COPD and has deleterious effects in the cardiovascular system. The comorbid cardiovascular diseases in COPD result in several difficulties in the holistic treatment of these patients and affect outcomes such as morbidity and mortality. Several studies have reported that mortality from cardiovascular causes is common among COPD patients, while the risk for acute cardiovascular events increases during COPD exacerbations and remains high for a long time even after recovery. In this review, we focus on the prevalence of cardiovascular comorbidities in COPD patients, presenting the evidence regarding the interaction of the pathophysiological pathways which characterize each disease. Furthermore, we summarize information regarding the effects of cardiovascular treatment on COPD outcomes and vice versa. Finally, we present the current evidence regarding the impact of cardiovascular comorbidities on exacerbations, quality of life and survival of COPD patients.

[1]  J. Varga,et al.  Cardiovascular effects of exercise induced dynamic hyperinflation in COPD patients—Dynamically hyperinflated and non-hyperinflated subgroups , 2023, PloS one.

[2]  Shuliang Guo,et al.  Combination therapy with long-acting bronchodilators and the risk of major adverse cardiovascular events in patients with COPD: a systematic review and meta-analysis , 2022, European Respiratory Journal.

[3]  D. Mannino,et al.  Definition and Nomenclature of Chronic Obstructive Pulmonary Disease: Time for its Revision. , 2022, American journal of respiratory and critical care medicine.

[4]  M. Newnham,et al.  Cardiovascular disease in chronic obstructive pulmonary disease: a narrative review , 2022, Thorax.

[5]  S. Bozinovski,et al.  Chronic obstructive pulmonary disease and atherosclerosis: common mechanisms and novel therapeutics , 2022, Clinical science.

[6]  Akshay S. Desai,et al.  Impact of Chronic Obstructive Pulmonary Disease in Patients With Heart Failure With Preserved Ejection Fraction: Insights From PARAGON‐HF , 2021, Journal of the American Heart Association.

[7]  J. Wedzicha,et al.  An Updated Definition and Severity Classification of COPD Exacerbations: The Rome Proposal. , 2021, American journal of respiratory and critical care medicine.

[8]  R. Jackson,et al.  Dual versus single long‐acting bronchodilator use could raise acute coronary syndrome risk by over 50%: A population‐based nested case–control study , 2021, Journal of internal medicine.

[9]  M. Alexandrou,et al.  Endothelial Dysfunction during Acute Exacerbations of Chronic Obstructive Pulmonary Disease: A Systematic Review and Meta-Analysis , 2021, COPD.

[10]  Jinghua Yang,et al.  Association of β-blocker use with survival and pulmonary function in patients with chronic obstructive pulmonary and cardiovascular disease: a systematic review and meta-analysis , 2020, European heart journal.

[11]  T. Martín Lorenzo,et al.  Impact of non-cardiovascular comorbidities on the quality of life of patients with chronic heart failure: a scoping review , 2020, Health and Quality of Life Outcomes.

[12]  P. Dorinsky,et al.  Triple Inhaled Therapy at Two Glucocorticoid Doses in Moderate-to-Very-Severe COPD. , 2020, The New England journal of medicine.

[13]  J. Díez-Manglano,et al.  Management of the COPD Patient with Comorbidities: An Experts Recommendation Document , 2020, International journal of chronic obstructive pulmonary disease.

[14]  Y. Mao,et al.  Beta-blockers in COPD: A systematic review based on recent research. , 2020, Life sciences.

[15]  J. Díez-Manglano,et al.  Insights into Chronic Obstructive Pulmonary Disease as Critical Risk Factor for Cardiovascular Disease , 2020, International journal of chronic obstructive pulmonary disease.

[16]  Y. Shyr,et al.  Mortality of cardiovascular events in COPD patients with preceding hospitalized acute exacerbation. , 2020, Chest.

[17]  Chung-Yu Chen,et al.  Protective Effect of Statins on Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease Patients: A Nationwide Retrospective, Matched Cohort Study , 2020, Scientific Reports.

[18]  A. Bottle,et al.  Hospitalisation and mortality in patients with comorbid COPD and heart failure: a systematic review and meta-analysis , 2020, Respiratory Research.

[19]  J. Hallas,et al.  Increased risk of major adverse cardiac events following the onset of acute exacerbations of COPD , 2019, Respirology.

[20]  J. Curtis,et al.  Metoprolol for the Prevention of Acute Exacerbations of COPD. , 2019, The New England journal of medicine.

[21]  H. Watz,et al.  Prevalence of cardiac comorbidities, and their underdetection and contribution to exertional symptoms in COPD: results from the COSYCONET cohort , 2019, International journal of chronic obstructive pulmonary disease.

[22]  E. McColl,et al.  Antiplatelet therapy in the primary prevention of cardiovascular disease in patients with chronic obstructive pulmonary disease: a randomised controlled proof-of-concept trial , 2019, ERJ Open Research.

[23]  Kuang-Yao Yang,et al.  Real-world effectiveness of medications on survival in patients with COPD-heart failure overlap , 2019, Aging.

[24]  S. Bozinovski,et al.  New frontiers in the treatment of comorbid cardiovascular disease in chronic obstructive pulmonary disease , 2019, Clinical science.

[25]  Meilan K. Han,et al.  Aspirin Use and Respiratory Morbidity in COPD: A Propensity Score‐Matched Analysis in Subpopulations and Intermediate Outcome Measures in COPD Study , 2019, Chest.

[26]  A. Khashan,et al.  Statins versus placebo for people with chronic obstructive pulmonary disease. , 2019, The Cochrane database of systematic reviews.

[27]  Mohammad Hossein Khosravi,et al.  Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980–2017: a systematic analysis for the Global Burden of Disease Study 2017 , 2018, Lancet.

[28]  Austin Carter,et al.  Forecasting life expectancy, years of life lost, and all-cause and cause-specific mortality for 250 causes of death: reference and alternative scenarios for 2016–40 for 195 countries and territories , 2018, The Lancet.

[29]  K. Rabe,et al.  Cardiovascular disease and COPD: dangerous liaisons? , 2018, European Respiratory Review.

[30]  L. Smeeth,et al.  Myocardial Infarction and Ischemic Stroke after Exacerbations of Chronic Obstructive Pulmonary Disease , 2018, Annals of the American Thoracic Society.

[31]  F. Martinez,et al.  Exacerbations of Chronic Obstructive Pulmonary Disease and Cardiac Events. A Post Hoc Cohort Analysis from the SUMMIT Randomized Clinical Trial , 2018, American journal of respiratory and critical care medicine.

[32]  E. Lehman,et al.  Preexisting Conditions Determine the Occurrence of Unplanned Readmissions after Procedures for Treatment of Peripheral Arterial Disease. , 2018, Annals of vascular surgery.

[33]  Chong-Jen Yu,et al.  Comparative effects of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on the risk of pneumonia and severe exacerbations in patients with COPD , 2018, International Journal of COPD.

[34]  J. Quint,et al.  Defining the relationship between COPD and CVD: what are the implications for clinical practice? , 2018, Therapeutic advances in respiratory disease.

[35]  A. Mebazaa,et al.  Characteristics, treatments and 1‐year prognosis of hospitalized and ambulatory heart failure patients with chronic obstructive pulmonary disease in the European Society of Cardiology Heart Failure Long‐Term Registry , 2018, European journal of heart failure.

[36]  Eric A. Hoffman,et al.  A Longitudinal Cohort Study of Aspirin Use and Progression of Emphysema‐like Lung Characteristics on CT Imaging: The MESA Lung Study , 2017, Chest.

[37]  T. To,et al.  Incident diuretic drug use and adverse respiratory events among older adults with chronic obstructive pulmonary disease , 2017, British journal of clinical pharmacology.

[38]  Mph Tadahiro Goto MD,et al.  Incidence of Acute Cardiovascular Event After Acute Exacerbation of COPD , 2018, Journal of General Internal Medicine.

[39]  D. Kim,et al.  Different impacts of respiratory symptoms and comorbidities on COPD-specific health-related quality of life by COPD severity , 2017, International journal of chronic obstructive pulmonary disease.

[40]  K. Onishi Total management of chronic obstructive pulmonary disease (COPD) as an independent risk factor for cardiovascular disease. , 2017, Journal of cardiology.

[41]  S. Suissa,et al.  Concurrent use of long-acting bronchodilators in COPD and the risk of adverse cardiovascular events , 2017, European Respiratory Journal.

[42]  Megha A. Parikh,et al.  Angiotensin‐Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi‐Ethnic Study of Atherosclerosis Lung Study , 2017, Annals of the American Thoracic Society.

[43]  R. Holle,et al.  Peripheral Artery Disease and Its Clinical Relevance in Patients with Chronic Obstructive Pulmonary Disease in the COPD and Systemic Consequences‐Comorbidities Network Study , 2017, American journal of respiratory and critical care medicine.

[44]  C. Butler,et al.  Risk of cardiovascular events, arrhythmia and all-cause mortality associated with clarithromycin versus alternative antibiotics prescribed for respiratory tract infections: a retrospective cohort study , 2017, BMJ Open.

[45]  R. Wilcox,et al.  β-Blockers, heart disease and COPD: current controversies and uncertainties , 2016, Thorax.

[46]  D. Sin,et al.  Chronic Obstructive Pulmonary Disease and Cardiac Diseases. An Urgent Need for Integrated Care. , 2016, American journal of respiratory and critical care medicine.

[47]  O. Nishiyama,et al.  Influence of comorbidities on the efficacy of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease , 2016, Geriatrics & gerontology international.

[48]  Volkmar Falk,et al.  2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure , 2016, Revista espanola de cardiologia.

[49]  N. Tzanakis,et al.  Acute exacerbation of COPD: is it the “stroke of the lungs”? , 2016, International journal of chronic obstructive pulmonary disease.

[50]  R. Ferrari,et al.  Antiplatelet Treatment Reduces All-Cause Mortality in COPD Patients: A Systematic Review and Meta-Analysis , 2016, COPD.

[51]  M. Cazzola,et al.  A Systematic Review With Meta-Analysis of Dual Bronchodilation With LAMA/LABA for the Treatment of Stable COPD. , 2016, Chest.

[52]  F. Martinez,et al.  Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial , 2016, The Lancet.

[53]  J. Bourbeau,et al.  Club Cell-16 and RelB as Novel Determinants of Arterial Stiffness in Exacerbating COPD Patients , 2016, PloS one.

[54]  A. Hofman,et al.  Chronic Obstructive Pulmonary Disease and the Risk of Stroke. The Rotterdam Study. , 2016, American journal of respiratory and critical care medicine.

[55]  R. Hancox,et al.  Cardiac dysfunction during exacerbations of chronic obstructive pulmonary disease. , 2016, The Lancet. Respiratory medicine.

[56]  N. Steen,et al.  Validation of the DECAF score to predict hospital mortality in acute exacerbations of COPD , 2016, Thorax.

[57]  S. Dias,et al.  Efficacy and safety of long-acting β-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis , 2015, Thorax.

[58]  L. Ferder,et al.  Inflammation, oxidative stress and renin angiotensin system in atherosclerosis. , 2015, World journal of biological chemistry.

[59]  N. Hansel,et al.  Comorbidities and Chronic Obstructive Pulmonary Disease: Prevalence, Influence on Outcomes, and Management , 2015, Seminars in Respiratory and Critical Care Medicine.

[60]  M. Sadatsafavi,et al.  Risk of cardiovascular comorbidity in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. , 2015, The Lancet. Respiratory medicine.

[61]  N. Scichilone,et al.  Prevalence of Co-morbidities and Severity of COPD , 2015, COPD.

[62]  M. Keltai,et al.  Ticagrelor Versus Clopidogrel in Patients With Acute Coronary Syndromes and Chronic Obstructive Pulmonary Disease: An Analysis From the Platelet Inhibition and Patient Outcomes (PLATO) Trial , 2015, Journal of the American Heart Association.

[63]  L. Smeeth,et al.  Closing the mortality gap after a myocardial infarction in people with and without chronic obstructive pulmonary disease , 2015, Heart.

[64]  G. Campo,et al.  Chronic Obstructive Pulmonary Disease and Ischemic Heart Disease Comorbidity: Overview of Mechanisms and Clinical Management , 2015, Cardiovascular Drugs and Therapy.

[65]  C. Gleissner,et al.  Inflammatory therapeutic targets in coronary atherosclerosis—from molecular biology to clinical application , 2014, Front. Physiol..

[66]  J. Bourbeau,et al.  Alterations in the Expression of the NF-κB Family Member RelB as a Novel Marker of Cardiovascular Outcomes during Acute Exacerbations of Chronic Obstructive Pulmonary Disease , 2014, PloS one.

[67]  J. Hallas,et al.  Statin use and exacerbations in individuals with chronic obstructive pulmonary disease , 2014, Thorax.

[68]  M. Decramer,et al.  Withdrawal of inhaled glucocorticoids and exacerbations of COPD. , 2014, The New England journal of medicine.

[69]  Longhua Sun,et al.  Decreased CD34+ cell number is correlated with cardiac dysfunction in patients with acute exacerbation of COPD. , 2014, Heart, lung & circulation.

[70]  V. Menon,et al.  Burden of cardiovascular disease in chronic obstructive pulmonary disease. , 2014, American journal of preventive medicine.

[71]  A. Junqueira-Kipnis,et al.  Interleukin-6 and interleukin-8 blood levels’ poor association with the severity and clinical profile of ex-smokers with COPD , 2014, International journal of chronic obstructive pulmonary disease.

[72]  D. Sajkov,et al.  Pulmonary Hypertension and Right Heart Dysfunction in Chronic Lung Disease , 2014, BioMed research international.

[73]  C. Rihal,et al.  Relation of chronic obstructive pulmonary disease to atrial and ventricular arrhythmias. , 2014, The American journal of cardiology.

[74]  C. Gaudio,et al.  Right Heart Functional Changes in the Acute, Hypercapnic Exacerbations of COPD , 2014, BioMed research international.

[75]  Meilan K. Han,et al.  Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. , 2014, The New England journal of medicine.

[76]  E. Ingelsson,et al.  Differential association of chronic obstructive pulmonary disease with myocardial infarction and ischemic stroke in a nation-wide cohort. , 2014, International journal of cardiology.

[77]  J. Pépin,et al.  Arterial stiffness in COPD. , 2014, Chest.

[78]  D. Matamis,et al.  Targeting occult heart failure in intensive care unit patients with acute chronic obstructive pulmonary disease exacerbation: effect on outcome and quality of life. , 2014, Journal of critical care.

[79]  P. Laveneziana,et al.  Chronic obstructive pulmonary disease: clinical integrative physiology. , 2014, Clinics in chest medicine.

[80]  J. Connett,et al.  Club cell protein 16 and disease progression in chronic obstructive pulmonary disease. , 2013, American journal of respiratory and critical care medicine.

[81]  E. Wouters,et al.  Arterial stiffness in patients with COPD: the role of systemic inflammation and the effects of pulmonary rehabilitation , 2013, European Respiratory Journal.

[82]  W. Self,et al.  Predictors of regional variations in hospitalizations following emergency department visits for atrial fibrillation. , 2013, The American journal of cardiology.

[83]  A. Agustí,et al.  Cardiovascular comorbidity in COPD: systematic literature review. , 2013, Chest.

[84]  W. Paulus,et al.  A novel paradigm for heart failure with preserved ejection fraction: comorbidities drive myocardial dysfunction and remodeling through coronary microvascular endothelial inflammation. , 2013, Journal of the American College of Cardiology.

[85]  T. Self,et al.  The clinical and economic burden of chronic obstructive pulmonary disease in the USA , 2013, ClinicoEconomics and outcomes research : CEOR.

[86]  M. Puhan,et al.  Impact of co-morbidities on self-rated health in self-reported COPD: An analysis of NHANES 2001–2008 , 2013, COPD.

[87]  D. Au,et al.  Combination antihypertensive therapy among patients with COPD. , 2013, Chest.

[88]  A. Akram,et al.  Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies , 2013, BMJ.

[89]  W. MacNee,et al.  Cardiovascular disease in COPD: mechanisms. , 2013, Chest.

[90]  M. Puhan,et al.  Determinants of endothelial function in patients with COPD , 2013, European Respiratory Journal.

[91]  M. Ekström,et al.  Effects of cardiovascular drugs on mortality in severe chronic obstructive pulmonary disease. , 2013, American journal of respiratory and critical care medicine.

[92]  B. Celli,et al.  Comorbidities and risk of mortality in patients with chronic obstructive pulmonary disease. , 2012, American journal of respiratory and critical care medicine.

[93]  J. Soriano,et al.  Comorbidities and short-term prognosis in patients hospitalized for acute exacerbation of COPD: the EPOC en Servicios de medicina interna (ESMI) study. , 2012, Chest.

[94]  John Steer,et al.  The DECAF Score: predicting hospital mortality in exacerbations of chronic obstructive pulmonary disease , 2012, Thorax.

[95]  S. Petersen,et al.  Chronic obstructive pulmonary disease: a modifiable risk factor for cardiovascular disease? , 2012, Heart.

[96]  G. Fonarow,et al.  Clinical characteristics and outcomes of hospitalized heart failure patients with systolic dysfunction and chronic obstructive pulmonary disease: findings from OPTIMIZE‐HF , 2012, European journal of heart failure.

[97]  J. Wedzicha,et al.  The impact of ischemic heart disease on symptoms, health status, and exacerbations in patients with COPD. , 2012, Chest.

[98]  B. Beghé,et al.  Link between chronic obstructive pulmonary disease and coronary artery disease: Implication for clinical practice , 2012, Respirology.

[99]  G. Lip,et al.  Atrial fibrillation , 2012, The Lancet.

[100]  D. Mapel Insights into COPD Comorbidities from the OLIN Study and Other Large Databases , 2011, COPD.

[101]  E. Clini,et al.  Dynamic hyperinflation is associated with a poor cardiovascular response to exercise in COPD patients , 2011, Respiratory research.

[102]  Anand A. Dalal,et al.  Clinical and economic burden of patients diagnosed with COPD with comorbid cardiovascular disease. , 2011, Respiratory medicine.

[103]  Olaf Holz,et al.  Physical activity is the strongest predictor of all-cause mortality in patients with COPD: a prospective cohort study. , 2011, Chest.

[104]  M. Decramer,et al.  Risk of Nonlower Respiratory Serious Adverse Events Following COPD Exacerbations in the 4-year UPLIFT® Trial , 2011, Lung.

[105]  L. Krakoff,et al.  Glucocorticoids and cardiovascular risk factors. , 2011, Endocrinology and metabolism clinics of North America.

[106]  Dong-Bin Kim,et al.  Prognosis of heart failure patients with reduced and preserved ejection fraction and coexistent chronic obstructive pulmonary disease , 2010, European journal of heart failure.

[107]  Joseph Lindsay,et al.  Impact of chronic obstructive pulmonary disease on acute-phase outcome of myocardial infarction. , 2010, The American journal of cardiology.

[108]  R. Stockley,et al.  Systemic inflammation and comorbidity in COPD: a result of ‘overspill’ of inflammatory mediators from the lungs? Review of the evidence , 2010, Thorax.

[109]  H. Magnussen,et al.  Decreasing cardiac chamber sizes and associated heart dysfunction in COPD: role of hyperinflation. , 2010, Chest.

[110]  L. Ferreira,et al.  Bronchodilators accelerate the dynamics of muscle O2 delivery and utilisation during exercise in COPD , 2010, Thorax.

[111]  R. Hubbard,et al.  Increased risk of myocardial infarction and stroke following exacerbation of COPD. , 2010, Chest.

[112]  J. Soriano,et al.  Comorbidity and gender-related differences in patients hospitalized for COPD. The ECCO study. , 2010, Respiratory medicine.

[113]  A. Vonk-Noordegraaf The shrinking heart in chronic obstructive pulmonary disease. , 2010, The New England journal of medicine.

[114]  Y. Başaran,et al.  Acute exacerbation impairs endothelial function in patients with chronic obstructive pulmonary disease. , 2010, Turk Kardiyoloji Dernegi arsivi : Turk Kardiyoloji Derneginin yayin organidir.

[115]  R. Hopkins,et al.  Pharmacological actions of statins: potential utility in COPD , 2009, European Respiratory Review.

[116]  P. Almagro,et al.  [Causes of mortality in COPD]. , 2009, Archivos de bronconeumologia.

[117]  A. Valipour,et al.  Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease. , 2008, American journal of respiratory and critical care medicine.

[118]  B. Celli,et al.  Effects of hyperinflation on the oxygen pulse as a marker of cardiac performance in COPD , 2008, European Respiratory Journal.

[119]  D. Mannino,et al.  Prevalence and outcomes of diabetes, hypertension and cardiovascular disease in COPD , 2008, European Respiratory Journal.

[120]  L. Edwards,et al.  Evaluation of serum CC-16 as a biomarker for COPD in the ECLIPSE cohort , 2008, Thorax.

[121]  B. Make,et al.  Comorbidities in chronic obstructive pulmonary disease. , 2008, Proceedings of the American Thoracic Society.

[122]  G. Criner,et al.  Cardiac disease in chronic obstructive pulmonary disease. , 2008, Proceedings of the American Thoracic Society.

[123]  T. Omland,et al.  Troponin T elevation and long-term mortality after chronic obstructive pulmonary disease exacerbation , 2008, European Respiratory Journal.

[124]  Preeti Gupta,et al.  Potential Adverse Effects of Bronchodilators in the Treatment of Airways Obstruction in Older People , 2008, Drugs & aging.

[125]  Peter H Edwards,et al.  Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease. , 2007, American journal of respiratory and critical care medicine.

[126]  Bartolome Celli,et al.  Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. , 2007, The New England journal of medicine.

[127]  Robert A Wise,et al.  Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee , 2007, Thorax.

[128]  T. Omland,et al.  Statin use is associated with reduced mortality in COPD , 2006, European Respiratory Journal.

[129]  J. Spertus,et al.  Impact of Chronic Obstructive Pulmonary Disease on Post-Myocardial Infarction Outcomes: P201 , 2006, The American journal of cardiology.

[130]  B. Celli,et al.  Systemic cytokines, clinical and physiological changes in patients hospitalized for exacerbation of COPD. , 2007, Chest.

[131]  N. Anthonisen,et al.  Mortality in COPD: role of comorbidities , 2006, European Respiratory Journal.

[132]  M. Meysman Angiotensin II blockers in obstructive pulmonary disease: a randomised controlled trial , 2006, European Respiratory Journal.

[133]  G. Ferguson,et al.  Why does the lung hyperinflate? , 2006, Proceedings of the American Thoracic Society.

[134]  D. Mannino,et al.  Global Initiative on Obstructive Lung Disease (GOLD) classification of lung disease and mortality: findings from the Atherosclerosis Risk in Communities (ARIC) study. , 2006, Respiratory medicine.

[135]  Judith K Jones,et al.  Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. , 2006, Annals of epidemiology.

[136]  S. Sidney,et al.  COPD and incident cardiovascular disease hospitalizations and mortality: Kaiser Permanente Medical Care Program. , 2005, Chest.

[137]  D. Kass,et al.  Mechanisms, pathophysiology, and therapy of arterial stiffness. , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[138]  K. Davis,et al.  Trends and Cardiovascular Co-morbidities of COPD Patients in the Veterans Administration Medical System, 1991–1999 , 2005, COPD.

[139]  S. Rennard Clinical approach to patients with chronic obstructive pulmonary disease and cardiovascular disease. , 2005, Proceedings of the American Thoracic Society.

[140]  E. Salpeter,et al.  Cardiovascular effects of beta-agonists in patients with asthma and COPD: a meta-analysis. , 2004, Chest.

[141]  S. Rennard Looking at the patient--approaching the problem of COPD. , 2004, The New England journal of medicine.

[142]  Don D. Sin,et al.  Why Are Patients With Chronic Obstructive Pulmonary Disease at Increased Risk of Cardiovascular Diseases?: The Potential Role of Systemic Inflammation in Chronic Obstructive Pulmonary Disease , 2003 .

[143]  P. Libby Inflammation in atherosclerosis , 2002, Nature.

[144]  S. Quintana,et al.  Mortality after hospitalization for COPD. , 2002, Chest.

[145]  D. Sin,et al.  The impact of chronic obstructive pulmonary disease on work loss in the United States. , 2002, American journal of respiratory and critical care medicine.

[146]  H. Folgering,et al.  Discontinuation of furosemide decreases PaCO(2) in patients with COPD. , 2002, Chest.

[147]  M. Alifano,et al.  Abnormalities of renal endothelin during acute exacerbation in chronic obstructive pulmonary disease. , 2001, Pulmonary pharmacology & therapeutics.

[148]  T. Seemungal,et al.  Acute Exacerbations of Chronic Obstructive Pulmonary Disease Are Accompanied by Elevations of Plasma Fibrinogen and Serum IL-6 Levels , 2000, Thrombosis and Haemostasis.

[149]  L. Shekerdemian,et al.  Cardiovascular effects of mechanical ventilation , 1999, Archives of disease in childhood.

[150]  M. Shipley,et al.  Breathlessness, chronic bronchitis and reduced pulmonary function as predictors of cardiovascular disease mortality among men in England, Scotland and the United States. , 1989, International journal of epidemiology.

[151]  K L Ebi-Kryston,et al.  Respiratory symptoms and pulmonary function as predictors of 10-year mortality from respiratory disease, cardiovascular disease, and all causes in the Whitehall Study. , 1988, Journal of clinical epidemiology.

[152]  R. Light,et al.  Serial pulmonary function in patients with acute heart failure. , 1983, Archives of internal medicine.

[153]  A. Siegelaub,et al.  Lung function and risk of myocardial infarction and sudden cardiac death. , 1976, The New England journal of medicine.