Management of the patient with severe COPD and cardiovascular disease
- Imre Noth, MD
Imre Noth, MD
- Professor of Medicine in Pulmonary and Critical Care
- University of Chicago School of Medicine
- Gregory A Schmidt, MD
Gregory A Schmidt, MD
- Professor of Medicine, Division of Pulmonary Diseases, Critical Care, and Occupational Medicine
- University of Iowa
- Section Editors
- James K Stoller, MD, MS
James K Stoller, MD, MS
- Section Editor — Chronic Obstructive Pulmonary Disease
- Jean Wall Bennett Professor of Medicine, Samson Global Leadership Academy Endowed Chair
- Cleveland Clinic Lerner College of Medicine
- Chairman, Education Institute, Cleveland Clinic
- Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
Juan Carlos Kaski, DSc, MD, DM (Hons), FRCP, FESC, FACC, FAHA
- Section Editor — Coronary Heart Disease
- Professor of Cardiovascular Science
- Director, Cardiovascular and Cell Sciences Research Institute
- St. George's, University of London
- Deputy Editors
- Helen Hollingsworth, MD
Helen Hollingsworth, MD
- Deputy Editor — Pulmonary, Critical Care, and Sleep Medicine
- Associate Professor of Medicine
- Boston University School of Medicine
- Gordon M Saperia, MD, FACC
Gordon M Saperia, MD, FACC
- Senior Deputy Editor — UpToDate
- Deputy Editor — Cardiology
- Assistant Professor of Medicine
- Tufts University School of Medicine
Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD), which includes coronary heart disease, peripheral artery disease, and cerebrovascular disease, share tobacco abuse as a major risk factor. Thus, these two disorders commonly coexist. In addition, CVD is a leading cause of death among patients with COPD.
The management of patients with severe COPD and CVD will be reviewed here. The diagnosis and management of COPD and coronary heart disease occurring independently are discussed separately. (See "Chronic obstructive pulmonary disease: Definition, clinical manifestations, diagnosis, and staging" and "Management of stable chronic obstructive pulmonary disease" and "Management of exacerbations of chronic obstructive pulmonary disease" and "Stable ischemic heart disease: Overview of care" and "Epidemiology of coronary heart disease" and "Screening for coronary heart disease".)
Chronic obstructive pulmonary disease (COPD) and cardiovascular disease (CVD) frequently coexist, and the presence of one can affect outcomes in the other . As symptoms can overlap, differentiating the relative contributions of these diseases to a given patient’s symptoms can be challenging.
Coexistence of COPD and CVD — The frequent coexistence of COPD and CVD has been observed in several studies [2-4]. As an example, a study from a large United Kingdom database of more than 1.2 million patients over age 35 identified almost 30,000 patients with COPD; these patients were nearly five times more likely to have cardiovascular disease than those without COPD . In a separate study of 351 patients with advanced COPD, clinically significant coronary disease was identified by angiography in 60 percent and was occult in 53 percent .
Impact of co-morbid disease on outcomes — A large number of observational studies have found that the coexistence of COPD and cardiovascular disease has an important impact on clinical outcomes.
- Global Strategy for the Diagnosis, Management and Prevention of COPD, Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2016. www.goldcopd.org (Accessed on March 17, 2016).
- Feary JR, Rodrigues LC, Smith CJ, et al. Prevalence of major comorbidities in subjects with COPD and incidence of myocardial infarction and stroke: a comprehensive analysis using data from primary care. Thorax 2010; 65:956.
- Reed RM, Eberlein M, Girgis RE, et al. Coronary artery disease is under-diagnosed and under-treated in advanced lung disease. Am J Med 2012; 125:1228.e13.
- Enriquez JR, de Lemos JA, Parikh SV, et al. Association of chronic lung disease with treatments and outcomes patients with acute myocardial infarction. Am Heart J 2013; 165:43.
- Donaldson GC, Hurst JR, Smith CJ, et al. Increased risk of myocardial infarction and stroke following exacerbation of COPD. Chest 2010; 137:1091.
- McGarvey LP, John M, Anderson JA, et al. Ascertainment of cause-specific mortality in COPD: operations of the TORCH Clinical Endpoint Committee. Thorax 2007; 62:411.
- Sin DD, Man SF. Chronic obstructive pulmonary disease as a risk factor for cardiovascular morbidity and mortality. Proc Am Thorac Soc 2005; 2:8.
- Wakabayashi K, Gonzalez MA, Delhaye C, et al. Impact of chronic obstructive pulmonary disease on acute-phase outcome of myocardial infarction. Am J Cardiol 2010; 106:305.
- Konecny T, Somers K, Orban M, et al. Interactions between COPD and outcomes after percutaneous coronary intervention. Chest 2010; 138:621.
- Enriquez JR, Parikh SV, Selzer F, et al. Increased adverse events after percutaneous coronary intervention in patients with COPD: insights from the National Heart, Lung, and Blood Institute dynamic registry. Chest 2011; 140:604.
- Campo G, Guastaroba P, Marzocchi A, et al. Impact of COPD on long-term outcome after ST-segment elevation myocardial infarction receiving primary percutaneous coronary intervention. Chest 2013; 144:750.
- Patel AR, Kowlessar BS, Donaldson GC, et al. Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2013; 188:1091.
- Abroug F, Ouanes-Besbes L, Nciri N, et al. Association of left-heart dysfunction with severe exacerbation of chronic obstructive pulmonary disease: diagnostic performance of cardiac biomarkers. Am J Respir Crit Care Med 2006; 174:990.
- McAllister DA, Maclay JD, Mills NL, et al. Diagnosis of myocardial infarction following hospitalisation for exacerbation of COPD. Eur Respir J 2012; 39:1097.
- Søyseth V, Bhatnagar R, Holmedahl NH, et al. Acute exacerbation of COPD is associated with fourfold elevation of cardiac troponin T. Heart 2013; 99:122.
- Rutten FH, Cramer MJ, Grobbee DE, et al. Unrecognized heart failure in elderly patients with stable chronic obstructive pulmonary disease. Eur Heart J 2005; 26:1887.
- Reid WD, Yamabayashi C, Goodridge D, et al. Exercise prescription for hospitalized people with chronic obstructive pulmonary disease and comorbidities: a synthesis of systematic reviews. Int J Chron Obstruct Pulmon Dis 2012; 7:297.
- Entwistle MD, Sommerville D, Tandon AP, Jones JG. Effect of hypoxaemia on the resting electrocardiogram (ECG) in patients with cardiac ischaemia. Ann Acad Med Singapore 1994; 23:460.
- Gill NP, Wright B, Reilly CS. Relationship between hypoxaemic and cardiac ischaemic events in the perioperative period. Br J Anaesth 1992; 68:471.
- Shih HT, Webb CR, Conway WA, et al. Frequency and significance of cardiac arrhythmias in chronic obstructive lung disease. Chest 1988; 94:44.
- Fuso L, Incalzi RA, Pistelli R, et al. Predicting mortality of patients hospitalized for acutely exacerbated chronic obstructive pulmonary disease. Am J Med 1995; 98:272.
- Long term domiciliary oxygen therapy in chronic hypoxic cor pulmonale complicating chronic bronchitis and emphysema. Report of the Medical Research Council Working Party. Lancet 1981; 1:681.
- Continuous or nocturnal oxygen therapy in hypoxemic chronic obstructive lung disease: a clinical trial. Nocturnal Oxygen Therapy Trial Group. Ann Intern Med 1980; 93:391.
- Petty TL. Supportive therapy in COPD. Chest 1998; 113:256S.
- Cason BA, Wisneski JA, Neese RA, et al. Effects of high arterial oxygen tension on function, blood flow distribution, and metabolism in ischemic myocardium. Circulation 1992; 85:828.
- Sassoon CS, Hassell KT, Mahutte CK. Hyperoxic-induced hypercapnia in stable chronic obstructive pulmonary disease. Am Rev Respir Dis 1987; 135:907.
- Aubier M, Murciano D, Milic-Emili J, et al. Effects of the administration of O2 on ventilation and blood gases in patients with chronic obstructive pulmonary disease during acute respiratory failure. Am Rev Respir Dis 1980; 122:747.
- Schmidt, GA, Hall, JB. Oxygen therapy and hypoxic drive to breathe: Is there danger in the patient with COPD?. Intensive Crit Care Dig 1989; 8:124.
- Celli B, Decramer M, Kesten S, et al. Mortality in the 4-year trial of tiotropium (UPLIFT) in patients with chronic obstructive pulmonary disease. Am J Respir Crit Care Med 2009; 180:948.
- Celli B, Decramer M, Leimer I, et al. Cardiovascular safety of tiotropium in patients with COPD. Chest 2010; 137:20.
- Hilleman DE, Malesker MA, Morrow LE, Schuller D. A systematic review of the cardiovascular risk of inhaled anticholinergics in patients with COPD. Int J Chron Obstruct Pulmon Dis 2009; 4:253.
- Suissa S, Assimes T, Ernst P. Inhaled short acting beta agonist use in COPD and the risk of acute myocardial infarction. Thorax 2003; 58:43.
- Ferguson GT, Funck-Brentano C, Fischer T, et al. Cardiovascular safety of salmeterol in COPD. Chest 2003; 123:1817.
- Tranfa CM, Pelaia G, Grembiale RD, et al. Short-term cardiovascular effects of salmeterol. Chest 1998; 113:1272.
- Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone propionate and survival in chronic obstructive pulmonary disease. N Engl J Med 2007; 356:775.
- Calverley PM, Anderson JA, Celli B, et al. Cardiovascular events in patients with COPD: TORCH study results. Thorax 2010; 65:719.
- Au DH, Udris EM, Fan VS, et al. Risk of mortality and heart failure exacerbations associated with inhaled beta-adrenoceptor agonists among patients with known left ventricular systolic dysfunction. Chest 2003; 123:1964.
- Bermingham M, O'Callaghan E, Dawkins I, et al. Are beta2-agonists responsible for increased mortality in heart failure? Eur J Heart Fail 2011; 13:885.
- Nannini LJ, Lasserson TJ, Poole P. Combined corticosteroid and long-acting beta(2)-agonist in one inhaler versus long-acting beta(2)-agonists for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2012; :CD006829.
- Hanania NA, Darken P, Horstman D, et al. The efficacy and safety of fluticasone propionate (250 microg)/salmeterol (50 microg) combined in the Diskus inhaler for the treatment of COPD. Chest 2003; 124:834.
- Vestbo J, Anderson JA, Brook RD, et al. Fluticasone furoate and vilanterol and survival in chronic obstructive pulmonary disease with heightened cardiovascular risk (SUMMIT): a double-blind randomised controlled trial. Lancet 2016; 387:1817.
- White WB, Cooke GE, Kowey PR, et al. Cardiovascular safety in patients receiving roflumilast for the treatment of COPD. Chest 2013; 144:758.
- Oba Y, Lone NA. Efficacy and safety of roflumilast in patients with chronic obstructive pulmonary disease: a systematic review and meta-analysis. Ther Adv Respir Dis 2013; 7:13.
- de Mey C, Nassr N, Lahu G. No relevant cardiac, pharmacokinetic or safety interactions between roflumilast and inhaled formoterol in healthy subjects: an open-label, randomised, actively controlled study. BMC Clin Pharmacol 2011; 11:7.
- Sessler CN, Cohen MD. Cardiac arrhythmias during theophylline toxicity. A prospective continuous electrocardiographic study. Chest 1990; 98:672.
- Bittar G, Friedman HS. The arrhythmogenicity of theophylline. A multivariate analysis of clinical determinants. Chest 1991; 99:1415.
- Suissa S, Hemmelgarn B, Blais L, Ernst P. Bronchodilators and acute cardiac death. Am J Respir Crit Care Med 1996; 154:1598.
- Foresi A, Cavigioli G, Signorelli G, et al. Is the use of beta-blockers in COPD still an unresolved dilemma? Respiration 2010; 80:177.
- Rutten FH, Zuithoff NP, Hak E, et al. Beta-blockers may reduce mortality and risk of exacerbations in patients with chronic obstructive pulmonary disease. Arch Intern Med 2010; 170:880.
- Dransfield MT, Rowe SM, Johnson JE, et al. Use of beta blockers and the risk of death in hospitalised patients with acute exacerbations of COPD. Thorax 2008; 63:301.
- van Gestel YR, Hoeks SE, Sin DD, et al. Impact of cardioselective beta-blockers on mortality in patients with chronic obstructive pulmonary disease and atherosclerosis. Am J Respir Crit Care Med 2008; 178:695.
- Stefan MS, Rothberg MB, Priya A, et al. Association between β-blocker therapy and outcomes in patients hospitalised with acute exacerbations of chronic obstructive lung disease with underlying ischaemic heart disease, heart failure or hypertension. Thorax 2012; 67:977.
- Puente-Maestu L, Calle M, Ortega-González A, et al. Multicentric study on the beta-blocker use and relation with exacerbations in COPD. Respir Med 2014; 108:737.
- Au DH, Bryson CL, Fan VS, et al. Beta-blockers as single-agent therapy for hypertension and the risk of mortality among patients with chronic obstructive pulmonary disease. Am J Med 2004; 117:925.
- Benson MK, Berrill WT, Cruickshank JM, Sterling GS. A comparison of four beta-adrenoceptor antagonists in patients with asthma. Br J Clin Pharmacol 1978; 5:415.
- Fogari R, Zoppi A, Tettamanti F, et al. Comparative effects of celiprolol, propranolol, oxprenolol, and atenolol on respiratory function in hypertensive patients with chronic obstructive lung disease. Cardiovasc Drugs Ther 1990; 4:1145.
- Chazan R. [Atenolol in the treatment of patients with airway obstruction]. Pol Merkur Lekarski 1998; 4:89.
- Salpeter S, Ormiston T, Salpeter E. Cardioselective beta-blockers for chronic obstructive pulmonary disease. Cochrane Database Syst Rev 2005; :CD003566.
- Salpeter SR, Ormiston TM, Salpeter EE, et al. Cardioselective beta-blockers for chronic obstructive pulmonary disease: a meta-analysis. Respir Med 2003; 97:1094.
- Salpeter SR, Ormiston TM, Salpeter EE. Cardioselective beta-blockers in patients with reactive airway disease: a meta-analysis. Ann Intern Med 2002; 137:715.
- van der Woude HJ, Zaagsma J, Postma DS, et al. Detrimental effects of beta-blockers in COPD: a concern for nonselective beta-blockers. Chest 2005; 127:818.
- Sirak TE, Jelic S, Le Jemtel TH. Therapeutic update: non-selective beta- and alpha-adrenergic blockade in patients with coexistent chronic obstructive pulmonary disease and chronic heart failure. J Am Coll Cardiol 2004; 44:497.
- Jabbour A, Macdonald PS, Keogh AM, et al. Differences between beta-blockers in patients with chronic heart failure and chronic obstructive pulmonary disease: a randomized crossover trial. J Am Coll Cardiol 2010; 55:1780.
- George RB, Manocha K, Burford JG, et al. Effects of labetalol in hypertensive patients with chronic obstructive pulmonary disease. Chest 1983; 83:457.
- Guazzi M, Agostoni P, Matturri M, et al. Pulmonary function, cardiac function, and exercise capacity in a follow-up of patients with congestive heart failure treated with carvedilol. Am Heart J 1999; 138:460.
- Criner GJ, Connett JE, Aaron SD, et al. Simvastatin for the prevention of exacerbations in moderate-to-severe COPD. N Engl J Med 2014; 370:2201.
- Ingebrigtsen TS, Marott JL, Nordestgaard BG, et al. Statin use and exacerbations in individuals with chronic obstructive pulmonary disease. Thorax 2015; 70:33.
- Wang MT, Lo YW, Tsai CL, et al. Statin use and risk of COPD exacerbation requiring hospitalization. Am J Med 2013; 126:598.
- Gao D, Grunwald GK, Rumsfeld JS, et al. Variation in mortality risk factors with time after coronary artery bypass graft operation. Ann Thorac Surg 2003; 75:74.
- Islamoglu F, Reyhanoglu H, Berber O, et al. Predictors of outcome after coronary artery bypass grafting in patients older than 75 years of age. Med Sci Monit 2003; 9:CR369.
- Medalion B, Katz MG, Cohen AJ, et al. Long-term beneficial effect of coronary artery bypass grafting in patients with COPD. Chest 2004; 125:56.
- Saleh HZ, Mohan K, Shaw M, et al. Impact of chronic obstructive pulmonary disease severity on surgical outcomes in patients undergoing non-emergent coronary artery bypass grafting. Eur J Cardiothorac Surg 2012; 42:108.
- Samuels LE, Kaufman MS, Morris RJ, et al. Coronary artery bypass grafting in patients with COPD. Chest 1998; 113:878.
- Cohen A, Katz M, Katz R, et al. Chronic obstructive pulmonary disease in patients undergoing coronary artery bypass grafting. J Thorac Cardiovasc Surg 1995; 109:574.
- Michalopoulos A, Geroulanos S, Papadimitriou L, et al. Mild or moderate chronic obstructive pulmonary disease risk in elective coronary artery bypass grafting surgery. World J Surg 2001; 25:1507.
- Fuster RG, Argudo JA, Albarova OG, et al. Prognostic value of chronic obstructive pulmonary disease in coronary artery bypass grafting. Eur J Cardiothorac Surg 2006; 29:202.
- COPD/CVD RELATIONSHIP
- Coexistence of COPD and CVD
- Impact of co-morbid disease on outcomes
- EVALUATION AND DIAGNOSIS OF CHD IN PATIENTS WITH COPD
- NONPHARMACOLOGIC THERAPIES
- Smoking cessation
- Cardiopulmonary rehabilitation
- Management of hypoxemia
- - Effect of hypoxemia on the heart
- - Indications for supplemental oxygen
- Noninvasive positive pressure ventilation
- TREATMENT OF COPD IN PATIENTS WITH CVD
- Inhaled anticholinergic medications
- Beta-2 agonists
- - Short-acting beta agonists
- - Long-acting beta agonists
- Combination inhaled bronchodilator plus glucocorticoid
- TREATMENT OF CVD IN PATIENTS WITH COPD
- Effects of beta-blockers on mortality and COPD exacerbations
- Effect of cardioselective beta blockers on lung function
- Effect of combination beta and alpha blockers on lung function
- Effect of statins on COPD exacerbations
- Revascularization in patients with severe COPD
- SUMMARY AND RECOMMENDATIONS