Cardiovascular Risk, Myocardial Injury, and Exacerbations of Chronic Obstructive Pulmonary Disease

Rationale: Patients with chronic obstructive pulmonary disease (COPD) have elevated cardiovascular risk, and myocardial injury is common during severe exacerbations. Little is known about the prevalence, magnitude, and underlying mechanisms of cardiovascular risk in community-treated exacerbations. Objectives: To investigate how COPD exacerbations and exacerbation frequency impact cardiovascular risk and myocardial injury, and whether this is related to airway infection and inflammation. Methods: We prospectively measured arterial stiffness (aortic pulse wave velocity [aPWV]) and cardiac biomarkers in 98 patients with stable COPD. Fifty-five patients had paired stable and exacerbation assessments, repeated at Days 3, 7, 14, and 35 during recovery. Airway infection was identified using polymerase chain reaction. Measurements and Main Results: COPD exacerbation frequency was related to stable-state arterial stiffness (rho=0.209; P=0.040). Frequent exacerbators had greater aPWV than infrequent exacerbators (mean +/- SD aPWV, 11.4 +/- 2.1 vs. 10.3 +/- 2.0 ms(-1); P=0.025). Arterial stiffness rose by an average of 1.2 ms(-1) (11.1%) from stable state to exacerbation (n=55) and fell slowly during recovery. In those with airway infection at exacerbation (n=24) this rise was greater (1.4 +/- 1.6 vs. 0.7 +/- 1.3 ms(-1); P=0.048); prolonged; and related to sputum IL-6 (rho=0.753; P<0.001). Increases in cardiac biomarkers at exacerbation were higher in those with ischemic heart disease (n=12) than those without (n=43) (mean +/- SD increase in troponin T, 0.011 +/- 0.009 vs. 0.003 +/- 0.006 mu g/L, P=0.003; N-terminal pro-brain natriuretic peptide, 38.1 +/- 37.7 vs. 5.9 +/- 12.3 pg/ml, P<0.001). Conclusions: Frequent COPD exacerbators have greater arterial stiffness than infrequent exacerbators. Arterial stiffness rises acutely during COPD exacerbations, particularly with airway infection. Increases in arterial stiffness are related to inflammation, and are slow to recover. Myocardial injury is common and clinically significant during COPD exacerbations, particularly in those with underlying ischemic heart disease.