Cardiovascular risk, myocardial injury, and exacerbations of chronic obstructive pulmonary disease

Abstract

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 μg/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.

Figures

Figure 1.

Frequent chronic obstructive pulmonary disease exacerbators (n = 72) had a higher stable-state arterial stiffness than infrequent exacerbators (n = 26) (mean ± SD aortic pulse wave velocity, 11.4 ± 2.1 vs. 10.3 ± 2.0 ms−1; P = 0.025).

Figure 2.

In 55 patients with chronic obstructive pulmonary disease, arterial stiffness increased acutely at exacerbation presentation compared with the paired stable state (mean ± SE aortic pulse wave velocity, 11.3 ± 0.4 vs. 10.1 ± 0.3 ms−1; P < 0.001).

Figure 3.

Arterial stiffness falls slowly during recovery from an acute chronic obstructive pulmonary disease exacerbation. Arterial stiffness fell from its peak at exacerbation presentation by an average of 0.017 ms−1day−1 (95% confidence interval, 0.001–0.033; P = 0.040). Extrapolating this average decline in arterial stiffness during the recovery period indicates a return to the stable-state level at 66 days postexacerbation presentation (95% confidence interval, 33–149 d) (n = 55 at stable state and exacerbation; n = 44 at Day 3; n = 39 at Day 7; n = 38 at Day 14; n = 25 at Day 35; dotted line represents mean stable-state aortic pulse wave velocity).

Figure 4.

The time course of changes in arterial stiffness during acute and recovery phases of 55 chronic obstructive pulmonary disease exacerbations. Those with airway infection detected at exacerbation (red) had a greater and more prolonged rise in arterial stiffness compared with those without detected airway infection (blue).

Figure 5.

The time course of changes in cardiac biomarkers during acute and recovery phases of 55 chronic obstructive pulmonary disease exacerbations. Those with known ischemic heart disease (red) had a higher and more prolonged rise in serum troponin T (A) and N-terminal pro–brain natriuretic peptide (B) compared with those without ischemic heart disease (blue).