Inflammatory markers and circulating extracellular matrix proteins in patients with chronic obstructive pulmonary disease and left ventricular diastolic dysfunction.

BACKGROUND

Left ventricular diastolic dysfunction (LVDD) is a frequent condition in chronic obstructive pulmonary disease (COPD). Tenascin-C (Tn-C) and matrix metalloproteinase-9 (MMP-9) are extracellular matrix proteins associated with myocardial fibrosis and wall remodeling because of inflammation.

OBJECTIVE

To determine whether the circulating levels of inflammatory markers, Tn-C and MMP-9 are associated with LVDD in COPD patients.

METHODS

Forty-two severe stable COPD patients (64 ± 8 years, 88% male, FEV1% 38 ± 5.7) and a control group (n = 11) were included. Pulmonary function tests and a Doppler echocardiography were performed on COPD patients. Baseline serum levels of C-reactive protein (CRP), leukocytes, fibrinogen, interleukins (IL) 6 and 8, Tn-C and MMP-9 were analyzed in all participants.

RESULTS

COPD patients were classified in two groups: LVDD (n = 35) and non-LVDD (n = 7). Serum levels of IL-6 and CRP were higher in the LVDD group compared to the non-LVDD group [median(IQR)] [3.46 pg/mL (2.36-4.74) vs 1.87 pg/mL (1.10-3.28), P = 0.045] and [6.0 mg/L (3.0-13.0) vs 1.0 mg/L (1.0-2.3), P = 0.001], respectively. The same trend was observed in the analysis adjusted by age and BMI, being significant for CRP (P = 0.04). Circulating IL-6 was associated with the type of LVDD, being higher in the type-II (P = 0.046). Obese patients with COPD-LVDD showed a higher level of inflammatory markers (P = 0.021). Tn-C were significantly higher in patients with LVDD type-II compared to type-I [1422 ng/mL (826-1948) vs 781 ng/mL (640-1139), P = 0.015], without differences in MMP-9.

CONCLUSIONS

Severe COPD patients with LVDD showed a different inflammatory pattern, suggesting a link between low-grade inflammation and the presence of LVDD. In COPD, high levels of Tn-C are related to LVDD type-II.