Arterial Stiffness Increases Over Time in Relation to Lung Diffusion Capacity: A Longitudinal Observation Study in COPD

Abstract

Background: Cardiovascular events are, after cancer, the most common cause of death in COPD patients. Arterial stiffness is an independent predictor of all-cause mortality and cardiovascular events. Several cross-sectional studies have confirmed increased arterial stiffness in patients with COPD. Various mechanisms in the development of arterial stiffness in COPD such as reduced lung function or systemic inflammation have been proposed. However, clinical predictors of arterial stiffness that had been reported in cross-sectional studies have not yet been confirmed in a longitudinal setting. We have assessed the course of augmentation index (AIx) - a measure of systemic arterial stiffness - and possible predictors in a cohort of COPD patients over a period of up to 7 years.

Methods: COPD patients underwent annual AIx measurement by applanation tonometry for a maximum duration of 7 years. Additionally, we performed annual assessments of lung function, blood gases, systemic inflammation, serum lipids and blood pressure. Associations between the course of AIx and potential predictors were investigated through a mixed effect model.

Results: Seventy-six patients (mean (SD) age 62.4 (7.1), male 67%) were included. The AIx showed a significant annual increase of 0.91% (95% CI 0.21/1.60) adjusted for baseline. The change in diffusion capacity (DLco), low-density lipoprotein (LDL), and high-sensitivity c-reactive protein (hsCRP) was independently associated with the increasing evolution of AIx (Coef. - 0.10, p<0.001, Coef. 1.37, p=0.003, and Coef. 0.07, p=0.033, respectively).

Conclusion: This study demonstrated a meaningful increase in arterial stiffness in COPD over time. A greater annual increase in arterial stiffness was associated with the severity of emphysema (measured by DLco), systemic inflammation, and dyslipidaemia.

Clinical trial registration: www.ClinicalTrials.gov, NCT01527773.

Keywords: COPD; arterial stiffness; cardiovascular risk; dyslipidaemia; emphysema; inflammation; longitudinal.

Conflict of interest statement

Prof. Dr. Malcolm Kohler reports grants and personal fees from Bayer, personal fees from Novartis, personal fees from Boehringer, personal fees from GSK, personal fees from Astra Zeneca, grants from Roche, personal fees from CSL Behring, and personal fees from Mundipharma, during the conduct of the study. The authors report no other conflicts of interest in this work.

© 2020 Roeder et al.

Figures

Figure 1

Schematic presentation of the pulse wave curve measured at the A. radialis. After the foot of the pulse (T0), indicating the onset of ejection, the pressure wave rises to an initial peak where it forms a shoulder (P1). This is the peak of the primary left ventricular ejection pressure. The second shoulder (P2) represents the peak of the arterial reflection wave. The difference between P2 and P1 is called augmentation pressure (AP). The end of ejection (ED) is the point of the closure of the aortic valve and time of the end of systole. The augmentation index (AIx) is calculated as the difference between the second (P2) and first (P1) systolic peak pressure and is expressed as a percentage of the central PP: AIx (%) = [(P2−P1)/PP] ×100.

Figure 2

Study flow chart. Abbreviations: AIx, augmentation index; FU, follow-up; LTPL, lung transplantation.

Figure 3

The figure shows the estimation of the course of AIx over time according to the influence of change in DLco % pred based on the unadjusted regression model. The mean (CI) AIx at baseline (0) and follow-up visits (1–4) is estimated for a yearly change in DLco % pred. of −40, −20, 0, and 10. Abbreviation: DLco, diffusion capacity.

Figure 4

The figure demonstrates the estimated course of AIx over time dependent on hsCRP values based on the unadjusted regression model. The mean (CI) AIx at baseline (0) and yearly follow-up (1–4) is estimated for hsCRP values of 5, 20, 50 and 70 mg/l. Abbreviations: AIx, augmentation index; hsCRP, high-sensitivity C-reactive protein.