The role of pulmonary arterial stiffness in COPD

Abstract

COPD is the second most common cause of pulmonary hypertension, and is a common complication of severe COPD with significant implications for both quality of life and mortality. However, the use of a rigid diagnostic threshold of a mean pulmonary arterial pressure (mPAP) of ≥25mHg when considering the impact of the pulmonary vasculature on symptoms and disease is misleading. Even minimal exertion causes oxygen desaturation and elevations in mPAP, with right ventricular hypertrophy and dilatation present in patients with mild to moderate COPD with pressures below the threshold for diagnosis of pulmonary hypertension. This has significant implications, with right ventricular dysfunction associated with poorer exercise capability and increased mortality independent of pulmonary function tests.The compliance of the pulmonary artery (PA) is a key component in decoupling the right ventricle from the pulmonary bed, allowing the right ventricle to work at maximum efficiency and protecting the microcirculation from large pressure gradients. PA stiffness increases with the severity of COPD, and correlates well with the presence of exercise induced pulmonary hypertension. A curvilinear relationship exists between PA distensibility and mPAP and pulmonary vascular resistance (PVR) with marked loss of distensibility before a rapid rise in mPAP and PVR occurs with resultant right ventricular failure. This combination of features suggests PA stiffness as a promising biomarker for early detection of pulmonary vascular disease, and to play a role in right ventricular failure in COPD. Early detection would open this up as a potential therapeutic target before end stage arterial remodelling occurs.

A randomized trial of once-daily fluticasone furoate/vilanterol or vilanterol versus placebo to determine effects on arterial stiffness in COPD

“…Evidence of endothelial dysfunction and vascular re-modeling have been detected both in individuals with COPD and in “healthy” individuals who smoke 18. This could be due to shared risk factors such as cigarette smoking, which in addition to being a risk factor for airway obstruction,16 is also known to induce vascular endothelial dysfunction 18. Notably in this study, the smoking history (including years smoked, cigarettes per day, pack-years, and smoking status) was similar across the groups.…”

“…Systemic endothelial dysfunction and vascular re-modeling (including proliferation of smooth muscle cells, elastin degradation, and collagen deposition, which may be followed by calcification and ultimately result in arterial stiffening),18 are also evident at all severities of COPD and further contribute to arterial stiffening 19. Additional impacts of COPD, such as reduced ability to exercise, may also contribute to arterial stiffening by altering vascular hemodynamics 16…”

Elastic properties of pulmonary artery in chronic obstructive pulmonary disease

“…PA elastic properties were researched by ultrasound method [4] and calculated following indexes: pulsatility (Puls, %), compliance (Comp, mm 2 /mm Hg), distensibility (Dist, %/mm Hg), elasticity module (EM, mm Hg) and stiffness index B (SI-B). Mean pulmonary arterial pressure (PAP) (mPAP, mm Hg) was calculated by Kitabatake equation, systolic PAP (sPAP, mm Hg) was calculated by tricuspid regurgitation, diastolic PAP (dPAP, mm Hg) and pulse PAP (pPAP, mm Hg) counted as derived from mPAP and sPAP.…”

“…Obvious information about PA stiffness associated with the severity of COPD [4], obstructive respiratory disorders and pulmonary hypertension [5]. It is proved, that the violation of elastic properties of PA adversely affects the structural and functional condition of pulmonary vessels and leads to right ventricular overload [6].…”

Pulmonary arterial stiffening in COPD and its implications for right ventricular remodelling

“…As a result marked loss of pulmonary artery distensibility occurs without commensurate loss of ventricular function until only minimal distensibility remains when a rapid decompensation of the right ventricle occurs [8]. Thus pulmonary arterial stiffness may be a key early indicator of pulmonary vascular remodelling, and act as a biomarker for future dysfunction before significant adverse remodelling occurs [9]. …”