Short summary

Pulmonary hypertension (PH) develops due to increased blood pressure in the lung circulation. Group 3 is PH associated with lung disease or hypoxia, including patients with chronic obstructive pulmonary disease (COPD), and is a common cause for PH. Hypoxia is deemed as the main driver for development of PH among COPD patients due to vasoconstriction. We theorize, that patients with COPD, who have had RAAS inhibited medically will have lower pulmonary pressure than none medicinated COPD-patients.

Rationale

Pulmonary hypertension (PH) develops due to increased blood pressure in the heart and lung circulation and is commonly categorised into five groups due to underlying causality. Common causes for PH Group 3 development are underlying chronic lung diseases as e.g., chronic obstructive pulmonary disease (COPD) that alongside increasing disease severity induce hypoxia. PH Group 3 patients are divided into and non-severe and severe PH previously defined by a mean pulmonary arterial pressure (mPAP) >35 mmHg; severe PH is now defined by pulmonary vascular resistance > 5 wood units. Using the old definition, Kessler et al. showed that patients with COPD and a mPAP of just > 18 mmHg had significantly more exacerbations and hospital admissions. Acute exacerbations in COPD has been shown to be an independent indication of poor prognosis. Thus one can speculate, that even persistent and minor increases in pulmonary pressure could predict increased mortality among COPD-patients. Besides optimal COPD treatment, there is currently no specific pharmacological treatment of PH among COPD-patients, except lung transplantation. However, long term oxygenation therapy has been shown to slow the progression of PH, slightly reduce the mPAP and mortality. Hypoxaemia is deemed as the main driver for development of PH among COPD patients due to vasoconstriction. However, two studies on COPD-patients found a significantly increase in the renin-angiotensin-aldosterone-system (RAAS) among those with PH. This has further been substantiated by studies on animals and humans focusing on the angiotensin 1 receptors in the lungs, where coexisting hypoxia was found to: Increase angiotensin converting enzyme (ACE)-activity, downregulate angiotensin type 2 receptors and smooth muscle cell proliferation, but also reduce secretion of vasodilating factors as ACE2 and angiotensin (1-7). Additionally, ACE-inhibitors and ACE2-activators (resorcinolnaphthalein) showed a protective effect against developing PH during hypoxia in animal studies. Furthermore, giving hypoxic rats or mice a mineralocorticoid inhibitor (e.g., spironolactone or eplerenone) prevented some of the hallmarks of PH; right ventricular dysfunction, right ventricular hypertrophy, increased systolic pulmonary artery pressure and endothelial fibrosis. Patients with COPD are characterized by hypoxemia, either episodic or chronically, and approximately 30 % develop PH. The pathogenesis behind this, as depicted above, is influenced by the RAAS-system. We theorize, that patients with COPD, who have had RAAS inhibited with an ACE-inhibitor, angiotensin II-inhibitor or a mineralocorticoid inhibitor, will have lower pulmonary pressure compared to patients with COPD who did not receive these treatments.

Description of the cohort

The patient needs to have a COPD-diagnosis and have been in contact with the cardiology department at Odense University Hospital within the past 5 years.

Data and biological material

The design is a retrospective cohort study. We wish to examine clinical data from patients with COPD, who have had performed an echocardiography. Further, we wish to correlate the degree of pulmonary hypertension as depicted by the tricuspid regurgitation gradient with the number of years the patient has received ACE-inhibitors, angiotensin-II inhibitors and/or mineralocorticoid inhibitors.

Collaborating researchers and departments

Department of Cardiology, Odense University Hospital

• Gro Egholm

Department of Pulmonology, Odense University Hospital

• Casper Falster
• Jesper Davidsen