Beyond the Lungs: Systemic Manifestations of Pulmonary Arterial Hypertension

• Published in: American journal of respiratory and critical care medicine Vol. 201; no. 2; pp. 148 - 157
• Main Authors: Nickel, Nils P., Yuan, Ke, Dorfmuller, Peter, Provencher, Steeve, Lai, Yen-Chun, Bonnet, Sebastien, Austin, Eric D., Koch, Carl D., Morris, Alison, Perros, Frédéric, Montani, David, Zamanian, Roham T., de Jesus Perez, Vinicio A.
• Format: Journal Article
• Language: English
• Published: United States American Thoracic Society 15.01.2020
• Subjects: Bronchial Arteries - pathology; Bronchial Arteries - physiopathology; Cardiology and cardiovascular system; Cerebrovascular Circulation; Cerebrovascular Disorders - physiopathology; Concise Clinical Review; Coronary Artery Disease - metabolism; Coronary Artery Disease - physiopathology; Endothelium, Vascular - physiopathology; Human health and pathology; Humans; Kidney diseases; Kidney Diseases - metabolism; Kidney Diseases - physiopathology; Life Sciences; Muscular Diseases - metabolism; Muscular Diseases - physiopathology; Pulmonary Arterial Hypertension - metabolism; Pulmonary Arterial Hypertension - physiopathology; Pulmonary arteries; Pulmonary Artery - pathology; Pulmonary Artery - physiopathology; Pulmonary hypertension; Respiratory Muscles - physiopathology; Scleroderma, Systemic - metabolism; Scleroderma, Systemic - physiopathology; Vasodilation; Ventricular Dysfunction, Right - metabolism; Ventricular Dysfunction, Right - physiopathology; coronary artery disease; kidney disease; cerebrovascular disease; pulmonary hypertension; respiratory muscle dysfunction
• ISSN: 1073-449X; 1535-4970; 1535-4970
• DOI: 10.1164/rccm.201903-0656CI

Pulmonary arterial hypertension (PAH) is a disease characterized by progressive loss and remodeling of the pulmonary arteries, resulting in right heart failure and death. Until recently, PAH was seen as a disease restricted to the pulmonary circulation. However, there is growing evidence that patients with PAH also exhibit systemic vascular dysfunction, as evidenced by impaired brachial artery flow-mediated dilation, abnormal cerebral blood flow, skeletal myopathy, and intrinsic kidney disease. Although some of these anomalies are partially due to right ventricular insufficiency, recent data support a mechanistic link to the genetic and molecular events behind PAH pathogenesis. This review serves as an introduction to the major systemic findings in PAH and the evidence that supports a common mechanistic link with PAH pathophysiology. In addition, it discusses recent studies describing morphological changes in systemic vessels and the possible role of bronchopulmonary anastomoses in the development of plexogenic arteriopathy. On the basis of available evidence, we propose a paradigm in which metabolic abnormalities, genetic injury, and systemic vascular dysfunction contribute to systemic manifestations in PAH. This concept not only opens exciting research possibilities but also encourages clinicians to consider extrapulmonary manifestations in their management of patients with PAH.