Progress in the understanding and management of pulmonary arterial hypertension

INTRODUCTION In 1981 the “Patient Registry for the Characterization of Primary Pulmonary Hypertension” was set up, supported by the National Heart, Lung and Blood Institute, and recruited 194 patients across 32 clinical centres over 4 years in the United States. The estimated median survival of these incident cases of primary pulmonary hypertension (which approximates to what we would now term idiopathic pulmonary arterial hypertension, IPAH) was 2.8 years, with a 68% survival rate at 1 year, 48% at 3 years and 35% at 5 years. Since 2000 a number of national registries have been set-up across the world to study the developing epidemiology of pulmonary arterial hypertension (PAH). The largest of these is the REVEAL (Registry to Evaluate Early and Long-term Pulmonary Arterial Hypertension Disease Management) Registry in the United States. Between 2006 and 2009, 2635 prevalent and incident cases were included in survival analysis across 55 centres. For IPAH, there was a 91% survival rate at 1 year, 74% at 3 years and 65% at 5 years. The Spanish registry also recruited 866 prevalent and incident cases of IPAH between 2007 and 2008 and calculated 1-, 3and 5-year survival rates of 87%, 75% and 65% respectively. In the French registry, which also analysed prevalent and incident cases, for a sub-population of 190 patients with IPAH, hereditary PAH (HPAH) and anorexigen-associated PAH cases (which all have similar baseline characteristics and outcomes) between 2002 and 2003, a 1-year survival rate of 83% and 3-year of 58% was calculated. In the UK there was a focus on incident cases, and 482 patients with IPAH, HPAH, and anorexigen-associated PAH were included between 2001 and 2009 and had 1-, 3and 5-year survival rates of 93%, 73% and 61% respectively. Although there is debate about the inclusion of both prevalent and incident cases in these registries (owing to survivor bias), there is broad agreement over current survival rates across these registries. Measurable progress has been made in the management of pulmonary arterial hypertension over the last 33 years – now, at 5 years, a larger proportion of people are living with the disease, rather than dying from it. In this review article we take a historical approach to reflect on the journey that has brought us to where we are today, focussing on the key milestones in the management of pulmonary arterial hypertension, signposted by the World Health Organisation (WHO) “World Symposia in Pulmonary Hypertension”. It will become apparent that this mirrors the developments and movements in medicine over the last 150 years: from pathology to physiology, from physiology to pharmacology, from pharmacology to cell biology, from cell biology to genetics.