**2. Epidemiology**

Pulmonary arterial hypertension (PAH) is a rare disease, with an estimated prevalence of 15-50 cases per million.[4] Idiopathic PAH (IPAH) has an annual incidence of 1-2 cases per million people in the US and Europe and is 2-4 times as common in women as in men.[5], [6] The REVEAL Registry demonstrates a 4.1:1 female-to-male ratio among patients with IPAH, and a 3.8:1 ratio among those with associated pulmonary arterial hypertension (APAH). [4] The mean age at diagnosis is around 45 years.[7] IPAH accounts for at least 40% of cases of PAH, with APAH accounting for the majority of the remaining cases. [8]

The REVEAL Registry population tends to be overweight, with a BMI of 29 kg/m[2]; hence, obesity may be a risk factor for the development of PAH. A variety of comorbid conditions were identified, including systemic hypertension, obstructive lung disease, sleep apnea, and prior venous thrombo-embolism, which were not believed to represent the principal cause for the patients' pulmonary hypertension. [6]

The median interval from symptom onset to diagnosis remains unacceptably high at 1.1 years in current registry data, [6] unchanged from the experience from the 1980's.[9] Overall survival has improved somewhat, with 3-year survival of 48% in the NIH registry [10], compared to 67% in both US [11] and French [12] contemporary registries.
