Scleroderma patients with symptomatic pulmonary hypertension (PHTN) have a mean survival of one year; there is limited effective therapy and no way to determine who is at risk. If physicians could predict risk, early intervention could be directed toward those at highest risk. Using a cohort of more tha 950 patients seen at the Johns Hopkins and University of Maryland Scleroderma Center, we propose the following. Specif Aim 1: To differentiate the subpopulations of patients with PHTN using a cross-sectional analysis. We plan to test the hypothesis that the subpopulation of patients with combined pulmonary fibrosis and hypertension have distinctive clinical and demographic features and a worse prognosis than those with isolated PHTN.
Specific Aim 2 : To ascertain the clinical and demographic features than predict severe PHTN as a complication of scleroderma using a retrospective, longitudinal cohort study of patients who present without PHTN. We hypothesize that PHTN is a vascular abnormality preceded by other vascular symptoms such as severe Raynaud?s leading to amputation. We intend to determine the features associated with severe PHTN.
Specific Aim 3 : To assess the relationship between lung function measures, patient disease characteristics, and PHTN using a longitudinal cohort of scleroderma patients. The nature of the Diffusion Capacity of Carbon Monoxide (DLCO) relationship with PHTN is unclear. We believe that early changes in DLCO will predict PHTN risk.
Specific Aim 4 : To determine if anti-fibrillarin antibody is an early marker of severe PHTN by a nested case control study of patients who develop PHTN. We hypothesize that this serum marker can be used to predict who is at high risk for PHTN. With these specific aims, we hope to develop a predictive model for risk assessment for severe PHTN; this is critical to direct early intervention at preventing or delaying hypertension development.
