Case-Control Study of Methamphetamine in Pulmonary Arterial Hypertension

The long-term objectives of this application are to establish the epidemiological association between methamphetamine use and pulmonary arterial hypertension. Methamphetamine and other stimulant abuse have been increasing across the United States and the world with several known complications. Pulmonary arterial hypertension has been suspected to occur as a sequela, however this has never been studied in a rigorous multicenter epidemiologic study. Preliminary findings have suggested that carboxylesterase 1 (CES1) may be an important genetic modifier in the setting of methamphetamine use leading to pulmonary arterial hypertension. The Specific Aims are 1) to determine whether methamphetamine use is associated with PAH in a case-control study and whether this association is modified by genetic variants in (or activity of) CES1; 2) to determine the risk factors for clinical worsening in patients with methamphetamine-associated pulmonary arterial hypertension in comparison with idiopathic pulmonary arterial hypertension in a prospective cohort study; and 3) to understand if reductions in CES1 activity result in human pulmonary endothelial cell damage in methamphetamine-associated pulmonary arterial hypertension. Patient-oriented research studies will be conducted in a multicenter study group to address these epidemiologic questions.