Vascular Subphenotypes of Lung Disease in HIV & COPD

The goal of the project is to identify and characterize populations at risk for developing
pulmonary arterial hypertension (PAH). The project will establish a PAH subphenotype core
cohort (CORE) to evaluate mechanistic pathways and test novel therapeutic agents. This core
cohort serves as a resource for the Translational Program Project grant, Vascular
Subphenotypes of Lung Disease (Mark Gladwin, PI). In order to construct the CORE, we have
chosen to recruit COPD and HIV patients, two populations with advanced lung and systemic
diseases that are enriched for PAH. We have selected these as prototypic conditions because:
A) both COPD patients and HIV-infected patients develop PAH at a rate significantly greater
than the general population, B) morbidity and mortality are greatly increased in
dually-affected persons, C) mechanisms responsible for development of the PAH "subphenotype"
are not well-understood, D) clinical and genetic characteristics of the subgroup with PAH
are not known, and E) effects of PAH therapies in subphenotypes are incompletely studied.
There is also some overlap between COPD and HIV, with HIV-infected patients having
accelerated COPD even with effective antiretroviral therapy. Participants with COPD, HIV, or
HIV-uninfected controls will be recruited to the study based on entry criteria of elevated
N-terminal pro-brain natriuretic peptide (NT-proBNP) and/or an abnormal echocardiogram.
These subjects will then undergo a 6-minute walk test, blood collection, questionnaire,
medical record review, and echocardiography (if not previously performed). Selected subjects
will then be recruited to undergo right heart catheterization. The goals of the study are to
establish a pulmonary hypertension cohort for translational investigations, to determine the
utility of NT-proBNP as a biomarker of PAH, to determine clinical characteristics and
relationship of lung function to PAH in COPD and HIV, and to establish a biorepository for
mechanistic studies of PAH phenotypes.

Inclusion Criteria:

- Male/Female 18-80 years of age.

- Subject has been previously enrolled in PACT/MAC/ECRC study.

- Must have recent ProBNP test >120pg/ml or abnormal echocardiogram (right ventricular
systolic pressure >or=40mmHg) without evidence of left sided heart failure.

Exclusion Criteria:

- Previous diagnosis of congenital heart failure.

- If evidence of Left ventricular systolic or diastolic dysfunction, echo will be
reviewed by the PI on a case by case basis.

- Creatine clearance <60ml/min per 1.73 m2.

- Undiagnosed chest pain or myocardial infarction, stroke or cardiovascular event
within 3 months.

- Pregnancy.

- Subjects receiving chronic anticoagulant.

- Inability to complete the 6 minute walk test.