Increased levels of asymmetric dimethylarginine are associated with pulmonary arterial hypertension in HIV infection.

Abstract

OBJECTIVE:

To examine the relationship between asymmetric dimethylarginine (ADMA) and HIV-associated pulmonary arterial hypertension (PAH).

DESIGN:

HIV infection is an independent risk factor for PAH, but the underlying pathogenesis remains unclear. Chronic inflammation resulting in nitric oxide-mediated endothelial dysfunction is a key mechanism underlying other types of PAH. ADMA is an endogenous inhibitor of endothelial nitric oxide synthase. Among uninfected individuals, ADMA is associated with PAH and predicts disease-related mortality.

METHODS:

We measured ADMA, high sensitivity C-reactive protein, interleukin-6 (IL-6), D-dimer, and pulmonary artery systolic pressure (PASP) using echocardiography in HIV-infected individuals. Right heart catheterization (RHC) was performed in individuals with a PASP at least 30  mmHg. We performed multivariable analysis to identify factors associated with high PASP by echocardiogram and PAH by RHC.

RESULTS:

Among 214 HIV-infected individuals, the median age was 50 years, 82% were men, 71% were on antiretroviral therapy, and 4.2% carried a prior diagnosis of PAH. ADMA and IL-6 were associated with increased values of PASP following multivariable adjustment (7.2% per 0.1 μmol/l, P = 0.0049 and 3.9% per doubling, P = 0.027, respectively). In adjusted analysis among the 85 participants who underwent RHC, ADMA and IL-6 were associated with higher values of mean PAP (14.2% per 0.1 μmol/l, P = 0.0014 and 5.8% per doubling, P = 0.038, respectively). However, only ADMA was associated with PAH (prevalence ratio = 1.74, P = 0.029).

CONCLUSION:

Elevated levels of ADMA are independently associated with PAH among HIV-infected individuals. Our findings suggest that chronic HIV-associated inflammation leading to an accumulation of ADMA and subsequent nitric oxide-mediated endothelial dysfunction may represent a novel mechanism for HIV-associated PAH.

• Authors: Rushi V Parikh, Rebecca Scherzer, Elaine M Nitta, Anna Leone, Sophia Hur, Vanita Mistry, John S Macgregor, Jeffrey N Martin, Steven G Deeks, Peter Ganz, Priscilla Y Hsue
• Journal: AIDS (London, England) (AIDS) Vol. 28 Issue 4 Pg. 511-9 (Feb 20 2014) ISSN: 1473-5571 [Electronic] England
• PMID: 24469026 (Publication Type: Journal Article, Observational Study, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Biomarkers
• N,N-dimethylarginine
• Arginine

Topics

• Adult
• Arginine (analogs & derivatives, blood)
• Biomarkers (blood)
• Blood Pressure
• Catheterization, Swan-Ganz
• Cohort Studies
• Echocardiography
• Familial Primary Pulmonary Hypertension
• Female
• HIV Infections (complications)
• Humans
• Hypertension, Pulmonary (diagnosis, pathology)
• Male
• Middle Aged
• Prospective Studies