Increased levels of asymmetric dimethylarginine are associated with pulmonary arterial hypertension in HIV infection
Year: 2014
Type: article
Study design: Observational Study
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.
Source: AIDS
Language: English
Subfield: Pulmonary and Respiratory Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: green
Awards: Clinical and Translational Science Institute, CVD and Metabolic Complications of HIV/AIDS Data Coordinating Center, Impact of HIV-associated inflammation on disease, G2839755957, G3181090803, G3322721267, Inflammation, Viral Replication, and Atherosclerosis in Treated HIV Infection, G3917235369, Epidemiology and Pathogenesis of Pulmonary Hypertension in HIV Patients, The impact of early antiretroviral therapy on HIV persistence and inflammation, G758528517, CFAR Network of Integrated Clinical Systems (CNICS), UCSF-Bay Area Center for AIDS Research
OpenAlex ID: W1992444597