Elevated NT-pro-brain natriuretic peptide level is independently associated with all-cause mortality in HIV-infected women in the early and recent HAART eras in the Women's Interagency HIV Study cohort.

Matthew R Gingo,Yanxia Chu,Jason M Lazar,Mark T Gladwin,David B Hanna,Jong-Hyeon Jeong,Alison Morris,Lorrie Lucht,Quanwei Yang,Kidane B Ghebrehawariat,Yingze Zhang

doi:10.1371/journal.pone.0123389

Abstract

BackgroundHIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminal-pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women.DesignProspective cohort study.Methods and ResultsWe measured NT-proBNP in 936 HIV-infected and 387 age-matched HIV-uninfected women early (10/11/94 to 7/17/97) and 1082 HIV-infected and 448 HIV-uninfected women late (4/1/08 to 10/7/08) in the highly active antiretroviral therapy (HAART) periods in the Women’s Interagency HIV Study. An NT-proBNP >75th percentile was more likely in HIV-infected persons, but only statistically significant in the late period (27% vs. 21%, unadjusted p = 0.03). In HIV-infected participants, NT-proBNP>75th percentile was independently associated with worse 5-year survival in the early HAART period (HR 1.8, 95% CI 1.3–2.4, p<0.001) and remained a predictor of mortality in the late HAART period (HR 2.8, 95% CI 1.4–5.5, p = 0.002) independent of other established risk covariates (age, race/ethnicity, body mass index, smoking, hepatitis C serostatus, hypertension, renal function, and hemoglobin). NT-proBNP level was not associated with mortality in HIV-uninfected women.ConclusionNT-proBNP is a novel independent marker of mortality in HIV-infected women both when HAART was first introduced and currently. As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women.

Highlights

Targeted supplemental funding for specific projects is provided by the National Institute of Dental and Craniofacial Research (NIDCR), the National Institute on Alcohol Abuse and Alcoholism (NIAAA), the National Institute on Deafness and other Communication Disorders (NIDCD), and the National Institutes of Health (NIH) Office of Research on Women’s Health
As NT-proBNP is often associated with both pulmonary hypertension and left ventricular dysfunction, these findings suggest that these conditions may contribute significantly to adverse outcomes in this population, requiring further definition of causes and treatments of elevated NT-proBNP in HIV-infected women
While highly active antiretroviral therapy (HAART) has reduced mortality related to infectious complications in people with HIV, they are more likely than HIV-uninfected persons to have subclinical cardiovascular disease[1] or be diagnosed with myocardial infarction, congestive heart failure, cardiomyopathy, pulmonary hypertension, and chronic obstructive pulmonary disease (COPD).[2,3,4,5,6]

Summary

Introduction

Several studies have linked markers of inflammation and altered coagulation with increased cardiovascular disease and mortality in HIV.[9,10,11] C-reactive protein (CRP), interleukin (IL), and D-dimer correlate with traditional markers of HIV infection severity, CD4 count and plasma HIV RNA levels, but are independently associated with mortality in HIV-infected persons. Similar to HIV-uninfected populations, these markers and other inflammatory markers correlate with comorbid cardiovascular and pulmonary disease.[12,13]. HIV-infected individuals are at increased risk of right and left heart dysfunction. N-terminalpro-brain natriuretic peptide (NT-proBNP), a marker of cardiac ventricular strain and systolic dysfunction, may be associated with all-cause mortality in HIV-infected women. The aim of this study was to determine if elevated levels of NT-proBNP is associated with increased mortality in HIV-infected women

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Conclusion