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      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

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          Abstract

          Background

          HIV-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.

          Design

          Prospective cohort study.

          Methods and Results

          We 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.

          Conclusion

          NT-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.

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          Most cited references37

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          Prediction of creatinine clearance from serum creatinine.

          Paige Gault, H Gault, D Cockcroft (1975)
          A formula has been developed to predict creatinine clearance (Ccr) from serum creatinine (Scr) in adult males: (see article)(15% less in females). Derivation included the relationship found between age and 24-hour creatinine excretion/kg in 249 patients aged 18-92. Values for Ccr were predicted by this formula and four other methods and the results compared with the means of two 24-hour Ccr's measured in 236 patients. The above formula gave a correlation coefficient between predicted and mean measured Ccr's of 0.83; on average, the difference predicted and mean measured values was no greater than that between paired clearances. Factors for age and body weight must be included for reasonable prediction.
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            Pulmonary hypertension as a risk factor for death in patients with sickle cell disease.

            Mark Gladwin, Vandana Sachdev, Maria Jison … (2004)
            The prevalence of pulmonary hypertension in adults with sickle cell disease, the mechanism of its development, and its prospective prognostic significance are unknown. We performed Doppler echocardiographic assessments of pulmonary-artery systolic pressure in 195 consecutive patients (82 men and 113 women; mean [+/-SD] age, 36+/-12 years). Pulmonary hypertension was prospectively defined as a tricuspid regurgitant jet velocity of at least 2.5 m per second. Patients were followed for a mean of 18 months, and data were censored at the time of death or loss to follow-up. Doppler-defined pulmonary hypertension occurred in 32 percent of patients. Multiple logistic-regression analysis, with the use of the dichotomous variable of a tricuspid regurgitant jet velocity of less than 2.5 m per second or 2.5 m per second or more, identified a self-reported history of cardiovascular or renal complications, increased systolic blood pressure, high lactate dehydrogenase levels (a marker of hemolysis), high levels of alkaline phosphatase, and low transferrin levels as significant independent correlates of pulmonary hypertension. The fetal hemoglobin level, white-cell count, and platelet count and the use of hydroxyurea therapy were unrelated to pulmonary hypertension. A tricuspid regurgitant jet velocity of at least 2.5 m per second, as compared with a velocity of less than 2.5 m per second, was strongly associated with an increased risk of death (rate ratio, 10.1; 95 percent confidence interval, 2.2 to 47.0; P<0.001) and remained so after adjustment for other possible risk factors in a proportional-hazards regression model. Pulmonary hypertension, diagnosed by Doppler echocardiography, is common in adults with sickle cell disease. It appears to be a complication of chronic hemolysis, is resistant to hydroxyurea therapy, and confers a high risk of death. Therapeutic trials targeting this population of patients are indicated. Copyright 2004 Massachusetts Medical Society
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              HIV infection and risk for incident pulmonary diseases in the combination antiretroviral therapy era.

              David Rimland, Tamar Goulet, Kristina Crothers … (2011)
              In aging HIV-infected populations comorbid diseases are important determinants of morbidity and mortality. Pulmonary diseases have not been systematically assessed in the combination antiretroviral therapy (ART) era. To determine the incidence of pulmonary diseases in HIV-infected persons compared with HIV-uninfected persons. We analyzed data from the Veterans Aging Cohort Study Virtual Cohort, consisting of 33,420 HIV-infected veterans and 66,840 age, sex, race and ethnicity, and site-matched HIV-uninfected veterans. Using Poisson regression, incidence rates and adjusted incidence rate ratios were calculated to determine the association of HIV with pulmonary disease. The Virtual Cohort was merged with the 1999 Veterans Large Health Survey to adjust for self-reported smoking in a nested sample (14%). Incident chronic obstructive pulmonary disease, lung cancer, pulmonary hypertension, and pulmonary fibrosis, as well as pulmonary infections, were significantly more likely among HIV-infected patients compared with uninfected patients in adjusted analyses, although rates of asthma did not differ by HIV status. Bacterial pneumonia and chronic obstructive pulmonary disease were the two most common incident pulmonary diseases, whereas opportunistic pneumonias were less common. Absolute rates of most pulmonary diseases increased with age, although the relative differences between those with and without HIV infection were greatest in younger persons. Chronic obstructive pulmonary disease and asthma, as well as pulmonary infections, were less likely in those with lower HIV RNA levels and use of ART at baseline. Pulmonary diseases among HIV-infected patients receiving care within the Veterans Affairs Healthcare System in the combination ART era reflect a substantial burden of non-AIDS-defining and chronic conditions, many of which are associated with aging.
              Article 0 comments Cited 129 times – based on 0 reviews     Review now
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                Author and article information

                Contributors
                Claudio Passino: Role: Academic Editor
                Journal
                Journal ID (nlm-ta): PLoS One
                Journal ID (iso-abbrev): PLoS ONE
                Journal ID (publisher-id): plos
                Journal ID (pmc): plosone
                Title: PLoS ONE
                Publisher: Public Library of Science (San Francisco, CA USA )
                ISSN (Electronic): 1932-6203
                Publication date (Electronic): 26 March 2015
                Publication date Collection: 2015
                Volume: 10
                Issue: 3
                Electronic Location Identifier: e0123389
                Affiliations
                [1 ]Division of Pulmonary, Allergy, and Critical Care Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
                [2 ]Department of Biostatistics, University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, United States of America
                [3 ]Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, United States of America
                [4 ]Department of Medicine, SUNY Downstate Medical Center, Brooklyn, NY, United States of America
                [5 ]Heart, Lung, Blood and Vascular Medicine Institute, University of Pittsburgh and UPMC, Pittsburgh, PA, United States of America
                [6 ]Department of Immunology, University of Pittsburgh School of Medicine, Pittsburgh, PA, United States of America
                Fondazione G. Monasterio, ITALY
                Author notes

                Competing Interests: The corresponding author has read the journal's policy and the authors of this manuscript have the following competing interests: Gilead and Roche provided financial support in the form of investigator-initiated research grants. Gilead and Roche had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. This does not alter the authors’ adherence to PLOS ONE policies on sharing data and materials.

                Conceived and designed the experiments: MRG MTG AM. Performed the experiments: MRG YZ YC QY LL. Analyzed the data: MRG KBG JHJ DBH AM. Contributed reagents/materials/analysis tools: MRG YZ KBG JHJ YC QY LL DBH JML MTG AM. Wrote the paper: MRG YZ KBG JHJ YC QY LL DBH JML MTG AM.

                Article
                Publisher ID: PONE-D-14-46657
                DOI: 10.1371/journal.pone.0123389
                PMC ID: 4374715
                PubMed ID: 25811188
                SO-VID: 863b42ea-cd19-4ac9-901d-834f9c82de9f
                Copyright statement: Copyright @ 2015
                License:

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

                History
                Date received : 20 October 2014
                Date accepted : 18 February 2015
                Page count
                Figures: 1, Tables: 4, Pages: 14
                Funding
                The Women’s Interagency HIV Study (WIHS) collected data in this manuscript. The contents of this publication are solely the responsibility of the authors and do not represent the official views of the National Institutes of Health (NIH). WIHS (Principal Investigators): UAB-MS WIHS (Michael Saag), U01-AI-103401; Atlanta WIHS (Ighovwerha Ofotokun and Gina Wingood), U01-AI-103408; Bronx WIHS (Kathryn Anastos), U01-AI-035004; Brooklyn WIHS (Howard Minkoff and Deborah Gustafson), U01-AI-031834; Chicago WIHS (Mardge Cohen), U01-AI-034993; Metropolitan Washington WIHS (Mary Young), U01-AI-034994; Miami WIHS (Margaret Fischl and Lisa Metsch), U01-AI-103397; UNC WIHS (Adaora Adimora), U01-AI-103390; Connie Wofsy Women’s HIV Study, Northern California (Ruth Greenblatt, Bradley Aouizerat, and Phyllis Tien), U01-AI-034989; WIHS Data Management and Analysis Center (Stephen Gange and Elizabeth Golub), U01-AI-042590; Southern California WIHS (Alexandra Levine and Marek Nowicki), U01-HD-032632 (WIHS I – WIHS IV). The WIHS is funded primarily by the National Institute of Allergy and Infectious Diseases (NIAID), with additional co-funding from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), the National Cancer Institute (NCI), the National Institute on Drug Abuse (NIDA), and the National Institute on Mental Health (NIMH). Targeted supplemental funding for specific projects is also 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 NIH Office of Research on Women’s Health. WIHS data collection is also supported by UL1-TR000004 (UCSF CTSA) and UL1-TR000454 (Atlanta CTSA). Investigator-initiated research grants were from Gilead and Roche. This study was supported by the following NIH grants: K23 HL108697 (to MRG); P01 HL103455 (to MTG, AM); R01 HL090339 (to AM). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Subject: Research Article
                Custom metadata
                Data Availability The authors do not own the data underlying this study. Data are available from the Women's Interagency HIV Study. Information for requesting data can be obtained at the website http://statepiaps.jhsph.edu/wihs/index-invest-info.htm.

                ScienceOpen disciplines: Uncategorized
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