Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals

Abstract Objectives This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with...

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Veröffentlicht in:JACC. Heart failure 2015-08, Vol.3 (8), p.591-599
Hauptverfasser: Secemsky, Eric A., MD, Scherzer, Rebecca, PhD, Nitta, Elaine, MPH, Wu, Alan H.B., PhD, Lange, David C., MD, Deeks, Steven G., MD, Martin, Jeffrey N., MD, Snider, James, PhD, Ganz, Peter, MD, Hsue, Priscilla Y., MD
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container_end_page 599
container_issue 8
container_start_page 591
container_title JACC. Heart failure
container_volume 3
creator Secemsky, Eric A., MD
Scherzer, Rebecca, PhD
Nitta, Elaine, MPH
Wu, Alan H.B., PhD
Lange, David C., MD
Deeks, Steven G., MD
Martin, Jeffrey N., MD
Snider, James, PhD
Ganz, Peter, MD
Hsue, Priscilla Y., MD
description Abstract Objectives This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality. Background HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information. Methods Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction 
doi_str_mv 10.1016/j.jchf.2015.03.007
format Article
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Background HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information. Methods Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction &lt;50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index. Results Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy. Conclusions Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.</description><identifier>ISSN: 2213-1779</identifier><identifier>EISSN: 2213-1787</identifier><identifier>DOI: 10.1016/j.jchf.2015.03.007</identifier><identifier>PMID: 26164679</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Adult ; biomarkers ; Biomarkers - blood ; Cardiovascular ; cardiovascular dysfunction ; Cohort Studies ; death ; Echocardiography ; Female ; Heart Failure - blood ; Heart Failure - diagnosis ; Heart Failure, Diastolic - blood ; Heart Failure, Diastolic - diagnosis ; HIV ; HIV Infections - blood ; HIV Infections - diagnosis ; Humans ; Hypertension, Pulmonary - blood ; Hypertension, Pulmonary - diagnosis ; Interleukin-1 Receptor-Like 1 Protein ; Male ; Middle Aged ; mortality ; Natriuretic Peptide, Brain - blood ; Outcome Assessment (Health Care) ; Peptide Fragments - blood ; Predictive Value of Tests ; Receptors, Cell Surface - blood ; Reference Values ; Survival Rate</subject><ispartof>JACC. Heart failure, 2015-08, Vol.3 (8), p.591-599</ispartof><rights>American College of Cardiology Foundation</rights><rights>2015 American College of Cardiology Foundation</rights><rights>Copyright © 2015 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c580t-db618f624dde1088be5460fe11d91a5f2495bafb4864c37502b3a53e2fb7ab213</citedby><cites>FETCH-LOGICAL-c580t-db618f624dde1088be5460fe11d91a5f2495bafb4864c37502b3a53e2fb7ab213</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26164679$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Secemsky, Eric A., MD</creatorcontrib><creatorcontrib>Scherzer, Rebecca, PhD</creatorcontrib><creatorcontrib>Nitta, Elaine, MPH</creatorcontrib><creatorcontrib>Wu, Alan H.B., PhD</creatorcontrib><creatorcontrib>Lange, David C., MD</creatorcontrib><creatorcontrib>Deeks, Steven G., MD</creatorcontrib><creatorcontrib>Martin, Jeffrey N., MD</creatorcontrib><creatorcontrib>Snider, James, PhD</creatorcontrib><creatorcontrib>Ganz, Peter, MD</creatorcontrib><creatorcontrib>Hsue, Priscilla Y., MD</creatorcontrib><title>Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals</title><title>JACC. Heart failure</title><addtitle>JACC Heart Fail</addtitle><description>Abstract Objectives This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality. Background HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information. Methods Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction &lt;50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index. Results Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy. Conclusions Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.</description><subject>Adult</subject><subject>biomarkers</subject><subject>Biomarkers - blood</subject><subject>Cardiovascular</subject><subject>cardiovascular dysfunction</subject><subject>Cohort Studies</subject><subject>death</subject><subject>Echocardiography</subject><subject>Female</subject><subject>Heart Failure - blood</subject><subject>Heart Failure - diagnosis</subject><subject>Heart Failure, Diastolic - blood</subject><subject>Heart Failure, Diastolic - diagnosis</subject><subject>HIV</subject><subject>HIV Infections - blood</subject><subject>HIV Infections - diagnosis</subject><subject>Humans</subject><subject>Hypertension, Pulmonary - blood</subject><subject>Hypertension, Pulmonary - diagnosis</subject><subject>Interleukin-1 Receptor-Like 1 Protein</subject><subject>Male</subject><subject>Middle Aged</subject><subject>mortality</subject><subject>Natriuretic Peptide, Brain - blood</subject><subject>Outcome Assessment (Health Care)</subject><subject>Peptide Fragments - blood</subject><subject>Predictive Value of Tests</subject><subject>Receptors, Cell Surface - blood</subject><subject>Reference Values</subject><subject>Survival Rate</subject><issn>2213-1779</issn><issn>2213-1787</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9ksFu1DAQhiMEolXpC3BAPnLoBtuJ7URClWBp6UoVPRS4Wo49Zp1m7WInkfbtcbRlBRzwZWz5n9-e-aYoXhNcEkz4u77s9daWFBNW4qrEWDwrTikl1YqIRjw_7kV7Upyn1OO8GkaapnlZnFBOeM1Fe1psv4QZBvTRhZ2KDxATChatVTROaXQ_Rkjp4nAOs0p6GlREn_bJTl6PLvgLpLxBd9Ooww4Sch7dbL6vNt6CHsGgjTdudmZSQ3pVvLA5wPlTPCu-XV99Xd-sbu8-b9YfbleaNXhcmY6TxnJaGwMEN00HrObYAiGmJYpZWresU7arG17rSjBMu0qxCqjthOpyyWfF5cH3cep2YDT4MapBPkaXC9zLoJz8-8a7rfwRZlkz2gpRZ4O3TwYx_JwgjXLnkoZhUB7ClCQRmHJW1bTKUnqQ6hhSimCPzxAsF0qylwsluVCSuJKZUk568-cHjym_mWTB-4MAcptmB1Em7cBrMC7mtkoT3P_9L_9J14PzTqvhAfaQ-jBFnwFIIhOVWN4vc7KMCWEYU9Hy6heZmLmO</recordid><startdate>20150801</startdate><enddate>20150801</enddate><creator>Secemsky, Eric A., MD</creator><creator>Scherzer, Rebecca, PhD</creator><creator>Nitta, Elaine, MPH</creator><creator>Wu, Alan H.B., PhD</creator><creator>Lange, David C., MD</creator><creator>Deeks, Steven G., MD</creator><creator>Martin, Jeffrey N., MD</creator><creator>Snider, James, PhD</creator><creator>Ganz, Peter, MD</creator><creator>Hsue, Priscilla Y., MD</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20150801</creationdate><title>Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals</title><author>Secemsky, Eric A., MD ; Scherzer, Rebecca, PhD ; Nitta, Elaine, MPH ; Wu, Alan H.B., PhD ; Lange, David C., MD ; Deeks, Steven G., MD ; Martin, Jeffrey N., MD ; Snider, James, PhD ; Ganz, Peter, MD ; Hsue, Priscilla Y., MD</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c580t-db618f624dde1088be5460fe11d91a5f2495bafb4864c37502b3a53e2fb7ab213</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Adult</topic><topic>biomarkers</topic><topic>Biomarkers - blood</topic><topic>Cardiovascular</topic><topic>cardiovascular dysfunction</topic><topic>Cohort Studies</topic><topic>death</topic><topic>Echocardiography</topic><topic>Female</topic><topic>Heart Failure - blood</topic><topic>Heart Failure - diagnosis</topic><topic>Heart Failure, Diastolic - blood</topic><topic>Heart Failure, Diastolic - diagnosis</topic><topic>HIV</topic><topic>HIV Infections - blood</topic><topic>HIV Infections - diagnosis</topic><topic>Humans</topic><topic>Hypertension, Pulmonary - blood</topic><topic>Hypertension, Pulmonary - diagnosis</topic><topic>Interleukin-1 Receptor-Like 1 Protein</topic><topic>Male</topic><topic>Middle Aged</topic><topic>mortality</topic><topic>Natriuretic Peptide, Brain - blood</topic><topic>Outcome Assessment (Health Care)</topic><topic>Peptide Fragments - blood</topic><topic>Predictive Value of Tests</topic><topic>Receptors, Cell Surface - blood</topic><topic>Reference Values</topic><topic>Survival Rate</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Secemsky, Eric A., MD</creatorcontrib><creatorcontrib>Scherzer, Rebecca, PhD</creatorcontrib><creatorcontrib>Nitta, Elaine, MPH</creatorcontrib><creatorcontrib>Wu, Alan H.B., PhD</creatorcontrib><creatorcontrib>Lange, David C., MD</creatorcontrib><creatorcontrib>Deeks, Steven G., MD</creatorcontrib><creatorcontrib>Martin, Jeffrey N., MD</creatorcontrib><creatorcontrib>Snider, James, PhD</creatorcontrib><creatorcontrib>Ganz, Peter, MD</creatorcontrib><creatorcontrib>Hsue, Priscilla Y., MD</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>JACC. Heart failure</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Secemsky, Eric A., MD</au><au>Scherzer, Rebecca, PhD</au><au>Nitta, Elaine, MPH</au><au>Wu, Alan H.B., PhD</au><au>Lange, David C., MD</au><au>Deeks, Steven G., MD</au><au>Martin, Jeffrey N., MD</au><au>Snider, James, PhD</au><au>Ganz, Peter, MD</au><au>Hsue, Priscilla Y., MD</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals</atitle><jtitle>JACC. Heart failure</jtitle><addtitle>JACC Heart Fail</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>3</volume><issue>8</issue><spage>591</spage><epage>599</epage><pages>591-599</pages><issn>2213-1779</issn><eissn>2213-1787</eissn><abstract>Abstract Objectives This study sought to determine whether biomarkers ST2, growth differentiation factor (GDF)-15, N-terminal pro–B-type natriuretic peptide (NT-proBNP), and high-sensitivity troponin I are elevated in patients infected with human immunodeficiency virus (HIV) and are associated with cardiovascular dysfunction and all-cause mortality. Background HIV-infected patients have high rates of cardiovascular disease. Markers of myocardial stress may identify at-risk patients and provide additional prognostic information. Methods Biomarkers and echocardiograms were assessed in 332 HIV-infected patients and 50 age- and sex-matched control subjects. Left ventricular systolic dysfunction was defined as ejection fraction &lt;50%, diastolic dysfunction (DD) as stage 1 or higher, and pulmonary hypertension as pulmonary artery systolic pressure ≥35 mm Hg. Mortality data were obtained from the National Death Index. Results Patients with HIV had a median age of 49 years, and 80% were male. Compared with control subjects, HIV-infected patients had higher adjusted percent estimates of all biomarkers except ST2 and interleukin-6. Among HIV-infected patients, 45% had DD; only ST2 was associated with DD (relative risk [RR]: 1.36; p = 0.047). Left ventricular systolic dysfunction was rare in this cohort (5%). Pulmonary hypertension was present in 27% of HIV-infected patients and was associated with GDF-15 (RR: 1.18; p = 0.04), NT-proBNP (RR: 1.18; p = 0.007), and cystatin C (RR: 1.54; p = 0.03). Thirty-eight deaths occurred among HIV-infected patients over a median of 6.1 years. In adjusted analysis, all-cause mortality was independently predicted by ST2 (hazard ratio [HR]: 2.04; p = 0.010), GDF-15 (HR: 1.42; p = 0.0054), high-sensitivity C-reactive protein (HR: 1.25; p = 0.023), and D-dimer (HR: 1.49; p = 0.029). Relationships were unchanged when analyses were restricted to virally suppressed HIV-infected patients receiving antiretroviral therapy. Conclusions Among HIV-infected patients, ST2 and GDF-15 were associated with both cardiovascular dysfunction and all-cause mortality, and these variables may be useful at identifying those at risk for developing cardiovascular events and death.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>26164679</pmid><doi>10.1016/j.jchf.2015.03.007</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record>
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subjects Adult
biomarkers
Biomarkers - blood
Cardiovascular
cardiovascular dysfunction
Cohort Studies
death
Echocardiography
Female
Heart Failure - blood
Heart Failure - diagnosis
Heart Failure, Diastolic - blood
Heart Failure, Diastolic - diagnosis
HIV
HIV Infections - blood
HIV Infections - diagnosis
Humans
Hypertension, Pulmonary - blood
Hypertension, Pulmonary - diagnosis
Interleukin-1 Receptor-Like 1 Protein
Male
Middle Aged
mortality
Natriuretic Peptide, Brain - blood
Outcome Assessment (Health Care)
Peptide Fragments - blood
Predictive Value of Tests
Receptors, Cell Surface - blood
Reference Values
Survival Rate
title Novel Biomarkers of Cardiac Stress, Cardiovascular Dysfunction, and Outcomes in HIV-Infected Individuals
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