Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis

Judith M Haissman; Anna Karen Haugaard; Andreas Knudsen; Ulrik Sloth Kristoffersen; Ingebjørg Seljeflot; Karin K Pedersen; Anne-Mette Lebech; Philip Hasbak; Andreas Kjær; Sisse Rye Ostrowski; Jan Gerstoft; Marius Trøseid; Susanne D Nielsen

doi:10.1097/QAI.0000000000001148

Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis

Judith M Haissman, Anna Karen Haugaard, Andreas Knudsen, Ulrik Sloth Kristoffersen, Ingebjørg Seljeflot, Karin K Pedersen, Anne-Mette Lebech, Philip Hasbak, Andreas Kjær, Sisse Rye Ostrowski, Jan Gerstoft, Marius Trøseid, Susanne D Nielsen

Institut for Klinisk Medicin

8 Citationer (Scopus)

Abstract

BACKGROUND: Cardiovascular disease contributes to excess morbidity and mortality in HIV infection, and endothelial dysfunction may contribute to this pattern. We aimed to determine the endothelial function in treated and untreated HIV-infected individuals and investigate potential associations with viral replication, immune activation, coagulation, platelet function, and subclinical atherosclerosis.

METHODS: Asymmetric dimethylarginine (ADMA, marker of endothelial dysfunction) and soluble CD14 (sCD14, marker of monocyte activation) were measured in plasma from two previously established cross-sectional cohorts: cohort A including 50 untreated and 50 antiretroviral therapy (ART)-treated HIV-infected individuals with previously assessed coagulation and platelet function and cohort B including 105 HIV-infected individuals on ART and 105 uninfected controls with previously assessed coronary artery calcium score, myocardial perfusion defects, and carotid intima-media thickness.

RESULTS: Concentrations of ADMA were higher in HIV-infected individuals compared with uninfected controls, and higher ADMA was found in ART-treated compared with untreated HIV-infected individuals. ADMA was associated with viral load, sCD14, D-dimer, and low CD4 T-cell count in untreated HIV infection. Only viral load remained significant in multivariate analyses. In ART-treated HIV-infected individuals, ADMA was not associated with coronary artery calcium score, myocardial perfusion defects, or intima-media thickness.

CONCLUSIONS: Evidence of endothelial dysfunction was found in HIV infection and in untreated compared with treated HIV infection. In untreated HIV infection, the main driver of endothelial dysfunction was viral replication. Importantly, in treated HIV infection, ADMA was not associated with subclinical atherosclerosis. Thus, our data question the potential of ADMA as a useful biomarker of early atherosclerosis in treated HIV infection.

Originalsprog	Engelsk
Tidsskrift	J A I D S
Vol/bind	73
Udgave nummer	5
Sider (fra-til)	507-513
Antal sider	7
ISSN	1525-4135
DOI	https://doi.org/10.1097/QAI.0000000000001148
Status	Udgivet - 15 dec. 2016

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10.1097/QAI.0000000000001148

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Haissman, J. M., Haugaard, A. K., Knudsen, A., Kristoffersen, U. S., Seljeflot, I., Pedersen, K. K., Lebech, A-M., Hasbak, P., Kjær, A., Ostrowski, S. R., Gerstoft, J., Trøseid, M., & Nielsen, S. D. (2016). Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis. J A I D S, 73(5), 507-513. https://doi.org/10.1097/QAI.0000000000001148

Haissman, JM, Haugaard, AK, Knudsen, A, Kristoffersen, US, Seljeflot, I, Pedersen, KK, Lebech, A-M, Hasbak, P, Kjær, A, Ostrowski, SR , Gerstoft, J, Trøseid, M & Nielsen, SD 2016, 'Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis', J A I D S, bind 73, nr. 5, s. 507-513. https://doi.org/10.1097/QAI.0000000000001148

@article{62942a73257d446b8a3e917488bc1390,

title = "Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis",

abstract = "BACKGROUND: Cardiovascular disease contributes to excess morbidity and mortality in HIV infection, and endothelial dysfunction may contribute to this pattern. We aimed to determine the endothelial function in treated and untreated HIV-infected individuals and investigate potential associations with viral replication, immune activation, coagulation, platelet function, and subclinical atherosclerosis.METHODS: Asymmetric dimethylarginine (ADMA, marker of endothelial dysfunction) and soluble CD14 (sCD14, marker of monocyte activation) were measured in plasma from two previously established cross-sectional cohorts: cohort A including 50 untreated and 50 antiretroviral therapy (ART)-treated HIV-infected individuals with previously assessed coagulation and platelet function and cohort B including 105 HIV-infected individuals on ART and 105 uninfected controls with previously assessed coronary artery calcium score, myocardial perfusion defects, and carotid intima-media thickness.RESULTS: Concentrations of ADMA were higher in HIV-infected individuals compared with uninfected controls, and higher ADMA was found in ART-treated compared with untreated HIV-infected individuals. ADMA was associated with viral load, sCD14, D-dimer, and low CD4 T-cell count in untreated HIV infection. Only viral load remained significant in multivariate analyses. In ART-treated HIV-infected individuals, ADMA was not associated with coronary artery calcium score, myocardial perfusion defects, or intima-media thickness.CONCLUSIONS: Evidence of endothelial dysfunction was found in HIV infection and in untreated compared with treated HIV infection. In untreated HIV infection, the main driver of endothelial dysfunction was viral replication. Importantly, in treated HIV infection, ADMA was not associated with subclinical atherosclerosis. Thus, our data question the potential of ADMA as a useful biomarker of early atherosclerosis in treated HIV infection.",

author = "Haissman, {Judith M} and Haugaard, {Anna Karen} and Andreas Knudsen and Kristoffersen, {Ulrik Sloth} and Ingebj{\o}rg Seljeflot and Pedersen, {Karin K} and Anne-Mette Lebech and Philip Hasbak and Andreas Kj{\ae}r and Ostrowski, {Sisse Rye} and Jan Gerstoft and Marius Tr{\o}seid and Nielsen, {Susanne D}",

year = "2016",

month = dec,

day = "15",

doi = "10.1097/QAI.0000000000001148",

language = "English",

volume = "73",

pages = "507--513",

journal = "J A I D S",

issn = "1525-4135",

publisher = "Lippincott Williams & Wilkins",

number = "5",

}

TY - JOUR

T1 - Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis

AU - Haissman, Judith M

AU - Haugaard, Anna Karen

AU - Knudsen, Andreas

AU - Kristoffersen, Ulrik Sloth

AU - Seljeflot, Ingebjørg

AU - Pedersen, Karin K

AU - Lebech, Anne-Mette

AU - Hasbak, Philip

AU - Kjær, Andreas

AU - Ostrowski, Sisse Rye

AU - Gerstoft, Jan

AU - Trøseid, Marius

AU - Nielsen, Susanne D

PY - 2016/12/15

Y1 - 2016/12/15

N2 - BACKGROUND: Cardiovascular disease contributes to excess morbidity and mortality in HIV infection, and endothelial dysfunction may contribute to this pattern. We aimed to determine the endothelial function in treated and untreated HIV-infected individuals and investigate potential associations with viral replication, immune activation, coagulation, platelet function, and subclinical atherosclerosis.METHODS: Asymmetric dimethylarginine (ADMA, marker of endothelial dysfunction) and soluble CD14 (sCD14, marker of monocyte activation) were measured in plasma from two previously established cross-sectional cohorts: cohort A including 50 untreated and 50 antiretroviral therapy (ART)-treated HIV-infected individuals with previously assessed coagulation and platelet function and cohort B including 105 HIV-infected individuals on ART and 105 uninfected controls with previously assessed coronary artery calcium score, myocardial perfusion defects, and carotid intima-media thickness.RESULTS: Concentrations of ADMA were higher in HIV-infected individuals compared with uninfected controls, and higher ADMA was found in ART-treated compared with untreated HIV-infected individuals. ADMA was associated with viral load, sCD14, D-dimer, and low CD4 T-cell count in untreated HIV infection. Only viral load remained significant in multivariate analyses. In ART-treated HIV-infected individuals, ADMA was not associated with coronary artery calcium score, myocardial perfusion defects, or intima-media thickness.CONCLUSIONS: Evidence of endothelial dysfunction was found in HIV infection and in untreated compared with treated HIV infection. In untreated HIV infection, the main driver of endothelial dysfunction was viral replication. Importantly, in treated HIV infection, ADMA was not associated with subclinical atherosclerosis. Thus, our data question the potential of ADMA as a useful biomarker of early atherosclerosis in treated HIV infection.

AB - BACKGROUND: Cardiovascular disease contributes to excess morbidity and mortality in HIV infection, and endothelial dysfunction may contribute to this pattern. We aimed to determine the endothelial function in treated and untreated HIV-infected individuals and investigate potential associations with viral replication, immune activation, coagulation, platelet function, and subclinical atherosclerosis.METHODS: Asymmetric dimethylarginine (ADMA, marker of endothelial dysfunction) and soluble CD14 (sCD14, marker of monocyte activation) were measured in plasma from two previously established cross-sectional cohorts: cohort A including 50 untreated and 50 antiretroviral therapy (ART)-treated HIV-infected individuals with previously assessed coagulation and platelet function and cohort B including 105 HIV-infected individuals on ART and 105 uninfected controls with previously assessed coronary artery calcium score, myocardial perfusion defects, and carotid intima-media thickness.RESULTS: Concentrations of ADMA were higher in HIV-infected individuals compared with uninfected controls, and higher ADMA was found in ART-treated compared with untreated HIV-infected individuals. ADMA was associated with viral load, sCD14, D-dimer, and low CD4 T-cell count in untreated HIV infection. Only viral load remained significant in multivariate analyses. In ART-treated HIV-infected individuals, ADMA was not associated with coronary artery calcium score, myocardial perfusion defects, or intima-media thickness.CONCLUSIONS: Evidence of endothelial dysfunction was found in HIV infection and in untreated compared with treated HIV infection. In untreated HIV infection, the main driver of endothelial dysfunction was viral replication. Importantly, in treated HIV infection, ADMA was not associated with subclinical atherosclerosis. Thus, our data question the potential of ADMA as a useful biomarker of early atherosclerosis in treated HIV infection.

U2 - 10.1097/QAI.0000000000001148

DO - 10.1097/QAI.0000000000001148

M3 - Journal article

C2 - 27509250

SN - 1525-4135

VL - 73

SP - 507

EP - 513

JO - J A I D S

JF - J A I D S

IS - 5

ER -

Marker of Endothelial Dysfunction Asymmetric Dimethylarginine Is Elevated in HIV Infection but Not Associated With Subclinical Atherosclerosis

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