Factors associated with D-dimer levels in HIV-infected individuals

Alvaro H Borges; Jemma L O'Connor; Andrew N Phillips; Jason V Baker; Michael J Vjecha; Marcelo H Losso; Hartwig Klinker; Gustavo Lopardo; Ian Williams; Jens D Lundgren; INSIGHT SMART Study Group

doi:10.1371/journal.pone.0090978

Factors associated with D-dimer levels in HIV-infected individuals

Alvaro H Borges, Jemma L O'Connor, Andrew N Phillips, Jason V Baker, Michael J Vjecha, Marcelo H Losso, Hartwig Klinker, Gustavo Lopardo, Ian Williams, Jens D Lundgren, INSIGHT SMART Study Group

Department of Clinical Medicine

39 Citations (Scopus)

Abstract

BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.

METHODS: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.

RESULTS: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.

CONCLUSIONS: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.

Original language	English
Article number	e90978
Journal	PloS one
Volume	9
Issue number	3
Pages (from-to)	1-11
Number of pages	11
ISSN	1932-6203
DOIs	https://doi.org/10.1371/journal.pone.0090978
Publication status	Published - 13 Mar 2014

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title = "Factors associated with D-dimer levels in HIV-infected individuals",

abstract = "BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.METHODS: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.RESULTS: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.CONCLUSIONS: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.",

author = "Borges, {Alvaro H} and O'Connor, {Jemma L} and Phillips, {Andrew N} and Baker, {Jason V} and Vjecha, {Michael J} and Losso, {Marcelo H} and Hartwig Klinker and Gustavo Lopardo and Ian Williams and Lundgren, {Jens D} and {INSIGHT SMART Study Group}",

year = "2014",

month = mar,

day = "13",

doi = "10.1371/journal.pone.0090978",

language = "English",

volume = "9",

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journal = "PLoS Computational Biology",

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TY - JOUR

T1 - Factors associated with D-dimer levels in HIV-infected individuals

AU - Borges, Alvaro H

AU - O'Connor, Jemma L

AU - Phillips, Andrew N

AU - Baker, Jason V

AU - Vjecha, Michael J

AU - Losso, Marcelo H

AU - Klinker, Hartwig

AU - Lopardo, Gustavo

AU - Williams, Ian

AU - Lundgren, Jens D

AU - INSIGHT SMART Study Group

PY - 2014/3/13

Y1 - 2014/3/13

N2 - BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.METHODS: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.RESULTS: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.CONCLUSIONS: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.

AB - BACKGROUND: Higher plasma D-dimer levels are strong predictors of mortality in HIV+ individuals. The factors associated with D-dimer levels during HIV infection, however, remain poorly understood.METHODS: In this cross-sectional study, participants in three randomized controlled trials with measured D-dimer levels were included (N = 9,848). Factors associated with D-dimer were identified by linear regression. Covariates investigated were: age, gender, race, body mass index, nadir and baseline CD4+ count, plasma HIV RNA levels, markers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6]), antiretroviral therapy (ART) use, ART regimens, co-morbidities (hepatitis B/C, diabetes mellitus, prior cardiovascular disease), smoking, renal function (estimated glomerular filtration rate [eGFR] and cystatin C) and cholesterol.RESULTS: Women from all age groups had higher D-dimer levels than men, though a steeper increase of D-dimer with age occurred in men. Hepatitis B/C co-infection was the only co-morbidity associated with higher D-dimer levels. In this subgroup, the degree of hepatic fibrosis, as demonstrated by higher hyaluronic acid levels, but not viral load of hepatitis viruses, was positively correlated with D-dimer. Other factors independently associated with higher D-dimer levels were black race, higher plasma HIV RNA levels, being off ART at baseline, and increased levels of CRP, IL-6 and cystatin C. In contrast, higher baseline CD4+ counts and higher high-density lipoprotein cholesterol were negatively correlated with D-dimer levels.CONCLUSIONS: D-dimer levels increase with age in HIV+ men, but are already elevated in women at an early age due to reasons other than a higher burden of concomitant diseases. In hepatitis B/C co-infected individuals, hepatic fibrosis, but not hepatitis viral load, was associated with higher D-dimer levels.

U2 - 10.1371/journal.pone.0090978

DO - 10.1371/journal.pone.0090978

M3 - Journal article

C2 - 24626096

SN - 1932-6203

VL - 9

SP - 1

EP - 11

JO - PLoS Computational Biology

JF - PLoS Computational Biology

IS - 3

M1 - e90978

ER -

Factors associated with D-dimer levels in HIV-infected individuals

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