Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment

Robert C. Kaplan, Alan L. Landay, Howard N. Hodis, Stephen J. Gange, Philip J. Norris, Mary Young, Kathryn Anastos, Phyllis C. Tien, Xiaonan (Nan) Xue, Jason Lazar, Christina M. Parrinello, Lorie Benning, Russell P. Tracy

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). Methods: In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound. Results: Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 μg/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness. Conclusions: Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.

Original languageEnglish (US)
Pages (from-to)359-368
Number of pages10
JournalJournal of Acquired Immune Deficiency Syndromes
Volume60
Issue number4
DOIs
StatePublished - Aug 1 2012

Fingerprint

Cardiovascular Diseases
Highly Active Antiretroviral Therapy
HIV
Interleukin-2 Receptors
Tumor Necrosis Factor-alpha
Hemostasis
Interleukin-10
Therapeutics
Carotid Intima-Media Thickness
Chemokine CCL2
Biomarkers
Carotid Arteries
HIV Infections
Interleukin-6
Atherosclerosis
Inflammation
Fibrinogen
Blood Vessels
fibrin fragment D

Keywords

  • antiretroviral therapy
  • cardiovascular diseases
  • cytokines
  • hemostasis
  • HIV
  • inflammation

ASJC Scopus subject areas

  • Infectious Diseases
  • Pharmacology (medical)

Cite this

Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment. / Kaplan, Robert C.; Landay, Alan L.; Hodis, Howard N.; Gange, Stephen J.; Norris, Philip J.; Young, Mary; Anastos, Kathryn; Tien, Phyllis C.; Xue, Xiaonan (Nan); Lazar, Jason; Parrinello, Christina M.; Benning, Lorie; Tracy, Russell P.

In: Journal of Acquired Immune Deficiency Syndromes, Vol. 60, No. 4, 01.08.2012, p. 359-368.

Research output: Contribution to journalArticle

Kaplan, RC, Landay, AL, Hodis, HN, Gange, SJ, Norris, PJ, Young, M, Anastos, K, Tien, PC, Xue, XN, Lazar, J, Parrinello, CM, Benning, L & Tracy, RP 2012, 'Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment', Journal of Acquired Immune Deficiency Syndromes, vol. 60, no. 4, pp. 359-368. https://doi.org/10.1097/QAI.0b013e31825b03be
Kaplan, Robert C. ; Landay, Alan L. ; Hodis, Howard N. ; Gange, Stephen J. ; Norris, Philip J. ; Young, Mary ; Anastos, Kathryn ; Tien, Phyllis C. ; Xue, Xiaonan (Nan) ; Lazar, Jason ; Parrinello, Christina M. ; Benning, Lorie ; Tracy, Russell P. / Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment. In: Journal of Acquired Immune Deficiency Syndromes. 2012 ; Vol. 60, No. 4. pp. 359-368.
@article{334f067d9d5c48aba026188e6631e421,
title = "Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment",
abstract = "Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). Methods: In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound. Results: Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 μg/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness. Conclusions: Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.",
keywords = "antiretroviral therapy, cardiovascular diseases, cytokines, hemostasis, HIV, inflammation",
author = "Kaplan, {Robert C.} and Landay, {Alan L.} and Hodis, {Howard N.} and Gange, {Stephen J.} and Norris, {Philip J.} and Mary Young and Kathryn Anastos and Tien, {Phyllis C.} and Xue, {Xiaonan (Nan)} and Jason Lazar and Parrinello, {Christina M.} and Lorie Benning and Tracy, {Russell P.}",
year = "2012",
month = "8",
day = "1",
doi = "10.1097/QAI.0b013e31825b03be",
language = "English (US)",
volume = "60",
pages = "359--368",
journal = "Journal of Acquired Immune Deficiency Syndromes",
issn = "1525-4135",
publisher = "Lippincott Williams and Wilkins",
number = "4",

}

TY - JOUR

T1 - Potential cardiovascular disease risk markers among HIV-infected women initiating antiretroviral treatment

AU - Kaplan, Robert C.

AU - Landay, Alan L.

AU - Hodis, Howard N.

AU - Gange, Stephen J.

AU - Norris, Philip J.

AU - Young, Mary

AU - Anastos, Kathryn

AU - Tien, Phyllis C.

AU - Xue, Xiaonan (Nan)

AU - Lazar, Jason

AU - Parrinello, Christina M.

AU - Benning, Lorie

AU - Tracy, Russell P.

PY - 2012/8/1

Y1 - 2012/8/1

N2 - Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). Methods: In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound. Results: Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 μg/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness. Conclusions: Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.

AB - Background: Inflammation and hemostasis perturbation may be involved in vascular complications of HIV infection. We examined atherogenic biomarkers and subclinical atherosclerosis in HIV-infected adults before and after beginning highly active antiretroviral therapy (HAART). Methods: In the Women's Interagency HIV Study, 127 HIV-infected women studied pre and post HAART were matched to HIV-uninfected controls. Six semiannual measurements of soluble CD14, tumor necrosis factor (TNF) alfa, soluble interleukin (IL) 2 receptor, IL-6, IL-10, monocyte chemoattractant protein 1, D-dimer, and fibrinogen were obtained. Carotid artery intima-media thickness was measured by B-mode ultrasound. Results: Relative to HIV-uninfected controls, HAART-naive HIV-infected women had elevated levels of soluble CD14 (1945 vs 1662 ng/mL, Wilcoxon signed rank P < 0.0001), TNF-α (6.3 vs 3.4 pg/mL, P < 0.0001), soluble IL-2 receptor (1587 vs 949 pg/mL, P < 0.0001), IL-10 (3.3 vs 1.9 pg/mL, P < 0.0001), monocyte chemoattractant protein 1 (190 vs 163 pg/mL, P < 0.0001), and D-dimer (0.43 vs 0.31 μg/mL, P < 0.01). Elevated biomarker levels declined after HAART. Although most biomarkers normalized to HIV-uninfected levels, in women on effective HAART, TNF-α levels remained elevated compared with HIV-uninfected women (+0.8 pg/mL, P = 0.0002). Higher post-HAART levels of soluble IL-2 receptor (P = 0.02), IL-6 (P = 0.05), and D-dimer (P = 0.03) were associated with increased carotid artery intima-media thickness. Conclusions: Untreated HIV infection is associated with abnormal hemostasis (eg, D-dimer), proatherogenic (eg, TNF-α), and antiatherogenic (eg, IL-10) inflammatory markers. HAART reduces most inflammatory mediators to HIV-uninfected levels. Increased inflammation and hemostasis are associated with subclinical atherosclerosis in recently treated women. These findings have potential implications for long-term risk of cardiovascular disease in HIV-infected patients, even with effective therapy.

KW - antiretroviral therapy

KW - cardiovascular diseases

KW - cytokines

KW - hemostasis

KW - HIV

KW - inflammation

UR - http://www.scopus.com/inward/record.url?scp=84864278251&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864278251&partnerID=8YFLogxK

U2 - 10.1097/QAI.0b013e31825b03be

DO - 10.1097/QAI.0b013e31825b03be

M3 - Article

C2 - 22592585

AN - SCOPUS:84864278251

VL - 60

SP - 359

EP - 368

JO - Journal of Acquired Immune Deficiency Syndromes

JF - Journal of Acquired Immune Deficiency Syndromes

SN - 1525-4135

IS - 4

ER -