Predicting Subclinical Cardiovascular Disease in HIV-infected Women using a Biomarker Score Open Access

Moran, Caitlin Anne (2017)

Permanent URL: https://etd.library.emory.edu/concern/etds/bk128b67q?locale=en
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Abstract

HIV infection is a well-established independent risk factor for cardiovascular disease (CVD). The risk of CVD is especially increased among younger individuals and women with HIV, compared with age- and sex-matched controls in the general population. However, CVD risk-stratification tools underperform in this setting. Biomarkers, including high-sensitivity C-reactive protein (hsCRP), d-dimer, heat shock protein 70 (HSP-70), and bilirubin, are associated with CVD risk in the general population, but their utility in enhancing CVD prediction in the HIV-infected population is unknown. In this retrospective cohort study of HIV-infected and at-risk HIV-uninfected women in the Women's Interagency HIV Study (WIHS) vascular substudy, hsCRP, d-dimer, HSP-70, and bilirubin, levels measured at the initial substudy visit above or below pre-specified cutpoints made up a composite biomarker score from 0-4. Multivariable regression modeling was used to determine the association between the biomarker score and the presence and progression of subclinical CVD [increased carotid intima-media thickness (CIMT), development of common carotid artery (CCA) lesions (IMT >1.5 mm), and/or increased carotid artery echolucency] as measured by high resolution B-mode ultrasonography. 783 women (572 HIV-infected, 211 HIV-uninfected) were followed for a median of 6.6 years. The composite biomarker score was not associated with baseline prevalence or progression of subclinical CVD. However, in HIV-uninfected women, hsCRP was associated with CCA plaque progression [RR 2.00, 95% confidence interval (CI) 1.21-3.29, p=0.007] and CIMT progression (mean difference 5.4, 95% CI 0.2-10.7, p=0.04]. No association was seen in HIV-infected women. These findings suggest that the pathogenesis of CVD may be different in the setting of HIV infection and further research is warranted.

Table of Contents

Introduction 1

Background 3

Methods 7

Results 16

Discussion/Conclusions 20

References 25

Table 1: Baseline demographic and clinical data for all women and by HIV

serostatus and biomarker score 33

Table 2: Subclinical CVD outcomes for all participants and by HIV

serostatus and biomarker score 36

Table 3: Median baseline biomarker values for all participants by HIV serostatus 37

Table 4: Unadjusted odds ratios or mean differences for baseline CCA plaque

formation, CIMT, or carotid echolucency according to biomarker levels for all

participants, and by HIV serostatus 38

Table 5: Unadjusted odds ratios or mean differences for change in CCA plaque

formation, CIMT, or carotid echolucency according to biomarker levels for all

participants, and by HIV serostatus 41

Table 6: Adjusted odds ratios or mean differences for baseline CCA plaques,

CIMT, or carotid echolucency according to biomarker levels for all participants,

and by HIV serostatus 44

Table 7: Adjusted rate ratios or mean differences for change in CCA plaques,

CIMT,or carotid echolucency according to biomarker levels for all participants,

and by HIV serostatus 47

Figure 1: Study design for the WIHS vascular substudy 50

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