Abstract
Objective To study the relationship between endothelial dysfunction, HIV infection, and stroke in Malawians.
Methods Using a cross-sectional design, we measured plasma levels of intercellular adhesion molecule-1 (ICAM-1), plasminogen activator inhibitor-1 (PAI-1), vascular endothelial growth factor (VEGF), and soluble thrombomodulin (sTM) in stroke patients and controls, stratified by HIV status. These biomarkers were measured using ELISA. After dichotomization, each biomarker was used as the dependent variable in a multivariable logistic regression model. Primary independent variables included HIV and stroke status. Adjustment variables were age, sex, hypertension, diabetes mellitus, tobacco and alcohol consumption, personal/family history of stroke, antiretroviral therapy status, and hypercholesterolemia.
Results Sixty-one stroke cases (19 HIV+) and 168 controls (32 HIV+) were enrolled. The median age was 55 years (38.5–65.0) for controls and 52 years (38.0–73.0) for cases (p = 0.38). The median CD4+ T-cell count was 260.1 cells/mm3 (156.3–363.9) and 452 cells/mm3 (378.1–527.4) in HIV-infected cases and controls, respectively. HIV infection was independently associated with high levels of ICAM-1 (OR = 3.6, 95% CI: 1.3–10.6, p = 0.018) in controls but not in stroke cases even after excluding patients with a viral load >1,000 RNA copies/mL (OR = 4.1, 95% CI: 1.3–13.1, p = 0.017). There was no association between the clinical profiles of HIV-positive controls or HIV-positive stroke and high levels of PAI-1, VEGF, and sTM.
Conclusions HIV infection is associated with endothelial activation despite antiretroviral treatment. Our findings underscore the need for larger clinical cohorts to better understand the contribution of this perturbation of the endothelial function to the increasing burden of cardiovascular diseases in sub-Saharan Africa.
Glossary
- ART=
- antiretroviral therapy;
- CV=
- coefficient of variability;
- ICAM=
- intercellular adhesion molecule;
- IQR=
- interquartile range;
- PAI=
- plasminogen activator inhibitor;
- sTM=
- soluble thrombomodulin;
- VEGF=
- vascular endothelial growth factor
Footnotes
Funding information and disclosures are provided at the end of the article. Full disclosure form information provided by the authors is available with the full text of this article at Neurology.org/NN.
The Article Processing Charge was funded by the University of Liverpool on behalf of the Wellcome Trust.
- Received July 2, 2018.
- Accepted in final form October 16, 2018.
- Copyright © 2018 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Neurology.
This is an open access article distributed under the terms of the Creative Commons Attribution License 4.0 (CC BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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