Andreas Knudsen1, Terese L Katzenstein, Thomas Benfield, Niklas R Jørgensen, Gitte Kronborg, Jan Gerstoft, Niels Obel, Andreas Kjær, Anne-Mette Lebech. 1. aDepartment of Infectious Diseases, Copenhagen University Hospital, Hvidovre bDepartment of Clinical Physiology, Nuclear Medicine & PET, Copenhagen University Hospital, Rigshospitalet and Cluster for Molecular Imaging, Faculty of Health and Medical Sciences, University of Copenhagen cDepartment of Infectious Diseases, Copenhagen University Hospital, Rigshospitalet dResearch Center for Ageing and Osteoporosis, Departments of Diagnostics and Medicine, Copenhagen University Hospital, Glostrup, Denmark.
Abstract
OBJECTIVES: Biomarkers of endothelial dysfunction, inflammation and coagulation are associated with atherosclerosis and cardiovascular disease, but their association and possible predictive value remain controversial among HIV-1-infected individuals. We sought to investigate the association of seven biomarkers with first-time myocardial infarction (MI) in an HIV-1-infected population. DESIGN: A matched case-control study of 54 cases and 54 controls. METHODS: We compared 54 HIV-1-infected patients with verified first-time MI and 54 HIV-1-infected controls matched for age, duration of antiretroviral therapy, sex, smoking and no known cardiovascular disease. Levels of high-sensitivity C-reactive protein, soluble endothelial selectin, soluble vascular cell adhesion molecule, soluble intercellular adhesion molecule, matrix metalloprotease 9, myeloperoxidase, and plasminogen activator inhibitor 1 (PAI-1) were measured using a Luminex assay in plasma samples from routine visits both 12 and 2 months prior to the case patient's MI. RESULTS: The two groups had similar HIV characteristics and traditional cardiovascular risk factors. In univariate analysis, PAI-1 levels were associated with MI, whereas none of the other markers showed any association.In multivariate analyses adjusting for the D:A:D risk score, HIV viral load and high-sensitivity C-reactive protein, PAI-1 levels in the highest quartile were associated with a six to seven-fold increased risk of MI in both samples. CONCLUSION: High levels of PAI-1 were associated with risk of first-time MI in HIV-1-infected individuals independently of cardiovascular risk factors, HIV parameters and antiretroviral therapy. Therefore PAI-1 may be used for risk stratification and prediction of CHD, but further studies are needed.
OBJECTIVES: Biomarkers of endothelial dysfunction, inflammation and coagulation are associated with atherosclerosis and cardiovascular disease, but their association and possible predictive value remain controversial among HIV-1-infected individuals. We sought to investigate the association of seven biomarkers with first-time myocardial infarction (MI) in an HIV-1-infected population. DESIGN: A matched case-control study of 54 cases and 54 controls. METHODS: We compared 54 HIV-1-infectedpatients with verified first-time MI and 54 HIV-1-infected controls matched for age, duration of antiretroviral therapy, sex, smoking and no known cardiovascular disease. Levels of high-sensitivity C-reactive protein, soluble endothelial selectin, soluble vascular cell adhesion molecule, soluble intercellular adhesion molecule, matrix metalloprotease 9, myeloperoxidase, and plasminogen activator inhibitor 1 (PAI-1) were measured using a Luminex assay in plasma samples from routine visits both 12 and 2 months prior to the case patient's MI. RESULTS: The two groups had similar HIV characteristics and traditional cardiovascular risk factors. In univariate analysis, PAI-1 levels were associated with MI, whereas none of the other markers showed any association.In multivariate analyses adjusting for the D:A:D risk score, HIV viral load and high-sensitivity C-reactive protein, PAI-1 levels in the highest quartile were associated with a six to seven-fold increased risk of MI in both samples. CONCLUSION: High levels of PAI-1 were associated with risk of first-time MI in HIV-1-infected individuals independently of cardiovascular risk factors, HIV parameters and antiretroviral therapy. Therefore PAI-1 may be used for risk stratification and prediction of CHD, but further studies are needed.
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