Plasma plasminogen activator inhibitor-1 predicts myocardial infarction in HIV-1-infected individuals
Andreas Knudsen1, Terese L Katzenstein, Thomas Benfield
1aDepartment 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.
Insights
High levels of plasminogen activator inhibitor-1 (PAI-1) are linked to a significantly increased risk of myocardial infarction (MI) in individuals with HIV-1. This finding suggests PAI-1 can aid in predicting cardiovascular events in this population.
Area of Science:
- Cardiovascular Disease Research
- HIV/AIDS Research
- Biomarker Discovery
Background:
- Endothelial dysfunction, inflammation, and coagulation biomarkers are implicated in atherosclerosis and cardiovascular disease (CVD).
- Their predictive value for CVD in HIV-1-infected individuals remains debated.
- Myocardial infarction (MI) is a significant concern in the HIV-1 population.
Purpose of the Study:
- To investigate the association between seven specific biomarkers and first-time MI in HIV-1-infected individuals.
- To determine if these biomarkers can predict MI risk independently of traditional risk factors and HIV parameters.
Main Methods:
- A matched case-control study involving 54 HIV-1-infected patients with first-time MI and 54 matched controls.
- Measurement of high-sensitivity C-reactive protein, soluble selectin, soluble adhesion molecules, matrix metalloprotease 9, myeloperoxidase, and plasminogen activator inhibitor 1 (PAI-1) via Luminex assay.
- Plasma samples were collected 12 and 2 months prior to MI in cases.
Main Results:
- Univariate analysis showed PAI-1 levels were associated with MI; other markers were not.
- Multivariate analyses, adjusting for D:A:D risk score, HIV viral load, and hs-CRP, indicated that the highest quartile of PAI-1 was associated with a 6-7 fold increased risk of MI.
- No significant differences in HIV characteristics or traditional CVD risk factors were observed between cases and controls.
Conclusions:
- Elevated PAI-1 levels are independently associated with the risk of first-time MI in HIV-1-infected individuals.
- PAI-1 may serve as a valuable biomarker for cardiovascular risk stratification and prediction of coronary heart disease (CHD) in this cohort.
- Further research is warranted to confirm these findings and explore clinical applications.
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.
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