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Lipoprotein-associated phospholipase A2 and cardiovascular disease risk in HIV infection
A Ross Eckard1, C T Longenecker, Y Jiang
1Emory University School of Medicine and Children's Healthcare of Atlanta, Atlanta, GA, USA.
Insights
Lipoprotein-associated phospholipase A2 (Lp-PLA2) is elevated in most HIV patients on antiretroviral therapy (ART), indicating high cardiovascular disease (CVD) risk. This biomarker may help identify at-risk individuals early.
Area of Science:
- Cardiology
- Infectious Diseases
- Immunology
Background:
- HIV-infected patients on antiretroviral therapy (ART) face elevated cardiovascular disease (CVD) risk due to persistent inflammation and immune activation.
- Traditional cardiovascular risk factors and lipid profiles may not fully capture this heightened risk in the HIV population.
- Lipoprotein-associated phospholipase A2 (Lp-PLA2) is a known predictor of CVD events in the general population.
Purpose of the Study:
- To investigate the association between Lp-PLA2 levels and markers of CVD risk, systemic inflammation, immune activation, and coagulation in HIV-infected individuals on stable ART.
- To determine if Lp-PLA2 can serve as an early biomarker for CVD risk in this population, independent of traditional risk factors.
Main Methods:
- A cohort of 100 HIV-infected patients on stable ART with normal low-density lipoprotein (LDL) cholesterol was studied.
- Plasma Lp-PLA2 concentrations were measured using ELISA, with >200 ng/mL considered high risk.
- Assessments included subclinical atherosclerosis, endothelial function, inflammation, immune activation markers, and coagulation parameters.
Main Results:
- The majority of patients (57%) had elevated Lp-PLA2 levels (>200 ng/mL).
- Lp-PLA2 positively correlated with markers of inflammation and immune activation (e.g., TNF-RII, ICAM-1, VCAM-1, CD14) and negatively with coagulation markers (D-dimer, fibrinogen).
- No significant correlation was found with lipids or measures of atherosclerosis (coronary artery calcium, flow-mediated vasodilation), though a trend was observed with carotid intima-media thickness.
Conclusions:
- Elevated Lp-PLA2 is common in HIV patients on ART with normal LDL cholesterol, suggesting a high CVD risk.
- Lp-PLA2 is linked to inflammation and immune activation in HIV, potentially reflecting ongoing pathophysiological processes.
- Lp-PLA2 may serve as a valuable early biomarker for cardiovascular risk in HIV infection, preceding detectable subclinical atherosclerosis.
Objectives:
HIV-infected patients on antiretroviral therapy (ART) have an increased cardiovascular disease (CVD) risk as a result of heightened inflammation and immune activation, despite at times having normal lipids and few traditional risk factors. Biomarkers are needed to identify such patients before a clinical event. Lipoprotein-associated phospholipase A2 (Lp-PLA2 ) predicts CVD events in the general population. This study investigated the relationship between Lp-PLA2 and markers of CVD risk, systemic inflammation, immune activation, and coagulation in HIV infection.
Methods:
One hundred subjects on stable ART with normal fasting low-density lipoprotein (LDL) cholesterol were enrolled in the study. Plasma Lp-PLA2 concentrations were measured by enzyme-linked immunosorbent assay (ELISA; > 200 ng/mL was considered high CVD risk). Subclinical atherosclerosis, endothelial function, inflammation, immune activation and fasting lipids were also evaluated.
Results:
The median age of the patients was 47 years and 77% were male. Median (range) Lp-PLA2 was 209 (71-402) ng/mL. Fifty-seven per cent of patients had Lp-PLA2 concentrations > 200 ng/mL. Lp-PLA2 was positively correlated with soluble markers of inflammation or immune activation (tumour necrosis factor receptor-II, intercellular and vascular cellular adhesion molecules, and CD14; all R = 0.3; P < 0.01), and negatively correlated with coagulation markers (D-dimer and fibrinogen; both R = -0.2; P < 0.04). Lp-PLA2 was not correlated with lipids, coronary artery calcium score, or flow-mediated vasodilation, but trended towards a significant correlation with carotid intima-media thickness (R = 0.2; P = 0.05).
Conclusions:
In this population with stable ART and normal LDL cholesterol, Lp-PLA2 was in the high CVD risk category in the majority of subjects. Lp-PLA2 appears to be associated with inflammation/immune activation, but also with anti-thrombotic effects. Lp-PLA2 may represent a valuable early biomarker of CVD risk in HIV infection before subclinical atherosclerosis can be detected.
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