Lipoprotein-associated phospholipase A2 and cardiovascular disease risk in HIV infection

ObjectivesHIV-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 A(2) (Lp-PLA(2)) predicts CVD events in the general population. This study investigated the relationship between Lp-PLA(2) and markers of CVD risk, systemic inflammation, immune activation, and coagulation in HIV infection. MethodsOne hundred subjects on stable ART with normal fasting low-density lipoprotein (LDL) cholesterol were enrolled in the study. Plasma Lp-PLA(2) concentrations were measured by enzyme-linked immunosorbent assay (ELISA; >200ng/mL was considered high CVD risk). Subclinical atherosclerosis, endothelial function, inflammation, immune activation and fasting lipids were also evaluated. ResultsThe median age of the patients was 47 years and 77% were male. Median (range) Lp-PLA(2) was 209 (71-402) ng/mL. Fifty-seven per cent of patients had Lp-PLA(2) concentrations >200ng/mL. Lp-PLA(2) 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-PLA(2) 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). ConclusionsIn this population with stable ART and normal LDL cholesterol, Lp-PLA(2) was in the high CVD risk category in the majority of subjects. Lp-PLA(2) appears to be associated with inflammation/immune activation, but also with anti-thrombotic effects. Lp-PLA(2) may represent a valuable early biomarker of CVD risk in HIV infection before subclinical atherosclerosis can be detected.