Abstract 1690: Pre-Beta HDL and Lecithin:Cholesterol Acyltransferase Levels Are Strong Positive Diagnostic Risk Markers for Ischemic Heart Disease in Subjects with Both High and Low HDL-C Levels in the Copenhagen City Heart Study

Abstract

Objective: We hypothesize that patients with high HDL-C levels and Ischemic Heart Disease (IHD) may have dysfunctional HDL or unrecognized non-conventional risk factors. Methods: Subjects with IHD and either high HDL-C (n = 53; women:≥ 73.5mg/dL; men: ≥ 61.9mg/dL) or low HDL-C (n = 42; women: ≤ 38.7mg/dL; men: ≤ 34.1mg/dL) were compared with subjects without IHD and matched HDL-C levels (n = 110). All subjects had normal LDL-C (< 160mg/dL) and triglyceride levels (< 150mg/dL) and none were treated with lipid-lowering medications. Pre-beta HDL and Phospholipid Transfer Protein (PLTP) levels were measured using commercial kits and Lecithin:Cholesterol Acyltransferase (LCAT) activity, using a proteoliposome cholesterol esterification assay. Results: Pre-beta HDL levels were 2–3 fold higher in subjects with IHD in the high (p < 0.0001) and low HDL-C (p = 0.001) groups. Interestingly, low LCAT activity was found in the same subjects with IHD and high (p = 0.002) or low (p = 0.03) HDL-C. Furthermore, higher PLTP levels were observed in the group with high HDL-C and IHD when compared to individuals without disease (p < 0.0001). Receiver operating characteristic curve for pre-beta HDL in the high HDL-C groups yielded an area under curve of 0.71 for predicting IHD, which increased to 0.92 when LCAT values were included. Similar results were obtained for the low HDL-C groups. A strong inverse correlation between LCAT activity and pre-beta HDL-C ( r 2 = 0.30, p < 0.0001), which was especially strong in the low HDL-C group ( r 2 = 0.56, p < 0.0001) was observed. Individuals with high HDL-C and IHD had approximately 15% more apoA-I (p = 0.001) and apoA-II (p = 0.002) and nearly 10% more phospholipid (p = 0.007) than subjects with similar HDL-C and no IHD. Likewise, the group with low HDL-C had 30% more apoE (p = 0.035) and approximately 10% more phospholipid (p = 0.047) than the group with similar HDL-C levels and no IHD. Conclusions: IHD was associated with high pre-beta HDL and low LCAT levels. Measuring both gave correct classification in 92% of cases with IHD, thus making pre-beta HDL and LCAT activity a powerful diagnostic tool for IHD, particularly in commonly found patients wtih isolated low HDL-C levels with low to intermediate risk of IHD based on conventional risk factors.