Abstract 1390: Composition Analysis of High Density Lipoproteins in Patients with extreme HDL-C Levels with or without Ischemic Heart Disease

Abstract

Objective: We hypothesize that patients with high HDL-C levels and Ischemic Heart Disease (IHD) may have dysfunctional HDL or have unrecognized non-conventional risk factors. Methods: Individuals with verified IHD with either high HDL-C (n=53; female: ≥73.5mg/dL; male: ≥61.9mg/dL) or low HDL-C (n=42; female:≤38.7mg/dL; male: ≤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 LDL-C-lowering medications. After removal of apoB lipoproteins, apoA-I, apoA-II, apoE, triglycerides, free cholesterol, cholesteryl ester, and phospholipids were analyzed (Cobas-Fara). HDL and LDL-subclasses were examined by linear gradient gel electrophoresis (Lipoprint®) and by Segmented Gradient Gel Electrophoresis (S-GGE). Cholesterol (RLP-C) and triglyceride (RLP-TG) content of remnant-like lipoprotein particles were measured by an immunoseparation technique. Results: Subjects with high HDL-C levels and IHD had lower apo-AI (p<0.001) and cholesteryl ester (p<0.01) levels compared to controls with high HDL and no IHD. Subjects with low HDL-C and IHD had lower triglyceride (p=0.01) levels compared to controls with matched HDL-C levels and no IHD. The HDL subclass, using S-GGE, with density 1.063–1.100g/ml and diameter 98 –130Å correlated with levels of HDL-C (r 2 =0.66, p<0.0001). LDL subclasses using Lipoprint® exhibited higher fraction of Intermediate Density Lipoproteins (IDL-C) in patients with high HDL-C and IHD when compared with individuals with same HDL-C and no IHD (p=0.006). This was also true in the low HDL-C groups (p=0.01). This was further supported by higher levels of RLP-C and RLP-TG in individuals with high HDL and IHD (p=0.03 and p=0.03, respectively) when compared with respective controls. Conclusions: These results suggest that HDL composition rather than HDL-C levels is important in deciphering the protective role of HDL in IHD and that measurement of remnant-like lipoproteins may be useful for identifying patients with high HDL-C that are still at risk for developing IHD.