Background. There is an unmet need to improve risk assessment of vascular diseases by lipoprotein profiling beyond plasma and LDL lipids.

Aims. (i) To study the relation of various lipoprotein lipid and apolipoprotein (apo) measures on the Friedewald inputs, i.e., plasma triglycerides (TG), cholesterol (TC), and HDL-C. (ii) Build up regression models for the appropriate measures based solely on the Friedewald inputs.

Methods. Data were available for 1,775 plasma samples from which VLDL, IDL, LDL and HDL were also isolated by ultracentrifugation. For HDL2-C and apolipoproteins 343 and 247 samples were available, respectively.

Results. Accurate models were obtained for VLDL-TG (cross-validation r=0.98), LDL-C (r=0.91), HDL2-C (r=0.92), apoA-I (r=0.92) and apoB (r=0.95). A semi-quantitative model was obtained for IDL-C (r=0.78). Due to the anticipated role of IDL-C in atherosclerosis, it was still kept within the accepted models and pursued further. The associations of the estimates with premature deaths were studied in 4,084 patients with type 1 diabetes. The behavior of IDL-C and LDL-C was markedly different, the best predictors of mortality being apoB, apoB to apoA-I ratio, and IDL-C.

Conclusions. The new models allow identification of clinically relevant lipoprotein profiles with no added cost to the conventional Friedewald formula.

Objective: Hydrolysis of LDL by phospholipase A2 (PLA2) generates nonesterified fatty acids (NEFAs) and lysophospholipids (lysoPCs). Binding of the PLA2-modified LDL to proteoglycans, and their uptake by macrophages are increased. Since the extracellular pH is decreased in advanced atherosclerotic plaques, we examined the effects of acidic pH on PLA2-induced LDL modification and its proatherogenic consequences.

Results: sPLA2-V hydrolyzed LDL particles avidly at pH range 7.55.5. With decreasing pH, the ability of albumin to sequester the formed NEFAs and lysoPCs from the sPLA2-V-modified LDL particles decreased, and, as a consequence, more of the hydrolytic products accumulated in the particles. At acidic pH, such sPLA2-V-modified LDL particles had higher binding strength to human aortic proteoglycans, and their uptake by human monocytederived macrophages and ensuing foam cell formation were enhanced.

Conclusions: The present data show that the proatherogenic effects exerted by sPLA2-V-induced lipolysis of LDL are enhanced with decreasing pH and suggest that sPLA2-V is particularly atherogenic in advanced atherosclerotic lesions, in which local acidic conditions prevail.