The objective of the study was to assess the association between plasma levels of lipoprotein(a) [Lp(a)] and the presence of angiographically defined coronary artery disease (aCAD). Patients (346 men and 184 women) undergoing selective coronary angiography (SCA) were classified into groups with positive [aCAD(+)] and negative [aCAD(–)] findings and their age, body mass index (BMI), waist circumference, blood pressure, smoking, plasma total, LDL-, HDL-cholesterol (TC, LDL-C, HDL-C), triglycerides (TG), apolipoprotein B (apoB), Log(TG/HDL-C) and TC/HDL-C were determined. Concentration of plasma Lp(a) was estimated using the commercial solid phase two-side immunoradiometric assay of apolipoprotein apo(a). The plasma Lp(a) was significantly higher in both women and men with aCAD(+) compared to those with aCAD(–). While there was no significant difference in the Lp(a) level between men and women with aCAD(–) (median 138 vs. 145 units/l), the women with aCAD(+) had almost twice as high Lp(a) levels as men (median 442 vs. 274 units/l, p<0.001). Women with aCAD(+) had also significantly lower HDL cholesterol levels (1.09 vs. 1.20 mmol/l, p<0.05), higher triglycerides (1.82 vs. 1.46 mmol/l, p<0.05) and Log(TG/HDL-C) than women with aCAD(–). The differences in Lp(a) between positive and negative findings remained highly significant (p<0.001 in women, p<0.05 in men) after the adjustment for age, plasma HDL- and LDL-cholesterol and triglycerides in logistic regression analyses. In logistic regression model the Lp(a) and Log(TG/HDL-C) and smoking in women but smoking and age in men were the most powerful predictors of positive aCAD findings. Our findings suggest that Lp(a) is more strongly associated with aCAD+ in women than in men.
The distribution of differently sized HDL particles in the plasma can be assessed by measurement of the fractional rate of cholesterol esterification (FERhdl). We have characterized the isotopic assay and compared it to the enzymatic measurement of the decrease in HDL free cholesterol (mass assay). The normal values of FERhdl were established in 116 apparently healthy individuals. The isotopic assay is particularly sensitive to changes in the incubation temperature above 37 °C. The reproducibility of the assay in aliquots of plasma stored at -20 °C and -70 °C for 3 months and even up to 2 years was high. Intraindividual variability of FERhdl is low. In the subjects in whom FERhdl was measured over a 3-month and 2-5 years’ period, FERhdl showed a low variability (97.5±2.6 % and 101+6.0 % respectively in a paired t-test). Comparison of the isotopic assay and the mass assay revealed that the isotopic assay was much more reproducible. Normal values of FERhdl and the HDL subspecies distribution (using gradient gel electrophoresis) were established in 63 men and 56 women. The average values of FERhdl were significantly higher in men (16.8±4.5 %/h) than in women (10.6±3.6 %/h) and correlated well with the distribution of the HDL subspecies. FERhdl radioassay as a highly reproducible method for the assessment of HDL subspecies distribution which may be suitable for both retrospective and prospective studies of diseases of atherogenous origin.
Traditionally, lecithinxholesterol acyltransferase (LCAT) role in the reverse cholesterol transport (RCT) has been considered "antiatherogenic" as the cholesterol esterification is the prerequisite for the formation of mature high density lipoprotein (HDL) particles and may create a gradient necessary for the flow of unesterified cholesterol (UC) from tissues to plasma. However, newer data suggest that a higher esterification rate is not necessarily protective. Here we review the available data on the role of LCAT in RCT and propose that the LCAT-mediated esterification of plasma cholesterol promotes RCT only in the presence of sufficient concentrations of HDL2 while this reaction may be atherogenic in the presence of high concentration of plasma low density lipoprotein (LDL) cholesteroL Thus, the "protective" or potentially "atherogenic" role of LCAT depends on the quality of HDL and concentration of LDL. This hypothesis is consistent with the known high predictive value of LDL/HDL cholesterol ratio.