The plasma parameter log (TG/HDL-C) as an atherogenic index: correlation with lipoprotein particle size and esterification rate inapob-lipoprotein-depleted plasma (FERHDL)
Introduction
Atherogenic lipoprotein profile of plasma is an important risk factor for coronary artery disease (CAD). It is characterized by high ratio of low-density lipoprotein cholesterol (LDL-C) to high-density lipoprotein cholesterol (HDL-C) and increased level of triglycerides (TG’s) [1]. Predominance in plasma of small dense LDL and small HDL particles is associated with an increased risk of CAD while large HDL particles are associated with decreased risk [2], [3], [4], [5], [6], [7]. Thus, to estimate the risk of atherosclerosis more accurately the measurement of particle size distribution in LDL by gradient gel electrophoresis (GGE) has been recommended [8]. Recently we and others have reported that particle size distribution in both HDL [9], [10], [11], [12] and LDL [13], [14] is reflected in the fractional esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT) in plasma depleted of apoB containing lipoproteins (FERHDL). Predominance of small HDL particles (HDL3b,c) increases the FERHDL, while increased proportion of large HDL2b has the opposite effect [2], [9], [10], [11], [12]. Male sex [11], [12], hypertension [9], [15], diabetes mellitus [16], positive findings on coronary angiography and symptomatic CAD [17], [18] all result in higher FERHDL. FERHDL values are also highly correlated with LDL particle size of the original whole plasma sample [13], [14] probably because of the association of both HDL and LDL particle size with the concentration of plasma TG and HDL cholesterol: the higher TG and the lower HDL-cholesterol levels the smaller the lipoprotein particles and vice versa. As FERHDL (an indirect measure of lipoprotein particle size) also correlates well with plasma concentration of TG’s and HDL cholesterol we hypothesized that it is likely that the ratio of TG/HDL-C will also predict the value of FERHDL and therefore atherogenicity of plasma lipoproteins [19]. Examination of the data from cohorts with various atherogenic risk has revealed highly significant correlation between FERHDL and logarithmically transformed ratio TG/HDL-C as well as the LDL particle size. Based on these findings, we suggest that Log(TG/HDL-C) may be used as a simple, readily calculated parameter about atherogenicity of plasma lipoproteins.
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Subjects and assays
All subjects (Czechs, Slovaks and Canadians) had lipids measured after an overnight fast by standard methods; the assay of FERHDL has been previously described in detail [2], [11], [20]. Briefly, apo B-containing lipoproteins are precipitated from EDTA plasma (that can be stored at −20°C up to 4 months or at −70°C for up to 3 yr without changes in absolute values of FERHDL) by phosphotungstic acid and MgCl2. To the supernatant which contains plasma with HDL only, is added a filter paper disk
Results
Number of subjects in each cohort, their age, calculated logarithm of TG/HDL-C ratio, FERHDL (%/h) and correlation coefficient r between Log(TG/HDL-C) and FERHDL are shown in Table 1.
There was a good correlation (r = 0.67) between FERHDL (which is largely determined by particle sizes of both HDL and LDL) and the ratio of plasma TG/HDL-C in the 1433 subjects studied. Because of extreme skewness of this ratio we used logarithmic transformation and obtained a good approximation of normal
Discussion
A number of lipid related parameters have been used to predict risk of CAD. These include concentration of plasma lipids and lipoproteins, apoproteins, the ratio of TC (or LDL-C) to HDL-C, or a combination with other parameters [24]. According to Grover’s model [25] either the ratio of LDL-C/HDL-C or TC/HDL-C is the best lipid related predictor of future cardiovascular events.
Recently, the role of plasma triglycerides as an independent risk factor for CAD has been once again discussed [26], [27]
Acknowledgments
The authors would like to acknowledge the competent technical assistance of Mrs. L. Adler and Mrs. M. Schutzová. This work was supported by grants from the Grant Agency of the Czech Republic no. 306/96/k220, Grant IGA NE5465 to 3/1999, and the British Columbia Heart & Stroke Foundation.
We are indebted to co-authors of previous studies whose patients data we analyzed in this study: Drs. A. Mydlilová, J. Pitha, R. Poledne, K. Ras̆lová, M. s̆amánek, J. Str̆ı́brná, Meng-Hee Tan and Z. Urbanová.
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