Cholesterol esterification and atherogenic index of plasma correlate with lipoprotein size and findings on coronary angiography.

We examined the association between rate of cholesterol esterification in plasma depleted of apolipoprotein B-containing lipoproteins (FER(HDL)), atherogenic index of plasma (AIP) [(log (TG/HDL-C)], concentrations, and size of lipoproteins and changes in coronary artery stenosis in participants in the HDL-Atherosclerosis Treatment Study. A total of 160 patients was treated with simvastatin (S), niacin (N), antioxidants (A) and placebo (P) in four regimens. FER(HDL) was measured using a radioassay; the size and concentration of lipoprotein subclasses were determined by nuclear magnetic resonance spectroscopy. The S+N and S+N+A therapy decreased AIP and FER(HDL), reduced total VLDL (mostly the large and medium size particles), decreased total LDL particles (mostly the small size), and increased total HDL particles (mostly the large size). FER(HDL) and AIP correlated negatively with particle sizes of HDL and LDL, positively with VLDL particle size, and closely with each other (r = 0.729). Changes in the proportions of small and large lipoprotein particles, which were reflected by FER(HDL) and AIP, corresponded with findings on coronary angiography. Logistic regression analysis of the changes in the coronary stenosis showed that probability of progression was best explained by FER(HDL) (P = 0.005). FER(HDL) and AIP reflect the actual composition of the lipoprotein spectrum and thus predict both the cardiovascular risk and effectiveness of therapy. AIP is already available for use in clinical practice as it can be readily calculated from the routine lipid profile.

Fenofibrate and rosiglitazone improve quality of lipoproteins in patients with type 2 diabetes mellitus.

BACKGROUND: Particle size distribution in both HDL and LDL is reflected in the fractional esterification rate of cholesterol by lecithin cholesterol acyltransferase (LCAT) in plasma depleted of apoB containing lipoproteins (FER(HDL)). We studied FER(HDL) in a group of patients with type 2 diabetes and determined the impact of two different PPAR agonists (fenofibrate and rosiglitazone) on this marker of lipoprotein particle quality. PATIENTS AND METHODS: 66 patients with type 2 diabetes (26 women) and 32 control subjects (19 women) were included in the study. 33 patients received fenofibrate and 33 rosiglitazone as add on therapy. Average duration of treatment was 4 months. Plasma lipoprotein glucose levels were determined using an automated analyzer (COBAS Mira, Roche). LDL cholesterol concentrations were calculated by Friedewald formula. FER(HDL) was determined by a radioassay after precipitating apo-B containing particles of plasma. The assays were performed at baseline and at the end of each treatment. SPSS base program was used for statistical evaluation. RESULTS: Both fenofibrate and rosiglitazone resulted in a significant decrease of FER(HDL) (24.62 +/- 11.27%/h vs. 19.93 +/- 10.34%/h; 20.0 +/- 6.1%/h vs. 15.8 +/- 5.8%/h, p < 0.001). Rosiglitazone was significantly more effective in FER(HDL) lowering than fenofibrate (p < 0,02) CONCLUSIONS: Both fenofibrate and rosiglitazone improve FER(HDL) in patients with type 2 diabetes. The effect is more pronounced for rosiglitazone. Qualitative change of plasma lipoproteins reflected by FER(HDL) can contribute to antiatherogenic action of PPAR agonists. On contrary, changes of lipoprotein composition induced by PPAR agonists cannot explain adverse cardiovascular effects observed in some large clinical trials with PPAR agonists.

Fractional esterification rate of cholesterol and ratio of triglycerides to HDL-cholesterol are powerful predictors of positive findings on coronary angiography.

BACKGROUND: We examined the predictive value of various clinical and biochemical markers for angiographically defined coronary artery disease (aCAD). Specifically, we assessed the value of the ratio of plasma triglyceride (TGs) to HDL-cholesterol (HDL-C) and the fractional esterification rate of cholesterol in plasma depleted of apolipoprotein B (apoB)-containing lipoproteins (FER(HDL)), a functional marker of HDL and LDL particle size. METHODS: Patients (788 men and 320 women) undergoing coronary angiography were classified into groups with positive [aCAD(+)] and negative [aCAD(-)] findings. Patient age, body mass index, waist circumference, blood pressure (BP), medications, drinking, smoking, exercise habits, and plasma total cholesterol (TC), LDL-cholesterol (LDL-C), HDL-unesterified cholesterol, HDL-C, TGs, FER(HDL), apoB, log(TG/HDL-C), and TC/HDL-C were assessed. Lipids and apoproteins were measured by standard laboratory procedures; FER(HDL) was determined by a radioassay. RESULTS: Members of the aCAD(+) group were older and had a higher incidence of smoking and diabetes than those in the aCAD(-) group. The aCAD(+) group also had higher TG, apoB, FER(HDL), and log(TG/HDL-C) and lower HDL-C values. aCAD(+) women had greater waist circumference and higher plasma TC and TC/HDL-C. aCAD(+) men, but not women, had higher plasma LDL-C. In the multivariate logistic model, the significant predictors of the presence of aCAD(+) were FER(HDL), age, smoking, and diabetes. If only laboratory tests were included in the multivariate logistic model, FER(HDL) appeared as the sole predictor of aCAD(+). Log(TG/HDL-C) was an independent predictor when FER(HDL) was omitted from multivariate analysis. CONCLUSIONS: FER(HDL) was the best laboratory predictor of the presence of coronary atherosclerotic lesions.