Effects of bezafibrate on lipoprotein subclasses and inflammatory markers in patients with hypertriglyceridemia—a nuclear magnetic resonance study
Introduction
There is a growing body of evidence that, in addition to LDL-cholesterol (C), increased TG-rich lipoproteins (increased remnants), decreased HDL-C and small dense LDL comprise a new cluster of atherogenic dyslipidemia. This type of dyslipidemia represents metabolic perturbations as a consequence of abdominal obesity and involves metabolic abnormalities over entire lipoprotein spectrums and more importantly associates with the increased risk for coronary artery disease (CAD) [1].
Bezafibrate, one of fibrate derivatives, has been considered to be highly effective in treating hypertriglyceridemia and provided a benefit in CAD patients with high TG and low HDL-C levels [2]. Previous studies also revealed that bezafibrate increased HDL-C and altered LDL particles size in favor of decreasing small dense LDL [3], [4]. While these studies all employed laborious ultracentrifugation and gradient gel electrophoresis methodologies to quantify lipoprotein subclasses, a new technology utilizing proton nuclear magnetic resonance (NMR) has drawn more attentions recently [5], [6]. This new method uses signals emitted from methyl groups of lipids. Overall NMR signals from these lipids were computationally decomposed to yield 16 lipoproteins subclasses concentrations, together with particle numbers and sizes. The NMR method does not require fractionation of lipoproteins, is rapid measurement, and NMR-determined lipoprotein subclasses concentrations correspond well to those by the established methods [7]. Furthermore, recent studies [8], [9], [10] have shown clinical values of NMR-measured lipoprotein subclasses concentrations as the risk of CAD. In the present study, we, for the first time, utilized NMR method to investigate the effect of bezafibrate on lipoprotein metabolism in hypertriglyceridemic patients. We also focused on potential effects of bezafibrate on inflammatory markers.
Section snippets
Methods
Twenty four hypertriglyceridemic patients were recruited for this study from out-patients clinic of Jikei University School of Medicine Hospital. Eligibility criteria included age between 30 and 70 years, body mass index (BMI) less than 30 kg/m2 and fasting triglyceride values ≥150 mg/dl both at screening and at the end of run-in period. None of the study subjects had poorly controlled diabetes (HbA1c>8%) or evidence of thyroid, liver or renal dysfunction (creatinine>2 mg/dl) and none were
Baseline demographic measures
Baseline characteristics of the study subjects are summarized in Table 1. The study subjects were mostly comprised of men (91.7%) and the average age of 53.8 years old. The average BMI of 25.1 kg/m2 was equal to the cut-off point to define obesity in Japan and, in fact, 10 patients (42%) were obese. Percentage of hypertension and diabetes are 50% and 25%, respectively. Current smokers comprised 42%. All patients, except for one patient who underwent coronary artery bypass surgery, were free
Discussion
In addition to elevated LDL-C, increased TG-rich lipoproteins (increased remnants), decreased HDL-C and small dense LDL comprise a new cluster of atherogenic dyslipidemia. Unlike hypercholesterolemia in which HMG-CoA reductase inhibitors are now widely accepted as the first choice, fibrate derivatives are considered to be an ideal treatment for this type of dyslipidemia. A recent intervention trials further supported this strategy by demonstrating that gemfibrozil provided a benefit when used
Acknowledgements
This study was funded by a grant from Kissei Pharmaceutical, Tokyo, Japan and Health and Labor Sciences Research Grants for Comprehensive Research on Aging and Health (H15-Choju-012), Japan.
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