Hong Sook Ko

Effect of fenofibrate on lipoprotein(a) in hypertriglyceridemic patients: impact of change in triglyceride level and liver function.

We investigated the effect of fenofibrate on lipoprotein(a) levels in hypertriglyceridemic patients and the parameters relating to its effect. Patients with a triglyceride level ≥300 mg/dL or with a triglyceride level ≥200 mg/dL and a high density lipoprotein cholesterol level ≤40 mg/dL were treated either with 200 mg of fenofibrate (Fenofibrate group, n = 56) or with general measures (Control group, n = 56). Lipid and lipoprotein levels were measured at baseline and 2 months. Baseline lipoprotein(a) levels were negatively correlated with triglyceride (r = −0.30, P = 0.001) and alanine aminotransferase levels (r = −0.24, P = 0.012). Fenofibrate therapy increased lipoprotein(a) level from 9.4 ± 10.6 to 15.6 ± 17.5 mg/dL (P = 0.000). The more triglyceride levels decreased, the more lipoprotein(a) levels increased in all subjects (r = −0.46, P = 0.000) and in Control (r = −0.35, P = 0.008) and Fenofibrate groups (r = −0.35, P = 0.008). Fenofibrate elevated lipoprotein(a) level greater in patients with a normal liver function. When Fenofibrate group was divided into two subgroups according to the degree of percentage change in lipoprotein(a) level, change in triglyceride level and alanine aminotransferase level were independent predictors by forward logistic regression analysis. In summary, fenofibrate therapy increases lipoprotein(a) level, and this elevation is associated with change in triglyceride level and liver function.

Overweight and Effect of Hormone Replacement Therapy on Lipid Profiles in Postmenopausal Women

Background Many experimental and observational studies have suggested that hormone replacement therapy (HRT) in postmenopausal women is cardioprotective. However, the results of randomized controlled trials have been discouraging. We attempted to evaluate the influence of overweight, a frequent risk factor for coronary artery disease, on the lipid-modifying effects of HRT. Methods A total of 345 postmenopausal women were divided into 2 groups according to body mass index (BMI): the control group; BMI<25 Kg/m2 (n=248) and the overweight group; BMI≥25 Kg/m2 (n=97). All women received either 0.625 mg conjugated equine estrogen (CEE)(n=139), CEE plus 5 mg medroxyprogesterone acetate (MPA)(n=97) or CEE plus 10 mg MPA (n=109). Lipid profiles were measured before and 12 months after HRT. Results In both the control and overweight groups, HRT reduced low density lipoprotein cholesterol (LDL-C) (p=0.000 and p=0.000 respectively) and lipoprotein (a) [Lp(a)] levels (p=0.000 and p=0.000 respectively) and raised high density lipoprotein cholesterol (HDL-C) levels (p=0.000 and p=0.002 respectively). However, the elevation of the HDL-C level was higher in the control group than in overweight group (17.5% vs. 10.4%, p=0.015), and this was significant after adjusting for changes in body weights (p=0.016). There were no differences in the reduction of LDL-C (p=0.20) and Lp(a) (p=0.09) levels between the two groups. Conclusion HRT had less favorable effects on HDL-C levels in overweight postmenopausal women than in women with normal body weight. This finding may be partially associated with no cardioprotective effect of HRT in postmenopausal patients at a high risk due to multiple risk factors including obesity.

New Parameters for Left Ventricular Function in Atrial Fibrillation: Based on the Relationship between RR Interval and Performance

This study was designed to obtain new parameters representing left ventricular (LV) function independent of irregular RR intervals in atrial fibrillation (AF). AF patients were divided into Normal (n=9) and LV Dysfunction (n=9) groups. The relations between LV outflow peak ejection velocity (Vpe) and preceding (RR-1) or pre-preceding RR intervals (RR-2) were obtained using logarithmic equations, from which the squared correlation coefficient (r2), slope, Vpe at RR-1 or RR-2=1 sec (Vpe-1), and the ratio of slope to Vpe-1 (Slope/Vpe-1) were calculated. Among the parameters between RR-1 and Vpe, Slope/Vpe-1 was higher in LV Dysfunction group than in Normal group (p=0.05). When only coordinates with RR-1 from 0.6 to 1 sec were included, Slope/Vpe-1 (p=0.001) was higher in LV Dysfunction group than in Normal group. Among the parameters between RR-2 and Vpe, Slope/Vpe-1, slope, and r2 were different between the two groups. In multivariate analysis, Slope/Vpe-1 between RR-2 and Vpe was only independent parameter. However, Slope/Vpe-1 between RR-1 and Vpe in the coordinates with RR-1 from 0.6 to 1 sec had the highest discriminating power. New parameters derived from the relations between RR intervals and LV performance might be useful to evaluate LV function quantitatively in AF.

Characterization of Binding and Phagocytosis of Oxidatively Damaged Erythrocyte to Macrophage

Background: Scavenger receptors are thought to be involved in the recognition of oxidized low-density lipoprotein (oxLDL) and oxidized erythrocyte (oxRBC). However, there are controversies about the kind of receptors and ligands related to the binding. Macrophages lacking class A scavenger receptor show identical binding of oxRBC with wild-type ones. Methods: RBCs were oxidized with ascorbic acid and CuSO4. Lipid oxidation was measured indirectly by measuring TBARS semiquantitatively. The binding and phagocytosis were measured by counting the number of oxRBC bound or taken up after incubation at 4°C or 37°C for 60 minutes to 100 macrophages differentiated from human monocytic leukemia cell line. Results: The degree of oxidation and the binding of oxRBCs were dependent on the concentration of CuSO4. The binding and phagocytosis of oxRBC were inhibited by 99% with oxLDL. Fucoidan, competing class A scavenger receptor, inhibited the binding by more than 90%. The binding of oxRBC was higher at 37°C than at 4°C by 3 times. The binding of oxRBCs was maximal at pH 6.5 and higher than at physiologic pH by 2.8 times. At pH 8.5 and 9.5, binding decreased by 67 and 88%, respectively. Conclusion: OxRBCs might bind and be taken up to macrophages not mainly through class A nor B scavenger receptors, but through other scavenger receptors and/or pathways. These processes are dynamic and ionic strength might be involved.