Wang Seong Ryu

Effects of the Transition from Premenopause to Postmenopause on Lipids and Lipoproteins: Quantification and Related Parameters

Background/Aims The aim of this study was to quantitatively measure changes in lipids and lipoproteins during perimenopause and to identify variables related to these changes. Methods Among women who had three regular health evaluations over a span of 2-4 years, 34 women remained in the premenopausal state, 34 premenopausal women transitioned to the postmenopausal state, and 36 postmenopausal women were enrolled. The menopausal state was determined not only by a history of amenorrhea but also by levels of female sex hormones. Yearly changes in lipids were calculated using a linear regression of the three measurements. Results The transition from premenopause to postmenopause was associated with increased total cholesterol and low-density lipoprotein (LDL) cholesterol levels by 7.4 ± 8.0 mg/dL (4.2 ± 4.9%) and 6.9 ± 6.5 mg/dL (6.8 ± 7.0%) over one year, resulting in an elevation of 19.6 ± 22.6 mg/dL (10.9 ± 13.0%) and 18.9 ± 19.5 mg/dL (18.6 ± 20.3%), respectively, during perimenopause. There were no changes observed in premenopausal and postmenopausal women. Body weight, blood pressure, high-density lipoprotein (HDL) cholesterol, and triglycerides did not change in any of the three groups. In all women, changes in both total cholesterol and LDL cholesterol were associated with changes in follicle stimulating hormone (r = 0.40, p < 0.001 and r = 0.38, p < 0.001, respectively). Changes in triglycerides were associated with changes in body weight (r = 0.28, p = 0.005). Conclusions During perimenopause, total and LDL cholesterol levels increase and these changes in cholesterol are mainly dependent on changes in female sex hormones.

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.

Atherosclerotic Progression Attenuates the Expression of Nogo-B in Autopsied Coronary Artery: Pathology and Virtual Histology Intravascular Ultrasound Analysis

The relation of Nogo-B to atherosclerotic plaque progression is not well understood. Thus, the purpose of this study was to assess the expression of Nogo-B in fibroatheromas (FA) of different stages, classified using virtual histology intravascular ultrasound (VH-IVUS) analysis in 19 autopsied cases of non-sudden cardiac death. VH-IVUS imaging analysis was performed 30 mm from the ostium of each coronary artery. VH-IVUS revealed 11 early FAs (34.5±8.3 yr), 12 late FAs (42.6±16.6 yr), 8 thick-cap FAs (TkCFAs) (46.4±11.1 yr), and 6 thin-cap FAs (TCFAs) (51.8±6.8 yr). TkCFAs and TCFAs were defined as advanced FA. FA progression advanced with age (P=0.04). VH-IVUS analysis of small, early FAs showed smaller necrotic cores and relatively less calcium compared to more advanced FAs with large necrotic cores (P<0.001). Histopathology and immunohistochemical stains demonstrated that early or late FAs had smaller necrotic cores, less empty space of decalcification, and greater Nogo-B expression compared to advanced FAs (vs. early FA, P=0.013; vs. late FA, P=0.008, respectively). These findings suggest that FA progression is inversely associated with Nogo-B expression. Local reduction of Nogo-B may contribute to plaque formation and/or instability.

Relationship between coronary artery plaque composition by virtual histology intravascular ultrasound analysis and brachial-ankle pulse wave velocity in patients with coronary artery disease.

ObjectiveBrachial-ankle pulse wave velocity (baPWV) is an indicator of atherosclerotic cardiovascular risks. To identify patients with coronary atherosclerosis before the onset of angina pectoris or myocardial infarction will be desirable. MethodsWe measured the ankle-brachial index and baPWV in 150 consecutive patients with coronary artery disease (CAD). Virtual histology intravascular ultrasound (VH-IVUS) imaging was available in target lesions of 130 patients with symptomatic CAD before percutaneous intervention. Patients were divided into two groups: baPWV of greater than or equal to 1600 cm/s (74 patients) and baPWV of less than 1600 cm/s (56 patients). ResultsPatient age was 66±8.33 years in baPWV of greater than or equal to 1600 cm/s group versus 56±10.27 years in baPWV of less than 1600 cm/s group (P<0.0001). Although plaque burden and remodeling index were similar, minimal lumen area was smaller in baPWV of greater than or equal to 1600 cm/s group (P=0.039); and lesion length was longer in the baPWV of greater than or equal to 1600 cm/s group (P=0.033). VH-IVUS analysis of coronary artery plaque composition showed that percent mean and percent maximum dense calcium were higher in the baPWV of greater than or equal to 1600 cm/s group (P=0.0037), and percent maximal calcium correlated with baPWV (r=0.278, P=0.001). ConclusionWe concluded that there is a significant relationship between baPWV and the VH-IVUS assessment of CAD. A high baPWV indicates more severe CAD (smaller minimal lumen area and longer lesion length) and greater atherosclerosis disease complexity (more calcified coronary plaque).

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.

Acute Embolic Occlusion of the Left Common Iliac Artery Treated With Intra-Arterial Thrombolysis and Percutaneous Thrombectomy

Acute embolic occlusion of the common iliac artery is a rare medical emergency that is not only limb-threatening, but also potentially life-threatening. Several treatment options exist for acute limb ischemia, although no treatment is clearly best. We report a case of acute embolic occlusion of the left common iliac artery in a patient with atrial fibrillation who was treated successfully using mechanical thrombectomy following intra-arterial thrombolysis.

Progression and Observational Frequency of Atheromatous Plaques in Autopsied Coronary Arteries

Background and Objectives Virtual histology-intravascular ultrasound (VH-IVUS) studies on early-stage fibroatheroma, the probable precursor lesion of progression to thin-cap fibroatheroma (TCFA), have only rarely been done in man. We investigated the progression and observational frequency of fibroatheromas, and compared plaque components between early-stage and advance-staged fibroatheromas in the general population. Subjects and Methods We assessed coronary fibroatheromas using VH-IVUS and histopathologic analysis of 109 coronary lesions from 40 autopsied cases that were not due to sudden cardiac death (NSCD cases). Fibroatheromas were grouped into early fibroatheroma, late fibroatheroma, thick-cap fibroatheroma (TkCFA), and thin-cap fibroatheroma. Results Mean patient age was 45±11 years old and 71% were males. Of 109 lesions, 27% were early fibroatheromas, 53% late fibroatheromas, 9% TkCFA, and 11% TCFA. VH-IVUS showed that there was relatively less fibrotic and fibrofatty plaque and more dense calcium deposits as fibroatheromas progressed. Furthermore, the relative amounts of fibrotic and fibrofatty plaque decreased (r=0.773, p<0.001 and r=0.538, p<0.001, respectively) as the necrotic core increased, while the relative area of dense calcium increased (r=0.665, p<0.001) as the size of the necrotic core increased. Conclusion Of NSCD cases in Korea, 27% were early fibroatheromas, 53% were late fibroatheromas, 9% were TkCFA, and 11% were TCFA. Advance-staged fibroatheromas show more necrotic core volume and more dense calcium than small, early-stage fibroatheromas.

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.

Effects of ezetimibe added to ongoing statin therapy on C-reactive protein levels in hypercholesterolemic patients.

Background and Objectives Ezetimibe alone does not decrease C-reactive protein (CRP) levels in hypercholesterolemic patients. However, several reports have suggested that ezetimibe might potentiate the effect of statin not only on cholesterol but also on CRP when administered together. We investigated the effect of ezetimibe on CRP levels in patients taking statins. Subjects and Methods Patients who had not achieved recommended low density lipoprotein-cholesterol (LDL-C) goals with statin therapy were divided into two groups, the ezetimibe group (n=60) and the control group (n=60). A third group of hypercholesterolemic patients without statin therapy was treated with statin (n=59). Patients with CRP level 10 mg/L were excluded. Lipid and CRP levels were measured before therapy commenced, and after 2 months of therapy. Results Ezetimibe decreased cholesterol and LDL-C levels by 20.2% (p=0.000) and 28.1% (p=0.000) respectively. However, ezetimibe did not reduce CRP levels (from 0.83±0.68 to 1.14±1.21 mg/dL, p=0.11). CRP levels remained unchanged in the control group (p=0.42). In contrast, statin lowered CRP levels (from 0.82±0.73 to 0.65±0.57 mg/dL, p=0.008). In patients taking statins, changes in CRP levels were not associated with changes in LDL-C (r=-0.02, p=0.87), but with baseline CRP levels (r=-0.38, p=0.000). Conclusion Ezetimibe failed to reduce CRP levels in hypercholesterolemic patients taking statins despite significant reduction of LDL-C. This finding suggests that the anti-inflammatory effect of statin may not be secondary to cholesterol reduction, but via other mechanisms.