Effects of risperidone and olanzapine on remnant-like lipoprotein particle cholesterol (RLP-C) in schizophrenic patients

Second generation antipsychotics are associated with the risk of metabolic disorders such as diabetes mellitus and hyperlipidemia. Remnant-like lipoprotein particles cholesterol (RLP-C) are a known risk factor for cardiovascular events. The present study was performed to determine possible differences in fasting blood RLP-C levels between schizophrenic patients treated with risperidone as compared to olanzapine. Patients on olanzapine had significantly higher RLP-C levels than those on risperidone (p < 0.01). In olanzapine-treated patients there was no abnormality in fasting blood glucose levels, but fasting insulin levels and homeostasis model assessment of insulin resistance (HOMA-IR) were elevated. RLP-C levels were significantly correlated with plasma triglyceride concentrations in both the olanzapine- (p < 0.01) and risperidone-treated patients (p < 0.01). The regression line slope was greater for the olanzapine group, suggesting a greater influence of olanzapine on RLP-C. There was a significant correlation between RLP-C and HOMA-IR in the risperidone group (p < 0.01) but not in the olanzapine group (p = 0.80). These results suggest that blood glucose monitoring may not be sufficient to detect metabolic disorder and that measurement of RLP-C might be helpful for the screening for metabolic disorders associated with olanzapine therapy.     

Plasma remnant-like lipoprotein particles or LDL-C as major pathologic factors in sudden cardiac death cases

We have previously reported that the majority of sudden cardiac death (SCD) events were associated with postprandial hyperlipidemia in Japanese subjects. In this investigation, we have compared LDL-cholesterol (LDL-C) and remnant-like lipoprotein particles (RLP) as cardiovascular risk factors in SCD cases, especially in Pokkuri death syndrome (PDS) cases who had nearly normal coronary arteries. To predict the risk of plasma RLP-cholesterol, triglyceride (RLP-C, RLP-TG) and LDL-C in fatal clinical events associated with SCD cases with or without atherosclerosis (PDS), we calculated the cut-off values and likelihood ratio of these lipoproteins from ROC analysis. Sixty-eight percent of SCD cases were above cut-off value of RLP-C (>12.8 mg/dL) versus 32% for control death cases (P < 0.0001) and the likelihood ratio of RLP-C was 2.12. Significantly higher incidence of RLP-C above cut-off value (>10.1 mg/dL) was seen in PDS compared to controls (P < 0.0001) and the likelihood ratio was 3.13. Similarly, significantly higher incidence of RLP-TG above cut-off values, SCD > 53 mg/dL and PDS > 67 mg/dL, was seen compared to controls (P < 0.0001) and the likelihood ratio was 1.86 and 2.73, respectively. Further, significantly higher incidence of LDL-C above cut-off value (>93 mg/dL) was seen in SCD compared to controls (P < 0.0001) and the likelihood ratio was 1.68. However, the incidence of LDL-C above cut-off value (LDL-C > 106 mg/dL) was not significantly different between PDS and controls and the likelihood ratio was 1.52.

In conclusion, this study has shown high levels of plasma remnant lipoproteins in PDS and that PDS cases did not present with atherosclerotic lesions or elevated LDL-C. In contrast, SCD cases showed high levels of plasma remnant lipoproteins together with elevated plasma LDL-C. Accordingly, we believe that plasma remnant lipoproteins level rather than plasma LDL-C is a major pathologic factor in cardiovascular events.     

Exercise attenuates the increase in plasma monounsaturated fatty acids and high-density lipoprotein cholesterol but not high-density lipoprotein 2b cholesterol caused by high-oleic ground beef in women

We hypothesized that dietary monounsaturated fatty acids (MUFA) and exercise increase high-density lipoprotein cholesterol (HDL-C) by independent mechanisms, so there would be additive effects between a single, intensive session of exercise and high-MUFA ground beef on HDL-C and blood risk factors for cardiovascular disease. Seventeen postmenopausal women completed a 2-way crossover design in which they consumed five 114-g ground beef patties per week for two 6-week periods separated by a 4-week washout (habitual diet) period. The ground beef patties contained 21% total fat with either 9.97 (low-MUFA) or 12.72 (high-MUFA) g total MUFA. Blood was taken at entry, at the end of each 6-week diet period, after the 4-week washout period, and 24 hours after aerobic exercise sessions (75% VO_2peak, 2.07 MJ). After the ground beef intervention, the high-MUFA ground beef increased plasma palmitoleic acid and oleic acid, low-density lipoprotein (LDL) particle density, HDL-C, and HDL_2b-C (all P < .05), whereas the low-MUFA ground beef increased LDL density. After the washout (habitual diet) period, the single exercise session increased serum LDL cholesterol, HDL-C, and HDL_2a and decreased TAG and oleic acid. After the low-MUFA ground beef diet, exercise increased LDL size and HDL density and decreased LDL density and very low-density lipoprotein cholesterol, but had no effect on HDL-C fractions. After the high-MUFA ground beef intervention, exercise decreased palmitioleic acid, oleic acid, HDL-C, and HDL_2a-C, but not HDL_2b-C. Contrary to our hypothesis, the effects of exercise and a high-MUFA diet were not additive; instead, exercise attenuated the effects of the high-MUFA ground beef on HDL-C and plasma MUFAs. The differential effects of high-MUFA ground beef and exercise on HDL_2a-C and HDL_2b-C indicate that diet and exercise affect HDL-C by different mechanisms.     

Effects of ezetimibe on glucose metabolism in patients with type 2 diabetes: A 12-week, open-label, uncontrolled, pilot study

Background: A potential effect of ezetimibe, a novel cholesterol-absorption inhibitor, on insulin resistance has been reported in an animal model.Objective: The aim of this study was to evaluate the effects of ezetimibe on glucose metabolism in patients with type 2 diabetes mellitus (T2DM).Methods: Between March and June 2008, outpatients with T2DM who were being treated at Yokohama Sakae Kyosai Hospital, Yokohama, Japan, were enrolled in this pilot study if they had not achieved the target lipid levels recommended by the Japan Atherosclerosis Society Guidelines despite diet and exercise or a statin therapy for ≥3 months. At baseline and at 4 and 12 weeks after open-label treatment with ezetimibe 10 mg/d, the levels of lipid parameters, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA_1c), and high-sensitivity C-reactive protein were measured. Adverse effects (AEs) were assessed at each study visit by patient interviews and laboratory testing.Results: A total of 21 consecutive patients (10 men, 11 women; mean [SD] age, 72 [9] years; weight, 63.4 [10.5] kg; body mass index, 25.5 [3.2] kg/m²) were enrolled in this study. The mean (SD) level of LDL-C decreased significantly from 146 (31) to 114 (27) mg/dL (−21%; P < 0.001) after 12 weeks of treatment with ezetimibe. The mean level of remnant-like particle cholesterol also decreased significantly from 6.5 (3.8) to 4.8 (2.2) mg/dL (−15%; P = 0.03). Treatment with ezetimibe was associated with a reduction in FPG level from 127 (31) to 119 (30) mg/dL (P = 0.02), and HbAlc from 6.3% (0.6%) to 6.1% (0.7%) (P = 0.003). No AEs were observed or reported during the study period.Conclusion: In this small, open-label, uncontrolled, pilot study, ezetimibe was associated with a significant decrease in lipid parameters and improvement in glucose metabolism in these patients with T2DM.     

Elevated apolipoprotein B-48 and remnant-like particle-cholesterol in heterozygous familial hypercholesterolaemia

Apolipoprotein B-48 (apoB-48) is a marker of triglyceride-rich lipoprotein (TRL) remnants of intestinal origin. Chylomicron remnants are causally related to atherosclerosis. We have shown previously that fasting plasma apoB-48 may predict postprandial lipaemia. Remnant-like particle-cholesterol (RLP-C) may also reflect TRL remnants. We aimed to determine whether subjects with heterozygous familial hypercholesterolaemia (FH) had an accumulation of remnants of intestinal origin, as reflected by fasting plasma apoB-48 and RLP-C levels. The fasting plasma concentrations of apoB-48 and RLP-C were measured in 15 subjects with heterozygous FH and 15 age- and sex-matched, normolipidaemic subjects. ApoB-48 was determined using SDS-PAGE and a western blotting/enhanced chemi-luminescence technique. RLP-C was measured using an immuno-separation assay. Serum apolipoprotein B-100 (apoB-100) levels were measured using immunonephelometry; lipids were assayed enzymatically. Compared with controls, FH subjects had significantly elevated plasma concentrations of apoB-48 (29.3 median, 16.7-45.1 mg L-1 range vs. 12.8, 7.3-28.6; P < 0.001) and RLP-C (16.2, 1.5-114.3 mg dL-1 vs. 8.5, 5.0-13.5; P = 0.003), as well as serum total apoB-100 (1.9, 1.3-2.6 g L-1 vs. 1.0, 0.3-1.3; P < 0.001), LDL-cholesterol (8.1, 4.6-10.4 mmol L-1 vs. 3.5, 2.4-4.4; P < 0.001) and triglyceride (1.5, 0.6-5.6 mmol L-1 vs. 1.0, 0.4-1.8; P = 0.018). There was no significant difference in HDL cholesterol. The findings suggest that patients with heterozygous FH have elevated plasma concentrations of TRL remnants, including those of intestinal origin. This may be a consequence of decreased clearance of these particles by the LDL-receptor.     

颈动脉粥样硬化患者不同中医证型的血脂水平及血清RLP-C、sICAM-1、sVCAM-1含量差异分析研究

目的 研究颈动脉粥样硬化患者不同中医证型的血脂水平及血清脂蛋白残粒(RLP-C)、 细胞间黏附分子1(sICAM-1)和血管细胞黏附分子1(sVCAM-1)含量差异.方法 筛选2015年1月至2015年12月就诊于航天中心医院的颈动脉粥样硬化的患者90例设为中医组,同时筛选健康体检者90例设为正常组,取患者晨起空腹静脉血进行检测.观察颈动脉粥样硬化患者痰浊阻遏证、脾肾阳虚证、肝肾阴虚证、阴虚阳亢证以及气滞血瘀证情况,比较不同中医证候类型患者与正常组的血脂水平及其血清RLP-C、sICAM-1及sVCAM-1含量.结果 90例颈动脉粥样硬化患者中,54例为痰浊阻遏证,占总患病人数的60.00%,显著高于脾肾阳虚证、肝肾阴虚证、阴虚阳亢证以及气滞血瘀证患者,差异具有统计学意义(P<0.05);不同中医证候类型患者的血清TG、TC和LDL-C水平要高于正常组,而HDL-C含量要低于正常组,差异均具有统计学意义(P<0.05);此外,痰浊阻遏证患者的TG、TC、LDL-C含量高于其他中医证候型患者,而HDL-C含量低于其他中医证候型患者,差异均具有统计学意义(P<0.05);不同中医证候类型患者的血清RLP-C、sICAM-1及sVCAM-1水平要高于正常组,且痰浊阻遏证患者血清RLP-C、sICAM-1及sVCAM-1水平要高于其他中医证候型患者,差异均具有统计学意义(P<0.05).结论 颈动脉粥样硬化患者主要为痰浊阻遏证候,且颈动脉粥样硬化患者与健康体检者的RLP-C及其相关指标差异显著,其中痰浊阻遏证患者最为明显.     

Ezetimibe: cholesterol lowering and beyond

Ezetimibe is a cholesterol absorption inhibitor that blocks the intestinal absorption of both biliary and dietary cholesterol. It appears to exert its effect by blocking intestinal sterol transporters, specifically Niemann–Pick C1-like 1 proteins, thereby inhibiting the intestinal absorption of cholesterol, phytosterols and certain oxysterols. Ezetimibe monotherapy and in combination with statin therapy is primarily indicated for lowering LDL-cholesterol levels. In addition, it may favorably affect other parameters that could potentially further reduce atherosclerotic coronary heart disease risk, such as raising HDL-cholesterol and lowering levels of triglycerides, non-HDL-cholesterol, apolipoprotein B and remnant-like particle cholesterol. Further effects of ezetimibe include a reduction in circulating phytosterols and oxysterols and, when used in combination with statins, a reduction in high-sensitivity C-reactive protein. The clinical significance of the LDL-cholesterol lowering and other effects of ezetimibe is being evaluated in clinical outcome studies.