Effects of patient‐tailored atorvastatin therapy on ameliorating the levels of atherogenic lipids and inflammation beyond lowering low‐density lipoprotein cholesterol in patients with type 2 diabetes

Aims/Introduction

Recently, patient‐tailored statin therapy was proven effective for achieving target low‐density lipoprotein (LDL) cholesterol levels. It is unclear, however, whether this therapeutic modality would be effective for atherogenic lipid profiles and inflammation in patients with type 2 diabetes.

Materials and Methods

The present study was an 8‐week, multicenter, single‐step titration trial of patient‐tailored atorvastatin therapy (10, 20 and 40 mg) according to baseline LDL cholesterol levels in 440 patients with type 2 diabetes. We measured the LDL particle size by polyacrylamide gel electrophoresis, and used high‐sensitivity C‐reactive protein (hsCRP) and adiponectin as surrogate markers of inflammation.

Results

In the intention‐to‐treat analysis, 91% of the patients achieved their LDL cholesterol targets (<2.6 mmol/L) at week 8. There were significant reductions at week 8 in total cholesterol, triglycerides, non‐high‐density lipoprotein cholesterol (HDL) cholesterol, and the total cholesterol:HDL cholesterol ratio compared with the baseline values for all of the doses. The mean LDL particle size was significantly increased, and the small, dense LDL cholesterol levels were decreased in a dose‐dependent manner over the study period. In addition, the hsCRP levels were decreased in those high‐risk patients with baseline hsCRP levels over 3 mg/L (P < 0.001), and the adiponectin levels tended to increase with all of the doses (P = 0.004) at 8 weeks.

Conclusions

Patient‐tailored atorvastatin therapy based on LDL cholesterol at baseline was effective in ameliorating atherogenic LDL particle size and inflammation, in addition to achieving the target LDL cholesterol level without an undesirable effect on glycemic control in patients with type 2 diabetes. This trial was registered with ClinicalTrials.gov (no. NCT01239849).     

Small dense low‐density lipoprotein cholesterol is a promising biomarker for secondary prevention in older men with stable coronary artery disease

Aim

The study objective was to investigate whether small dense low‐density lipoprotein cholesterol (sdLDL‐C) is superior to low‐density lipoprotein cholesterol (LDL‐C) and other biomarkers to predict future cardiovascular events (CE) in secondary prevention.

Methods

sdLDL‐C measured by a homogeneous assay, remnant lipoprotein cholesterol, LDL particle diameter and other biomarkers were compared in 345 men aged ≥65 years with stable coronary artery disease. Baseline LDL‐C was 100.5 ± 30.1 mg/dL. CE including cardiovascular death, onset of acute coronary syndrome, need for arterial revascularization, hospitalization for heart failure, surgery procedure for cardiovascular disease and hospitalization for stroke were monitored for 5 years.

Results

CE occurred in 96 patients during the study period. LDL‐C, sdLDL‐C non‐high‐density lipoprotein cholesterol, apolipoprotein B, remnant lipoprotein cholesterol, glucose, glycated hemoglobin and brain natriuretic peptide were significantly higher; LDL particle diameter and apolipoprotein A‐1 were significantly lower in patients with than in those without CE. Age‐adjusted Cox regression analysis showed that sdLDL‐C per 10 mg/dL, but not LDL‐C, was significantly associated with CE (HR 1.206, 95% CI 1.006–1.446). A significant association of sdLDL‐C and incident CE was observed in statin users (HR 1.252, 95% CI 1.017–1.540), diabetes patients (HR 1.219, 95% CI 1.018–1.460), patients without diabetes (HR 1.257, 95% CI 1.019–1.551) and patients with hypertriglyceridemia (HR 1. 376, 95% CI 1.070–1.770).

Conclusions

sdLDL‐C was the most effective predictor of residual risk of future CE in stable coronary artery disease patients using statins and in high‐risk coronary artery disease patients with diabetes or hypertriglyceridemia. Geriatr Gerontol Int 2018; 18: 965–972 .     

Evaluation of serum high-density lipoprotein cholesterol levels as a prognostic factor in gastric cancer patients

Background and Aim: Although there are some reports of an adverse effect of low serum high-density lipoprotein cholesterol (HDL-C) levels on gastrointestinal cancers, the specific correlation between serum HDL-C levels and gastric cancer remains unknown. Methods: Preoperative serum HDL-C levels were retrospectively examined in 184 patients who had undergone gastrectomy. The patients who had undergone gastrectomy were divided into two groups: the normal-HDL-C group and the low-HDL-C group. We examined the characteristics and outcomes of these two groups. Univariate and multivariate analyses were performed to investigate the association between serum HDL-C levels and gastric cancer. Results: There was no significant difference between the groups in terms of the progression of gastric cancer. In the low-HDL-C group, lymphatic and vascular invasion was significantly increased. The prognosis of the patients in the normal-HDL-C group was significantly better than those in the low-HDL-C group. Conclusions: In this study, a positive correlation between low preoperative serum HDL-C levels and prognosis for gastric cancer was demonstrated. Serum HDL-C level may be a clinical prognostic factor for gastric cancer patients.     

Diabetes mellitus,but not small dense low‐density lipoprotein,is predictive of cardiovascular disease: A Korean community‐based prospective cohort study

Aims/Introduction

Small dense low‐density lipoprotein (sdLDL) has been suggested to be a potential risk factor for cardiovascular diseases (CVD).

Materials and Methods

We carried out a prospective nested case–control study in the Korean Health and Genome Study. Participants were men and women aged 40–69 years who developed CVD (n = 313), and were matched by age and sex to controls who remained free of CVD (n = 313) during the 8‐years follow‐up period (from 2001 to 2009). LDL subfractions were analyzed in frozen samples collected from the 626 participants using polyacrylamide tube gel electrophoresis.

Results

Patients with CVD had a significantly higher glycated hemoglobin level compared with the controls (5.72 vs 5.56). The proportion of patients with diabetes mellitus (DM) was higher in those who developed CVD during follow up (8.0% vs 1.9%). The frequency of CVD according to each tertile of LDL particle size and the number of metabolic syndrome components did not differ significantly. In the multivariate analysis, DM (odds ratio 4.244, 95% confidence interval 1.693–10.640, P = 0.002) was the only independent predictive factor of CVD. LDL particle size was not associated with the risk for future CVD.

Conclusions

Small dense LDL might not be a significant predictor of CVD in this Korean community‐based prospective cohort study.     

Efficacy of ezetimibe for the treatment of non‐alcoholic steatohepatitis: An open‐label,pilot study

Aim: Non‐alcoholic steatohepatitis (NASH) is considered a hepatic manifestation of metabolic syndrome. However, effective drug therapy for NASH has not been established yet. In the present study, we evaluated the efficacy of 6 months of ezetimibe treatment for NASH patients with dyslipidemia for the comparison of improvement of the clinical parameters and histological alterations. Methods: We prospectively evaluated 10 consecutive NASH patients with dyslipidemia who agreed to participate in this study. The patients were given ezetimibe (10 mg/day) for 6 months, and clinical parameters and histological alterations were comparatively evaluated before and after treatment. All the patients were given standard calorie diet (30 kcal/kg per day, carbohydrate 50–60%, fat 20–30%, protein 15–20%) and exercise counseling from 3 months before the ezetimibe treatment. Results: The serum aspartate aminotransferase, alanine aminotransferase, γ‐glutamyl transpeptidase, low‐density lipoprotein cholesterol, high‐sensitivity C‐reactive protein and type IV collagen 7 s levels were significantly improved by the treatment with ezetimibe for 6 months. In histological observations, follow‐up liver biopsies revealed that the NAS score and steatosis grade were also significantly improved. The fibrosis stage did not change significantly, but six of the 10 patients exhibited an improvement in their fibrosis stage. Conclusion: Major clinical parameters and histological observations were significantly improved by the treatment with ezetimibe. Our pilot study demonstrated the efficacy of ezetimibe for drug therapy of NASH and may lead to a large‐scale clinical trial in the future.     

低密度脂蛋白胆固醇异常在2型糖尿病家系中的家族聚集性及相关因素分析

目的探讨低密度脂蛋白胆固醇(LDL-C)异常在北京地区2型糖尿病(T2DM)家系一级亲属中是否存在遗传倾向以及相关因素。方法收集北京地区具有两个或以上T2DM患者的家系295个,共978例,将每一家系中先证者按LDL-C<2.6 mmol/L和≥2.6 mmol/L分为正常LDL-C组131例和高LDL-C组163例,比较两组患者T2DM和非T2DM一级亲属的LDL-C水平,用多因素逐步回归分析了解其相关因素。结果高LDL-C组的T2DM一级亲属的年龄、空腹血糖(FPG)、糖化血红蛋白(HbA1c)、总胆固醇(TCHO)和LDL-C高于正常LDL-C组(P<0.05)。多因素逐步回归分析显示,T2DM一级亲属的LDL-C与先证者LDL-C、HbA1c及年龄独立相关。高LDL-C组的非T2DM一级亲属的TCHO和LDL-C高于正常LDL-C组(P<0.05)。多因素逐步回归分析显示,非T2DM一级亲属的LDL-C与先证者LDL-C、HbA1c及年龄独立相关。结论在中国北京地区T2DM家系中LDL-C异常存在家族聚集现象,且LDL-C与HbA1c和年龄独立相关。     

首发未服药抑郁症患者血清非高密度脂蛋白胆固醇水平及相关因素分析

目的探讨抑郁症患者血清非高密度脂蛋白胆固醇(non-HDLC)水平,并对其相关因素进行分析。方法选取2014年6月至2015年11月期间在华北理工大学附属开滦精神卫生中心住院治疗的150例抑郁症患者,分别测定其总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC)、低密度脂蛋白胆固醇(LDLC)的水平,并通过抑郁自评量表(SDS)对其抑郁症状进行测评,采用SPSS 17.0软件,运用独立样本t检验、单因素方差分析、偏相关分析及逐步多元回归分析对数据进行统计分析。结果抑郁症患者血清non-HDLC水平低于正常人,差异有统计学意义(P0.05);不同性别、年龄、文化程度及抑郁严重程度的抑郁症患者non-HDLC水平差异有统计学意义(P0.05);在控制了性别、年龄及文化程度影响因素后,抑郁症患者SDS标准分与TC、TG、LDLC及non-HDLC水平均存在显著负相关(P0.05);抑郁症患者SDS标准分对non-HDLC水平有显著的负向预测力(β=-0.682,P0.05)。结论抑郁症与血清non-HDLC水平存在相关,应积极关注抑郁患者发生心脑血管疾病的风险和机制。