阿托伐他汀低剂量与高剂量对 2 型糖尿病患者脂蛋白代谢和炎症细胞因子影响的比较：来自糖尿病阿托伐他汀肾病预防（PANDA）随机试验的结果。

A comparison of the effects of low- and high-dose atorvastatin on lipoprotein metabolism and inflammatory cytokines in type 2 diabetes: Results from the Protection Against Nephropathy in Diabetes with Atorvastatin (PANDA) randomized trial.

机构信息

Cardiovascular Trials Unit, The Old St Mary's Hospital, Central Manchester University Hospitals, Manchester, United Kingdom; Division of Cardiovascular Sciences, Cardiovascular Research Group, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.

Division of Cardiovascular Sciences, Cardiovascular Research Group, School of Medical Sciences, University of Manchester, Manchester, United Kingdom.

出版信息

J Clin Lipidol. 2018 Jan-Feb;12(1):44-55. doi: 10.1016/j.jacl.2017.10.011. Epub 2017 Nov 13.

DOI:10.1016/j.jacl.2017.10.011

PMID:29246729

Abstract

BACKGROUND

Statin therapy is recommended in type 2 diabetes (T2DM) although views on treatment intensity and therapeutic targets remain divided.

OBJECTIVES

Our objectives were to compare the effects of high-intensity and moderate-intensity atorvastatin treatment on lipoprotein metabolism and inflammatory markers and how frequently treatment goals are met in high-risk T2DM patients.

METHODS

Patients with T2DM and albuminuria (urinary albumin:creatinine ratio >5 mg/mmol, total cholesterol <7 mmol/L, proteinuria <2 g/d, creatinine <200 μmol/L) were randomized to receive atorvastatin 10 mg (n = 59) or 80 mg (n = 60) daily. Baseline and 1-year follow-up data are reported.

RESULTS

Patients were at high cardiovascular disease risk (observed combined mortality and nonfatal cardiovascular disease annual event rate 4.8%). The non-high-density lipoprotein cholesterol (HDL-C) goal of <2.6 mmol/L was achieved in 72% of participants receiving high-dose atorvastatin, but only in 40% on low-dose atorvastatin (P < .005). The proportion achieving apolipoprotein B (apoB) <0.8 g/L on high-dose and low-dose atorvastatin was 82% and 70%, respectively (NS). Total cholesterol, triglycerides, low-density lipoprotein (LDL) cholesterol, non-HDL-C, oxidized LDL, apoB, glyc-apoB, apolipoprotein E, and lipoprotein-associated phospholipase A2 decreased significantly, more so in participants on high-dose atorvastatin. Adiponectin increased and serum amyloid A decreased without dose dependency. Neither dose produced significant changes in HDL-C, cholesterol efflux, high-sensitivity C-reactive protein, glycated hemoglobin, serum paraoxonase-1, lecithin:cholesterol acyltransferase, or cholesteryl ester transfer protein.

CONCLUSIONS

High-dose atorvastatin is more effective in achieving non-HDL-C therapeutic goals and in modifying LDL-related parameters. Recommended apoB treatment targets may require revision. Despite the increase in adiponectin and the decrease in serum amyloid A, HDL showed no change in functionality.

摘要

背景

尽管对于治疗强度和治疗目标的看法仍存在分歧，但他汀类药物治疗仍推荐用于 2 型糖尿病（T2DM）。

目的

我们的目的是比较高强度和中强度阿托伐他汀治疗对脂蛋白代谢和炎症标志物的影响，以及高风险 T2DM 患者达到治疗目标的频率。

方法

患有 T2DM 和白蛋白尿（尿白蛋白/肌酐比值>5mg/mmol，总胆固醇<7mmol/L，蛋白尿<2g/d，肌酐<200μmol/L）的患者被随机分为阿托伐他汀 10mg（n=59）或 80mg（n=60）每日治疗组。报告了基线和 1 年随访的数据。

结果

患者具有较高的心血管疾病风险（观察到的复合死亡率和非致命性心血管疾病年事件发生率为 4.8%）。接受高剂量阿托伐他汀治疗的患者中，72%达到了非高密度脂蛋白胆固醇（HDL-C）<2.6mmol/L的目标，但仅 40%接受低剂量阿托伐他汀治疗的患者达到了该目标（P<0.005）。高剂量和低剂量阿托伐他汀治疗组分别有 82%和 70%的患者载脂蛋白 B（apoB）<0.8g/L，差异无统计学意义（NS）。总胆固醇、甘油三酯、低密度脂蛋白（LDL）胆固醇、非高密度脂蛋白胆固醇、氧化型 LDL、apoB、糖基化 apoB、载脂蛋白 E 和脂蛋白相关磷脂酶 A2 显著降低，高剂量阿托伐他汀治疗组降低更明显。脂联素增加，血清淀粉样蛋白 A 降低，但与剂量无关。两种剂量均未使高密度脂蛋白胆固醇、胆固醇流出、高敏 C 反应蛋白、糖化血红蛋白、血清对氧磷酶 1、卵磷脂：胆固醇酰基转移酶或胆固醇酯转移蛋白发生显著变化。