Chemello Kévin, Guedon Alexis F, Techer Romuald, Jaafar Ali K, Guilhen Sam, Swietek Michael J, Lambert Gilles, Gallo Antonio
Université de La Réunion, Inserm, UMR1188 Diabète Athérothrombose Thérapies Réunion Océan Indien (DéTROI) Sainte-Pierre (Réunion) France.
School of Biomedical Sciences, Faculty of Medicine and Health University of New South Wales Sydney NSW Australia.
J Am Heart Assoc. 2025 May 6;14(9):e036630. doi: 10.1161/JAHA.124.036630. Epub 2025 Apr 16.
In the SPARCL (Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial, atorvastatin (80 mg per day) was compared with placebo in patients with recent stroke or transient ischemic attack and no known coronary artery disease. Given the central role of apoE (apolipoprotein E) in lipoprotein metabolism and in the central nervous system, we assessed the contribution of apoE to subsequent cerebrovascular and cardiovascular events in this trial.
ApoE concentrations and major isoforms (E2/E3/E4) were determined by liquid-chromatography high resolution mass-spectrometry in plasma samples collected at baseline from 4348 SPARCL participants. Patients in the lowest quartile were compared with those in the highest quartiles of apoE concentrations. Multivariable-adjusted hazard-ratios (HR) and 95% CIs were calculated using Cox proportional hazards regression models. We found a significant association between low apoE concentrations and the risk of recurrent strokes or cerebrovascular events (HR, 1.401 [95% CI, 1.154-1.701], <0.001 and 1.467 [95% CI, 1.260-1.708], <0.001) driven by a higher incidence of ischemic strokes and transient ischemic attacks in the entire cohort as well as separately in each treatment arm of SPARCL. In contrast, apoE concentrations did not significantly associate with the incidence of hemorrhagic strokes in SPARCL. We also found a significant association between reduced apoE concentrations and the risk of subsequent coronary events (HR, 1.373 ([95% CI, 1.064-1.772], =0.015) in the entire cohort that was, however, significant only in the placebo arm of SPARCL.
Low apoE concentrations are predictive of recurring cerebrovascular events in patients with a history of stroke or transient ischemic attack.
URL: https://www.clinicaltrials.gov; Identifier: NTC00147602.
在强化降低胆固醇水平预防卒中（SPARCL）试验中，将阿托伐他汀（每日80毫克）与安慰剂用于近期发生卒中或短暂性脑缺血发作且无已知冠状动脉疾病的患者。鉴于载脂蛋白E（apoE）在脂蛋白代谢和中枢神经系统中的核心作用，我们在该试验中评估了apoE对随后脑血管和心血管事件的影响。
通过液相色谱高分辨率质谱法测定了4348名SPARCL参与者基线时采集的血浆样本中的apoE浓度和主要异构体（E2/E3/E4）。将apoE浓度处于最低四分位数的患者与处于最高四分位数的患者进行比较。使用Cox比例风险回归模型计算多变量调整风险比（HR）和95%置信区间（CI）。我们发现，apoE浓度低与复发性卒中或脑血管事件风险之间存在显著关联（HR，1.401[95%CI，1.154 - 1.701]，P<0.001；以及1.467[95%CI，1.260 - 1.708]，P<0.001），这是由整个队列以及SPARCL每个治疗组中缺血性卒中和短暂性脑缺血发作的较高发生率所驱动的。相比之下，apoE浓度与SPARCL中出血性卒中的发生率无显著关联。我们还发现，apoE浓度降低与随后冠状动脉事件风险之间存在显著关联（HR，1.373[95%CI，1.064 - 1.772]，P = 0.015），然而，这仅在SPARCL的安慰剂组中显著。
apoE浓度低可预测有卒中或短暂性脑缺血发作病史患者的复发性脑血管事件。
