Ip Wendy T K, Chandramouli Chanchal, Smith Julian A, McLennan Peter L, Pepe Salvatore, Delbridge Lea M D
Cardiac Phenomics Laboratory, Department of Physiology, University of Melbourne, Melbourne, Vic, Australia.
Department of Cardiothoracic Surgery, Monash Health, Monash University, Melbourne, Vic, Australia; Department of Surgery, School of Clinical Sciences at Monash Health, Monash University, Melbourne, Vic, Australia.
Heart Lung Circ. 2017 Aug;26(8):846-855. doi: 10.1016/j.hlc.2016.12.007. Epub 2017 Feb 6.
Epidemiological studies and randomised clinical trials (RCTs) report disparate findings in relation to omega-3 polyunsaturated fatty acids (n-3 PUFA) benefit for cardiac patients. With RCTs interpretation is potentially confounded by background n-3 PUFA intake. The goal of this pilot, small cohort, pre-surgical supplementation study was to evaluate postoperative atrial fibrillation (AF) and cardiac molecular expression profiles employing two data analysis approaches - by treatment randomisation and by stratification using measured n-3 PUFA.
Patients (n=20) received 3g/day of fish or placebo oil (FO vs PO) in a double blind randomised protocol prior to elective coronary artery graft and valve surgery. Groups were matched for age, gender, and mean treatment duration (∼20 days). Resected atrial myocardium was sampled for assay of viability metabolic markers, and blood obtained for erythrocyte membrane lipid measurement.
There was substantial overlap of cell membrane n-3 PUFA content across PO and FO groups, and no group treatment effects on AF incidence or myocardial molecular marker levels were detected. In contrast, data stratification using membrane n-3 PUFA content (at 8% total membrane lipid) achieved significant separation of patients (by n-6:n-3 PUFA ratio), a significant differential cardiac expression of the marker peroxisomal proliferator-activated receptor, but no difference in AF incidence.
This small n-3 PUFA case study demonstrates that the same cohort may yield differing findings when evaluated using randomisation or stratification approaches based on direct molecular measures in cell membranes.
流行病学研究和随机临床试验(RCT)报告了ω-3多不饱和脂肪酸(n-3 PUFA)对心脏病患者益处的不同研究结果。对于RCT,其解读可能会因n-3 PUFA的背景摄入量而产生混淆。这项小型队列术前补充研究的目的是采用两种数据分析方法——治疗随机化和根据测量的n-3 PUFA进行分层,来评估术后房颤(AF)和心脏分子表达谱。
20例患者在择期冠状动脉搭桥和瓣膜手术前,按照双盲随机方案接受3克/天的鱼油或安慰剂油(鱼油组与安慰剂组)。两组在年龄、性别和平均治疗持续时间(约20天)方面相匹配。采集切除的心房心肌样本用于检测活力代谢标志物,并采集血液用于测量红细胞膜脂质。
安慰剂组和鱼油组细胞膜n-3 PUFA含量有很大重叠,未检测到组间治疗对房颤发生率或心肌分子标志物水平的影响。相比之下,使用膜n-3 PUFA含量(占总膜脂质的8%)进行数据分层,实现了患者的显著分离(按n-6:n-3 PUFA比例),过氧化物酶体增殖物激活受体标志物的心脏表达有显著差异,但房颤发生率无差异。
这项小型n-3 PUFA病例研究表明,当基于细胞膜中的直接分子测量,使用随机化或分层方法进行评估时,同一队列可能会得出不同的结果。