CGH Medical Center, Sterling, IL, USA; Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Ciccarone Center for the Prevention of Heart Disease, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
J Clin Lipidol. 2018 May-Jun;12(3):741-747.e11. doi: 10.1016/j.jacl.2018.03.077. Epub 2018 Mar 9.
The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides and Impact on Global Health Outcomes) trial failed to demonstrate incremental clinical benefit of extended-release niacin (ERN) in 3414 statin-treated patients with established cardiovascular (CV) disease who had low baseline levels of high-density lipoprotein cholesterol (HDL-C) as compared to placebo. A previous secondary analysis suggested that ERN provided outcome benefits in ERN-treated patients with high triglycerides (TGs; >200 mg/dL) and very low HDL-C (<32 mg/dL) at baseline. The current analysis sought to ascertain how changes in TG-enriched lipoproteins and HDL subfractions impact residual risk in the comparator treatment arms.
We evaluated the relationship between niacin treatment, lipoproteins and their subfractions, and CV outcomes in a non-prespecified, post hoc analysis of the AIM-HIGH trial.
Lipoprotein subfraction analysis was performed with zonal ultracentrifugation in 2457 AIM-HIGH participants at baseline and 1 year of treatment. Hazard ratios were estimated using Cox proportional hazards models for relationships between lipoproteins and the composite primary endpoint of CV death, myocardial infarction, acute coronary syndrome, ischemic stroke, or symptom-driven revascularization. Analyses were performed for the entire cohort and in participants with TGs > 200 mg/dL and HDL-C < 32 mg/dL.
Apoprotein B-containing lipoproteins and their subfractions decreased significantly in both treatment arms but decreased more with ERN treatment. HDL-C and its subfractions increased significantly in both treatment groups, but more so in patients treated with ERN. For the entire study population, neither apoB- nor apoA1-containing lipoprotein subfractions predicted risk at baseline or at 1 year of follow-up. In the high TG and low HDL-C subgroup treated with placebo, changes at 1 year in HDL-C, total cholesterol/HDL-C, and non-HDL-C/HDL-C may be associated with increased CV events, whereas in the ERN treatment arm, changes at 1 year in very low-density lipoprotein cholesterol and very low-density lipoprotein subfractions, total remnant lipoproteins, and various risk ratios may be associated with increased CV events, while HDL-C may be associated with reduced risk.
We provide hypothesis-generating findings that ERN may confer benefit in patients with coronary heart disease who have high TGs and low HDL by reducing serum levels of remnant lipoprotein cholesterol and increasing HDL-C.
AIM-HIGH（代谢综合征中载脂蛋白 B 升高伴高密度脂蛋白胆固醇降低/甘油三酯升高与全球健康结局的干预研究）试验未能证明与安慰剂相比，在已患有心血管疾病且基线时高密度脂蛋白胆固醇（HDL-C）水平较低的 3414 名接受他汀类药物治疗的患者中，延长释放烟酸（ERN）可带来额外的临床获益。先前的二次分析表明，ERN 可使基线时甘油三酯（TG）较高（>200mg/dL）和 HDL-C 极低（<32mg/dL）的 ERN 治疗患者获得获益。目前的分析旨在确定 TG 丰富的脂蛋白和 HDL 亚组分的变化如何影响对照治疗组的残余风险。
我们在 AIM-HIGH 试验的非预设事后分析中评估了烟酸治疗、脂蛋白及其亚组分与心血管结局之间的关系。
在基线和治疗 1 年时，对 AIM-HIGH 试验的 2457 名参与者进行脂蛋白亚组分分析，采用区带超速离心法。使用 Cox 比例风险模型估计风险比，以评估脂蛋白与心血管死亡、心肌梗死、急性冠脉综合征、缺血性卒中和症状驱动的血运重建的复合主要终点之间的关系。对整个队列以及 TG>200mg/dL 和 HDL-C<32mg/dL 的参与者进行了分析。
在两种治疗组中，载脂蛋白 B 含脂蛋白及其亚组分均显著降低，但 ERN 治疗组降低更为明显。HDL-C 及其亚组分在两组治疗中均显著增加，但 ERN 治疗组增加更为明显。对于整个研究人群，载脂蛋白 B 和载脂蛋白 A1 含脂蛋白亚组分在基线或 1 年随访时均不能预测风险。在接受安慰剂治疗的高 TG 和低 HDL-C 亚组中，1 年时 HDL-C、总胆固醇/HDL-C 和非 HDL-C/HDL-C 的变化可能与心血管事件增加相关，而在 ERN 治疗组中，1 年时极低密度脂蛋白胆固醇和极低密度脂蛋白亚组分、总残粒脂蛋白以及各种风险比的变化可能与心血管事件增加相关，而 HDL-C 可能与降低风险相关。
我们提供了一些假设生成的发现，ERN 可能通过降低血清残余脂蛋白胆固醇水平和增加 HDL-C，为患有高 TG 和低 HDL-C 的冠心病患者带来获益。
