Martin Seth S, Faridi Kamil F, Joshi Parag H, Blaha Michael J, Kulkarni Krishnaji R, Khokhar Arif A, Maddox Thomas M, Havranek Edward P, Toth Peter P, Tang Fengming, Spertus John A, Jones Steven R
Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
Atherotech Diagnostics Laboratory, Birmingham, Alabama.
Clin Cardiol. 2015 Nov;38(11):660-7. doi: 10.1002/clc.22470. Epub 2015 Oct 13.
Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that, like other apolipoprotein B-containing lipoproteins, are atherogenic. Prior observational studies suggest paradoxically better outcomes in hypercholesterolemic patients who sustain an acute myocardial infarction (AMI), one of several known recurrent risk paradoxes. To date, the association of directly measured remnant lipoprotein cholesterol (RLP-C) with survival after an AMI has not been examined.
Higher RLP-C levels may be paradoxically associated with lower mortality.
We examined 2465 AMI survivors in a prospective, 24-center US study of AMI outcomes. Lipoprotein cholesterol subfractions were directly measured by ultracentrifugation. RLP-C was defined as intermediate-density lipoprotein cholesterol (IDL-C) + very-low-density lipoprotein cholesterol subfraction 3 (VLDL3 -C). Given a linear relationship between RLP-C and mortality, we examined RLP-C by tertiles and continuously. Cox regression hazard ratios (HRs) were adjusted for the Global Registry of Acute Coronary Events (GRACE) score and 23 other covariates.
Participants were age 58 ± 12 years (mean ± SD), and 68% were men. After 2 years of follow-up, 226 (9%) participants died. The mortality proportion was 12.4% in the lowest tertile of RLP-C (0-15 mg/dL), 8.5% in the middle tertile (16-23 mg/dL), and 6.8% in the highest tertile (24-120 mg/dL; P < 0.001). A 1-SD increase in RLP-C (11 mg/dL) predicted a 24% lower adjusted risk of 2-year mortality (HR: 0.76, 95% confidence interval [CI]: 0.64-0.91). Similar results were found for a 1-SD increase in IDL-C (HR per 8 mg/dL: 0.80, 95% CI: 0.67-0.96), VLDL3 -C (HR per 4 mg/dL: 0.74, 95% CI: 0.61-0.89), and very-low-density lipoprotein cholesterol (VLDL-C; HR per 8 mg/dL: 0.69, 95% CI: 0.55-0.85).
Higher RLP-C levels were associated with lower mortality 2 years after AMI despite rigorous adjustment for known confounders. Unknown protective factors or a lead-time bias likely explains the paradox.
残余颗粒是部分水解的、富含甘油三酯的脂蛋白，与其他含载脂蛋白B的脂蛋白一样，具有致动脉粥样硬化作用。先前的观察性研究表明，在发生急性心肌梗死（AMI）的高胆固醇血症患者中，结果反而更好，这是几种已知的复发风险悖论之一。迄今为止，尚未研究直接测量的残余脂蛋白胆固醇（RLP-C）与AMI后生存率之间的关联。
较高的RLP-C水平可能反而与较低的死亡率相关。
我们在美国一项针对AMI结局的前瞻性、24中心研究中，对2465例AMI幸存者进行了研究。通过超速离心直接测量脂蛋白胆固醇亚组分。RLP-C定义为中间密度脂蛋白胆固醇（IDL-C）+极低密度脂蛋白胆固醇亚组分3（VLDL3-C）。鉴于RLP-C与死亡率之间存在线性关系，我们按三分位数和连续变量对RLP-C进行了研究。Cox回归风险比（HR）针对急性冠状动脉事件全球注册（GRACE）评分和其他23个协变量进行了调整。
参与者年龄为58±12岁（均值±标准差），68%为男性。经过2年随访，226例（9%）参与者死亡。RLP-C最低三分位数（0-15mg/dL）的死亡率为12.4%，中间三分位数（16-23mg/dL）为8.5%，最高三分位数（24-120mg/dL；P<0.001）为6.8%。RLP-C增加1个标准差（11mg/dL）预测2年调整后死亡风险降低24%（HR：0.76，95%置信区间[CI]：0.64-0.91）。IDL-C增加1个标准差（每8mg/dL的HR：0.80，95%CI：0.67-0.96）、VLDL3-C（每4mg/dL的HR：0.74，95%CI：0.61-0.89）和极低密度脂蛋白胆固醇（VLDL-C；每8mg/dL的HR：0.69，95%CI：0.55-0.85）也发现了类似结果。
尽管对已知混杂因素进行了严格调整，但较高的RLP-C水平与AMI后2年较低的死亡率相关。未知的保护因素或领先时间偏倚可能解释了这一悖论。
