低密度脂蛋白载脂蛋白B与低密度脂蛋白胆固醇比值：与心血管死亡率的关联及小而密低密度脂蛋白的生物标志物
The LDL Apolipoprotein B-to-LDL Cholesterol Ratio: Association with Cardiovascular Mortality and a Biomarker of Small, Dense LDLs.
作者信息
Silbernagel Günther, Scharnagl Hubert, Saely Christoph H, Reinthaler Markus, Rief Martin, Kleber Marcus E, Larcher Barbara, Chapman John, Schaefer Juergen R, Drexel Heinz, März Winfried
机构信息
Division of Angiology, Department of Internal Medicine, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
Clinical Institute of Medical and Chemical Laboratory Diagnostics, Medical University of Graz, Auenbruggerplatz 15, 8036 Graz, Austria.
出版信息
Biomedicines. 2022 Jun 2;10(6):1302. doi: 10.3390/biomedicines10061302.
Background and Objective: Small, dense low-density lipoproteins (LDLs) are considered more atherogenic than normal size LDLs. However, the measurement of small, dense LDLs requires sophisticated laboratory methods, such as ultracentrifugation, gradient gel electrophoresis, or nuclear magnetic resonance. We aimed to analyze whether the LDL apolipoprotein B (LDLapoB)-to-LDL cholesterol (LDLC) ratio is associated with cardiovascular mortality and whether this ratio represents a biomarker for small, dense LDLs. Methods: LDLC and LDLapoB were measured (beta-quantification) and calculated (according to Friedewald and Baca, respectively) for 3291 participants of the LURIC Study, with a median (inter-quartile range) follow-up for cardiovascular mortality of 9.9 (8.7−10.7) years. An independent replication cohort included 1660 participants. Associations of the LDLapoB/LDLC ratio with LDL subclass particle concentrations (ultracentrifugation) were tested for 282 participants. Results: In the LURIC Study, the mean (standard deviation) LDLC and LDLapoB concentrations were 117 (34) and 85 (22) mg/dL, respectively; 621 cardiovascular deaths occurred. Elevated LDLapoB/LDLC (calculated and measured) ratios were significantly and independently associated with increased cardiovascular mortality in the entire cohort (fourth vs. first quartile: hazard ratio (95% confidence interval) = 2.07 (1.53−2.79)) and in statin-naïve patients. The association between calculated LDLapoB/LDLC ratio and cardiovascular mortality was replicated in an independent cohort. High LDLapoB/LDLC ratios were associated with higher LDL5 and LDL6 concentrations (both p < 0.001), but not with concentrations of larger LDLs. Conclusions: Elevated measured and calculated LDLapoB/LDLC ratios are associated with increased cardiovascular mortality. Use of LDLapoB/LDLC ratios allows estimation of the atherogenic risk conferred by small, dense LDLs.
背景与目的
小而密的低密度脂蛋白（LDL）被认为比正常大小的LDL更具致动脉粥样硬化性。然而，测量小而密的LDL需要复杂的实验室方法，如超速离心、梯度凝胶电泳或核磁共振。我们旨在分析LDL载脂蛋白B（LDLapoB）与LDL胆固醇（LDLC）的比值是否与心血管死亡率相关，以及该比值是否代表小而密LDL的生物标志物。方法：对LURIC研究的3291名参与者测量（β定量法）并计算（分别根据Friedewald法和Baca法）LDLC和LDLapoB，心血管死亡率的中位（四分位间距）随访时间为9.9（8.7 - 10.7）年。一个独立的重复队列包括1660名参与者。对282名参与者测试LDLapoB/LDLC比值与LDL亚类颗粒浓度（超速离心法）之间的关联。结果：在LURIC研究中，LDLC和LDLapoB的平均（标准差）浓度分别为117（34）和85（22）mg/dL；发生了621例心血管死亡。LDLapoB/LDLC（计算值和测量值）比值升高与整个队列（第四四分位数与第一四分位数相比：风险比（95%置信区间）= 2.07（1.53 - 2.79））以及未服用他汀类药物的患者心血管死亡率增加显著且独立相关。计算得到的LDLapoB/LDLC比值与心血管死亡率之间的关联在一个独立队列中得到重复。高LDLapoB/LDLC比值与较高的LDL5和LDL6浓度相关（均p < 0.001），但与较大LDL的浓度无关。结论：测量值和计算值升高的LDLapoB/LDLC比值与心血管死亡率增加相关。使用LDLapoB/LDLC比值可估计小而密LDL所带来的致动脉粥样硬化风险。
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