LIFE -Leipzig Research Center for Civilization Diseases, Leipzig University, Philipp-Rosenthal-Strasse 27, 04103 Leipzig, Germany; Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Strasse 13-15, 04103 Leipzig, Germany.
LIFE -Leipzig Research Center for Civilization Diseases, Leipzig University, Philipp-Rosenthal-Strasse 27, 04103 Leipzig, Germany; Institute of Laboratory Medicine, Clinical Chemistry and Molecular Diagnostics, University Hospital Leipzig, Paul-List-Strasse 13-15, 04103 Leipzig, Germany; Department of Internal Medicine / Cardiology, University of Leipzig Heart Center, Struempellstrasse 39, 04289 Leipzig, Germany.
Atherosclerosis. 2019 Feb;281:17-24. doi: 10.1016/j.atherosclerosis.2018.11.006. Epub 2018 Nov 9.
BACKGROUND AND AIMS: Dyslipidemia is a major risk factor for atherosclerotic cardiovascular disease (ASCVD). As key regulators of lipoprotein metabolism, apolipoproteins (apos) are discussed as vascular risk factors. This study aimed to analyze associations of major plasma apos with coronary artery disease (CAD), peripheral artery disease (PAD) and carotid artery plaque (CAP) to elucidate their diagnostic potential in risk assessment. METHODS: ApoA-I, apoA-II, apoA-IV, apoB-100, apoC-I, apoC-III, apoE, and apoJ were simultaneously quantified in 3 μL EDTA-plasma by LC-MS/MS in a case-control subgroup of the Leipziger LIFE-Heart Study (N = 911). Confounder analysis with demographic, clinical covariates and serum lipids, cardiac, inflammatory, and hepatic markers were performed. Apos were associated with CAD, CAP, and PAD in a multivariate regression model. RESULTS: Fasting and statin therapy showed strongest effects on apo concentrations. Inverse correlations of HDL-related apos A-I, A-II, A-IV, and C-I were observed for troponin T and interleukin 6. Concentrations of apos A-II, B-100, C-I, and E were decreased under statin therapy. After adjustment for influencing factors and related lipids, only apoB-100 (odds ratio per one SD [OR], 1.39; 95% confidence interval [CI], 1.05-1.84) was independently associated with CAD while apoA-IV (OR, 0.74; 95% CI 0.58-0.95) indicated PAD. ApoB-100 (OR, 1.55; 95% CI, 1.18-2.04), apoC-III (OR, 1.30; 95% CI, 1.06-1.58), and apoE (OR, 1.34; 95% CI, 1.13-1.58) were associated with CAP. CONCLUSIONS: Triglyceride rich lipoproteins (TRLs) associated apos A-IV, B-100, C-III, and E are independently associated with stable ASCVD, providing further evidence for a potential role of TRLs in atherogenesis.
背景与目的：血脂异常是动脉粥样硬化性心血管疾病（ASCVD）的主要危险因素。载脂蛋白（apos）作为脂蛋白代谢的关键调节剂，被认为是血管危险因素。本研究旨在分析主要血浆 apos 与冠心病（CAD）、外周动脉疾病（PAD）和颈动脉斑块（CAP）的相关性，以阐明其在风险评估中的诊断潜力。
方法：采用 LC-MS/MS 法同时检测莱比锡生命心脏研究（Leipziger LIFE-Heart Study）病例对照亚组 3µL EDTA 血浆中的载脂蛋白 A-I、A-II、A-IV、B-100、C-I、C-III、E 和 apoJ。采用多元回归模型对人口统计学、临床协变量和血清脂质、心脏、炎症和肝脏标志物进行混杂因素分析。
结果：禁食和他汀类药物治疗对 apo 浓度的影响最大。载脂蛋白 A-I、A-II、A-IV 和 C-I 与肌钙蛋白 T 和白细胞介素 6 呈负相关。他汀类药物治疗时，apoA-II、B-100、C-I 和 E 浓度降低。调整影响因素和相关脂质后，仅 apoB-100（每 SD 比值 [OR]，1.39；95%置信区间 [CI]，1.05-1.84）与 CAD 独立相关，而 apoA-IV（OR，0.74；95%CI，0.58-0.95）提示 PAD。apoB-100（OR，1.55；95%CI，1.18-2.04）、apoC-III（OR，1.30；95%CI，1.06-1.58）和 apoE（OR，1.34；95%CI，1.13-1.58）与 CAP 相关。
结论：富含甘油三酯的脂蛋白（TRLs）相关 apo A-IV、B-100、C-III 和 E 与稳定的 ASCVD 独立相关，进一步证明 TRLs 在动脉粥样形成中的潜在作用。
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