Serum modified high-density lipoprotein and risk of atherosclerotic cardiovascular disease in a Japanese community-based nested case-control study
Serum modified high-density lipoprotein and risk of atherosclerotic cardiovascular disease in a Japanese community-based nested case-control study
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日本社区巢式病例对照研究中血清修饰高密度脂蛋白与动脉粥样硬化性心血管疾病的风险
DOI：
10.1093/eurjpc/zwab142
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
Okamura T.
中科院分区：
文献类型：
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作者：
Sata M;Kakino A;Hirata A;Iida M;Usami Y;Harada S;Fujita Y;Kohsaka S;Izawa Y;Sawano M;Oki K;Sugiyama D;Takahashi S;Takebayashi T;Sawamura T;Okamura T.
高密度脂蛋白胆固醇（HDL-C）与冠心病（CHD）风险呈负相关。然而，据报道，HDL-C水平异常高的人发生动脉粥样硬化性心血管疾病（ASCVD）或相关死亡率的风险反而更高。1，2 HDL发生氧化和糖化后，失去了抗动脉粥样硬化的功能，其过量会增加发生动脉粥样硬化的风险。3修饰的HDL被怀疑通过与凝集素样氧化低密度脂蛋白（LDL）受体-1（LOX-1）结合而促进动脉粥样硬化的进展。4.建立了一种新的测定与LOX-1结合的各种修饰HDL的方法，命名为LOX-1配体含载脂蛋白AI（LAA）。4本研究的目的是在一项大规模的日本社区队列研究中研究LAA作为功能障碍性HDL的标志物对ASCVD发病率的影响。鹤冈代谢组学队列研究是一项前瞻性研究，涉及日本山形县鹤冈市11002名35- 74岁的居民。基线调查于2012年4月至2015年3月进行。我们进行了一项巢式病例对照研究，包括从基线调查到2017年12月31日发生的52例新ASCVD病例。日本东京庆应义塾大学医学院医学伦理委员会批准了本研究（批准编号20110264），所有参与者均提供了书面知情同意书。为了确定ASCVD事件（即CHD和动脉粥样硬化血栓性脑梗死）的发生率，对疑似ASCVD的参与者的病历进行了审查，并由一组经验丰富的医生（包括至少两名以上的心脏病专家和神经科医生）根据患者的症状、心电图、冠状动脉造影、计算机断层扫描和磁共振成像对首次发病进行了最终诊断。我们还对公共死亡证明进行了检索，以确定致命的ASCVD相关事件。对于每个ASCVD病例，从参与者中随机选择三名没有心血管疾病史的对照，将其与基线年份，性别，年龄（三年内）和健康检查设施相匹配。在鹤冈代谢组学队列研究的所有参与者中，本巢式病例对照研究共选择了208名参与者（52例病例和156例对照）。在Hokenkagaku West Co. Ltd.，日本京都。根据先前描述的方法，使用基于LOX-1结合的酶联免疫吸附测定，用重组LOX-1和抗apoAI抗体测量LAA。4批内和批间变异系数分别为6.9%（n= 16）和12.7%（n= 13）。根据体重指数、高血压、糖尿病、抗高胆固醇血症药物、LDL-C、HDL-C、慢性肾病、当前吸烟、当前饮酒和改良LDL校正的对数转换LAA水平的四分位数和1-标准差（SD）增量，使用条件logistic回归模型计算ASCVD发生率的比值比（OR）和95%置信区间（CI），命名为LOX-1配体，
High-density lipoprotein cholesterol (HDL-C) is inversely associated with the risk of coronary heart disease (CHD). However, persons with abnormally high HDL-C levels reportedly have a paradoxically higher risk of developing atherosclerotic cardiovascular disease (ASCVD) or related mortality. 1, 2 HDL that undergoes oxidation and glycation loses its anti-atherosclerotic function, and its excess increases the risk of developing atherosclerosis. 3 Modified HDL is suspected of contributing to the progression of atherosclerosis by binding to the lectin-like oxidized low-density lipoprotein (LDL) receptor-1 (LOX-1). 4 A novel method for measuring various types of modified HDL that bind to LOX-1, designated as LOX-1 ligand containing apoAI (LAA), was developed. 4 The present study aimed to investigate the effect of LAA as a marker of dysfunctional HDL on the incidence of ASCVD in a large-scale Japanese community-based cohort study. The Tsuruoka Metabolomics Cohort Study is a prospective study involving 11 002 dwellers aged 35–74years in Tsuruoka City, Yamagata Prefecture, Japan. The baseline survey was conducted from April 2012 until March 2015. We conducted a nested case–control study, including 52 new ASCVD cases developed from the baseline survey to 31 December 2017. The Medical Ethics of the Keio University School of Medicine, Tokyo, Japan, approved the study (approval no. 20110264), and all participants provided written informed consent. To determine the incidence of ASCVD events, ie CHD and atherothrombotic cerebral infarction, the medical records of participants, suspected to have ASCVD were reviewed, and the final diagnoses of the first incidence were made by a panel of experienced physicians including at least two more of cardiologists and neurologists based on patient’s symptoms, electrocardiogram, coronary angiography, computed tomography, and magnetic resonance imaging. We also performed a search of public death certificates to identify fatal ASCVD-related events. For each ASCVD case, three controls without a history of cardiovascular diseases were randomly selected from the participants by matching them with the baseline year, sex, age (within three years), and health check-up facility. Of all participants in Tsuruoka Metabolomics Cohort Study, a total of 208 participants (52 cases and 156 controls) were selected in the present nested case–control study. The baseline serum samples of participants had been stored at À80 C until the analysis was conducted in Hokenkagaku West Co. Ltd., Kyoto, Japan. According to the previously described method, LAA was measured using a LOX-1 binding-based enzyme-linked immunosorbent assay with recombinant LOX-1 and anti-apoAI antibodies. 4 The intra-assay and inter-assay coefficients of variance were 6.9%(n= 16) and 12.7%(n= 13), respectively. Conditional logistic regression models were used to calculate the odds ratio (OR) and 95% confidence interval (CI) of the incidence of ASCVD according to quartiles and 1-standard deviation (SD) increment of log-transformed LAA levels adjusted for body mass index, hypertension, diabetes, anti-hypercholesterolaemia medication, LDL-C, HDL-C, chronic kidney disease, current smoking, current drinking, and modified LDL, designated as LOX-1 ligand containing