Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom.
PLoS One. 2020 Nov 9;15(11):e0241993. doi: 10.1371/journal.pone.0241993. eCollection 2020.
The aim of this study was to systematically collate and appraise the available evidence regarding the associations between small, dense low-density lipoprotein (sdLDL) and incident coronary heart disease (CHD), focusing on cholesterol concentration (sdLDL-C) and sdLDL particle characteristics (presence, density, and size).
Coronary heart disease (CHD) is the leading cause of death worldwide. Small, dense low-density lipoprotein (sdLDL) has been hypothesized to induce atherosclerosis and subsequent coronary heart disease (CHD). However, the etiological relevance of lipoprotein particle size (sdLDL) versus cholesterol content (sdLDL-C) remains unclear.
PubMed, MEDLINE, Web of Science, and EMBASE were systematically searched for studies published before February 2020. CHD associations were based on quartile comparisons in eight studies of sdLDL-C and were based on binary categorization in fourteen studies of sdLDL particle size. Reported hazards ratios (HR) and odds ratios (OR) with 95% confidence interval (CI) were standardized and pooled using a random-effects meta-analysis model.
Data were collated from 21 studies with a total of 30,628 subjects and 5,693 incident CHD events. The average age was 67 years, and 53% were men. Higher sdLDL and sdLDL-C levels were both significantly associated with higher risk of CHD. The pooled estimate for the high vs. low categorization of sdLDL was 1.36 (95% CI: 1.21, 1.52) and 1.07 (95% CI: 1.01, 1.12) for comparing the top quartiles versus the bottom of sdLDL-C. Several studies suggested a dose response relationship.
The findings show a positive association between sdLDL or sdLDL-C levels and CHD, which is supported by an increasing body of genetic evidence in favor of its causality as an etiological risk factor. Thus, the results support sdLDL and sdLDL-C as a risk marker, but further research is required to establish sdLDL or sdLDL-C as a potential therapeutic marker for incident CHD risk reduction.
本研究旨在系统地整理和评估有关小而密低密度脂蛋白（sdLDL）与新发冠心病（CHD）之间关联的现有证据，重点关注胆固醇浓度（sdLDL-C）和 sdLDL 颗粒特征（存在、密度和大小）。
冠心病（CHD）是全球范围内导致死亡的主要原因。小而密低密度脂蛋白（sdLDL）被假设为诱导动脉粥样硬化和随后的冠心病（CHD）。然而，脂蛋白颗粒大小（sdLDL）与胆固醇含量（sdLDL-C）的病因学相关性尚不清楚。
系统检索了 2020 年 2 月之前发表的 PubMed、MEDLINE、Web of Science 和 EMBASE 中的研究。CHD 相关性基于 8 项 sdLDL-C 四分位比较研究，基于 14 项 sdLDL 颗粒大小的二分分类研究。使用随机效应荟萃分析模型对报告的风险比（HR）和优势比（OR）及其 95%置信区间（CI）进行标准化和汇总。
共纳入了 21 项研究，共计 30628 名受试者和 5693 例新发 CHD 事件。平均年龄为 67 岁，53%为男性。较高的 sdLDL 和 sdLDL-C 水平均与 CHD 风险增加显著相关。sdLDL 高 vs. 低分类的合并估计值为 1.36（95%CI：1.21，1.52），sdLDL-C 最高四分位数与最低四分位数相比为 1.07（95%CI：1.01，1.12）。一些研究表明存在剂量反应关系。
研究结果表明，sdLDL 或 sdLDL-C 水平与 CHD 之间存在正相关，这得到了越来越多的遗传证据的支持，这些证据支持其作为病因风险因素的因果关系。因此，结果支持 sdLDL 和 sdLDL-C 作为风险标志物，但需要进一步研究以确定 sdLDL 或 sdLDL-C 是否可作为降低新发 CHD 风险的潜在治疗标志物。
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