Small Dense Low-Density Lipoprotein Cholesterol Is the Most Atherogenic Lipoprotein Parameter in the Prospective Framingham Offspring Study.
Small Dense Low-Density Lipoprotein Cholesterol Is the Most Atherogenic Lipoprotein Parameter in the Prospective Framingham Offspring Study.
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DOI：
10.1161/jaha.120.019140
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发表时间：
2021-03
影响因子：
5.4
通讯作者：
Schaefer EJ
中科院分区：
文献类型：
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作者：
Ikezaki H;Lim E;Cupples LA;Liu CT;Asztalos BF;Schaefer EJ
直接低密度脂蛋白胆固醇（LDL-C）、小密度LDL-C（sdLDL-C）、低密度脂蛋白（LDL）甘油三酯、甘油三酯、富甘油三酯脂蛋白胆固醇、残余脂蛋白颗粒胆固醇和脂蛋白（a）的血浆水平升高均与动脉粥样硬化性心血管疾病（ASCVD）事件相关。我们的目标是评估哪些参数与ASCVD风险最密切相关。使用标准化自动分析（变异系数<5.0%）测量3094例无ASCVD的空腹受试者的血浆总胆固醇、甘油三酯、高密度脂蛋白胆固醇、直接LDL-C、sdLDL-C、LDL甘油三酯、残余脂蛋白颗粒胆固醇、富含甘油三酯的脂蛋白胆固醇和脂蛋白（a）。在这些受试者中，20.2%在16年内发生ASCVD。在单变量分析中，所有ASCVD风险因素与ASCVD事件以及以下特定脂蛋白参数显著相关：sdLDL‐C、LDL甘油三酯、甘油三酯、富含甘油三酯的脂蛋白胆固醇、残余脂蛋白颗粒胆固醇和直接LDL‐C。在多变量分析和校正标准风险因素（年龄、性别、高血压、糖尿病、吸烟、总胆固醇和高密度脂蛋白胆固醇）后的净重新分类中，只有sdLDL-C、直接LDL-C和脂蛋白（a）具有显著性。使用合并队列方程，许多专门的脂蛋白参数单独增加了重要信息，但一旦sdLDL‐C（风险比，1.42; P<0.0001）进入模型，则没有参数增加重要信息。与LDL甘油三酯相比，sdLDL-C的这些结果通过校正的不一致性分析与计算的非高密度脂蛋白胆固醇得到证实。在多变量分析中，sdLDL-C、直接LDL-C和脂蛋白（a）均对ASCVD风险有显著贡献，但一旦模型中包含sdLDL-C，则没有参数向汇总队列方程添加显著风险信息。我们的数据表明，小而密LDL是最易致动脉粥样硬化的脂蛋白参数。
Elevated plasma levels of direct low‐density lipoprotein cholesterol (LDL‐C), small dense LDL‐C (sdLDL‐C), low‐density lipoprotein (LDL) triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and lipoprotein(a) have all been associated with incident atherosclerotic cardiovascular disease (ASCVD). Our goal was to assess which parameters were most strongly associated with ASCVD risk. Plasma total cholesterol, triglycerides, high‐density lipoprotein cholesterol, direct LDL‐C, sdLDL‐C, LDL triglycerides, remnant lipoprotein particle cholesterol, triglyceride‐rich lipoprotein cholesterol, and lipoprotein(a) were measured using standardized automated analysis (coefficients of variation, <5.0%) in samples from 3094 fasting subjects free of ASCVD. Of these subjects, 20.2% developed ASCVD over 16 years. On univariate analysis, all ASCVD risk factors were significantly associated with incident ASCVD, as well as the following specialized lipoprotein parameters: sdLDL‐C, LDL triglycerides, triglycerides, triglyceride‐rich lipoprotein cholesterol, remnant lipoprotein particle cholesterol, and direct LDL‐C. Only sdLDL‐C, direct LDL‐C, and lipoprotein(a) were significant on multivariate analysis and net reclassification after adjustment for standard risk factors (age, sex, hypertension, diabetes mellitus, smoking, total cholesterol, and high‐density lipoprotein cholesterol). Using the pooled cohort equation, many specialized lipoprotein parameters individually added significant information, but no parameter added significant information once sdLDL‐C (hazard ratio, 1.42; P<0.0001) was in the model. These results for sdLDL‐C were confirmed by adjusted discordance analysis versus calculated non–high‐density lipoprotein cholesterol, in contrast to LDL triglycerides. sdLDL‐C, direct LDL‐C, and lipoprotein(a) all contributed significantly to ASCVD risk on multivariate analysis, but no parameter added significant risk information to the pooled cohort equation once sdLDL‐C was in the model. Our data indicate that small dense LDL is the most atherogenic lipoprotein parameter.