Department of Nutrition, Harvard T.H. Chan School of Public Health, Boston, MA.
Division of General Medicine and Primary Care, Beth Israel Deaconess Medical Center, Boston, MA.
J Am Heart Assoc. 2018 Mar 14;7(6):e007824. doi: 10.1161/JAHA.117.007824.
Apolipoprotein C-III (apoC-III), a small proinflammatory protein present on 6% to 7% of high-density lipoprotein (HDL) particles, defines a subspecies of HDL adversely associated with coronary heart disease in primarily white cohorts. In a multi-ethnic population free of clinical cardiovascular disease, we evaluated the relationship between apoC-III-defined HDL subspecies and subclinical markers of atherosclerotic pathology.
We investigated cross-sectional associations between apolipoprotein A-I concentrations of apoC-III-defined HDL subspecies, measured via ELISA and imaging measures of subclinical atherosclerosis, among 4659 participants in the MESA (The Multi-Ethnic Study of Atherosclerosis) at baseline (2000-2002). HDL particles containing and lacking apoC-III were divergently associated with coronary artery calcification in women (-heterogeneity=0.002) but not in men (-heterogeneity=0.31) and with carotid plaque score (-heterogeneity=0.02) and intima-media thickness (-heterogeneity=0.06) in the overall study population. HDL lacking apoC-III was inversely associated with all outcome measures (coronary artery calcification, women: odds ratio per SD=0.81 [95% confidence interval [CI], 0.73-0.90]; carotid plaque, overall: odds ratio per SD=0.92 [95% CI, 0.84-1.00]; intima-media thickness, overall: mean difference per SD=-14.0 µm [95% CI, -21.1 to -6.7 μm]), whereas HDL containing apoC-III was positively associated (coronary artery calcification, women: odds ratio=1.10 [95% CI, 0.99-1.22]; plaque, overall: odds ratio=1.10 [95% CI, 1.01-1.19]) or unassociated. Neither total HDL nor HDL subspecies was associated with changes in subclinical atherosclerosis measures up to 10 years later.
The presence of apoC-III defined a subspecies of HDL not inversely associated with baseline measures of subclinical atherosclerosis, supporting a role of apoC-III in the pathophysiology of cardiovascular disease.
载脂蛋白 C-III（apoC-III）是一种存在于 6%至 7%高密度脂蛋白（HDL）颗粒上的小促炎蛋白，其定义了一种与白人队列中的冠心病不良相关的 HDL 亚类。在一个没有临床心血管疾病的多民族人群中，我们评估了 apoC-III 定义的 HDL 亚类与动脉粥样硬化病理的亚临床标志物之间的关系。
我们通过酶联免疫吸附试验（ELISA）和亚临床动脉粥样硬化的影像学测量，研究了 MESA（动脉粥样硬化的多民族研究）中 4659 名参与者的 apoC-III 定义的 HDL 亚类的载脂蛋白 A-I 浓度与亚临床动脉粥样硬化标志物之间的横断面关联。载脂蛋白 C-III 存在或不存在的 HDL 颗粒与女性的冠状动脉钙化呈相反关系（异质性=0.002），但与男性的冠状动脉钙化无明显关系（异质性=0.31），与颈动脉斑块评分（异质性=0.02）和内膜-中层厚度（异质性=0.06）在整个研究人群中呈相反关系。不含 apoC-III 的 HDL 与所有结局指标呈负相关（冠状动脉钙化，女性：每标准差的优势比=0.81 [95%置信区间（CI），0.73-0.90]；颈动脉斑块，整体：每标准差的优势比=0.92 [95% CI，0.84-1.00]；内膜-中层厚度，整体：每标准差的平均差异=-14.0 µm [95% CI，-21.1 至-6.7 µm]），而含有 apoC-III 的 HDL 则呈正相关（冠状动脉钙化，女性：优势比=1.10 [95% CI，0.99-1.22]；斑块，整体：优势比=1.10 [95% CI，1.01-1.19]）或无关联。在接下来的 10 年里，总 HDL 或 HDL 亚类都与亚临床动脉粥样硬化指标的变化无关。
apoC-III 的存在定义了一种与基线亚临床动脉粥样硬化标志物无反比关系的 HDL 亚类，支持 apoC-III 在心血管疾病的病理生理学中的作用。
