Nishikura Tenjin, Koba Shinji, Yokota Yuya, Hirano Tsutomu, Tsunoda Fumiyoshi, Shoji Makoto, Hamazaki Yuji, Suzuki Hiroshi, Itoh Yasuki, Katagiri Takashi, Kobayashi Youichi
The Department of Medicine, Division of Cardiology, Showa University School of Medicine.
J Atheroscler Thromb. 2014;21(8):755-67. doi: 10.5551/jat.23465. Epub 2014 Apr 8.
The aim of the present study was to investigate how small dense low-density lipoprotein cholesterol (sdLDL-C) compared with LDL-C affect the long-term prognosis in patients with stable coronary artery disease (CAD).
sdLDL-C measured by heparin magnesium precipitation and LDL particle size measured by non-denatured gradient-gel electrophoresis were compared in 190 consecutive CAD patients who underwent coronary arteriography between 2003 and 2004 who did or did not develop cardiovascular events during a seven-year follow-up period. Cardiovascular events were death caused by cardiovascular diseases(CVDs), onset of acute coronary syndrome, need for coronary and peripheral arterial revascularization, hospitalization for heart failure, surgical procedure for any CVDs, and/or hospitalization for stroke.
First-time cardiovascular events were observed in 72 patients. Those who experienced cardiovascular events were older and had higher prevalence rates of hypertension and diabetes; significantly higher Gensini coronary atherosclerotic scores; significantly higher levels of sdLDL-C, sdLDL-C/LDL-C, and LDL-C/high-density lipoprotein cholesterol (HDL-C) ratios; and greater glycated hemoglobin(Hb)A1c and brain natriuretic peptide (BNP) levels. They also had significantly smaller LDL particle sizes, HDL-C, apolipoprotein A-1, and estimated glomerular filtration rate (GFR) compared with patients without cardiovascular events. Conversely, LDL-C, non-HDL-C, apolipoprotein B, remnantlike particle cholesterol, and high-sensitivity C-reactive protein (hs-CRP) levels were similar between the two groups. A Kaplan-Meyer event-free survival curve demonstrated that patients with sdLDL-C≥35 mg/dL (median level) had significantly poorer prognosis compared with those with lower sdLDL-C levels, while patients with LDL-C ≥100 mg/dL had a non-significantly lower survival rate.
These results confirm that sdLDL-C is a very promising biomarker to predict future cardiovascular events in the secondary prevention of stable CAD.
本研究旨在探讨与低密度脂蛋白胆固醇（LDL-C）相比，小而密低密度脂蛋白胆固醇（sdLDL-C）如何影响稳定型冠状动脉疾病（CAD）患者的长期预后。
对2003年至2004年间接受冠状动脉造影的190例连续性CAD患者进行研究，采用肝素镁沉淀法测定sdLDL-C，非变性梯度凝胶电泳法测定LDL颗粒大小，观察这些患者在7年随访期内是否发生心血管事件。心血管事件包括心血管疾病（CVD）导致的死亡、急性冠状动脉综合征的发作、冠状动脉和外周动脉血运重建的需求、因心力衰竭住院、任何CVD的外科手术和/或因中风住院。
72例患者发生首次心血管事件。发生心血管事件的患者年龄更大，高血压和糖尿病患病率更高；Gensini冠状动脉粥样硬化评分显著更高；sdLDL-C、sdLDL-C/LDL-C和LDL-C/高密度脂蛋白胆固醇（HDL-C）比值显著更高；糖化血红蛋白（Hb）A1c和脑钠肽（BNP）水平更高。与未发生心血管事件的患者相比，他们的LDL颗粒大小、HDL-C、载脂蛋白A-1和估计肾小球滤过率（GFR）也显著更小。相反，两组之间的LDL-C、非HDL-C、载脂蛋白B、残粒样颗粒胆固醇和高敏C反应蛋白（hs-CRP）水平相似。Kaplan-Meier无事件生存曲线表明，sdLDL-C≥35 mg/dL（中位数水平）的患者与sdLDL-C水平较低的患者相比，预后显著更差，而LDL-C≥100 mg/dL的患者生存率略低但无统计学意义。
这些结果证实，sdLDL-C是预测稳定型CAD二级预防中未来心血管事件的一个非常有前景的生物标志物。
