Departamento de Endocrinología, Instituto Nacional de Cardiología Ignacio Chávez, Mexico City, Mexico.
Am J Cardiol. 2012 Mar 1;109(5):636-41. doi: 10.1016/j.amjcard.2011.10.017. Epub 2011 Dec 9.
In 69 statin-treated male coronary patients with low-density lipoprotein cholesterol at goal levels (<70 mg/dl), the investigators tested whether low high-density lipoprotein (HDL) cholesterol (<40 mg/dl) and high triglyceride (>150 mg/dl) are associated with dysfunctional HDL particles and abnormal insulin, adiponectin, C-reactive protein serum levels. Thirty-four patients with low HDL cholesterol and high triglyceride (dyslipidemia) and 35 patients with low-density lipoprotein cholesterol, HDL cholesterol, and triglyceride at target levels (normolipidemia) were studied. Twenty healthy men were also studied. High-sensitivity C-reactive protein was measured using immunonephelometry, insulin using a radioimmunometric assay, and total adiponectin by enzyme-linked immunosorbent assay. Cell cholesterol efflux to serum and total isolated HDL was assayed using rat hepatoma Fu5AH cells for scavenger receptor class B type 1-mediated efflux. Compared to the normolipidemia and healthy groups, and after adjustment for age and waist circumference, patients with dyslipidemia showed higher fasting insulin (14, 9.9, and 8.5 μU/ml, respectively), homeostasis model assessment of insulin resistance values (3.4, 2.3, and 1.8, respectively), lower adiponectin concentrations (5.1, 8.1, and 11 μg/ml, respectively), and reduced cholesterol efflux to serum (14%, 15%, and 19%, respectively) and to HDL fractions (4.4%, 4.6%, and 5.6%, respectively) (p <0.05 for all variables). Multivariate analysis showed that adiponectin and apolipoprotein A1 accounted for 10.7% and 3.9%, respectively, of the variance in cholesterol efflux. In conclusion, the decreased cholesterol efflux and metabolic abnormalities found in the dyslipidemia group may contribute to the residual risk observed in the large statin trials and the higher morbidity and mortality in statin-treated coronary patients with low HDL cholesterol even when attaining low-density lipoprotein cholesterol <70 mg/dl.
在 69 名接受他汀类药物治疗的男性冠心病患者中，他们的低密度脂蛋白胆固醇水平达到目标值（<70mg/dl），研究人员检测了低高密度脂蛋白（HDL）胆固醇（<40mg/dl）和高甘油三酯（>150mg/dl）是否与功能失调的 HDL 颗粒和异常胰岛素、脂联素、C 反应蛋白血清水平有关。研究了 34 名低 HDL 胆固醇和高甘油三酯（血脂异常）的患者和 35 名 LDL 胆固醇、HDL 胆固醇和甘油三酯达到目标值（正常血脂）的患者。还研究了 20 名健康男性。采用免疫比浊法测定高敏 C 反应蛋白，放射免疫法测定胰岛素，酶联免疫吸附法测定总脂联素。用大鼠肝癌 Fu5AH 细胞检测细胞胆固醇向血清和总分离 HDL 的流出情况，用于清道夫受体 B 型 1 介导的流出。与正常血脂组和健康组相比，调整年龄和腰围后，血脂异常组的空腹胰岛素水平较高（分别为 14、9.9 和 8.5μU/ml），胰岛素抵抗稳态模型评估值较高（分别为 3.4、2.3 和 1.8），脂联素浓度较低（分别为 5.1、8.1 和 11μg/ml），血清胆固醇流出率降低（分别为 14%、15%和 19%）和 HDL 分数（分别为 4.4%、4.6%和 5.6%）（所有变量的 p 值均<0.05）。多变量分析显示，脂联素和载脂蛋白 A1 分别占胆固醇流出率变异的 10.7%和 3.9%。结论：在血脂异常组中发现的胆固醇流出减少和代谢异常可能导致大剂量他汀类药物试验中观察到的残余风险，并导致即使 LDL 胆固醇<70mg/dl 时，他汀类药物治疗的低 HDL 胆固醇冠心病患者的发病率和死亡率更高。
