高预-β1 高密度脂蛋白浓度和低卵磷脂：胆固醇酰基转移酶活性是缺血性心脏病的强烈阳性风险标志物，且独立于高密度脂蛋白胆固醇。
High pre-beta1 HDL concentrations and low lecithin: cholesterol acyltransferase activities are strong positive risk markers for ischemic heart disease and independent of HDL-cholesterol.
机构信息
NIH, National Heart Lung and Blood Institute, Lipoprotein Metabolism Section, Bethesda, MD, USA.
出版信息
Clin Chem. 2010 Jul;56(7):1128-37. doi: 10.1373/clinchem.2009.139931. Epub 2010 May 28.
BACKGROUND
We hypothesized that patients with high HDL-cholesterol (HDL-C) and ischemic heart disease (IHD) may have dysfunctional HDL or unrecognized nonconventional risk factors.
METHODS
Individuals with IHD (Copenhagen University Hospital) and either high HDL-C (n = 53; women >or=735 mg/L; men >or=619 mg/L) or low HDL-C (n = 42; women <or=387 mg/L; men <or=341 mg/L) were compared with individuals without IHD (Copenhagen City Heart Study) matched by age, sex, and HDL-C concentrations (n = 110). All participants had concentrations within reference intervals for LDL-C (<1600 mg/L) and triglyceride (<1500 mg/L), and none were treated with lipid-lowering medications. Pre-beta(1) HDL and phospholipid transfer protein concentrations were measured by using commercial kits and lecithin:cholesterol acyltransferase (LCAT) activity by using a proteoliposome cholesterol esterification assay.
RESULTS
Pre-beta(1) HDL concentrations were 2-fold higher in individuals with IHD vs no IHD in both the high [63 (5.7) vs 35 (2.3) mg/L; P < 0.0001] and low HDL-C [49 (5.0) vs 27 (1.5) mg/L; P = 0.001] groups. Low LCAT activity was also associated with IHD in the high [95.2 (6.7) vs 123.0 (5.3) micromol x L(-1) x h(-1); P = 0.002] and low [93.4 (8.3) vs 113.5 (4.9) micromol x L(-1) . h(-1); P = 0.03] HDL-C groups. ROC curves for pre-beta(1) HDL in the high-HDL-C groups yielded an area under the curve of 0.71 (95% CI: 0.61-0.81) for predicting IHD, which increased to 0.92 (0.87-0.97) when LCAT was included. Similar results were obtained for low HDL-C groups. An inverse correlation between LCAT activity and pre-beta(1) HDL was observed (r(2) = 0.30; P < 0.0001) in IHD participants, which was stronger in the low HDL-C group (r(2) = 0.56; P < 0.0001).
CONCLUSIONS
IHD was associated with high pre-beta(1) HDL concentrations and low LCAT levels, yielding correct classification in more than 90% of the IHD cases for which both were measured, thus making pre-beta(1) HDL concentration and LCAT activity level potentially useful diagnostic markers for cardiovascular disease.
背景
我们假设 HDL 胆固醇（HDL-C）水平较高且患有缺血性心脏病（IHD）的患者可能存在功能失调的 HDL 或尚未识别的非传统危险因素。
方法
本研究比较了在哥本哈根大学医院诊断为 IHD（n = 53；女性> 735mg/L；男性> 619mg/L）或 HDL-C 水平较低（n = 42；女性< 387mg/L；男性< 341mg/L）的患者与在哥本哈根城市心脏研究中匹配年龄、性别和 HDL-C 浓度的无 IHD 患者（n = 110）。所有参与者的 LDL-C（<1600mg/L）和甘油三酯（<1500mg/L）浓度均处于参考范围内，且均未接受降脂药物治疗。采用商业试剂盒检测前-β1 高密度脂蛋白（HDL）和磷脂转移蛋白浓度，采用脂蛋白胆固醇酯化测定法检测卵磷脂：胆固醇酰基转移酶（LCAT）活性。
结果
在高 HDL-C 组 [63（5.7）mg/L 比 35（2.3）mg/L；P < 0.0001] 和低 HDL-C 组 [49（5.0）mg/L 比 27（1.5）mg/L；P = 0.001]，IHD 患者的前-β1 HDL 浓度均是无 IHD 患者的 2 倍。在高 HDL-C 组 [95.2（6.7）μmol/L·h 比 123.0（5.3）μmol/L·h；P = 0.002] 和低 HDL-C 组 [93.4（8.3）μmol/L·h 比 113.5（4.9）μmol/L·h；P = 0.03]，低 LCAT 活性与 IHD 相关。在前-β1 HDL 高 HDL-C 组中，ROC 曲线的曲线下面积为 0.71（95%CI：0.61-0.81），预测 IHD，当包括 LCAT 时，该面积增加到 0.92（0.87-0.97）。在低 HDL-C 组中也得到了相似的结果。在 IHD 患者中，LCAT 活性与前-β1 HDL 呈负相关（r²=0.30；P < 0.0001），在低 HDL-C 组中相关性更强（r²=0.56；P < 0.0001）。
结论
IHD 与较高的前-β1 HDL 浓度和较低的 LCAT 水平相关，对于同时测量这两项指标的 IHD 患者，其分类准确率超过 90%，因此前-β1 HDL 浓度和 LCAT 活性水平可能是心血管疾病有价值的诊断标志物。
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