Paultre F, Pearson T A, Weil H F, Tuck C H, Myerson M, Rubin J, Francis C K, Marx H F, Philbin E F, Reed R G, Berglund L
Department of Medicine, Columbia University, New York, NY 10032, USA.
Arterioscler Thromb Vasc Biol. 2000 Dec;20(12):2619-24. doi: 10.1161/01.atv.20.12.2619.
Elevated levels of lipoprotein(a) [Lp(a)] and the presence of small isoforms of apolipoprotein(a) [apo(a)] have been associated with coronary artery disease (CAD) in whites but not in African Americans. Because of marked race/ethnicity differences in the distribution of Lp(a) levels across apo(a) sizes, we tested the hypothesis that apo(a) isoform size determines the association between Lp(a) and CAD. We related Lp(a) levels, apo(a) isoforms, and the levels of Lp(a) associated with different apo(a) isoforms to the presence of CAD (>/=50% stenosis) in 576 white and African American men and women. Only in white men were Lp(a) levels significantly higher among patients with CAD than in those without CAD (28.4 versus 16.5 mg/dL, respectively; P:=0.004), and only in this group was the presence of small apo(a) isoforms (<22 kringle 4 repeats) associated with CAD (P:=0.043). Elevated Lp(a) levels (>/=30 mg/dL) were found in 26% of whites and 68% of African Americans, and of those, 80% of whites but only 26% of African Americans had a small apo(a) isoform. Elevated Lp(a) levels with small apo(a) isoforms were significantly associated with CAD (P:<0.01) in African American and white men but not in women. This association remained significant after adjusting for age, diabetes mellitus, smoking, hypertension, HDL cholesterol, LDL cholesterol, and triglycerides. We conclude that elevated levels of Lp(a) with small apo(a) isoforms independently predict risk for CAD in African American and white men. Our study, by determining the predictive power of Lp(a) levels combined with apo(a) isoform size, provides an explanation for the apparent lack of association of either measure alone with CAD in African Americans. Furthermore, our results suggest that small apo(a) size confers atherogenicity to Lp(a).
脂蛋白(a)[Lp(a)]水平升高以及载脂蛋白(a)[apo(a)]小异构体的存在与白人的冠状动脉疾病(CAD)相关，但与非裔美国人无关。由于Lp(a)水平在apo(a)大小分布上存在明显的种族/民族差异，我们检验了apo(a)异构体大小决定Lp(a)与CAD之间关联的假设。我们将576名白人和非裔美国男性及女性的Lp(a)水平、apo(a)异构体以及与不同apo(a)异构体相关的Lp(a)水平与CAD(狭窄≥50%)的存在情况进行关联分析。仅在白人男性中，CAD患者的Lp(a)水平显著高于无CAD者(分别为28.4mg/dL和16.5mg/dL；P = 0.004)，且仅在该组中，小apo(a)异构体(<22个kringle 4重复序列)的存在与CAD相关(P = 0.043)。26%的白人及68%的非裔美国人Lp(a)水平升高(≥30mg/dL)，其中，80%的白人有小apo(a)异构体，而只有26%的非裔美国人有小apo(a)异构体。Lp(a)水平升高且伴有小apo(a)异构体在非裔美国人和白人男性中与CAD显著相关(P<0.01)，但在女性中并非如此。在调整年龄、糖尿病、吸烟、高血压、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇和甘油三酯后，这种关联仍然显著。我们得出结论，Lp(a)水平升高且伴有小apo(a)异构体可独立预测非裔美国人和白人男性患CAD的风险。我们的研究通过确定Lp(a)水平与apo(a)异构体大小相结合的预测能力，解释了非裔美国人中单独一项指标与CAD明显缺乏关联的现象。此外，我们的结果表明，小apo(a)大小赋予Lp(a)致动脉粥样硬化性。
