A prospective case-control study of lipoprotein(a) levels and apo(a) size and risk of coronary heart disease in Stanford Five-City Project participants.
A prospective case-control study of lipoprotein(a) levels and apo(a) size and risk of coronary heart disease in Stanford Five-City Project participants.
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一项针对斯坦福五城项目参与者的脂蛋白（a）水平和载脂蛋白（a）大小以及冠心病风险的前瞻性病例对照研究。
DOI：
10.1161/01.atv.17.2.239
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Marcovina,SM
中科院分区：
文献类型：
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作者：
Wild,SH;Fortmann,SP;Marcovina,SM
脂蛋白（a）[Lp（a）]是由LDL颗粒和富含碳水化合物的蛋白质载脂蛋白（a）[apo（a）]组装而成，载脂蛋白（a）[apo（a）]与纤溶酶原具有高度的结构同源性。虽然大多数回顾性研究发现Lp（a）水平与心血管疾病（CVD）之间存在关联，但迄今为止，少数前瞻性研究报告了相互矛盾的结果。我们使用斯坦福大学五城市项目（一项长期CVD预防试验）的参与者进行了一项巢式病例对照研究。将可能或明确发生心肌梗死或冠心病死亡的参与者与一名对照受试者在年龄、性别、种族、治疗或对照城市的居住地和调查时间方面进行匹配。这一过程产生了134个病例对照对，90名男性和44名女性，他们的血浆可用于Lp（a）分析。通过酶联免疫测定法测定Lp（a）值（以纳摩尔/升计），该测定法独立于载脂蛋白（a）大小多态性。通过SDS-琼脂糖凝胶电泳测定载脂蛋白（a）大小亚型。男性病例的Lp（a）中位水平几乎是对照组的两倍（41.8与21.2 nmol/L;P<0.01）;女性病例的Lp（a）中位水平比对照组高34%（32.5与21.2 nmol/L），但这种差异无统计学意义。在男性病例中，小apo（a）亚型的频率增加，而女性病例和对照组之间的apo（a）大小无显著差异。男性Lp（a）水平与病例对照状态之间的相关性与总胆固醇、HDL和非HDL胆固醇水平以及载脂蛋白（a）大小亚型、吸烟、血压和肥胖无关。在男性中，区分病例和对照组的最有效的Lp（a）浓度阈值为35 nmol/L;高于此水平的病例与低于此水平的病例相比的优势比为2.84（95%置信区间：1.53- 5.27，P <0.001）。这项研究提供了强有力的证据表明，Lp（a）水平是一个前瞻性的，独立的危险因素，为发展冠状动脉疾病的男性，并表明载脂蛋白（a）的大小也可能发挥作用。在女性中缺乏显著的相关性，值得在更大的研究中进一步评估。
Lipoprotein(a) [Lp(a)] is formed by the assembly of LDL particles and a carbohydrate-rich protein, apolipoprotein(a) [apo(a)], which has a high degree of structural homology with plasminogen. While the majority of retrospective studies have found an association between Lp(a) level and cardiovascular disease (CVD), the few prospective studies to date have reported contradictory results. We conducted a nested case-control study using the participants in the Stanford Five-City Project, a long-term CVD prevention trial. Participants with an incident possible or definite myocardial infarction or coronary death were matched to a single control subject for age, sex, ethnicity, residence in a treatment or control city, and time of survey. This process yielded 134 case-control pairs, 90 male and 44 female, for whom plasma was available for analysis of Lp(a). Lp(a) values in nanomoles per liter were determined by an enzyme-linked immunoassay that measures Lp(a) independently of apo(a) size polymorphism. Apo(a) size isoforms were determined by SDS–agarose gel electrophoresis. Median Lp(a) level in male cases was almost double that in control subjects (41.8 versus 21.2 nmol/L;P<.01); in female cases, median Lp(a) was 34% higher than in control subjects (32.5 versus 21.2 nmol/L), but this difference was not statistically significant. Among the male cases, there was an increased frequency of small apo(a) isoforms, while no significant difference was found in apo(a) size between female cases and control subjects. The association between Lp(a) level and case-control status in men was independent of total, HDL, and non-HDL cholesterol levels, as well as apo(a) size isoform, cigarette smoking, blood pressure, and obesity. In men, the most efficient threshold value of Lp(a) concentration for separating cases and control subjects was 35 nmol/L; the odds ratio for being a case above this level compared with below was 2.84 (95% confidence interval: 1.53-5.27,P<.001). This study provides strong evidence that Lp(a) level is a prospective, independent risk factor for developing coronary artery disease in men and indicates that the size of apo(a) may also play a role. The lack of a significant association in women deserves further evaluation in larger studies.