Wild S H, Fortmann S P, Marcovina S M
Center for Research in Disease Prevention, Stanford University School of Medicine, Calif., USA.
Arterioscler Thromb Vasc Biol. 1997 Feb;17(2):239-45. doi: 10.1161/01.atv.17.2.239.
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.
脂蛋白(a)[Lp(a)]由低密度脂蛋白颗粒与富含碳水化合物的载脂蛋白(a)[apo(a)]组装而成，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的结果相互矛盾。我们利用斯坦福五城市项目（一项长期的CVD预防试验）的参与者进行了一项巢式病例对照研究。将发生可能或确诊心肌梗死或冠状动脉死亡的参与者与一名对照对象按年龄、性别、种族、在治疗或对照城市的居住情况以及调查时间进行匹配。这一过程产生了134对病例对照，其中男性90对，女性44对，可获得其血浆用于Lp(a)分析。通过一种独立于apo(a)大小多态性来测量Lp(a)的酶联免疫测定法测定每升纳摩尔的Lp(a)值。通过SDS-琼脂糖凝胶电泳测定apo(a)大小异构体。男性病例的Lp(a)中位数水平几乎是对照对象的两倍(41.8对21.2 nmol/L；P<0.01)；在女性病例中，Lp(a)中位数比对照对象高34%(32.5对21.2 nmol/L)，但这一差异无统计学意义。在男性病例中，小apo(a)异构体的频率增加，而女性病例与对照对象之间的apo(a)大小未发现显著差异。男性中Lp(a)水平与病例对照状态之间的关联独立于总胆固醇、高密度脂蛋白胆固醇和非高密度脂蛋白胆固醇水平，以及apo(a)大小异构体、吸烟、血压和肥胖。在男性中，区分病例与对照对象的Lp(a)浓度的最有效阈值为35 nmol/L；高于此水平作为病例的比值比与低于此水平相比为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)水平是男性发生冠状动脉疾病的一个前瞻性独立危险因素，并表明apo(a)的大小可能也起作用。女性中缺乏显著关联值得在更大规模的研究中进一步评估。
