STABLE ISOTOPE STUDIES OF SYNTHESIS OF HUMAN LIPOPROTEIN[A] & OTHER P

心脏病是美国女性的主要死因。脂蛋白[a](Lp[a])已被确定为血浆浓度高于30 mg/dl的冠心病的独立危险因素，在绝经后妇女中随年龄增加而增加，绝经后妇女通常高于年龄匹配的绝经前妇女。激素替代治疗降低了绝经后妇女的Lp[a]浓度，一些证据表明，雌激素的降低Lp[a]的效果在初始Lp[a]浓度较高的受试者中更大。与白人女性相比，黑人女性的Lp[a]浓度高出三倍，而绝经后的西班牙裔女性的Lp[a]浓度比绝经后的白人女性低三分之一。此外，用激素替代疗法降低Lp[a]的黑人女性比白人女性更严重。因此，应该有可能区分黑人和白人女性之间、黑人和西班牙裔女性之间以及白人和西班牙裔女性之间的Lp[a]新陈代谢差异。这项研究旨在确定绝经后妇女中雌激素诱导的Lp[a]浓度降低是否是由于apo[a]或apoB100合成速率的改变，并确定雌激素降低Lp[a]的效果是否取决于受试者的种族。Lp[a]浓度大于30 mg/dl的同等数量的黑人、白人和西班牙裔正常血脂绝经后妇女将被随机分成两个治疗序列中的一个，这两个治疗序列都将包括两个交替的3个月的活跃和安慰剂激素替代疗法(每天1.25毫克的结合雌激素和10天/月的醋酸甲羟孕酮)，由3个月的冲洗期分开。载脂蛋白[a]表型将通过高分辨率琼脂糖凝胶电泳法确定。Lp[a]浓度将用ELISA法测定。Lp[a]中apo[a]和Lp[a]中apoB100、低密度脂蛋白、中密度脂蛋白和极低密度脂蛋白的体内合成速率将通过对这些蛋白质的[2H4]-赖氨酸富集率的质量谱定量来计算；测量将在激素替代治疗前后进行。

Heart disease is the leading cause of death in American women. Lipoprotein[a] (Lp[a]), which has been established as an independent risk factor for coronary heart disease at plasma concentrations greater than 30 mg/dl, increases with age in postmenopausal women and is generally higher in postmenopausal women than in age-matched premenopausal women. Hormone replacement therapy decreases Lp[a] concentration in postmenopausal women, and some evidence suggests that the Lp[a]-lowering effect of estrogen is greater in subjects with higher initial Lp[a] concentrations. Compared with white women, black women have three times higher Lp[a] concentrations, and postmenopausal Hispanic women have one third lower Lp[a] concentrations than postmenopausal white women. In addition, Lp[a] lowering with hormone replacement therapy is greater in black women than in white women. Therefore, it should be possible to distinguish differences in Lp[a] metabolism between black and white women, between black and Hispanic women, and possibly between white and Hispanic women. This study is designed to determine if estrogen-induced lowering of Lp[a] concentrations in postmenopausal women is due to altered rates of apo[a] or apoB100 synthesis and to determine if the efficacy of Lp[a] lowering by estrogen depends on the ethnicity of the subject. Equal numbers of black, white, and Hispanic normolipidemic postmenopausal women with Lp[a] concentration greater than 30 mg/dl will be randomized to one of two treatment sequences, both of which will include two alternating 3-month periods of active and placebo hormone replacement therapy (1.25 mg/day of conjugated estrogen and 10 mg/day for 10 days/month of medroxyprogesterone acetate) separated by a 3-month washout period. Apo[a] phenotypes will be determined by high-resolution agarose electrophoresis. Lp[a] concentrations will be measured by ELISA. The rates of synthesis in vivo of apo[a] in Lp[a] and of apoB100 in Lp[a], low-density lipoprotein, intermediate-density lipoprotein, and very-low-density lipoprotein will be computed from mass spectrometric quantification of [2H4]-lysine enrichment rates for these proteins; measurements will be performed before and after hormone replace- ment therapy.