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

心脏病是美国妇女死亡的主要原因。脂蛋白[a]（Lp[a]）已被确定为血浆浓度大于30 mg/dl时冠心病的独立危险因素，在绝经后女性中随年龄增加而增加，且绝经后女性通常高于年龄匹配的绝经前女性。 激素替代疗法可降低绝经后妇女的Lp[a]浓度，一些证据表明，雌激素降低Lp[a]的作用在初始Lp[a]浓度较高的受试者中更大。 与白色女性相比，黑人女性的Lp[a]浓度高3倍，绝经后西班牙裔女性的Lp[a]浓度比绝经后白色女性低1/3。 此外，激素替代疗法降低Lp[a]在黑人女性中的作用大于白色女性。因此，应该可以区分黑人和白色女性之间、黑人和西班牙裔女性之间以及白色和西班牙裔女性之间的Lp[a]代谢差异。本研究旨在确定雌激素诱导的绝经后女性Lp[a]浓度降低是否是由于apo[a]或apoB 100合成速率改变所致，并确定雌激素降低Lp[a]的疗效是否取决于受试者的种族。 将相同数量的黑人、白色和西班牙裔脂血正常且Lp[a]浓度大于30 mg/dl的绝经后女性随机分配至两个治疗序列之一，这两种疗法都将包括两个交替的3个月的活性和安慰剂激素替代疗法（1.25 mg/天的结合雌激素和10 mg/天的醋酸甲羟孕酮，持续10天/月），间隔3个月的洗脱期。 将通过高分辨率琼脂糖电泳测定Apo[a]表型。 将通过ELISA法测量Lp[a]浓度。 将通过质谱定量测定Lp[a]中apo[a]和Lp[a]、低密度脂蛋白、中密度脂蛋白和极低密度脂蛋白中apoB 100的体内合成速率计算这些蛋白质的[2 H4]-赖氨酸富集速率;将在激素替代治疗前后进行测量。

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.