HORMONE THERAPY EFFECTS ON CVD RISK FACTORS

摘要：心血管疾病是绝经后妇女的主要死亡原因。越来越多的证据表明，激素替代疗法可以减少心血管疾病和死亡率。这导致绝经后激素替代疗法被用于心脏病的一级预防，然而，还没有确定哪些女性可能从这种临床方法中受益最多。这是一个复杂的问题，因为激素治疗(HRT)可能提供心脏保护的许多潜在机制都涉及其中。绝经后雌激素/孕激素干预(PEPI)试验研究了四种激素疗法对一系列心血管疾病风险因素(如血脂、血压、胰岛素/血糖、止血因素)的相对影响。审判进行得很好；其数据经过了彻底编辑，并出版了一系列重要出版物。然而，到目前为止，出版物只关注平均效应，而没有彻底探索参与试验的875名受试者的各种影响的范围及其相互作用。我们建议扩大对PEPI数据的分析：1)针对心血管疾病的风险因素(脂类/脂蛋白、血压、胰岛素/血糖、止血因素)表征激素治疗反应的分布；2)检查这些心血管风险因素之间以及对其他结果(症状、骨骼、子宫内膜)的治疗效果的多变量模式；3)检查可能影响这些关系的临床和人口因素，并在这样做的过程中，表征可能因对雌激素和孕激素治疗的单独影响而不同的女性的特征；4)密切检查坚持治疗的模式及其与反应的关系。建议由一个经验丰富的统计学家/流行病学家小组进行并公布这些分析的结果。它的成员对Pepi试验的数据非常熟悉。拟议的分析结果预计将具有相当大的临床意义，并可能有助于解释基于事件的试验的新发现。

Abstract: Cardiovascular disease is the leading cause of death among postmenopausal women. Growing evidence exists that HRT may reduce cardiovascular disease and mortality. This has led to the use of postmenopausal HRT for primary prevention of heart disease, however it remains unresolved which women are likely to benefit most from this clinical approach. This is a complicated question because many potential mechanisms are involved by which hormone therapy (HRT) may confer cardioprotection. The Postmenopausal Estrogen/Progestins Intervention (PEPI) trial examined the relative impact of four regimens of hormone therapy on a range of cardiovascular disease risk factors (e.g. lipids, blood pressure, insulin/glucose, hemostasis factors). The trial was well conducted; its data have been thoroughly edited and have yielded a series of important publications. To date, however, publications have focused on average effects without a thorough exploration of the range of, and interplay among, the various effects across the 875 enrolled in the trial. We propose to extend the analysis of PEPI data: 1) characterize the distributions of responses to hormone therapy with respect to risk factors for cardiovascular disease (lipids/lipoproteins, blood pressure, insulin/glucose, hemostasis factors); 2) examine the multivariate patterns of treatment effects among these cardiovascular risk factors and on other outcomes (symptomatology, bone, endometrial); 3) examine clinical and demographic factors that may affect these relationships and, in doing so, characterize women who may vary with respect to their "sensitivity" to the separate effects of estrogen and progestin therapy; 4) examine closely patterns of adherence and their relationship to response. An experienced team of statisticians/epidemiologists is proposed to conduct and publish results from these analyses. Its members are thoroughly familiar with the data from the PEPI trial. The results of the proposed analyses are expected to hold considerable clinical significance and may help to interpret emerging findings from event-based trials.