Shlipak M G, Simon J A, Vittinghoff E, Lin F, Barrett-Connor E, Knopp R H, Levy R I, Hulley S B
Department of Medicine, University of California, and Veterans Affairs Medical Center, San Francisco, USA.
JAMA. 2000 Apr 12;283(14):1845-52. doi: 10.1001/jama.283.14.1845.
Lipoprotein(a) [Lp(a)] has been identified as an independent risk factor for coronary heart disease (CHD) events. However, few data exist on the clinical importance of Lp(a) lowering for CHD prevention. Hormone therapy with estrogen has been found to lower Lp(a) levels in women.
To determine the relationships among treatment with estrogen and progestin, serum Lp(a) levels, and subsequent CHD events in postmenopausal women.
The Heart and Estrogen/progestin Replacement Study (HERS), a randomized, blinded, placebo-controlled secondary prevention trial conducted from January 1993 through July 1998 with a mean follow-up of 4.1 years at 20 centers.
A total of 2763 postmenopausal women younger than 80 years with coronary artery disease and an intact uterus. Mean age was 66.7 years.
Participants were randomly assigned to receive either conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, in 1 tablet daily (n = 1380), or identical placebo (n = 1383).
Lipoprotein(a) levels and CHD events (nonfatal myocardial infarction and CHD death).
Increased baseline Lp(a) levels were associated with subsequent CHD events among women in the placebo arm. After multivariate adjustment, women in the second, third, and fourth quartiles of baseline Lp(a) level had relative hazards (RHs) (compared with the first quartile) of 1.01 (95% confidence interval [CI], 0.64-1.59), 1.31 (95% CI, 0.85-2.04), and 1.54 (95% CI, 0.99-2.39), respectively, compared with women in the lowest quartile (P for trend = .03). Treatment with estrogen and progestin reduced mean (SD) Lp(a) levels significantly (-5.8 [15] mg/dL) (-0.20 [0.53] micromol/L) compared with placebo (0.3 [17] mg/dL) (0.01 [0.60] micromol/L) (P<.001). In a randomized subgroup comparison, women with low baseline Lp(a) levels had less benefit from estrogen and progestin than women with high Lp(a) levels; the RH for women assigned to estrogen and progestin compared with placebo were 1.49 (95% CI, 0.97-2.26) in the lowest quartile and 1.05 (95% CI, 0.67-1.65), 0.78 (0.52-1.18), and 0.85 (0.58-1.25) in the second, third, and fourth quartiles, respectively (P for interaction trend = .03).
Our data suggest that Lp(a) is an independent risk factor for recurrent CHD in postmenopausal women and that treatment with estrogen and progestin lowers Lp(a) levels. Estrogen and progestin therapy appears to have a more favorable effect (relative to placebo) in women with high initial Lp(a) levels than in women with low levels. This apparent interaction needs confirmation in other trials.
脂蛋白(a)[Lp(a)]已被确认为冠心病（CHD）事件的独立危险因素。然而，关于降低Lp(a)对预防冠心病的临床重要性的数据却很少。已发现雌激素激素疗法可降低女性的Lp(a)水平。
确定绝经后女性中雌激素和孕激素治疗、血清Lp(a)水平与随后的冠心病事件之间的关系。
心脏和雌激素/孕激素替代研究（HERS），这是一项从1993年1月至1998年7月进行的随机、双盲、安慰剂对照的二级预防试验，在20个中心进行，平均随访4.1年。
共有2763名年龄小于80岁、患有冠状动脉疾病且子宫完整的绝经后女性。平均年龄为66.7岁。
参与者被随机分配接受每日1片含0.625mg结合马雌激素加2.5mg醋酸甲羟孕酮的药物（n = 1380），或相同的安慰剂（n = 1383）。
脂蛋白(a)水平和冠心病事件（非致命性心肌梗死和冠心病死亡）。
在安慰剂组中，基线Lp(a)水平升高与随后的冠心病事件相关。经过多变量调整后，基线Lp(a)水平处于第二、第三和第四四分位数的女性与最低四分位数的女性相比，相对风险（RHs）分别为1.01（95%置信区间[CI]，0.64 - 1.59）、1.31（95%CI，0.85 - 2.04）和1.54（95%CI，0.99 - 2.39）（趋势P值 = 0.03）。与安慰剂组（0.3[17]mg/dL）（0.01[0.60]μmol/L）相比，雌激素和孕激素治疗显著降低了平均（标准差）Lp(a)水平（-5.8[15]mg/dL）（-0.20[0.53]μmol/L）（P < 0.001）。在随机亚组比较中，基线Lp(a)水平低的女性从雌激素和孕激素治疗中获得的益处少于Lp(a)水平高的女性；与安慰剂相比，分配接受雌激素和孕激素治疗的女性在最低四分位数中的相对风险为1.49（95%CI，0.97 - 2.26），在第二、第三和第四四分位数中分别为1.05（95%CI，0.67 - 1.65）、0.78（0.52 - 1.18）和0.85（0.58 - 1.25）（交互趋势P值 = 0.03）。
我们的数据表明，Lp(a)是绝经后女性复发性冠心病的独立危险因素，且雌激素和孕激素治疗可降低Lp(a)水平。相对于安慰剂，雌激素和孕激素疗法在初始Lp(a)水平高的女性中似乎比在水平低的女性中具有更有利的效果。这种明显的相互作用需要在其他试验中得到证实。
