Maher V M, Brown B G, Marcovina S M, Hillger L A, Zhao X Q, Albers J J
Department of Medicine, University of Washington School of Medicine, Seattle, USA.
JAMA. 1995 Dec 13;274(22):1771-4.
To determine if lowering elevated low-density lipoprotein cholesterol (LDL-C) levels offsets the adverse effect of raised lipoprotein(a) (Lp[a]) levels on coronary artery disease (CAC) in men.
Randomized, double-blind, placebo-controlled trial of lipid lowering for CAD.
Post hoc analysis of the Familial Atherosclerosis Treatment Study.
A total of 146 men aged 62 years or younger with CAD and apolipoprotein B levels of at least 125 mg/dL.
Patients received a Step II Diet and lovastatin (40 mg daily) plus colestipol (30 g daily), niacin (4 g daily) plus colestipol, or placebo (plus colestipol if LDL-C > 90th percentile) for 2.5 years. They were grouped by their LDL-C responses: "minimal" if LDL-C decreased by 10% or less from baseline (mean [SD] change, +6% [13%]) and "substantial" if LDL-C decreased more than 10% (mean [SD] change, -40% [16%]).
Impact of lowering elevated LDL-C on the cardiac event rate (death, myocardial infarction, and revascularization for refractory ischemia) and CAD change associated with elevated Lp(a).
In multivariate analyses, the best correlate of baseline CAD severity was Lp(a) (r = 0.30; P < .001). For 36 patients with minimal LDL-C reduction, CAD progression correlated only with in-treatment Lp(a) levels (r = 0.45; P < .01), but for 84 patients with substantial LDL-C reduction, disease regressed and its change correlated with in-treatment LDL-C (r = 0.24; P < .05) but not with Lp(a) (r = -0.05). Lipoprotein(a) levels were not significantly altered in either group. For 40 patients with Lp(a) at the 90th percentile or higher, events were frequent (39%) if reduction of LDL-C was minimal, but were few (9%) if reduction was substantial (relative risk, 0.23; 95% confidence interval, 0.06 to 0.99).
In men with CAD and elevated LDL-C, Lp(a) levels were dominant correlates of baseline disease severity, its progression, and event rate over 2.5 years. However, with substantial LDL-C reductions, persistent elevations of Lp(a) were no longer atherogenic or clinically threatening. This provides a possible direction for treatment in such patients with elevated Lp(a) and LDL-C.
确定降低升高的低密度脂蛋白胆固醇（LDL-C）水平是否能抵消脂蛋白(a) [Lp(a)]水平升高对男性冠状动脉疾病（CAC）的不利影响。
针对冠心病的脂质降低的随机、双盲、安慰剂对照试验。
家族性动脉粥样硬化治疗研究的事后分析。
总共146名年龄在62岁及以下、患有冠心病且载脂蛋白B水平至少为125mg/dL的男性。
患者接受二期饮食和洛伐他汀（每日40mg）加考来替泊（每日30g）、烟酸（每日4g）加考来替泊，或安慰剂（如果LDL-C>第90百分位数则加考来替泊），持续2.5年。他们根据LDL-C反应分组：如果LDL-C较基线降低10%或更少（平均[标准差]变化，+6%[13%]）则为“最小”，如果LDL-C降低超过10%（平均[标准差]变化，-40%[16%]）则为“显著”。
降低升高的LDL-C对心脏事件发生率（死亡、心肌梗死以及难治性缺血的血运重建）的影响，以及与Lp(a)升高相关的CAD变化。
在多变量分析中，基线CAD严重程度的最佳相关因素是Lp(a)（r = 0.30；P < .001）。对于36名LDL-C降低最小的患者，CAD进展仅与治疗期间的Lp(a)水平相关（r = 0.45；P < .01），但对于84名LDL-C显著降低的患者，疾病有所消退，其变化与治疗期间的LDL-C相关（r = 0.24；P < .05），而与Lp(a)无关（r = -0.05）。两组的脂蛋白(a)水平均未显著改变。对于40名Lp(a)处于第90百分位数或更高的患者，如果LDL-C降低最小，事件发生率较高（39%），但如果降低显著则事件发生率较低（9%）（相对风险，0.23；95%置信区间，0.06至0.99）。
在患有冠心病且LDL-C升高的男性中，Lp(a)水平是基线疾病严重程度、其进展以及2.5年期间事件发生率的主要相关因素。然而，随着LDL-C的显著降低，Lp(a)的持续升高不再具有致动脉粥样硬化性或临床威胁性。这为此类Lp(a)和LDL-C升高的患者提供了一个可能的治疗方向。
