脂蛋白(a)水平极高与心血管风险预测改善。
Extreme lipoprotein(a) levels and improved cardiovascular risk prediction.
机构信息
Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Copenhagen, Denmark.
出版信息
J Am Coll Cardiol. 2013 Mar 19;61(11):1146-56. doi: 10.1016/j.jacc.2012.12.023. Epub 2013 Jan 30.
OBJECTIVES
The study tested whether extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes improve myocardial infarction (MI) and coronary heart disease (CHD) risk prediction beyond conventional risk factors.
BACKGROUND
Elevated lipoprotein(a) levels cause MI and CHD. Levels are primarily determined by variation in the LPA gene.
METHODS
We followed 8,720 Danish participants in a general population study from 1991 to 1994 through 2011 without losses to follow-up. During this period, 730 and 1,683 first-time MI and CHD events occurred. Using predefined cutpoints for extreme lipoprotein(a) levels and/or corresponding LPA risk genotypes (kringle IV type 2 [KIV-2]) repeat polymorphism, rs3798220, and rs10455872 single nucleotide polymorphisms), we calculated net reclassification indices from <10% to 10% to 19.9% to ≥20% absolute 10-year MI and CHD risk.
RESULTS
For individuals with lipoprotein(a) levels ≥80th percentile (≥47 mg/dl), 23% (p < 0.001) of MI events and 12% (p < 0.001) of CHD events were reclassified correctly, while no events were reclassified incorrectly for either endpoint. As some incorrect reclassification of individuals with no events occurred, addition of lipoprotein(a) levels ≥80th percentile overall yielded net reclassification indices of +16% (95% confidence interval: 8% to 24%) and +3% (-1% to 8%) for MI and CHD, respectively. Corresponding net reclassification indices for number of KIV-2 repeats ≤21st percentile were +12% (5% to 19%) and +4% (0% to 8%), for rs3798220 carrier status +15% (-14% to 44%) and +10% (-10% to 30%), and for rs10455872 carrier status +16% (6% to 26%) and +2% (-1% to 6%). Considering only individuals at 10% to 19.9% absolute 10-year MI and CHD risk, addition of extreme lipoprotein(a) levels or corresponding LPA risk genotypes improved risk prediction even further.
CONCLUSIONS
Extreme lipoprotein(a) levels or corresponding LPA KIV-2/rs10455872 risk genotypes substantially improved MI and CHD risk prediction.
目的
本研究旨在检验脂蛋白(a)水平极高和/或相应的脂蛋白(a)风险基因型是否可改善心肌梗死(MI)和冠心病(CHD)的风险预测，且作用优于传统危险因素。
背景
脂蛋白(a)水平升高可导致 MI 和 CHD。该水平主要由 LPA 基因变异决定。
方法
我们对丹麦一般人群研究中的 8720 名参与者进行了随访，随访时间从 1991 年至 1994 年直至 2011 年，期间无失访情况。在此期间，共有 730 例和 1683 例首次 MI 和 CHD 事件发生。根据脂蛋白(a)水平极高(<10%至 10%至 19.9%至≥20%)和相应的脂蛋白(a)风险基因型(kringle IV 型 2[KIV-2]重复多态性 rs3798220 和 rs10455872 单核苷酸多态性)的预设切点，我们计算了从<10%到 10%至 19.9%至≥20%绝对 10 年 MI 和 CHD 风险的净重新分类指数。
结果
脂蛋白(a)水平处于第 80 百分位数(≥47mg/dl)以上的患者中，23%(p<0.001)的 MI 事件和 12%(p<0.001)的 CHD 事件被正确重新分类，而对于任一终点，均未出现错误重新分类的情况。由于一些无事件患者被错误分类，脂蛋白(a)水平处于第 80 百分位以上总体上导致 MI 和 CHD 的净重新分类指数分别增加了+16%(95%置信区间：8%至 24%)和+3%(-1%至 8%)。相应的 KIV-2 重复次数≤第 21 百分位数的净重新分类指数为+12%(5%至 19%)和+4%(0%至 8%)，KIV-2 重复次数为 rs3798220 携带者状态+15%(-14%至 44%)和+10%(-10%至 30%)，rs10455872 携带者状态+16%(6%至 26%)和+2%(-1%至 6%)。仅考虑处于 10%至 19.9%绝对 10 年 MI 和 CHD 风险的患者，增加极高脂蛋白(a)水平或相应的脂蛋白(a)风险基因型可进一步改善风险预测。
结论
极高脂蛋白(a)水平或相应的脂蛋白(a)KIV-2/rs10455872 风险基因型可显著改善 MI 和 CHD 的风险预测。
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