Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease.
Clinical Utility of Lipoprotein(a) and LPA Genetic Risk Score in Risk Prediction of Incident Atherosclerotic Cardiovascular Disease.
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脂蛋白(a)和LPA遗传风险评分在动脉粥样硬化性心血管疾病发生风险预测中的临床应用
DOI：
10.1001/jamacardio.2020.5398
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发表时间：
2021-03-01
期刊：
影响因子：
24
通讯作者：
Natarajan P
中科院分区：
文献类型：
--
作者：
Trinder M;Uddin MM;Finneran P;Aragam KG;Natarajan P
脂蛋白(A)和/或LPA遗传风险评分(GRS)的测量在预测动脉粥样硬化性心血管疾病(ASCVD)发病风险方面是否具有临床实用价值？在英国生物库招募的283LPA540名成人队列中，测得的脂蛋白(A)和 GRs都与发生ASCVD事件的类似风险相关。除了测量的脂蛋白(A)外，LPA GRS没有产生额外的预后信息，而且与合并队列方程或QRISK3相比，测量的脂蛋白(A)和LPA GRS在区分ASCVD风险方面都有轻微的改善。脂蛋白(A)的心血管风险评估可以通过直接测量或LPA GRS来实现。脂蛋白(A)是一种高度遗传的生物标志物，与动脉粥样硬化性心血管疾病(ASCVD)独立相关。目前尚不清楚测定的脂蛋白(A)或与脂蛋白(A)相关的遗传因素是否能为一级预防提供可比的或额外的预后信息。目的：确定编码载脂蛋白(A)的LPA基因43个变异的遗传风险评分(GRS)在评估ASCVD风险方面是否具有临床实用价值，与脂蛋白(A)测量相比，以及在评估ASCVD风险方面。英国生物库是一项前瞻性的观察性研究，研究对象是2006年至2010年在英国22个地点招募的约500名 ，000名年龄在40岁至69岁之间的志愿者。使用外部派生的权重，计算了374LPA099个具有阵列派生的基因型和脂蛋白(A)测量的无关个体的 GRS。对2020年4月至2020年3月的数据进行了分析。测定脂蛋白(A)和LPA GRS。我们使用COX比例风险模型评估了测量的脂蛋白(A)和LPA GRS与ASCVD(外周动脉疾病、冠状动脉疾病、心肌梗死、缺血性中风和心血管死亡率)的发生率之间的关系。为了确定使用测量的脂蛋白(A)和LPA GR作为ASCVD风险增强剂的有效性，我们评估了QRISK3和合并队列方程在具有中等风险的个体(分别为n = 113 703和144 350)中在ASCVD风险识别方面的潜在改善。整个研究人群的平均年龄为57.6岁，其中女性204355人(54.6%)。在中位数为11.1年(四分位数范围，1.4年)的随访中，15名 444人发生了急性心肌梗死事件(5.1%)。LPA GRS解释了白人/欧洲人测得的脂蛋白(A)变化的大约60%。独立地，脂蛋白(A)和LPA GRS都与事件和复合ASCVD相关(每120nmol/L增加的危险比，1.26；95%可信区间，1.23-1.28vs危险比，1.29；95%可信区间，1.26-1.33；P <； .001)。在校正了测得的脂蛋白(A)后，LPA、GRS和ASCVD之间的关联性显著减弱。将测得的脂蛋白(A)或LPA GRS加入QRISK3中，对发生ASCVD事件(受试者工作曲线下面积，0.640；95%可信区间，0.633-0.647比0.642；95%可信区间，0.635-0.649；P = .005和P = .01)提供了适度的改善。如果需要，中年时用脂蛋白(A)进行的心血管风险评估可能包括直接测量或LPA GRS。这项研究调查了编码载脂蛋白(A)的LPA基因上43个变异的遗传风险评分在评估动脉粥样硬化性心血管疾病风险方面是否具有临床实用价值，与脂蛋白(A)测量相比，也是如此。
Does measurement of lipoprotein(a) and/or LPA genetic risk score (GRS) have clinical utility in risk prediction of incident atherosclerotic cardiovascular disease (ASCVD)? In this cohort of 283 540 adults recruited by the UK Biobank, both measured lipoprotein(a) and LPA GRS were associated with comparable risk of incident ASCVD events. The LPA GRS did not yield additional prognostic information beyond measured lipoprotein(a), and both measured lipoprotein(a) and LPA GRS yielded modest improvements in the discrimination of ASCVD risk relative to the Pooled Cohort Equations or QRISK3. Cardiovascular risk assessment with lipoprotein(a) may be achieved with either direct measurement or an LPA GRS. Lipoprotein(a) is a highly heritable biomarker independently associated with atherosclerotic cardiovascular disease (ASCVD). It is unclear whether measured lipoprotein(a) or genetic factors associated with lipoprotein(a) can provide comparable or additional prognostic information for primary prevention. To determine whether a genetic risk score (GRS) comprising 43 variants at the LPA gene, which encodes apolipoprotein(a), has clinical utility in assessing ASCVD risk compared with and in addition to lipoprotein(a) measurement. The UK Biobank is a prospective observational study of approximately 500 000 volunteers aged 40 to 69 years who were recruited from 22 sites across the United Kingdom between 2006 and 2010. Using externally derived weights, an LPA GRS was calculated for 374 099 unrelated individuals with array-derived genotypes and lipoprotein(a) measures. Data were analyzed from April 2020 to March 2020. Measured lipoprotein(a) and LPA GRS. We estimated the associations between measured lipoprotein(a) and LPA GRS with the incidence of ASCVD (peripheral arterial disease, coronary artery disease, myocardial infarction, ischemic stroke, and cardiovascular mortality) using Cox proportional hazards models. To determine the utility of using measured lipoprotein(a) and LPA GRS as risk enhancers for ASCVD, we assessed the potential improvement in ASCVD risk discrimination by QRISK3 and Pooled Cohort Equations among individuals with borderline to intermediate risk (n = 113 703 and 144 350, respectively). The mean age of the overall study population was 57.6 years, and 204 355 individuals were female (54.6%). During a median follow-up of 11.1 years (interquartile range, 1.4 years), 15 444 individuals developed an incident ASCVD event (5.1%). The LPA GRS explained approximately 60% of the variation in measured lipoprotein(a) for White/European individuals. Independently, both lipoprotein(a) and LPA GRS were associated with incident, composite ASCVD (hazard ratio per 120 nmol/L increase, 1.26; 95% CI, 1.23-1.28 vs hazard ratio, 1.29; 95% CI, 1.26-1.33; P < .001). The association between LPA GRS and ASCVD was substantially attenuated after adjusting for measured lipoprotein(a). Adding measured lipoprotein(a) or LPA GRS to QRISK3 provided modest improvements to the risk discrimination of incident ASCVD events (area under the receiver operating curve, 0.640; 95% CI, 0.633-0.647 vs 0.642; 95% CI, 0.635-0.649 for both; P = .005 and P = .01, respectively). When indicated, cardiovascular risk assessment with lipoprotein(a) at middle-age may include direct measurement or an LPA GRS. This study investigates whether a genetic risk score comprising 43 variants at the LPA gene, which encodes apolipoprotein(a), has clinical utility in assessing atherosclerotic cardiovascular disease risk compared with and in addition to lipoprotein(a) measurement.
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影响因子：
37.8
作者：
Khera AV;Everett BM;Caulfield MP;Hantash FM;Wohlgemuth J;Ridker PM;Mora S
通讯作者：
Mora S
影响因子：
64.8
作者：
Bycroft C;Freeman C;Petkova D;Band G;Elliott LT;Sharp K;Motyer A;Vukcevic D;Delaneau O;O'Connell J;Cortes A;Welsh S;Young A;Effingham M;McVean G;Leslie S;Allen N;Donnelly P;Marchini J
通讯作者：
Marchini J
英国生物库中的遗传分析将胰岛素抵抗和跨内皮迁移途径与冠状动脉疾病联系起来。
影响因子：
30.8
作者：
Klarin D;Zhu QM;Emdin CA;Chaffin M;Horner S;McMillan BJ;Leed A;Weale ME;Spencer CCA;Aguet F;Segrè AV;Ardlie KG;Khera AV;Kaushik VK;Natarajan P;CARDIoGRAMplusC4D Consortium;Kathiresan S
通讯作者：
Kathiresan S
影响因子：
120.7
作者：
Erqou, Sebhat;Kaptoge, Stephen;Perry, Philip L.;Di Angelantonio, Emanuele;Thompson, Alexander;White, Ian R.;Marcovina, Santica M.;Collins, Rory;Thompson, Simon G.;Danesh, John
通讯作者：
Danesh, John
影响因子：
15.9
作者：
BOERWINKLE, E;LEFFERT, CC;HOBBS, HH
通讯作者：
HOBBS, HH