LDL triglycerides, hepatic lipase activity, and coronary artery disease: An epidemiologic and Mendelian randomization study
LDL triglycerides, hepatic lipase activity, and coronary artery disease: An epidemiologic and Mendelian randomization study
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DOI：
10.1016/j.atherosclerosis.2018.12.024
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发表时间：
2019-03-01
期刊：
影响因子：
5.3
通讯作者：
Grammer, Tanja B.
中科院分区：
文献类型：
--
作者：
Silbernagel, Guenther;Scharnagl, Hubert;Grammer, Tanja B.
背景和目的：高浓度的低密度脂蛋白（LDL）甘油三酯与流行的冠状动脉造影疾病有关。本分析旨在调查低密度脂蛋白甘油三酯与心血管死亡率的关系，并探讨低密度脂蛋白甘油三酯与心血管风险之间的可能机制。方法：在路德维希港风险和心血管健康（LURIC）研究的3140名参与者中测量LDL甘油三酯。对他们进行心血管死亡率的前瞻性随访（中位持续时间9.9年）。在2900名LURIC参与者中，LDL甘油三酯的全基因组关联数据可用。遗传数据和肝脂肪酶活性的测量可用于478名参与者的HERITAGE家族研究。CARDIoGRAMplusC4D联盟的184,305名参与者可获得心血管疾病的全基因组关联数据。结果：低密度脂蛋白甘油三酯与心血管死亡率之间存在持续的正相关（第5五分位数vs第1五分位数的危险比= 2.53,p < 0.001），这种关联在男性和女性中相似。LURIC基因组全关联分析显示，LDL甘油三酯与肝脂肪酶区域的变异密切相关（rs1800588和rs10468017的p < 10(-15)）。rs1800588和rs10468017中LDL甘油三酯升高等位基因与HERITAGE患者肝脂肪酶活性低和CARDIoGRAMplusC4D患者心血管风险增加相关。以rs1800588和rs10468017为工具变量的双样本孟德尔随机化分析（HERITAGE和CARDIoGRAMplusC4D）表明，低肝脂肪酶活性可能导致心血管风险增加（p = 0.013）。结论：低肝脂肪酶活性可能将高LDL甘油三酯与心血管风险增加联系起来。
Background and aims: High concentrations of low density lipoprotein (LDL) triglycerides have been associated with prevalent angiographic coronary artery disease. The present analysis was designed to investigate the association of LDL triglycerides with cardiovascular mortality and to explore possible mechanisms that may link LDL triglycerides to cardiovascular risk.Methods: LDL triglycerides were measured in 3140 participants of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. They were prospectively followed for cardiovascular mortality (median duration 9.9 years). Genome wide association data for LDL triglycerides were available for 2900 LURIC participants. Genetic data and measurements of hepatic lipase activity were available for 478 participants of the HERITAGE Family study. Genome wide association data for cardiovascular disease were available for 184,305 participants of the CARDIoGRAMplusC4D consortium.Results: There was a continuous positive association between LDL triglycerides and cardiovascular mortality (hazard ratio for 5th vs. 1st quintile = 2.53, p < 0.001) and this association was similar in males and females. Genome wide association analysis in LURIC revealed that LDL triglycerides were strongly associated with variation in the hepatic lipase region (p < 10(-15) for rs1800588 and rs10468017). The LDL triglyceride raising alleles in rs1800588 and rs10468017 were associated with low hepatic lipase activity in HERITAGE and increased cardiovascular risk in CARDIoGRAMplusC4D. Two-sample Mendelian randomization analysis (HERITAGE and CARDIoGRAMplusC4D) using rs1800588 and rs10468017 as instrumental variable suggested that low hepatic lipase activity may cause increased cardiovascular risk (p = 0.013).Conclusions: Low hepatic lipase activity may link high LDL triglycerides to increased cardiovascular risk.