Chen Yanghui, Huang Man, Xuan Yunling, Li Ke, Xu Xin, Wang Linlin, Sun Yang, Xiao Lei, Xu Ping, Kong Wei, Wang Dao Wen
Division of Cardiology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China.
Hubei Key Laboratory of Genetics and Molecular Mechanism of Cardiologic Disorders, Huazhong University of Science and Technology, Wuhan 430000, China.
J Pers Med. 2021 Nov 10;11(11):1171. doi: 10.3390/jpm11111171.
Although the associations between serum lipid levels and aneurysms have been investigated in epidemiological studies, causality remains unknown. Thus, this study aimed to investigate the causal relationships of serum high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), and triglyceride (TG) levels on five types of aneurysms, using genetic variants associated with four lipid traits as instrumental variables in a Mendelian randomization (MR) analysis.
We performed two-sample Mendelian randomization (MR) analyses to evaluate the associations of HDL-C, LDL-C, TC, and TG levels with risks for five types of aneurysms and those of LDL-C- (, , , , and ) and TG-lowering targets ( and ) with aneurysms.
The sample sizes of the included studies ranged from nearly 80,000 to 410,000. We found inverse associations between genetically predicted HDL-C levels and aortic (OR = 0.74, 95% CI = 0.65-0.85) and abdominal aortic aneurysms (0.58, 0.45-0.75). A 1-SD increase in LDL-C and TC levels was associated with increased risks for aortic (1.41, 1.26-1.58 and 1.36, 1.18-1.56, respectively) and abdominal aortic aneurysms (1.82, 1.48-2.22 and 1.55, 1.25-1.93, respectively). TG levels were significantly associated with aortic (1.36, 1.18-1.56) and lower extremity artery aneurysms (2.76, 1.48-5.14), but limited to cerebral aneurysm (1.23, 1.06-1.42). Secondary analyses revealed a relationship between genetically proxied LDL-C-lowering targets and all types of aneurysms; however, the drug targets remained heterogeneous. We found a weak association between TG-lowering therapies and aortic (, 0.51, 0.29-0.89) and abdominal aortic aneurysms (, 0.64, 0.44-0.94).
According to genetic evidence, lipid dysfunction is a causal risk factor for aneurysms. Lipid-lowering drugs may be a potential effective strategy in preventing and managing aneurysms.
尽管在流行病学研究中已对血脂水平与动脉瘤之间的关联进行了调查，但因果关系仍不明确。因此，本研究旨在利用与四种脂质性状相关的基因变异作为孟德尔随机化（MR）分析中的工具变量，研究血清高密度脂蛋白胆固醇（HDL-C）、低密度脂蛋白胆固醇（LDL-C）、总胆固醇（TC）和甘油三酯（TG）水平与五种类型动脉瘤之间的因果关系。
我们进行了两样本孟德尔随机化（MR）分析，以评估HDL-C、LDL-C、TC和TG水平与五种类型动脉瘤风险之间的关联，以及降低LDL-C（ 、 、 、 、 和 ）和TG（ 和 ）目标与动脉瘤之间的关联。
纳入研究的样本量从近80,000到410,000不等。我们发现基因预测的HDL-C水平与主动脉瘤（OR = 0.74，95%CI = 0.65 - 0.85）和腹主动脉瘤（0.58，0.45 - 0.75）之间呈负相关。LDL-C和TC水平每增加1个标准差，与主动脉瘤（分别为1.41，1.26 - 1.58和1.36，1.18 - 1.56）和腹主动脉瘤（分别为1.82，1.48 - 2.22和1.55，1.25 - 1.93）风险增加相关。TG水平与主动脉瘤（1.36，1.18 - 1.56）和下肢动脉瘤（2.76，1.48 - 5.14）显著相关，但与脑动脉瘤的相关性有限（1.23，1.06 - 1.42）。二次分析揭示了基因代理的降低LDL-C目标与所有类型动脉瘤之间的关系；然而，药物靶点仍然存在异质性。我们发现降低TG治疗与主动脉瘤（ ，0.51，0.29 - 0.89）和腹主动脉瘤（ ，0.64，0.44 - 0.94）之间存在弱关联。
根据基因证据，脂质功能障碍是动脉瘤的一个因果危险因素。降脂药物可能是预防和管理动脉瘤的一种潜在有效策略。
