[1]于航天 赵妍 龚昂未 张帅丹 管成健 陈树晨 肖冰?/html>.血脂与心力衰竭风险的因果关系及冠状动脉疾病的中介作用:一项孟德尔随机化研究[J].心血管病学进展,2024,(1):91.[doi:10.16806/j.cnki.issn.1004-3934.2024.01.022]
 YU Hangtian,ZHAO Yan,GONG Angwei,et al.Causal Relationship Between Lipids and Heart Failure Risk and Mediating Effect of Coronary Artery Disease: a Mendelian Randomization Study[J].Advances in Cardiovascular Diseases,2024,(1):91.[doi:10.16806/j.cnki.issn.1004-3934.2024.01.022]
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血脂与心力衰竭风险的因果关系及冠状动脉疾病的中介作用:一项孟德尔随机化研究()
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《心血管病学进展》[ISSN:51-1187/R/CN:1004-3934]

卷:
期数:
2024年1期
页码:
91
栏目:
论著
出版日期:
2024-02-21

文章信息/Info

Title:
Causal Relationship Between Lipids and Heart Failure Risk and Mediating Effect of Coronary Artery Disease: a Mendelian Randomization Study
作者:
于航天 赵妍 龚昂未 张帅丹 管成健 陈树晨 肖冰?/html>
(河北医科大学第二医院心血管内科,河北 石家庄 050000)
Author(s):
YU HangtianZHAO YanGONG AngweiZHANG ShuaidanGUAN ChengjianCHEN ShuchenXIAO Bing
(Department of Cardiovascular Medicine,The Second Hospital of Hebei Medical University,Shijiazhuang 050000,Hebei,China)
关键词:
血脂心力衰竭孟德尔随机化中介分析
Keywords:
Blood lipidsHeart failureMendelian randomizationMediation analysis
DOI:
10.16806/j.cnki.issn.1004-3934.2024.01.022
摘要:
目的 利用孟德尔随机化分析方法,探究血脂与心力衰竭风险之间的因果关系及冠状动脉疾病的潜在中介效应。方法 主要采用逆方差加权方法,对 欧洲人群中的血脂水平(包括甘油三酯、低密度脂蛋白胆固醇、高密度脂蛋白胆固醇、载脂蛋白A1和载脂蛋白B)与心力衰竭的因果关系进行单变量孟德尔随机化分析。此外,采用中介分析方法探究冠状动脉疾病的潜在中介效应。结果 单变量孟德尔随机化分析结果显示,血脂与心力衰竭风险之间存在显著关联。其中甘油三酯( OR = 1.15,95% CI 1.09~1.21)、低密度脂蛋白胆固醇(OR = 1.15 ,95% CI 1.05~1.25)和载脂蛋白B水平的升高(OR = 1.16 ,95% CI 1.07~1.26)与心力衰竭风险呈正相关。此外,高密度脂蛋白胆固醇(OR = 0.88,95% CI 0.84~0.93)和载脂蛋白A1的升高(OR = 0.92 ,95% CI 0.87~0.97)与心力衰竭风险呈负相关。敏感性分析验证了以上结果的稳健性。中介分析结果显示冠状动脉疾病在甘油三酯、低密度脂蛋白胆固醇、载脂蛋白B、高密度脂蛋白胆固醇、载脂蛋白A1与心力衰竭风险的因果关系中起到部分中介作用(分别为10.63%、16.72%、23.82%、18.78%和16.14%)。 结论 孟德尔随机化方法表明,甘油三酯、低密度脂蛋白胆固醇和载脂蛋白B水平升高会增加心力衰竭风险,而高密度脂蛋白胆固醇和载脂蛋白A1水平升高则可能降低该风险。冠状动脉疾病在这一因果联系中存在部分中介作用。
Abstract:
Objective A univariable Mendelian randomization (MR) analysis was conducted to explore the causal relationship between lipids and the risk of heart failure (HF) and the potential mediating effect of coronary artery disease (CAD). Methods The inverse variance weighting was mainly applied for the MR analysis to examine the causal relationship between blood lipids (including triglycerides ,low-density lipoprotein cholesterol,high-density lipoprotein cholesterol,apolipoprotein A1 and apolipoprotein B) and HF in European population. Additionally,mediation analysis was conducted to investigate the potential mediating effect of CAD. Results The results of the univariable MR analysis revealed a significant association between blood lipids and the risk of HF. Elevated levels of triglycerides (OR = 1.15 ,95% CI 1.09~1.21),low-density lipoprotein cholesterol (OR = 1.15,95% CI 1.05~1.25) and apolipoprotein B (OR = 1.16 ,95% CI 1.07~1.26) were significantly associated with increased risk of HF. In addition,this analysis showed that elevated high-density lipoprotein cholesterol (OR = 0.88 ,95% CI 0.84~0.93) and apolipoprotein A1 (OR = 0.92 ,95% CI 0.87~0.97) were inversely associated with the risk of HF. Sensitivity analysis confirmed the robustness of these results. The results of the mediation analysis showed that CAD partially mediated the causal relationship between the above lipid indices(triglycerides,low-density lipoprotein cholesterol,apolipoprotein B, high-density lipoprotein cholesterol and apolipoprotein A1 ) and the risk of HF (10.63% ,16.72%,23.82%,18.78% and 16.14%,respectively). Conclusion M R indicates that elevated levels of triglycerides ,low-density lipoprotein cholesterol and apolipoprotein B increase the risk of HF,whereas higher levels of high-density lipoprotein cholesterol and apolipoprotein A1 may reduce this risk. CAD partially mediates this causal relationship.

参考文献/References:

[1]Heidenreich PA,Bozkurt B,Aguilar D,et al. 2022 AHA/ACC/HFSA Guideline for the Management of Heart Failure:A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines[J]. Circulation,2022,145(18):e876-e894.

[2]Ziaeian B,Fonarow GC. Epidemiology and aetiology of heart failure[J]. Nat Rev Cardiol,2016,13(6):368-378.

[3]Vos T,Flaxman AD,Naghavi M,et al. Years lived with disability(YLDs) for 1160 sequelae of 289 diseases and injuries 1990—2010:a systematic analysis for the Global Burden of Disease Study 2010[J]. Lancet,2012,380(9859):2163-2196.

[4]王华,刘宇佳,杨杰孚. 心力衰竭流行病学[J]. 临床心血管病杂志,2023,39(4):243-247.

[5]Garshick MS,Vaidean GD,Vani A,et al. Cardiovascular risk factor control and lifestyle factors in young to middle-aged adults with newly diagnosed obstructive coronary artery disease[J]. Cardiology,2019,142(2):83-90.

[6]谢玉霞,武刚,刘文宁,等. 血脂异常冠心病血管内皮损伤机制的研究[J]. 心血管康复医学杂志,2021,30(3):260-264.

[7]Kopin L,Lowenstein C. Dyslipidemia[J]. Ann Intern Med,2017,167(11):ITC81-ITC96.

[8]Bowden J,Holmes MV. Meta-analysis and Mendelian randomization:a review[J]. Res Synth Methods,2019,10(4):486-496.

[9]Colantonio LD,Bittner V,Reynolds K,et al. Association of serum lipids and coronary heart disease in contemporary observational studies[J]. Circulation,2016,133(3):256-264.

[10]Pagliaro BR,Cannata F,Stefanini GG,et al. Myocardial ischemia and coronary disease in heart failure[J]. Heart Fail Rev,2020,25(1):53-65.

[11]Richiardi L,Bellocco R,Zugna D. Mediation analysis in epidemiology:methods,interpretation and bias[J]. Int J Epidemiol,2013,42(5):1511-1519.

[12]Richardson TG,Sanderson E,Palmer TM,et al. Evaluating the relationship between circulating lipoprotein lipids and apolipoproteins with risk of coronary heart disease:a multivariable Mendelian randomisation analysis[J]. PLoS Med,2020,17(3):e1003062.

[13]van der Harst P,Verweij N. Identification of 64 novel genetic loci provides an expanded view on the genetic architecture of coronary artery disease[J]. Circ Res,2018,122(3):433-443.

[14]Shah S,Henry A,Roselli C,et al. Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure[J]. Nat Commun,2020,11(1):163.

[15]Yang S,Pudasaini R,Zhi H,et al. The relationship between blood lipids and risk of atrial fibrillation:univariable and multivariable Mendelian randomization analysis[J]. Nutrients,2021,14(1):181.

[16]Burgess S,Thompson SG,CRP CHD Genetics Collaboration. Avoiding bias from weak instruments in Mendelian randomization studies[J]. Int J Epidemiol,2011,40(3):755-764.

[17]Yang J,Ferreira T,Morris AP,et al. Conditional and joint multiple-SNP analysis of GWAS summary statistics identifies additional variants influencing complex traits[J]. Nat Genet,2012,44(4):369-375,S1-3.

[18]Hartwig FP,Davey Smith G,Bowden J. Robust inference in summary data Mendelian randomization via the zero modal pleiotropy assumption[J]. Int J Epidemiol,2017,46(6):1985-1998.

[19]Bowden J,Davey Smith G,Haycock PC,et al. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator[J]. Genet Epidemiol,2016,40(4):304-314.

[20]Gronau QF,Wagenmakers EJ. Limitations of Bayesian leave-one-out cross-validation for model selection[J]. Comput Brain Behav,2019,2(1):1-11.

[21]Bowden J,Del Greco MF,Minelli C,et al. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization[J]. Stat Med,2017,36(11):1783-1802.

[22]Bowden J,Davey Smith G,Burgess S. Mendelian randomization with invalid instruments:effect estimation and bias detection through Egger regression[J]. Int J Epidemiol,2015,44(2):512-525.

[23]Verbanck M,Chen CY,Neale B,et al. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases[J]. Nat Genet,2018,50(5):693-698.

[24]Holme I,Aastveit AH,Hammar N,et al. Lipoprotein components and risk of congestive heart failure in 84,740 men and women in the Apolipoprotein MOrtality RISk study(AMORIS)[J]. Eur J Heart Fail,2009,11(11):1036-1042.

[25]Ebong IA,Goff DC Jr ,Rodriguez CJ,et al. Association of lipids with incident heart failure among adults with and without diabetes mellitus:Multiethnic Study of Atherosclerosis[J]. Circ Heart Fail,2013,6(3):371-378.

[26]Cavigiolio C,Geier EG,Shao B,et al. Exchange of apolipoprotein A-I between lipid-associated and lipid-free states:a potential target for oxidative generation of dysfunctional high density lipoproteins[J]. J Biol Chem ,2010,285(24):18847-18857.

[27]Iwaoka M,Obata JE,Abe M,et al. Association of low serum levels of apolipoprotein A-I with adverse outcomes in patients with nonischemic heart failure[J]. J Card Fail,2007,13(4):247-253.

[28]Basu A,Bebu I,Jenkins AJ,et al. Serum apolipoproteins and apolipoprotein-defined lipoprotein subclasses:a hypothesis-generating prospective study of cardiovascular events in T1D[J]. J Lipid Res,2019,60(8):1432-1439.

[29]Xiao J,Ji J,Zhang N,et al. Association of genetically predicted lipid traits and lipid-modifying targets with heart failure[J]. Eur J Prev Cardiol,2023,30(4):358-366.

[30]Gupte AA,Hamilton DJ. Mitochondrial function in non-ischemic heart failure[J]. Adv Exp Med Biol,2017,982:113-126.

[31]Esan O,Wierzbicki AS. Triglycerides and cardiovascular disease[J]. Curr Opin Cardiol,2021,36(4):469-477.

[32]Zhang Y,Ren J. Role of cardiac steatosis and lipotoxicity in obesity cardiomyopathy[J]. Hypertension,2011,57(2):148-150.

[33]Orsó E,Grandl M,Schmitz G. Oxidized LDL-induced endolysosomal phospholipidosis and enzymatically modified LDL-induced foam cell formation determine specific lipid species modulation in human macrophages[J]. Chem Phys Lipids,2011,164(6):479-487.

[34]范平,阿丽米拉·赛依提江,高颖. 冠心病患者载脂蛋白A1、载脂蛋白B与血小板平均分布宽度水平变化及其相关性分析[J]. 新疆大学学报(自然科学版)(中英文),2022,39(4):470-475.

[35]曾谷雨,袁晋青. 高密度脂蛋白的蛋白质组学在冠心病中的研究进展[J]. 中国分子心脏病学杂志,2022,22(4):4853-4857.

[36]Schmidt AF,Joshi R,Gordillo-Mara?on M,et al. Biomedical consequences of elevated cholesterol-containing lipoproteins and apolipoproteins on cardiovascular and non-cardiovascular outcomes[J]. Commun Med (Lond),2023,3(1):9.

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