联合降脂治疗的降脂疗效及对糖代谢的影响
Lipid-Lowering Efficacy of Combined Lipid-Lowering Therapy and Its Effect on Glucose Metabolism
DOI: 10.12677/ACM.2023.132216, PDF,   
作者: 夏 源, 李桂琼*:重庆医科大学附属第二医院,重庆
关键词: 他汀类药物依折麦布PCSK9抑制剂糖代谢Statin Ezetimibe PCSK9 Inhibitors Glucose Metabolism
摘要: 中国居民动脉粥样硬化性心血管疾病(ASCVD)死亡位居单病种死亡首位。他汀类药物稳定的降脂疗效是其成为ASCVD预防首选药物的基础。但是已有研究证实长期使用他汀类药物有增加新发糖尿病的风险。新的降脂药依折麦布和PCSK9抑制剂已经被指南推荐使用,联合他汀类药物使用能进一步减少ASCVD风险,安全性获得肯定,暂未发现对糖代谢有负面影响。本文就联合降脂治疗的疗效及对糖代谢的影响进行阐述。
Abstract: Atherosclerotic cardiovascular disease (ASCVD) deaths among Chinese residents rank first in terms of single disease deaths. The stable lipid-lowering efficacy of statin is the basis for them being the drugs of choice for ASCVD prevention. However, studies have confirmed that long-term statin use has an increased risk of new-onset diabetes. The new lipid-lowering drugs ezetimibe and PCSK9 in-hibitors have been recommended by guidelines, and their use in combination with statin can fur-ther reduce the risk of ASCVD with a positive safety profile. This article describes the efficacy of combined lipid-lowering therapy and the effect on glucose metabolism.
文章引用:夏源, 李桂琼. 联合降脂治疗的降脂疗效及对糖代谢的影响[J]. 临床医学进展, 2023, 13(2): 1567-1573. https://doi.org/10.12677/ACM.2023.132216

参考文献

[1] Zhao, D., Liu, J., Wang, M., Zhang, X. and Zhou, M. (2019) Epidemiology of Cardiovascular Disease in China: Current Features and Implications. Nature Reviews Cardiology, 16, 203-212. [Google Scholar] [CrossRef] [PubMed]
[2] 中国心血管健康与疾病报告编写组. 中国心血管健康与疾病报告2021概要[J]. 中国循环杂志, 2022, 37(6): 553-578.
[3] Critchley, J., Liu, J., Zhao, D., Wei, W. and Capewell, S. (2004) Explaining the Increase in Coronary Heart Disease Mortality in Beijing between 1984 and 1999. Circulation, 110, 1236-1244. [Google Scholar] [CrossRef
[4] Reyes-Soffer, G., Ginsberg, H., Berglund, L., et al. (2022) Lipoprotein(a): A Genetically Determined, Causal, and Prevalent Risk Factor for Atherosclerotic Cardiovascular Disease: A Scientific Statement from the American Heart Association. Arteriosclerosis, Thrombosis, and Vascular Biol-ogy, 42, e48-e60. [Google Scholar] [CrossRef
[5] ESC Committee for Practice Guidelines (CPG) and ESC National Cardiac Societies (2019) 2019 ESC/EAS Guidelines for the Management of Dyslipidaemias: Lipid Modification to Reduce Cardiovascular Risk. Atherosclerosis, 290, 140-205. [Google Scholar] [CrossRef] [PubMed]
[6] 李苏宁, 张林峰, 王馨, 等. 2012~2015年我国≥35岁人群血脂异常状况调查[J]. 中国循环杂志, 2019, 34(7): 681-687.
[7] 赵旺, 叶平, 胡大一, 赵水平. 根据《中国成人血脂异常防治指南(2016年修订版)》再分析DYSIS-China横断面调查[J]. 中国心血管杂志, 2020, 25(1): 55-61.
[8] 诸骏仁, 高润霖, 赵水平, 等. 中国成人血脂异常防治指南(2016年修订版) [J]. 中国循环杂志, 2016, 31(10): 937-953.
[9] Warraich, H.J., Wong, N.D. and Rana, J.S. (2015) Role for combination Therapy in Diabetic Dyslipidemia. Current Cardiology Reports, 17, Article No. 32. [Google Scholar] [CrossRef] [PubMed]
[10] Lloyd-Jones, D., Morris, P., Ballantyne, C., et al. (2022) 2022 ACC Expert Consensus Decision Pathway on the Role of Nonstatin Therapies for LDL-Cholesterol Lowering in the Management of Atherosclerotic Cardiovascular Disease Risk: A Report of the American College of Cardiology Solution Set Oversight Committee. Journal of the American College of Cardiology, 80, 1366-1418. [Google Scholar] [CrossRef] [PubMed]
[11] 中华医学会心血管病学分会, 中国康复医学会心脏预防与康复专业委员会, 中国老年学和老年医学会心脏专业委员会, 中国医师协会心血管内科医师分会血栓防治专业委员会. 中国心血管病一级预防指南[J]. 中华心血管病杂志, 2020, 48(12): 1000-1038.
[12] Brown, M.S. and Goldstein, J.L. (1997) The SREBP Pathway: Regulation of Cholesterol Metabolism by Proteolysis of a Membrane-Bound Tran-scription Factor. Cell, 89, 331-340. [Google Scholar] [CrossRef
[13] Goldstein, J.L. and Brown, M.S. (2009) The LDL Receptor. Arteriosclerosis, Thrombosis, and Vascular Biology, 29, 431-438. [Google Scholar] [CrossRef
[14] Jia, Y., Wen, J., Qureshi, R., et al. (2021) Effect of Redun-dant Clinical Trials from Mainland China Evaluating Statins in Patients with Coronary Artery Disease: Cross Sectional Study. BMJ, 372, Article No. n48. [Google Scholar] [CrossRef] [PubMed]
[15] Baigent, C., Keech, A., Kearney, P., et al. (2005) Efficacy and Safety of Cho-lesterol-Lowering Treatment: Prospective Meta-Analysis of Data from 90,056 Participants in 14 Randomised Trials of Statins. Lancet, 366, 1267-1278. [Google Scholar] [CrossRef
[16] Collins, R.C., Reith, C., Emberson, J., et al. (2016) Interpre-tation of the Evidence for the Efficacy and Safety of Statin Therapy. Lancet, 388, 2532-2561. [Google Scholar] [CrossRef
[17] Sharma, A., Joshi, P.H., Rinehart, S., et al. (2016) Baseline Very Low-Density Lipoprotein Cholesterol Is Associated with the Magnitude of Triglyceride Lowering on Statins, Feno-fibric Acid, or Their Combination in Patients with Mixed Dyslipidemia. Journal of cardiovascular Translational Re-search, 7, 465-474. [Google Scholar] [CrossRef] [PubMed]
[18] Khera, A.V., Everett, B.M., Caulfield, M.P., et al. (2014) Lipo-protein(a) Concentrations, Rosuvastatin Therapy, and Residual Vascular Risk: An Analysis from the JUPITER Trial (Justification for the Use of Statins in Prevention: An Intervention Trial Evaluating Rosuvastatin). Circulation, 129, 635-642. [Google Scholar] [CrossRef
[19] Ridker, P., Danielson, E., Fonseca, F., et al. (2008) Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein. The New England Jour-nal of Medicine, 359, 2195-2207. [Google Scholar] [CrossRef
[20] Arnaboldi, L. and Corsini, A. (2015) Could Changes in Adiponectin Drive the Effect of Statins on the Risk of New- Onset Diabetes? The Case of Pitavastatin. Atherosclerosis Supplements, 16, 1-27. [Google Scholar] [CrossRef
[21] Go, A.S., Ambrosy, A.P., Kheder, K., et al. (2020) Statin Therapy and Risk of Incident Diabetes Mellitus in Adults with Cardiovascular Risk Factors. The American Journal of Cardiology, 125, 534-541. [Google Scholar] [CrossRef] [PubMed]
[22] Betteridge, D. and Carmena, R. (2016) The Diabetogenic Action of Statins - Mechanisms and Clinical Implications. Nature Reviews Endocrinology, 12, 99-110. [Google Scholar] [CrossRef] [PubMed]
[23] Abbasi, F., Lamendola, C., Harris, C., et al. (2021) Statins Are As-sociated with Increased Insulin Resistance and Secretion. Arteriosclerosis, Thrombosis, and Vascular Biology, 41, 2786-2797. [Google Scholar] [CrossRef
[24] Mansi, I., Chansard, M., Lingvay, I., et al. (2021) Associa-tion of Statin Therapy Initiation with Diabetes Progression: A Retrospective Matched-Cohort Study. JAMA Internal Medicine, 181, 1562-1574. [Google Scholar] [CrossRef] [PubMed]
[25] Wang, H.J., Park, J.Y., Kwon, O., et al. (2015) Chronic HMGCR/HMG-CoA Reductase Inhibitor Treatment Contributes to Dysglycemia by Upregulating Hepatic Gluconeo-genesis through Autophagy Induction. Autophagy, 11, 2089-2101. [Google Scholar] [CrossRef] [PubMed]
[26] Henriksbo, B.D., Lau, T.C., Cavallari, J.F., et al. (2014) Fluvastatin Causes NLRP3 Inflammasome-Mediated Adipose Insulin Resistance. Diabetes, 63, 3742-3747. [Google Scholar] [CrossRef] [PubMed]
[27] Henriksbo, B.D., Tamrakar, A.K., Xu, J., et al. (2019) Statins Promote In-terleukin-1β-Dependent Adipocyte Insulin Resistance through Lower Prenylation, Not Cholesterol. Diabetes, 68, 1441-1448. [Google Scholar] [CrossRef] [PubMed]
[28] Taniguchi, C., Emanuelli, B. and Kahn, C. (2006) Critical Nodes in Signal-ling Pathways: Insights into Insulin Action. Nature Reviews Molecular Cell Biology, 7, 85-96. [Google Scholar] [CrossRef] [PubMed]
[29] Hwang, J.-H., Kim, A.R., Kim, K.M., et al. (2019) TAZ Couples Hippo/Wnt Signalling and Insulin Sensitivity through Irs1 Expression. Nature Communications, 10, Article No. 421. [Google Scholar] [CrossRef] [PubMed]
[30] Yoon, J.C., Ng, A., Kim, B.H., et al. (2010) Wnt Signaling Reg-ulates Mitochondrial Physiology and Insulin Sensitivity. Genes & Development, 24, 1507-1518. [Google Scholar] [CrossRef] [PubMed]
[31] Azzolin, L., Zanconato, F., Bresolin, S., et al. (2012) Role of TAZ as Mediator of Wnt Signaling. Cell, 151, 1443-1456. [Google Scholar] [CrossRef] [PubMed]
[32] Chamberlain, L.H. (2001) Inhibition of Isoprenoid Biosynthesis Causes Insulin Resistance in 3T3-L1 Adipocytes. FEBS Letters, 507, 357-361. [Google Scholar] [CrossRef
[33] Sanvee, G.M., Panajatovic, M.V., Bouitbir, J. and Krähen-bühl, S. (2019) Mechanisms of Insulin Resistance by Simvastatin in C2C12 Myotubes and in Mouse Skeletal Muscle. Biochemical Pharmacology, 164, 23-33. [Google Scholar] [CrossRef] [PubMed]
[34] Shen, L., Gu, Y., Qiu, Y., et al. (2020) Atorvastatin Targets the Islet Mevalonate Pathway to Dysregulate mTOR Signaling and Reduce β-Cell Functional Mass. Diabetes, 69, 48-59. [Google Scholar] [CrossRef] [PubMed]
[35] Urbano, F., Bugliani, M., Filippello, A., et al. (2017) Atorvastatin but Not Pravastatin Impairs Mitochondrial Function in Human Pancreatic Islets and Rat β-Cells. Direct Effect of Oxidative Stress. Scientific Reports, 7, Article No. 11863. [Google Scholar] [CrossRef] [PubMed]
[36] Iwen, K., Backhaus, J., Cassens, M., et al. (2017) Cold-Induced Brown Adipose Tissue Activity Alters Plasma Fatty Acids and Improves Glucose Metabolism in Men. The Journal of Clinical Endocrinology and Metabolism, 102, 4226-4234. [Google Scholar] [CrossRef] [PubMed]
[37] Balaz, M., Becker, .A, Balazova, L., et al. (2019) Inhibition of Mevalonate Pathway Prevents Adipocyte Browning in Mice and Men by Affecting Protein Prenylation. Cell Metabolism, 29, 901-916. [Google Scholar] [CrossRef] [PubMed]
[38] Cheng, D., Wang, Y., Gao, S., et al. (2015) Atorvastatin Delays the Glucose Clearance Rate in Hypercholesterolemic Rabbits. Biomedicine & Pharmacotherapy, 72, 24-29. [Google Scholar] [CrossRef] [PubMed]
[39] Ochoa-Rosales, C., Portilla-Fernandez, E., Nano, J., et al. (2020) Epigenetic Link between Statin Therapy and Type 2 Diabetes. Diabetes Care, 43, 875-884. [Google Scholar] [CrossRef] [PubMed]
[40] Ge, L., Wang, J., Qi, W., et al. (2008) The Cholesterol Absorption Inhibitor Ezetimibe Acts by Blocking the Sterol- Induced Internalization of NPC1L1. Cell Metabolism, 7, 508-519. [Google Scholar] [CrossRef] [PubMed]
[41] Lee, J., Lee, S.H., Kim, H., et al. (2021) Low-Density Lipoprotein Cholesterol Reduction and Target Achievement after Switching from Statin Monotherapy to Statin/Ezetimibe Combina-tion Therapy: Real-World Evidence. Journal of Clinical Pharmacy and Therapeutics, 46, 134-142. [Google Scholar] [CrossRef] [PubMed]
[42] Lin Wu, F.-L., Wang, J., Ho, W., et al. (2017) Effectiveness of a Combina-tion of Ezetimibe and Statins in Patients with Acute Coronary Syndrome and Multiple Comorbidities: A 6-Year Popula-tion-Based Cohort Study. International Journal of Cardiology, 233, 43-51. [Google Scholar] [CrossRef] [PubMed]
[43] Kim, B.-K., Hong, S.-J., Lee, Y.-J., et al. (2022) Long-Term Ef-ficacy and Safety of Moderate-Intensity Statin with Ezetimibe Combination Therapy versus High-Intensity Statin Mono-therapy in Patients with Atherosclerotic Cardiovascular Disease (RACING): A Randomised, Open-Label, Non-Inferiority Trial. Lancet, 400, 380-390. [Google Scholar] [CrossRef
[44] Chiu, S.W., Pratt, C.M., Feinn, R. and Chatterjee, S. (2020) Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors and Ezetimibe on Risk of New-Onset Diabetes: A Systematic Review and Meta-Analysis of Large, Double-Blinded Randomized Controlled Trials. Journal of Cardiovascular Phar-macology and Therapeutics, 25, 409-417. [Google Scholar] [CrossRef] [PubMed]
[45] Wu, H., Shang, H. and Wu, J. (2018) Effect of Ezetimibe on Glycemic Control: A Systematic Review and Meta- Analysis of Randomized Controlled Trials. Endocrine, 60, 229-239. [Google Scholar] [CrossRef] [PubMed]
[46] Cho, Y., Kim, R.-H., Park, H., et al. (2020) Effect of Ezetimibe on Glucose Metabolism and Inflammatory Markers in Adipose Tissue. Biomedicines, 8, Article No. 512. [Google Scholar] [CrossRef] [PubMed]
[47] Sabatine, M.S., Giugliano, R.P., Keech, A.C., et al. (2017) Evolocumab and Clinical Outcomes in Patients with Cardiovascular Disease. The New England Journal of Medicine, 376, 1713-1722. [Google Scholar] [CrossRef
[48] O’Donoghue, M., Giugliano, R., Wiviott, S., et al. (2022) Long-Term Evolocumab in Patients with Established Atherosclerotic Cardiovascular Disease. Circulation, 146, 1109-1119. [Google Scholar] [CrossRef
[49] Bittner, V., Szarek, M., Aylward, P., et al. (2020) Effect of Alirocumab on Lipoprotein(a) and Cardiovascular Risk After Acute Coronary Syndrome. Journal of the Amer-ican College of Cardiology, 75, 133-144. [Google Scholar] [CrossRef] [PubMed]