脂蛋白a与中青年冠心病的研究进展
Study on the Correlation between Lipoprotein a and Coronary Heart Disease in Young- and Middle-Aged People
DOI: 10.12677/acm.2024.1451650, PDF,   
作者: 郭明燕, 刘 东*:西安医学院研究生工作部,陕西 西安
关键词: 中青年冠心病脂蛋白a治疗Young- and Middle-Aged Coronary Heart Disease Lipoprotein a Treatment
摘要: 近年来,尽管我国医疗水平得到高速发展,在冠状动脉粥样硬化的预防和治疗方面取得显著进展,冠心病的死亡率呈现降低趋势。然而中青年的冠心病死亡率并未得到明显实质性改善。作为CAD独立危险因素的Lp(a),不同于其他血脂,因其水平不能通过传统的生活方式干预和他汀类药物治疗来改变,因此被认为是比LDL更危险的胆固醇。目前能够远期且显著使Lp(a)水平保持较低水准的治疗方案相对缺乏,因此将Lp(a)作为新的治疗靶点,以此降低心血管事件风险具有重要临床意义及研究价值。
Abstract: In recent years, despite the rapid development of China’s medical level, remarkable progress has been made in the prevention and treatment of coronary atherosclerosis, and the mortality rate of coronary heart disease has shown a decreasing trend. However, coronary heart disease mortality in young- and middle-aged people has not been significantly improved. Lp(a), as an independent risk factor for CAD, differs from other lipids in which its levels cannot be altered by traditional lifestyle interventions and statin therapy, and is therefore considered a more dangerous cholesterol than LDL. At present, there is a relative lack of long-term treatment options that can significantly keep Lp(a) level low, so it is of great clinical significance and research value to use Lp(a) as a new therapeutic target to reduce the risk of cardiovascular events.
文章引用:郭明燕, 刘东. 脂蛋白a与中青年冠心病的研究进展[J]. 临床医学进展, 2024, 14(5): 2054-2062. https://doi.org/10.12677/acm.2024.1451650

参考文献

[1] 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2022概要[J]. 中国循环杂志, 2023, 38(6): 583-612.
[2] Arora, S., Stouffer, G.A., Kucharska-Newton, A., et al. (2019) Twenty Year Trends and Sex Differences in Young Adults Hospitalized with Acute Myocardial Infarction: The ARIC Community Surveillance Study. Circulation, 138, 1047-1056. [Google Scholar] [CrossRef
[3] Ahmad, O., Boschipinto, C., Lopez, A., et al. (2001) Age Standardization of Rates: A New WHO Standard. Global Programme on Evidence for Health Policy Discussion Paper Series: No. 31. [Google Scholar] [CrossRef
[4] Smith, C.L., Seigerman, M., Adusumalli, S., et al. (2021) Evolution and Outcomes of Premature Coronary Artery Disease. Current Cardiology Reports, 23, Article No. 36. [Google Scholar] [CrossRef] [PubMed]
[5] Wang, X., Gao, M., Zhou, S., et al. (2017) Trend in Young Coronary Artery Disease in China from 2010 to 2014: A Retrospective Study of Young Patients  ≤  45. BMC Cardiovascular Disorders, 17, Article No. 18. [Google Scholar] [CrossRef] [PubMed]
[6] Hoogeveen, R.C. and Ballantyne, C.M. (2021) Residual Cardiovascular Risk at Low LDL: Remnants, Lipoprotein(a), and Inflammation. Clinical Chemistry, 67, 143-153. [Google Scholar] [CrossRef] [PubMed]
[7] Tada, H., Takamura, M. and Kawashiri, M.A. (2019) Lipoprotein(a) as an Old and New Causal Risk Factor of Atherosclerotic Cardiovascular Disease. Journal of Atherosclerosis and Thrombosis, 26, 583-591. [Google Scholar] [CrossRef
[8] Burgess, S., Ference, B.A., et al. (2018) Association of LPA Variants with Risk of Coronary Disease and the Implications for Lipoprotein(a)-Lowering Therapies: A Mendelian Randomization Analysis. JAMA Cardiology, 3, 619-627. [Google Scholar] [CrossRef] [PubMed]
[9] Nordestgaard, B.G. and Langsted, A. (2016) Thematic Review Series: Lipoprotein (a): Coming of Age at Last: Lipoprotein (a) as a Cause of Cardiovascular Disease: Insights from Epidemiology, Genetics, and Biology. Journal of Lipid Research, 57, 1953-1975. [Google Scholar] [CrossRef
[10] Enas, E.A., Varkey, B., Dharmarajan, T.S., Pare, G. and Bahl, V.K. (2019) Lipoprotein(a): An Independent, Genetic, and Causal Factor for Cardiovascular Disease and Acute Myocardial Infarction. Indian Heart Journal, 71, 99-112. [Google Scholar] [CrossRef] [PubMed]
[11] 周鹏, 王烁, 任艳玲. 冠心病患者冠状动脉CT特征与血清脂蛋白(a)、脂联素、PTX3的相关性研究[J]. 分子诊断与治疗杂志, 2020, 12(2): 244-248.
[12] 桑国耀, 王丽娟, 张裕祥. 血清sCD14、Lp(a)、Gal-3与冠状动脉粥样硬化血管内皮功能及斑块易损性的关系分析[J]. 临床和实验医学杂志, 2023, 22(18): 1929-1934.
[13] Kaiser, Y., Daghem, M., Tzolos, E., et al. (2022) Association of Lipoprotein(a) with Atherosclerotic Plaque Progression. Journal of the American College of Cardiology, 79, 223-233. [Google Scholar] [CrossRef] [PubMed]
[14] Chua, S.K., Hung, H.F., Shyu, K.G., et al. (2010) Acute ST-Elevation Myocardial Infarction in Young Patients: 15 Years of Experience in a Single Center. Clinical Cardiology, 33, 140-148. [Google Scholar] [CrossRef] [PubMed]
[15] Zeitouni, M., Clare, R.M., Chiswell, K., et al. (2020) Risk Factor Burden and Long-Term Prognosis of Patients with Premature Coronary Artery Disease. Journal of the American Heart Association, 9, e017712. [Google Scholar] [CrossRef
[16] 郑刚. 冠状动脉粥样硬化斑块特征与临床预后相关性研究的进展[J]. 中华老年心脑血管病杂志, 2020, 22(3): 317-320.
[17] 申华, 张黛, 杜俣, 等. 光学相干断层成像下青年女性急性冠状动脉综合征患者的斑块特征分析[J]. 心肺血管病杂志, 2019, 38(4): 365-369.
[18] Rallidis, L.S., Pavlakis, G., Foscolou, A., et al. (2018) High Levels of Lipoprotein (a) and Premature Acute Coronary Syndrome. Atherosclerosis, 269, 29-34. [Google Scholar] [CrossRef] [PubMed]
[19] 付琳, 李瑾. 载脂蛋白基因多态性与冠心病发病风险关系的研究进展[J]. 中西医结合心脑血管病杂志, 2022, 20(4): 667-672.
[20] 北京心脏学会. 脂蛋白(a)与心血管疾病风险关系及临床管理的专家科学建议[J]. 中国循环杂志, 2021, 36(12): 1158-1167.
[21] Zekavat, S.M., Ruotsalainen, S., Handsaker, R.E., et al. (2020) Publisher Correction: Deep Coverage Whole Genome Sequences and Plasma Lipoprotein(a) in Individuals of European and African Ancestries. Nature Communications, 11, Article No. 1715. [Google Scholar] [CrossRef] [PubMed]
[22] Cybulska, B., Kosiewicz-Latoszek, L., Penson, P.E., et al. (2020) What Do We Know About The Role of Lipoprotein(a) in Atherogenesis 57 Years after Its Discovery? Progress in Cardiovascular Diseases, 63, 219-227. [Google Scholar] [CrossRef] [PubMed]
[23] Sharma, M., Redpath, G.M., Williams, M.J.A., et al. (2017) Recycling of Apolipoprotein(a) after PlgRKT-Mediated Endocytosis Lipoprotein(a). Circulation Research, 120, 1091-1102. [Google Scholar] [CrossRef
[24] Marcovina, S.M. and Albers, J.J. (2016) Lipoprotein(a) Measurements for Clinical Application. Journal of Lipid Research, 57, 526-537. [Google Scholar] [CrossRef
[25] Tsimikas, S. (2017) A Test in Context: Lipoprotein(a): Diagnosis, Prognosis, Controversies, and Emerging Therapies. Journal of the American College of Cardiology, 69, 692-711. [Google Scholar] [CrossRef] [PubMed]
[26] Kronenberg, F., Mora, S., Stroes, E.S.G., et al. (2022) Lipoprotein(a) in Atherosclerotic Cardiovascular Disease and Aortic Stenosis: A European Atherosclerosis Society Consensus Statement. European Heart Journal, 43, 3925-3946. [Google Scholar] [CrossRef] [PubMed]
[27] Björnson, E., Adiels, M., Taskinen, M.R., et al. (2024) Lipoprotein(a) Is Markedly More Atherogenic than LDL: An Apolipoprotein B-Based Genetic Analysis. Journal of the American College of Cardiology, 83, 385-395. [Google Scholar] [CrossRef] [PubMed]
[28] Marston, N.A., Melloni, G.E.M., Murphy, S.A.,et al. (2024) Per-Particle Cardiovascular Risk of Lipoprotein(a) vs Non-Lp(a) Apolipoprotein B-Containing Lipoproteins. Journal of the American College of Cardiology, 83, 470-472. [Google Scholar] [CrossRef] [PubMed]
[29] Tsimikas, S. and Bittner, V. (2024) Particle Number and Characteristics of Lipoprotein(a), LDL, and apoB: Perspectives on Contributions to ASCVD. Journal of the American College of Cardiology, 83, 396-400. [Google Scholar] [CrossRef] [PubMed]
[30] Kiechl, S. and Willeit, J. (2010) The Mysteries of Lipoprotein(a) and Cardiovascular Disease Revisited. Journal of the American College of Cardiology, 55, 2168-2170. [Google Scholar] [CrossRef] [PubMed]
[31] Labudovic, D., Kostovska, I., Trajkovska, K.T., et al. (2019) Lipoprotein(a)—Link between Atherogenesis and Thrombosis. Prague Medical Report, 120, 39-51. [Google Scholar] [CrossRef] [PubMed]
[32] Sabbah, N., Jaisson, S., Garnotel, R., et al. (2019) Small Size Apolipoprotein(a) Isoforms Enhance Inflammatory and Proteolytic Potential of Collagen-Primed Monocytes. Lipids in Health and Disease, 18, Article No. 166. [Google Scholar] [CrossRef] [PubMed]
[33] Jang, A.Y., Han, S.H., Sohn, I.S., et al. (2020) Lipoprotein(a) and Cardiovascular Diseases—Revisited. Circulation Journal, 84, 867-874. [Google Scholar] [CrossRef
[34] Van Der Valk, F.M., Bekkering, S., Kroon, J., et al. (2016) Oxidized Phospholipids on Lipoprotein(a) Elicit Arterial Wall Inflammation and an Inflammatory Monocyte Response in Humans. Circulation, 134, 611-624. [Google Scholar] [CrossRef
[35] Knig, M., Joshi, S., Leistner, D.M., et al. (2019) Cohort Profile: Role of Lipoproteins in Cardiovascular Disease—The LipidCardio Study. BMJ Open, 9, e030097. [Google Scholar] [CrossRef] [PubMed]
[36] Coassin, S. and Kronenberg, F. (2022) Lipoprotein(a) beyond the Kringle IV Repeat Polymorphism: The Complexity of Genetic Variation in the LPA Gene. Atherosclerosis, 349, 17-35. [Google Scholar] [CrossRef] [PubMed]
[37] Schmidt, K., Noureen, A., Kronenberg, F. and Utermann, G. (2016) Structure, Function, and Genetics of Lipoprotein(a). Journal of Lipid Research, 57, 1339-1359. [Google Scholar] [CrossRef
[38] Ruscica, M., Sirtori, C., Corsini, A., et al. (2021) Lipoprotein(a): Knowns, Unknowns and Uncertainties. Pharmacological Research, 173, Article ID: 105812. [Google Scholar] [CrossRef] [PubMed]
[39] Emdin, C.A., Khera, A.V., Natarajan, P., et al. (2016) Phenotypic Characterization of Genetically Lowered Human Lipoprotein(a) Levels. Journal of the American College of Cardiology, 68, 2761-2772. [Google Scholar] [CrossRef] [PubMed]
[40] Thanassoulis, G., Campbell, C.Y., Owens, D.S., et al. (2013) Genetic Associations with Valvular Calcification and Aortic Stenosis. The New England Journal of Medicine, 368, 503-512. [Google Scholar] [CrossRef
[41] Jubran, A., Zetser, A. and Zafrir, B. (2019) Lipoprotein(a) Screening in Young and Middle-Aged Patients Presenting with Acute Coronary Syndrome. Cardiology Journal, 26, 511-518. [Google Scholar] [CrossRef
[42] Zewinger, S., Kleber, M.E., Tragante, V., et al. (2017) Relations between Lipoprotein(a) Concentrations, LPA Genetic Variants, and the Risk of Mortality in Patients with Established Coronary Heart Disease: A Molecular and Genetic Association Study. The Lancet Diabetes & Endocrinology, 5, 534-543. [Google Scholar] [CrossRef
[43] Mack, S., Coassin, S., Rueedi, R., et al. (2017) A Genome-Wide Association Meta-Analysis on Lipoprotein(a) Concentrations Adjusted for Apolipoprotein(a) Isoforms. Journal of Lipid Research, 58, 1834-1844. [Google Scholar] [CrossRef
[44] Zhao, J., Feng, Q.P., Wu, P., et al. (2018) Using Topic Modeling via Non-Negative Matrix Factorization to Identify Relationships between Genetic Variants and Disease Phenotypes: A Case Study of Lipoprotein(a) (LPA). Cold Spring Harbor Laboratory, 14, e0212112. [Google Scholar] [CrossRef
[45] Erbel, R. and Budoff, M. (2012) Improvement of Cardiovascular Risk Prediction Using Coronary Imaging: Subclinical Atherosclerosis: The Memory of Lifetime Risk Factor Exposure. European Heart Journal, 33, 1201-1213. [Google Scholar] [CrossRef] [PubMed]
[46] Cardoso-Saldaa, G., Fragoso, J.M., Lale-Farjat, S., et al. (2019) The Rs10455872-G Allele of the LPA Gene Is Associated with High Lipoprotein(a) Levels and Increased Aortic Valve Calcium in a Mexican Adult Population. Genetics and Molecular Biology, 42, 519-525. [Google Scholar] [CrossRef] [PubMed]
[47] Arsenault, B.J., Boekholdt, S.M., Dubé, M.P., et al. (2014) Lipoprotein(a) Levels, Genotype, and Incident Aortic Valve Stenosis a Prospective Mendelian Randomization Study and Replication in a Case-Control Cohort. Circulation: Cardiovascular Genetics, 7, 304-310. [Google Scholar] [CrossRef
[48] Pechlivanis, S., Mahabadi, A.A., Hoffmann, P., et al. (2020) Association between Lipoprotein(a) (Lp(a)) Levels and Lp(a) Genetic Variants with Coronary Artery Calcification. BMC Medical Genetics, 21, Article No. 62. [Google Scholar] [CrossRef] [PubMed]
[49] Gencer, B., Kronenberg, F., Stroes, E.S., et al. (2017) Lipoprotein(a): The Revenant. European Heart Journal, 38, 1553-1560. [Google Scholar] [CrossRef] [PubMed]
[50] Claudia, L., Kronenberg, F., et al. (2019) Estimation of the Required Lipoprotein(a)-Lowering Therapeutic Effect Size for Reduction in Coronary Heart Disease Outcomes—A Mendelian Randomization Analysis. JAMA Cardiology, 4, 575-579. [Google Scholar] [CrossRef] [PubMed]
[51] Reyes-Soffer, G., Ginsberg, H.N., 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 Biology, 42, e48-e60. [Google Scholar] [CrossRef
[52] Farmakis, I., Doundoulakis, I., Pagiantza, A., et al. (2021) Lipoprotein(a) Reduction with Proprotein Convertase Subtilisin/Kexin Type 9 Inhibitors: A Systematic Review and Meta-Analysis. Journal of Cardiovascular Pharmacology, 77, 397-407. [Google Scholar] [CrossRef
[53] Ruscica, M., Tokgozoglu, L., Corsini, A., et al. (2019) PCSK9 Inhibition and Inflammation: A Narrative Review. Atherosclerosis, 288, 146-155. [Google Scholar] [CrossRef] [PubMed]
[54] Parish, S., Hopewell, J.C., Hill, M.R., et al. (2018) Impact of Apolipoprotein(a) Isoform Size on Lipoprotein(a) Lowering in the HPS2-THRIVE Study. Circulation: Genomic and Precision Medicine, 11, e001696. [Google Scholar] [CrossRef
[55] Nissen, S., Wolski, K., Balog, C., et al. (2022) Single Ascending Dose Study of a Short Interfering RNA Targeting Lipoprotein(a) Production in Individuals with Elevated Plasma Lipoprotein(a) Levels. JAMA, 327, 1679-1687. [Google Scholar] [CrossRef] [PubMed]
[56] Mehta, A. and Shapiro, M.D. (2022) Apolipoproteins in Vascular Biology and Atherosclerotic Disease. Nature Reviews Cardiology, 19, 168-179. [Google Scholar] [CrossRef] [PubMed]