随着全球人口老龄化的日益加重,钙化性主动脉瓣疾病(CAVD)已成为一种常见的心血管疾病。目前尚无药物治疗或延缓疾病的进展,外科主动脉瓣置换术(AVR)是有效治疗手段。CAVD与动脉粥样硬化有着相似的病理生理过程,与脂质代谢异常、慢性炎症密切相关。既往研究证实,脂蛋白(a)、炎症反应在主动脉瓣钙化过程中起着关键作用。本文主要简述了脂蛋白(a)、NLR、PLR与CAVD的相关性及发病机制,为CAVD的预防和治疗提供新的参考依据。
Calcified aortic valve disease (CAVD) has become a common cardiovascular disease with the in-creasing aging of the global population. There are currently no drugs to treat or slow the progres-sion of the disease, surgical aortic valve replacement (AVR) is an effective treatment. CAVD has a similar pathophysiological process with atherosclerosis, and is closely related to abnormal lipid metabolism and chronic inflammation. Previous studies have confirmed that lipoprotein (a) and in-flammatory response play key roles in the process of aortic valve calcification. In this paper, the correlation and pathogenesis of CAVD between lipoprotein (a), neutrophil-lymphocyte ratio, plate-let-lymphocyte ratio was briefly reviewed, providing a new reference for the prevention and treat-ment of CAVD.
Calcified aortic valve disease (CAVD) has become a common cardiovascular disease with the increasing aging of the global population. There are currently no drugs to treat or slow the progression of the disease, surgical aortic valve replacement (AVR) is an effective treatment. CAVD has a similar pathophysiological process with atherosclerosis, and is closely related to abnormal lipid metabolism and chronic inflammation. Previous studies have confirmed that lipoprotein (a) and inflammatory response play key roles in the process of aortic valve calcification. In this paper, the correlation and pathogenesis of CAVD between lipoprotein (a), neutrophil-lymphocyte ratio, platelet-lymphocyte ratio was briefly reviewed, providing a new reference for the prevention and treatment of CAVD.
张 萍,张亚萍. Lp(a)、NLR、PLR与钙化性主动脉瓣疾病的研究进展Research Progress of Lipoprotein (a), Neutrophil-Lymphocyte Ratio, Platelet-Lymphocyte Ratio and Calcified Aortic Valve Disease[J]. 临床医学进展, 2022, 12(10): 9104-9110. https://doi.org/10.12677/ACM.2022.12101316
参考文献ReferencesFurukawa, K. (2014) Recent Advances in Research on Human Aortic Valve Calcification. Journal of Pharmacological Sciences, 124, 129-137. <br>https://doi.org/10.1254/jphs.13R05CROtto, C. and Prendergast, B. (2014) Aor-tic-Valve Stenosis—From Patients at Risk to Severe Valve Obstruction. The New England Journal of Medicine, 371, 744-756. <br>https://doi.org/10.1056/NEJMra1313875Nishimura, R., Otto, C., Bonow, R., et al. (2017) 2017 AHA/ACC Focused Update of the 2014 AHA/ACC Guideline for the Management of Patients with Valvular Heart Dis-ease: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation, 135, e1159-e1195.
<br>https://doi.org/10.1161/CIR.0000000000000503Yutzey, K., Demer, L., Body, S., et al. (2014) Calcific Aortic Valve Disease: A Consensus Summary from the Alliance of Investigators on Calcific Aortic Valve Disease. Arterioscle-rosis, Thrombosis, and Vascular Biology, 34, 2387-2393.
<br>https://doi.org/10.1161/ATVBAHA.114.302523Small, A., Kiss, D., Giri, J., et al. (2017) Biomarkers of Cal-cific Aortic Valve Disease. Arteriosclerosis, Thrombosis, and Vascular Biology, 37, 623-632. <br>https://doi.org/10.1161/ATVBAHA.116.308615Erqou, S., Kaptoge, S., Perry, P., et al. (2009) Lipoprotein (a) Concentration and the Risk of Coronary Heart Disease, Stroke, and Nonvascular Mortality. JAMA, 302, 412-423. <br>https://doi.org/10.1001/jama.2009.1063Jang, A., Han, S., Sohn, I., et al. (2020) Lipoprotein (a) and Cardio-vascular Diseases-Revisited. Circulation Journal, 84, 867-874. <br>https://doi.org/10.1253/circj.CJ-20-0051Schmidt, K., Noureen, A., Kronenberg, F., et al. (2016) Structure, Function, and Genetics of Lipoprotein (a). Journal of Lipid Research, 57, 1339-1359. <br>https://doi.org/10.1194/jlr.R067314Arsenault, B., Boekholdt, S., Dubé, M., et al. (2014) Lipoprotein (a) Lev-els, Genotype, and Incident Aortic Valve Stenosis: A Prospective Mendelian Randomization Study and Replication in a Case-Control Cohort. Circulation. Cardiovascular Genetics, 7, 304-310. <br>https://doi.org/10.1161/CIRCGENETICS.113.000400Stewart, B.F., Siscovick, D., Lind, B.K., et al. (1997) Clinical Factors Associated with Calcific Aortic Valve Disease fn1fn1This Study Was Supported in Part by Contracts NO1-HC85079 through HC-850086 from the National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland. Journal of the American College of Cardiology, 29, 630-634. <br>https://doi.org/10.1016/S0735-1097(96)00563-3Zheng, K., Arsenault, B., Kaiser, Y., et al. (2019) ApoB/ApoA-I Ratio and Lp(a) Associations with Aortic Valve Stenosis Incidence: Insights from the EPIC-Norfolk Prospective Population Study. Journal of the American Heart Association, 8, e013020. <br>https://doi.org/10.1161/JAHA.119.013020Kamstrup, P., Hung, M., Witztum, J., et al. (2017) Oxidized Phospholipids and Risk of Calcific Aortic Valve Disease: The Copenhagen General Population Study. Arteriosclerosis, Thrombosis, and Vascular Biology, 37, 1570-1578.
<br>https://doi.org/10.1161/ATVBAHA.116.308761刘硕霖. 脂蛋白(a)与主动脉瓣钙化的相关性研究[D]: [硕士学位论文]. 北京: 北京协和医学院, 2020.Losi, M., Brevetti, G., Schiano, V., et al. (2010) Aortic Valve Sclerosis in Patients with Peripheral and/or Coronary Arterial Disease. Echocardiography, 27, 608-612. <br>https://doi.org/10.1111/j.1540-8175.2009.01109.xSzolc, P., Niewiara, Ł., Kawulak, M., et al. (2020) Neu-trophil-Lymphocyte Ratio and Platelet-Lymphocyte Ratio as Predictors of Coronary Microcirculatory Disease Occurrence and Outcome in Patients with Chronic Coronary Syndrome and No Significant Coronary Artery Stenosis. Wiadomosci lekarskie (Warsaw, Poland: 1960), 73, 2598-2606.
<br>https://doi.org/10.36740/WLek202012108Avci, A., Elnur, A., Göksel, A., et al. (2014) The Relationship be-tween Neutrophil/Lymphocyte Ratio and Calcific Aortic Stenosis. Echocardiography, 31, 1031-1035. <br>https://doi.org/10.1111/echo.12534Küçükseymen, S., Çağırcı, G., Güven, R., et al. (2017) Is Neutrophyl to Lymphocyte Ratio Really a Useful Marker for All Grades of Degenerative Aortic Stenosis? Türk Kardiyoloji Derneği Arşivi, 45, 506-513.
<br>https://doi.org/10.5543/tkda.2017.32389Akdag, S., Akyol, A., Asker, M., et al. (2015) Plate-let-to-Lymphocyte Ratio May Predict the Severity of Calcific Aortic Stenosis. Medical Science Monitor: International Medical Journal of Experimental and Clinical Research, 21, 3395-3400. <br>https://doi.org/10.12659/MSM.894774Yayla, Ç., Açikgöz, S., Yayla, K., et al. (2016) The Association be-tween Platelet-to-Lymphocyte Ratio and Inflammatory Markers with the Severity of Aortic Stenosis. Biomarkers in Medicine, 10, 367-373.
<br>https://doi.org/10.2217/bmm-2015-0016Edem, E., Reyhanoğlu, H., Küçükukur, M., et al. (2016) Predictive Value of Platelet-to-Lymphocyte Ratio in Severe Degenerative Aortic Valve Stenosis. Journal of Research in Medical Sciences: The Official Journal of Isfahan University of Medical Sciences, 21, 93. <br>https://doi.org/10.4103/1735-1995.192509Bian, W., Wang, Z., Sun, C., et al. (2021) Pathogenesis and Mo-lecular Immune Mechanism of Calcified Aortic Valve Disease. Frontiers in Cardiovascular Medicine, 8, Article ID: 765419. <br>https://doi.org/10.3389/fcvm.2021.765419Pasipoularides, A. (2016) Calcific Aortic Valve Disease: Part 1—Molecular Pathogenetic Aspects, Hemodynamics, and Adaptive Feedbacks. Journal of Cardiovascular Transla-tional Research, 9, 102-118.
<br>https://doi.org/10.1007/s12265-016-9679-zIzquierdo-Gómez, M., Hernández-Betancor, I., García-Niebla, J., et al. (2017) Valve Calcification in Aortic Stenosis: Etiology and Diagnostic Imaging Techniques. BioMed Research In-ternational, 2017, Article ID: 5178631.
<br>https://doi.org/10.1155/2017/5178631Erhart, G., Lamina, C., Lehtimäki, T., et al. (2018) Genetic Factors Ex-plain a Major Fraction of the 50% Lower Lipoprotein(a) Concentrations in Finns. Arteriosclerosis, Thrombosis, and Vascular Biology, 38, 1230-1241.
<br>https://doi.org/10.1161/ATVBAHA.118.310865Mahmut, A., Boulanger, M., El Husseini, D., et al. (2014) Elevated Expression of Lipoprotein-Associated Phospholipase A2 in Calcific Aortic Valve Disease: Implications for Valve Mineralization. Journal of the American College of Cardiology, 63, 460-469. <br>https://doi.org/10.1016/j.jacc.2013.05.105Sun, W., Li, H., Yu, Y., et al. (2009) MEKK3 Is Required for Lysophosphatidic Acid-Induced NF-κB Activation. Cellular Signalling, 21, 1488-1494. <br>https://doi.org/10.1016/j.cellsig.2009.05.007Bouchareb, R., Mahmut, A., Nsaibia, M., et al. (2015) Autotaxin Derived from Lipoprotein (a) and Valve Interstitial Cells Promotes Inflammation and Mineralization of the Aortic Valve. Circulation, 13, 677-690.
<br>https://doi.org/10.1161/CIRCULATIONAHA.115.016757Libby, P. and Ridker, P. (2004) Inflammation and Atherosclerosis: Role of C-Reactive Protein in Risk Assessment. The American Journal of Medicine, 116, 9S-16S. <br>https://doi.org/10.1016/j.amjmed.2004.02.006Miller, J., Weiss, R. and Heistad, D. (2011) Calcific Aortic Valve Stenosis: Methods, Models, and Mechanisms. Circulation Research, 108, 1392-1412. <br>https://doi.org/10.1161/CIRCRESAHA.110.234138Bogdanova, M., Kostina, A., Zihlavnikova Enayati, K., et al. (2018) Inflammation and Mechanical Stress Stimulate Osteogenic Differentiation of Human Aortic Valve Interstitial Cells. Frontiers in Physiology, 9, Article No. 1635.
<br>https://doi.org/10.3389/fphys.2018.01635Açar, G., Kalkan, M., Avci, A., et al. (2015) The Relation of Plate-let-Lymphocyte Ratio and Coronary Collateral Circulation in Patients with Stable Angina Pectoris and Chronic Total Oc-clusion. Clinical and Applied Thrombosis/Hemostasis: Official Journal of the International Academy of Clinical and Ap-plied Thrombosis/Hemostasis, 21, 462-468. <br>https://doi.org/10.1177/1076029613508599Langer, H., Weber, C., Gawaz, M., et al. (2013) The Platelet—Thrombosis and Beyond. Thrombosis and Haemostasis, 110, 857-858. <br>https://doi.org/10.1160/TH13-09-0805Smyth, S., Mcever, R., Weyrich, A., et al. (2009) Platelet Functions beyond Hemostasis. Journal of Thrombosis and Haemostasis: JTH, 7, 1759-1766. <br>https://doi.org/10.1111/j.1538-7836.2009.03586.xBlackshear, J., Wysokinska, E., Safford, R., et al. (2013) Indexes of von Willebrand Factor as Biomarkers of Aortic Stenosis Severity (from the Biomarkers of Aortic Stenosis Severity [BASS] Study). The American Journal of Cardiology, 111, 374-381. <br>https://doi.org/10.1016/j.amjcard.2012.10.015Page, C. and Pitchford, S. (2013) Neutrophil and Platelet Com-plexes and Their Relevance to Neutrophil Recruitment and Activation. International Immunopharmacology, 17, 1176-1184. <br>https://doi.org/10.1016/j.intimp.2013.06.004Rossebø, A., Pedersen, T., Boman, K., et al. (2008) Intensive Lipid Lowering with Simvastatin and Ezetimibe in Aortic Stenosis. The New England Journal of Medicine, 359, 1343-1356. <br>https://doi.org/10.1056/NEJMoa0804602Chan, K., Teo, K., Dumesnil, J., et al. (2010) Effect of Lipid Lowering with Rosuvastatin on Progression of Aortic Stenosis: Results of the Aortic Stenosis Progression Obser-vation: Measuring Effects of Rosuvastatin (Astronomer) Trial. Circulation, 121, 306-314. <br>https://doi.org/10.1161/CIRCULATIONAHA.109.900027