Биомаркеры риска и прогноза при фибрилляции предсердий

Фибрилляция предсердий (ФП) – одна из наиболее распространенных форм аритмии, которая связана с повышенным риском инсульта, тромбоэмболии, а также увеличением смертности среди пациентов с сердечно-сосудистыми заболеваниями. Определение пациентов с высоким риском развития фибрилляции предсердий и прогнозирование вероятности острых нарушений мозгового кровообращения кардиоэмболического генеза, а также других тромбоэмболических осложнений являются ключевыми для оптимизации лечебных стратегий и профилактики осложнений. В статье представлен всеобъемлющий обзор существующих и новых биомаркеров, применяемых для оценки риска возникновения и рецидивирования фибрилляции предсердий, а также безопасности антикоагулянтной терапии при этой аритмии. Подробно рассматриваются генетические, воспалительные и метаболические маркеры, а также роль окислительного стресса в контексте патофизиологических процессов, клинических проявлений заболевания и его осложнений. Особое внимание уделено оценке маркеров, которые могут быть использованы для предсказания неблагоприятных исходов и повышения точности диагностики. Обсуждаются ограничения в возможностях рутинного и широкомасштабного использования как существующих, так и перспективных биомаркеров. Рассматривается их клиническая значимость, экономическая эффективность и возможности интеграции в повседневную клиническую практику. Подчеркивается необходимость стандартизации подходов к комплексной оценке биомаркеров, важность междисциплинарного сотрудничества и разработки индивидуализированных подходов к лечению пациентов с фибрилляцией предсердий, в том числе с использованием данных биомаркеров. Оптимизация подходов к обследованию пациентов с фибрилляцией предсердий с применением современных и перспективных биомаркеров может помочь преодолеть существующие ограничения и способствовать их внедрению в клиническую практику, что, в свою очередь, улучшит диагностику, лечение и прогнозы пациентов.

1. Lippi G, Sanchis-Gomar F, Cervellin G. Global epidemiology of atrial fibrillation: An increasing epidemic and public health challenge. Int J Stroke. 2021;16(2):217–221. https://doi.org/10.1177/1747493019897870.

2. Ионин ВА, Павлова ВА, Ананьин АМ, Барашкова ЕИ, Заславская ЕЛ, Морозов АН, Баранова ЕИ. Фибрилляция предсердий у пациентов с синдромом обструктивного апноэ во время сна и метаболическим синдромом: роль цитокинов в развитии фиброза миокарда левого предсердия. Артериальная гипертензия. 2022;28(4):405–418. https://doi.org/10.18705/1607-419X-2022-28-4-405-418.

3. Степаненко ИА, Сопова ДИ, Салухов ВВ, Заславская ЕЛ, Тарасов ВА, Новиков ИИ. Возможности скрининга бессимптомной фибрилляции предсердий в клинической практике. Фарматека. 2023;(1-2):117–127. https://doi.org/10.18565/pharmateca.2023.1-2.117-127.

4. Lip GYH, Collet JP, Haude M, Byrne R, Chung EH, Fauchier L et al. 2018 Joint European consensus document on the management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous cardiovascular interventions: a joint consensus document of the European Heart Rhythm Association (EHRA), European Society of Cardiology Working Group on Thrombosis, European Association of Percutaneous Cardiovascular Interventions (EAPCI), and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), Latin America Heart Rhythm Society (LAHRS), and Cardiac Arrhythmia Society of Southern Africa (CASSA). Europace. 2019;21(2):192–193. https://doi.org/10.1093/europace/euy174.

5. Shoamanesh A, Preis SR, Beiser AS, Kase CS, Wolf PA, Vasan RS et al. Circulating biomarkers and incident ischemic stroke in the Framingham Offspring Study. Neurology. 2016;87(12):1206–1211. https://doi.org/10.1212/WNL.0000000000003115.

6. Berg DD, Ruff CT, Morrow DA. Biomarkers for Risk Assessment in Atrial Fibrillation. Clin Chem. 2021;67(1):87–95. https://doi.org/10.1093/clinchem/hvaa298.

7. Hijazi Z, Oldgren J, Siegbahn A, Wallentin L. Application of Biomarkers for Risk Stratification in Patients with Atrial Fibrillation. Clin Chem. 2017;63(1):152–164. https://doi.org/10.1373/clinchem.

8. Noubiap JJ, Sanders P, Nattel S, Lau DH. Biomarkers in Atrial Fibrillation: Pathogenesis and Clinical Implications. Card Electrophysiol Clin. 2021;13(1):221–133. https://doi.org/10.1016/j.ccep.2020.10.006.

9. Yenikomshian M, Jarvis J, Patton C, Yee C, Mortimer R, Birnbaum H et al. Cardiac arrhythmia detection outcomes among patients monitored with the Zio patch system: a systematic literature review. Curr Med Res Opin. 2019;35(10):1659–1670. https://doi.org/10.1080/03007995.2019.1610370.

10. Аракелян МГ, Бокерия ЛА, Васильева ЕЮ, Голицын СП, Голухова ЕЗ, Горев МВ и др. Фибрилляция и трепетание предсердий. Клинические рекомендации 2020. Российский кардиологический журнал. 2021;26(7):4594. https://doi.org/10.15829/1560-4071-2021-4594.

11. Olesen JB, Lip GYH, Hansen ML, Hansen PR, Tolstrup JS, Lindhardsen J et al. Validation of risk stratification schemes for predicting stroke and thromboembolism in patients with atrial fibrillation: nationwide cohort study. BMJ. 2011;342:d124. https://doi.org/10.1136/bmj.d124.

12. Friberg L, Rosenqvist M, Lip GYH. Evaluation of risk stratification schemes for ischaemic stroke and bleeding in 182 678 patients with atrial fibrillation: the Swedish Atrial Fibrillation cohort study. Eur Heart J. 2012;33(12):1500–1510. https://doi.org/10.1093/eurheartj/ehr488.

13. Збышевская ЕВ, Макеева ТИ, Битакова ФИ, Бахолдина МН, Сивцова ЕВ, Семенова ГМ, Зайцева ОБ. Актуальные вопросы поражения сердечнососудистой системы у больных новой коронавирусной инфекцией COVID-19. Клинико-морфологическое исследование. Известия Российской военномедицинской академии. 2021;40(2);63–68. https://doi.org/10.17816/rmmar81196.

14. Broersen LHA, Stengl H, Nolte CH, Westermann D, Endres M, Siegerink B et al. Association Between High-Sensitivity Cardiac Troponin and Risk of Stroke in 96 702 Individuals: A Meta-Analysis. Stroke. 2020;51(4):1085–1093. https://doi.org/10.1161/STROKEAHA.119.028323.

15. Aimo A, Januzzi JL, Vergaro G, Ripoli A, Latini R, Masson S et al. Prognostic Value of High-Sensitivity Troponin T in Chronic Heart Failure: An Individual Patient Data Meta-Analysis. Circulation. 2018;137(3):286–297. https://doi.org/10.1161/CIRCULATIONAHA.117.031560.

16. Twerenbold R, Jaffe A, Reichlin T, Reiter M, Mueller C. High-sensitive troponin T measurements: what do we gain and what are the challenges? Eur Heart J. 2012;33(5):579-586. https://doi.org/10.1093/eurheartj/ehr492.

17. Schnabel RB, Wild PS, Wilde S, Ojeda FM, Schulz A, Zeller T et al. Multiple biomarkers and atrial fibrillation in the general population. PloS ONE. 2014;9(11):e112486. https://doi.org/10.1371/journal.pone.0112486.

18. Hijazi Z, Oldgren J, Andersson U, Connolly SJ, Ezekowitz MD, Hohnloser SH et al. Cardiac biomarkers are associated with an increased risk of stroke and death in patients with atrial fibrillation: a Randomized Evaluation of Long-term Anticoagulation Therapy (RE-LY) substudy. Circulation. 2012;125(13):1605–1616. https://doi.org/10.1161/CIRCULATIONAHA.111.038729.

19. Clerico A, Giannoni A, Vittorini S, Emdin M. The paradox of low BNP levels in obesity. Heart Fail Rev. 2012;17(1):81–96. https://doi.org/10.1007/s10741-011-9249-z.

20. Matsuura H, Murakami T, Hina K, Yamamoto K, Kawamura H, Sogo T et al. Association of elevated plasma B-type natriuretic peptide levels with paroxysmal atrial fibrillation in patients with nonobstructive hypertrophic cardiomyopathy. Clin Biochem. 2008;41(3):134–139. https://doi.org/10.1016/j.clinbiochem.2007.10.015.

21. Hijazi Z, Wallentin L, Siegbahn A, Andersson U, Christersson C, Ezekowitz J et al. N-terminal pro-B-type natriuretic peptide for risk assessment in patients with atrial fibrillation: insights from the ARISTOTLE Trial (Apixaban for the Prevention of Stroke in Subjects With Atrial Fibrillation). J Am Coll Cardiol. 2013;61(22):2274–2284. https://doi.org/10.1016/j.jacc.2012.11.082.

22. Healey JS, Alings M, Ha A, Leong-Sit P, Birnie DH, de Graaf JJ et al. Subclinical Atrial Fibrillation in Older Patients. Circulation. 2017;136(14):1276–1283. https://doi.org/10.1161/CIRCULATIONAHA.117.028845.

23. Крюков ЕВ, Прокофьев АБ, Данько АА, Дмитриев АИ, Мельников ЕС, Родина ТА, Белков СА. Возможности контроля эффективности и безопасности применения ривароксабана у пациентов, страдающих фибрилляцией предсердий. Вестник Российской военно-медицинской академии. 2021;23(2):9–16. https://doi.org/10.17816/brmma64961.

24. Hemker HC, Giesen P, AlDieri R, Regnault V, de Smed E, Wagenvoord R et al. The calibrated automated thrombogram (CAT): a universal routine test for hyperand hypocoagulability. Pathophysiol Haemost Thromb. 2002;32(5-6):249–253. https://doi.org/10.1159/000073575.

25. Крюков ЕВ, Кучмин АН, Уманская ЕП, Нагорный МБ, Шевелев АА, Рожкова АМ. Возможности антитромботической терапии у больных сахарным диабетом. Вестник Российской военно-медицинской академии. 2022;24(4):737–750. https://doi.org/10.17816/brmma108793.

26. Binder NB, Depasse F, Mueller J, Wissel T, Schwers S, Germer Mv Clinical use of thrombin generation assays. J Thromb Haemost. 2021;19(12):2918–2929. https://doi.org/10.1111/jth.15538.

27. Gardiner C, Coleman R, de Maat MPM, Dorgalaleh A, Echenagucia M, Gosselin RC et al. International Council for Standardization in Haematology (ICSH) laboratory guidance for the verification of haemostasis analyserreagent test systems. Part 2: Specialist tests and calibrated assays. Int J Lab Hematol. 2021;43(5):907–916. https://doi.org/10.1111/ijlh.13550.

28. Visscher PM, Wray NR, Zhang Q, Sklar P, McCarthy MI, Brown MA et al. 10 Years of GWAS Discovery: Biology, Function, and Translation. Am J Hum Genet. 2017;101(1):5–22. https://doi.org/10.1016/j.ajhg.2017.06.005.

29. Tam V, Patel N, Turcotte M, Bossé Y, Paré G, Meyre D. Benefits and limitations of genome-wide association studies. Nat Rev Genet. 2019;20(8):467–84. https://doi.org/10.1038/s41576-019-0127-1.

30. Ellinor PT, Lunetta KL, Glazer NL, Pfeufer A, Alonso A, Chung MK et al. Common variants in KCNN3 are associated with lone atrial fibrillation. Nat Genet. 2010;42(3):240–244. https://doi.org/10.1038/ng.537.

31. Low SK, Takahashi A, Ebana Y, Ozaki K, Christophersen IE, Ellinor PT et al. Identification of six new genetic loci associated with atrial fibrillation in the Japanese population. Nat Genet. 2017;49(6):953–958. https://doi.org/10.1038/ng.3842.

32. Nielsen JB, Thorolfsdottir RB, Fritsche LG, Zhou W, Skov MW, Graham SE et al. Biobank-driven genomic discovery yields new insight into atrial fibrillation biology. Nat Genet. 2018;50(9):1234–1239. https://doi.org/10.1038/s41588-018-0171-3.

33. Kirchhof P, Kahr PC, Kaese S, Piccini I, Vokshi I, Scheld HH et al. PITX2c is expressed in the adult left atrium, and reducing Pitx2c expression promotes atrial fibrillation inducibility and complex changes in gene expression. Circ Cardiovasc Genet. 2011;4(2):123–133. https://doi.org/10.1161/CIRCGENETICS.110.958058.

34. Tada H, Shiffman D, Smith JG, Sjögren M, Lubitz SA, Ellinor PT et al. Twelvesingle nucleotide polymorphism genetic risk score identifies individuals at increased risk for future atrial fibrillation and stroke. Stroke. 2014;45(10):2856–2862. https://doi.org/10.1161/STROKEAHA.114.006072.

35. Roselli C, Chaffin MD, Weng LC, Aeschbacher S, Ahlberg G, Albert CM et al. Multi-ethnic genome-wide association study for atrial fibrillation. Nat Genet. 2018;50(9):1225–1233. https://doi.org/10.1038/s41588-018-0133-9.

36. Christophersen IE, Rienstra M, Roselli C, Yin X, Geelhoed B, Barnard J et al. Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation. Nat Genet. 2017;49(6):946–852. https://doi.org/10.1038/ng.3843.

37. Sachidanandam R, Weissman D, Schmidt SC, Kakol JM, Stein LD, Marth G et al. A map of human genome sequence variation containing 1.42 million single nucleotide polymorphisms. Nature. 2001;409(6822):928–933. https://doi.org/10.1038/35057149.

38. Collins FS, Brooks LD, Chakravarti A. A DNA polymorphism discovery resource for research on human genetic variation. Genome Res. 1998;8(12):1229–1231. https://doi.org/10.1101/gr.8.12.1229.

39. Gudbjartsson DF, Arnar DO, Helgadottir A, Gretarsdottir S, Holm H, Sigurdsson A et al. Variants conferring risk of atrial fibrillation on chromosome 4q25. Nature. 2007;448(7151):353–357. https://doi.org/10.1038/nature06007.

40. Zhang XD, Timofeyev V, Li N, Myers RE, Zhang DM, Singapuri A et al. Critical roles of a small conductance Ca2+-activated K+ channel (SK3) in the repolarization process of atrial myocytes. Cardiovasc Res. 2014;101(2):317–325. https://doi.org/10.1093/cvr/cvt262.

41. Yang P, Kanki H, Drolet B, Yang T, Wei J, Viswanathan PC et al. Allelic variants in long-QT disease genes in patients with drug-associated torsades de pointes. Circulation. 2002;105(16):1943–1948. https://doi.org/10.1161/01.cir.0000014448.19052.4c.

42. Kushner I, Rzewnicki D, Samols D. What does minor elevation of C-reactive protein signify? Am J Med. 2006;119(2):166.E17–166.E28. https://doi.org/10.1016/j.amjmed.2005.06.057.

43. Emerging Risk Factors Collaboration, Kaptoge S, Di Angelantonio E, Lowe G, Pepys MB, Thompson SG et al. C-reactive protein concentration and risk of coronary heart disease, stroke, and mortality: an individual participant meta-analysis. Lancet Lond Engl. 2010;375(9709):132–140. https://doi.org/10.1016/S0140-6736(09)61717-7.

44. Aviles RJ, Martin DO, Apperson-Hansen C, Houghtaling PL, Rautaharju P, Kronmal RA et al. Inflammation as a risk factor for atrial fibrillation. Circulation. 2003;108(24):3006–3010. https://doi.org/10.1161/01.CIR.0000103131.70301.4F.

45. Conen D, Ridker PM, Everett BM, Tedrow UB, Rose L, Cook NR et al. A multimarker approach to assess the influence of inflammation on the incidence of atrial fibrillation in women. Eur Heart J. 2010;31(14):1730–1736. https://doi.org/10.1093/eurheartj/ehq146.

46. Ramlawi B, Otu H, Mieno S, Boodhwani M, Sodha NR, Clements RT et al. Oxidative stress and atrial fibrillation after cardiac surgery: a case-control study. Ann Thorac Surg. 2007;84(4):1166–1172. https://doi.org/10.1016/j.athoracsur.2007.04.126.

47. Hu YF, Chen YJ, Lin YJ, Chen SA. Inflammation and the pathogenesis of atrial fibrillation. Nat Rev Cardiol. 2015;12(4):230–243. https://doi.org/10.1038/nrcardio.2015.2.

48. Chua SK, Shyu KG, Lu MJ, Lien LM, Lin CH, Chao HH et al. Clinical utility of CHADS2 and CHA2DS2-VASc scoring systems for predicting postoperative atrial fibrillation after cardiac surgery. J Thorac Cardiovasc Surg. 2013;146(4):919–926. https://doi.org/10.1016/j.jtcvs.2013.03.040.

49. Guo Y, Lip GYH, Apostolakis S. Inflammation in atrial fibrillation. J Am Coll Cardiol. 2012;60(22):2263–2270. https://doi.org/10.1016/j.jacc.2012.04.063.

50. Rafaqat S, Afzal S, Khurshid H, Safdar S, Rafaqat S, Rafaqat S. The Role of Major Inflammatory Biomarkers in the Pathogenesis of Atrial Fibrillation. J Innov Card Rhythm Manag. 2022;13(12):5265–5277. https://doi.org/10.19102/icrm.2022.13125.

51. Hu X, Wang J, Li Y, Wu J, Qiao S, Xu S et al. The β-fibrinogen gene 455G/A polymorphism associated with cardioembolic stroke in atrial fibrillation with low CHA2DS2-VaSc score. Sci Rep. 2017;7(1):17517. https://doi.org/10.1038/s41598-017-17537-1.

52. Semczuk-Kaczmarek K, Płatek AE, Ryś A, Adamowicz J, Legosz P, Kotkowski M et al. CHA2DS2-VASc score and fibrinogen concentration in patients with atrial fibrillation. Adv Clin Exp Med. 2019;28(11):1451–1457. https://doi.org/10.17219/acem/104557.

53. Bao J, Gao Z, Hu Y, Liu W, Ye L, Wang L. Serum fibrinogen-to-albumin ratio predicts new-onset atrial fibrillation risk during hospitalization in patients with acute myocardial infarction after percutaneous coronary intervention: a retrospective study. BMC Cardiovasc Disord. 2023;23(1):432. https://doi.org/10.1186/s12872-023-03480-9.

54. Tilly MJ, Geurts S, Pezzullo AM, Bramer WM, de Groot NMS, Kavousi M, de Maat MPM. The association of coagulation and atrial fibrillation: a systematic review and meta-analysis. Europace. 2023;25(1):28–39. https://doi.org/10.1093/europace/euac130.

55. Ионин ВА, Барашкова ЕИ, Заславская ЕЛ, Нифонтов СЕ, Баженова ЕА, Беляева ОД, Баранова ЕИ. Биомаркеры воспаления, параметры, характеризующие ожирение и ремоделирование сердца, у пациентов с фибрилляцией предсердий и метаболическим синдромом. Российский кардиологический журнал. 2021;26(3):4343. https://doi.org/10.15829/1560-4071-2021-4343.

56. Lazzerini PE, Laghi-Pasini F, Acampa M, Srivastava U, Bertolozzi I, Giabbani B et al. Systemic Inflammation Rapidly Induces Reversible Atrial Electrical Remodeling: The Role of Interleukin-6-Mediated Changes in Connexin Expression. J Am Heart Assoc. 2019;8(16):e011006. https://doi.org/10.1161/JAHA.118.011006.

57. Крюков ЕВ, Черкашин ДВ, Кружалин ЕЕ, Кутелев ГГ, Аланичев АЕ. Роль воспаления в развитии фибрилляции предсердий. Вестник Российской военно-медицинской академии. 2023;25(1):107–120. https://doi.org/10.17816/brmma112458.

58. Von Vietinghoff S, Ley K. Interleukin 17 in vascular inflammation. Cytokine Growth Factor Rev. 2010;21(6):463–469. https://doi.org/10.1016/j.cytogfr.2010.10.003.

59. Racca V, Torri A, Grati P, Panzarino C, Marventano I, Saresella M et al. Inflammatory Cytokines During Cardiac Rehabilitation After Heart Surgery and Their Association to Postoperative Atrial Fibrillation. Sci Rep. 2020;10(1):8618. https://doi.org/10.1038/s41598-020-65581-1.

60. Azzi A. Oxidative Stress: What Is It? Can It Be Measured? Where Is It Located? Can It Be Good or Bad? Can It Be Prevented? Can It Be Cured? Antioxidants (Basel). 2022;11(8):1431. https://doi.org/10.3390/antiox11081431.

61. Korantzopoulos P, Letsas K, Fragakis N, Tse G, Liu T. Oxidative stress and atrial fibrillation: an update. Free Radic Res. 2018;52(11-12):1199–1209. https://doi.org/10.1080/10715762.2018.1500696.

62. De Lange P, Lombardi A, Silvestri E, Cioffi F, Giacco A, Iervolino S et al. Physiological Approaches Targeting Cellular and Mitochondrial Pathways Underlying Adipose Organ Senescence. Int J Mol Sci. 2023;24(14):11676. https://doi.org/10.3390/ijms241411676.

63. Shin SK, Cho HW, Song SE, Im SS, Bae JH, Song DK. Oxidative stress resulting from the removal of endogenous catalase induces obesity by promoting hyperplasia and hypertrophy of white adipocytes. Redox Biol. 2020;37:101749. https://doi.org/10.1016/j.redox.2020.101749.

64. Fillmore N, Mori J, Lopaschuk GD. Mitochondrial fatty acid oxidation alterations in heart failure, ischaemic heart disease and diabetic cardiomyopathy. Br J Pharmacol. 2014;171(8):2080–2090. https://doi.org/10.1111/bph.12475.

65. Wiersma M, van Marion DMS, Wüst RCI, Houtkooper RH, Zhang D, de Groot NMS et al. Mitochondrial Dysfunction Underlies Cardiomyocyte Remodeling in Experimental and Clinical Atrial Fibrillation. Cells. 2019;8(10):1202. https://doi.org/10.3390/cells8101202.

66. Michałek M, Tabiś A, Noszczyk-Nowak A. Serum Total Antioxidant Capacity and Enzymatic Defence of Dogs with Chronic Heart Failure and Atrial Fibrillation: A Preliminary Study. J Vet Res. 2020;64(3):439–444. https://doi.org/10.2478/jvetres-2020-0047.

67. Wu Y, Zhang K, Zhao L, Guo J, Hu X, Chen Z. Increased serum HMGB1 is related to oxidative stress in patients with atrial fibrillation. J Int Med Res. 2013;41(6):1796–1802. https://doi.org/10.1177/0300060513503917.

68. Hecker JG, McGarvey M. Heat shock proteins as biomarkers for the rapid detection of brain and spinal cord ischemia: a review and comparison to other methods of detection in thoracic aneurysm repair. Cell Stress Chaperones. 2011;16(2):119–131. https://doi.org/10.1007/s12192-010-0224-8.

69. Hu X, Li J, van Marion DMS, Zhang D, Brundel BJJM. Heat shock protein inducer GGA*-59 reverses contractile and structural remodeling via restoration of the microtubule network in experimental Atrial Fibrillation. J Mol Cell Cardiol. 2019;134:86–97. https://doi.org/10.1016/j.yjmcc.2019.07.006.

70. Lin SZ, Crawford TC, Mandal K. Role of Heat Shock Proteins in Atherosclerosis and Atrial Fibrillation. Curr Immunol Rev Discontin. 2002;13(1):71–81. https://doi.org/10.1161/01.atv.0000029720.59649.50.

71. Liu J, Wang W, Qi Y, Yong Q, Zhou G, Wang M et al. Association between the lipoprotein-associated phospholipase A2 activity and the progression of subclinical atherosclerosis. J Atheroscler Thromb. 2014;21(6):532–542. https://doi.org/10.5551/jat.20941.

72. Silva IT, Mello APQ, Damasceno NRT. Antioxidant and inflammatory aspects of lipoprotein-associated phospholipase A₂ (Lp-PLA₂): a review. Lipids Health Dis. 2011;10:170. https://doi.org/10.1186/1476-511X-10-170.

73. Garg PK, McClelland RL, Jenny NS, Criqui MH, Greenland P, Rosenson RS et al. Lipoprotein-associated phospholipase A2 and risk of incident cardiovascular disease in a multi-ethnic cohort: The multi ethnic study of atherosclerosis. Atherosclerosis. 2015;241(1):176–182. https://doi.org/10.1016/j.atherosclerosis.2015.05.006.

74. Schnabel RB, Larson MG, Yamamoto JF, Kathiresan S, Rong J, Levy D et al. Relation of multiple inflammatory biomarkers to incident atrial fibrillation. Am J Cardiol. 2009;104(1):92–96. https://doi.org/10.1016/j.amjcard.2009.02.053.

75. Garg PK, Bartz TM, Norby FL, Jorgensen NW, McClelland RL, Ballantyne CM et al. Association of lipoprotein-associated phospholipase A2 and risk of incident atrial fibrillation: Findings from 3 cohorts. Am Heart J. 2018;197:62–69. https://doi.org/10.1016/j.ahj.2017.11.010.

76. Wang Q. Plasma lipoprotein-associated phospholipase A2 is associated with acute ischemic stroke in patients with atrial fibrillation. J Clin Neurosci. 2022;101:239–243. https://doi.org/10.1016/j.jocn.2022.05.018.

77. Dong XJ, Wang BB, Hou FF, Chen KP, Zhou HD, Guo JW et al. Homocysteine (HCY) levels in patients with atrial fibrillation (AF): A meta-analysis. Int J Clin Pract. 2021;75(12):e14738. https://doi.org/10.1111/ijcp.14738.

78. Acampa M, Lazzerini PE, Martini G. Postoperative atrial fibrillation and ischemic stroke: The role of homocysteine. Eur Stroke J. 2018;3(1):92–93. https://doi.org/10.1111/ijcp.14738.

79. Acampa M, Lazzerini PE, Guideri F, Tassi R, Martini G. Ischemic Stroke after Heart Transplantation. J Stroke. 2016;18(2):157–168. https://doi.org/10.5853/jos.2015.01599.

80. Yao Y, Shang MS, Gao LJ, Zhao JH, Yang XH, Liu T et al. Elevated homocysteine increases the risk of left atrial/left atrial appendage thrombus in non-valvular atrial fibrillation with low CHA2DS2-VASc score. Europace. 2018;20(7):1093–1098. https://doi.org/10.1093/europace/eux189.

81. Yao Y, Yao W, Bai R, Lu ZH, Tang RB, Long DY et al. Plasma homocysteine levels predict early recurrence after catheter ablation of persistent atrial fibrillation. Europace. 2017;19(1):66–71. https://doi.org/10.1093/europace/euw081.

82. Rafaqat S, Rafaqat S, Ijaz H. The Role of Biochemical Cardiac Markers in Atrial Fibrillation. J Innov Card Rhythm Manag. 2023;14(10):5611–5621. https://doi.org/10.19102/icrm.2023.14101.

83. Garg PK, Guan W, Karger AB, Steffen BT, O’Neal W, Heckbert SR et al. Lp(a) (Lipoprotein (a)) and Risk for Incident Atrial Fibrillation: Multi-Ethnic Study of Atherosclerosis. Circ Arrhythm Electrophysiol. 2020;13(5):e008401. https://doi.org/10.1161/CIRCEP.120.008401.

84. Ding M, Wennberg A, Gigante B, Walldius G, Hammar N, Modig K. Lipid levels in midlife and risk of atrial fibrillation over 3 decades-Experience from the Swedish AMORIS cohort: A cohort study. PLoS Med. 2022;9(8):e1004044. https://doi.org/10.1371/journal.pmed.1004044.

85. Салухов ВВ, Кадин ДВ. Ожирение как фактор онкологического риска. Обзор литературы. Медицинский совет. 2019;(4):94–102. https://doi.org/10.21518/2079-701X-2019-4-94-102.

86. Watt MJ, Miotto PM, De Nardo W, Montgomery MK. The Liver as an Endocrine Organ-Linking NAFLD and Insulin Resistance. Endocr Rev. 2019;40(5):1367–1393. https://doi.org/10.1210/er.2019-00034.

87. Alpert MA, Karthikeyan K, Abdullah O, Ghadban R. Obesity and Cardiac Remodeling in Adults: Mechanisms and Clinical Implications. Prog Cardiovasc Dis. 2018;61(2):114–123. https://doi.org/10.1016/j.pcad.2018.07.012.

88. Chan YH, Chang GJ, Lai YJ, Chen WJ, Chang SH, Hung LM et al. Atrial fibrillation and its arrhythmogenesis associated with insulin resistance. Cardiovasc Diabetol. 2019;18(1):125. https://doi.org/10.1186/s12933-019-0928-8.

89. Ling Y, Fu C, Fan Q, Liu J, Jiang L, Tang S. Triglyceride-Glucose Index and New-Onset Atrial Fibrillation in ST-Segment Elevation Myocardial Infarction Patients After Percutaneous Coronary Intervention. Front Cardiovasc Med. 2022;9:838761. https://doi.org/10.3389/fcvm.2022.838761.

90. Wei Z, Zhu E, Ren C, Dai J, Li J, Lai Y. Triglyceride-Glucose Index Independently Predicts New-Onset Atrial Fibrillation After Septal Myectomy for Hypertrophic Obstructive Cardiomyopathy Beyond the Traditional Risk Factors. Front Cardiovasc Med. 2021;8:692511. https://doi.org/10.3389/fcvm.2021.692511.

91. Yin C, Hou Q, Qi Q, Han Q, Wang X, Wu S et al. Triglyceride-Glucose Index Predicts Major Adverse Cardiovascular and Cerebrovascular Events in Patients with Atrial Fibrillation. Int Heart J. 2024;65(3):373–379. https://doi.org/10.1536/ihj.23-413.