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Vol 26, No 1 (2020)
Review paper
Published online: 2020-03-25

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Selected biomarkers of atherosclerosis - clinical aspects

Stanisław Surma1, Tomasz Czober2, Tomasz Lepich1, Oskar Sierka1, Grzegorz Bajor1
DOI: 10.5603/AA.2020.0005
Acta Angiologica 2020;26(1):28-39.

Abstract

Atherosclerosis is a inflammatory-immunological-degenerative process. Cardiovascular diseases account for 42% of premature deaths among men and 52% of premature deaths among woman. Identification of classical biomarkers of atherosclerosis, such as LDL, HDL and triglycerides may not be helpful in patients with moderate or unusual cardiovascular risk. Non-classical indicators of atherosclerosis include markers of the inflammatory proces, mar-kers of atherosclerotic plaque injury, acute phase proteins, ischemic markers, markers of tissue necrosis, markers of myocardial dysfunction. The identification of CVD biomarkers enables the classification of patients to appropriate cardiovascular risk groups. Knowledge about the CVD risk group makes it possible to take rapid therapeutic intervention aimed at limiting this risk. Pharmacotherapy for cardiovascular diseases is primarily based on lowering cholesterol’s level in the blood. Additional properties of statins (the most important lipid-lowering drugs) enable their pleiotropic effect by limiting the progression of atherosclerotic lesions by reducing the volume of atherosclerotic plaque. Further research on the pathogenesis of atherosclerosis will allow to learn new risk factors and new biomarkers of this disease.

Keywords: biomarkersatherosclerosiscardiovascular riskcardiovascular diseasesstatins

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References

  1. Zieske AW, Malcom GT, Strong JP. Natural history and risk factors of atherosclerosis in children and youth: the PDAY study. Pediatr Pathol Mol Med. 2002; 21(2): 213–237.
    CrossRefPubMed
  2. Wang JC, Bennett M. Aging and atherosclerosis: mechanisms, functional consequences, and potential therapeutics for cellular senescence. Circ Res. 2012; 111(2): 245–259.
    CrossRefPubMed
  3. Nichols M, Townsend N, Scarborough P, et al. Cardiovascular disease in Europe: epidemiological update. Eur Heart J. 2013; 34(39): 3028–3034.
    CrossRefPubMed
  4. Olinic DM, Spinu M, Olinic M, et al. Epidemiology of peripheral artery disease in Europe: VAS Educational Paper. Int Angiol. 2018; 37(4): 327–334.
    CrossRefPubMed
  5. Brown NJ. Eplerenone: cardiovascular protection. Circulation. 2003; 107(19): 2512–2518.
    CrossRefPubMed
  6. Ezzati M, Riboli E. Behavioral and dietary risk factors for noncommunicable diseases. N Engl J Med. . 2013; 369(10): 954–964.
  7. Wielkoszyński T, Zalejska-Fiolka J, Strzelczyk JK, et al. Oxysterols Increase Inflammation, Lipid Marker Levels and Reflect Accelerated Endothelial Dysfunction in Experimental Animals. Mediators Inflamm. 2018; 2018: 2784701.
    CrossRefPubMed
  8. Kluk MK. Current review of cardiovascular risk biomarkers. Folia Cardiol. 2017; 12(3): 335–336.
  9. Wang J, Tan GJ, Han LN, et al. Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol. 2017; 14(2): 135–150.
    CrossRefPubMed
  10. Fernández-Friera L, Peñalvo JL, Fernández-Ortiz A, et al. Prevalence, Vascular Distribution, and Multiterritorial Extent of Subclinical Atherosclerosis in a Middle-Aged Cohort: The PESA (Progression of Early Subclinical Atherosclerosis) Study. Circulation. 2015; 131(24): 2104–2113.
    CrossRefPubMed
  11. Węgierek-Szostak D, Cybulska B. History of research on atherosclerosis. ITEM Publishing Warszawa, Warszawa 2016.
  12. Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1995; 92(5): 1355–1374.
    CrossRefPubMed
  13. Strong JP, Malcom GT, McMahan CA, et al. Prevalence and extent of atherosclerosis in adolescents and young adults: implications for prevention from the Pathobiological Determinants of Atherosclerosis in Youth Study. JAMA. 1999; 281(8): 727–735.
    CrossRefPubMed
  14. McGill HC, McMahan CA, Zieske AW, et al. Association of Coronary Heart Disease Risk Factors with microscopic qualities of coronary atherosclerosis in youth. Circulation. 2000; 102(4): 374–379.
    CrossRefPubMed
  15. Stary HC, Chandler AB, Dinsmore RE, et al. A definition of advanced types of atherosclerotic lesions and a histological classification of atherosclerosis. A report from the Committee on Vascular Lesions of the Council on Arteriosclerosis, American Heart Association. Circulation. 1995; 92(5): 1355–1374.
    CrossRefPubMed
  16. Falk E, Shah PK, Fuster V. Coronary plaque disruption. Circulation. 1995; 92(3): 657–671.
    CrossRefPubMed
  17. Sosnowski C, Pasierski T, Janeczko-Sosnowska E, et al. Peripheral artery atherosclerosis in subjects with suspected coronary heart disease. Folia Cardiol. 2005; 12(9): 635–643.
  18. Li YSJ, Haga JH, Chien S. Molecular basis of the effects of shear stress on vascular endothelial cells. J Biomech. 2005; 38(10): 1949–1971.
    CrossRefPubMed
  19. Tymińska A, Kapłon-Cieślicka A. Vascular age – in whom and how to evaluate it? Can we „rejuvenate” the vessels of our patients ? ChSiN. 2019; 16(2): 118–129.
  20. Harris TB, Ferrucci L, Tracy RP, et al. Associations of elevated interleukin-6 and C-reactive protein levels with mortality in the elderly. Am J Med. 1999; 106(5): 506–512.
    CrossRefPubMed
  21. Mendall MA, Patel P, Asante M, et al. Relation of serum cytokine concentrations to cardiovascular risk factors and coronary heart disease. Heart. 1997; 78(3): 273–277.
    CrossRefPubMed
  22. Ridker PM, Rifai N, Stampfer MJ, et al. Plasma concentration of interleukin-6 and the risk of future myocardial infarction among apparently healthy men. Circulation. 2000; 101(15): 1767–1772.
    CrossRefPubMed
  23. Reiss AB, Siegart MN, DeLeon J. Interleukin-6 in atherosclerosis: atherogenic or atheroprotective? Clinical Lipidology. 2017; 12(1): 14–23.
  24. Liu SC, Yi TC, Weng HY, et al. [Prognostic value of myeloperoxidase concentration in patients with acute coronary syndrome]. Zhonghua Xin Xue Guan Bing Za Zhi. 2018; 46(4): 284–291.
    CrossRefPubMed
  25. Zhang H, Park Y, Wu J, et al. Role of TNF-alpha in vascular dysfunction. Clin Sci (Lond). 2009; 116(3): 219–230.
    CrossRefPubMed
  26. Libby P, Jaffer FA, Calfon MA, et al. Leducq Transatlantic Network on Atherothrombosis. Inflammation in atherosclerosis. Nature. 2002; 420(6917): 868–874.
    CrossRefPubMed
  27. Bruunsgaard H, Skinhøj P, Pedersen AN, et al. Ageing, tumour necrosis factor-alpha (TNF-alpha) and atherosclerosis. Clin Exp Immunol. 2000; 121(2): 255–260.
    CrossRefPubMed
  28. Heo SH, Cho CH, Kim HOk, et al. Plaque rupture is a determinant of vascular events in carotid artery atherosclerotic disease: involvement of matrix metalloproteinases 2 and 9. J Clin Neurol. 2011; 7(2): 69–76.
    CrossRefPubMed
  29. Lehrke M, Greif M, Broedl UC, et al. MMP-1 serum levels predict coronary atherosclerosis in humans. Cardiovasc Diabetol. 2009; 8: 50.
    CrossRefPubMed
  30. Jefferis BJ, Whincup P, Welsh P, et al. Prospective study of matrix metalloproteinase-9 and risk of myocardial infarction and stroke in older men and women. Atherosclerosis. 2010; 208(2): 557–563.
    CrossRefPubMed
  31. Ley K, Huo Y. VCAM-1 is critical in atherosclerosis. J Clin Invest. 2001; 107(10): 1209–1210.
    CrossRefPubMed
  32. Cybulsky MI, Iiyama K, Li H, et al. A major role for VCAM-1, but not ICAM-1, in early atherosclerosis. J Clin Invest. 2001; 107(10): 1255–1262.
    CrossRefPubMed
  33. Varona JF, Ortiz-Regalón R, Sánchez-Vera I, et al. Soluble ICAM 1 and VCAM 1 Blood Levels Alert on Subclinical Atherosclerosis in Non Smokers with Asymptomatic Metabolic Syndrome. Arch Med Res. 2019; 50(2): 20–28.
    CrossRefPubMed
  34. Shrivastava A, Singh H, Raizada A, et al. C-reactive protein, inflammation and coronary heart disease. The Egyptian Heart Journal. 2015; 67(2): 89–97.
    CrossRef
  35. Nissen SE, Tuzcu EM, Schoenhagen P, et al. Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) Investigators. Statin therapy, LDL cholesterol, C-reactive protein, and coronary artery disease. N Engl J Med. 2005; 352(1): 29–38.
    CrossRefPubMed
  36. Patanè S. Growth differentiation factor-15 in chronic heart failure. JACC: Heart Failure. 2018; 6(2): 177.
    CrossRef
  37. Wollert KC, Kempf T, Wallentin L, et al. Growth differentiation factor-15: a new biomarker in cardiovascular disease. Herz. 2009; 34(8): 594–599.
    CrossRefPubMed
  38. Wollert KC, Kempf T, Lagerqvist Bo, et al. Growth differentiation factor 15 for risk stratification and selection of an invasive treatment strategy in non ST-elevation acute coronary syndrome. Circulation. 2007; 116(14): 1540–1548.
    CrossRefPubMed
  39. Krobot K, Hense HW, Cremer P, et al. Determinants of plasma fibrinogen: relation to body weight, waist-to-hip ratio, smoking, alcohol, age, and sex. Results from the second MONICA Augsburg survey 1989-1990. Arterioscler Thromb. 1992; 12(7): 780–788.
    CrossRefPubMed
  40. Stec JJ, Silbershatz H, Tofler GH, et al. Association of fibrinogen with cardiovascular risk factors and cardiovascular disease in the Framingham Offspring Population. Circulation. 2000; 102(14): 1634–1638.
    CrossRefPubMed
  41. Duran M, Kalay N, Akpek M, et al. High levels of serum uric acid predict severity of coronary artery disease in patients with acute coronary syndrome. Angiology. 2012; 63(6): 448–452.
    CrossRefPubMed
  42. Enomoto M, Adachi H, Hirai Y, et al. LDL-C/HDL-C Ratio Predicts Carotid Intima-Media Thickness Progression Better Than HDL-C or LDL-C Alone. J Lipids. 2011; 2011: 549137.
    CrossRefPubMed
  43. Marcovina SM, Albers JJ. Lipoprotein (a) measurements for clinical application. J Lipid Res. 2016; 57(4): 526–537.
    CrossRefPubMed
  44. Orsó E, Schmitz G. Lipoprotein(a) and its role in inflammation, atherosclerosis and malignancies. Clin Res Cardiol Suppl. 2017; 12(Suppl 1): 31–37.
    CrossRefPubMed
  45. Zhang J, Du R, Peng K, et al. Serum lipoprotein (a) is associated with increased risk of stroke in Chinese adults: A prospective study. Atherosclerosis. 2019; 289: 8–13.
    CrossRefPubMed
  46. Sadkowska M, Kubica J, Radomski M, et al. Evaluation of serum homocysteine, lipoprotein (a) and oxidized LDL levels in patients before coronarograph. Folia Cardiologica Excerpta. 2004; 11(2): 111–119.
  47. Hartley A, Haskard D, Khamis R. Oxidized LDL and anti-oxidized LDL antibodies in atherosclerosis - Novel insights and future directions in diagnosis and therapy<sup/>. Trends Cardiovasc Med. 2019; 29(1): 22–26.
    CrossRefPubMed
  48. Fefer P, Tsimikas S, Segev A, et al. The role of oxidized phospholipids, lipoprotein (a) and biomarkers of oxidized lipoproteins in chronically occluded coronary arteries in sudden cardiac death and following successful percutaneous revascularization. Cardiovasc Revasc Med. 2012; 13(1): 11–19.
    CrossRefPubMed
  49. Uno M, Harada M, Takimoto O, et al. Elevation of plasma oxidized LDL in acute stroke patients is associated with ischemic lesions depicted by DWI and predictive of infarct enlargement. Neurol Res. 2005; 27(1): 94–102.
    CrossRefPubMed
  50. van den Berg VJ, Vroegindewey MM, Kardys I, et al. Anti-Oxidized LDL Antibodies and Coronary Artery Disease: A Systematic Review. Antioxidants (Basel). 2019; 8(10).
    CrossRefPubMed
  51. Schönbeck U, Libby P. CD40 signaling and plaque instability. Circ Res. 2001; 89(12): 1092–1103.
    CrossRefPubMed
  52. Varo N, de Lemos JA, Libby P, et al. Soluble CD40L: risk prediction after acute coronary syndromes. Circulation. 2003; 108(9): 1049–1052.
    CrossRefPubMed
  53. Erturan I, Köroğlu BK, Adiloğlu A, et al. Evaluation of serum sCD40L and homocysteine levels with subclinical atherosclerosis indicators in patients with psoriasis: a pilot study. Int J Dermatol. 2014; 53(4): 503–509.
    CrossRefPubMed
  54. Pervanidou P, Chouliaras G, Akalestos A, et al. Increased placental growth factor (PlGF) concentrations in children and adolescents with obesity and the metabolic syndrome. Hormones (Athens). 2014; 13(3): 369–374.
    CrossRefPubMed
  55. Tang SL, Zhao ZW, Liu SM, et al. Pregnancy-Associated Plasma Protein-A Accelerates Atherosclerosis by Regulating Reverse Cholesterol Transport and Inflammation. Circ J. 2019; 83(3): 515–523.
    CrossRefPubMed
  56. Oemrawsingh RM, Lenderink T, Akkerhuis KM, et al. CAPTURE investigators. Multimarker risk model containing troponin-T, interleukin 10, myeloperoxidase and placental growth factor predicts long-term cardiovascular risk after non-ST-segment elevation acute coronary syndrome. Heart. 2011; 97(13): 1061–1066.
    CrossRefPubMed
  57. Shao D, Lian Z, Di Y, et al. Dietary compounds have potential in controlling atherosclerosis by modulating macrophage cholesterol metabolism and inflammation via miRNA. NPJ Sci Food. 2018; 2: 13.
    CrossRefPubMed
  58. Stanek A, Cholewka A, Wielkoszyński T, et al. Increased Levels of Oxidative Stress Markers, Soluble CD40 Ligand, and Carotid Intima-Media Thickness Reflect Acceleration of Atherosclerosis in Male Patients with Ankylosing Spondylitis in Active Phase and without the Classical Cardiovascular Risk Factors. Oxid Med Cell Longev. 2017; 2017: 9712536.
    CrossRefPubMed
  59. Stanek A, Cholewka A, Wielkoszyński T, et al. Whole-Body Cryotherapy Decreases the Levels of Inflammatory, Oxidative Stress, and Atherosclerosis Plaque Markers in Male Patients with Active-Phase Ankylosing Spondylitis in the Absence of Classical Cardiovascular Risk Factors. Mediators Inflamm. 2018; 2018: 8592532.
    CrossRefPubMed
  60. Haroon NN, Paterson JM, Li P, et al. Patients With Ankylosing Spondylitis Have Increased Cardiovascular and Cerebrovascular Mortality: A Population-Based Study. Ann Intern Med. 2015; 163(6): 409–416.
    CrossRefPubMed
  61. Karakas M, Koenig W. Lp-PLA2 Inhibition-The Atherosclerosis Panacea? Pharmaceuticals (Basel). 2010; 3(5): 1360–1373.
    CrossRefPubMed
  62. Murakami M, Sato H, Miki Y, et al. A new era of secreted phospholipase A₂. J Lipid Res. 2015; 56(7): 1248–1261.
    CrossRefPubMed
  63. Reinstadler SJ, Klug G, Feistritzer HJ, et al. Copeptin testing in acute myocardial infarction: ready for routine use? Dis Markers. 2015; 2015: 614145.
    CrossRefPubMed
  64. Falkentoft AC, Rørth R, Iversen K, et al. MR-proADM as a Prognostic Marker in Patients With ST-Segment-Elevation Myocardial Infarction-DANAMI-3 (a Danish Study of Optimal Acute Treatment of Patients With STEMI) Substudy. J Am Heart Assoc. 2018; 7(11).
    CrossRefPubMed
  65. Toutouzas K, Benetos G, Karanasos A, et al. Vulnerable plaque imaging: updates on new pathobiological mechanisms. Eur Heart J. 2015; 36(45): 3147–3154.
    CrossRefPubMed
  66. Sun Z. Aging, arterial stiffness, and hypertension. Hypertension. 2015; 65(2): 252–256.
    CrossRefPubMed
  67. Fang J, Madhavan S, Alderman MH. Pulse pressure: a predictor of cardiovascular mortality among young normotensive subjects. Blood Press. 2000; 9(5): 260–266.
    CrossRefPubMed
  68. Safar ME, Blacher J, Jankowski P. Arterial stiffness, pulse pressure, and cardiovascular disease-is it possible to break the vicious circle? Atherosclerosis. 2011; 218(2): 263–271.
    CrossRefPubMed
  69. Iantorno M, Campia U, Di Daniele N, et al. Obesity, inflammation and endothelial dysfunction. J Biol Regul Homeost Agents. 2014; 28(2): 169–176.
    PubMed
  70. Förstermann U. Oxidative stress in vascular disease: causes, defense mechanisms and potential therapies. Nat Clin Pract Cardiovasc Med. 2008; 5(6): 338–349.
    CrossRefPubMed
  71. Oesterle A, Laufs U, Liao JK. Pleiotropic Effects of Statins on the Cardiovascular System. Circ Res. 2017; 120(1): 229–243.
    CrossRefPubMed
  72. Hoshiga M, Arishiro K, Nakakoji T, et al. Switching to aggressive statin improves vascular endothelial function in patients with stable coronary artery disease. J Atheroscler Thromb. 2010; 17(7): 705–711.
    CrossRefPubMed
  73. Kumbhani DJ, Steg PhG, Cannon CP, et al. REACH Registry Investigators. Statin therapy and long-term adverse limb outcomes in patients with peripheral artery disease: insights from the REACH registry. Eur Heart J. 2014; 35(41): 2864–2872.
    CrossRefPubMed
  74. Puri R, Nissen SE, Shao M, et al. Antiatherosclerotic effects of long-term maximally intensive statin therapy after acute coronary syndrome: insights from Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin. Arterioscler Thromb Vasc Biol. 2014; 34(11): 2465–2472.
    CrossRefPubMed
  75. Auscher S, Heinsen L, Nieman K, et al. Effects of intensive lipid-lowering therapy on coronary plaques composition in patients with acute myocardial infarction: Assessment with serial coronary CT angiography. Atherosclerosis. 2015; 241(2): 579–587.
    CrossRefPubMed
  76. Gupta S. LDL cholesterol, statins and PCSK 9 inhibitors. Indian Heart J. 2015; 67(5): 419–424.
    CrossRefPubMed
  77. Koren MJ, Scott R, Kim JB, et al. Efficacy, safety, and tolerability of a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 as monotherapy in patients with hypercholesterolaemia (MENDEL): a randomised, double-blind, placebo-controlled, phase 2 study. Lancet. 2012; 380(9858): 1995–2006.
    CrossRefPubMed
  78. Raal F, Scott R, Somaratne R, et al. Low-density lipoprotein cholesterol-lowering effects of AMG 145, a monoclonal antibody to proprotein convertase subtilisin/kexin type 9 serine protease in patients with heterozygous familial hypercholesterolemia: the Reduction of LDL-C with PCSK9 Inhibition in Heterozygous Familial Hypercholesterolemia Disorder (RUTHERFORD) randomized trial. Circulation. 2012; 126(20): 2408–2417.
    CrossRefPubMed
  79. Sullivan D, Olsson AG, Scott R, et al. Effect of a monoclonal antibody to PCSK9 on low-density lipoprotein cholesterol levels in statin-intolerant patients: the GAUSS randomized trial. JAMA. 2012; 308(23): 2497–2506.
    CrossRefPubMed
  80. Stein EA, Honarpour N, Wasserman SM, et al. Effect of the proprotein convertase subtilisin/kexin 9 monoclonal antibody, AMG 145, in homozygous familial hypercholesterolemia. Circulation. 2013; 128(19): 2113–2120.
    CrossRefPubMed

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