Review of major epidemiological studies of blood viscosity in cardiovascular diseases

Integrative Medicine (Boulder)

Volumn 12, Issue 6, 2013, Pages 24-35

  Sloop, Gregory D ^a   Holsworth, Ralph ^b   Weidman, Joseph ^c  

^a Benefis Health System   (United States)

^b Long Term Care Center   (United States)

^c THOMAS JEFFERSON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 84921327402     PISSN: 1546993X     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (113)

1. Sloop GD A unifying theory of atherogenesis. Med Hypotheses. 1996; 47(4):321-325.
2. Devereux RB, Case DB, Alderman MH, Pickering TG, Chien S, Laragh JH. Possible role of increased blood viscosity in the hemodynamics of systemic hypertension. Am J Cardiol. 2000; 85(10):1265-1268.
3. Fowkes FG, Lowe GD, Rumley A, Lennie SE, Smith FB, Donnan PT. The relationship between blood viscosity and blood pressure in a random sample of the population aged 55 to 74 years. Eur Heart J. 1993; 14(5):597-601.
4. Letcher RL, Chien S, Pickering TG, Sealey JE, Laragh JH. Direct relationship between blood pressure and blood viscosity in normal and hypertensive subjects: role of fibrinogen and concentration. Am J Med. 1981; 70(6):1195-1202.
5. Stamos TD, Rosenson RS. Low high density lipoprotein levels are associated with an elevated blood viscosity. Atherosclerosis. 1999; 146(1):161-165.
6. Sloop GD, Garber D W. The effects of low-density lipoprotein and high-density lipoprotein on blood viscosity correlate with their association with risk of atherosclerosis in humans. Clin Sci (Lond). 1997; 92(5):473-479.
7. Rosenson RS, McCormick A, Uretz EF. Distribution of blood viscosity values and biochemical correlates in healthy adults. Clin Chem. 1996; 42(8, pt 1):1189-1195.
8. Rosenson RS, Shott S, Tangney CC. Hypertriglyceridemia is associated with an elevated blood viscosity Rosenson: triglycerides and blood viscosity. Atherosclerosis. 2002; 161(2):433-439.
9. Lowe GD Blood viscosity, lipoproteins, and cardiovascular risk. Circulation. 1992; 85(6):2329-2331.
10. de Simone G, Devereux RB, Chien S, Alderman MH, Atlas SA, Laragh JH. Relation of blood viscosity to demographic and physiologic variables and to cardiovascular risk factors in apparently normal adults. Circulation. 1990; 81(1):107-117.
11. Jax T W, Peters AJ, Plehn G, Schoebel FC. Hemostatic risk factors in patients with coronary artery disease and type 2 diabetes - a two year follow-up of 243 patients. Cardiovasc Diabetol. September 2009; 8:48.
12. Tamariz LJ, Young JH, Pankow JS, et al. Blood viscosity and hematocrit as risk factors for type 2 diabetes mellitus: the Atherosclerosis Risk in Communities (ARIC) study. Am J Epidemiol. 2008; 168(10):1153-1160.
13. Hoieggen A, Fossum E, Moan A, Enger E, Kjeldsen SE. Whole-blood viscosity and the insulin-resistance syndrome. J Hypertens. 1998; 16(2):203-210.
14. Ernst E, Weihmayr T, Schmid M, Baumann M, Matrai A. Cardiovascular risk factors and hemorheology: physical fitness, stress and obesity. Atherosclerosis. 1986; 59(3):263-269.
15. Ernst E. Haemorheological consequences of chronic cigarette smoking. J Cardiovasc Risk. 1995; 2(5):435-439.
16. Levenson J, Simon AC, Cambien FA, Beretti C. Cigarette smoking and hypertension: factors independently associated with blood hyperviscosity and arterial rigidity. Arteriosclerosis. 1987; 7(6):572-577.
17. Ernst E, Koenig W, Matrai A, Filipiak B, Stieber J. Blood rheology in healthy cigarette smokers: results from the MONICA project, Augsburg. Arteriosclerosis. 1988; 8(4):385-388.
18. Lowe GD, Drummond MM, Forbes CD, Barbenel JC. The effects of age and cigarette-smoking on blood and plasma viscosity in men. Scott Med J. 1980; 25(1):13-17.
19. Kameneva M V, Watach MJ, Borovetz HS. Gender difference in rheologic properties of blood and risk of cardiovascular diseases. Clin Hemorheol Microcirc. 1999; 21(3-4):357-363.
20. Fowkes FG, Pell J P, Donnan PT, et al. Sex differences in susceptibility to etiologic factors for peripheral atherosclerosis: importance of plasma fibrinogen and blood viscosity. Arterioscler Thromb. 1994; 14(6):862-868.
21. Coppola L, Caserta F, De Lucia D, et al. Blood viscosity and aging. Arch Gerontol Geriatr. 2000; 31(1):35-42.
22. Zarins CK, Giddens DP, Bharadvaj BK, Sottiurai VS, Mabon R F, Glagov S. Carotid bifurcation atherosclerosis: quantitative correlation of plaque localization with flow velocity profiles and wall shear stress. Circ Res. 1983; 53(4):502-514.
23. Malek AM, Alper SL, Izumo S. Hemodynamic shear stress and its role in atherosclerosis. JAMA. 1999; 282(21):2035-2042.
24. Frangos SG, Gahtan V, Sumpio B. Localization of atherosclerosis: role of hemodynamics. Arch Surg. 1999; 134(10):1142-1149.
25. Davies PF Hemodynamic shear stress and the endothelium in cardiovascular pathophysiology. Nat Clin Pract Cardiovasc Med. 2009; 6(1):16-26.
26. Kensey KR The mechanistic relationships between hemorheological characteristics and cardiovascular disease. Curr Med Res Opin. 2003; 19(7):587-596.
27. Baskurt OK, Meiselman HJ. Blood rheology and hemodynamics. Semin Thromb Hemost. 2003; 29(5):435-450.
28. Sloop GD, Mercante DE. Opposite effects of low-density and high-density lipoprotein on blood viscosity in fasting subjects. Clin Hemorheol Microcirc. 1998; 19(3):197-203.
29. Stoltz J F, Singh M, Riha P. Hemorheology in Practice. Washington, DC: IOS Press; 1999.
30. Brun J F, Bouchahda C, Chaze D, Benhaddad AA, Micallef J P, Mercier J. The paradox of hematocrit in exercise physiology: which is the "normal" range from an hemorheologist's viewpoint? Clin Hemorheol Microcirc. 2000; 22(4):287-303.
31. Gaehtgens P, Pries AR, Ley K. Structural, hemodynamic and rheological characteristics of blood flow in the circulation. In: Chien S, Dormandy J, Ernst E, Matrai A, eds. Clinical Hemorheology. Dordrecht, Netherlands: Martinus Nijhoff Publishers; 1987:97-124.
32. Leonhardt H, Arntz HR, Klemens UH. Studies of plasma viscosity in primary hyperlipoproteinaemia. Atherosclerosis. 1977; 28(1):29-40.
33. Seplowitz AH, Chien S, Smith FR. Effects of lipoproteins on plasma viscosity. Atherosclerosis. 1981; 38(1-2):89-95.
34. Lowe GD, Lee AJ, Rumley A, Price JF, Fowkes FG. Blood viscosity and risk of cardiovascular events: the Edinburgh Artery Study. Br J Haematol. 1997; 96(1):168-173.
35. Lee AJ, Mowbray PI, Lowe GD, Rumley A, Fowkes FG, Allan PL. Blood viscosity and elevated carotid intima-media thickness in men and women: the Edinburgh Artery Study. Circulation. 1998; 97(15):1467-1473.
36. Lowe GD, Fowkes FG, Dawes J, Donnan PT, Lennie SE, Housley E. Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburgh Artery Study. Circulation. 1993; 87(6):1915-1920.
37. Dormandy JA, Hoare E, Postlethwaite J. Importance of blood viscosity: rheological claudication. Proc R Soc Med. 1974; 67(6, pt 1):446-447.
38. Coull BM, Beamer N, de Garmo P, et al. Chronic blood hyperviscosity in subjects with acute stroke, transient ischemic attack, and risk factors for stroke. Stroke. 1991; 22(2):162-168.
39. Ciuffetti G, Schillaci G, Lombardini R, Pirro M, Vaudo G, Mannarino E. Prognostic impact of low-shear whole blood viscosity in hypertensive men. Eur J Clin Invest. 2005; 35(2):93-98.
40. Resch KL, Ernst E, Matrai A, Buhl M, Schlosser P, Paulsen H F. Can rheologic variables be of prognostic relevance in arteriosclerotic diseases? Angiology. 1991; 42(12):963-970.
41. Skovborg F, Nielsen AV, Schlichtkrull J, Ditzel J. Blood-viscosity in diabetic patients. Lancet. 1966; 1(7429):129-131.
42. Lowe GD, Lowe JM, Drummond MM, et al. Blood viscosity in young male diabetics with and without retinopathy. Diabetologia. 1980; 18(5):359-363.
43. Barnes AJ, Locke P, Scudder PR, Dormandy TL, Dormandy JA, Slack J. Is hyperviscosity a treatable component of diabetic microcirculatory disease? Lancet. 1977; 2(8042):789-791.
44. 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. Arterioscler Thromb Vasc Biol. 1995; 15(9):1512-1531.
45. Duguid JB The thrombogenic hypothesis and its implications. Postgrad Med J. April 1960; 36:226-229.
46. van der Steeg WA, Holme I, Boekholdt SM, et al. High-density lipoprotein cholesterol, high-density lipoprotein particle size, and apolipoprotein A-I: significance for cardiovascular risk: the IDEAL and EPIC-Norfolk studies. J Am Coll Cardiol. 2008; 51(6):634-642.
47. Antle EA Who needs a therapeutic phlebotomy? Clin J Oncol Nurs. 2010; 14(6):694-696.
48. Tefferi A. A contemporary approach to the diagnosis and management of polycythemia vera. Curr Hematol Rep. 2003; 2(3):237-241.
49. Vautier G, Murray M, Olynyk JK. Hereditary haemochromatosis: detection and management. Med J Aust. 2001; 175(8):418-421.
50. Gagnon DR, Zhang TJ, Brand FN, Kannel WB. Hematocrit and the risk of cardiovascular disease - the Framingham study: a 34-year follow-up. Am Heart J. 1994; 127(3):674-682.
51. Salonen JT, Tuomainen T P, Salonen R, Lakka TA, Nyyssonen K. Donation of blood is associated with reduced risk of myocardial infarction: the Kuopio Ischaemic Heart Disease Risk Factor Study. Am J Epidemiol. 1998; 148(5):445-451.
52. Kim D, Cho YI, Kensey K. Reduction of major amputation by therapeutic phlebotomy in patients with chronic critical limb ischemia. Presented at: 6th International Conference on Clinical Hemorheology. 2008; College Park, PA.
53. Chien S, Usami S, Dellenback RJ, Gregersen MI. Blood viscosity: influence of erythrocyte deformation. Science. 1967; 157(3790):827-829.
54. Waugh RE, Narla M, Jackson C W, Mueller TJ, Suzuki T, Dale GL. Rheologic properties of senescent erythrocytes: loss of surface area and volume with red blood cell age. Blood. 1992; 79(5):1351-1358.
55. Fossum E, Hoieggen A, Moan A, Nordby G, Velund TL, Kjeldsen SE. Whole blood viscosity, blood pressure and cardiovascular risk factors in healthy blood donors. Blood Press. 1997; 6(3):161-165.
56. Cliville X, Bofill C, Joven J, et al. Hemorheological, coagulative and fibrinolytic changes during autologous blood donation. Clin Hemorheol Microcirc. 1998; 18(4):265-272.
57. Tuomainen T P, Salonen R, Nyyssonen K, Salonen JT. Cohort study of relation between donating blood and risk of myocardial infarction in 2682 men in eastern Finland. BM J. 1997; 314(7083):793-794.
58. Hemila H, Paunio M. Blood donation, body iron stores, and risk of myocardial infarction: confidence intervals and possible selection bias call study results into question. BM J. 1997; 314(7097):1830-1831.
59. Kreimeier U, Messmer K. Hemodilution in clinical surgery: state of the art 1996. World J Surg. 1996; 20(9):1208-1217.
60. Bianchin G, Russi G, Romano N, Fioravanti P. Treatment with HELP-apheresis in patients suffering from sudden sensorineural hearing loss: a prospective, randomized, controlled study. Laryngoscope. 2010; 120(4):800-807.
61. Walzl M, Lechner H, Walzl B, Schied G. Improved neurological recovery of cerebral infarctions after plasmapheretic reduction of lipids and fibrinogen. Stroke. 1993; 24(10):1447-1451.
62. Rubba P, Iannuzzi A, Postiglione A, et al. Hemodynamic changes in the peripheral circulation after repeat low density lipoprotein apheresis in familial hypercholesterolemia. Circulation. 1990; 81(2):610-616.
63. Digiesi V, Cerchiai G, Mannini L, Masi F, Nassi F. Hemorheologic and blood cell changes in humans during partial immersion, with a therapeutic method, in 38 C water [in Italian]. Minerva Med. 1986; 77(30-31):1407-1411.
64. Verrazzo G, Coppola L, Luongo C, et al. Hyperbaric oxygen, oxygen-ozone therapy, and rheologic parameters of blood in patients with peripheral occlusive arterial disease. Undersea Hyperb. Med. 1995; 22(1):17-22.
65. Giunta R, Coppola A, Luongo C, et al. Ozonized autohemotransfusion improves hemorheological parameters and oxygen delivery to tissues in patients with peripheral occlusive arterial disease. Ann Hematol. 2001; 80(12):745-748.
66. Chevalier G, Sinatra ST, Oschman JL, Delany RM. Earthing (grounding) the human body reduces blood viscosity-a major factor in cardiovascular disease. J Altern Complement Med. 2013; 19(2):102-110.
67. Berman W Jr, Berman N, Pathak D, Wood SC. Effects of pentoxifylline (Trental) on blood flow, viscosity, and oxygen transport in young adults with inoperable cyanotic congenital heart disease. Pediatric Cardiol. 1994; 15(2):66-70.
68. Sonkin PL, Sinclair SH, Hatchell DL. The effect of pentoxifylline on retinal capillary blood flow velocity and whole blood viscosity. Am J Ophthalmol. 1993; 115(6):775-780.
69. Perego M, Sergio G, Artale F, Giunti P, Danese C. Haemorrheological improvement by pentoxifylline in patients with peripheral arterial occlusive disease. Curr Med Res Opin. 1986; 10(2):135-138.
70. Solerte SB, Fioravanti M, Cerutti N, et al. Retrospective analysis of long-term hemorheologic effects of pentoxifylline in diabetic patients with angiopathic complications. Acta Diabetol. 1997; 34(2):67-74.
71. Di Perri T, Carandente O, Vittoria A, Guerrini M, Messa GL. Studies of the clinical pharmacology and therapeutic efficacy of pentoxifylline in peripheral obstructive arterial disease. Angiology. 1984; 35(7):427-435.
72. Ott E, Lechner H, Fazekas F. Hemorheological effects of pentoxifylline on disturbed flow behavior of blood in patients with cerebrovascular insufficiency. Eur Neurol. 1983; 22(suppl 1):105-107.
73. Dawson DL, Zheng Q, Worthy SA, Charles B, Bradley DV Jr Failure of pentoxifylline or cilostazol to improve blood and plasma viscosity, fibrinogen, and erythrocyte deformability in claudication. Angiology. 2002; 53(5):509-520.
74. Karandashov VI, Petukhov EB, Zrodnikov VS. Effects of pentoxyphyllin drugs and UV photohemotherapy on blood viscosity. Bull Exp Biol Med. 1998; 126(11):579-580.
75. Brown MM Effect of oxpentifylline on blood viscosity and cerebral blood flow in man. Br J Clin Pharmacol. 1989; 28(4):488-492.
76. Billett HH, Kaul DK, Connel MM, Fabry ME, Nagel RL. Pentoxifylline (Trental) has no significant effect on laboratory parameters in sickle cell disease. Nouv Rev Fr Hematol. 1989; 31(6):403-407.
77. Reilly DT, Quinton DN, Barrie W W. A controlled trial of pentoxifylline (Trental 400) in intermittent claudication: clinical, haemostatic and rheological effects. N Z Med J. 1987; 100(828):445-447.
78. Perhoniemi V, Salmenkivi K, Sundberg S, Johnsson R, Gordin A. Effects of flunarizine and pentoxifylline on walking distance and blood rheology in claudication. Angiology. 1984; 35(6):366-372.
79. Tsuda Y, Satoh K, Kitadai M, Takahashi T, Izumi Y, Hosomi N. Effects of pravastatin sodium and simvastatin on plasma fibrinogen level and blood rheology in type II hyperlipoproteinemia. Atherosclerosis. 1996; 122(2):225-233.
80. Koenig W, Hehr R, Ditschuneit HH, et al. Lovastatin alters blood rheology in primary hyperlipoproteinemia: dependence on lipoprotein(a)? J Clin Pharmacol. 1992; 32(6):539-545.
81. Koppensteiner R, Minar E, Ehringer H. Effect of lovastatin on hemorheology in type II hyperlipoproteinemia. Atherosclerosis. 1990; 83(1):53-58.
82. Empen K, Geiss HC, Lehrke M, Otto C, Schwandt P, Parhofer KG. Effect of atorvastatin on lipid parameters, LDL subtype distribution, hemorrheological parameters and adhesion molecule concentrations in patients with hypertriglyceridemia. Nutr Metab Cardiovasc Dis. 2003; 13(2):87-92.
83. Bozzo J, Hernandez MR, Ordinas A. Reduced red cell deformability associated with blood flow and platelet activation: improved by dipyridamole alone or combined with aspirin. Cardiovasc Res. 1995; 30(5):725-730.
84. Bozzo J, Escolar G, Hernandez MR, Galan AM, Ordinas A. Prohemorrhagic potential of dipyrone, ibuprofen, ketorolac, and aspirin: mechanisms associated with blood flow and erythrocyte deformability. J Cardiovasc Pharmacol. 2001; 38(2):183-190.
85. Rosenson RS, Wolff D, Green D, Boss AH, Kensey KR. Aspirin: aspirin does not alter native blood viscosity. J Thromb Haemost. 2004; 2(2):340-341.
86. Rosenson RS Treatment with aspirin and dipyridamole is more effective than aspirin in reducing low shear blood viscosity. Microcirculation. 2008; 15(7):615-620.
87. ESPRIT Study Group; Halkes PH, van Gijn J, Kappelle LJ, Koudstaal PJ, Algra A. Aspirin plus dipyridamole versus aspirin alone after cerebral ischaemia of arterial origin (ESPRIT): randomised controlled trial. Lancet. 2006; 367(9523):1665-1673.
88. Ciuffetti G, Lombardini R, Pirro M, Lupattelli G, Mannarino E. Clopidogrel: hemorheological effects in subjects with subclinical atherosclerosis. Clin Hemorheol Microcirc. 2001; 25(1):31-39.
89. Jan KM, Powers E, Reinhart W, et al. Altered rheological properties of blood following administrations of tissue plasminogen activator and streptokinase in patients with acute myocardial infarction. Adv Exp Med Biol. 1990; 281:409-417.
90. Gheeraert P, De Buyzere M, Delanghe J, De Scheerder I, Bury J, Rosseneu M. Plasma and erythrocyte lipids in two families with heterozygous hypobetalipoproteinemia. Clin Biochem. 1988; 21(6):371-377.
91. Bell WR Jr. Defibrinogenating enzymes. Drugs. 1997; 54(suppl 3):18-30; discussion 30-31
92. Chan J, Knutsen SF, Blix GG, Lee J W, Fraser GE. Water, other fluids, and fatal coronary heart disease: the Adventist Health Study. Am J Epidemiol. 2002; 155(9):827-833.
93. Doi T, Sakurai M, Hamada K, et al. Plasma volume and blood viscosity during 4 h sitting in a dry environment: effect of prehydration. Aviat Space Environ Med. 2004; 75(6):500-504.
94. Sommerfield T, Price J, Hiatt WR. Omega-3 fatty acids for intermittent claudication. Cochrane Database Syst Rev. October 2007; (4):CD003833.
95. Woodcock BE, Smith E, Lambert WH, et al. Beneficial effect of fish oil on blood viscosity in peripheral vascular disease. Br Med J (Clin Res Ed). 1984; 288(6417):592-594.
96. Gans RO, Bilo HJ, Weersink EG, et al. Fish oil supplementation in patients with stable claudication. Am J Surg. 1990; 160(5):490-495.
97. Leng GC, Lee AJ, Fowkes FG, et al. Randomized controlled trial of gammalinolenic acid and eicosapentaenoic acid in peripheral arterial disease. Clin Nutr. 1998; 17(6):265-271.
98. Watanabe N, Watanabe Y, Kumagai M, Fujimoto K. Administration of dietary fish oil capsules in healthy middle-aged Japanese men with a high level of fish consumption. Int J Food Sci Nutr. 2009; 60(suppl 5):136-142.
99. Mueller BA, Talbert RL. Biological mechanisms and cardiovascular effects of omega-3 fatty acids. Clin Pharm. 1988; 7(11):795-807.
100. Chen SH, Sun Y P, Chen XS. Effect of jiangtangkang on blood glucose, sensitivity of insulin and blood viscosity in non-insulin dependent diabetes mellitus [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 1997; 17(11):666-668.
101. Zheng L. Short-term effect and the mechanism of radix Angelicae on pulmonary hypertension in chronic obstructive pulmonary disease [in Chinese]. Zhonghua Jie He He Hu Xi Za Zhi. 1992; 15(2):95-97, 127.
102. Wu HN, Sun H. Study on clinical therapeutic effect of composite Salvia injection matched with Western medicine in treating diabetic foot [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2003; 23(10):727-729.
103. Tian XH, Xue WJ, Ding XM. Application of Danshen injection on early stage of renal transplantation [in Chinese]. Zhongguo Zhong Xi Yi Jie He Za Zhi. 2005; 25(5):404-407.
104. Giugliano D, Marfella, R, Verrazzo G, et al. The vascular effects of L-Arginine in humans: the role of endogenous insulin. J Clin Invest. 1997; 99(3):433-438.
105. Zou QZ, Bi RG, Li JM, et al. Effects of motherwort on blood hyperviscosity. Am J Chin Med. 1989; 17(1-2):65-70.
106. Feher G, Koltai K, Kesmarky G, et al. Effect of parenteral or oral vinpocetine on the hemorheological parameters of patients with chronic cerebrovascular diseases. Phytomedicine. 2009; 16(2-3):111-117.
107. Galduroz JC, Antunes HK, Santos RF. Gender- and age-related variations in blood viscosity in normal volunteers: a study of the effects of extract of Allium sativum and Ginkgo biloba. Phytomedicine. 2007; 14(7-8):447-451.
108. Santos RF, Galduroz JC, Barbieri A, Castiglioni ML, Ytaya LY, Bueno OF. Cognitive performance, SPECT, and blood viscosity in elderly non-demented people using Ginkgo biloba. Pharmacopsychiatry. 2003; 36(4):127-133.
109. Kato T, Yoneda S, Kako T, Koketsu M, Hayano I, Fujinami T. Reduction in blood viscosity by treatment with coenzyme Q10 in patients with ischemic heart disease. Int J Clin Pharmacol Ther Toxicol. 1990; 28(3):123-126.
110. Pais E, Alexy T, Holsworth RE Jr, Meiselman HJ. Effects of nattokinase, a profibrinolytic enzyme, on red blood cell aggregation and whole blood viscosity. Clin Hemorheol Microcirc. 2006; 35(1-2):139-142.
111. Wannamethee SG, Lowe GD, Rumley A, Bruckdorfer KR, Whincup PH. Associations of vitamin C status, fruit and vegetable intakes, and markers of inflammation and hemostasis. Am J Clin Nutr. 2006; 83(3):567-574.
112. Abdulah R, Koyama H, Miyazaki K, Nara M, Murakami M. Selenium supplementation and blood rheological improvement in Japanese adults. Biol Trace Elem Res. 2006; 112(1):87-96.
113. Ernst E, Pietsch L, Matrai A, Eisenberg J. Blood rheology in vegetarians. Br J Nutr. 1986; 56(3):555-560.