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Atherosclerosis

  • Y. Nishizawa
  • H. Koyama

Abstract

Atherosclerosis is a cause of cardiovascular disease, one of the most common causes of death. Since high plasma concentrations of cholesterol are one of the principal risk factors for atherosclerosis, the process of atherogenesis has been considered to mainly consist of the accumulation of lipids within the arterial wall. Recently, in broad outline, atherosclerosis can be considered to be a form of chronic inflammation resulting from the interaction between modified lipoproteins, monocyte-derived macrophages, T cells, and the normal cellular elements of the arterial wall [1]. This inflammatory process can ultimately lead to the development of complex lesions, or plaques, which are frequently associated with calcium accumulation (calcification). Importantly, these complexed lesions are sometimes complicated with plaque rupture and thrombosis, resulting in the acute clinical complications of myocardial infarction and stroke. Calcium deposition in atherosclerosis lesions is known to occur just after fatty streak formation. Microscopic analysis has shown small aggregates of crystalline calcium among the lipid particles of lipid cores in lesions of young adults [2]. Deposition of calcium is found in greater amounts in elderly and more advanced lesions. Atherosclerotic calcification is now known to be an organised, regulated process similar to bone formation that occurs only when other aspects of atherosclerosis are also present [3]. Osteocalcin, osteopontin and its mRNA and bone mor- phogenetic protein-2a, known to be involved in bone mineralisation and osteoblastic differentiation, have been identified in calcified atherosclerotic lesions.

Keywords

Vascular Smooth Muscle Cell Calcium Channel Blocker Coronary Artery Calcium Primary Hyperparathyroidism Coronary Artery Calcium Score 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Ross R. Atherosclerosis - an inflammatory disease. N Engl J Med 1999;340:115–26.PubMedCrossRefGoogle Scholar
  2. 2.
    Stary HC, Chandler AB, Dinsmore RE, Fuster V, Glagov S, Insull Jr W, etal. 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;92:1355–74. Google Scholar
  3. 3.
    Schinke T, McKee MD, Kiviranta R, Karsenty G. Molecular determinants of arterial calcification. Ann Med 1998;30:538–41.PubMedGoogle Scholar
  4. 4.
    Nayler WG. Review of preclinical data of calcium channel blockers and atherosclerosis. J Cardiovasc Pharmacol 1999;33:S7–11.PubMedCrossRefGoogle Scholar
  5. 5.
    Henry PD, Bentley KI. Suppression of atherogenesis in cholesterol-fed rabbits treated with nifedipine. J Clin Invest 1981;68:1366–9.PubMedCrossRefGoogle Scholar
  6. 6.
    Kramsch DM, Sharma RC. Limits of lipid-lowering therapy: the benefits of amlodipine as an anti- atherosclerotic agent. J Hum Hypertens 1995;9 Suppl 1:S3–9.PubMedGoogle Scholar
  7. 7.
    Thaulow E. Pharmacologic effects of calcium channel blockers on restenosis. J Cardiovasc Pharmacol 1999;33:S12–16.PubMedCrossRefGoogle Scholar
  8. 8.
    Habib JB, Bossaller C, Wells S, Williams C, Morrisett JD, Henry PD. Preservation of endothelium- dependent vascular relaxation in cholesterol-fed rabbits by treatment with the calcium blocker PN 200110. Circ Res 1986;58:305–9.PubMedGoogle Scholar
  9. 9.
    Kappagoda CT, Thomson AB, Senaratne MP. Effect of nisoldipine on atherosclerosis in the cholesterol fed rabbit: endothelium-dependent relaxation and aortic cholesterol content. Cardiovasc Res 1991;25:270–82.PubMedCrossRefGoogle Scholar
  10. 10.
    Rubanyi GM, Romero JC, Vanhoutte PM. Flow-induced release of endothelium-derived relaxing factor. Am J Physiol 1986;250:H 1145–9. Google Scholar
  11. 11.
    Joannides R, Haefeli WE, Linder L, Richard V, Bakkali EH, Thuillez C, etal. Nitric oxide is responsible for flow-dependent dilatation of human peripheral conduit arteries in vivo. Circulation 1995;91:1314–19.PubMedGoogle Scholar
  12. 12.
    Celermajer DS, Sorensen KE, Gooch VM, Spiegelhalter DJ, Miller OI, Sullivan ID, et al. Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis. Lancet 1992;340:1111–15.PubMedCrossRefGoogle Scholar
  13. 13.
    Celermajer DS, Sorensen KE, Georgakopoulos D, Bull C, Thomas O, Robinson J, et al. Cigarette smoking is associated with dose-related and potentially reversible impairment of endothelium-dependent dilation in healthy young adults. Circulation 1993;88:2149–55.PubMedGoogle Scholar
  14. 14.
    Alexander JJ, Miguel R, Piotrowski JJ. The effect of nifedipine on lipid and monocyte infiltration of the sub endothelial space. J Vase Surg 1993;17:841–7; discussion 847-8. CrossRefGoogle Scholar
  15. 15.
    Schmitz G, Robenek H, Beuck M, Krause R, Schurek A, Niemann R. Ca++ antagonists and ACAT inhibitors promote cholesterol efflux from macrophages by different mechanisms. I. Characterization of cellular lipid metabolism. Arteriosclerosis 1988;8:46–56.Google Scholar
  16. 16.
    Etingin OR, Hajjar DP. Calcium channel blockers enhance cholesteryl ester hydrolysis and decrease total cholesterol accumulation in human aortic tissue. Circ Res 1990;66:185–90.PubMedGoogle Scholar
  17. 17.
    Ondrias K, Misik V, Gergel D, Stasko A. Lipid peroxidation of phosphatidylcholine liposomes depressed by the calcium channel blockers nifedipine and verapamil and by the antiarrhythmic-antihypoxic drug stobadine. Biochim Biophys Acta 1989;1003:238–45.PubMedGoogle Scholar
  18. 18.
    Jackson CL, Bush RC, Bowyer DE. Inhibitory effect of calcium antagonists on balloon catheter-induced arterial smooth muscle cell proliferation and lesion size. Atherosclerosis 1988;69:115–22.PubMedCrossRefGoogle Scholar
  19. 19.
    Nilsson J, Sjolund M, Palmberg L, Von Euler AM, Jonzon B, Thyberg J. The calcium antagonist nifedipine inhibits arterial smooth muscle cell proliferation. Atherosclerosis 1985;58:109–22.PubMedCrossRefGoogle Scholar
  20. 20.
    Nomoto A, Mutoh S, Hagihara H, Yamaguchi I. Smooth muscle cell migration induced by inflammatory cell products and its inhibition by a potent calcium antagonist, nilvadipine. Atherosclerosis 1988;72:213–19.PubMedCrossRefGoogle Scholar
  21. 21.
    Pales J, Palacios-Araus L, Lopez A, Gual A. Effects of dihydropyridines and inorganic calcium blockers on aggregation and on intracellular free calcium in platelets. Biochim Biophys Acta 1991;1064:169–74.PubMedCrossRefGoogle Scholar
  22. 22.
    Zucker ML, Budd SE, Dollar LE, Chernoff SB, Altman R. Effect of diltiazem and low-dose aspirin on platelet aggregation and ATP release induced by paired agonists. Thromb Haemost 1993;70:332–5.PubMedGoogle Scholar
  23. 23.
    Rosenblum IY, Flora L, Eisenstein R. The effect of disodium ethane-1-hydroxy-1,1-diphosphonate (EHDP) on a rabbit model of athero-arteriosclerosis. Atherosclerosis 1975;22:411–24.PubMedCrossRefGoogle Scholar
  24. 24.
    Kramsch DM, Chan CT. The effect of agents interfering with soft tissue calcification and cell pro-liferation on calcific fibrous-fatty plaques in rabbits. Circ Res 1978;42:562–71.PubMedGoogle Scholar
  25. 25.
    Kramsch DM, Aspen AJ, Rozler LJ. Atherosclerosis: Prevention by agents not affecting abnormal levels of blood lipids. Science 1981;213:1511–12.PubMedCrossRefGoogle Scholar
  26. 26.
    Ylitalo R, Oksala O, Yla-Herttuala S, Ylitalo P. Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. J Lab Clin Med 1994;123: 769–76.PubMedGoogle Scholar
  27. 27.
    Hollander W, Paddock J, Nagraj S, Colombo M, Kirkpatrick B. Effects of anticalcifying and antifibrobrotic drugs on pre-established atherosclerosis in the rabbit. Atherosclerosis 1979;33:111–23.PubMedCrossRefGoogle Scholar
  28. 28.
    Daoud AS, Frank AS, Jarmolych J, Fritz KE. The effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) on necrosis of atherosclerotic lesions. Atherosclerosis 1987;67:41–8.PubMedCrossRefGoogle Scholar
  29. 29.
    Koshiyama H, Nakamura Y, Tanaka S, Minamikawa J. Decrease in carotid intima-media thickness after 1-year therapy with etidronate for osteopenia associated with type 2 diabetes. J Clin Endocrinol Metab 2000;85:2793–6.PubMedCrossRefGoogle Scholar
  30. 30.
    Ylitalo R, Monkkonen J, Urtti A, Ylitalo P. Accumulation of bisphosphonates in the aorta and some other tissues of healthy and atherosclerotic rabbits. J Lab Clin Med 1996;127:200–6.PubMedCrossRefGoogle Scholar
  31. 31.
    Ylitalo R, Monkkonen J, Yla-Herttuala S. Effects of liposome-encapsulated bisphosphonates on acetylated LDL metabolism, lipid accumulation and viability of phagocyting cells. Life Sei 1998;62:413–22.CrossRefGoogle Scholar
  32. 32.
    Palmer M, Adami HO, Bergstrom R, Akerstrom G, Ljunghall S. Mortality after surgery for primary hyperparathyroidism: a follow-up of 441 patients operated on from 1956 to 1979. Surgery 1987; 102:1–7.PubMedGoogle Scholar
  33. 33.
    Niederle B, Roka R, Woloszczuk W, Klaushofer K, Kovarik J, Schernthaner G. Successful parathyroidectomy in primary hyperparathyroidism: a clinical follow-up study of 212 consecutive patients. Surgery 1987;102:903–9.PubMedGoogle Scholar
  34. 34.
    Roberts WC, Waller BF. Effect of chronic hypercalcemia on the heart. An analysis of 18 necropsy patients. Am J Med 1981;71:371–84. Google Scholar
  35. 35.
    Palmer M, Adami HO, Bergstrom R, Jakobsson S, Akerstrom G, Ljunghall S. Survival and renal function in untreated hypercalcaemia. Population-based cohort study with 14 years of follow-up. Lancet 1987;1:59–62. Google Scholar
  36. 36.
    Chan CT, Wells H, Kramsch DM. Suppression of calcific fibrous-fatty plaque formation in rabbits by agents not affecting elevated serum cholesterol levels. The effect of thiophene compounds. Circ Res 1978;43:115–25. Google Scholar
  37. 37.
    Hines TG, Jacobson NL, Beitz DC, Littledike ET. Dietary calcium and vitamin D: risk factors in the development of atherosclerosis in young goats. J Nutr 1985;115:167–78.PubMedGoogle Scholar
  38. 38.
    Stimpel M, Neyses L, Locher R, Knorr M, Vetter W. High density lipoproteins - modulators of the calcium channel? J Hypertens 1985;Suppl 3:S49–51. Google Scholar
  39. 39.
    De Bacquer D, De Henauw S, De Backer G, Kornitzer M. Epidemiological evidence for an association between serum calcium and serum lipids. Atherosclerosis 1994;108:193–200.PubMedCrossRefGoogle Scholar
  40. 40.
    Klatsky AL, Friedman GD, Armstrong MA. The relationships between alcoholic beverage use and other traits to blood pressure: a new Kaiser Permanente study. Circulation 1986;73:628–36.PubMedCrossRefGoogle Scholar
  41. 41.
    Staessen J, Sartor F, Roels H, Bulpitt CJ, Claeys F, Ducoffre G, etal. The association between blood pressure, calcium and other divalent cations: a population study. J Hum Hypertens 1991;5:485–94.PubMedGoogle Scholar
  42. 42.
    Cooper RS, Shamsi N. Ionized serum calcium in black hypertensives: absence of a relationship with blood pressure. J Clin Hypertens 1987;3:514–19.PubMedGoogle Scholar
  43. 43.
    Neunteufl T, Katzenschlager R, Abela C, Kostner K, Niederle B, Weidinger F, etal. Impairment of endothelium-independent vasodilation in patients with hypercalcemia. Cardiovasc Res 1988;40: 396–401.CrossRefGoogle Scholar
  44. 44.
    Neunteufl T, Heher S, Prager G, Katzenschlager R, Abela C, Niederle B, etal. Effects of successful parathyroidectomy on altered arterial reactivity in patients with hypercalcaemia: results of a 3-year follow-up study. Clin Endocrinol (Oxf) 2000;53:229–33.CrossRefGoogle Scholar
  45. 45.
    Nickols GA. Actions of parathyroid hormone in the cardiovascular system. Blood Vessels 1987;24:120–4.PubMedGoogle Scholar
  46. 46.
    Smogorzewski M, Zayed M, Zhang YB, Roe J, Massry SG. Parathyroid hormone increases cytosolic calcium concentration in adult rat cardiac myocytes. Am J Physiol 1993;264:H 1998–2006. Google Scholar
  47. 47.
    Bogin E, Massry SG, Harary I. Effect of parathyroid hormone on rat heart cells. J Clin Invest 1981;67:1215–27.PubMedCrossRefGoogle Scholar
  48. 48.
    Saglikes Y, Massry SG, Iseki K, Nadler JL, Campese VM. Effect of PTH on blood pressure and response to vasoconstrictor agonists. Am J Physiol 1985;248:F674–81.PubMedGoogle Scholar
  49. 49.
    Nickols GA, Nana AD, Nickols MA, DiPette DJ, Asimakis GK. Hypotension and cardiac stimulation due to the parathyroid hormone-related protein, humoral hypercalcemia of malignancy factor. Endocrinology 1989;125:834–41.PubMedCrossRefGoogle Scholar
  50. 50.
    Nishizawa Y, Okui Y, Inaba M, Okuno S, Yukioka K, Miki T, etal. Calcium/calmodulin-mediated action of calcitonin on lipid metabolism in rats. J Clin Invest 1988;82:1165–72.PubMedCrossRefGoogle Scholar
  51. 51.
    Carthy EP, Yamashita W, Hsu A, Ooi BS. 1,25-Dihydroxyvitamin D3 and rat vascular smooth muscle cell growth. Hypertension 1989;13:954–9.PubMedGoogle Scholar
  52. 52.
    Mitsuhashi T, Morris Jr RC, Ives HE. 1,25-dihydroxyvitamin D3 modulates growth of vascular smooth muscle cells. J Clin Invest 1991;87:1889–95.PubMedCrossRefGoogle Scholar
  53. 53.
    Wakasugi M, Noguchi T, Inoue M, Kazama Y, Tawata M, Kanemaru Y, et al. Vitamin D3 stimulates the production of prostacyclin by vascular smooth muscle cells. Prostaglandins 1991;42:127–36.PubMedCrossRefGoogle Scholar
  54. 54.
    Suematsu Y, Nishizawa Y, Shioi A, Hino M, Tahara H, Inaba M, et al. Effect of 1,25-dihydroxyvitamin D3 on induction of scavenger receptor and differentiation of 12-O-tetradecanoylphorbol-13-acetate- treated THP-1 human monocyte-like cells. J Cell Physiol 1995;165:547–55.PubMedCrossRefGoogle Scholar
  55. 55.
    Mohtai M, Yamamoto T. Smooth muscle cell proliferation in the rat coronary artery induced by vitamin D. Atherosclerosis 1987;63:193–202.PubMedCrossRefGoogle Scholar
  56. 56.
    Jono S, Nishizawa Y, Shioi A, Morii H. 1,25-Dihydroxyvitamin D3 increases in vitro vascular calcification by modulating secretion of endogenous parathyroid hormone-related peptide. Circulation 1998;98:1302–6.PubMedGoogle Scholar
  57. 57.
    Kawagishi T, Nishizawa Y, Konishi T, Kawasaki K, Emoto M, Shoji T, etal. High-resolution B-mode ultrasonography in evaluation of atherosclerosis in uremia. Kidney Int 1995;48:820–6.PubMedCrossRefGoogle Scholar
  58. 58.
    Mautner GC, Mautner SL, Froehlich J, Feuerstein IM, Proschan MA, Roberts WC, et al. Coronary artery calcification: assessment with electron beam CT and histomorphometric correlation. Radiology 1994;192:619–23.PubMedGoogle Scholar
  59. 59.
    Detrano R, Froelicher V. A logical approach to screening for coronary artery disease. Ann Intern Med 1987;106:846–52.PubMedGoogle Scholar
  60. 60.
    Loecker TH, Schwartz RS, Cotta CW, Hickman Jr JR. Fluoroscopic coronary artery calcification and associated coronary disease in asymptomatic young men. J Am Coll Cardiol 1992;19:1167–72.PubMedCrossRefGoogle Scholar
  61. 61.
    Shemesh J, Apter S, Rozenman J, Lusky A, Rath S, Itzchak ·· etal. Calcification of coronary arteries: detection and quantification with double-helix CT. Radiology 1995;197:779–83. PubMedGoogle Scholar
  62. 62.
    Wexler L, Brundage B, Crouse J, Detrano R, Fuster V, Maddahi J, etal. Coronary artery calcification: pathophysiology, epidemiology, imaging methods, and clinical implications. A statement for health professionals from the American Heart Association. Writing Group. Circulation 1996;94:1175–92.Google Scholar
  63. 63.
    Rumberger JA, Simons DB, Fitzpatrick LA, Sheedy PF, Schwartz RS. Coronary artery calcium area by electron-beam computed tomography and coronary atherosclerotic plaque area. A histopathologic correlative study. Circulation 1995;92:2157–62.Google Scholar
  64. 64.
    Detrano RC, Wong ND, Doherty TM, Shavelle RM, Tang W, Ginzton LE, et al. Coronary calcium does not accurately predict near-term future coronary events in high-risk adults. Circulation 1999;99: 2633–8.PubMedGoogle Scholar
  65. 65.
    Arad Y, Spadaro LA, Goodman K, Newstein D, Guerci AD. Prediction of coronary events with electron beam computed tomography. J Am Coll Cardiol 2000;36:1253–60.PubMedCrossRefGoogle Scholar
  66. 66.
    Wong ND, Hsu JC, Detrano RC, Diamond G, Eisenberg H, Gardin JM. Coronary artery calcium evaluation by electron beam computed tomography and its relation to new cardiovascular events. Am J Cardiol 2000;86:495–8.PubMedCrossRefGoogle Scholar
  67. 67.
    Libby P. Molecular bases of the acute coronary syndromes. Circulation 1995;91:2844–50.PubMedGoogle Scholar
  68. 68.
    Cheng GC, Loree HM, Kamm RD, Fishbein MC, Lee RT. Distribution of circumferential stress in ruptured and stable atherosclerotic lesions. A structural analysis with histopathological correlation. Circulation 1993;87:1179–87. Google Scholar
  69. 69.
    Doherty TM, Detrano RC. Coronary arterial calcification as an active process: a new perspective on an old problem. Calcif Tissue Int 1994;54:224–30.PubMedCrossRefGoogle Scholar
  70. 70.
    Demer LL, Watson KE, Bostrom K. Mechanism of calcification in atherosclerosis. Trends Cardiovasc Med 1994;4:45–49.PubMedCrossRefGoogle Scholar
  71. 71.
    Roberts WC. Morphologic features of the normal and abnormal mitral valve. Am J Cardiol 1983;51:1005–28.PubMedCrossRefGoogle Scholar
  72. 72.
    Boon A, Cheriex E, Lodder J, Kessels F. Cardiac valve calcification: characteristics of patients with calcification of the mitral annulus or aortic valve. Heart 1997;78:472–4.PubMedGoogle Scholar
  73. 73.
    Adler Y, Herz I, Vaturi M, Fusman R, Shohat-Zabarski R, Fink N, et al. Mitral annular calcium detected by transthoracic echocardiography is a marker for high prevalence and severity of coronary artery disease in patients undergoing coronary angiography. Am J Cardiol 1998;82:1183–6.PubMedCrossRefGoogle Scholar
  74. 74.
    Adler Y, Koren A, Fink N, Tanne D, Fusman R, Assali A, etal. Association between mitral annulus calcification and carotid atherosclerotic disease. Stroke 1998;29:1833–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Boon A, Lodder J, Cheriex E, Kessels F. Risk of stroke in a cohort of 815 patients with calcification of the aortic valve with or without stenosis. Stroke 1996;27:847–51.PubMedCrossRefGoogle Scholar
  76. 76.
    Otto CM, Lind BK, Kitzman DW, Gersh BJ, Siscovick DS. Association of aortic-valve sclerosis with cardiovascular mortality and morbidity in the elderly. N Engl J Med 1999;341:142–7.PubMedCrossRefGoogle Scholar
  77. 77.
    Nayler WG. The antiatherogenic effects of amlodipine: promise of preclinical data. J Hum Hypertens 1992;6 Suppl 1:S19–23.PubMedGoogle Scholar
  78. 78.
    Willis AL, Nagel B, Churchill V, Whyte MA, Smith DL, Mahmud I, et al. Antiatherosclerotic effects of nicardipine and nifedipine in cholesterol-fed rabbits. Arteriosclerosis 1985;5:250–5.PubMedCrossRefGoogle Scholar
  79. 79.
    Nomoto A, Hirosumi J, Sekiguchi C, Mutoh S, Yamaguchi I, Aoki H. Antiatherogenic activity of FR34235 (Nilvadipine), a new potent calcium antagonist. Effect on cuff-induced intimal thickening of rabbit carotid artery. Atherosclerosis 1987;64:255–61.Google Scholar
  80. 80.
    Blumlein SL, Sievers R, Kidd P, Parmley WW. Mechanism of protection from atherosclerosis by verapamil in the cholesterol-fed rabbit. Am J Cardiol 1984;54:884–9.PubMedCrossRefGoogle Scholar
  81. 81.
    Hansen BF, Mortensen A, Hansen JF, Frandsen H. (-)-anipamil retards atherosclerosis in Watanabe heritable hyperlipidemic rabbits. J Cardiovasc Pharmacol 1995;26:485–9.PubMedCrossRefGoogle Scholar
  82. 82.
    Sugano M, Nakashima Y, Matsushima T, Takahara K, Takasugi M, Kuroiwa A, et al. Suppression of atherosclerosis in cholesterol-fed rabbits by diltiazem injection. Arteriosclerosis 1986;6:237–41.PubMedCrossRefGoogle Scholar
  83. 83.
    Corcos T, David PR, Val PG, Renkin J, Dangoisse V, Rapold HG, et al. Failure of diltiazem to prevent restenosis after percutaneous transluminal coronary angioplasty. Am Heart J 1985;109:926–31.PubMedCrossRefGoogle Scholar
  84. 84.
    Whitworth HB, Roubin GS, Hollman J, Meier B, Leimgruber PP, Douglas Jr JS, etal. Effect of nifedipine on recurrent stenosis after percutaneous transluminal coronary angioplasty. J Am Coll Cardiol 1986;8:1271–6.PubMedCrossRefGoogle Scholar
  85. 85.
    Hoberg E, Schwartz F, Schmig A. Prevention of restenosis by verapamil in the Verapamil Angioplasty Study (VAS) [abstract]. Circulation 1990;82 (Suppl 3):III–428. Google Scholar
  86. 86.
    O’Keefe Jr JH, Giorgi LV, Hartzler GO, Good TH, Ligon RW, Webb DL, etal. Effects of diltiazem on complications and restenosis after coronary angioplasty. Am J Cardiol 1991;67:373–6.PubMedCrossRefGoogle Scholar
  87. 87.
    Unverdorben M, Kunkel B, Leucht M, Bachman K. Reduction of restenosis after PTCA by diltiazem [abstract]. Circulation 1992;86:1–53.Google Scholar
  88. 88.
    Hillegass WB, Ohman EM, Leimberger JD, Califf RM. A meta-analysis of randomized trials of calcium antagonists to reduce restenosis after coronary angioplasty. Am J Cardiol 1994;73:835–9.PubMedCrossRefGoogle Scholar

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Authors and Affiliations

  • Y. Nishizawa
  • H. Koyama

There are no affiliations available

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