Skip to main content
Log in

Copper and ischemic heart disease

  • Published:
Biological Trace Element Research Aims and scope Submit manuscript

Abstract

Absolute or relative deficiency of copper is hypothesized to be of prime importance in the etiology of ischemic heart disease. According to recent estimates, only 25% of the diets in the United States contain the 2 mg of copper thought to be required daily by adults. Some of these diets have ratios of zinc to copper greater than those that have produced hypercholesteremia in animals. There are many epidemiologic associations between the ratio of zinc to copper and dietary characteristics, organ analyses, clinical status, and environmental features that relate the metabolism of these elements to the anatomy, chemistry, pathology, pharmacology, and physiology of ischemic heart disease. Animals deficient in copper or exposed to a high dietary ratio of zinc to copper, which can produce a relative copper deficiency, are hypercholesteremic and hyperuricemic, and have glucose intolerance and abnormalities of the electrocardiogram. Their hearts and arteries have abnormal connective tissue, lipid deposits, and inflammatory changes; they die suddenly, often with ruptured hearts. Hypercholesteremia and glucose intolerance have been found in men depleted of copper and in children with Menkes’ disease, an inability to absorb copper.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. L.M. Klevay, inMetabolism of Trace Metals in Man: Developmental Biology and Genetic Implications, O. M. Rennert and W.-Y. Chan, eds.,CRC Press, Boca Raton, in press.

  2. P. N. Hopkins and R. Williams,AtheroscIerosis 40, 1 (1981).

    Article  CAS  Google Scholar 

  3. T. Strasser,World Health Forum 3, 85 (1982).

    Google Scholar 

  4. L.M. Klevay, inAdvances in Nutritional Research, Vol. 1, H. H. Draper, ed., Plenum, New York, 1977, pp. 227–252.

    Google Scholar 

  5. W. Insull, Jr.,Coronary Risk Handbook, American Heart Association, New York, 1973, pp. 3, 14, 15, 24, 25.

    Google Scholar 

  6. W. B. Kannell,Am. J. Cardiol. 37, 269 (1976).

    Article  Google Scholar 

  7. A. Keys,Seven Countries: A Multivariate Analysis of Death and Coronary Heart Disease, Cambridge, Harvard University Press, 1980, pp. 251–252.

    Google Scholar 

  8. A. Keys, N. Kimura, A. Kusukawa, B. Bronte-Stewart, N. Larsen, and M. H. Keys,Am. J. Med. 48, 83 (1958).

    CAS  Google Scholar 

  9. M. Toor, A. Katchalsky, J. Agmon, and D. Allalouf,Circulation 22, 265 (1960).

    PubMed  CAS  Google Scholar 

  10. J. Hankin, D. Reed, D. Labarthe, M. Nichaman, and R. Stallones,Am. J. Clin. Nutr. 23, 346 (1970).

    PubMed  CAS  Google Scholar 

  11. J. Brown, G. J. Bourke, G. F. Gearty, A. Finnegan, M. Hill, F. C. Heffernan-Fox, D. E. Fitzgerald, J. Kennedy, R. W. Chitders, W. J. E. Jessop, M. F. Trutson, M. C. Latham, S. Cronin, M. B. McCann, R. E. Clancy, I. Gore, H. W. Stoudt, D. M. Hegsted, and F. J. Stare,World Rev. Nutr. Dieter. 12, 1 (1970).

    CAS  Google Scholar 

  12. S.M. Gain, W. D. Block, and M. A. Solomon,Am. J. Clin. Nutr. 33, 1714 (1980).

    Google Scholar 

  13. L. M. Klevay,Perspect. Biol. Med. 20, 186 (1977).

    PubMed  CAS  Google Scholar 

  14. L. M. Klevay, inInflammatory Diseases and Copper, J. R. J. Sorenson, ed., Humana Press, Clifton, New Jersey, 1982, pp. 123–136.

    Google Scholar 

  15. E. H. Ahrens, Jr.,Ann. Intern. Med. 85, 87 (1976).

    PubMed  Google Scholar 

  16. W. J. Zukel, R. H. Lewis, P. E. Enterline, R. C. Painter, L. S. Ralston, R. M. Fawcett, A. P. Meredith, and B. Peterson,Am. J. Public Health 49, 1630 (1959).

    Article  CAS  Google Scholar 

  17. O. Paul, M. H. Lepper, W. H. Phelan, G. W. Dupertuis, A. MacMillan, H. McKean, and H. Park,Circulation 28, 20 (1963).

    PubMed  CAS  Google Scholar 

  18. J. A. Little, H. M. Shanoff, A. C. Sima, S. E. Redmond, and R. Yano,Lancet 1, 933 (1965).

    PubMed  CAS  Google Scholar 

  19. O. A. Papp, L. Padilla, and A. L. Johnson,Lancet 2, 259 (1965).

    Article  PubMed  CAS  Google Scholar 

  20. J. A. Little, H. A. Shanoff, and A. Csima,Am. J. Clin. Nutr. 20, 133 (1967).

    PubMed  CAS  Google Scholar 

  21. A. Finegan, N. Hickey, B. Maurer, and R. Mulcahy,Am. J. Clin. Nutr. 21, 143 (1968).

    Google Scholar 

  22. D. R. Bassett, M. Abel, R. C. Moellering, Jr., G. Rosenblatt, and J. Stokes, III,Am. J. Clin. Nutr. 22, 1483 (1969).

    PubMed  CAS  Google Scholar 

  23. I. Obeyeskere,Isr. J. Med. Sci. 5, 561 (1969).

    Google Scholar 

  24. T. Gordon,The Framingham Study, Section 24, USDHEW, National Institutes of Health, Washington, DC 1970.

    Google Scholar 

  25. J. N. Morris, J. W. Marr, and D. G. Clayton,Br. Med. J. 2, 1307 (1977).

    PubMed  CAS  Google Scholar 

  26. F. H. Epstein, R. Simpson, and E. P. Boas,Am. J. Clin. Nutr. 4, 10 (1956).

    PubMed  CAS  Google Scholar 

  27. M. M. Hard and N. C. Esselbaugh,Am. J. Clin. Nutr. 8, 346 (1960).

    PubMed  CAS  Google Scholar 

  28. S. F. Adelson and A. Keys, Agricultural Research Service, USDA, Washington, DC, Pub. No. ARS 62-11, 1962.

    Google Scholar 

  29. W. B. Kannell, A. Kagan, T. R. Dawber, and N. Revotskie,Geriatrics 17, 675 (1962).

    Google Scholar 

  30. J. N. Morris, J. W. Marr, J. A. Heady, G. L. Mills, and T. R. E. Pilkington,Br. Med. J. 1, 571 (1963).

    Google Scholar 

  31. C. Den Hartog, Th. F. S. Van Schaik, L. M. Dalderup, E. F. Orion. and T. Malder,Voeding 26, 184 (1965).

    Google Scholar 

  32. S. C. Stulb, J. R. McDonough, D. G. Greenberg, and C. G. Haines,Am. J. Clin. Nutr. 16, 238 (1965).

    PubMed  CAS  Google Scholar 

  33. R. E. Hodges and W. A. Krehl,Am. J. Clin. Nutr. 17, 200 (1965).

    PubMed  CAS  Google Scholar 

  34. V. A. Beale,J. Am Dietet. Assoc. 46, 457 (1965).

    Google Scholar 

  35. J.H. Browe, O. M. Morlley, V. M. Logrillo, and J. T. Doyle,J. Am. Dietet. Assoc. 50, 376 (1967).

    CAS  Google Scholar 

  36. S. L. Malhotra,Am. J. Clin. Nutr. 20, 462 (1967).

    PubMed  CAS  Google Scholar 

  37. H. A. Kahn, J. H. Medalie, H. N. Neufetd, E. Riss, M. Balogh, and J. J. Groen,Isr. J. Med. Sci. 5, 1117 (1969).

    PubMed  CAS  Google Scholar 

  38. R. B. McGandy,Bull. NY Acad. Med. 47, 590 (1971).

    CAS  Google Scholar 

  39. M. R. Garcia-Palmieri,Am. J. Clin. Nutr. 26, 1133 (1973).

    PubMed  CAS  Google Scholar 

  40. A. B. Nichols, C. Ravenscroft, D. E. Lamphiear, and L. D. Ostrander, Jr.,J. Am. Meal. Assoc. 236, 1948 (1976).

    Article  CAS  Google Scholar 

  41. A. B. Nichols, C. Ravenscroft, D. E. Lamphiear, and L. D. Ostrander, Jr.,Am. J. Clin. Nutr. 29, 1384 (1976).

    PubMed  CAS  Google Scholar 

  42. L. Räsänen, M. Wilska, R. Kantero, V. Näntö, A. Ahtström, and N. Hallman,Am. J. Clin. Nutr. 31, 1050 (1978).

    PubMed  Google Scholar 

  43. W. H. Weidman, L. R. Elveback, R. A. Nelson, P. A. Hodgson, and R. D. Ellefson,Pediatrics 61, 354 (1978).

    PubMed  CAS  Google Scholar 

  44. C. J. Lee,Am. J. Clin. Nutr. 31, 1453 (1978).

    PubMed  CAS  Google Scholar 

  45. M. Jägerstad, Å Nordén and B. Åkesson,Scand. J. Gastroenterol. 14, Suppl. 52, 236 (1979).

    Google Scholar 

  46. R. P. Clarke, E. D. Schlenker, and S. B. Merrow,Am. J. Clin. Nutr. 34, 1743 (1981).

    PubMed  CAS  Google Scholar 

  47. T.R. Dawber, R. J. Nickerson, F. N. Brand, and J. Pool,Am. J. Clin. Nutr. 36, 617 (1982).

    PubMed  CAS  Google Scholar 

  48. R. B. Shekelle, A. M. Shryock, O. Paul, M. Lepper, J. Stamler, S. Liu, and W. J. Raynor,New Engl. J. Med. 304, 65 (1981).

    PubMed  CAS  Google Scholar 

  49. M.el Lozy,New Engl. J. Med. 304, 1168 (1981).

    Google Scholar 

  50. R. E. Olson,New Engl. J. Med. 304, 1169 (1981).

    Google Scholar 

  51. A. M. Fehily, J. E. Milbank, J. W. G. Yarnell, T. M. Hayes, A. J. Kubiki, and R. D. Eastham,Am. J. Clin. Nutr. 36, 890 (1982).

    PubMed  CAS  Google Scholar 

  52. G. V. Mann,New Engl. J. Med. 297, 644 (1977).

    PubMed  CAS  Google Scholar 

  53. W. J. Walker et al.New Engl. J. Med. 298, 106, 164 (1978).

    Article  Google Scholar 

  54. J. McMichael,Br. Med. J. 1, 173 (1979).

    PubMed  CAS  Google Scholar 

  55. L. Werkö,Acta Med. Scand. 206, 435 (1979).

    PubMed  Google Scholar 

  56. H. Malmros,Acta Med. Scand. 207, 145 (1980).

    PubMed  CAS  Google Scholar 

  57. J. McMichael,Acta Med. Scand. 207, 151 (1980).

    PubMed  CAS  Google Scholar 

  58. A. Keys,Acta Med. Scand. 207, 153 (1980).

    PubMed  CAS  Google Scholar 

  59. J. Stamler,Acta Med. Scand. 207, 433 (1980).

    PubMed  CAS  Google Scholar 

  60. O. Paul et al.JAMA 248, 1465 (1982).

    Article  Google Scholar 

  61. S. M. Grundy, D. Bilheimer, H. Blackburn, W. V. Brown, P. O. Kwiterovich, F. Mattson, G. Schonfeld, W. H. Weidman,Circulation 65, 839A (1982).

    PubMed  CAS  Google Scholar 

  62. L. M. Klevay,Am. J. Clin. Nutr. 26, 1060 (1973).

    PubMed  CAS  Google Scholar 

  63. L. M. Klevay,Am. J. Clin. Nutr. 28, 764 (1975).

    PubMed  CAS  Google Scholar 

  64. L. M. Klevay,Ann. NYAcad. Sci. 355, 140 (1980).

    Article  CAS  Google Scholar 

  65. L. M. Klevay,J. Environ. Path. Tox. 4, 281 (1980).

    CAS  Google Scholar 

  66. L. M. Klevay, inNutrition and Heart Disease, H. K. Naito, ed. S. P. Medical and Scientific Books, New York, 1982, pp. 61–67.

    Google Scholar 

  67. K. Y. Lei,Nutr. Repo Int. 15, 597 (1977).

    CAS  Google Scholar 

  68. B. L. O’Dell, inProceedings of the New Zealand Workshop on Trace Elements in New Zealand, University of Otago, Dunedin, 1981, pp. 157–164.

    Google Scholar 

  69. P. W. Harvey and K. D. G. Allen,J. Nutr. 111, 1855 (1981).

    PubMed  CAS  Google Scholar 

  70. F.H. Nielsen, T. J. Zimmerman, and T. R. Shuler,Biol. Trace Element Res. 4, 125 (1982).

    Article  CAS  Google Scholar 

  71. L.M. Klevay, inTrace Substances in Environmental Health-VIII, D. D. Hemphill, ed., University of Missouri Press, Columbia, Missouri, 1974, pp. 9–14.

    Google Scholar 

  72. L. M. Klevay,Nutr. Rep. Int. 9, 393 (1974).

    CAS  Google Scholar 

  73. J.T. Anderson, F. Grande, and A. Keys,J. Am. Dietet. Assoc. 62, 133 (1973).

    CAS  Google Scholar 

  74. L.M. Klevay, K. P. Vo-Khactu, and R. A. Jacob, inTrace Substances in Environmental Health-IX, D. D. Hemphill, ed., University of Missouri Press, Columbia, Missouri, 1975, pp. 131–138.

    Google Scholar 

  75. H. C. Lukaski, L. M. Klevay, W. W. Bolonchuk, J. R. Mahalko, D. B. Milne, L. K. Johnson, and H. H. Sandstead,Fed. Proc. 41, 275 (1982).

    Google Scholar 

  76. L. M. Klevay,Nutr. Rep. Int. 26, 405 (1982).

    CAS  Google Scholar 

  77. Anon.,Recommended Dietary Allowances, Food and Nutrition Board, National Research Council, National Academy of Sciences, Washington, DC, 1974, pp. 95–96.

  78. H. H. Sandstead,Am. J. Clin. Nutr. 35, 809 (1982).

    PubMed  CAS  Google Scholar 

  79. L. M. Klevay, L. Inman, L. K. Johnson, M. R. Lawler, J. R. Mahalko, D. B. Milne, and H. H. Sandstead,Clin. Res. 28, 758A (1980).

    Google Scholar 

  80. H. S. White,J. Am. Diet. Assoc. 55, 38 (1969).

    PubMed  CAS  Google Scholar 

  81. A. Gormican,J. Am. Diet. Assoc. 56, 397 (1970).

    PubMed  CAS  Google Scholar 

  82. N. O. Price, G. E. Bunce, and R. W. Engel,Am. J. Clin. Nutr. 23, 258 (1970).

    PubMed  CAS  Google Scholar 

  83. R. Willvonseder, N. P. Goldstein, J. T. McCall, R. E. Yoss, and W. N. Tauxe,Neurol. 23, 1039 (1973).

    CAS  Google Scholar 

  84. E. D. Brown, M. P. Howard and J. C. Smith, Jr.,Fed. Proc. Fed. Am. Soc. Exp. Biol. 36, 1122 (1977).

    Google Scholar 

  85. G.P. Van Berge Henegouwen, T. N. Tangedahl, A. F. Hoffmann, T. C. Northfield, N. F. LaRusso, and J. T. McCall,Gastroenterology 72, 1228 (1977).

    PubMed  Google Scholar 

  86. J.L. Greger, S.C. Zaikis, R. P. Abernathy, O. A. Bennett, and J. Huffman,J. Nutr. 108, 1449 (1978).

    PubMed  CAS  Google Scholar 

  87. J. M. Holden, W. R. Wolf, and W. Mertz,J. Am. Diet. Assoc. 75, 23 (1979).

    PubMed  CAS  Google Scholar 

  88. L. M. Klevay, S. J. Reck, and D. F. Barcome,JAMA 241, 1916 (1979).

    Article  PubMed  CAS  Google Scholar 

  89. H. Spencer, C. R. Asmussen, R. B. Holtzman, and L. Kramer,Am. J. CIin. Nutr. 32, 1867 (1979).

    CAS  Google Scholar 

  90. D. B. Milne, D. D. Schnakenberg, H. L. Johnson, and G. L. Kuhl,J. Am. Diet. Assoc. 76, 41 (1980).

    PubMed  CAS  Google Scholar 

  91. L. J. Taper, M. L. Hinners, and S. J. Ritchey,Am. J. Clin. Nutr. 33, 1077 (1980).

    PubMed  CAS  Google Scholar 

  92. K. Y. Lei,Nutr. Rep. Int. 22, 459 (1980).

    CAS  Google Scholar 

  93. M. G. Crews, L. J. Taper, and S. J. Ritchey,Am. J. Clin. Nutr. 33, 1940 (1980).

    PubMed  CAS  Google Scholar 

  94. D. M. Burke, F. J. DeMicco, L. J. Taper, and S. J. Ritchey,J. Gerontol. 36, 558 (1981).

    PubMed  CAS  Google Scholar 

  95. S. M. Snedeker, S. A. Smith, and J. L. Greger,J. Nutr. 112, 136 (1982).

    PubMed  CAS  Google Scholar 

  96. P. Koivistoinen, A. Ahlstrom, H. Nissinen, M. Pekkarinen, and P. Roine,Suom. Kemistil. B43, 426 (1970).

    Google Scholar 

  97. T. H. Hartley, J. B. Dawson, and A. Hodgkinson,Clin. Chim. Acta. 52, 321 (1974).

    Article  PubMed  CAS  Google Scholar 

  98. B. E. Guthrie and M. F. Robinson,Br. J. Nutr. 38, 55 (1977).

    Article  PubMed  CAS  Google Scholar 

  99. M. Abdulla and S. Svensson,Scand. J. Gastroenterol. 14 Suppl. 42, 172 (1979).

    CAS  Google Scholar 

  100. H. L. Keil and V. E. Nelson,J. Biol. Chem. 106, 343 (1934).

    CAS  Google Scholar 

  101. A.M. Cohen, A. Teitelbaum, E. Miller, V. Ben-Tor, R. Hirt, and M. Fields,Isr. J. Med. Sci. 18, 840 (1982).

    PubMed  CAS  Google Scholar 

  102. L. M. Klevay,Nutr. Rep. Int. 26, 329 (1982).

    CAS  Google Scholar 

  103. L. M. Klevay, and K. E. Viestenz,Am. J. Physiol. 240, (Heart Circ. Physiol. 9), H185 (1981).

    PubMed  CAS  Google Scholar 

  104. K. E. Viestenz and L. M. Klevay,Am. J. Clin. Nutr. 35, 258 (1982).

    PubMed  CAS  Google Scholar 

  105. H. Newland,Med. Hypothesis 1, 152 (1975).

    Article  CAS  Google Scholar 

  106. W. B. Kannel, W. P. Castelli, and T. Gordon,Ann. Intern. Med. 90, 85 (1979).

    PubMed  CAS  Google Scholar 

  107. L. M. Klevay,Nutr. Rep. Int. 22, 617 (1980).

    CAS  Google Scholar 

  108. P.R. Blackett, D. D. Donaldson, D. Lee, W. Y. Chan, J. H. Holcombe, and O. M. Rennert,Ped. Res. 15 (No. 4, Part 2), 626 (1981).

    Article  Google Scholar 

  109. L. M. Klevay, W. K. Canfield, S. K. Gallagher, L. K. Henriksen, W. Bolonchuk, L. K. Johnson, H. C. Lukaski, D. B. Milne, and H. H. Sandstead,Am. J. Clin. Nutr. 37, 717 (1983).

    Google Scholar 

  110. P.L. Hooper, L. Visconti, P. J. Garry, and G. E. Johnson,JAMA 244, 1960 (1980).

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Klevay, L.M. Copper and ischemic heart disease. Biol Trace Elem Res 5, 245–255 (1983). https://doi.org/10.1007/BF02987211

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02987211

Index Entries

Navigation