Advertisement

The natural history of atherosclerosis: an ecologic perspective

  • Harold N. Mozar
    Correspondence
    Correspondence to: Harold N. Mozar, Chronic Disease Control Branch, California State Department of Health Services, 714 P. Street, P.O. Box 942732, Sacramento, CA 94234-7320, U.S.A. Phone: (916) 322-4787.
    Affiliations
    Chronic Diseases Control Branch, California State Department of Health Services, Sacramento, CA 94234-7320 U.S.A.
    Search for articles by this author
  • Dileep G. Bal
    Affiliations
    Chronic Diseases Control Branch, California State Department of Health Services, Sacramento, CA 94234-7320 U.S.A.
    Search for articles by this author
  • Saleem A. Farag
    Affiliations
    Chronic Diseases Control Branch, California State Department of Health Services, Sacramento, CA 94234-7320 U.S.A.
    Search for articles by this author
      This paper is only available as a PDF. To read, Please Download here.

      Abstract

      Virologic findings reported in recent atherosclerosis literature may have profound implications. To assess them, we have viewed atherosclerosis in a broad biologic context and against a background of environmental, behavioral, and social change. Reasonable grounds exist, we believe, for regarding atherosclerosis as a chronic, low-grade infectious macroangiopathy which is aggravated by hypercholesterolemia and other recognized risk factors. There are probably multiple infective pathogens and transmission routes. The putative agents that initiate atherosclerosis might include ubiquitous viruses that produce clinically unapparent infections in many animal species. Pathways for their transmission to humans may include the food chain and contaminated water. Food-chain transmission may have been largely responsible for the parallel increases of meat consumption and mortality from coronary heart disease in the United States during the middle third of the century. It provides a hypothetical basis for considering thermal intervention as a heretofore unrecognized factor that may actually best account for the surprising reversal of climbing heart disease mortality rates. Improved sanitation and food hygiene as well as improvements in diet, lifestyle, and medical care may have shaped the downward mortality curve. The virus hypothesis may reconcile apparent epidemiologic conflicts and elucidate the natural history of atherosclerosis.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

      1. Arch. Intern. Med. 1988; : 36
        • Steinberg D.
        • Parthasarathy S.
        • Carew T.E.
        • Khoo J.C.
        • Witztum J.L.
        Beyond cholesterol — modifications of low-density lipoprotein that increase its atherogenicity.
        N. Engl. J. Med. 1989; 320: 915
        • Kannel W.B.
        The role of cholesterol in atherosclerosis.
        Med. Clin. N. Am. 1974; 58: 363
        • Kritchevsky D.
        Nutrition and heart disease.
        Food Technology. 1979; 33: 39
        • Leaf A.
        Cardiovascular effects of n − 3 fatty acids.
        N. Engl. J. Med. 1988; 319: 363
        • Cottrell R.C.
        Cholesterol lowering and the risk of coronary heart disease.
        Lancet. 1984; 1: 520
        • Ceville N.F.
        Cell Pathology.
        in: Iowa State University Press, Ames, IA1983: 635
        • Virchow R.
        Phlogose and Thrombose im Gefäss-system. Gesammelte Abhandlungen zur Wissenschaftlichen Medizin.
        F. Meidinger, Frankfurt1856
        • Klotz O.
        • Manning M.F.
        Fatty streaks in the intima of arteries.
        J. Pathol. Bacteriol. 1912; 16: 211
        • Frothingham Jr., C.
        The relation between acute infectious diseases and arterial lesions.
        Arch. Intern. Med. 1911; 8: 153
        • Aschoff L.
        Verh. Dtsch. Pathol. Gesellsch. 1907; 10: 106
        • Anitschkow N.
        • Chalatow S.
        On experimental cholesterin steatosis and its significance in the origin of some pathological processes.
        Centrall. Allg. Pathol. Pathol. Anat. 1913; 24 (Transl. by Pebias M.Z.): 1
        • Anitschkow N.
        • Chalatow S.
        Arteriosclerosis. 1983; 3: 178
        • Saphir O.
        Inflammatory factors in arteriosclerosis.
        in: Blumenthal H.T. Cowdry's Arteriosclerosis. Charles C Thomas, Springfield, IL1967: 415
        • Ross R.
        • Glomset J.A.
        The pathogenesis of atherosclerosis.
        N. Engl. J. Med. 1976; 295 (Part I): 369
        • Ross R.
        • Glomset J.A.
        The pathogenesis of atherosclerosis.
        N. Engl. J. Med. 1976; 295 (part II): 420
        • Ross R.
        The pathogenesis of atherosclerosis — an update.
        N. Engl. J. Med. 1986; 314: 488
        • Robbins S.L.
        • Cotran R.S.
        • Kumar V.
        Pathologic Basis of Disease.
        in: W.B. Saunders Company, Philadelphia, PA1984: 593
        • Burch G.E.
        Of atherosclerosis in infants and children and viral infections.
        Am. Heart J. 1978; 96: 107
        • Kolata G.
        Virus-heart link studied.
        Science. 1985; 227: 735
        • Culliton B.J.
        Endothelial cells to the rescue.
        Science. 1989; 246: 749
        • Burch G.E.
        • Tsui C.Y.
        • Harb J.M.
        Pathologic changes of aorta and coronary arteries of mice infected with Coxsackie B4 virus (35641).
        in: Proc. Soc. Exp. Med. Biol.137. 1971: 657
        • Burch G.E.
        Viruses and atherosclerosis.
        Am. Heart J. 1974; 87: 407
        • Fabricant C.G.
        • Krook L.
        • Gillespie J.H.
        Virus-induced cholesterol crystals.
        Science. 1973; 181: 566
        • Benditt E.P.
        • Benditt J.M.
        Evidence for a monoclonal origin of human atherosclerotic plaque.
        in: Proc. Natl. Acad. Sci. USA. 70. 1973: 1753
        • Fabricant C.G.
        • Fabricant J.
        • Litrenta M.M.
        • Minick C.R.
        Virus-induced atherosclerosis.
        J. Exp. Med. 1978; 148: 335
        • Minick C.R.
        • Fabricant C.G.
        • Fabricant J.
        • Litrenta M.M.
        Athero-arteriosclerosis induced by infection with a herpesvirus.
        Am. J. Pathol. 1979; 96: 673
        • Benditt E.P.
        • Barrett T.
        • McDougall J.K.
        Viruses in the etiology of atherosclerosis.
        in: Proc. Natl. Acad. Sci. USA. 80. 1983: 6386
        • Grattan M.T.
        • Moreno-Cabral C.E.
        • Starnes V.A.
        • Oyer P.E.
        • Stinson E.B.
        • Shumway N.E.
        Cytomegalovirus infection is associated with cardiac allograft rejection and atherosclerosis.
        JAMA. 1989; 261: 3561
        • Hajjar D.P.
        • Fabricant C.G.
        • Minick C.R.
        • Fabricant J.
        Virus-induced atherosclerosis — herpesvirus infection alters aortic cholesterol metabolism and accumulation.
        Am. J. Pathol. 1986; 122: 62
        • Melnick J.L.
        • Petrie B.L.
        • Dreesman G.R.
        • Burek J.
        • McCollum C.H.
        • DeBakey M.E.
        Cytomegalovirus antigen with human arterial smooth muscle cells,.
        Lancet. 1983; 2: 644
        • Adam E.
        • Melnick J.L.
        • Probtsfield J.L.
        • Bailey K.R.
        • McCollum C.H.
        • DeBakey M.E.
        High levels of cytomegalovirus antibody in patients requiring vascular surgery for atherosclerosis.
        Lancet. 1987; 2: 291
        • Yamashiroya H.M.
        • Ghosh L.
        • Yang R.
        • Robertson Jr., A.L.
        Herpesviridae in the coronary arteries and the aorta of young trauma victims.
        Am. J. Pathol. 1988; 130: 71
        • Mozar H.N.
        • Bal D.G.
        • Farag S.A.
        Human cancer and the food chain: an alternative etiologic perspective.
        Nutr. Cancer. 1989; 12: 29
        • Mayr A.
        New emerging viral zoonoses.
        Vet. Rec. 1980; 106: 407
        • Bohorquez F.
        • Stout C.
        Arteriosclerosis in exotic animals.
        Atherosclerosis. 1972; 16: 225
        • T-W-Fiennes R.N.
        Atherosclerosis in wild animals.
        in: Roberts J.C. Straus R. Comparative Atherosclerosis. Harper and Row, New York, NY1965: 113-126
      2. Sherman, M., Comparative, veterinary, and primate cardiovascular research. A review of research grants supported by the National Heart Institute Extramural Programs, Bethesda, MD, pp. 81–82.

        • McKinney B.
        Atherosclerosis in wild animals.
        Lancet. 1962; 2: 281
        • McCullagh K.G.
        Arteriosclerosis in the African elephant.
        Atherosclerosis. 1972; 16: 307
        • Howard Jr., C.F.
        Aortic atherosclerosis in normal and spontaneously diabetic Macaca nigra.
        Atherosclerosis. 1979; 33: 479
        • Detweiler D.K.
        • Ratcliffe H.L.
        • Luginbuhl H.
        The significance of naturally-occurring coronary and cerebral artery disease in animals.
        Ann. N.Y. Acad. Sci. 1968; 149: 868
        • Stehbens W.E.
        Intimal proliferation and spontaneous lipid deposition in the cerebral arteries of sheep and steers.
        J. Arterioscler. Res. 1965; 5: 556
        • Knieriem H.J.
        Electron-microscopic study of bovine arteriosclerotic lesions.
        Am. J. Pathol. 1967; 50: 1035
        • Moss N.S.
        • Benditt E.P.
        The ultrastructure of spontaneous and experimentally induced arterial lesions. II. The spontaneous plaque in the chicken.
        Lab. Invest. 1970; 23: 231
        • Clarkson T.B.
        • Prichard R.W.
        • Bullock B.C.
        • Lehner N.D.M.
        • Lofland H.B.
        • St. Clair R.W.
        Animal Models for Biomedical Research. National Academy of Sciences, Washington, DC1970: 22-41
        • Saunders R.L.
        • Farrell A.P.
        Coronary arteriosclerosis in Atlantic salmon.
        Arteriosclerosis. 1988; 8: 378
        • McKenzie J.E.
        • House E.W.
        • McWilliams J.G.
        • Johnson D.W.
        Coronary degeneration in sexually mature rainbow and steelhead trout, Salmo gairdneri.
        Atherosclerosis. 1978; 29: 431
        • Stout C.
        • Groover Jr., M.E.
        Spontaneous versus experimental atherosclerosis.
        Ann. N.Y. Acad. Sci. 1969; 162: 89
        • Moriyama I.M.
        Statistical studies of heart disease and allied causes of death in relation to age changes in the population.
        Public Health Rep. 1948; 63: 573
        • Levy R.I.
        The decline in cardiovascular disease mortality.
        Annu. Rev. Public Health. 1981; 2: 49
        • Campbell M.
        Death rate from diseases of the heart: 18761959.
        Br. Med. J. 1963; 2: 528
        • Carroll K.K.
        Hypercholesterolemia and atherosclerosis: effects of dietary protein.
        Fed. Res. 1982; 41: 2792
        • Gortner W.A.
        Nutrition in the United States, 1900 to 1974.
        Cancer Res. 1975; 35: 3246
        • Borhani N.O.
        • Hechter H.H.
        Recent changes in CVR disease mortality in California.
        Public Health Rep. 1964; 79: 147
        • Stallones R.A.
        The rise and fall of ischemic heart disease.
        Sci. Am. 1980; 243: 53
        • Gordon T.
        Recent decline in coronary disease mortality in the United States: part of a general decline in mortality.
        Am. Heart J. 1982; 103: 151
        • Wing S.
        • Hayes C.
        • Knowles J.E.
        • Riggan W.
        • Tyroler H.A.
        Geographic variation in the onset of ischemic heart disease mortality in the United States.
        Am. J. Public Health. 1986; 76: 1404
        • Wing S.
        • Casper M.
        • Hayes C.
        • Tyroler H.A.
        Socioenvironmental characteristics associated with the onset of decline of ischemic heart disease in the United States.
        Am. J. Public Health. 1988; 78: 923
        • Lyman D.O.
        Trichinellosis in California: a 52-year review.
        in: Kim C.W. Trichinellosis. Intext Educational Publishers, New York, NY1974: 571-577
        • Zimmermann W.J.
        The current status of trichinellosis in the United States.
        in: Kim C.W. trichinellosis. Intext Educational Publishers, New York, NY1974: 603-609
        • Plorde J.J.
        Parasitic infections.
        in: Berkow R. Fletcher A.J. Merck Manual Merck Sharp and Dohme Research Laboratories, Rahway, N.J1987: 197
        • Ducimetriere P.
        • Richard J.L.
        • Cambien P.
        • Rakotoao R.
        • Claude J.R.
        Coronary heart disease in middle-aged Frenchmen.
        Lancet. 1980; 1: 1346
        • La Veccia C.
        • Decarli A.
        Trends in ischemic heart disease mortality in Italy, 1968–1978.
        Am. J. Public Health. 1986; 76: 454
        • Thom T.J.
        • Epstein F.H.
        • Feldman J.J.
        • Leaverton P.E.
        Trends in total mortality and mortality from heart disease in 26 countries from 1950 to 1978.
        Int. J. Epidemiol. 1985; 14: 510
      3. MMWR. 1988; 37: 313
      4. MMWR. 1988; 37: 319
        • Kozar Z
        Incidence of Trichinella in the world and actual connected problems.
        in: Kozar Z. trichinellosis. PWN — Polish Scientific Publishers, Warsaw1962: 65
        • Davies J.W.
        • Semenciw R.M.
        • Mao Y.
        Cardiovascular disease mortality trends and related risk factors in Canada.
        Can. J. Cardiol. 1988; 4: 16A
        • Fleck A.
        Latitude and ischemic heart disease.
        Lancet. 1989; 1: 613
      5. World Health Statistics Annual 1987. World Health Organization, Geneva1987
        • Bang H.O.
        • Dyerberg J.
        • Nielsen A.B.
        Plasma lipid and lipoprotein pattern in Greenlandic West-Coast Eskimos.
        Lancet. 1971; 1: 1143
        • Poskanzer D.C.
        • Schapira K.
        • Miller H.
        Multiple sclerosis and poliomyelitis.
        Lancet. 1963; 2: 917
        • Alter M.
        • Loewenson R.
        • Harshe M.
        The geographic distribution of multiple sclerosis: an examination of mathematical models.
        J. Chron, Dis. 1973; 26: 755
        • Nathanson N.
        Slow viruses and chronic disease: the contribution of epidemiology.
        Public Health Rep. 1980; 95: 436
        • Post G.
        Textbook of Fish Health.
        in: T.F.H. Publications, Neptune City, NJ1987: 217
        • Ueshima H.
        • Tatara K.
        • Asakura S.
        Declining mortality from ischemic heart disease and changes in coronary risk factors in Japan, 1956–1980.
        Am. J. Epidemiol. 1987; 125: 62
        • Goldbourt U.
        • Kirk J.D.
        The epidemiology of coronary heart disease in the ethically and culturally diverse population of Israel.
        Isr. J. Med. Sci. 1982; 18: 1007
        • Guberan E.
        Surprising decline of cardiovascular mortality in Switzerland: 1951–1976.
        J. Epiderniol. Comm. Health. 1979; 33: 114
        • Welin L.
        • Larsson B.
        • Svardsudd K.
        • Wilhelmsen L.
        • Tibelin G.
        Why is the incidence of ischemic heart disease in Sweden increasing? Study of men born in 1913 and 1923.
        Lancet. 1983; 1: 1087
        • Trowell H.
        Hypertension, obesity, diabetes and coronary heart disease.
        in: Trowell H.C. Burkitt D.P. Western Diseases. Edward Arnold Publishers, London1981: 3
        • Keys A.
        Coronary heart disease — the global picture.
        Atherosclerosis. 1975; 22: 149
        • Barnes B.O.
        On the genesis of atherosclerosis.
        J. Am. Geriatr. Soc. 1973; 21: 350