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Original article| Volume 47, ISSUE 9, P961-969, September 1994

Serum total cholesterol and mortality in a Japanese population

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      Abstract

      Although the relation between serum total cholesterol and coronary heart disease is well established, the relation with mortality from non-coronary disease is controversial. Inverse relations of serum cholesterol with hemorrhagic stroke and cancer have stimulated the examination of cholesterol-non-coronary mortality associations. The population surveyed is 12,187 men and women aged 40–69 years living in Yao City, a suburb of Osaka, who undertook baseline examinations between 1975 and 1984 and had no history of stroke and coronary heart disease at baseline. The subjects were followed on average 8.9 years until the end of 1988 using systematic mortality surveillance. During the follow-up, there were 343 deaths, comprising 170 cancer deaths (International Classification of Death 9th edition: ICD-9, 140–239), 21 coronary heart disease deaths (ICD-9, 410–414), 67 other cardiovascular deaths (ICD-9, 390–458 excluding 410–414), and 85 non-cardiovascular, non-cancer deaths. There was a significant inverse association of serum cholesterol with total and cancer mortality for men, and no significant association for women. The cholesterol-disease association, although not significant, was positive for coronary heart disease and other cardiovascular disease deaths, and inverse for non-cardiovascular, non-cancer deaths in both sexes. The inverse association of serum cholesterol with total and cancer mortality for men remained significant after controlling for age, job classification, hypertension category, usual alcohol intake, cigarette smoking, and relative weight index. A 34 mg/dl (1 SD) lower serum cholesterol level was associated with a 21% (95% confidence interval (CI) = 4–42%) higher risk of total mortality and a 26% (95% CI interval = 2–56%) higher risk of cancer death. These inverse associations were stronger in current heavy drinkers (≧ 56 g ethanol per day) than in the other men. The inverse association between serum cholesterol and cancer was also significant when deaths within the first 5 years were excluded from the analysis. Whether the inverse association is explained by other factors or whether this association is causal requires further investigation.

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      References

        • WHO Expert Committee on Prevention of Coronary Heart Disease
        Prevention of coronary heart disease.
        in: 2nd edition. World Health Organization Technical Report Series 678. World Health Organization, Geneva1982
        • Komachi Y.
        • Ozawa H.
        • Iida M.
        • et al.
        Characteristics of cardiovascular disease in Japan (in Japanese).
        Kosei no Sihyou. 1966; 13: 1-12
        • Komachi Y.
        • Iida M.
        • Shimamoto T.
        • et al.
        Geographic and occupational comparisons of risk factors in cardiovascular diseases in Japan.
        Jpn Circ J. 1971; 35: 189-207
        • Ueshima H.
        • Iida M.
        • Shimamoto T.
        • et al.
        Multivariate analysis of risk factor for stroke: eight-year follow-up study of farming villages in Akita, Japan.
        Prev Med. 1980; 9: 722-740
        • Tanaka H.
        • Ueda Y.
        • Hayashi M.
        • et al.
        Risk factors for cerebral hemorrhage and cerebral infarction in a Japanese rural community.
        Stroke. 1982; 13: 62-73
        • Kagan A.
        • Popper J.S.
        • Rhoads G.G.
        Factors related to stroke incidence in Hawaiian Japanese men, the Honolulu Heart Study.
        Stroke. 1980; 11: 14-21
        • Yano K.
        • Reed D.M.
        • Maclean C.J.
        Serum cholesterol and hemorrhagic stroke in the Honolulu Heart Program.
        Stroke. 1989; 20: 1460-1465
        • Iso H.
        • Jacobs Jr, D.R.
        • Wentworth D.
        • Neaton J.D.
        • Cohen J.D.
        Serum cholesterol levels and six-year mortality from stroke in 350,977 men screened for the Multiple Risk Factor Intervention Trial.
        N Engl J Med. 1989; 320: 904-910
        • Neaton J.D.
        • Blackburn H.
        • Jacobs D.
        • et al.
        Serum cholesterol level and mortality: findings for men screened in the Multiple Risk Factor Intervention Trial.
        Arch Intern Med. 1992; 152: 1490-1500
        • Rose G.
        • Shipley M.
        Plasma lipids and mortality: a source of error.
        Lancet. 1980; 1: 523-526
        • Cambien F.
        • Ducimetiere P.
        • Richard J.
        Total serum cholesterol and cancer mortality in a middle-aged male population.
        Am J Epidemiol. 1980; 112: 388-394
        • Keys A.
        • Aravanis C.
        • Blackburn H.
        • et al.
        Serum cholesterol and cancer mortality in the Seven Countries Study.
        Am J Epidemiol. 1985; 121: 870-883
        • Sherwin R.W.
        • Wentworth D.N.
        • Cutler J.A.
        • Hulley S.B.
        • Kuller L.H.
        • Stamler J.
        Serum cholesterol levels and cancer mortality in 361,622 men screened for the Multiple Risk Factor Intervention Trial.
        JAMA. 1987; 257: 943-948
        • Tornberg S.A.
        • Holm L.E.
        • Carstensen J.M.
        • Eklund G.A.
        Cancer incidence and cancer mortality in relation to serum cholesterol.
        J Natl Cancer Inst. 1989; 81: 1917-1921
        • Garcia-Palmiere M.R.
        • Sorlie P.D.
        • Costas R.
        • Havlik R.J.
        An apparent inverse relationship between serum cholesterol and cancer mortality in Puerto Rico.
        Am J Epidemiol. 1981; 114: 29-40
        • Kozarevic D.J.
        • McGee D.
        • Vojovodic N.
        • et al.
        Serum cholesterol and mortality: the Yugoslavia Cardiovascular Disease Study.
        Am J Epidemiol. 1981; 114: 21-28
        • Kagan A.
        • McGee D.L.
        • Yano K.
        • Rhoads G.G.
        • Nomura A.
        Serum cholesterol and mortality in a Japanese-American population.
        Am J Epidemiol. 1981; 114: 11-20
        • Bottiger L.E.
        • Carlson L.A.
        Risk factors for death for males and females: a study of the death pattern in the Stockholm Prospective Study.
        Acta Med Scand. 1982; 211: 437-442
        • Peterson B.
        • Trell E.
        Premature mortality in middle-aged men: serum cholesterol as risk factor.
        Klin Wochenschr. 1983; 63: 795-801
        • Salmond C.G.
        • Beaglehole R.
        • Prior I.A.M.
        Are low cholesterol values associated with excess mortality?.
        Br Med J. 1985; 290: 422-424
        • Isles C.G.
        • Hole D.J.
        • Gillis C.R.
        • Hawthorne V.M.
        • Lever A.F.
        Plasma cholesterol, coronary heart disease, and cancer in the Renfrew and Paisley Survey.
        Br Med J. 1989; 298: 920-924
        • Cowan L.D.
        • O'Connell D.L.
        • Criqui M.H.
        • Barrett-Connor E.
        • Bush T.L.
        • Wallace R.B.
        Cancer mortality and lipid and lipoprotein levels: the Lipid Research Clinics Program Mortality Follow-up Study.
        Am J Epidemiol. 1990; 131: 468-482
        • Pekkanen J.
        • Nissinen A.
        • Punsar S.
        • Karvonen M.J.
        Short- and long-term association with mortality. The 25-year follow-up of the Finnish cohorts of the Seven Countries Study.
        Am J Epidemiol. 1992; 135: 1251-1258
        • Smith G.D.
        • Shipley M.J.
        • Marmot M.G.
        • Rose G.
        Plasma cholesterol concentration and mortality. The Whitehall Study.
        JAMA. 1992; 267: 70-76
        • Frank J.W.
        • Reed D.M.
        • Grove J.S.
        • Benfante R.
        Will lowering population levels of serum cholesterol affect total mortality? Expectations from The Honolulu Heart Program.
        J Clin Epidemiol. 1992; 45: 333-346
        • Harris T.
        • Feldman J.J.
        • Kleinman J.C.
        • Ettinger Jr, W.H.
        • Makuc D.M.
        • Schatzkin A.G.
        The low cholesterolmortality association in a national cohort.
        J Clin Epidemiol. 1992; 45: 595-601
        • Jacobs D.J.
        • Blackburn H.
        • Higgins M.
        • et al.
        Report of the Conference on Low Blood Cholesterol: Mortality Associations.
        Circulation. 1992; 86: 1046-1060
        • Dyer A.R.
        • Stamler J.
        • Paul O.
        • et al.
        Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies.
        J Chron Dis. 1981; 34: 249-260
        • Wingard D.L.
        • Criqui M.H.
        • Holdbook M.J.
        • Barrett-Connor E.
        Plasma cholesterol and cancer mortality and morbidity in an adult community.
        J Chron Dis. 1984; 37: 401-406
        • Kromhout D.
        • Bosschieter E.B.
        • Drijver M.
        • Coulander C.
        Serum cholesterol and 25-year incidence of and mortality from myocardial infarction and cancer: The Zutphen Study.
        Arch Intern Med. 1988; 148: 1051-1055
        • Shaper A.G.
        • Phillips A.N.
        • Pocock S.J.
        Plasma cholesterol, coronary heart disease and cancer (letter).
        Br Med J. 1989; 298: 1381
        • Farchi G.
        • Menotti A.
        • Conti S.
        Coronary disease and survival probability from coronary and other causes of death.
        Am J Epidemiol. 1987; 126: 400-408
        • Yaari S.
        • Even-Zohar S.
        • Goldbourt U.
        • Neufeld H.N.
        Associations of serum high density lipoprotein and total mortality with total, cardiovascular, and cancer mortality in a 7-year prospective study of 10,000 men.
        Lancet. 1981; : 1011-1015
        • Salonen J.T.
        Risk of cancer and death in relation to serum cholesterol. A longitudinal study in an eastern Finnish population with high overall cholesterol level.
        Am J Epidemiol. 1982; 116: 622-630
        • Persson B.
        • Johansson B.W.
        The Kockum Study: twentytwo-year Follow-up. Coronary heart disease in a population in the South of Sweden.
        Acta Med Scand. 1984; 216: 485-493
        • Muldoon M.F.
        • Manuck S.B.
        • Matthews K.A.
        Lowering cholesterol concentrations and mortality: a review of primary prevention trials.
        Br Med J. 1990; 301: 309-314
        • Holme I.
        An analysis of randomized trials evaluating the effect of cholesterol reduction on total mortality and coronary heart disease incidence.
        Circulation. 1990; 82: 1916-1924
        • Strandberg T.E.
        • Salomaa V.V.
        • Naukkarinen V.A.
        • Vanhanen H.T.
        • Sarna S.J.
        • Miettinen T.A.
        Long term mortality after 5-year multifactorial primary prevention of cardiovascular diseases in middle-aged men.
        JAMA. 1991; 266: 1225-1229
      1. Technicon Method No. SE4-0026FC4: Cholesterol (direct). Technicon Instruments Corporation, Tarrytown, New York1984
        • Nakamura M.
        • Morita M.
        • Yabuuchi E.
        • et al.
        The evaluation and the results of cooperative cholesterol and triglyceride standardization program by WHOCDC (in Japanese).
        Rinsho Byori. 1982; 30: 325-332
        • Minowa S.
        Study on standard weights for Japanese adults: Charts of Minowa's relative weight index (in Japanese).
        Jpn J Med. 1962; 1988: 24-28
        • Health and Welfare Statistics Association
        Kokumin Eisei No Doukou.
        (in Japanese)in: Health and Welfare Statistics Association, Tokyo1992: 396-407
        • Tornberg S.A.
        • Holm L.E.
        • Cartensen J.M.
        • Eklund G.A.
        • Odent D.
        Risk of cancer of the colon and rectum in relation to serum cholesterol and beta-lipoprotein.
        N Engl J Med. 1986; 315: 1629-1633
        • Iribarren C.
        • Dwyer J.H.
        • Burchfiel C.M.
        • Reed D.M.
        Can the U-shaped relation between mortality and serum cholesterol be explained by confounding? Abstract.
        Circulation. 1993; 87: 7
        • Vitols S.
        • Fjorkholm M.
        • Gahrton G.
        • Peterson C.
        Hypocholesterolaemia in malignancy due to elevated lowdensity-lipoprotein-receptor activity in tumor cells: Evidence from studies in patients with leukemia.
        Lancet. 1985; 2: 1150-1154
        • Budd D.
        • Ginsberg H.
        Hypocholesterolemia and acute myelogenous leukemia: Association between disease activity and plasma low-density lipoprotein cholesterol concentrations.
        Cancer. 1986; 58: 1361-1365
        • Henriksson P.
        • Eriksson M.
        • Ericsson S.
        • et al.
        Hypocholesterolaemia and increased elimination of lowdensity lipoproteins in metastatic cancer of the prostate.
        Lancet. 1989; 2: 1178-1180
        • Sabine J.
        Cholesterol.
        Marcel Dekker, Inc, New York1977
        • Heiniger H.J.
        • Brunner K.T.
        • Cerottini J.C.
        Cholesterol is a critical cellular component to T-lymphocyte cytotoxicity.
        in: 2nd edition. Proc Natl Acad Sci USA. 75. 1978: 5683-5687
        • Herbeth B.
        • Spyckerelle Y.
        • Deschamps J.P.
        Determinants of plasma retinol, beta-carotene, and alpha-tocopherol during adolescence.
        Am J Clin Nutr. 1991; 54: 884-889
        • Rubinstein H.M.
        • Dietz A.A.
        • Srinavasan R.
        Relation of vitamin E and serum lipids.
        Clin Chim Acts. 1969; 23: 1-6
        • Kark J.D.
        • Smith A.H.
        • Hames C.G.
        Serum retinol and the inverse relationship between serum cholesterol and cancer.
        Br Med J. 1982; 284: 152-154
        • Stahelin H.B.
        • Gey K.F.
        • Eichholzer M.
        • Ludin E.
        Betacarotene and cancer prevention: the Basel Study.
        Am J Clin Nutr. 1991; 53: 265S-269S
        • Menkens M.S.
        • Comstock G.W.
        • Vuillemier J.P.
        • et al.
        Serum beta-carotene, vitamins A and E, selenium, and the risk of lung cancer.
        N Engl J Med. 1986; 315: 1250-1254
        • Wald N.J.
        • Boreham J.
        • Hayward J.L.
        • et al.
        Plasma retinol, beta-carotene and vitamin E levels in relation to the future risk of breast cancer.
        Br J Cancer. 1984; 49: 321-324
        • Knekt P.
        • Aromaa A.
        • Maatela J.
        • et al.
        Serum vitamin E and risk of cancer among Finnish men during a 10-year follow-up.
        Am J Epidemiol. 1988; 127: 28-41
        • Knekt P.
        • Reunaken A.
        • Aromaa A.
        • Heliovaara M.
        • Hakulinen T.
        • Hakama M.
        Serum cholesterol and subsequent risk of cancer in a cohort of 39,000 men and women.
        J Clin Epidemiol. 1988; 41: 519-530
        • The Ministry of Health and Welfare
        2nd edition. Manual for Health Examination under the Health Law for the Aged. Japan Public Health Association, Tokyo1987 (in Japanese)