0
June 28, 1995, Vol 273, No. 24 >
ARTICLE | June 28, 1995

Serum Total Cholesterol and Mortality: Title and subTitle BreakConfounding Factors and Risk Modification in Japanese-American Men FREE

Carlos Iribarren, MD, MPH, PhD; Dwayne M. Reed, MD, PhD; Cecil M. Burchfiel, PhD; James H. Dwyer, PhD
[+] Author Affiliations

Presented in part at the 33rd Annual Conference on Cardiovascular Disease Epidemiology and Prevention, Santa Fe, NM, March 19, 1993, and received the American Heart Association Jeremiah Stamler Research Award for New Investigators.

Reprint requests to Institute for Prevention Research, Department of Preventive Medicine, University of Southern California School of Medicine, 1540 Alcazar St, CHP 205E, Los Angeles, CA 90033 (Dr Dwyer).


JAMA. 1995;273(24):1926-1932. doi:10.1001/jama.1995.03520480046038
Text Size: A A A
Published online
Article
References

Objective.  —To further investigate the relationship between serum total cholesterol (TC) level and mortality due to major causes. In particular, is the elevated mortality among persons with low TC levels due to confounding conditions that both lower TC level and increase the risk of mortality, and is the association between low or high TC level and mortality homogeneous in the population or, alternatively, restricted to persons with other risk factors?

Study Design.  —Prospective cohort study.

Setting.  —Free-living population in Oahu, Hawaii.

Participants.  —A total of 7049 middle-aged men of Japanese ancestry.

Main Outcome Measures.  —Age- and risk factor—adjusted mortality due to coronary heart disease, hemorrhagic stroke, cancer, chronic obstructive pulmonary disease, nonmalignant liver disease, trauma, miscellaneous and unknown, and all causes.

Results.  —During 23 years of follow-up, a total of 1954 deaths were documented (38% cancer, 25% cardiovascular, and 37% other). Men with low serum TC levels (<4.66 mmol/L [<180 mg/dL]) were found to have several adverse health characteristics, including a higher prevalence of current smoking, heavy drinking, and certain gastrointestinal conditions. In an age-adjusted model, and in relation to the reference group (4.66 to 6.19 mmol/L [180 to 239 mg/dL]), those in the lowest TC group (<4.66 mmol/L [<180 mg/dL]) were at significantly higher risk of mortality due to hemorrhagic stroke (relative risk [RR], 2.41; 95% confidence interval [CI], 1.45 to 4.00), cancer (RR, 1.41; 95% CI, 1.17 to 1.69), and all causes (RR, 1.23; 95% CI, 1.09 to 1.38). Adjustment for confounders in multivariate analysis (and exclusion of cases with prevalent disease at baseline and deaths through year 5) did not explain the risk of fatal hemorrhagic stroke but reduced the excess risk of cancer mortality by 51% (to 1.20 from 1.41) and reduced the excess risk of all-cause mortality by 56% (to 1.10 from 1.32) in the low TC group. In addition, there were clear differences in the patterns of risk when comparing men with and without selected risk factors (ie, smoking, alcohol consumption, and untreated hypertension).

Conclusions.  —We conclude that the excess mortality at low TC levels can be partially explained by confounding with other determinants of death and by preexisting disease at baseline, and TC-mortality associations are not homogeneous in the population. In our study, TC level was not associated with increased cancer or all-cause mortality in the absence of smoking, high alcohol consumption, and untreated hypertension.(JAMA. 1995;273:1926-1932)

REFERENCES

1 +
Williams RR, Sorlie PD, Feinleib M, McNamara PM, Kannel WB, Dawber TR.  Cancer incidence by levels of cholesterol. JAMA . 1981;;245:247-252.
2 +
Anderson KM, CasteIIi WP, Levy D.  Cholesterol and mortality: 30 years of follow-up from the Framingham study. JAMA . 1987;;257:2176-2180.
3 +
Garcia-Palmieri MR, Sorlie PD, Costas R, Havlik RJ.  An apparent inverse relationship between serum cholesterol and cancer mortality in Puerto Rico. Am J Epidemiol . 1981;;114:29-40.
4 +
Kozarevic D, McGee D, Vojvodic N, et al.  Serum cholesterol and mortality: the Yugoslavia Cardiovascular Disease study. Am J Epidemiol . 1981;;114:21-28.
5 +
Salmond CE, Beaglehole R, Prior IAM.  Are low cholesterol values associated with excess mortality? BMJ . 1985;;290:422-424.
6 +
Martin MJ, Hulley SB, Browner WS, Kuller LH, Wentworth D.  Serum cholesterol, blood pressure, and mortality. Lancet . 1986;;2:933-936.
7 +
Isles CG, Hole DJ, Gillis CR, Hawthorne VM, Lever AF.  Plasma cholesterol, coronary heart disease, and cancer in the Renfrew and Paisley survey. BMJ . 1989;;298:920-924.
8 +
Kagan A, McGee DL, Yano K, Rhoads GG, Nomura A.  Serum cholesterol and mortality in a Japanese-American population. Am J Epidemiol . 1981;; 114:11-20.
9 +
Stemmermann GN, Chyou PH, Kagan A, Nomura AM, Yano K.  Serum cholesterol and mortality among Japanese-American men: the Honolulu (Hawaii) Heart Program. Arch Intern Med . 1991;; 151:969-972.
10 +
Frank JW, Reed DM, Grove JS, 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.
11 +
Neaton JD, Blackburn H, Jacobs DR, 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.
12 +
Kark JD, Smith AH, Hames CG.  The relationship of serum cholesterol to the incidence of cancer in Evans County, Georgia. J Chronic Dis . 1980;;33: 311-322.
13 +
White AD, Hames CG, Tyroler HA.  Serum cholesterol and 20-year mortality in black and white men and women aged 65 and older in the Evans County study. Ann Epidemiol . 1992;;2:85-91.
14 +
Higgins M, Keller JB.  Cholesterol, coronary heart disease, and total mortality in middle-aged and elderly men and women in Tecumseh. Ann Epidemiol . 1992;;2:69-76.
15 +
Harris T, Feldman JJ, Kleinman JC, Ettinger WH, Makuc DM, Schatzkin AG.  The low cholesterolmortality association in a national cohort. J Clin Epidemiol . 1992;;45:595-601.
16 +
Schatzkin A, Hoover RN, Taylor PR, et al.  Serum cholesterol and cancer in the NHANES I epidemiologic follow-up study. Lancet . 1987;;2:298-301.
17 +
Schatzkin AS, Hoover RN, Taylor PR, et al.  Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I epidemiologic follow-up study. Cancer Res . 1988;;48:452-458.
18 +
Cowan LD, O'Connell DL, Criqui MH, Barrett-Connor E, Bush TL, Wallace RB.  Cancer mortality and lipid and lipoprotein levels: the Lipid Research Clinics Program Mortality Follow-up Study. Am J Epidemiol . 1990;;131:468-482.
19 +
Iso H, Naito Y, Kitamura A, et al.  Serum total cholesterol and mortality in a Japanese population. J Clin Epidemiol . 1994;;47:961-969.
20 +
Rose G, Shipley MJ.  Plasma lipids and mortality: a source of error. Lancet . 1980;;1:523-526.
21 +
Yaari S, Goldbourt U, Even-Zohar S, Neufeld HN.  Associations of serum high density lipoprotein and total cholesterol with total, cardiovascular, and cancer mortality in a 7-year prospective study of 10,000 men. Lancet . 1981;;1:1011-1015.
22 +
Dyer AR, Stamler J, Paul O, et al.  Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies. J Chronic Dis . 1981;;34:249-260.
23 +
Peterson B, Trell E, Sternby NH.  Low cholesterol level as risk factor for noncoronary death in middle-aged men. JAMA . 1981;;245; (20) :2056-2057.
24 +
Schuit AJ, Van Dijk CE, Dekker JM, Schouten EG, Kok FJ.  Inverse association between serum total cholesterol and cancer mortality in Dutch civil servants. Am J Epidemiol . 1993;;137:966-976.
25 +
Baptiste MS, Nasca PC, Doyle JT, et al.  Cholesterol and cancer in a population of male civil service workers. Int J Epidemiol . 1992;;21:16-21.
26 +
Wald NJ, Thompson SG, Law MR, Densem JW, Bailey A.  Serum cholesterol and subsequent risk of cancer: results from the BUPA study. Br J Cancer . 1989;;59:938-940.
27 +
Smith GD, Shipley MJ, Marmot MG, Rose G.  Plasma cholesterol concentration and mortality: the Whitehall study. JAMA . 1992;;267:70-76.
28 +
Worth RM, Kagan A.  Ascertainment of men of Japanese ancestry in Hawaii through World War II Selective Service registration. J Chronic Dis . 1970;; 23:389-397.
29 +
Belsky JL, Kagan A, Syme DL. Epidemiologic Studies of Coronary Heart Disease and Stroke in Japanese Men Living in Japan, Hawaii, and California: Research Plan . Hiroshima, Japan: Atomic Bomb Casualty Commission; 1971;. Technical report 12-71.
30 +
Technicon Instruments Corp. Technicon Auto-Analyzer Methodology . Tarrytown, NY: Technicon Instruments Corp; 1965;.
31 +
TIllotson JT, Kato H, Nichaman MZ, Miller DC, Gay ML, Johnson KG.  Epidemiology of coronary heart disease and stroke in Japanese men living in Japan, Hawaii, and California: methodology for comparison of diet. Am J Clin Nutr . 1973;;26:177-184.
32 +
Watt BK, Merrill AL. Composition of Foods: Raw, Processed, Prepared . Washington, DC: US Government Printing Office; 1963;. US Dept of Agriculture Handbook No. 8.
33 +
Kannel WB, Sorlie P.  Some health benefits of physical activity: the Framingham study. Arch Intern Med . 1979;;139:857-861.
34 +
Miettinen OS, Cook EF.  Confounding: essence and detection. Am J Epidemiol . 1981;;114:593-603.
35 +
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.  Report of the National Cholesterol Educational Program. Arch Intern Med . 1988;;148:36-69.
36 +
Breslow NE, Day NE. Statistical Methods in Cancer Research, Volume II: The Design and Analysis of Cohort Studies . Lyon, France: International Agency for Research on Cancer; 1987;.
37 +
SAS/STAT Software Version 6.04: The PHREG Procedure . Cary, NC: SAS Institute Inc; 1987;.
38 +
Aiken LS, West SG. Multiple Regression: Testing and Interpreting Interactions . 3rd ed. London, England: Sage Publications; 1991;:67-78.
39 +
Reed DM.  The paradox of high risk of stroke in populations with low risk of coronary heart disease. Am J Epidemiol . 1990;;131:579-588.
40 +
Manolio TA, Ettinger WH, Tracy RP, et al.  Epidemiology of low cholesterol in older adults: the Cardiovascular Health Study. Circulation . 1993;; 87:728-737.
41 +
Chen Z, Keech A, Collins R, et al.  Prolonged infection with hepatitis B virus and association between low blood cholesterol concentration and liver cancer. BMJ . 1993;;306:890-894.
42 +
Stemmermann GN, Heilbrun L, Nomura A, Rhoads GG, Glober GA.  Late mortality after partial gastrectomy. Int J Epidemiol . 1984;;13:299-303.
43 +
Goldberg RJ, Burchfiel CM, Reed DM, Wergowske G, Chiu D.  A prospective study of the health effects of alcohol consumption in middle-aged and elderly men: the Honolulu Heart Program. Circulation . 1994;;89:651-659.
44 +
Boffeta P, Garfinkel L.  Alcohol drinking and mortality among men enrolled in an American Cancer Society prospective study. Epidemiology . 1990;; 1:342-348.
45 +
Law MR, Thompson SG.  Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control . 1991;;2:253-2611.
46 +
Clayton D.  Models for the longitudinal analysis of cohort and case-control studies with inaccurately measured exposures.  In: Dwyer JH, Feinleib M, Lippert P, Hoffmeister H, eds. Statistical Models for Longitudinal Studies of Health . New York, NY: Oxford University Press Inc; 1992;:301-331.
47 +
Iso H, Jacobs DR Jr, Wentworth D, Neaton JD, Cohen JD.  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.
48 +
Iso H, Folsom AR, Wu KK, et al.  Hemostatic variables in Japanese men and caucasian men: plasma fibrinogen, factor VIIc, factor VIIIc, and von Willebrand factor and their relations to cardiovascular disease risk factors. Am J Epidemiol . 1989;;130:925-933.
49 +
Bonithon-Kopp C, Scarabin PY, Bara L, Castanier M, Jacqueson A, Roger M.  Relationship between sex hormones and haemostatic factors in healthy middle-aged men. Atherosclerosis . 1988;;71: 71-76.
50 +
Meade TW, Vickers MV, Thompson SG, Stirling Y, Haines AP, Miller GJ.  Epidemiological characteristics of platelet aggregability. BMJ . 1985;;290: 428-432.
51 +
Rogers S, Yarnell JWG, Fehily AM.  Nutritional determinants of hemostatic factors in the Caerphilly study. Eur J Clin Nutr . 1988;;42:197-205.
52 +
Kark JF, Smith AH, Hames CG.  Serum retinol and the inverse relationship between serum cholesterol and cancer. BMJ . 1982;;284:152-154.
53 +
Russell-Briefel R, Bates MW, Kuller LH.  The relationship of plasma carotenoids to health and biochemical factors in middle-aged men. Am J Epidemiol . 1985;;122:741-749.
54 +
Sinha R, Patterson BH, Mangels AR, et al.  Determinants of plasma vitamin E in healthy males. Cancer Epidemiol Biomarkers Prev . 1993;;2:473-479.
55 +
Stahelin HB, Gey KF, Eichholzer M, et al.  Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow-up of the prospective Basel study. Am J Epidemiol . 1991;;133: 766-775.
56 +
Menkes MS, Comstock GW, Vuilleumier JP, Helsing KJ, Rider AA, Brookmeyer R.  Serum beta carotene, vitamins A and E, selenium, and the risk of lung cancer. N Engl J Med . 1986;;315:1250-1254.
57 +
Westlund K, Nicolaysen R.  Ten-year mortality and morbidity related to serum cholesterol. Scand J Clin Lab Invest . 1972;;30( (suppl 127) ):2-24.
58 +
Klag MJ, Ford DE, Mead LA, et al.  Serum cholesterol in young men and subsequent cardiovascular disease. N Engl J Med . 1993;;328:313-318.

Figures

Tables

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Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature

Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal

1 +
Williams RR, Sorlie PD, Feinleib M, McNamara PM, Kannel WB, Dawber TR.  Cancer incidence by levels of cholesterol. JAMA . 1981;;245:247-252.
2 +
Anderson KM, CasteIIi WP, Levy D.  Cholesterol and mortality: 30 years of follow-up from the Framingham study. JAMA . 1987;;257:2176-2180.
3 +
Garcia-Palmieri MR, Sorlie PD, Costas R, Havlik RJ.  An apparent inverse relationship between serum cholesterol and cancer mortality in Puerto Rico. Am J Epidemiol . 1981;;114:29-40.
4 +
Kozarevic D, McGee D, Vojvodic N, et al.  Serum cholesterol and mortality: the Yugoslavia Cardiovascular Disease study. Am J Epidemiol . 1981;;114:21-28.
5 +
Salmond CE, Beaglehole R, Prior IAM.  Are low cholesterol values associated with excess mortality? BMJ . 1985;;290:422-424.
6 +
Martin MJ, Hulley SB, Browner WS, Kuller LH, Wentworth D.  Serum cholesterol, blood pressure, and mortality. Lancet . 1986;;2:933-936.
7 +
Isles CG, Hole DJ, Gillis CR, Hawthorne VM, Lever AF.  Plasma cholesterol, coronary heart disease, and cancer in the Renfrew and Paisley survey. BMJ . 1989;;298:920-924.
8 +
Kagan A, McGee DL, Yano K, Rhoads GG, Nomura A.  Serum cholesterol and mortality in a Japanese-American population. Am J Epidemiol . 1981;; 114:11-20.
9 +
Stemmermann GN, Chyou PH, Kagan A, Nomura AM, Yano K.  Serum cholesterol and mortality among Japanese-American men: the Honolulu (Hawaii) Heart Program. Arch Intern Med . 1991;; 151:969-972.
10 +
Frank JW, Reed DM, Grove JS, 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.
11 +
Neaton JD, Blackburn H, Jacobs DR, 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.
12 +
Kark JD, Smith AH, Hames CG.  The relationship of serum cholesterol to the incidence of cancer in Evans County, Georgia. J Chronic Dis . 1980;;33: 311-322.
13 +
White AD, Hames CG, Tyroler HA.  Serum cholesterol and 20-year mortality in black and white men and women aged 65 and older in the Evans County study. Ann Epidemiol . 1992;;2:85-91.
14 +
Higgins M, Keller JB.  Cholesterol, coronary heart disease, and total mortality in middle-aged and elderly men and women in Tecumseh. Ann Epidemiol . 1992;;2:69-76.
15 +
Harris T, Feldman JJ, Kleinman JC, Ettinger WH, Makuc DM, Schatzkin AG.  The low cholesterolmortality association in a national cohort. J Clin Epidemiol . 1992;;45:595-601.
16 +
Schatzkin A, Hoover RN, Taylor PR, et al.  Serum cholesterol and cancer in the NHANES I epidemiologic follow-up study. Lancet . 1987;;2:298-301.
17 +
Schatzkin AS, Hoover RN, Taylor PR, et al.  Site-specific analysis of total serum cholesterol and incident cancer in the National Health and Nutrition Examination Survey I epidemiologic follow-up study. Cancer Res . 1988;;48:452-458.
18 +
Cowan LD, O'Connell DL, Criqui MH, Barrett-Connor E, Bush TL, Wallace RB.  Cancer mortality and lipid and lipoprotein levels: the Lipid Research Clinics Program Mortality Follow-up Study. Am J Epidemiol . 1990;;131:468-482.
19 +
Iso H, Naito Y, Kitamura A, et al.  Serum total cholesterol and mortality in a Japanese population. J Clin Epidemiol . 1994;;47:961-969.
20 +
Rose G, Shipley MJ.  Plasma lipids and mortality: a source of error. Lancet . 1980;;1:523-526.
21 +
Yaari S, Goldbourt U, Even-Zohar S, Neufeld HN.  Associations of serum high density lipoprotein and total cholesterol with total, cardiovascular, and cancer mortality in a 7-year prospective study of 10,000 men. Lancet . 1981;;1:1011-1015.
22 +
Dyer AR, Stamler J, Paul O, et al.  Serum cholesterol and risk of death from cancer and other causes in three Chicago epidemiological studies. J Chronic Dis . 1981;;34:249-260.
23 +
Peterson B, Trell E, Sternby NH.  Low cholesterol level as risk factor for noncoronary death in middle-aged men. JAMA . 1981;;245; (20) :2056-2057.
24 +
Schuit AJ, Van Dijk CE, Dekker JM, Schouten EG, Kok FJ.  Inverse association between serum total cholesterol and cancer mortality in Dutch civil servants. Am J Epidemiol . 1993;;137:966-976.
25 +
Baptiste MS, Nasca PC, Doyle JT, et al.  Cholesterol and cancer in a population of male civil service workers. Int J Epidemiol . 1992;;21:16-21.
26 +
Wald NJ, Thompson SG, Law MR, Densem JW, Bailey A.  Serum cholesterol and subsequent risk of cancer: results from the BUPA study. Br J Cancer . 1989;;59:938-940.
27 +
Smith GD, Shipley MJ, Marmot MG, Rose G.  Plasma cholesterol concentration and mortality: the Whitehall study. JAMA . 1992;;267:70-76.
28 +
Worth RM, Kagan A.  Ascertainment of men of Japanese ancestry in Hawaii through World War II Selective Service registration. J Chronic Dis . 1970;; 23:389-397.
29 +
Belsky JL, Kagan A, Syme DL. Epidemiologic Studies of Coronary Heart Disease and Stroke in Japanese Men Living in Japan, Hawaii, and California: Research Plan . Hiroshima, Japan: Atomic Bomb Casualty Commission; 1971;. Technical report 12-71.
30 +
Technicon Instruments Corp. Technicon Auto-Analyzer Methodology . Tarrytown, NY: Technicon Instruments Corp; 1965;.
31 +
TIllotson JT, Kato H, Nichaman MZ, Miller DC, Gay ML, Johnson KG.  Epidemiology of coronary heart disease and stroke in Japanese men living in Japan, Hawaii, and California: methodology for comparison of diet. Am J Clin Nutr . 1973;;26:177-184.
32 +
Watt BK, Merrill AL. Composition of Foods: Raw, Processed, Prepared . Washington, DC: US Government Printing Office; 1963;. US Dept of Agriculture Handbook No. 8.
33 +
Kannel WB, Sorlie P.  Some health benefits of physical activity: the Framingham study. Arch Intern Med . 1979;;139:857-861.
34 +
Miettinen OS, Cook EF.  Confounding: essence and detection. Am J Epidemiol . 1981;;114:593-603.
35 +
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.  Report of the National Cholesterol Educational Program. Arch Intern Med . 1988;;148:36-69.
36 +
Breslow NE, Day NE. Statistical Methods in Cancer Research, Volume II: The Design and Analysis of Cohort Studies . Lyon, France: International Agency for Research on Cancer; 1987;.
37 +
SAS/STAT Software Version 6.04: The PHREG Procedure . Cary, NC: SAS Institute Inc; 1987;.
38 +
Aiken LS, West SG. Multiple Regression: Testing and Interpreting Interactions . 3rd ed. London, England: Sage Publications; 1991;:67-78.
39 +
Reed DM.  The paradox of high risk of stroke in populations with low risk of coronary heart disease. Am J Epidemiol . 1990;;131:579-588.
40 +
Manolio TA, Ettinger WH, Tracy RP, et al.  Epidemiology of low cholesterol in older adults: the Cardiovascular Health Study. Circulation . 1993;; 87:728-737.
41 +
Chen Z, Keech A, Collins R, et al.  Prolonged infection with hepatitis B virus and association between low blood cholesterol concentration and liver cancer. BMJ . 1993;;306:890-894.
42 +
Stemmermann GN, Heilbrun L, Nomura A, Rhoads GG, Glober GA.  Late mortality after partial gastrectomy. Int J Epidemiol . 1984;;13:299-303.
43 +
Goldberg RJ, Burchfiel CM, Reed DM, Wergowske G, Chiu D.  A prospective study of the health effects of alcohol consumption in middle-aged and elderly men: the Honolulu Heart Program. Circulation . 1994;;89:651-659.
44 +
Boffeta P, Garfinkel L.  Alcohol drinking and mortality among men enrolled in an American Cancer Society prospective study. Epidemiology . 1990;; 1:342-348.
45 +
Law MR, Thompson SG.  Low serum cholesterol and the risk of cancer: an analysis of the published prospective studies. Cancer Causes Control . 1991;;2:253-2611.
46 +
Clayton D.  Models for the longitudinal analysis of cohort and case-control studies with inaccurately measured exposures.  In: Dwyer JH, Feinleib M, Lippert P, Hoffmeister H, eds. Statistical Models for Longitudinal Studies of Health . New York, NY: Oxford University Press Inc; 1992;:301-331.
47 +
Iso H, Jacobs DR Jr, Wentworth D, Neaton JD, Cohen JD.  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.
48 +
Iso H, Folsom AR, Wu KK, et al.  Hemostatic variables in Japanese men and caucasian men: plasma fibrinogen, factor VIIc, factor VIIIc, and von Willebrand factor and their relations to cardiovascular disease risk factors. Am J Epidemiol . 1989;;130:925-933.
49 +
Bonithon-Kopp C, Scarabin PY, Bara L, Castanier M, Jacqueson A, Roger M.  Relationship between sex hormones and haemostatic factors in healthy middle-aged men. Atherosclerosis . 1988;;71: 71-76.
50 +
Meade TW, Vickers MV, Thompson SG, Stirling Y, Haines AP, Miller GJ.  Epidemiological characteristics of platelet aggregability. BMJ . 1985;;290: 428-432.
51 +
Rogers S, Yarnell JWG, Fehily AM.  Nutritional determinants of hemostatic factors in the Caerphilly study. Eur J Clin Nutr . 1988;;42:197-205.
52 +
Kark JF, Smith AH, Hames CG.  Serum retinol and the inverse relationship between serum cholesterol and cancer. BMJ . 1982;;284:152-154.
53 +
Russell-Briefel R, Bates MW, Kuller LH.  The relationship of plasma carotenoids to health and biochemical factors in middle-aged men. Am J Epidemiol . 1985;;122:741-749.
54 +
Sinha R, Patterson BH, Mangels AR, et al.  Determinants of plasma vitamin E in healthy males. Cancer Epidemiol Biomarkers Prev . 1993;;2:473-479.
55 +
Stahelin HB, Gey KF, Eichholzer M, et al.  Plasma antioxidant vitamins and subsequent cancer mortality in the 12-year follow-up of the prospective Basel study. Am J Epidemiol . 1991;;133: 766-775.
56 +
Menkes MS, Comstock GW, Vuilleumier JP, Helsing KJ, Rider AA, Brookmeyer R.  Serum beta carotene, vitamins A and E, selenium, and the risk of lung cancer. N Engl J Med . 1986;;315:1250-1254.
57 +
Westlund K, Nicolaysen R.  Ten-year mortality and morbidity related to serum cholesterol. Scand J Clin Lab Invest . 1972;;30( (suppl 127) ):2-24.
58 +
Klag MJ, Ford DE, Mead LA, et al.  Serum cholesterol in young men and subsequent cardiovascular disease. N Engl J Med . 1993;;328:313-318.

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