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ARTICLE |

Lack of Association Between Cholesterol and Coronary Heart Disease Mortality and Morbidity and All-Cause Mortality in Persons Older Than 70 Years FREE

Harlan M. Krumholz, MD; Teresa E. Seeman, PhD; Susan S. Merrill, PhD; Carlos F. Mendes de Leon, PhD; Viola Vaccarino, MD; David I. Silverman, MD; Reiko Tsukahara, MD; Adrian M. Ostfeld, MD; Lisa F. Berkman, PhD
[+] Author Affiliations

Reprint requests to the Section of Cardiovascular Medicine, Yale University School of Medicine, 333 Cedar St, PO Box 208017, New Haven, CT 06520-8017 (Dr Krumholz).


JAMA. 1994;272(17):1335-1340. doi:10.1001/jama.1994.03520170045034
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Objectives.  —To determine whether elevated serum cholesterol level is associated with all-cause mortality, mortality from coronary heart disease, or hospitalization for acute myocardial infarction and unstable angina in persons older than 70 years. Also, to evaluate the association between low levels of high-density lipoprotein cholesterol (HDL-C) and elevated ratio of serum cholesterol to HDL-C with these outcomes.

Design.  —Prospective, community-based cohort study with yearly interviews.

Participants.  —A total of 997 subjects who were interviewed in 1988 as part of the New Haven, Conn, cohort of the Established Population for the Epidemiologic Study of the Elderly (EPESE) and consented to have blood drawn.

Main Outcome Measures.  —The risk factor—adjusted odds ratios of the 4-year incidence of all-cause mortality, mortality from coronary heart disease, and hospitalization for myocardial infarction or unstable angina were calculated for the following: subjects with total serum cholesterol levels greater than or equal to 6.20 mmol/L (≥240 mg/dL) compared with subjects with cholesterol levels less than 5.20 mmol/L (<200 mg/dL); subjects in the lowest tertile of HDL-C level compared with those in the highest tertile; and subjects in the highest tertile of the ratio of total serum cholesterol to HDL-C level compared with those in the lowest tertile.

Results.  —Elevated total serum cholesterol level, low HDL-C, and high total serum cholesterol to HDL-C ratio were not associated with a significantly higher rate of all-cause mortality, coronary heart disease mortality, or hospitalization for myocardial infarction or unstable angina after adjustment for cardiovascular risk factors. The risk factor—adjusted odds ratio for all-cause mortality was 0.99 (95% confidence interval [CI], 0.56 to 2.69) for the group who had cholesterol levels greater than or equal to 6.20 mmol/L (≥240 mg/dL) compared with the group that had levels less than 5.20 mmol/L (<200 mg/dL); 1.00 (95% CI, 0.59 to 1.70) for the group in the lowest tertile of HDL-C compared with those in the highest tertile; and 1.03 (95% CI, 0.62 to 1.71) for subjects in the highest tertile of the ratio of total serum cholesterol to HDL-C compared with those in the lowest tertile.

Conclusions.  —Our findings do not support the hypothesis that hypercholesterolemia or low HDL-C are important risk factors for all-cause mortality, coronary heart disease mortality, or hospitalization for myocardial infarction or unstable angina in this cohort of persons older than 70 years.(JAMA. 1994;272:1335-1340)

REFERENCES

Ettinger WH, Wahl PW, Kuller LH, et al.  Lipoprotein lipids in older people: results from the Cardiovascular Health Study. Circulation . 1992;;86:858-869.
The Lipids Research Clinic Program Epidemiology Committee.  Plasma lipid populations in selected North American populations. Circulation . 1979;;60:427-439.
Curb JD, Reed DM, Yano K, Kautz JA, Albers JJ.  Plasma lipids and lipoproteins in elderly Japanese-American men. J Am Geriatr Soc . 1986;;34: 773-780.
Johnson CL, Rifkind BM, Sempos CT, et al.  Declining serum total cholesterol levels among US adults. JAMA . 1993;;269:3002-3008.
Manolio TT, Furberg CD, Wahl PW, et al.  Eligibility for cholesterol referral in community-dwelling older adults. Ann Intern Med . 1992;;116:641-649.
Kafonek S, Kwiterovich P.  Treatment of hypercholesterolemia in the elderly. Ann Intern Med . 1990;;112:723-725.
US Senate Subcommittee on Aging. Aging America . Washington, DC: US Dept of Health and Human Services; 1991;:273.
Denke MA, Grundy SM.  Hypercholesterolemia in elderly persons: resolving the treatment dilemma. Ann Intern Med . 1990;;112:780-792.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.  Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 1993;;269:3015-3023.
Castelli WP.  Epidemiology of coronary heart disease. Am J Med . 1984;;76:4-12.
Stamler J, Wentworth DN, Neaton JD.  Is the relationship between serum cholesterol and risk of premature death from coronary heart disease continuous or graded? findings in 356 222 primary screenees of the Multiple Risk Factor Intervention Trail (MRFIT). JAMA . 1986;;256:2823-2828.
Rubin SM, Sidney S, Black DM, Browner WS, Hulley SB, Cummings SR.  High blood cholesterol in elderly men and the excess risk for coronary heart disease. Ann Intern Med . 1990;;113:916-920.
Benfante R, Reed D.  Is elevated serum cholesterol a risk factor for coronary heart disease in the elderly? JAMA . 1990;;263:393-396.
Castelli WP, Wilson PW, Levy D, Anderson K.  Cardiovascular risk factors in the elderly. Am J Cardiol . 1989;;63( (suppl) ):12H-19H.
Barrett-Connor E, Suarez L, Khaw K, Criqui MH, Wingard DL.  Ischemic heart disease risk factors after age 50. J Chronic Dis . 1984;;37:903-908.
Manolio TA, Pearson TA, Wenger NK, Barrett-Connor E, Payne GH, Harlan WR.  Cholesterol and heart disease in older persons and women: review of an NHBLI workshop. Ann Epidemiol . 1992;;2: 161-176.
Zimetbaum P, Frishman WH, Ooi WL, et al.  Plasma lipids and lipoproteins and the incidence of cardiovascular disease in the very elderly. Artertioscler Thromb . 1992;;12:416-423.
Kronmal RA, Cain KC, Ye ZS, Omenn G.  Total serum cholesterol levels and mortality risk as a function of age. Arch Intern Med . 1993;;153:1065-1073.
Cornoni-Huntley J, Ostfeld AM, Taylor J, et al.  Established populations for epidemiologic studies of the elderly: study design and methodology. Aging Clin Exp Res . 1993;;5:27-37.
Hypertension Detection and Follow-up Program Cooperative Group.  Blood pressure studies in 14 communities: a two-stage screen for hypertension. JAMA . 1977;;237:2385-2391.
International Classification of Diseases, Ninth Revision, Clinical Modification . Washington, DC: Public Health Service, US Dept of Health and Human Services; 1988;.
Ischemic Heart Disease Registers. Report of the Fifth Working Group on Ischemic Heart Disease Registers . Copenhagen, Denmark: World Health Organization; 1971;.
Peto R, Pike MC, Armitage P, et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient, part 2: analysis and examples. Br J Cancer . 1977;;35:1-39.
Seeman TS, Mendes de Leon CF, Berkman LF, Ostfeld AM.  Risk factors for coronary heart disease among older men and women: a prospective study of community-dwelling elderly. Am J Epidemiol . 1993;;138:1037-1049.
LaCroix AZ, Guralnick JM, Curb JO, Wallace RB, Ostfeld AM, Hennekens CH.  Chest pain and coronary heart disease mortality among older men and women in three communities. Circulation . 1990;; 81:437-446.
Hulley SB, Walsh JM, Newman TB.  Health policy on blood cholesterol. Circulation . 1992;;86: 1026-1029.
Freeman DH, Livingston MM, Leaf PJ, Berkman LF.  Sampling strategies for studying older populations.  In: Wallace R, Woolson R, eds. The Epidemiologic Study of the Elderly . New York, NY: Oxford University Press; 1992;:46-59.
Lipid Research Clinics Program.  The Lipid Research Clinics Coronary Drug Project Trial results: reduction in the incidence of coronary heart disease. JAMA . 1984;;251:351-364.
Sempos CT, Cleeman JI, Carroll MD, et al.  Prevalence of high blood cholesterol among US adults. JAMA . 1993;;269:3009-3014.
Aronow WS, Herzig AH, Etinenne F, D'Alba P, Ronquillo J.  41-month follow-up of risk factors correlated with new coronary events in 708 elderly patients. J Am Geriatr Soc . 1989;;37:501-506.
Wong ND, Wilson PWF, Kannel WB.  Serum cholesterol as a prognostic factor after myocardial infarction: the Framingham study. Ann Intern Med . 1991;;115:687-693.

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Ettinger WH, Wahl PW, Kuller LH, et al.  Lipoprotein lipids in older people: results from the Cardiovascular Health Study. Circulation . 1992;;86:858-869.
The Lipids Research Clinic Program Epidemiology Committee.  Plasma lipid populations in selected North American populations. Circulation . 1979;;60:427-439.
Curb JD, Reed DM, Yano K, Kautz JA, Albers JJ.  Plasma lipids and lipoproteins in elderly Japanese-American men. J Am Geriatr Soc . 1986;;34: 773-780.
Johnson CL, Rifkind BM, Sempos CT, et al.  Declining serum total cholesterol levels among US adults. JAMA . 1993;;269:3002-3008.
Manolio TT, Furberg CD, Wahl PW, et al.  Eligibility for cholesterol referral in community-dwelling older adults. Ann Intern Med . 1992;;116:641-649.
Kafonek S, Kwiterovich P.  Treatment of hypercholesterolemia in the elderly. Ann Intern Med . 1990;;112:723-725.
US Senate Subcommittee on Aging. Aging America . Washington, DC: US Dept of Health and Human Services; 1991;:273.
Denke MA, Grundy SM.  Hypercholesterolemia in elderly persons: resolving the treatment dilemma. Ann Intern Med . 1990;;112:780-792.
Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults.  Summary of the second report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA . 1993;;269:3015-3023.
Castelli WP.  Epidemiology of coronary heart disease. Am J Med . 1984;;76:4-12.
Stamler J, Wentworth DN, Neaton JD.  Is the relationship between serum cholesterol and risk of premature death from coronary heart disease continuous or graded? findings in 356 222 primary screenees of the Multiple Risk Factor Intervention Trail (MRFIT). JAMA . 1986;;256:2823-2828.
Rubin SM, Sidney S, Black DM, Browner WS, Hulley SB, Cummings SR.  High blood cholesterol in elderly men and the excess risk for coronary heart disease. Ann Intern Med . 1990;;113:916-920.
Benfante R, Reed D.  Is elevated serum cholesterol a risk factor for coronary heart disease in the elderly? JAMA . 1990;;263:393-396.
Castelli WP, Wilson PW, Levy D, Anderson K.  Cardiovascular risk factors in the elderly. Am J Cardiol . 1989;;63( (suppl) ):12H-19H.
Barrett-Connor E, Suarez L, Khaw K, Criqui MH, Wingard DL.  Ischemic heart disease risk factors after age 50. J Chronic Dis . 1984;;37:903-908.
Manolio TA, Pearson TA, Wenger NK, Barrett-Connor E, Payne GH, Harlan WR.  Cholesterol and heart disease in older persons and women: review of an NHBLI workshop. Ann Epidemiol . 1992;;2: 161-176.
Zimetbaum P, Frishman WH, Ooi WL, et al.  Plasma lipids and lipoproteins and the incidence of cardiovascular disease in the very elderly. Artertioscler Thromb . 1992;;12:416-423.
Kronmal RA, Cain KC, Ye ZS, Omenn G.  Total serum cholesterol levels and mortality risk as a function of age. Arch Intern Med . 1993;;153:1065-1073.
Cornoni-Huntley J, Ostfeld AM, Taylor J, et al.  Established populations for epidemiologic studies of the elderly: study design and methodology. Aging Clin Exp Res . 1993;;5:27-37.
Hypertension Detection and Follow-up Program Cooperative Group.  Blood pressure studies in 14 communities: a two-stage screen for hypertension. JAMA . 1977;;237:2385-2391.
International Classification of Diseases, Ninth Revision, Clinical Modification . Washington, DC: Public Health Service, US Dept of Health and Human Services; 1988;.
Ischemic Heart Disease Registers. Report of the Fifth Working Group on Ischemic Heart Disease Registers . Copenhagen, Denmark: World Health Organization; 1971;.
Peto R, Pike MC, Armitage P, et al.  Design and analysis of randomized clinical trials requiring prolonged observation of each patient, part 2: analysis and examples. Br J Cancer . 1977;;35:1-39.
Seeman TS, Mendes de Leon CF, Berkman LF, Ostfeld AM.  Risk factors for coronary heart disease among older men and women: a prospective study of community-dwelling elderly. Am J Epidemiol . 1993;;138:1037-1049.
LaCroix AZ, Guralnick JM, Curb JO, Wallace RB, Ostfeld AM, Hennekens CH.  Chest pain and coronary heart disease mortality among older men and women in three communities. Circulation . 1990;; 81:437-446.
Hulley SB, Walsh JM, Newman TB.  Health policy on blood cholesterol. Circulation . 1992;;86: 1026-1029.
Freeman DH, Livingston MM, Leaf PJ, Berkman LF.  Sampling strategies for studying older populations.  In: Wallace R, Woolson R, eds. The Epidemiologic Study of the Elderly . New York, NY: Oxford University Press; 1992;:46-59.
Lipid Research Clinics Program.  The Lipid Research Clinics Coronary Drug Project Trial results: reduction in the incidence of coronary heart disease. JAMA . 1984;;251:351-364.
Sempos CT, Cleeman JI, Carroll MD, et al.  Prevalence of high blood cholesterol among US adults. JAMA . 1993;;269:3009-3014.
Aronow WS, Herzig AH, Etinenne F, D'Alba P, Ronquillo J.  41-month follow-up of risk factors correlated with new coronary events in 708 elderly patients. J Am Geriatr Soc . 1989;;37:501-506.
Wong ND, Wilson PWF, Kannel WB.  Serum cholesterol as a prognostic factor after myocardial infarction: the Framingham study. Ann Intern Med . 1991;;115:687-693.
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