Effects of age, gender, and menopausal status on plasma low density lipoprotein cholesterol and apolipoprotein B levels in the Framingham Offspring Study.

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      Plasma low density lipoprotein (LDL) cholesterol, non-high density lipoprotein (HDL) cholesterol, and apolipoprotein (apo) B, the major protein constituent of LDL, were measured in 1,533 men (mean age 49 +/- 10 years) and 1,597 women (mean age 49 +/- 10 years) participating in the 3rd examination cycle of the Framingham Offspring Study. Mean plasma levels of LDL cholesterol and apoB were higher in men than in women (136 versus 132 mg/dl, P < 0.0001; and 109 versus 95 mg/dl, P < 0.0001, respectively). Increased age was associated with higher plasma LDL cholesterol and apoB levels, especially in women. After adjustment for age and body mass index, LDL cholesterol and apoB levels were still significantly higher in postmenopausal than in premenopausal women, indicating a hormonal effect on LDL metabolism. The associations between coronary heart disease (CHD) and LDL cholesterol, non-HDL cholesterol, apoB, and other plasma lipid and lipoprotein parameters were examined by dividing participants in four groups, based on approximate quartiles for these parameters. Elevated LDL cholesterol levels were not significantly associated with CHD in men, but were in women. This result, at variance with that of several longitudinal studies, is likely due to the cross-sectional design of our analysis. Elevated non-HDL cholesterol and apoB levels were significantly associated with the presence of CHD, in both males and females. A plasma apoB value > or = 125 mg/dl may be associated with an increased risk for CHD. Low plasma levels of HDL cholesterol were also significantly associated with CHD. Plasma triglyceride levels, age and body mass index were strong determinants of LDL cholesterol, non-HDL cholesterol, and apoB levels in men and women. In women, postmenopausal status and elevated blood pressure were also significantly associated with elevated levels of these parameters.

      REFERENCES

        • Anderson K.M.
        • Castelli W.P.
        • Levy D.
        Cholesterol and mortality: 30 years of follow-up from the Framingham Heart Study.
        J. Am. Med. Assoc. 1989; 257: 2176-2180
        • Castelli W.P.
        • Garrison R.J.
        • Wilson P.W.F.
        • Abbott R.D.
        • Kalousdian S.
        • Kannel W.B.
        Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Heart Study.
        J. Am. Med. Assoc. 1986; 256: 2835-2838
        • Stamler J.
        • Wentworth D.
        • Neaton J.D.
        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 Trial (MRFIT).
        J. Am. Med. Assoc. 1986; 256: 2823-2828
      1. Lipid Research Clinics Program. 1984. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. J. Am. Med. Assoc. 251: 351-364.

        • Frick M.H.
        • Elo O.
        • Haapa K.
        • Heinonen O.P.
        • Hein-salmi P.
        • Helo P.
        • Huttunen J.K.
        • Kaitaniemi P.
        • Koskinen P.
        • Manninen V.
        • et al.
        Helsinki Heart Study: primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety in treatment, changes in risk factors, and incidence of coronary heart disease.
        N. Engl. J. Med. 1987; 317: 1237-1245
        • Miller N.E.
        • Lewis B.
        Lipoproteins, Atherosclerosis and Coronary Heart Disease.
        Elsevier, Amsterdam, Netherlands1981
      2. The Expert Panel. 1993. 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 (Adult Treatment Panel II) NHLBI. J. Am. Med. Assoc. 269: 3015-3023.

        • Kannel W.B.
        • Feinleib M.
        • McNamara P.M.
        • Garrison R.J.
        • Castelli W.P.
        An investigation of coronary heart disease in families. The Framingham Offspring Study.
        Am. J. Epidemiol. 1979; 110: 281-290
        • Avogaro P.
        • Bittolo Bon G.
        • Cazzolato G.
        • Quinci G.B.
        Are apolipoproteins better discriminators than lipids for atherosclerosis.
        Lancet. 1979; 1: 901-903
        • Durrington P.N.
        • Hunt L.
        • Ishola M.
        • Kane J.
        • Stephens W.P.
        Serum apolipoproteins A-I and B and lipoproteins in middle-aged men with and without previous myocardial infarction.
        Br. Heart J. 1986; 56: 206-212
        • Kottke B.A.
        • Zinsmeister A.R.
        • Holmes Jr., D.R.
        • Kneller R.W.
        • Hallaway B.J.
        • Mao S.J.T.
        Apolipoproteins and coronary artery disease.
        Mayo Clin. Proc. 1986; 61: 313-320
        • Stampfer M.J.
        • Sacks F.M.
        • Salvini S.
        • Willett W.C.
        • Henneckens C.H.
        A prospective study of cholesterol, apolipoproteins, and the risk of myocardial infarction.
        N. Engl. J. Med. 1991; 325: 373-381
      3. The Lipid Research Clinics. 1980. Population studies data book. Vol. 1. The prevalence study. Bethesda, MD. US Department of Health and Human Services. NIH (NIH Publication 80-1527).

        • Gordon T.
        • Shurtleff D.
        Means at the examination and inter-examination variation of specified characteristics: the Framingham Study, exam 1 to exam 10. Section 29. In The Framingham Study..
        in: Kannel W.B. Gordon T. NIH (DHEW Publication), Washington, DC.1974: 74-478
        • Heiss G.
        • Tamir T.
        • Davis C.E.
        • Tyroler H.A.
        • Rif-kind B.M.
        • Schonfeld G.
        • Jacobs D.
        • Frantz I.D.
        Lipoprotein cholesterol distributions in selected North American populations: the Lipid Research Clinics Program prevalence study.
        Circulation. 1980; 61: 302-315
        • Olofsson S-O.
        • Bjursell G.
        • Bostrom K.
        • Carlsson P.
        • Elovson J.
        • Protter A.A.
        • Reuben M.A.
        • Bondjers G.
        Apolipoprotein B: structure, biosynthesis and role in the lipoprotein assembly process.
        Atherosclerosis. 1987; 68: 1-17
        • Brown M.S.
        • Goldstein J.L.
        A receptor-mediated pathway for cholesterol homeostasis.
        Science. 1986; 232: 34-47
        • Sniderman A.
        • Shapiro S.
        • Marpole D.
        • Skinner B.
        • Teng B.
        • Kwiterovich Jr., P.O.
        Association of coronary atherosclerosis with hyperapobetalipoproteinemia [increased protein but normal cholesterol levels in human plasma low density (|3) lipoproteins].
        Proc. Natl. Acad. Sci. USA. 1980; 77: 604-608
        • Sniderman A.D.
        • Wolfson C.
        • Teng B.
        • Franklin F.A.
        • Bachorik P.S.
        • Kwiterovich Jr., P.O.
        Association of hyperapobetalipoproteinemia with endogenous hypertriglyceridemia and atherosclerosis.
        Ann. Intern. Med. 1982; 97: 833-839
        • Wilson P.W.F.
        • Christiansen J.C.
        • Anderson K.
        • Kannel W.B.
        Impact of national guidelines for cholesterol risk factor screening: the Framingham Offspring Study.
        J. Am. Med. Assoc. 1989; 262: 41-44
        • Warnick G.R.
        • Benderson J.
        • Albers J.J.
        Dextran sulfate-Mg2* precipitation procedure for quantification of high density lipoprotein cholesterol.
        Clin. Chem. 1982; 28: 1379-1388
        • McNamara J.R.
        • Schaefer E.J.
        Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions.
        Clin. Chim. Acta. 1987; 166: 1-8
        • Friedewald W.T.
        • Levy R.I.
        • Fredrickson D.S.
        Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.
        Clin. Chem. 1972; 18: 499-502
      4. Laboratory Methods Committee of the Lipid Research Clinics Program of the National Heart, Lung, and Blood Institute. 1977. Cholesterol and triglyceride concentrations in serum/plasma pairs. Clin. Chem. 23: 60-63.

        • McNamara J.R.
        • Campos H.
        • Ordovas J.M.
        • Peterson J.
        • Wilson P.W.F.
        • Schaefer E.J.
        Effect of gender, age, and lipid status on low density lipoprotein subfraction distribution. Results from the Framingham Offspring Study.
        Arteriosclerosis. 1987; 7: 483-490
        • Krauss R.M.
        • Burke D.J.
        Identification of multiple subclasses of plasma low density lipoproteins in normal humans.
        J. Lipid Res. 1982; 23: 97-104
        • Campos H.
        • Blijlevens E.
        • McNamara J.R.
        • Ordovas J.M.
        • Posner B.P.
        • Wilson P.W.F.
        • Castelli W.P.
        • Schaefer E.J.
        LDL particle size distribution. Results from the Framingham Offspring Study.
        Arterioscler. Thromb. 1992; 12: 1410-1419
        • Ordovas J.M.
        • Peterson J.P.
        • Santaniello P.
        • Cohn J.S.
        • Wilson P.W.F.
        • Schaefer E.J.
        Enzyme-linked immunosorbent assay for human plasma apolipoprotein B..
        J. Lipid Res. 1987; 28: 1216-1224
        • Lowry O.H.
        • Rosebrough N.J.
        • Farr A.L.
        • Randall R.J.
        Protein measurement with the Folin phenol reagent.
        J. Biol. Chem. 1951; 193: 265-275
        • Grundy S.M.
        • Mok H.Y.I.
        Chylomicron clearance in normal and hyperlipidemic men.
        Metabolism. 1976; 25: 1225-1239
        • Cohn J.S.
        • McNamara J.R.
        • Cohn S.D.
        • Ordovas J.M.
        • Schaefer E.J.
        Plasma apolipoprotein changes in the triglyceride-rich lipoprotein fraction of human subjects fed a fat-rich meal.
        J. Lipid Res. 1988; 29: 925-936
      5. Kennel, W. B., and T. J. Thom. 1986. Incidence, prevalence, and mortality of cardiovascular disease. In The Heart. J. W. Hurst, editor. Sixth edition. McGraw-Hill, New york, NY. 557-565.

        • Gordon D.J.
        • Probstfield J.L.
        • Garrison R.J.
        • Nea-ton J.D.
        • Castelli W.P.
        • Knoke J.D.
        • Jacobs Jr., D.R.
        • Bang-diwala S.
        • Tyroler H.A.
        High density lipoprotein cholesterol and cardiovascular disease: four prospective American studies.
        Circulation. 1989; 79: 8-15
      6. Fulwood, R., W. Kalsbeck, B. Rilkind, R. Russell-Briefel, R. Muesing, J. LaRosa, and K. Lippel. 1984. Total serum cholesterol levels of adults 20-74 years of age: United States, 1976-80. In Vital and Health Statistics. Ser II, No. 236. DHHS Pub. No. (PHS) 86-1686. National Center for Health Statistics. Public Health Service, Washington, DC.

        • Hainline Jr., A.
        • Karon J.M.
        • Winn C.L.
        • Gill J.B.
        Accuracy and comparability of long-term measurements of cholesterol.
        Clin. Chem. 1986; 32: 611-615
        • Albers J.J.
        • Marcovina S.M.
        • Kennedy H.
        International Federation of Clinical Chemistry Standardization Project for measurement of apolipoproteins A-I and B. Evaluation and selection of candidate reference materials.
        Clin. Chem. 1992; 38: 658-662
        • Avogaro P.
        • Bittolo Bon G.
        • Belussi F.
        • Quinci G.B.
        • Cazzolato G.
        Values of apoA-I and apoB in humans according to age.
        Clin. Chim. Acta. 1975; 95: 311-315
        • Assmann G.
        • Schulte H.
        Triglycerides and atherosclerosis. Results from the Prospective Cardiovascular Münster Study.
        Atheroscler. Rev. 1991; 22: 51-57
        • Vermaak W.J.H.
        • Kotze J.P.
        • van der Merwe A.M.
        • Becker P.J.
        • Ubbink J.B.
        • Barnard H.C.
        • Roux F.G.
        • Sch'oeman J.J.
        • Strydom G.L.
        Epidemiological reference ranges for low-density lipoprotein cholesterol and apolipoprotein B for identification of increased risk of ischaemic heart disease.
        S. AJr. Med. J. 1991; 79: 367-371
        • Zunic G.
        • Jelic-Ivanovic Z.
        • Spasic S.
        • Stojiljkovic A.
        • Majkic-Singh N.
        Reference values for apolipoproteins A-I and B in healthy subjects, by age.
        Clin. Chem. 1992; 38: 566-569
        • Kinlay S.
        • Dobson A.J.
        • Heller R.F.
        • Dickeson J.E.
        • Ryan S.
        Lipid and apolipoprotein levels in an Australian community.
        Med. J. Aust. 1991; 154: 170-175
        • Abbott R.D.
        • Garrison R.J.
        • Wilson P.W.F.
        • Epstein F.H.
        • Castelli W.P.
        • Feileib M.
        • LaRue C.
        Joint distribution of lipoprotein cholesterol classes. The Framingham Study.
        Arteriosclerosis. 1983; 3: 260-272
        • Ericsson S.
        • Eriksson M.
        • Vitols S.
        • Einarsson K.
        • Berglund L.
        • Angelin B.
        Influence of age on the metabolism of plasma low density lipoproteins in healthy males.
        J. Clin. Invest. 1991; 87: 591-596
        • Granfone A.
        • Campos H.
        • McNamara J.R.
        • Schaefer M.M.
        • Lamon-Fava S.
        • Ordovas J.M.
        • Schaefer E.J.
        Effects of estrogen replacement on plasma lipoproteins and apolipoproteins in postmenopausal, dys-lipidemic women.
        Metabolism. 1992; 41: 1193-1198
        • Tikkanen M.J.
        • Nikkila E.A.
        • Vartianen E.
        Natural estrogen as an effective treatment for type-II hyperlipoproteinemia in postmenopausal women.
        Lancet. 1978; 2: 490-491
        • Kovanen P.T.
        • Brown M.S.
        • Goldstein J.L.
        Increased binding of low density lipoprotein to liver membranes from rats treated with 17'alpha-ethinyl estradiol.
        J. Biol. Chem. 1979; 254: 11367-11373
        • Nestel P.J.
        • Hirsch E.Z.
        • Couzenz E.A.
        The effects of chlorophenoxyisobutyric acid and ethinyl estradiol on cholesterol turnover.
        J. Clin. Invest. 1965; 44: 841-896
        • Kushwaha R.S.
        • Hazzard W.R.
        Effect of exogenous estrogens on catabolism of VLDL in cholesterol-fed rabbits.
        Am. J. Physiol. 1981; 241: E372-E377
        • Campos H.
        • Wilson P.W.F.
        • Jimenez D.
        • McNamara J.R.
        • Ordovas J.M.
        • Schaefer E.J.
        Differences in apolipoproteins and low-density lipoprotein subfractions in postmenopausal women on and off estrogen therapy: results from the Framingham Offspring Study.
        Metabolism. 1990; 39: 1033-1038
        • Campos H.
        • McNamara J.R.
        • Wilson P.W.F.
        • Ordovas J.M.
        • Schaefer E.J.
        Differences in low density lipoprotein subfractions and apolipoproteins in premenopausal and postmenopausal women.
        J. Clin. Endocrinol. Metab. 1988; 67: 30-35
        • Kronmal R.A.
        • Cain K.C.
        • Ye Z.
        • Omenn G.S.
        Total serum cholesterol levels and mortality risk as a function of age. A report based on the Framingham data.
        Arch. Intern. Med. 1993; 153: 1065-1073
        • Genest Jr., J.J.
        • Martin-Munley S.S.
        • McNamara J.R.
        • Ordovas J.M.
        • Jenner J.
        • Myers R.H.
        • Silberman S.R.
        • Wilson P.W.F.
        • Salem D.N.
        • Schaefer E.J.
        Familial lipoprotein disorders in patients with premature coronary artery disease.
        Circulation. 1992; 85: 2025-2033
        • Genest Jr., J.J.
        • McNamara J.R.
        • Ordovas J.M.
        • Jenner J.L.
        • Silberman S.R.
        • Anderson K.M.
        • Wilson P.W.F.
        • Salem D.N.
        • Schaefer E.J.
        Lipoprotein cholesterol, apolipoprotein A-I and B and lipoproteinfa] abnormalities in men with premature coronary artery disease.
        J. Am. Coll. Cardiol. 1992; 19: 792-802
        • Kauppinen-Makelin R.
        • Nikkila E.A.
        Serum lipoproteins in patients with myocardial infarction.
        Atherosclerosis. 1988; 74: 65-74
        • Schaefer E.J.
        • Levy R.I.
        • Ernst N.D.
        • VanSant F.D.
        • Brewer Jr., H.B.
        The effects of low cholesterol, high polyunsaturated fat and low fat diets on plasma lipids and lipoprotein cholesterol levels in normal and hyper-cholesterolemic subjects.
        Am. J. Clin. Nutr. 1981; 34: 1758-1763
        • Wolinsky H.
        The effects of beta-adrenergic blocking agents on blood lipid levels.
        Clin. Cardiol. 1987; 10: 561-566
        • Genest Jr., J.J.
        • McNamara J.R.
        • Salem D.N.
        • Schaefer E.J.
        Prevalence of risk factors in men with premature coronary artery disease.
        Am. J. Cardiol. 1991; 67: 1185-1189
        • Huff M.W.
        • Evans A.J.
        • Sawyez C.G.
        • Wolfe B.M.
        • Nestel P.J.
        Cholesterol accumulation inJ774 macrophages induced by triglyceride-rich lipoproteins: comparisons of VLDL from subjects with type III, IV, and V hyperlipoproteinemias.
        Arterioscler. Thromb. 1991; 11: 221-233
        • Dahlen G.H.
        • Guyton J.R.
        • Attar M.
        • Farmer J.A.
        • Kautz J.A.
        • Gotto A.M.
        Association of levels of lipoprotein [a], plasma lipids, and other lipoproteins with coronary artery disease documented by angiography.
        Circulation. 1986; 74: 758-765
        • Rosengren A.
        • Wilhelmsen L.
        • Eriksson E.
        • Risberg B.
        • Wedel H.
        Lipoprotein [a] and coronary heart disease: a prospective case-control study in a general population sample of middle-aged men.
        Br. Med. J. 1990; 301: 1248-1251
        • Feinleib M.
        • Garrison R.J.
        • Fabsitz R.
        • Christian J.C.
        • Hrubec Z.
        • Borhani N.O.
        • Kannel W.B.
        • Rosenman R.
        • Schwartz J.T.
        • Wagner J.O.
        The NHLBI Twin Study of cardiovascular disease risk factors. Methodology and summary of results.
        Am. J. Epidemiol. 1977; 106: 284-295
        • Lamon-Fava S.
        • Jimenez D.
        • Christian J.C.
        • Fabsitz R.R.
        • Reed T.
        • Carmelli D.
        • Castelli W.P.
        • Ordovas J.M.
        • Wilson P.W.F.
        • Schaefer E.J.
        The NHLBI Twin study: heritability of apolipoprotein A-1, B, and low density lipoprotein subclasses and concordance for lipoproteinfa].
        Atherosclerosis. 1991; 91: 97-106
        • Williams R.R.
        • Hunt S.C.
        • Hopkins P.N.
        • Stults B.M.
        • Hasstedt S.J.
        • Barlow G.K.
        • Stephenson S.H.
        • Lalouel J-M.
        • Kuida H.
        Familial dyslipidémie hypertension. Evidence from 58 Utah families for a syndrome present in approximately 12% of patients with essential hypertension.
        J. Am. Med. Assoc. 1988; 259: 3579-3586
        • Selby J.V.
        • Newman B.
        • Quiroga J.
        • Christian J.C.
        • Austin M.A.
        • Fabsitz R.R.
        Concordance for dyslipidémie hypertension in male twins.
        J. Am. Med. Assoc. 1991; 265: 2079-2084
        • Denke M.A.
        • Sempos C.T.
        • Grundy S.M.
        Excess body weight. An under-recognized contributor to high blood cholesterol levels in white American men.
        Arch. Intern. Med. 1993; 153: 1093-1103