Sex and time differences in the associations of non–high-density lipoprotein cholesterol versus other lipid and lipoprotein factors in the prediction of cardiovascular death (The Rancho Bernardo Study)


      Non–high-density lipoprotein (HDL) cholesterol (total cholesterol [TC] minus HDL cholesterol) has been suggested as the preferred lipid fraction to predict cardiovascular disease. We compared the ability of lipids, lipoproteins, the ratio of total to HDL cholesterol (TC/HDL), and non-HDL cholesterol to predict fatal coronary heart disease (CHD) and cardiovascular disease in 1,386 women and 1,094 men (mean age 69 years). After 10 years, there were more deaths in men (n = 310) than women (n = 268), but the proportions of deaths attributed to CHD (23% and 25%, respectively) and cardiovascular disease (48% and 47%) were similar. In men, age-adjusted values for non-HDL cholesterol, TC/HDL ratio, and triglycerides each predicted a significantly increased risk of CHD and cardiovascular disease; none of these associations was independent of pack-years of smoking, systolic blood pressure, fasting plasma glucose, body mass index, and physical activity. In women, age-adjusted non-HDL cholesterol levels did not predict CHD or cardiovascular disease events before or after adjusting for these covariates and for estrogen replacement therapy. In women, only the ratio of TC to HDL cholesterol predicted CHD and cardiovascular disease deaths independent of estrogen use and other risk factors. Observed associations were sensitive to time, being evident in women at 3 and 5 years, and lost thereafter, but not apparent before 10 years in men. Thus, non-HDL cholesterol is not superior to individual lipids, lipoproteins, or their ratios in the prediction of cardiovascular death in older adults.
      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 to American Journal of Cardiology
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect


        • NCEP Expert Panel
        Executive Summary of the Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III).
        JAMA. 2001; 285: 2486-2497
        • Cui Y.
        • Blumenthal R.S.
        • Flaws J.A.
        • Whiteman M.K.
        • Langenberg P.
        • Bachorik P.S.
        • Bush T.L.
        Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality.
        Arch Intern Med. 2001; 161: 1413-1419
        • Frost P.H.
        • Davis B.R.
        • Burlando A.J.
        • Curb J.D.
        • Stamler J.
        • Guthrie G.P.
        • Isaacsohn J.L.
        • Wassertheil-Smoller S.
        • Wilson A.C.
        • Stamler J.
        Serum lipids and incidence of coronary heart disease. Findings from the Systolic Hypertension in the Elderly Program (SHEP).
        Circulation. 1996; 94: 2381-2388
        • Gardner C.D.
        • Fortmann S.P.
        • Krauss R.M.
        Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women.
        JAMA. 1996; 276: 875-881
        • Bush T.L.
        • Barrett-Connor E.
        • Cowan L.D.
        • Criqui M.H.
        • Wallace R.B.
        • Suchindran C.M.
        • Tyroler H.A.
        • Rifkind B.M.
        Cardiovascular mortality and noncontraceptive use of estrogen in women.
        Circulation. 1987; 75: 1102-1109
        • Goldbourt U.
        • Medalie J.H.
        High density lipoprotein cholesterol and incidence of coronary heart disease. The Israeli Ischemic Heart Disease Study.
        Am J Epidemiol. 1979; 109: 296-308
        • Castelli W.P.
        Cardiovascular disease in women.
        Am J Obstet Gynecol. 1988; 158: 1553-1560
        • Langer R.D.
        • Klauber M.R.
        • Criqui M.H.
        • Barrett-Connor E.
        Exercise and survival in the very old.
        Am J Geriatr Cardiol. 1994; 3: 24-34
      1. National Heart and Lung Institute Lipid Research Clinics Program Laboratory Methods Committee. Manual of Laboratory Operations: Lipid and Lipoprotein Analysis. 2 Ed. Washington, DC: US Government Printing Office, DHEW publication No 75–628, 1974

        • Bass K.M.
        • Newschaffer C.J.
        • Klag M.J.
        • Bush T.L.
        Plasma lipoprotein levels as predictors of cardiovascular death in women.
        Arch Intern Med. 1993; 153: 2209-2216
        • Gordon D.J.
        • Probstfield J.L.
        • Garrison R.J.
        • Neaton J.D.
        • Castelli W.P.
        • Knoke J.D.
        • Jacobs D.R.
        • Bangdiwala S.
        • Tyroler H.A.
        High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies.
        Circulation. 1989; 79: 8-15
        • Criqui M.H.
        Triglycerides and ischemic heart disease.
        Atherosclerosis Rev. 1991; 22: 75-79
        • Ballantyne C.M.
        • Andrews T.C.
        • Hsia J.A.
        • Kramer J.H.
        • Shear C.
        Correlation of non-high-density lipoprotein cholesterol with apolipoprotein B.
        Am J Cardiol. 2001; 88: 265-269
        • Havel R.J.
        • Rapaport E.
        Management of primary hyperlipidemia.
        N Engl J Med. 1995; 332: 1491-1498
        • Denke M.A.
        • Sempos C.T.
        • Grundy S.M.
        Excess body weight. An under-recognized contributor to dyslipidemia in white American women.
        Arch Intern Med. 1994; 154: 401-410
        • Davidson M.H.
        • Testolin L.M.
        • Maki K.C.
        • von Duvillard S.
        • Drennan K.B.
        A comparison of estrogen replacement, pravastatin, and combined treatment for the management of hypercholesterolemia in postmenopausal women.
        Arch Intern Med. 1997; 157: 1186-1192
        • Ashraf T.
        • Hay J.W.
        • Pitt B.
        • Wittels E.
        • Crouse J.
        • Davidson M.
        • Furberg C.D.
        • Radican L.
        Cost-effectiveness of pravastatin in secondary prevention of coronary artery disease.
        Am J Cardiol. 1996; 78: 409-414
        • Williams P.T.
        • Dreon D.M.
        • Blanche P.J.
        • Krauss R.M.
        Variability of plasma HDL subclass concentrations in men and women over time.
        Arterioscler Thromb Vasc Biol. 1997; 17: 702-706
        • Marcovina S.M.
        • Gaur V.P.
        • Albers J.J.
        Biological variability of cholesterol, triglycerides, low- and high-density lipoprotein cholesterol, lipoprotein(a), and apolipoproteins A-I and B.
        Clin Chem. 1994; 40: 574-578
        • Pieper R.M.
        • Arnett D.K.
        • McGovern P.G.
        • Shahar E.
        • Blackburn H.
        • Luepker R.V.
        Trends in cholesterol knowledge and screening and hypercholesterolemia awareness and treatment, 1980–1992; The Minnesota Heart Survey.
        Arch Intern Med. 1997; 157: 2326-2332
        • Lemaitre R.N.
        • Furberg C.D.
        • Newman A.B.
        • Hulley S.B.
        • Gordon D.J.
        • Gottdiener J.S.
        • McDonald R.H.
        • Psaty B.M.
        Time trends in the use of cholesterol-lowering agents in older adults.
        Arch Intern Med. 1998; 158: 1761-1768
        • Sacks F.M.
        • Handysides G.H.
        • Marais G.E.
        • Rosner B.
        • Kass E.H.
        Effects of a low-fat diet on plasma lipoprotein levels.
        Arch Intern Med. 1986; 146: 1573-1577
        • Hubert H.B.
        • Eaker E.D.
        • Garrison R.J.
        • Castelli W.P.
        Life-style correlates of risk factor change in young adults.
        Am J Epidemiol. 1987; 125: 812-831
        • Kuller L.H.
        • Hulley S.B.
        • LaPorte R.E.
        • Neaton J.
        • Dai W.S.
        Environmental determinants, liver function, and high density lipoprotein cholesterol levels.
        Am J Epidemiol. 1983; 117: 406-418
        • The Writing Group for the PEPI Trial
        Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/Progestin Interventions (PEPI) Trial.
        JAMA. 1995; 273: 199-208
        • Harrell Jr, F.E.
        • Lee K.L.
        • Pollock B.G.
        Regression models in clinical studies.
        J Natl Cancer Inst. 1988; 80: 1198-1202