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When is equal not equal?

Published:February 01, 2010DOI:https://doi.org/10.1016/j.jacl.2010.01.005

      Abstract

      The meta-analysis of the Emerging Risk Factor Collaboration demonstrated that the hazard ratios (HR) of the major cholesterol markers and the major apolipoproteins for vascular disease did not differ significantly in the studies they examined. Their conclusion was that they were functionally interchangeable. We believe there are important limitations in the execution of this study. Nevertheless, even if their findings are correct for groups, their conclusions do not follow for individuals. Conventionally, the HR expresses the increase in risk per standard deviation change for that parameter in a group. However, the predicted risk of vascular disease from an atherogenic parameter depends on its concentration within the individual. Depending on the composition of the apoB lipoproteins, individuals may have either concordant or discordant levels of cholesterol and apoB. For those who are concordant, the two markers predict equal risk. For those who are discordant, the predicted risks for the individual are different. We demonstrate that substantial discordance in the individual HR of non-high-density lipoprotein cholesterol and apoB is common. The result is that even with identical overall HR, apoB points to higher risk in a substantial number of individuals whereas the converse is the case for non- high-density lipoprotein cholesterol. Because we are concerned with risks in individuals, not groups, this discordance is important to appreciate and analyze. Our objective should be to learn how to combine the information from parameters rather than eliminate them and we need to focus on evaluation of risk in individuals and not just groups.

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      References

        • Danesh J.
        The Emerging Risk Factors Collaboration. Major lipids, apolipoproteins, and risk of vascular disease.
        J Am Med Assoc. 2009; 302: 1993-2000
        • Sniderman A.D.
        • de Groot E.
        • Couture P.
        ApoB and the atherogenic ApoB dyslipoproteinemias.
        in: Kwiterovich Jr., P.O. The Johns Hopkins Textbook of Dylipidemia. Lippincott Williams & Wilkins, Philadelphia, PA2009: 196-210
        • McQueen M.J.
        • Hawken S.
        • Wang X.
        • et al.
        The relative importance of lipids, lipoproteins, and apolipoproteins as risk markers associated with myocardial infarction in 52 countries.
        Lancet. 2008; 372: 224-233
        • Parish S.
        • Peto R.
        • Palmer A.
        • et al.
        The joint effects of apolipoprotein B, apolipoprotein A1, LDL cholesterol, and HDL cholesterol on risk: 3510 cases of acute myocardial infarction and 9805 controls.
        Eur Heart J. 2009; 30: 2137-2146
        • Barter P.J.
        • Ballantyne C.M.
        • Carmena R.
        • et al.
        ApoB versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel.
        J Intern Med. 2006; 259: 247-258
      1. NHANES Investigators. NHANES Analytic Guidelines 2003–2004. Available at: http://www.cdc.gov/nchs/data/nhanes/nhanes_03_04/nhanes_analytic_guidelines_dec_2005.pdf. Accessed February 16, 2009.

        • Wilson P.W.F.
        • D'Agostino R.B.
        • Levy D.
        • Belanger A.M.
        • Halit S.
        • Kannel W.B.
        Prediction of coronary heart disease using risk factor categories.
        Circulation. 1998; 97: 1837-1847
        • D'Agostino R.B.
        • Russell M.W.
        • Huse D.M.
        • Ellison R.C.
        • Silbershatz H.
        • Wilson P.W.
        • et al.
        Primary and subsequent coronary risk appraisal: new results from the Framingham study.
        Am Heart J. 2000; 139: 272-281
        • Ridker P.M.
        • Danielson E.
        • Fonseca F.A.
        • et al.
        Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.
        N Engl J Med. 2008; 359: 2195-2207
        • Sniderman A.
        • Williams K.
        • Cobbaert C.
        ApoB versus non-HDLC: What to do when they disagree.
        Curr Atheroscler Rep. 2009; 11: 358-363
        • Ridker P.M.
        • Danielson E.
        • Fonseca F.A.
        • et al.
        Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial.
        Lancet. 2009; 373: 1175-1182
        • Sniderman A.D.
        • Tremblay A.
        • Bergeron J.
        • Gagne C.
        • Couture P.
        Diagnosis of type III hyperlipoproteinemia from plasma total cholesterol, triglyceride, and apolipoprotein B.
        J Clin Lipidol. 2007; 1: 256-263
        • de Graaf J.
        • Couture P.
        • Sniderman A.
        A diagnostic algorithm for the atherogenic apolipoprotein B dyslipoproteinemias.
        Nat Clin Endocrinol Metab. 2008; 4: 608-618
        • Cromwell W.C.
        • Otvos J.D.
        • Keyes M.J.
        • et al.
        LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study—Implications for LDL management.
        J Clin Lipidol. 2007; 1: 583-592