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Research Article| Volume 74, SUPPLEMENT 1, S17-S22, June 30, 2000

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The role of small, dense low density lipoprotein (LDL): a new look

      Abstract

      Plasma low density lipoprotein (LDL) plays a central role in atherogenesis, and elevated levels of LDL are associated with an increased risk of coronary heart disease (CHD). Studies have now revealed that LDL is structurally heterogeneous, based on its size and density. Patients with combined hyperlipidemia exhibit a lipid profile — the so-called atherogenic lipoprotein phenotype — that is associated with elevated triglyceride levels, low levels of high density lipoprotein and a preponderance of atherogenic, small, dense LDL particles. Such individuals are at an increased risk of CHD events, regardless of their total LDL circulating mass. Evidence suggests that when plasma triglycerides exceed a critical threshold of approximately 133 mg/dl (1.5 mmol/l), this favours the formation of small, dense LDL from larger, less dense species. Lipid-lowering agents that are capable of lowering triglyceride levels below this threshold value will cause a shift to a less dense and, therefore, less atherogenic LDL profile. This effect has been demonstrated for the HMG-CoA reductase inhibitor atorvastatin which, in addition to its ability to markedly decrease the total LDL circulating mass, can also shift the LDL profile towards less dense, larger species. This suggests that atorvastatin may also affect the atherogenic lipoprotein phenotype found in patients with combined hyperlipidemia.

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      References

        • Castelli W.P.
        • Garrison R.J.
        • Wilson P.W.F.
        • et al.
        Incidence of coronary heart disease and lipoprotein cholesterol levels. The Framingham Study.
        J Am Med Assoc. 1986; 256: 2835-2838
        • Gofman J.W.
        • Delalla O.
        • Glazier F.
        • et al.
        The serum lipoprotein transport system in health, metabolic disorders, atherosclerosis and coronary artery disease.
        Plasma. 1954; 2: 413
        • Fisher W.R.
        Heterogeneity of plasma low density lipoprotein manifestations of the physiologic phenomenon in man.
        Metabolism. 1983; 32: 283
        • Krauss R.M.
        • Blanche P.J.
        Detection and quantitation of LDL subfractions.
        Curr Opin Lipidol. 1992; 3: 377-383
        • Swinkels D.W.
        • Demacker P.N.M.
        • Hendriks J.C.M.
        • Van’t Laar A.
        Low density lipoprotein subfractions and relationships to other risk factors for coronary artery disease in healthy individuals.
        Arteriosclerosis. 1989; 9: 604-613
        • Griffin B.A.
        • Freeman D.J.
        • Tait G.W.
        • et al.
        Role of plasma triglyceride in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk.
        Atherosclerosis. 1994; 106: 241-253
        • Packard C.J.
        • Shepherd J.
        Lipoprotein heterogeneity and apolipoprotein B metabolism.
        Arterioscler Thromb Vasc Biol. 1997; 17: 3542-3556
        • Austin M.A.
        • King M.C.
        • Vranizan K.M.
        • Krauss R.M.
        Atherogenic lipoprotein phenotype. A proposed genetic marker for coronary heart disease risk.
        Circulation. 1990; 82: 495-506
        • Campos H.
        • Genest Jr., J.J.
        • Blijlevens E.
        • et al.
        Low density lipoprotein particle size and coronary artery disease.
        Arterioscler Thromb. 1992; 12: 187-195
        • Tan C.E.
        • Forster L.
        • Caslake M.J.
        • et al.
        Relations between plasma lipids and postheparin plasma lipases and VLDL and LDL subfractions in normolipemic men and women.
        Arterioscler Thromb Vasc Biol. 1995; 15: 1839-1848
        • Reaven G.M.
        • Chen Y.-D.I.
        • Jeppesen J.
        • Maheux P.
        • Krauss R.M.
        Insulin resistance and hyperinsulinemia in individuals with small, dense, low density lipoprotein particles.
        J Clin Invest. 1993; 92: 141-146
        • Tan K.C.
        • Cooper M.B.
        • Ling K.L.E.
        • et al.
        Fasting and postprandial determinants for the occurrence of small, dense LDL species in non-insulin dependent diabetic patients with and without hypertriglyceridemia: the involvement of insulin, insulin precursor species and insulin resistance.
        Atherosclerosis. 1995; 113: 273-287
        • Zambon A.
        • Austin M.A.
        • Brown B.G.
        • Hokanson J.E.
        • Brunzell J.D.
        Effect of hepatic lipase on LDL in normal men and those with coronary artery disease.
        Arterioscler Thromb. 1993; 13: 147-153
        • Anber V.
        • Griffin B.A.
        • McConnell M.
        • Packard C.J.
        • Shepherd J.
        Influence of plasma lipid and LDL-subfraction profile on the interaction between low density lipoprotein with human arterial wall proteoglycans.
        Atherosclerosis. 1996; 124: 261-271
        • Superko H.R.
        • Krauss R.M.
        Different effects of nicotinic acid in subjects with different LDL subclass patterns.
        Atherosclerosis. 1992; 95: 69-76
        • Gaw A.
        • Packard C.J.
        • Caslake M.J.
        Effects of ciprofibrate on LDL metabolism in man.
        Atherosclerosis. 1994; 108: 137-148
        • Guerin M.
        • Bruckert E.
        • Dolphin P.J.
        • Turpin G.
        • Chapman M.J.
        Fenofibrate reduces cholesteryl ester transfer from HDL to VLDL and normalises the atherogenic, dense LDL profile in combined hyperlipidemia.
        Arterioscler Thromb Vasc Biol. 1996; 16: 763-772
        • Gaw A.
        • Packard C.J.
        • Murray E.F.
        Effects of simvastatin on apoB metabolism and LDL subfraction distribution.
        Arterioscler Thromb. 1993; 13: 170-189
        • Dart A.
        • Jerums G.
        • Nicholson G.
        • et al.
        A multicenter, double-blind, one-year study comparing safety and efficacy of atorvastatin versus simvastatin in patients with hypercholesterolemia.
        Am J Cardiol. 1997; 80: 39-44
        • Jones P.
        • Kafonek S.
        • Laurora I.
        • et al.
        For the CURVES investigators. Comparative dose efficacy study of atorvastatin versus simvastatin, pravastatin, lovastatin and fluvastatin in patients with hypercholesterolemia (the CURVES study).
        Am J Cardiol. 1998; 81: 582-587
      1. Caslake MJ, Forster LF, Stewart G, Roger E, Shepherd J, Packard CJ, Effects of atorvastatin and simvastatin on the LDL subfraction profile in combined hyperlipidemia. Abstract presented at the International Congress on Vascular Disease Prevention, 4–8 May 1998, Glasgow, UK.