Cholesterol and Lipoprotein Risk Factors

Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults

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    Cholesterol and Lipoprotein Risk Factors

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    • Total Cholesterol

      Total Cholesterol

      B = All Lipoproteins containing an ApoB100 (non-HDL Cholesterol)
      Apolipoprotein B (Apo B) is the major apolipoprotein of all atherogenic particles i.e total apo B represents the sum of all atherogenic particles in the blood. Studies have clearly indicated it as a better predictor of coronary artery disease than total LDL cholesterol in select patients, namely those patients with cardiometabolic risk (i.e. insulin resistance, metabolic syndrome). Total apo B has been shown to have a strong predictive power for severity of coronary atherosclerosis and CHD events.

    • A = All Lipoproteins containing an ApoAI &/or AII (HDL Cholesterol)
      The major apoproteins of HDL are apo AI and apoAII. However, currently apoAI is of most interest as it is the major apoprotein that is linked to CAD reduction. Interestingly as well is the fact that people with normal HDL can still have low apoAI levels which predispose them to CAD risk. In fact, if one has high HDL i.e. >60mg/dL this could be a sign of nonfunctional HDL and these patients should have their apoAI numbers checked.



    • Low Density Lipoprotein Cholesterol (LDL-C)

      Low Density Lipoprotein Cholesterol (LDL-C)

      LDL cholesterol has been, and will continue to be the focus of risk reduction intervention strategies. Despite the usefulness of total LDL cholesterol for CVD prediction on a population level, the measurement has significant limitations for individual risk assessment. LDL is not present in the circulation as one well-defined structure, but rather as particles in a continuum of size and density. Knowing LDL cholesterol breakdown is consistent with the recommendation outlined by the Working Group on Lipoprotein Measurments.

    • LDL Size/Density Pattern.
      Small, dense LDL occurs in 40% to 50% of patients with CAD; this information is not provided by the routine lipid panel. Dense LDL (Pattern B) is associated with a 4 fold increased risk for CAD and a 6.9 fold risk for myocardial infarction. By contrast, even very high total cholesterol and total LDL are associated with only a 2-fold increase in risk for CAD. Small dense LDL is a risk factor for CAD even in patients with normal cholesterol.

    • LDL component Lipoprotein (a).
      Lp(a) has been proven to be an independent and critical risk factor for CAD. It is highly correlated with risk of premature coronary artery disease and appears to have strong negative synergies when other lipid abnormalities are present. The prevalence of elevated Lp(a) has been reported to be 16–32% in the offspring of patients with premature myocardial infarction. High Lp(a) plus low HDL was recently found in PROCAM to increase risk 8.3 times. When the atherogenic dyslipidemia (low HDL2, small dense LDL, etc.) is present then Lp(a) contributes a relative risk of 25 times normal. Lp(a) is also a powerful and independent predictor of stroke. In type 2 diabetics, elevated Lp(a) levels were independently associated with coronary heart disease with an increased risk of 3.5. Lp(a) levels are under strong genetic control, with minimal environmental influences.

    • LDL component Intermediate density lipoprotein (IDL)
      IDL, represents a lipoprotein transition between VLDL and LDL particles. Data from a number of angiographic trials, show IDL is significantly more atherogenic than LDL alone. IDL concentration is under strong genetic control, and diet and exercise have little effect on IDL levels.

    • It is important to note that in the traditional lipid profile “LDL cholesterol concentration” actually represents the sum of real LDL-C, IDL-C, and Lp(a)-C concentrations.



    • High Density Lipoprotein Cholesterol (HDL-C)

      High Density Lipoprotein Cholesterol (HDL-C)

      High density lipoprotein cholesterol (HDL) is clearly established as the “good cholesterol”. Low levels of HDL were first identified as a coronary disease risk factor in 1951.

    • HDL2 is considered the most protective sub-fraction or “best cholesterol”. Total HDL measurements (if mostly HDL3) may under-estimate the real atherogenic risk to patients. Low HDL2 is a risk for CAD even in patients with normal cholesterol. It is also an independent risk factor for diabetics with peripheral vascular disease.

    • Very Low Density Lipoprotein Cholesterol (VLDL-C)

      Very Low Density Lipoprotein Cholesterol (VLDL-C)

      VLDL, the main lipoprotein transporting triglycerides in the circulation, is like LDL in that it is also present in a gradient of particle size and density. Large buoyant VLDL is atherogenic by shifting LDL particle size to smaller, denser forms. Small dense VLDL3 is directly atherogenic, and can lead to direct foam cell transformation and raised plaque formation.

    • Triglycerides (TG)

      Elevated triglycerides have been associated with increased cardiovascular risk since 1959, and multiple studies have shown a near linear relationship between triglyceride concentration and coronary heart disease event rates. Special populations such as diabetics and post-menopausal women are especially affected. As a result of non-genetic causes. Hypertriglyceridemia (triglyceride concentrations over 100mg/dL to 150mg/dL) cause a shift in LDL to a smaller, denser, more atherogenic form.

    • Non-HDL Cholesterol

      The sum of VLDL+LDL cholesterol is called non-HDL cholesterol. Non-HDL cholesterol is highly correlated with total apolipoprotein B (apo B); apolipoprotein B is the major apolipoprotein of all atherogenic lipoproteins. Serum total apo B also has been shown to have a strong predictive power for severity of coronary atherosclerosis and CHD events. Because of the high correlation between non-HDL cholesterol and apolipoprotein B levels, non-HDL cholesterol represents an acceptable surrogate marker for total apolipoprotein B in routine clinical practice When triglyceride levels are =200 mg/dL, VLDL cholesterol levels are distinctly raised, and LDL-cholesterol concentrations are less well correlated with VLDL and LDL (non-HDL) cholesterol levels; consequently, LDL cholesterol alone inadequately defines the risk associated with atherogenic lipoproteins. In the presence of high serum triglycerides, non-HDL cholesterol therefore will better represent the concentrations of all atherogenic lipoproteins than will LDL cholesterol alone.

      Atherogenic Particles

    • Metabolic Syndrome

      Metabolic Syndrome

      There is little doubt that this syndrome taken in aggregate enhances the risk for CHD at any given LDL-cholesterol level. The lipid component of this condition consists of abnormal levels of triglycerides and apoB, small LDL particles, and low HDL-C. The metabolic syndrome and its associated risk factors have emerged as a coequal partner to cigarette smoking as contributors to premature CHD. In addition, the insulin resistance accompanying the metabolic syndrome is one of the underlying causes of type 2 diabetes. For these reasons, NCEP places increased emphasis on the metabolic syndrome as a risk enhancer. The root causes of the metabolic syndrome are overweight/obesity, physical inactivity, and genetic factors.

      ApoB-100
      ApoB is found in chylomicrons, VLDL, IDL, LDL, and Lp(a) particles. Since each of these particles contains a single apoB molecule, measurements of apoB represent the total burden of particles considered most atherogenic. Apolipoprotein B, or apo B, is a marker for all atherogenic lipoproteins. It has been proposed as an alternative to LDL cholesterol as a risk factor Limited epidemiological and clinical trial evidence supports its superiority over LDL cholesterol in risk prediction. Although LDL cholesterol and apolipoprotein B are highly correlated in persons with normal triglyceride levels, the apolipoprotein B level typically is disproportionately higher in persons with hypertriglyceridemia.



    • Novel Risk Factors

      Coronary calcium. Another indication of subclinical coronary atherosclerosis is coronary calcium as detected by electron beam computed tomography (EBCT) or spiral CT. Amounts of coronary calcium correlate positively with coronary plaque burden. Therefore, a high coronary calcium score should carry predictive power for major coronary events. Several studies indicate that, in persons with multiple risk factors, a concomitantly high coronary calcium score places persons in the range of a CHD risk equivalent.


    • Carotid intimal medial thickening. One test in this category is carotid sonography used to measure intimal medial thickness (IMT) of the carotid arteries. The extent of carotid atherosclerosis correlates positively with the severity of coronary atherosclerosis. Furthermore, recent studies show that severity of IMT independently correlates with risk for major coronary events. Thus, measurement of carotid IMT theoretically could be used as an adjunct in CHD risk assessment.


    • References

      Genest J, McNamara JR, Ordovas JM, Jenner JL, Silberman SR, Anderson KM, Wilson PW, Salem DN, Schaefer EJ. Lipoprotein cholesterol, apolipoprotein A-1 and B and lipoprotein (a) abnormalities in men with premature coronary artery disease. J Am Coll Cardiol 1992;19:792-802


    • Reaven GM, Chen YD, Jeppesen J, Maheux P, Krauss RM. Insulin resistance and hyperinsulinemia in individuals with small, dense low density lipoprotein particles. J Clin Investigation 1993 Jul;92(1):141-146


    • Superko HR. Did grandma give you heart disease? The new battle against coronary artery disease. Am J Card 1998 Nov 5;82(9A):34Q-46Q.


    • Chu JW, Abbasi F, Kulkarni K, Lamendola C, McLaughlin T, Scalisi J, Reaven GM. Multiple Lipoprotein Abnormalities Associated with Insulin Resistance in Healthy Volunteers Identified by the Vertical Auto Profile-II Methodology. Clin Chem 2003 June 49(6):1014-1017.


    • Akosah KO, MD, Schaper A, Cogbill C, Schoenfeld P. Preventing Myocardial Infarction in the Young Adult in the First Place: How Do the National Cholesterol Education Panel III Guidelines Perform? J Amer Coll Card 2003 May;41(9):1475-1479.


    • Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis 1996 124 S1-S9.


    • Third Report of the Expert Panel on Detection, Evaluation and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) Executive Summary. U.S. Dept. of Health and Human Services, National Institutes of Health. NIH Publication No. 01-3670, 2001 May.


    • Bachorik PS, Ross JW. The NCEP Working Group on Lipoprotein Measurement: National Cholesterol Education Program recommendations for measurement of low-density lipoprotein cholesterol: executive summary. Clin Chem 1995;41:1414-20.


    • Marniemi J, Maki J, Maatela J, Jarvisalo J, Impivaara O. Poor applicability of the Friedewald formula in the Assessment of Serum LDL Cholesterol for Clinical Purposes. Clin Biochem 1995;28(3):285-289.


    • Senti M, Pedro-Botet J, Rubies-Prat J, Vidal-Barraquer F. Secondary prevention of coronary heart disease in patients with extracoronary atherosclerosis: a need for accuracy of low density lipoporotein determination. Angiology 1996 Mar;47(3):241-6.


    • Scharnagl H, Nauck M, Wieland H, Marz W. The Friedewald Formula Underestimates LDL Cholesterol at Low Concentrations. Clin Chem Lab Med 2001; 39(5):426–431.


    • Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without the use of the preparative ultracentrifuge. Clin Chem. 1972;18:499-502


    • West of Scotland Coronary Prevention Study Group. Influence of Pravastatin and Plasma Lipids on Clinical Events in the West of Scotland Coronary Prevention Study (WOSCOPS). Circulation. 1998;97:1440-1445.


    • Frank M. Sacks, MD; Petar Alaupovic, PhD; Lemuel A. Moye, MD, PhD; Thomas G. Cole, PhD; Bruce Sussex, MD; Meir J. Stampfer, MD, DPH; Marc A. Pfeffer, MD, PhD; Eugene Braunwald, MD. VLDL, Apolipoproteins B, CIII, and E, and Risk of Recurrent Coronary Events in the Cholesterol and Recurrent Events (CARE) Trial. Circulation. 2000;102:1886-1892.


    • Heart Protection Study Collaborative Group*. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20 536 high-risk individuals: a randomized placebocontrolled trial. Lancet. 2002; 360:7-22


    • James A. de Lemos, MD, Michael A. Blazing, MD, Stephen D. Wiviott, MD, Eldrin F. Lewis, MD, Keith A. A. Fox, MB, ChB, Harvey D. White, DSc, Jean-Lucien Rouleau, MD, Terje R. Pedersen, MD, Laura H. Gardner, BSPH, Robin Mukherjee, PhD, Karen E. Ramsey, BS, RPh, Joanne Palmisano, MD, David W. Bilheimer, MD, Marc A. Pfeffer, MD, PhD, Robert M. Califf, MD, Eugene Braunwald, MD. Early Intensive vs a Delayed Conservative Simvastatin Strategy in Patients With Acute Coronary Syndromes. JAMA. 2004;292:1307-1316.


    • Peter S Sever, Björn Dahlöf, Neil R Poulter, Hans Wedel, Gareth Beevers, Mark Caulfield, Rory Collins, Sverre E Kjeldsen, Arni Kristinsson, Gordon T McInnes, Jesper Mehlsen, Markku Nieminen, Eoin O’Brien, Jan Östergren. Prevention of coronary and stroke events with atorvastatin in hypertensive patients who have average or lower-than-average cholesterol concentrations, in the Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm (ASCOT-LLA): a multicentre randomised controlled trial. Lancet 2003; 361: 1149–58.


    • R. John Simes, MD; Ian C. Marschner, PhD; David Hunt, MD; David Colquhoun, MD; David Sullivan, MD; Ralph A.H. Stewart, MD; Wendy Hague, MD; Anthony Keech, MD; Peter Thompson, MD; Harvey White, MD, DSc; John Shaw, MD; Andrew Tonkin, MD; on Behalf of the LIPID Study Investigators. Relationship Between Lipid Levels and Clinical Outcomes in the Long-Term Intervention With Pravastatin in Ischemic Disease (LIPID) Trial. Circulation. 2002;105:1162-1169.


    • Terje R. Pedersen, MD; Anders G. Olsson, MD; Ole Færgeman, MD; John Kjekshus, MD; Hans Wedel, PhD; Kåre Berg, MD; Lars Wilhelmsen, MD; Torben Haghfelt, MD; Gudmundur Thorgeirsson, MD; Kalevi Pyo¨ra¨la¨, MD; Tatu Miettinen, MD; Bjørn Christophersen, MD; Jonathan A. Tobert, MD, PhD; Thomas A. Musliner, MD; Thomas J. Cook, MS; for The Scandinavian Simvastatin Survival Study Group. Lipoprotein Changes and Reduction in the Incidence of Major Coronary Heart Disease Events in the Scandinavian Simvastatin Survival Study (4S). Circulation. 1998;97:1453-1460.


    • Seman LJ, Deluca c, Jenner JL, Cupples LA, McNamara JR, Wilson PWF, Castelli WP, Ordovas JM, Schaefer EJ. Lipoprotein(a)-Cholesterol and Coronary Heart Disease in the Framingham Heart Study. Clin Chem 1999 45:7:1039-1046.


    • Crouse JR 3rd. New developments in the use of niacin for treatment of hyperlipidemia: new considerations in the use of an old drug. Coron Artery Dis 1996 Apr;7(4):321-6.


    • Farnier M; Bonnefous F; Debbas N; Irvine A. Comparative efficacy and safety of micronized fenofibrate and simvastatin in patients with primary type IIa or IIb hyperlipidemia. Arch Intern Med 1994 Feb 28;154(4):441-449.


    • Shlipak MG et al. Estrogen and Progestin, Lipoprotein(a), and the Risk of Recurrent Coronary Heart Disease Events After Menopause. JAMA 2000 Apr 12;283(14):1845-1852.


    • Brian W. Walsh, MD; Lewis H. Kuller, MD; Robert A. Wild, MD; Sofia Paul, PhD; Mildred Farmer, MD; Jeffry B. Lawrence, MD; Aarti S. Shah, PhD; Pamela W. Anderson, MD. Effects of Raloxifene on Serum Lipids and Coagulation Factors in Healthy Postmenopausal Women. JAMA 1998 May 13;279(18):1445-1451.


    • Krauss RM. Dense low density lipoproteins and coronary artery disease. Am J Cardiol. 1995 Feb 23;75(6):53B-75B.


    • Griffin BA, Freeman DJ, Tait GW, Thomson J, Caslake MJ, Packard CJ. Role of plasma triglycerides in the regulation of plasma low density lipoprotein (LDL) subfractions: relative contribution of small, dense LDL to coronary heart disease risk. Atherosclerosis 1994 Apr;106(2):241-53.


    • Brown BG, et al. Use of niacin, statins, and resins in patients with combined hyperlipidemia. Am J Cardiol. 1998 Feb 26;81(4A):52B-59B.


    • Miller BD, et al. Predominance of dense low-density lipoprotein particles predicts angiographic benefit of therapy in the Stanford Coronary Risk Intervention Project. Circulation 1996 Nov 1;94(9):2146-53.


    • Vakkailanen J, et al. Relationships Between Low-Density Lipoprotein Particle Size, Plasma Lipoproteins, and Progression of Coronary Artery Disease. Circulation 2003;107:1733-37.


    • Watts GF, Mandalia S, Brunt JN et al. Independent associations between plasma lipoprotein subfraction levels and the course of coronary artery disease in the St. Thomas’ Atherosclerosis Regression Study (STARS). Metabolism 1993; 42:1461–1467.


    • Zhao XQ et al. Prediction of native coronary artery disease progression following PTCA or CABG in the Emory Angioplasty Versus Surgery Trial. Med Sci Monit 2003 Feb;9(2):CR48-


    • Brown BG, Zambon A, Otvos JD, Lanman RB, Morse JS, Krauss RM. LDL size or density, by four methods, as correlates of coronary stenosis change. AHA Annual Meeting abstract 2003.


    • Kazumi T, et al. Low density lipoprotein particle diameter in young, non-obese, normolipidemic Japanese men. Atherosclerosis 1999 Jan;142(1):113-9.


    • Austin MA, King MC, Vranizan KM, Krauss RM. Atherogenic lipoprotein phenotype. A proposed genetic market for coronary heart disease risk. Circulation 1990 Aug;82(2):495-506.


    • Minihane AM, Khan S, Leigh-Firbank EC, Talmud P, Wright JW, Murphy MC, Griffin BA, Williams CM. ApoE Polymorphism and Fish Oil Supplementation in Subjects With an Atherogenic Lipoprotein Phenotype. Arterioscler Thromb Vasc Biol. 2000;20:1990-1997.


    • Tavani A, Pelucchi, C, Negri E, Bertuzzi M, La Vecchia C. N-3 Polyunsaturated Fatty Acids, Fish, and Nonfatal Acute Myocardial Infarction. Circulation November 6, 2001:2269-2272.


    • Hu FB; Bronner L, Willett WC, Stampfer MJ, Rexrode KM, Albert CM, Hunter D, Manson JE. Fish and Omega-3 Fatty Acid Intake and Risk of Coronary Heart Disease in Women.  JAMA. 2002;287:1815-1821


    • Danesh J, Collins R, Peto R. Lipoprotein (a) and coronary heart disease. Meta-analysis of prospective studies. Circulation 2000 Sep 5;102(10):1082-5.


    • Bostom AG, Cupples LA, Jenner JL, Ordovas JM, Seman LJ, Wilson PW, Schaefer EJ, Acstelli WP. Elevated plasma lipoprotein (a) and coronary heart disease in men aged 55 years and younger. A prospective study. JAMA 1996 Aug 21;276(7):544-8.


    • von Eckardstein A, Schulte H, Cullen P, Assmann G. Lipoprotein(a) Further Increases the Risk of Coronary Events in Men With High Global Cardiovascular Risk. J Am Coll Card. 2001 Feb; 37(2):434–9.


    • Hopkins PN, Wu LL, Hunt SC, James BC, Vincent GM, Williams RR. Lipoprotein (a) interactions with lipid and nonlipid risk factors in early familial coronary artery disease. Arterioscler Thromb Vasc Biol. 1997 Nov;17(11):2783-92.


    • Jurgens Q, Taddei-Peters WC, Koltringer P, Petek W, Chen Q, Greilberger J, Macomber PF, Butman BT, Stead AG, Ransom JH. Lipoprotein (a) serum concentration and apolipoprotein (a) phenotype correlate with severity and presence of ischemic cerebrovascular disease. Stroke 1995 Oct;26(10):1841-8.


    • Ruiz J, Thillet J, Huby T, James RW, Erlich D, Flandre P, Froguel P, Chapman J, Passa P. Association of elevated lipoprotein (a) levels and coronary heart disease in NIDDM patients. Relationship with apolipoprotein (a) phenotypes. Diabetologia 1994 Jun;37(6):585-91.


    • Routi T, Ronnemaa T, Jokinen E, Viikari J, Niinikoski H, Leino A, Simell O. Correlation of toddlers’ serum lipoprotein(a) concentration with parental values and grandparents’ coronary heart disease: the STRIP baby study. Acta Paediatr 1996 Apr;85(4)407-12.


    • Cantin B, et al. Is Lp(a) an independent risk factor for ischemic heart disease in men? The Quebec Cardiovascular Study. J Am Coll Card 1998 Mar 1;31(3):519.-25


    • Daida H, Lee YJ, Yokoi H, Kanoh T, Ishiwata S, Kato K, Nishikawa H, Takatsu F, Kato H, Kutsunii Y, et al. Prevention of restenosis after percutaneous transluminal coronary angioplasty by reducing lipoprotein (a) levels with low-density lipoprotein apheresis. Low Density Lipoprotein Apheresis Angioplasty Restenosis Trial (L-ART) Group. Am J Cardiol. 1994 Jun 1;73(15):1037-40.


    • Marcovina SM et al. Use of a Reference Material Proposed by the International Federation of Clinical Chemistry and Laboratory Medicine to Evaluate Analytical Methods for the Determination of Plasma Lipoprotein(a). Clin Chem 2000 46:12: 1956-1967.


    • Lamarche B, Moorjani S, Cantin B, Dagenis GR, Lupien PJ, Despres JP. Associations of HDL2 and HDL3 subfractions with ischemic heart disease in men. Prospective results from the Quebec Cardiovascular Study. Arterioscler Thromb Vasc Biol. 1997 Jun; 17(6):1098-105.


    • Campos H, Roederer GO, Lussier-Cacan S, Davignon L, Krauss RM. Predominance of large LDL and reduced HDL2 cholesterol in normolipidemic men with coronary artery disease. Arterioscler Thromb Vasc Biol 1995 Aug;15(8):1043-8.


    • Laakso M, Pyorala K. Lipid and lipoprotein abnormalities in diabetic patients with peripheral vascular disease. Atherosclerosis 1989 Nov;74(1-2):55-63.


    • Moskowitz WB, Mosteller M, Schieken RM, Bossano R, Hewitt JK, Bodurtha IN, Segrest JP. Lipoprotein and oxygen transport alterations in passive smoking preadolescent children. The MCV Twin Study. Circulation 1990 Feb;81(2):586-92.


    • Vadlamudi S, MacLean P, Israe4l RG, Marks RH, Hickey M, Otvos J, Barakat H. Effects of oral combined hormone replacement therapy on plasma lipids and lipoproteins. Metabolism 1998 Oct;47(10):1222-6.


    • Brown BG et al. Simvastatin and Niacin, Antioxidant Vitamins, or the Combination for the Prevention of Coronary Disease. NEJM 2001 Nov 29:345(22):1583-1592.


    • Kulkarni KR, Marcovina SM, Krauss RM, et al. Quantification of HDL2 and HLD3 cholesterol by the Vertical Auto Profile-II (VAP-II) methodology. J Lipid Res, Nov 1997, 38(11): 2353-64.


    • Hodis HN. Triglyceride rich lipoprotein remnant particles and risk of atherosclerosis. Circulation 1999;99:2852-2854.


    • Kulkarni KR, Garber DW, Marcovina SM, Segrest JP. Quantification of cholesterol in all lipoprotein classes by the VAP-II method. J Lipid Res 1994 Jan;35(1):159-68.


    • Kulkarni KR, Garber DW, Jones MK Segrest JP. Identification and cholesterol quantification of low density lipoprotein subclasses in young adults by VAP-II methodology. J Lipid Res, Nov 1995; 36(11): 2291-302.


    • Collins R. Heart protection study finds simvastatin reduces vascular risk in a wide range of high-risk patients. Am J Manag Care 2002 Jan;Suppl:6.


    • Zambon A, et al. Evidence for a New Pathophysiological Mechanism for Coronary Artery Disease Regression: Hepatic Lipase–Mediated Changes in LDL Density. Circulation Apr 1999; 1959-1964.


    • St-Pierre AC et al. Comparison of Various Electrophoretic Characteristics of LDL Particles and Their Relationship to the Risk of Ischemic Heart Disease. Circulation 2001;104: 2295-2299.


    • Rosenson RS et al. Relations of Lipoprotein Subclass Levels and LDL Particle Size to Progression of Coronary Artery Disease in the PLAC-I Trial. Am J Card 2002; 90: 80-94.