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High Density Lipoproteins, Dyslipidemia, and Heart Disease: Past, Present, and Future

  • Ernst J. Schaefer
  • Raul D. Santos
Chapter

Abstract

The current focus of lipid management is on the treatment of elevated low density lipoprotein (LDL) cholesterol (>160 mg/dl) to decrease the risk of coronary heart disease (CHD), as well as less commonly to treat markedly elevated triglyceride levels (>1,000 mg/dl) to decrease the risk of pancreatitis. However, physicians and scientists have recognized that despite lifestyle and statin therapy, there is still a substantial residual risk of CHD, especially in patients with low high density lipoprotein (HDL) cholesterol levels (<40 mg/dl). In this atlas and book, the reader has been introduced to lipoprotein composition and metabolism, as well as lipid disorders. Thereafter, the focus has been on the regulation of apolipoprotein (apo) A-I gene expression, the composition of HDL particles, the modeling and metabolism of these particles, as well as HDL structure, function, and its anti-inflammatory properties. Next, we have provided the reader with information on disease states characterized by apoA-I deficiency, apoA-I variants, Tangier disease due to lack of ABCA1 function, the ABCG1 transporter, the interaction of HDL particles with transporters and receptors, human lecithin:cholesterol acyl transferase (LCAT) deficiency, human cholesteryl ester transfer protein (CETP deficiency, and the role of the scavenger receptor BI (SR-B1) in HDL metabolism. Thereafter, we provide the reader with information on the genetics of HDL in the general population, the role of nutrition, alcohol, and exercise in modulating HDL metabolism, and the effects of estrogens, niacin, statins, fibrates, CETP inhibitors, and HDL infusion therapy on HDL metabolism and coronary heart disease (CHD) risk reduction. Our goal in this concluding chapter is to focus on the current and future status of CHD risk assessment, the diagnosis and management of lipoprotein disorders, with a special focus on HDL. In our view, HDL raising is the next frontier in CHD risk reduction, and we will be using niacin products, CETP inhibitors, and HDL infusion therapy.

Keywords

High Density Lipoprotein High Density Lipoprotein Cholesterol Coronary Heart Disease Risk Cholesteryl Ester Transfer Protein Coronary Heart Disease Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Expert Panel (2001) 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). J Am Med Assoc 285:2486–2497Google Scholar
  2. 2.
    Patel MD, Thompson PD (2006) Phytosterols and vascular disease. Atherosclerosis 186:12–19PubMedCrossRefGoogle Scholar
  3. 3.
    Keren Z, Falik-Zaccel TC (2009) Cerebrotendinous xanthomatosis (CTX), a treatable lipid storage disorder. Pediatr Endocrinol Rev 7:6–11PubMedGoogle Scholar
  4. 4.
    McNamara JR, Schaefer EJ (1987) Automated enzymatic standardized lipid analyses for plasma and lipoprotein fractions. Clin Chim Acta 166:1–8PubMedCrossRefGoogle Scholar
  5. 5.
    Ginns EI, Barranger JA, McClean SW, Sliva C, Young R, Schaefer EJ, Goodman SI, McCabe RB (1984) A juvenile form of glycerol kinase deficiency with episodic vomiting, acidemia, and stupor. J Pediatr 5:736–739Google Scholar
  6. 6.
    Barr DP, Russ E, Eder HA (1951) Protein-lipid relationships in human plasma. II. In atherosclerosis and related conditions. Am J Med 1:480–493CrossRefGoogle Scholar
  7. 7.
    Fredrickson DS, Levy RI, Lees RS (1967) Fat transport in lipoproteins - an integrated approach to mechanisms and disorders. N Engl J Med 276:34-42, 94-103, 148-156, 215-225, 273-281 (five part review article)Google Scholar
  8. 8.
    Goldstein JL, Hazzard WR, Schrott HG, Bierman EL (1973) Hyperlipidemia in coronary heart disease. I. Lipid levels in 500 survivors of myocardial infarction. J Clin Invest 52:1533–1543PubMedCrossRefGoogle Scholar
  9. 9.
    Goldstein JL, Hazzard WR, Schrott HG, Bierman EL (1973) Hyperlipidemia in coronary heart disease. II. Genetic analyses of lipid levels in 176 families and delineation of a new inherited disorder, combined hyperlipidemia. J Clin Invest 52:1544–1568PubMedCrossRefGoogle Scholar
  10. 10.
    DeLalla OF, Elliott HA, Gofman JW (1954) Ultracentrifugal studies of high density serum lipoproteins in clinically healthy subjects. Am J Physiol 179:333–337PubMedGoogle Scholar
  11. 11.
    Havel RJ, Eder HA, Bragdon JH (1955) The distribution and chemical composition of ultracentrifugally separated lipoproteins in human serum. J Clin Invest 34:1345–1353PubMedCrossRefGoogle Scholar
  12. 12.
    Gofman JW, Young W, Tandy R (1966) Ischemic heart disease, atherosclerosis, and longevity. Circulation 34:679–697PubMedGoogle Scholar
  13. 13.
    Chapman MJ, Goldstein S, Lagrange D, Lapaud PM (1981) A density gradient ultracentrifugal procedure for the isolation of the major lipoprotein density classes from human serum. J Lipid Res 22:339–358PubMedGoogle Scholar
  14. 14.
    Patsch JR, Sailer S, Kostner G, Sandhofer F, Holasek A, Braunsteiner H (1974) Seperation of the main lipoprotein density classes from human plasma by rate zonal ultracentrifugation. J Lipid Res 15:356–366PubMedGoogle Scholar
  15. 15.
    Chung BH, Wilkinson T, Geer JC, Segrest JP (1980) Preparative and quantitative isolation of plasma lipoproteins: rapid single density gradient ultracentrifugation in a vertical rotor. J Lipid Res 21:284–291PubMedGoogle Scholar
  16. 16.
    Chung BH, Segrest JP, Cone JT, Pfau J, Geer JC, Duncan LA (1981) High resolution plasma lipoprotein cholesterol profile by a rapid high volume semi-automated method. J Lipid Res 22:1003–1114PubMedGoogle Scholar
  17. 17.
    Kulkarni KR, Marcovina SM, Krauss RM, Garber DW, Glasscock AM, Segrest JP (1997) Quantitation of HDL2 and HDL3 cholesterol by the vertical auto-profile-II (VAP-II) methodology. J Lipid Res 38:2353–2364PubMedGoogle Scholar
  18. 18.
    Anderson DW, Nichols AV, Forte TM, Lindgren FT (1977) Particle distribution of human serum high density lipoproteins. Biochim Biophys Acta 493:55–68PubMedGoogle Scholar
  19. 19.
    Austin MA, Breslow JL, Hennekens CH, Buring JE, Willett WC, Krauss RM (1988) Low density lipoprotein subclass patterns and risk of myocardial infarction. JAMA 260:1917–1921PubMedCrossRefGoogle Scholar
  20. 20.
    Campos H, Genest JJ, Blijlevens E, McNamara JR, Jenner J, Ordovas JM, Wilson PWF, Schaefer EJ (1992) Low density lipoprotein particle size and coronary artery disease. Arterioscler Thromb 12:187–195PubMedGoogle Scholar
  21. 21.
    Campos H, Blijlevens E, McNamara JR, Ordvoas JM, Wilson PWF, Schaefer EJ (1992) LDL particle size distribution: results from the Framingham Offspring Study. Arterioscler Thromb 12:1410–1419PubMedGoogle Scholar
  22. 22.
    McNamara JR, Jenner JL, Li Z, Wilson PWF, Schaefer EJ (1992) Change in low density lipoprotein particle size is associated with change in plasma triglyceride concentration. Arterioscler Thromb 12:1284–1290PubMedGoogle Scholar
  23. 23.
    Li Z, McNamara JR, Ordovas JM, Schaefer EJ (1994) Analysis of high density lipoproteins by a modified gradient gel electrophoresis method. J Lipid Res 35:1698–1711PubMedGoogle Scholar
  24. 24.
    Caulfield MP, Li S, Lee G, Blanche PJ, Salameh WA, Benner WH, Reitz RE, Krauss RM (2008) Direct determination of lipoprotein particle sizes and concentrations by ion mobility analysis. Clin Chem 54:1307–1316PubMedCrossRefGoogle Scholar
  25. 25.
    Chau P, Nakamura Y, Fielding CJ, Fielding PE (2006) Mechanisms of pre-beta HDL formation and activation. Biochemistry 45:3981–3987PubMedCrossRefGoogle Scholar
  26. 26.
    Asztalos BF, Sloop CH, Wong L, Roheim PS (1993) Two dimensional electrophoresis of plasma lipoproteins: recognition of new apoA-I containing subpopulations. Biochim Biophys Acta 1169:291–300PubMedGoogle Scholar
  27. 27.
    Asztalos BF, De la Llera-Moya M, Dallal GE, Horvath KV, Schaefer EJ, Rothblat GH (2005) Differential effects of HDL subpopulations on cellular ABCA1 and SRB1-mediated cholesterol efflux. J Lipid Res 46:2246–2253PubMedCrossRefGoogle Scholar
  28. 28.
    Asztalos BF, Cupples LA, Demissie S, Horvath KV, Cox CE, Batista MC, Schaefer EJ (2004) High-density lipoprotein subpopulation profile and coronary heart disease prevalence in male participants in the Framingham Offspring Study. Arterioscler Thromb Vasc Biol 24:2181–2187PubMedCrossRefGoogle Scholar
  29. 29.
    Asztalos BF, Collins D, Cupples LA, Demissie S, Horvath KV, Bloomfield HE, Robins SJ, Schaefer EJ (2005) Value of high density lipoprotein (HDL) subpopulations in predicting recurrent cardiovascular events in the Veterans Affairs HDL Intervention Trial. Arterioscler Thromb Vasc Biol 25:2185–2191PubMedCrossRefGoogle Scholar
  30. 30.
    Asztalos BF, Batista M, Horvath KV, Cox CE, Dallal GE, Morse JS, Brown GB, Schaefer EJ (2003) Change in alpha 1 HDL concentration predicts progression in coronary artery stenosis. Arterioscler Thromb Vasc Biol 23:847–852PubMedCrossRefGoogle Scholar
  31. 31.
    Santos RD, Schaefer EJ, Asztalos BF, Polisecki E, Hegele RA, Martinez L, Miname M, Coimbra SR, Da Luz P, Rochitte CE, Maranhao R (2008) Characterization of high density lipoprotein particles in familial apolipoprotein A-I deficiency with premature coronary atherosclerosis, corneal arcus and opacification, and tubo-eruptive and planar xanthomas. J Lipid Res 49:349–357PubMedCrossRefGoogle Scholar
  32. 32.
    Asztalos BF, Brousseau ME, McNamara JR, Horvath KV, Roheim PS, Schaefer EJ (2001) Subpopulations of high-density lipoproteins in homozygous and heterozygous Tangier disease. Atherosclerosis 156:217–225PubMedCrossRefGoogle Scholar
  33. 33.
    Asztalos BF, Schaefer EJ, Horvath KV, Yamashita S, Miller M, Franceschini G, Calabresi L (2007) Role of LCAT in HDL remodeling: an investigation in LCAT deficiency states. J Lipid Res 48:592–599PubMedCrossRefGoogle Scholar
  34. 34.
    Asztalos BF, Horvath KV, Kajinami K, Nartsupha C, Cox CE, Batista M, Schaefer EJ, Inazu A, Mabuchi H (2004) Apolipoprotein composition of HDL in cholesteryl ester transfer protein deficiency. J Lipid Res 45:448–455PubMedCrossRefGoogle Scholar
  35. 35.
    Otvos JD, Collins D, Freedman DS, Shalaurova I, Schaefer EJ, McNamara JR, Bloomfield HE, Robins SJ (2006) Low density and high density lipoprotein particle subclasses predict coronary events and are favorably changed by gemfibrozil therapy in the Veteran Affairs High Density Lipoprotein Intervention Trial. Circulation 113:1556–1563PubMedCrossRefGoogle Scholar
  36. 36.
    Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, Wilson PW, D’Agostino RB (2007) LDL particle number and risk of future cardiovascular disease in the Framingham Offspring Study - Implications for LDL Management. J Clin Lipidol 1:583–592PubMedCrossRefGoogle Scholar
  37. 37.
    Mora S, Otvos JD, Rifai N, Rosenson RS, Buring JE, Ridker PM (2009) Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipid and apolipoproteins in predicting incident cardiovascular disease in women. Circulation 119:931–939PubMedCrossRefGoogle Scholar
  38. 38.
    Burstein M, Morfin R (1969) Precipitation des lipoproteins seriques et par des polysaccharide sulfates en presence de chlorure manganese. Nouv Rev Fr Hematol 9:231–244PubMedGoogle Scholar
  39. 39.
    Burstein M, Scholnick HR, Morfin R (1970) Rapid method for the isolation of lipoproteins from human serum by precipitation with polyanions. J Lipid Res 11:583–595PubMedGoogle Scholar
  40. 40.
    Burstein M, Scholnick HR (1973) Lipoprotein-polyanion-metal interactions. Adv Lipid Res 11:67–108PubMedGoogle Scholar
  41. 41.
    Manual of Laboratory Operations. Lipid Research Clinics Program (1975) Lipid and lipoprotein analysis. DHEW Pub (NIH) 75–628Google Scholar
  42. 42.
    Warnick GR, Albers JJ (1978) A comprehensive evaluation of the heparin-manganese precipitation procedure for estimating high density lipoprotein HDL cholesterol. J Lipid Res 19:65–76PubMedGoogle Scholar
  43. 43.
    Warnick GR, Benderson J, Albers JJ (1982) Dextran sulfate-Mg2+ precipitation procedure for quantitation of high-density lipoprotein cholesterol. Clin Chem 28:1379–1388PubMedGoogle Scholar
  44. 44.
    Miller GJ, Miller NE (1975) Plasma high density lipoprotein concentration and the development of ischemic heart disease. Lancet 1:16–19PubMedCrossRefGoogle Scholar
  45. 45.
    Castelli WP, Doyle JT, Gordon T, Hames CG, Hjortland MC, Hulley SB, Kagan A, Zukel WJ (1977) HDL cholesterol and other lipids in coronary heart disease. The Cooperative Lipoprotein Phenotyping Project. Circulation 55:767–772PubMedGoogle Scholar
  46. 46.
    Schaefer EJ, Levy RI, Anderson DW, Danner RN, Brewer HB Jr, Blackwelder WC (1978) Plasma-triglycerides in regulation of HDL-cholesterol levels. Lancet 2:391–393PubMedCrossRefGoogle Scholar
  47. 47.
    Genest JJ, Martin-Munley S, McNamara JR, Ordovas JM, Jenner J, Meyers R, Wilson PWF, Schaefer EJ (1992) Prevalence of familial lipoprotein disorders in patients with premature coronary artery disease. Circulation 85:2025–2033PubMedGoogle Scholar
  48. 48.
    Sugiuchi H, Uji Y, Okabe H, Irie T, Uekama K, Kayahara N, Miyauchi K (1995) Direct measurement of high-density lipoprotein cholesterol in serum with polyethylene glycol-modified enzymes and sulfated alpha-cyclodextrin. Clin Chem 41:717–723PubMedGoogle Scholar
  49. 49.
    Otokozawa S, Ai M, Asztalos BF, White CC, Demissie-Banjaw S, Cupples LA, Nakajima K, Wilson PW, Schaefer EJ (in press). Direct assessment of plasma low density lipoprotein and high density lipoprotein cholesterol. AtherosclerosisGoogle Scholar
  50. 50.
    Wilson PW, D’Agostino RA, Levy D, Belanger AM, Silbershatz H, Kannel W (1998) Prediction of coronary heart disease using risk factor categories. Circulation 97:1837–1847PubMedGoogle Scholar
  51. 51.
    Friedewald WT, Levy RI, Fredrickson DS (1972) Estimation of the concentration of low density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem 18:499–502PubMedGoogle Scholar
  52. 52.
    McNamara JR, Cohn JS, Wilson PWF, Schaefer EJ (1990) Calculated values for low-density lipoprotein cholesterol in the assessment of lipid abnormalities and coronary disease risk. Clin Chem 36:36–42PubMedGoogle Scholar
  53. 53.
    McNamara JR, Cole TG, Contois JH, Ferguson CA, Ordovas JM, Schaefer EJ (1995) Immunoseparation method for measuring low-density lipoprotein cholesterol directly from serum evaluated. Clin Chem 41:232–240PubMedGoogle Scholar
  54. 54.
    Sugiuchi H, Irie T, Yoshinori U, Ueno T, Chaen T, Uekama K, Okabe H (1998) Homogeneous assay for measuring low-density lipoprotein cholesterol in serum with triblock copolymer and alpha-cyclodextrin. Clin Chem 44:522–531PubMedGoogle Scholar
  55. 55.
    Gidez LI, Miller GJ, Burstein M, Slagle S, Eder HA (1982) Seperation and quantitation of subclasses of plasma high density lipoproteins by a simple precipitation procedure. J Lipid Res 23:1206–1223PubMedGoogle Scholar
  56. 56.
    Hirano T, Nohtomi K, Koba S, Muroi A, Ito Y (2008) A simple and precise method for measuring HDL cholesterol subfractions by a single precipitation followed by homogeneous HDL-C assay. J Lipid Res 49:1130–1136PubMedCrossRefGoogle Scholar
  57. 57.
    McNamara JR, Shah PK, Nakajima K, Cupples LA, Wilson PWF, Ordovas JM, Schaefer EJ (1998) Remnant lipoprotein cholesterol and triglyceride reference ranges from the Framingham Heart Study. Clin Chem 44:1224–1232PubMedGoogle Scholar
  58. 58.
    McNamara JR, Shah PK, Nakajima K, Cupples LA, Wilson PWF, Ordovas JM, Schaefer EJ (2001) Remnant-like particle (RLP) cholesterol is an independent cardiovascular disease risk factor in women: results from the Framingham Heart Study. Atherosclerosis 154:229–236PubMedCrossRefGoogle Scholar
  59. 59.
    Schaefer EJ, Audelin MC, McNamara JR, Shah PK, Tayler T, Daly JA, Augustin JL, Seman LJ, Rubenstein JL (2001) Comparison of fasting and postprandial plasma lipoproteins in subjects with and without coronary heart disease. Am J Cardiol 88:1129–1133PubMedCrossRefGoogle Scholar
  60. 60.
    Schaefer EJ, McNamara JR, Shah PK, Nakajima K, Cupples LA, Ordovas JM, Wilson PWF (2002) Elevated remnant-like particle cholesterol and triglyceride levels in diabetic men and women in the Framingham Offspring Study. Diabetes Care 25:989–994PubMedCrossRefGoogle Scholar
  61. 61.
    Seman LJ, Jenner JL, McNamara JR, Schaefer EJ (1994) Quantification of lipoprotein (a) in plasma by assaying cholesterol in lectin bound plasma fraction. Clin Chem 40:400–403PubMedGoogle Scholar
  62. 62.
    Seman LJ, DeLuca C, Jenner JL, Cupples LA, McNamara JR, Wilson PWF, Castelli WP, Ordovas JM, Schaefer EJ (1999) Lipoprotein(a)-cholesterol and coronary heart disease in the Framingham Heart Study. Clin Chem 45(7):1039–1046PubMedGoogle Scholar
  63. 63.
    Hirano T, Ito Y, Saegusa H, Yoshino G (2003) A novel and simple method for quantification of small dense LDL. J Lipid Res 44:2193–2220PubMedCrossRefGoogle Scholar
  64. 64.
    Koba S, Yokota Y, Hirano T, Ito Y, Ban Y, Tsunoda F, Sato T, Shoji M, Suzuki H, Geshi E, Kobayashi Y, Katgiri T (2008) Small LDL-cholesterol is superior to LDL-cholesterol for determining severity of coronary atherosclerosis. J Atheroscler Thromb 15:350–360Google Scholar
  65. 65.
    Sniderman AD, Marcovina SM (2006) Apolipoprotein AI and B. Clin Lab Med 26:733–750PubMedCrossRefGoogle Scholar
  66. 66.
    Ingelsson E, Schaefer EJ, Contois JH, McNamara JR, Sullivan L, Keyes MJ, Pencina MJ, Schoonmaker C, Wilson PW, D’Agostino RB, Vasan RS (2007) Clinical utility of different lipid measures for prediction of coronary heart disease in men and women. JAMA 298:776–785PubMedCrossRefGoogle Scholar
  67. 67.
    Avogaro P, Bob GB, Cazzolato G, Quinci GB (1979) Are apolipoproteins better discriminators than lipids for atherosclerosis. Lancet 1:101–103Google Scholar
  68. 68.
    Sniderman AD, Wolfson C, Teng B, Franklin FA, Bachorik PS, Kwiterovich PO Jr (1982) Association of hyperapobetalipoproteinemia with endogenous hypertriglyceridemia and atherosclerosis. Ann Intern Med 97:833–839PubMedGoogle Scholar
  69. 69.
    Schaefer EJ, Lamon-Fava S, Jenner JL, Ordovas JM, Davis CE, Lippel K, Levy RI (1994) Lipoprotein(a) levels predict coronary heart disease in the lipid research clinics coronary prevention trial. JAMA 271:999–1003PubMedCrossRefGoogle Scholar
  70. 70.
    Erqou S, Kaptoge S, Perry PC, DiAngelantino E, Thompson A, White IR, Marcovina SM, Collins R, Thompson SG, Danesh J; Emerging Risk Factors Collaboration (2009) Lipoprotein(a) as a risk factor for coronary heart disease and stroke. JAMA 302:412–423Google Scholar
  71. 71.
    Otokozawa S, Ai M, Asztalos BF, Tanaka A, Stein E, Jones PH, Schaefer EJ (2009) Effects of maximal atorvastatin and rosuvastatin therapy on apolipoprotein B-48 and remnant lipoprotein cholesterol levels. Atherosclerosis 205:197–201PubMedCrossRefGoogle Scholar
  72. 72.
    Otokozawa S, Ai M, Diffenderfer M, Asztalos BF, Lamon-Fava S, Schaefer EJ (2009) Fasting and post-prandial apolipoprotein B-48 levels in healthy, obese, and hyperlipidemic subjects. Metabolism 58:1136–1142CrossRefGoogle Scholar
  73. 73.
    Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, Koenig W, Libby P, Lorenzatti AJ, MacFayden JG, Nordestgaard BG, Shepherd J, Willerson JT, Glynn RJ; JUPITER Trial Study Group (2009) Reduction in C reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet 373:1175–1182Google Scholar
  74. 74.
    Davidson MH, Corson MA, Alberts MJ, Anderson JL, Gorelick PB, Jones PH, Lerman A, McDonnell JP, Weintraub HS (2008) Consensus panel recommendation for incorporating lipoprotein-associated phospholipase A2 testing into cardiovascular disease risk assessment guidelines. Am J Cardiol 101:51F-57FPubMedCrossRefGoogle Scholar
  75. 75.
    Rader DJ (2007) Effect of insulin resistance, dyslipidemia, and intraabdominal adiposity on the development of cardiovascular disease and diabetes mellitus. Am J Med 20:S12-S18CrossRefGoogle Scholar
  76. 76.
    Asztalos BF, Swarbrick MM, Schaefer EJ, Dallal GE, Horvath KV, Ai M, Stanhope KL, Austrheim-Smith J, Wolfe BM, Ali M, Havel PJ (2009) Effects of weight loss, induced by gastric bypass surgery, on HDL remodeling in obese women. J Lipid ResGoogle Scholar
  77. 77.
    Schaefer EJ, McNamara JR, Asztalos BF, Tayler T, Daly JA, Gleason JL, Seman LJ, Ferrara A, Rubenstein JL (2005) Effects of atorvastatin versus other statins on fasting and post-prandial C-reactive protein and lipoprotein associated phospholipase A2 in patients with coronary artery disease versus control subjects. Am J Cardiol 95:1025–1032PubMedCrossRefGoogle Scholar
  78. 78.
    Greenland P, LaBree L, Azen SP, Doherty TM, Detrano R (2004) Coronary calcium score combined with Framingham risk score for risk prediction in asymptomatic individuals. JAMA 291:210–215PubMedCrossRefGoogle Scholar
  79. 79.
    Vliegenthart R, Oudkerk M, Hofman A, Oei HH, van Dijck W, van Rooij FC, Witteman JC (2005) Coronary calcification improves cardiovascular risk prediction. Circulation 112:572–577PubMedCrossRefGoogle Scholar
  80. 80.
    Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, Liu K, Shea S, Szklo M, Bluemke DA, O’Leary DH, Drely R (2008) Coronary calcification as a predictor of coronary events in 4 racial or ethnic groups. New Engl J Med 358:1336–1345PubMedCrossRefGoogle Scholar
  81. 81.
    Folsom AR, Kronmal RA, Detrano RA, Detrano RC, O’Leary DH, Bild DE, Bluemke DA, Budoff MJ, Liu K, Shea S, Szklo M, Tracy RP, Watson KE, Burke GL (2008) Coronary artery calcification as compared with carotid intimal medial thickness in the prediction of cardiovascular disease incidence: the Multi-Ethnic Study of Atherosclerosis (MESA). Arch Intern Med 168:1333–1339PubMedCrossRefGoogle Scholar
  82. 82.
    Budoff MJ, Shaw LJ, Liu ST, Weinstein SR, Mosier TP, Tseng PH, Flores FR, Callister TQ, Raggi P, Berman DS (2007) Long term prognosis associated with coronary calcification: observations from a registry of 25,253 patients. J Am Coll Cardiol 49:1860–1870PubMedCrossRefGoogle Scholar
  83. 83.
    Boyar A (2006) Creating a web application that combines Framingham risk with electron beam CT coronary calcium score to calculate a new event risk. J Thorac Imaging 21:91–96PubMedCrossRefGoogle Scholar
  84. 84.
    Budoff MJ, Nasir K, McClelland RL, Detrano R, Wong N, Blumenthal RS, Kondos G, Kronmal RA (2009) Coronary calcium predicts events even better with absolute calcium score than age, sex, race, ethnic percentiles. J Am Coll Cardiol 53:345–352PubMedCrossRefGoogle Scholar
  85. 85.
    Santos RD, Miname MH, Martinez LR, Rochitte CE, Chacra AP, Nakandakare ER, Chen D, Schaefer EJ (2008) Non-invasive detection of aortic and coronary atherosclerosis in homozygous familial hypercholesterolemia by 64 slice multi-detector row computed tomography angiography. Atherosclerosis 197:910–915PubMedCrossRefGoogle Scholar
  86. 86.
    Sprecher DS, Schaefer EJ, Kent K, Gregg RE, Zech LA, Hoeg JM, McManus B, Roberts D, Brewer HB Jr (1984) Cardiovascular features of homozygous familial hypercholesterolemia: analysis of 16 patients. Am J Cardiol 54:20–30PubMedCrossRefGoogle Scholar
  87. 87.
    Santos RD, Miname L, Asztalos BF, Polisecki E, Schaefer EJ (2008) Clinical presentation, laboratory values, and coronary heart disease risk in marked high density lipoprotein deficiency states. J Clin Lipidol 2:237–247CrossRefGoogle Scholar
  88. 88.
    Schaefer EJ, Heaton WH, Wetzel MG, Brewer HB Jr (1982) Plasma apolipoprotein A-I absence associated with marked reduction of high density lipoproteins and premature coronary artery disease. Arteriosclerosis 2:16–26PubMedGoogle Scholar
  89. 89.
    Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, Paternak RC, Smith SC Jr, Stone NJ (2004) Implications of recent clinical trials for the National Cholesterol Education Adult Treatment Panel III guidelines. Circulation 110:227–239PubMedCrossRefGoogle Scholar
  90. 90.
    Pencina MJ, D’Agostino RB, Larson MG, Massaro JM, Vasan RS (2009) Predicting the 30-year risk of cardiovascular disease. The Framingham Study. Circulation 119:3078–3084PubMedCrossRefGoogle Scholar
  91. 91.
    Ridker PM, Buring JE, Rifai N, Cook NR (2007) Development and validation of improved algorithms for the assessment of global cardiovascular risk in women. The Reynolds Risk Score. JAMA 297:611–619PubMedCrossRefGoogle Scholar
  92. 92.
    Ridker PM, Paynter NP, Rifai N, Gaziano JM, Cook NR (2008) C-reactive protein and parental history improve global risk prediction: the Reynolds Risk Score for men. Circulation 118:2243–2251PubMedCrossRefGoogle Scholar
  93. 93.
    Assman G, Schulte H, Cullen P, Sedorf U (2007) Assessing risk of myocardial infarction and stroke; new data from the Prospective Cardiovascular Muenster (PROCAM) Study. Eur J Clin Invest 37:925–932CrossRefGoogle Scholar
  94. 94.
    Liu J, Hong Y, D’Agostino RB Sr, Wu Z, Wang W, Sun J, Wilson PW, Kannel WB, Zhao D (2004) Predictive value for the Chinese population of the Framingham coronary heart disease risk assessment tool as compared with the Chinese Multi-Provincial Cohort Study. JAMA 291:2491–2599Google Scholar
  95. 95.
    Critchley J, Liu J, Zhao D, Wei W, Capewell S (2004) Explaining the in increase in coronary heart disease mortality in Beijing between 1984 and 1999. Circulation 110:1236–1244PubMedCrossRefGoogle Scholar
  96. 96.
    Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Larras F, McQueen M, Budaf A, Pais P, Varigos J, Lishery L; Interheart Study Investigators (2004) Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART Study) case-control study. Lancet 364:937–952Google Scholar
  97. 97.
    Wald NJ, Law MR (2003) A strategy to reduce cardiovascular disease by more than 80%. BMJ 326:1419–1420PubMedCrossRefGoogle Scholar
  98. 98.
    The Indian Polycap Study (2009) Effects of a polypill (Polycap) on risk factors in middle-aged individuals withouts cardiovascular disease (TIPS): a phase II, double blind, randomized trial. Lancet 373:1341–1351CrossRefGoogle Scholar
  99. 99.
    Rubins HB, Robins SJ, Collins D, Nelson DB, Elam MB, Schaefer EJ, Faas FH, Anderson JW; VA-HIT Study Group (2002) Diabetes, plasma insulin, and cardiovascular disease. Subgroup analysis from the Department of Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT). Arch Intern Med 162:2597–2604Google Scholar
  100. 100.
    Schaefer EJ, Asztalos BF (2007) Increasing high density lipoprotein cholesterol, inhibition of cholesteryl ester transfer protein, and heart disease risk reduction. Am J Cardiol 100:S25-S31CrossRefGoogle Scholar
  101. 101.
    Schaefer EJ (2002) E.V. McCollum Award Lecture: lipoproteins, nutrition, and heart disease. Am J Clin Nutr 75:191–212PubMedGoogle Scholar
  102. 102.
    Asztalos BF, Horvath KV, McNamara JR, Roheim PS, Rubenstein JJ, Schaefer EJ (2002) Comparing the effects of five different statins on the HDL subpopulation profiles of coronary heart disease patients. Atherosclerosis 164:361–369PubMedCrossRefGoogle Scholar
  103. 103.
    Asztalos BF, Horvath KV, McNamara JR, Roheim PS, Rubenstein JJ, Schaefer EJ (2002) Effects of atorvastatin on the HDL subpopulation profile of coronary heart disease patients. J Lipid Res 43:1701–1707PubMedCrossRefGoogle Scholar
  104. 104.
    Asztalos BF, LeMaulf F, Dallal GE, Stein E, Jones PH, Horvath KV, McTaggert F, Schaefer EJ (2007) Comparison of the effects of high doses of rosuvastatin versus atorvastatin on the subpopulations of high density lipoproteins. Am J Cardiol 99:681–685PubMedCrossRefGoogle Scholar
  105. 105.
    Lamon-Fava S, Diffenderfer MR, Barrett PH, Buchsbaum A, Matthan NR, Lichtenstein AH, Dolnikowski GG, Horvath K, Asztalos BF, Zago V, Schaefer EJ (2007) Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism. J Lipid Res 48:1746–1753PubMedCrossRefGoogle Scholar
  106. 106.
    Pedersen TR, Olsson AG, Faergeman O et al (1998) Lipoprotein changes and reduction the incidence of major coronary heart disease events in the Scandinavian Simvastatin Survival Study (4S). Circulation 97:1453–1460PubMedGoogle Scholar
  107. 107.
    Nicholls SJ, Tuzxu EM, Sipathi I, Grasso AW, Schoenhagen P, Hu T, Wolski K, Crowe T, Desai MY, Hazen SL, Kapadia SR, Nissen SE (2007) Statins, high-density lipoprotein cholesterol and regression of coronary atherosclerosis. JAMA 297:499–508PubMedCrossRefGoogle Scholar
  108. 108.
    Staels B, Dallongeville J, Auwerx J, Schoonjans K, Leitersdorf E, Fruchart JC (1998) Mechanisms of action of fibrates on lipid and lipoprotein metabolism. Circulation 98:2088–2093PubMedGoogle Scholar
  109. 109.
    Schaefer EJ, Lamon Fava S, Cole T, Sprecher DL, Cilla DD Jr, Balagtas CC, Rowan JP, Black DM (1996) Effects of regular and extended-release gemfibrozil on plasma lipoproteins and apolipoproteins in hypercholesterolemic patients with decreased HDL cholesterol levels. Atherosclerosis 127:113–122PubMedCrossRefGoogle Scholar
  110. 110.
    Asztalos BF, Collins D, Horvath KV, Bloomfield HE, Robins SJ, Schaefer EJ (2008) Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial. Metabolism 57:77–83PubMedCrossRefGoogle Scholar
  111. 111.
    Saku K, Gartside PS, Hynd BA, Kashyap MI (1985) Mechanism of action of gemfibrozil on lipoprotein metabolism. J Clin Invest 75:1702–1712PubMedCrossRefGoogle Scholar
  112. 112.
    Watts GF, Barrett PH, Ji J, Serone AP, Chan DC, Croft KD, Loehrer F, Johnson AG (2003) Differential effects of atorvastatin and fenofibrate on lipoprotein kinetics in subjects with the metabolic syndrome. Diabetes 52:803–811PubMedCrossRefGoogle Scholar
  113. 113.
    Chan DC, Watts GF, Ooi EM, Rye KA, Ji J, Jophnson AG, Barrett PH (2009) Regulatory of the effects fenofibrate and atorvastatin on lipoprotein A-I and lipoprotein A-I:A-II in the metabolic syndrome. Diabetes Care 32(11):2111–2113PubMedCrossRefGoogle Scholar
  114. 114.
    Millar JS, Dufy D, Gadi R, Bloedon LT, Dunbar RL, Wolfe ML, Mowa R, Shah A, Fuki IV, McCoy M, Harris CJ, Wang MD, Howey DC, Rader DJ (2009) Potent and selective PPAR alpha agonist LY51867 upregulates both apoA-I production and catabolism in human subjects with the metabolic syndrome. Arterioscler Thromb Vasc Biol 29:140–146PubMedCrossRefGoogle Scholar
  115. 115.
    Manninen V, Elo O, Frick HH et al (1988) Lipid alterations and decline in the incidence of coronary heart disease in the Helsinki Heart Study. J Am Med Assoc 260:641–651CrossRefGoogle Scholar
  116. 116.
    Robins SJ, Collins D, Wittes JT, Papademetriou V, Deedwania PC, Schaefer EJ, McNamara JR, Kashyap ML, Hershman JM, Wexler LF, Rubins HB (2001) for the VA-HIT Study Group. Relation of gemfibrozil treatment and lipid levels with major coronary events. VA-HIT: a randomized controlled trial. J Am Med Assoc 285:1585–1591CrossRefGoogle Scholar
  117. 117.
    The DAIS Investigators (2001) Effect of fenofibrate on the progression of coronary artery disease in type 2 diabetes: the Diabetes Atherosclerosis Intervention Study (DAIS): a randomized trial. Lancet 357:1890–1895Google Scholar
  118. 118.
    Keech AC, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, Forder P, Pillai A, Davis T, Glasziou P, Drury P, Kesaniemi YA, Sullivan D, Hunt D, Colman P, d’Emden M, Whiting M, Ehnholm C, Laakso M; FIELD Investigators (2005) Effects of long term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): a randomized controlled trial. Lancet 366:1849–1861Google Scholar
  119. 119.
    Keech AC, Mitchell P, Summanen PA, O’Day J, Davis TM, Moffitt MS, Taskinen MR, Simes RJ, Tse D, Williamson E, Merrifield A, Laatikainen LT, d’Emden MC, Crimet DC, O’Connell RL, Colman P; FIELD Study Investigators (2007) Effect of fenofibrate on the need for laser treatment for diabetic retinopathy (FIELD Study): a randomized controlled trial. Lancet 370:1687–1697Google Scholar
  120. 120.
    Rajamani K, Colman PG, Li LP, Best JD, Voysey M, D’Emden MC, Laakso M, Baker JR, Keech AC (2009) Effect of fenofibrate on amputation events in people with type 2 diabetes mellitus (FIELD study): a prespecified analysis of a randomised controlled trial. Lancet 373:1780–1788PubMedCrossRefGoogle Scholar
  121. 121.
    Canner PL, Berge KG, Wenger NK, Stamler J, Freedman L, Prineas RJ, Friedewald W (1986) Fifteen year mortality in Coronary Drug Project patients: long term benefits with niacin. J Am Coll Cardiol 8:1245–1255PubMedCrossRefGoogle Scholar
  122. 122.
    Berge KG, Canner PL (1991) Coronary drug project: experience with niacin. Coronary Drug Project Research Group. Eur J Clin Pharm 40(Suppl 1):S49-S51CrossRefGoogle Scholar
  123. 123.
    Canner PL, Furberg CD, Terrin ML, McGovern ME (2005) Benefits of niacin by glycemic status in patients with healed myocardial infarction. From the Coronary Drug Project. Am J Cardiol 95:254–257PubMedCrossRefGoogle Scholar
  124. 124.
    Canner PL, Furberg CD, McGovern ME (2006) Benefits of niacin in patients with versus without the metabolic syndrome and healed myocardial infarction; from the Coronary Drug project. Am J Cardiol 97:477–479PubMedCrossRefGoogle Scholar
  125. 125.
    Brown GB, Zhao XQ, Chait A, Fisher LD, Cheung M, Morse JS, Dowdy AA, Marino EK, Bolson EL, Alaupovic P, Frohlich J, Albers JJ (2001) Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary artery disease. N Engl J Med 345:1583–1592PubMedCrossRefGoogle Scholar
  126. 126.
    Lamon-Fava S, Diffenderfer MR, Barrett PHR, Buchsbaum A, Nyaku M, Horvath K, Asztalos BF, Otokozawa S, Ai M, Matthan NR, Lichtenstein AH, Dolnikowski GG, Schaefer EJ (2008) Extended-release niacin alters the metabolism of plasma apolipoprotein (apo) A-I and apoB-containing lipoproteins. Arterioscler Thromb Vasc Biol 28:1672–1678PubMedCrossRefGoogle Scholar
  127. 127.
    Sudhop T, Lutjohann D, Kodal A, Igel M, Tribble DL, Shah S, Perevozskaya I, von Bergmann K (2002) Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation 106:1943–1948PubMedCrossRefGoogle Scholar
  128. 128.
    Pearson TA, Ballantyne CM, Veltri E, Shah A, Bird S, Lin J, Rosenberg E, Tershakovec AM (2009) Pooled analysis of effects on C reactive protein and low density lipoprotein cholesterol in placebo controlled trials of ezetimibe or ezetimibe added to baseline statin therapy. Am J Cardiol 103:369–374PubMedCrossRefGoogle Scholar
  129. 129.
    The Lipid Clinics Coronary Primary Prevention Trial results: II. (1984) The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. J Am Med Assoc 251:365–374Google Scholar
  130. 130.
    Fonseca VA, Rosenstock J, Wang K, Truitt KE, Jones MR (2008) Colesevelam HCL improves glycemic control and lowers LDL-C in patients with inadequate control of type II diabetes on sulfonylurea therapy. Diabetes Care 31:1479–1484PubMedCrossRefGoogle Scholar
  131. 131.
    Phillipson BE, Rothrock DW, Connor WE, Harris WS, Illingworth DR (1985) Reduction of plasma lipids, lipoproteins, and apolipoproteins by dietary fish oils in patients with hypertriglyceridemia. N Engl J Med 312:1210–1216PubMedCrossRefGoogle Scholar
  132. 132.
    Endres S, Ghorbani R, Kelley VE, Georgilis K, Lonneman G, Van Der Meer JWM, Cannon JG, Klempner M, Schaefer EJ, Wolff SM, Dinarello CA (1989) Dietary n-3 polyunsaturated fatty acids suppress synthesis of interleukin-1 and tumor necrosis factor. N Eng J Med 320:265–271CrossRefGoogle Scholar
  133. 133.
    Meydani SN, Lichtenstein AH, Cornwall S, Meydani M, Goldin BR, Rasmussen H, Dinarello CA, Schaefer EJ (1993) Immunologic effects of National Cholesterol Panel Step 2 diets with and without fish derived omega 3 fatty acid enrichment. J Clin Invest 92:105–113PubMedCrossRefGoogle Scholar
  134. 134.
    Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, Ballantyne CM, Ginsberg HN (2007) Combination prescription omega 3 fatty acids with simvastatin (COMBOS). Clin Ther 29:1354–1367PubMedCrossRefGoogle Scholar
  135. 135.
    Chan DC, Watts GF, Mori TA, Barrett PH, Redgrave TG, Beilin LJ (2003) Randomized controlled trial of the effects of n-3 fatty acid supplementation on the metabolism of apolipoprotein B-100 and chylomicron remnants in men with visceral adiposity. Am J Clin Nutr 77:300–307PubMedGoogle Scholar
  136. 136.
    Burr ML, Gilbert JF, Rogers S, Holliday RM, Sweetnam PM, Elwood PC, Deadman NM (1989) Effects of changes in fat, fish, and fibre intakes on death and myocardial infarction. Lancet 2:757–761PubMedCrossRefGoogle Scholar
  137. 137.
    Burr ML (2007) Secondary prevention of coronary heart disease in UK men: the Diet and Reinfarction Trial and its sequel. Proc Nutr Soc 66:9–15PubMedCrossRefGoogle Scholar
  138. 138.
    Gissi Prevenzione Investigators (1999) Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the Gissi Prevenzione Trial. Lancet 354:447–455CrossRefGoogle Scholar
  139. 139.
    Yokoyama M, Oryasa H, Matzuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Itakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; Japan EPA lipid intervention study (JELIS) investigators (2007) Effects of eicosapentaenoic acid on major coronary events in hypercholesterolemic patients (JELIS): a randomized open label, blinded endpoint analysis. Lancet 370:1090–1098Google Scholar
  140. 140.
    Tanaka K, Ishikawa Y, Yokoyama M, Oryasa H, Matsusaki M, Saito Y, Matsuzawa Y, Sasaki J, Oikawa S, Hishida H, Kakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; JELIS Investigators Japan (2008) Reduction in the recurrence of stroke by EPA for hypercholesterolemic patients:subanalysis of the JELIS trial. Stroke 39:2052–2058Google Scholar
  141. 141.
    Saito Y, Yokohama M, Oryasa H, Matsuzaki M, Matsuzawa Y, Ishikawa Y, Oikawa S, Sasaki J, Hishida H, Hakura H, Kita T, Kitabatake A, Nakaya N, Sakata T, Shimada K, Shirato K; JELIS Investigators Japan (2008) Effects of EPA on coronary artery disease in hypercholesterolemic patients with multiple risk factors: sub-analysis of primary prevention cases from the Japan EPA Lipid Intervention Study (JELIS). Atherosclerosis 200:135–140Google Scholar
  142. 142.
    Brouwer IA, Riatt MH, Dallemeijjer C, Kraemer DF, Zock PL, Morris C, Katan MB, Connor WE, Camm JA, Schouten EJ, McAnulty J (2009) Effect of fish oil on ventricular tachyarrhythmia in 3 studies in patients with implantable cardioverter defibrillators. Eur Heart J 30:820–826PubMedCrossRefGoogle Scholar
  143. 143.
    Schaefer EJ, Bongard V, Beiser AS, Tucker KL, Kyle DJ, Wilson PWF, Wolf PA (2006) Plasma phosphatidylcholine docosahexaenoic acid content, and risk of dementia and Alzheimer’s disease: The Framingham Study. Arch Neurol 63:1545–1550PubMedCrossRefGoogle Scholar
  144. 144.
    Nissen SE, Tsunoda T, Tuzcu EM, Schoenhagen P, Cooper CJ, Yasin M, Eaton GM, Lauer MA, Sheldon WS, Grines CL, Halpern S, Crowe T, Blankenship JC, Kerensky R (2003) Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial. JAMA 290:2292–2300PubMedCrossRefGoogle Scholar
  145. 145.
    Tardif JC, Grégoire J, L'Allier PL, Ibrahim R, Lesperance J, Heinonen TM, Kouz S, Berry C, Basser R, Lavoie MA, Guertin MC, Rodes-Cabau J; Effect of rHDL on Atherosclerosis-Safety and Efficacy (ERASE) Investigators (2007) Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial. JAMA 297:1675–1682Google Scholar
  146. 146.
    Brown BG, Stukowsky KH, Zhao XQ (2006) Simultaneous low-density lipoprotein-C lowering and high-density lipoprotein-C elevation for optimum cardiovascular disease prevention with various drug classes, and the combination: a meta-analysis of 23 randomized lipid trials. Curr Opin Lipidol 17:631–636PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media, LLC 2010

Authors and Affiliations

  1. 1.Lipid Metabolism LaboratoryTufts UniversityBostonUSA

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