The Low-HDL Syndrome: Epidemiology and Pathophysiology

  • Guido Franceschini
  • Barbara Villa
  • Monica Gomaraschi
  • Laura Calabresi
Part of the Medical Science Symposia Series book series (MSSS, volume 18)


Fifty years ago, Barr et al. [1] noted that concentrations of high density lipoprotein cholesterol (HDL-C) were lower in patients with coronary heart disease (CHD) than in healthy men. Fifteen years later, Gofman et al. used an analytical ultracentrifuge to separate the plasma lipoprotein fractions, and showed that patients who developed CHD had low levels of HDL-C [2], but HDL-C was largely forgotten until the appearance of Miller and Miller’s seminal publication in 1975 [3]. The Framingham Heart Study and other prospective studies confirmed the association between HDL-C and cardiovascular risk and, during the 1980s, HDL-C attracted a great deal of attention. In the 1990s the results of the statin trials have shifted the focus almost exclusively to low density lipoprotein cholesterol (LDL-C), and to the great benefit of LDL-C lowering in preventing the development of major coronary events in both primary and secondary prevention [4]. However, following the publication of the Veterans Affairs-High Density Lipoprotein Intervention Trial, which shows that raising HDL-C with gemfibrozil leads to a significant reduction of CHD events [5], HDL-C is again assuming considerable importance in the prevention and treatment of CHD. This review discusses the epidemiological and biochemical evidence for low HDL-C as a risk factor for CHD.


Coronary Heart Disease Risk Reverse Cholesterol Transport Coronary Heart Disease Patient High Density Lipoprotein Cholesterol Level Major Coronary Event 
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  1. 1.
    Barr DP, Russ EM, Eder HA. Protein-lipid relationships in human plasma. Am J Med 1951;11:480–85.PubMedCrossRefGoogle Scholar
  2. 2.
    Gofman JW, Young W, Tandy R. Ischemic heart disease, atherosclerosis, and longevity. Circulation 1966;34:679–97.PubMedCrossRefGoogle Scholar
  3. 3.
    Miller GJ, Miller NE. Plasma-high-density-lipoprotein concentration and development of ischaemic heart-disease. Lancet 1975;1:16–19.PubMedCrossRefGoogle Scholar
  4. 4.
    LaRosa JC, He J, Vupputuri S. Effect of statins on risk of coronary disease: a metaanalysis of randomized controlled trials. JAMA 1999;282:2340–46.PubMedCrossRefGoogle Scholar
  5. 5.
    Rubins HB, Robins SJ, Collins D, et al. Gemfibrozil for the secondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. N Engl J Med 1999;341:410–18.PubMedCrossRefGoogle Scholar
  6. 6.
    Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. The Framingham Study. Am J Med 1977;62:707–14.PubMedCrossRefGoogle Scholar
  7. 7.
    Stampfer MJ, Sacks FM, Salvini S, Willet WC, Hennekens CH. A prospective study of cholesterol, apolipoproteins, and the risk of miocardial infarction. N Engl J Med 1991;325:373–81.PubMedCrossRefGoogle Scholar
  8. 8.
    Berge KG, Canner PL, Hainline A, Jr. High-density lipoprotein cholesterol and prognosis after myocardial infarction. Circulation 1982;66:1176–78.PubMedCrossRefGoogle Scholar
  9. 9.
    Miller M, Seidler A, Kwiterovich PO, Jr., Pearson TA. Long-term predictors of subsequent cardiovascular events with coronary artery disease and ‘desirable’ levels of plasma total cholesterol. Circulation 1992;86:1165–70.PubMedCrossRefGoogle Scholar
  10. 10.
    van Lennep JE, Westerveld HT, van Lennep HW, et al. Apolipoprotein concentrations during treatment and recurrent coronary artery disease events. Arterioscler Thromb Vase Biol 2000;20:2408–13.CrossRefGoogle Scholar
  11. 11.
    Gordon DJ, Probstfield JL, Garrison RJ, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation 1989;79:8–15.PubMedCrossRefGoogle Scholar
  12. 12.
    Franceschini G, Maderna P, Sirtori CR. Reverse cholesterol transport: physiology and pharmacology. Atherosclerosis 1991;88:99–107.PubMedCrossRefGoogle Scholar
  13. 13.
    Eriksson M, Carlson LA, Miettinen TA, Angelin B. Stimulation of fecal steroid excretion after infusion of recombinant proapolipoprotein A-I. Potential reverse cholesterol transport in humans. Circulation 1999;100:594–98.PubMedCrossRefGoogle Scholar
  14. 14.
    Sirtori CR, Calabresi L, Franceschini G. Recombinant apolipoproteins for the treatment of vascular diseases. Atherosclerosis 1999;142:29–40.PubMedCrossRefGoogle Scholar
  15. 15.
    Paszty C, Maeda N, Verstuyft J, Rubin EM. Apolipoprotein AI transgene corrects apolipoprotein E deficiency-induced atherosclerosis in mice. J Clin Invest 1994;94:899–903.PubMedCrossRefGoogle Scholar
  16. 16.
    Duverger N, Kruth H, Emmanuel F, et al. Inhibition of atherosclerosis development in cholesterol-fed human apolipoprotein A-I-transgenic rabbits. Circulation 1996;94:713–17.PubMedCrossRefGoogle Scholar
  17. 17.
    Cockerill GW, Rye KA, Gamble JR, Vadas MA, Barter PJ. High-density lipoproteins inhibit cytokine-induced expression of endothelial cell adhesion molecules. Arterioscler Thromb Vase Biol 1995;15:1987–94.CrossRefGoogle Scholar
  18. 18.
    Calabresi L, Franceschini G, Sirtori CR, et al. Inhibition of VCAM-1 expression in endothelial cells by reconstituted high density lipoproteins. Biochem Biophys Res Commun 1997;238:61–65.PubMedCrossRefGoogle Scholar
  19. 19.
    Banka CL. High density lipoprotein and lipoprotein oxidation. Curr Opin Lipidol 1996; 7:139–42.PubMedCrossRefGoogle Scholar
  20. 20.
    Sirtori CR, Calabresi L, Franceschini G, et al. Cardiovascular status of carriers of the apolipoprotein A-IMilano mutant. The Limone sul Garda Study. Circulation 2001; 103:1949–54.PubMedCrossRefGoogle Scholar
  21. 21.
    James RW, Blatter Garin MC, Calabresi L, et al. Modulated serum activities and concentrations of paraoxonase in high density lipoprotein deficiency states. Atherosclerosis 1998;139:77–82.PubMedCrossRefGoogle Scholar
  22. 22.
    The Bezafibrate Infarction Prevention (BIP) Study Group. Lipids and lipoproteins in symptomatic coronary heart disease. Distribution, intercorrelations, and significance for risk classification in 6,700 men and 1,500 women. Circulation 1992;86:839–48.CrossRefGoogle Scholar
  23. 23.
    Rubins HB, Robins SJ, Collins D, et al. Distribution of lipids in 8,500 men with coronary artery disease. Department of Veterans Affairs HDL Intervention Trial Study Group. Am J Cardiol 1995;75:1196–1201.PubMedCrossRefGoogle Scholar
  24. 24.
    Genest JJ, Martin Munley SS, McNamara JR, et al. Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation 1992;85:2025–33.PubMedCrossRefGoogle Scholar
  25. 25.
    Frick MH, Elo O, Haapa K, et al. Helsinki Heart Study: Primary-prevention trial with gemfibrozil in middle-aged men with dyslipidemia. Safety of treatment, changes in risk factors, and incidence of coronary heart disease. N Engl J Med 1987;317:1237–45.PubMedCrossRefGoogle Scholar

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© Springer Science+Business Media Dordrecht 2002

Authors and Affiliations

  • Guido Franceschini
  • Barbara Villa
  • Monica Gomaraschi
  • Laura Calabresi

There are no affiliations available

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