low HDL (summary and causes of)

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High-density lipoprotein cholesterol (HDL-C) levels are inversely associated with coronary heart disease, independent of total and low-density lipoprotein cholesterol (LDL-C) levels. Low HDL-C may be secondary to factors such as:

  • cigarette smoking
  • obesity - particularly visceral fat
  • very low fat diets e.g. vegetarian often have low HDL-C
  • drugs, including:
    • beta-adrenergic blocking agents (beta-blockers)
    • anabolic steroids such as testosterone
    • androgenic progestins

However some individuals low HDL-C levels may have a genetic, or primary, cause, including abnormalities in:

  • ApoA-I
    • complete apoA-I deficiency
    • ApoA-I mutations (eg, ApoA-I Milano)
  • lecithin:cholesterol acyl transferase (LCAT)
    • complete LCAT deficiency
    • partial LCAT deficiency (fish-eye disease)
  • ABC1
    • Tangier disease
      • homozygous
      • heterozygous
    • Familial hypoalphalipoproteinemia (some families)
  • unknown genetic aetiology
    • Familial hypoalphalipoproteinemia (most families)
    • Familial combined hyperlipidemia with low HDL-C
    • metabolic syndrome

References:

  1. Genest JJ Jr, Martin-Munley SS, McNamara JR, et al. Familial lipoprotein disorders in patients with premature coronary artery disease. Circulation. 1992;85:2025-2033.
  2. Assmann G, von Eckardstein A, Funke H. High-density lipoproteins, reverse transport of cholesterol, and coronary artery disease: insights from mutations. Circulation. 1993;87:III-28-III-34
  3. Lawn RM, Wade DP, Garvin MR, et al. The Tangier disease gene product ABC1 controls the cellular apolipoprotein-mediated lipid removal pathway. J Clin Invest. 1999;104:425-431.
  4.  Criqui MH, Wallace RB, Heiss G, et al. Cigarette smoking and plasma high-density lipoprotein cholesterol: the Lipid Research Clinics Program Prevalence Study. Circulation. 1980;62:IV70-IV76
  5. Glueck CJ, Taylor HL, Jacobs D, et al. Plasma high-density lipoprotein cholesterol: association with measurements of body mass. The Lipid Research Clinics Program Prevalence Study. Circulation. 1980;62:IV62-IV69.
  6. Knopp RH, Walden CE, Retzlaff BM, et al. Long-term cholesterol-lowering effects of 4 fat-restricted diets in hypercholesterolemic and combined hyperlipidemic men: the Dietary Alternatives Study. JAMA.1997;278:1509-1515.
  7. van Brummelen P. The relevance of intrinsic sympathomimetic activity for beta-blocker-induced changes in plasma lipids. J Cardiovasc Pharmacol. 1983;5:S51-S55.
  8. Sacks FM, Gerhard M, Walsh BW. Sex hormones, lipoproteins, and vascular reactivity. Curr Opin Lipidol. 1995;6:161-166.
  9. Teran AZ, Greenblatt RB, Chaddha JS. Changes in lipoproteins with various sex steroids. Obstet Gynecol Clin North Am. 1987;14:107-119.

Last reviewed 06/2021

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