high or increased HDL cholesterol

Last edited 11/2020 and last reviewed 08/2021

Elevated high-density lipoprotein cholesterol (HDL-C) is epidemiologically associated with a decreased risk of coronary artery disease

• Causes of high HDL-C may be primary (ie, genetic) or secondary
  • the only known genetic causes of high HDL are deficiencies in the genes for cholesteryl ester transfer protein (CETP) and hepatic lipase
  • primary hyperalphalipoproteinemia is a term used for familial elevated HDL-C that is not due to CETP or hepatic lipase deficiencies and for which the cause is unknown

Serum high-density lipoprotein (HDL) cholesterol may be increased by secondary causes, for example (1,2,3,4,5):

• regular vigorous sustained aerobic exercise
• regular substantial consumption of alcohol
• insulin treatment
• oestrogen replacement therapy
• very-high fat diet
• drugs e.g. phenytoin, insulin

Are high levels of HDL anti-atherogenic? (6)

• .."According to HEART UK experts the protective effect of HDL appears to reach its maximum when levels are roughly 1.5mmol/L. Beyond this, higher levels of HDL may not provide additional protection and current research is suggesting that levels in excess of 2.3mmol/L may behave more like LDL cholesterol, raising the risk of developing cardiovascular disease and heart problems, particularly in women who are going through, or are post menopause...
• If you have a family history of early heart disease and your HDL is very high (above 3 mmol/L) and there is no obvious cause then ideally you should be referred to a lipid clinic for further investigations. If both total and HDL cholesterol are high (total cholesterol over 7.5 mmol/L with HDL cholesterol over 2.5 mmol/L in women) then treatment decisions are better guided by the levels of bad cholesterol (LDL and/or non-HDL-cholesterol) than by the Total/HDL-cholesterol ratio which may be misleading in these circumstances.."

Reference:

1. Kokkinos PF, Holland JC, Naravan P, et al. Miles run per week and high-density lipoprotein cholesterol levels in healthy, middle-aged men: a dose-response relationship. Arch Intern Med. 1995;155:415-420.
2. West CF, Sullivan DR, Katan MB, Halferkamps IL, van der Torre HW. Boys from populations with high carbohydrate intake have higher fasting triglyceride levels than boys from populations with high fat intake. Am J Epidemiol. 1990;131:271-282.
3. Savolainen MJ. How does alcohol raise HDL-cholesterol concentration? Ann Med. 1990;22:141-142.
4. Editorial. Walsh BW, Schiff I, Rosner B, et al. Effects of postmenopausal estrogen replacement on the concentrations and metabolism of plasma lipoproteins.
5. N Engl J Med. 1991;325:1196-1204. Goerdt C, Keith M, Rubins HB. Effects of phenytoin on plasma high-density lipoprotein cholesterol levels in men with low levels of high-density lipoprotein cholesterol. J Clin Pharmacol. 1995;35:767-775.
6. High Density Lipoprotein (HDL). HEART UK Factsheet (Accessed 30/11/2020)