HDL cholesterol levels

HDL cholesterol is a high-density lipoprotein, commonly known as "good cholesterol" because it is responsible for the storage and excretion of cholesterol, which has been linked to a lower risk of heart attack or stroke.

HDL cholesterol (high density lipoprotein) is a lipoprotein of the chylomicron group whose functions are to transport lipids such as phospholipids, triglycerides or cholesterol. It differs from other lipoproteins such as LDL by its higher density, due to having a greater amount of proteins in its composition.

The main function of HDL is the transport of cholesterol from peripheral tissues to the liver, playing a role in lipid biodistribution. It is commonly known as "good cholesterol" due to its anti-atherogenic and anti-inflammatory properties, thanks to its uptake and return to the liver of cholesterol stored in the foam cells of atherosclerotic plaques. It thus reduces plaque size and its associated inflammation, reducing the risk of atherosclerosis, a precursor of myocardial infarction, transient ischemic attack and stroke.

It is well established that elevated HDL levels (>40 mg/dL) are associated with a lower risk of coronary heart disease and are thought to play a role in predicting cardiovascular risk.

HDL cholesterol levels can vary for different reasons. Genetic factor is among the factors influencing the levels of this lipoprotein. Compared to genetically determined abnormalities of HDL metabolism, low HDL-C levels occur much more frequently in patients with metabolic syndrome or diabetes mellitus. Low HDL-C levels are also associated with systemic inflammation, e.g., smoking, chronic inflammatory diseases or chronic kidney disease (Fig. 3) [45, 46]. In cases of extremely low HDL-C, a rare diagnosis, e.g., neoplasia or an increased risk of sepsis, may be considered.

Some established HDL cholesterol levels based on their relationship to cardiovascular disease risk are mentioned below:

  • Less than 40 mg/dL in men = low HDL (increased risk).
  • Less than 50 mg/dL in women = low HDL (higher risk)
  • 40 to 59 mg/dL = Higher is better
  • 60 mg/dL and above = high HDL (lower risk)

It is known that blood lipid levels are affected by genetics, so the heritability of this trait affects the variability in the levels of parameters such as low density cholesterol (LDL), high density cholesterol (HDL), total cholesterol or triglyceride level. One of the GWAS studies carried out in recent years has studied the role of genetic mutations in lipid levels. From this study, carried out on 95.The LIPL gene, which produces the enzyme hepatic lipase, also involved in the transport of HDL cholesterol and involved in transformation processes between the different forms of cholesterol; and the LPL gene, which produces lipoprotein lipase, an enzyme involved in the catabolism and degradation of triglycerides and lipoproteins. Many of these identified markers have in turn been strongly associated with cardiovascular and metabolic traits, such as coronary artery disease, type 2 diabetes, blood pressure, waist-to-hip ratio, and body mass index.

Number of observed variants

13.5 million variants

Number of loci analyzed in the study

143 loci

Bibliography

Willer C.J., Schmidt E.M., et al. Discovery and refinement of loci associated with lipid levels. Nature Genetics, 06 Oct 2013, 45(11):1274-1283

Bailey A. et Mohiuddin S.S. (2021) Biochemistry, High Density Lipoprotein. StatPearls.

März W., Kleber M.E., et al. HDL cholesterol: reappraisal of its clinical relevanceClin Res Cardiol. 2017; 106(9): 663–675.

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