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Published on: October 12, 2017
HDL cholesterol: reappraisal of its clinical relevance
Winfried März1,2,3, Marcus E Kleber1,4, Hubert Scharnagl2
1Medizinische Klinik V (Nephrologie, Hypertensiologie, Rheumatologie, Endokrinologie, Diabetelogie), Medizinische Fakultät Mannheim der Universität Heidelberg, Heidelberg, Germany.
Insights
High-density lipoprotein cholesterol (HDL-C) is not always "good cholesterol" and may not predict cardiovascular risk in all individuals. Lifestyle changes can improve HDL-C, but it is not a reliable drug therapy target.
Area of Science:
- Cardiovascular Medicine
- Lipid Metabolism
- Atherosclerosis Research
Background:
- Elevated low-density lipoprotein cholesterol (LDL-C) is a known cause of atherosclerosis.
- High-density lipoprotein cholesterol (HDL-C) has been traditionally considered atheroprotective.
- Emerging evidence necessitates a re-evaluation of HDL-C's clinical significance.
Purpose of the Study:
- To review the current understanding of HDL-C's role in cardiovascular health.
- To assess the clinical utility of HDL-C as a cardiovascular risk marker.
- To evaluate the impact of HDL-C levels and composition on cardiovascular outcomes.
Main Methods:
- Selective literature review of relevant studies.
- Analysis of the relationship between HDL-C concentrations and cardiovascular events.
- Examination of HDL particle composition and function.
Main Results:
- Low HDL-C is linked to cardiovascular risk in healthy individuals, but this association may not hold for patients with metabolic disorders or cardiovascular disease.
- HDL particle number and composition, not just HDL-C concentration, influence its atheroprotective or atherogenic functions.
- Pharmacological interventions aimed at increasing HDL-C have not consistently reduced cardiovascular outcomes.
Conclusions:
- HDL-C's correlation with cardiovascular risk is primarily observed in healthy populations.
- Low HDL-C warrants investigation into underlying metabolic and inflammatory conditions.
- Lifestyle modifications like smoking cessation and exercise positively impact HDL-C; however, HDL-C is not a validated target for pharmacological intervention.
Background:
While several lines of evidence prove that elevated concentrations of low-density lipoproteins (LDL) causally contribute to the development of atherosclerosis and its clinical consequences, high-density lipoproteins are still widely believed to exert atheroprotective effects. Hence, HDL cholesterol (HDL-C) is in general still considered as "good cholesterol". Recent research, however, suggests that this might not always be the case and that a fundamental reassessment of the clinical significance of HDL-C is warranted.
Method:
This review article is based on a selective literature review.
Results:
In individuals without a history of cardiovascular events, low concentrations of HDL-C are inversely associated with the risk of future cardiovascular events. This relationship may, however, not apply to patients with metabolic disorders or manifest cardiovascular disease. The classical function of HDL is to mobilise cholesterol from extrahepatic tissues for delivery to the liver for excretion. These roles in cholesterol metabolism as well as many other biological functions of HDL particles are dependent on the number as well as protein and lipid composition of HDL particles. They are poorly reflected by the HDL-C concentration. HDL can even exert negative vascular effects, if its composition is pathologically altered. High serum HDL-C is therefore no longer regarded protective. In line with this, recent pharmacological approaches to raise HDL-C concentration have not been able to show reductions of cardiovascular outcomes.
Conclusion:
In contrast to LDL cholesterol (LDL-C), HDL-C correlates with cardiovascular risk only in healthy individuals. The calculation of the ratio of LDL-C to HDL-C is not useful for all patients. Low HDL-C should prompt examination of additional metabolic and inflammatory pathologies. An increase in HDL-C through lifestyle change (smoking cessation, physical exercise) has positive effects and is recommended. However, HDL-C is currently not a valid target for drug therapy.
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