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High density lipoprotein in atherosclerosis and coronary heart disease: Where do we stand today?
Evangelia Zvintzou1, Dimitra Sotiria Karampela1, Aggeliki Vakka1
1University of Patras, School of Medicine, Department of Pharmacology, Rio Achaias, TK 26500, Greece.
Insights
High density lipoprotein cholesterol (HDL-C) levels and cardiovascular disease (CVD) risk follow a U-shaped curve. HDL particle function, not just levels, impacts atherosclerosis, questioning HDL-C-raising drug efficacy.
Area of Science:
- Biochemistry
- Epidemiology
- Pharmacology
Background:
- Cardiovascular disease (CVD) risk is linked to high density lipoprotein cholesterol (HDL-C) levels, exhibiting a U-shaped curve.
- Optimal HDL-C ranges vary by sex: 40-70 mg/dl for men and 50-70 mg/dl for women.
- HDL particles have diverse structural and functional attributes, influencing their role as antiatherogenic or proatherogenic.
Purpose of the Study:
- To critically review current literature on HDL, focusing on biochemistry, epidemiology, and pharmacology.
- To evaluate the suitability of experimental drugs and clinical trial designs targeting HDL-C-raising hypotheses.
- To discuss HDL's role in atherosclerosis prevention based on structure and function.
Main Methods:
- Compilation and critical analysis of existing scientific literature on HDL.
- Review of data from clinical trials investigating HDL-C.
- Examination of HDL structure and function in relation to atherosclerosis.
Main Results:
- The relationship between HDL-C and CVD risk is complex, not linear.
- HDL particle heterogeneity suggests function is more critical than mere concentration.
- Clinical trials targeting HDL-C-raising have yielded questionable results.
Conclusions:
- The efficacy of HDL-C-raising strategies is doubtful due to HDL particle diversity.
- Understanding HDL structure and function is crucial for effective atherosclerosis prevention.
- Discrepancies between mouse models and human responses may explain failed pharmacological interventions.
Abstract:
Epidemiological studies during the last five years suggest that a relation between high density lipoprotein cholesterol (HDL-C) levels and the risk for cardiovascular disease (CVD) does exist but follows rather a "U-shaped" curve with an optimal range of HDL-C concentration between 40 and 70 mg/dl for men and 50-70 mg/dl for women. Moreover, as research in the field of lipoproteins progresses it becomes increasingly apparent that HDL particles possess different attributes and depending on their structural and functional characteristics, they may be "antiatherogenic" or "proatherogenic". In light of this information, it is highly doubtful that the choice of experimental drugs and the design of respective clinical trials that put the HDL-C raising hypothesis at test, were the most suitable. Here, we compile the existing literature on HDL, providing a critical up-to-date view that focuses on key data from the biochemistry, epidemiology and pharmacology of HDL, including data from clinical trials. We also discuss the most up-to-date information on the contribution of HDL structure and function to the prevention of atherosclerosis. We conclude by summarizing important differences between mouse models and humans, that may explain why pharmacological successes in mice turn out to be failures in humans.
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