+1 (502) 904-2126   One Westbrook Corporate Center, Suite 300, Westchester, IL 60154, USA   Site Map
ISSN: 2574 -1241

Impact Factor : 0.548

  Submit Manuscript

Short CommunicationOpen Access

The Role of Dysfunctional HDL in Clinical Practice and Research Volume 53- Issue 4

Rodney G Bowden*

  • Professor and Brown Foundation Endowed Chair, Department of Public Health, Baylor University, USA

Received: November 01, 2023;   Published: November 09, 2023

*Corresponding author: Rodney G Bowden, PhD, Professor and Brown Foundation Endowed Chair, Department of Public Health, Baylor University, USA

DOI: 10.26717/BJSTR.2023.53.008437

Abstract PDF


Cardiovascular disease (CVD) remains one of the leading causes of mortality globally [1]. An established risk factor for CVD is dyslipidemia, characterized by high levels of low-density lipoprotein cholesterol (LDL), elevated triglycerides and low levels of high-density lipoprotein cholesterol (HDL) [2]. HDL has long been considered to offer protection against CVD due to its role in reverse cholesterol transport and anti-inflammatory properties [3]. In clinical practice, HDL measurements are utilized to assess cardiovascular risk, inform treatment decisions, and guide preventive strategies. Increasing HDL levels is a therapeutic goal to improve the overall lipid profile, reduce cardiovascular risk, and guide medication decisions. It should be noted that recent research has suggested the functional properties of HDL, such as its ability to promote reverse cholesterol transport and reduce inflammation, are equally important in assessing the significance of a protective role in CVD risk [4]. Recent research findings suggest HDL may lose cardio-protective functions (known as dysfunctional HDL) and may even promote atherosclerosis and heart disease [5-8]. Dysfunctional HDL has been linked to various cardiovascular diseases, including atherosclerosis and heart disease. One of the key mechanisms leading to HDL dysfunction is oxidative modification [9]. Under conditions of inflammation and oxidative stress, HDL particles can become oxidized, rendering them less effective in promoting reverse cholesterol transport and anti-inflammatory actions with downstream effects of persistent inflammation with increased levels of LDL and triglycerides in peripheral tissues. This process may turn HDL into a pro-inflammatory agent, contributing to endothelial dysfunction, CVD and atherosclerosis. Additionally, glycation, the non-enzymatic binding of sugars to proteins, can also alter HDL function[10]. Glycated HDL has reduced capacity to promote cholesterol efflux and may contribute to the development of atherosclerotic plaques. The glycation of HDL may be a consequence of prolonged hyperglycemia in individuals with diabetes [11]. Study authors have reported that individuals with a higher proportion of dysfunctional HDL are at an increased risk of developing CVD [12].

This underscores the importance of identifying and understanding the role of dysfunctional HDL in cardiovascular health. Accurate identification and measurement of dysfunctional HDL is essential for assessing CVD risk accurately. Continued research is necessary to develop specific assays and diagnostic markers to distinguish functional from dysfunctional HDL. Consequently, several therapeutic approaches should continue to be explored to mitigate the impact of dysfunctional HDL. These include lifestyle modifications, such as diet and exercise, as well as pharmacological interventions that target oxidative stress and inflammation. The use of HDL in clinical practice holds significant clinical implications. It can serve as a valuable tool for assessing cardiovascular risk, guide treatment decisions, and monitor the effectiveness of interventions. However, HDL’s clinical utility is not without challenges, such as variations in measurement methods and the emerging complexity of assessing HDL function. Identifying the mechanisms that lead to HDL dysfunction and developing effective therapeutic strategies to address this issue are critical steps in a deeper understanding of CVD progression. Further research and clinical studies are needed to better characterize dysfunctional HDL, improve diagnostic tools, and evaluate the efficacy of emerging therapies. Understanding and addressing the role of dysfunctional HDL in heart disease may ultimately lead to more effective prevention and treatment strategies in the future.


  1. Kim Y, Lee S, Lee Y, Min Woo Kang, Sehoon Park, et al. (2021) Predictive value of triglyceride/high-density lipoprotein cholesterol for major clinical outcomes in advanced chronic kidney disease: a nationwide population-based study. Clinical Kidney Journal 14(8): 1961-1968.
  2. Bajaj A, Xie D, Cedillo Couvert E, Jeanne Charleston, Jing Chen, et al. (2019) Lipids, Apolipoproteins, and Risk of Atherosclerotic Cardiovascular Disease in Persons With CKD. American Journal of Kidney Diseases 73(6): 827-836.
  3. Bermudez Lopez M, Forne C, Amigo N, Milica Bozic, David Arroyo, et al. (2019) An in-depth analysis shows a hidden atherogenic lipoprotein profile in non-diabetic chronic kidney disease patients. Expert Opinion on Therapeutic Targets 23(7): 619-630.
  4. Vaziri ND (2016) HDL abnormalities in nephrotic syndrome and chronic kidney disease. Nature reviews Nephrology 12(1): 37-47.
  5. Bonizzi A, Piuri G, Corsi F, Cazzola R, Mazzucchelli S (2021) HDL Dysfunctionality: Clinical Relevance of Quality Rather Than Quantity. Biomedicines 9(7): 729.
  6. Pirillo A, Catapano AL, Norata GD (2019) Biological Consequences of Dysfunctional HDL. Curr Med Chem 26(9): 1644-1664.
  7. Jakob P, Lüscher TF (2019) Dysfunctional HDL and inflammation: A noxious liaison in adolescents with type 1 diabetes. European Heart Journal 40(43): 3567-3570.
  8. Chiesa ST, Charakida M (2019) High Density Lipoprotein Function and Dysfunction in Health and Disease. Cardiovasc Drugs Ther 33(2): 207-219.
  9. Maeba R, Kojima K ichiro, Nagura M, Aya Komori, Megumi Nishimukai, et al. (2018) Association of cholesterol efflux capacity with plasmalogen levels of high-density lipoprotein: A cross-sectional study in chronic kidney disease patients. Atherosclerosis 270: 102-109.
  10. Li X, Su T, Xiao H, Peichun Gao, Chongxiang Xiong, et al. (2020) Association of the HDL-c Level with HsCRP, IL-6, U-NAG, RBP and Cys-C in Type 2 Diabetes Mellitus, Hypertension, and Chronic Kidney Disease: An Epidemiological Survey. Diabetes, Metabolic Syndrome and Obesity 13: 3645-3654.
  11. Moradi H, Vaziri ND (2018) Molecular mechanisms of disorders of lipid metabolism in chronic kidney disease. Frontiers in bioscience (Landmark edition) 23(1): 146-161.
  12. You A, Li Y, Tomlinson B, Longfei Yue, Kaijie Zhao, et al (2021) Association Between Renal Dysfunction and Low HDL Cholesterol Among the Elderly in China. Frontiers in Cardiovascular Medicine, p. 8.