High-density lipoprotein (HDL) cholesterol  – more complicated than we think?

Nessler, Katarzyna; Windak, Adam; Grzybczak, Rafał; Nessler, Michał Bohdan; Siniarski, Aleksander; Gajos, Grzegorz

doi:10.26444/aaem/92350

Cited by 14 publications

(14 citation statements)

References 90 publications

(110 reference statements)

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“…However, patients without CVD at baseline in the lower HDL tertile showed a slightly increased risk for all-cause mortality, thus confirming the well-known negative role of low HDL cholesterol serum concentration in individuals in primary prevention [30]. The effectiveness of HDL cholesterol quantity as a trustworthy marker for CV protection has been recently questioned [2]. Mutant ApoA-I Milano is a paradigmatic example of this incongruence: carriers of this mutation display very low levels of HDL cholesterol and are markedly protected from CVD [31].…”

Section: All-cause and Specific-cause Mortalitymentioning

confidence: 71%

“…The high heterogeneity of HDL subspecies accounts for their different capabilities in reverse cholesterol transport and in atheroprotection [34,35]. In the presence of chronic subclinical inflammation, such as in coronary artery disease, impaired HDL vesselprotecting functions have been reported even without alteration in HDL cholesterol blood concentrations, which may remain in the normal range [2,4,5,7]. Similarly, in T2DM patients, characterized by chronic subclinical inflammation status and by the aforementioned atherogenic dyslipidemia, reaching normal or even high HDL cholesterol levels might not be effective in conferring atheroprotection [4,13].…”

Section: All-cause and Specific-cause Mortalitymentioning

confidence: 99%

“…HDL particles are known to be highly heterogeneous in structure and content. The chronic inflammatory state and non-enzymatic apolipoprotein glycation that occur in T2DM contribute to altering the relative composition of HDL and impairing HDL-associated anti-inflammatory and anti-atherogenic properties [2,[14][15][16][17], thus hampering the protective effect of HDL on vessels.…”

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confidence: 99%

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Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study

et al. 2020

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Background: The protective role of high HDL cholesterol levels against cardiovascular diseases has been recently questioned. Limited data are available on this specific topic in patients with type 2 diabetes mellitus (T2DM). We aimed to evaluate the association of HDL cholesterol concentrations with all-cause and cause-specific mortality in a historical cohort of T2DM patients with 14 years of follow-up. Methods: This is a retrospective population-based cohort study involving 2113 T2DM patients attending the Diabetic Clinic of Asti. Survival analyses were performed to assess hazard ratios for overall and specific-cause mortality by HDL cholesterol tertiles, using the middle HDL cholesterol tertile as a reference. Results: The mean age was 66 ± 11 years; 51.4% of patients had low HDL-cholesterol levels. After a 14-year follow-up, 973/2112 patients had died (46.1%). The HDL cholesterol tertile cutoff points were 37.5 and 47.5 mg/dL (males) and 41.5 and 52.0 mg/dL (females). No associations between lower and upper HDL cholesterol tertiles respectively and all-cause (HR = 1.12; 95% CI 0.96-1.32; HR = 1.11; 0.95-1.30), cardiovascular (HR = 0.97; 0.77-1.23; HR = 0.94; 0.75-1.18) or cancer (HR = 0.92; 0.67-1.25; HR = 0.89; 0.66-1.21) mortality were found. A significantly increased risk for infectious disease death was found both in the lower (HR = 2.62; 1.44-4.74) and the upper HDL-cholesterol tertiles (HR = 2.05; 1.09-3.85) when compared to the reference. Individuals in the upper tertile showed an increased risk for mortality due to diabetes-related causes (HR = 1.87; 1.10-3.15). Conclusions: Our results corroborate the hypothesis that HDL cholesterol levels are nonprotective in T2DM patients. The U-shaped association between HDL-cholesterol levels and mortality associated with infectious diseases should be verified by further studies.

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Section: All-cause and Specific-cause Mortalitymentioning

confidence: 71%

Section: All-cause and Specific-cause Mortalitymentioning

confidence: 99%

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confidence: 99%

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Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study

et al. 2020

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“…Under pathological conditions, abnormal HDLs are not simply related to the overall amount of HDL-c herein contained, but their status is a direct consequence of their overall composition. Therefore, the quality of the HDL-c appears to be a better biomarker than the quantity of HDLs [5,46,59,60]. This evidence has increased interest in studying the dysfunctional HDLs in pathological conditions characterized by systemic inflammation and oxidative stress such as obesity, T2DM, and CVD [2,5,59,61,62].…”

Section: Dysfunctional Hdls: From Quantity To Qualitymentioning

confidence: 99%

HDL Dysfunctionality: Clinical Relevance of Quality Rather Than Quantity

et al. 2021

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High-density lipoproteins (HDLs) represent a class of lipoproteins very heterogeneous in structure, composition, and biological functions, which carry out reverse cholesterol transport, antioxidant, anti-inflammatory, antithrombotic, and vasodilator actions. Despite the evidence suggesting a clear inverse relationship between HDL cholesterol (HDL-c) concentration and the risk for cardiovascular disease, plasma HDL cholesterol levels do not predict the functionality and composition of HDLs. The importance of defining both the amount of cholesterol transported and lipoprotein functionality has recently been highlighted. Indeed, different clinical conditions such as obesity, diabetes mellitus type 2 (T2DM), and cardiovascular disease (CVD) can alter the HDL functionality, converting normal HDLs into dysfunctional ones, undergoing structural changes, and exhibiting proinflammatory, pro-oxidant, prothrombotic, and proapoptotic properties. The aim of the current review is to summarize the actual knowledge concerning the physical–chemical alteration of HDLs related to their functions, which have been found to be relevant in several pathological conditions associated with systemic inflammation and oxidative stress.

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“…In liver, HDL-C particles release lipid cargo and then lipid-poor HDL particles return to the circulation in order to repeat the cycle [15,16]. Experimental studies have demonstrated that under normal conditions HDL possesses antiatherogenic properties [15,27,28]. According to studies, HDL stimulates macrophage reverse cholesterol transport, which involves the extraction of excess cholesterol from lipid-laden macrophage foam cells present in the atherosclerotic plaque, the efflux of free cholesterol to mature HDL-C or extracellular lipid-poor apoA-I, and its transport to the liver for excretion in the bile [16,29].…”

Section: Hdl Role and Functionsmentioning

confidence: 99%

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

Rysz

Gluba-Brzózka

Rysz-Górzyńska

et al. 2020

IJMS

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Chronic kidney disease (CKD) is a worldwide health problem with steadily increasing occurrence. Significantly elevated cardiovascular morbidity and mortality have been observed in CKD. Cardiovascular diseases are the most important and frequent cause of death of CKD patients globally. The presence of CKD is related to disturbances in lipoprotein metabolism whose consequences are dyslipidemia and the accumulation of atherogenic particles. CKD not only fuels the reduction of high-density lipoprotein (HDL) cholesterol concentration, but also it modifies the composition of this lipoprotein. The key role of HDL is the participation in reverse cholesterol transport from peripheral tissues to the liver. Moreover, HDL prevents the oxidation of low-density lipoprotein (LDL) cholesterol by reactive oxygen species (ROS) and protects against the adverse effects of oxidized LDL (ox-LDL) on the endothelium. Numerous studies have demonstrated the ability of HDL to promote the production of nitric oxide (NO) by endothelial cells (ECs) and to exert antiapoptotic and anti-inflammatory effects. Increasing evidence suggests that in patients with chronic inflammatory disorders, HDLs may lose important antiatherosclerotic properties and become dysfunctional. So far, no therapeutic strategy to raise HDL, or alter the ratio of HDL subfractions, has been successful in slowing the progression of CKD or reducing cardiovascular disease in patients either with or without CKD.

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High-density lipoprotein (HDL) cholesterol – more complicated than we think?

Cited by 14 publications

References 90 publications

Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study

Is HDL cholesterol protective in patients with type 2 diabetes? A retrospective population-based cohort study

HDL Dysfunctionality: Clinical Relevance of Quality Rather Than Quantity

The Role and Function of HDL in Patients with Chronic Kidney Disease and the Risk of Cardiovascular Disease

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