Levels of high-density lipoprotein cholesterol (HDL-C) among children with steady-state sickle cell disease

Abstract Abstract 1547 Poster Board I-570 Introduction Levels of high-density lipoprotein cholesterol have been correlated with anti-inflammatory, anti-oxidative, anti-aggregation, anti-coagulant and pro-fibrinolytic activities. We hypothesized that lipoprotein cholesterol and triglycerides have important roles in sickle cell disease pathogenesis. Patients and Methods A prospective study of biochemical and hematological analyses of 152 steady-state children with sickle cell disease and 132 healthy subjects using immunochemistry, immunoassay and electronic cell counter respectively. Clinical data were collected from patient medical records. Data analyses were performed using Prism 5.01 (Graphpad Software, San Diego, CA), EPIinfo 6.04 (CDC, Atlanta, Georgia) and STATA SE 10 software (StataCorp, Texas, USA). Results There was a significant positive association of high-density lipoprotein cholesterol with hemoglobin (p<0.001), hematocrit (p<0.001) and total cholesterol (p<0.001) and a negative association with reticulocytes (p=0.046), leukocytes (p=0.015), monocytes (p=0.004) and platelets (p=0.005), bilirubins [total bilirubin (p<0.001), direct bilirubin (p<0.001) and indirect bilirubin (p<0.001], iron (p<0.001), aminotransferases [aspartate aminotransferase (p=0.004), alanine aminotransferase (p=0.035)], lactate dehydrogenase (p<0.001), urea (p=0.030), alpha 1-antitrypsin (p<0.001), very low-density lipoprotein cholesterol (p=0.003), triglycerides (p=0.005) and hemoglobin S (p=0.002). Low high-density lipoprotein cholesterol concentration was associated with cardiac abnormalities (p<0.025), pneumonia history (p=0.033) and blood transfusion use (p=0.025). Triglycerides (p=0.047), very low-density lipoprotein cholesterol (p=0.044), low-density lipoprotein cholesterol (p=0.033), total cholesterol (p=0.007), alpha 1-antitrypsin (p=0.040) and ferritin (p=0.008) levels were associated with cholelithiasis. Conclusion We hypothesize that some SCD patients can have a specific dyslipidemic subphenotype characterized by hypertriglyceridemia, high VLDL-C and low plasma LDL-C and HDL-C in association with other biomarkers, including those related to inflammation. This represents an important step toward a more reliable clinical prognosis. We suggest further studies and continued research into new mechanisms involving this complex network of markers in order to establish their role in SCD pathogenesis. Disclosures No relevant conflicts of interest to declare.

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Normal Non-HDL Cholesterol, Low Total Cholesterol, and HDL Cholesterol Levels in Sickle Cell Disease Patients in the Steady State: A Case-Control Study of Tema Metropolis

Journal of Lipids ◽

10.1155/2016/7650530 ◽

2016 ◽

Vol 2016 ◽

pp. 1-5 ◽

Cited By ~ 5

Author(s):

Richard K. D. Ephraim ◽

Patrick Adu ◽

Edem Ake ◽

Hope Agbodzakey ◽

Prince Adoba ◽

...

Keyword(s):

Blood Pressure ◽

Steady State ◽

Sickle Cell Disease ◽

Total Cholesterol ◽

Sickle Cell ◽

Density Lipoprotein ◽

Hdl Cholesterol ◽

Lipoprotein Cholesterol ◽

Cell Disease ◽

Cross Sectional

Background.Abnormal lipid homeostasis in sickle cell disease (SCD) is characterized by defects in plasma and erythrocyte lipids and may increase the risk of cardiovascular disease. This study assessed the lipid profile and non-HDL cholesterol level of SCD patients.Methods.A hospital-based cross-sectional study was conducted in 50 SCD patients, in the steady state, aged 8–28 years, attending the SCD clinic, and 50 healthy volunteers between the ages of 8–38 years. Serum lipids were determined by enzymatic methods and non-HDL cholesterol calculated by this formula: non-HDL-C = TC-HDL-C.Results.Total cholesterol (TC) (p=0.001) and high-density lipoprotein cholesterol (HDL-C) (p<0.0001) were significantly decreased in cases compared to controls. The levels of non-HDL-C, low-density lipoprotein cholesterol (LDL-C), and triglyceride (TG) were similar among the participants. The levels of decrease in TC and HDL were associated with whether a patient was SCD-SS or SCD-SC. Systolic blood pressure and diastolic blood pressure were each significantly associated with increased VLDL [SBP,p=0.01, OR: 0.74 (CI: 0.6–0.93); DBP,p=0.023, OR: 1.45 (CI: 1.05–2.0)].Conclusion.Dyslipidemia is common among participants in this study. It was more pronounced in the SCD-SS than in SCD-SC. This dyslipidemia was associated with high VLDL as well as increased SBP and DBP.

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Featured Article: Depletion of HDL3 high density lipoprotein and altered functionality of HDL2 in blood from sickle cell patients

Experimental Biology and Medicine ◽

10.1177/1535370217706966 ◽

2017 ◽

Vol 242 (12) ◽

pp. 1244-1253 ◽

Cited By ~ 5

Author(s):

Eric Soupene ◽

Sandra K Larkin ◽

Frans A Kuypers

Keyword(s):

Sickle Cell Disease ◽

High Density Lipoprotein ◽

Sickle Cell ◽

Acute Phase ◽

Whole Blood ◽

Density Lipoprotein ◽

High Density ◽

High Density Lipoproteins ◽

Mrna Levels ◽

Cell Disease

In sickle cell disease (SCD), alterations of cholesterol metabolism is in part related to abnormal levels and activity of plasma proteins such as lecithin cholesterol acyltransferase (LCAT), and apolipoprotein A-I (ApoA-I). In addition, the size distribution of ApoA-I high density lipoproteins (HDL) differs from normal blood. The ratio of the amount of HDL2 particle relative to the smaller higher density pre-β HDL (HDL3) particle was shifted toward HDL2. This lipoprotein imbalance is exacerbated during acute vaso-occlusive episodes (VOE) as the relative levels of HDL3 decrease. HDL3 deficiency in SCD plasma was found to relate to a slower ApoA-I exchange rate, which suggests an impaired ABCA1-mediated cholesterol efflux in SCD. HDL2 isolated from SCD plasma displayed an antioxidant capacity normally associated with HDL3, providing evidence for a change in function of HDL2 in SCD as compared to HDL2 in normal plasma. Although SCD plasma is depleted in HDL3, this altered capacity of HDL2 could account for the lack of difference in pro-inflammatory HDL levels in SCD as compared to normal. Exposure of human umbilical vein endothelial cells to HDL2 isolated from SCD plasma resulted in higher mRNA levels of the acute phase protein long pentraxin 3 (PTX3) as compared to incubation with HDL2 from control plasma. Addition of the heme-scavenger hemopexin protein prevented increased expression of PTX3 in sickle HDL2-treated cells. These findings suggest that ApoA-I lipoprotein composition and functions are altered in SCD plasma, and that whole blood transfusion may be considered as a blood replacement therapy in SCD. Impact statement Our study adds to the growing evidence that the dysfunctional red blood cell (RBC) in sickle cell disease (SCD) affects the plasma environment, which contributes significantly in the vasculopathy that defines the disease. Remodeling of anti-inflammatory high density lipoprotein (HDL) to pro-inflammatory entities can occur during the acute phase response. SCD plasma is depleted of the pre-β particle (HDL3), which is essential for stimulation of reverse cholesterol from macrophages, and the function of the larger HDL2 particle is altered. These dysfunctions are exacerbated during vaso-occlusive episodes. Interaction of lipoproteins with endothelium increases formation of inflammatory mediators, a process counteracted by the heme-scavenger hemopexin. This links hemolysis to lipoprotein-mediated inflammation in SCD, and hemopexin treatment could be considered. The use of RBC concentrates in transfusion therapy of SCD patients underestimates the importance of the dysfunctional plasma compartment, and transfusion of whole blood or plasma may be warranted.

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Triglyceride to high density lipoprotein cholesterol ratio, total cholesterol to high density lipoprotein cholesterol ratio and low ankle brachial index in an elderly population

VASA ◽

10.1024/0301-1526/a000348 ◽

2014 ◽

Vol 43 (3) ◽

pp. 189-197 ◽

Cited By ~ 10

Author(s):

Yiqiang Zhan ◽

Jinming Yu ◽

Rongjing Ding ◽

Yihong Sun ◽

Dayi Hu

Keyword(s):

High Density Lipoprotein ◽

Total Cholesterol ◽

High Density Lipoprotein Cholesterol ◽

Ankle Brachial Index ◽

Density Lipoprotein ◽

High Density ◽

Lipoprotein Cholesterol ◽

Lipid Lowering ◽

Cholesterol Ratio ◽

Potential Biomarker

Background: The associations of triglyceride (TG) to high-density lipoprotein cholesterol ratio (HDL‑C) and total cholesterol (TC) to HDL‑C ratio and low ankle brachial index (ABI) were seldom investigated. Patients and methods: A population based cross-sectional survey was conducted and 2982 participants 60 years and over were recruited. TG, TC, HDL‑C, and low-density lipoprotein cholesterol (LDL-C) were assessed in all participants. Low ABI was defined as ABI ≤ 0.9 in either leg. Multiple logistic regression models were applied to study the association between TG/HDL‑C ratio, TC/HDL‑C ratio and low ABI. Results: The TG/HDL‑C ratios for those with ABI > 0.9 and ABI ≤ 0.9 were 1.28 ± 1.20 and 1.48 ± 1.13 (P < 0.0001), while the TC/HDL‑C ratios were 3.96 ± 1.09 and 4.32 ± 1.15 (P < 0.0001), respectively. After adjusting for age, gender, body mass index, obesity, current drinking, physical activity, hypertension, diabetes, lipid-lowering drugs, and cardiovascular disease history, the odds ratios (ORs) with 95 % confidence intervals (CIs) of low ABI for TG/HDL‑C ratio and TC/HDL‑C ratio were 1.10 (0.96, 1.26) and 1.34 (1.14, 1.59) in non-smokers. When TC was further adjusted, the ORs (95 % CIs) were 1.40 (0.79, 2.52) and 1.53 (1.21, 1.93) for TG/HDL‑C ratio and TC/HDL‑C ratio, respectively. Non-linear relationships were detected between TG/HDL‑C ratio and TC/HDL‑C ratio and low ABI in both smokers and non-smokers. Conclusions: TC/HDL‑C ratio was significantly associated with low ABI in non-smokers and the association was independent of TC, TG, HDL‑C, and LDL-C. TC/HDL‑C might be considered as a potential biomarker for early peripheral arterial disease screening.

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