scholarly journals HDL Particle Measurement: Comparison of 5 Methods

2018 ◽  
Vol 64 (3) ◽  
pp. 492-500 ◽  
Author(s):  
Robert Matera ◽  
Katalin V Horvath ◽  
Hari Nair ◽  
Ernst J Schaefer ◽  
Bela F Asztalos

Abstract BACKGROUND HDL cell cholesterol efflux capacity has been documented as superior to HDL cholesterol (HDL-C) in predicting cardiovascular disease risk. HDL functions relate to its composition. Compositional assays are easier to perform and standardize than functional tests and are more practical for routine testing. Our goal was to compare measurements of HDL particles by 5 different separation methods. METHODS HDL subfractions were measured in 98 samples using vertical auto profiling (VAP), ion mobility (IM), nuclear magnetic resonance (NMR), native 2-dimensional gel electrophoresis (2D-PAGE), and pre-β1-ELISA. VAP measured cholesterol in large HDL2 and small HDL3; IM measured particle number directly in large, intermediate, and small HDL particles; NMR measured lipid signals in large, medium, and small HDL; 2D-PAGE measured apolipoprotein (apo) A-I in large (α1), medium (α2), small (α3–4), and pre-β1 HDL particles; and ELISA measured apoA-I in pre-β1-HDL. The data were normalized and compared using Passing–Bablok, Lin concordance, and Bland–Altman plot analyses. RESULTS With decreasing HDL-C concentration, NMR measured a gradually lower percentage of large HDL, compared with IM, VAP, and 2D-PAGE. In the lowest HDL-C tertile, NMR measured 8% of large HDL, compared with IM, 22%; VAP, 20%; and 2D-PAGE, 18%. There was strong discordance between 2D-PAGE and NMR in measuring medium HDL (R2 = 0.356; rc = 0.042) and small HDL (R2 = 0.376; rc = 0.040). The 2D-PAGE assay measured a significantly higher apoA-I concentration in pre-β1-HDL than the pre-β1-ELISA (9.8 vs 1.6 mg/dL; R2 = 0.246; rc = 0.130). CONCLUSIONS NMR agreed poorly with the other methods in measuring large HDL, particularly in low HDL-C individuals. Similarly, there was strong discordance in pre-β1-HDL measurements between the ELISA and 2D-PAGE assays.

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Jacqueline S Dron ◽  
Jian Wang ◽  
Adam D McIntyre ◽  
John F Robinson ◽  
Matthew R Ban ◽  
...  

HDL cholesterol (HDL-C) levels strongly associate with cardiovascular disease risk, and as a complex trait, are influenced by genetic and environmental factors. Extreme HDL-C concentrations are largely genetically determined; monogenic disorders of HDL-C have been well-characterized, including the primary candidate genes driving each extreme phenotype, which typically show autosomal recessive or co-dominant inheritance. Within genes causing syndromes of both HDL-C extremes, numerous disease-causing variants have been identified and functionally validated. In a unique cohort of patients with extreme HDL-C profiles ( N =255), we applied our targeted next-generation sequencing panel LipidSeq TM , which is designed for clinical re-sequencing of genes associated with dyslipidemia and other metabolic disorders. We found that 20.6% and 11.8% of low ( N =136) and high ( N =119) HDL-C patients, respectively, carry heterozygous, large-effect mutations in pertinent genes explaining their phenotypes. To further characterize the genetic variation contributing to HDL-C levels, we next investigated the integrated polygenic contribution from multiple small-effect genetic variants using a polygenic trait score (PTS). We developed two scores to assess an individual’s burden of small-effect variants: one each for lowering and raising HDL-C levels. As a whole, low HDL-C patients had a significantly greater mean PTS for low HDL-C than normolipidemic controls ( P <0.001); furthermore, there was no difference in PTS among carriers and non-carriers of large-effect variants. In contrast, high HDL-C patients’ mean PTS for high HDL-C in carriers of large-effect variants was not different from non-carrier or controls, while PTS in non-carriers was significantly greater than controls (both P <0.001). The findings confirm the complexity of extreme HDL-C levels and the differences in contributions of rare large-effect and common small-effect variants to these extremes.


2018 ◽  
Vol 24 (17) ◽  
pp. 1905-1911 ◽  
Author(s):  
Maria Luz Fernandez ◽  
Minu Sara Thomas ◽  
Bruno S. Lemos ◽  
Diana M. DiMarco ◽  
Amanda Missimer ◽  
...  

Background: Telomerase Activator 65 (TA-65), a compound extracted from Astragalus membranaceus has been used in Chinese traditional medicine for extending lifespan. Scarce information exists on the effects of TA-65 on parameters of metabolic syndrome (MetS). Methods: We recruited 40 patients with MetS to determine the effects of TA-65 on dyslipidemias, hypertension, and oxidative stress in this at-risk population. The study was a double-blind, randomized crossover design in which patients were allocated to consume either 16 mg daily of a TA-65 supplement or a placebo for 12 weeks. Following a 3-week washout, participants were allocated to the alternate treatment for an additional 12 weeks. Anthropometric and biological markers were measured at the end of each treatment. Plasma lipids, glucose, CReactive Protein (CRP), liver enzymes, and glycosylated hemoglobin were measured using a Cobas c-111. Inflammatory cytokines were measured by Luminex technology and markers of oxidative stress by the use of spectroscopy. Results: Compared to the placebo period, HDL cholesterol (HDL-C) was higher while body mass index, waist circumference, and the LDL/HDL ratio were lower (p < 0.05) during TA-65 treatment. In addition, plasma tumor necrosis factor-α (TNF-α) was lower during the TA-65 period (p< 0.05). Positive correlations were observed in changes between the placebo and the TA-65 periods in HDL-C and CRP (r = -0.511, p < 0.01), alanine aminotransferase (r = -0.61, p < 0.001) and TNF-α (r = -0.550, p < 0.001) suggesting that the favorable changes observed in HDL were associated with decreases in inflammation. Conclusion: TA-65 improved key markers of cardiovascular disease risk, which were also associated with reductions in inflammation.


2020 ◽  
Vol 150 (12) ◽  
pp. 3161-3170
Author(s):  
Alicia Julibert ◽  
Maria del Mar Bibiloni ◽  
Laura Gallardo-Alfaro ◽  
Manuela Abbate ◽  
Miguel Á Martínez-González ◽  
...  

ABSTRACT Background High nut consumption has been previously associated with decreased prevalence of metabolic syndrome (MetS) regardless of race and dietary patterns. Objectives The aim of this study was to assess whether changes in nut consumption over a 1-y follow-up are associated with changes in features of MetS in a middle-aged and older Spanish population at high cardiovascular disease risk. Methods This prospective 1-y follow-up cohort study, conducted in the framework of the PREvención con DIeta MEDiterránea (PREDIMED)-Plus randomized trial, included 5800 men and women (55–75 y old) with overweight/obesity [BMI (in kg/m2) ≥27 and &lt;40] and MetS. Nut consumption (almonds, pistachios, walnuts, and other nuts) was assessed using data from a validated FFQ. The primary outcome was the change from baseline to 1 y in features of MetS [waist circumference (WC), glycemia, HDL cholesterol, triglyceride (TG), and systolic and diastolic blood pressure] and excess weight (body weight and BMI) according to tertiles of change in nut consumption. Secondary outcomes included changes in dietary and lifestyle characteristics. A generalized linear model was used to compare 1-y changes in features of MetS, weight, dietary intakes, and lifestyle characteristics across tertiles of change in nut consumption. Results As nut consumption increased, between each tertile there was a significant decrease in WC, TG, systolic blood pressure, weight, and BMI (P &lt; 0.05), and a significant increase in HDL cholesterol (only in women, P = 0.044). The interaction effect between time and group was significant for total energy intake (P &lt; 0.001), adherence to the Mediterranean diet (MedDiet) (P &lt; 0.001), and nut consumption (P &lt; 0.001). Across tertiles of increasing nut consumption there was a significant increase in extra virgin olive oil intake and adherence to the MedDiet; change in energy intake, on the other hand, was inversely related to consumption of nuts. Conclusions Features of MetS and excess weight were inversely associated with nut consumption after a 1-y follow-up in the PREDIMED-Plus study cohort. This trial was registered at isrctn.com as ISRCTN89898870.


2020 ◽  
Vol 14 (4) ◽  
pp. 571-572
Author(s):  
Cathy Sun ◽  
Diane Brisson ◽  
Christopher McCudden ◽  
Julie Shaw ◽  
Daniel Gaudet ◽  
...  

2003 ◽  
Vol 15 (1_suppl) ◽  
pp. S37-S40 ◽  
Author(s):  
AP James ◽  
K Slivkoff-Clark ◽  
JCL Mamo

Obese insulin resistant individuals often present with a dyslipidemic phenotype characterised by hypertriglyceridemia, low HDL cholesterol levels, essentially normal total- and LDL-cholesterol, but a propensity for smaller, denser LDL particles. We have reported that concentrations of chylomicrons are two to three folds greater than in age-matched lean controls. We have recently observed that in lean free-living subjects the flux of chylomicrons over a 12h period was just 25% greater in these subjects than basal chylomicron production. Constitutive secretion of chylomicrons appears to be of greater relevance to arterial exposure than postprandial fluctuations. Insulin critically regulates the metabolism of very low density lipoprotein (VLDL) and hence it would be expected that the hormone is also involved in the regulation of chylomicron metabolism. Impaired insulin action may therefore be responsible for the associated hyperchylomicronaemia. In this review we examine the hypothesis that insulin chronically modulates chylomicron metabolism and present evidence suggesting that hyperchylomicronaemia primarily results from impaired chylomicron production.


PPAR Research ◽  
2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Tara M. Henagan ◽  
Laura K. Stewart ◽  
Laura A. Forney ◽  
Lauren M. Sparks ◽  
Neil Johannsen ◽  
...  

PGC1α, a transcriptional coactivator, interacts with PPARs and others to regulate skeletal muscle metabolism.PGC1αundergoes splicing to produce several mRNA variants, with theNTPGC1αvariant having a similar biological function to the full lengthPGC1α(FLPGC1α). CVD is associated with obesity and T2D and a lower percentage of type 1 oxidative fibers and impaired mitochondrial function in skeletal muscle, characteristics determined byPGC1αexpression.PGC1αexpression is epigenetically regulated in skeletal muscle to determine mitochondrial adaptations, and epigenetic modifications may regulate mRNA splicing. We report in this paper that skeletal musclePGC1α  −1 nucleosome (−1N) position is associated with splice variantNTPGC1αbut notFLPGC1αexpression. Division of participants based on the −1N position revealed that those individuals with a −1N phased further upstream from the transcriptional start site (UP) expressed lower levels ofNTPGC1αthan those with the −1N more proximal to TSS (DN). UP showed an increase in body fat percentage and serum total and LDL cholesterol. These findings suggest that the −1N may be a potential epigenetic regulator ofNTPGC1αsplice variant expression, and −1N position andNTPGC1αvariant expression in skeletal muscle are linked to CVD risk. This trial is registered with clinicaltrials.gov, identifierNCT00458133.


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