LDL Particle Size Research Articles

Lipoprotein profiles associated with exposure to poly- and perfluoroalkyl substances (PFASs) in the EuroMix human biomonitoring study

Exposure to per- and polyfluoroalkyl substances (PFASs) is associated with increased blood cholesterol. Although elevated cholesterol is a well-established risk factor for cardiovascular diseases (CVD), it is not clear whether PFASs affect this risk. Lipoprotein subclasses are emerging biomarkers for disease risk and lipoprotein profiling may provide an insight to physiological implications of PFAS exposure. We explored the association between serum PFAS concentrations and lipoprotein subclasses in a cross-sectional study. We determined the concentrations and lipid composition of the major subclasses of lipoproteins in plasma samples from 127 adult participants of the EuroMix human biomonitoring study by nuclear magnetic resonance (NMR). Serum concentrations of 17 PFASs showed a detection frequency between 30 and 100% and were included in further analyses. We examined the associations between PFAS concentrations and lipoprotein subclasses by linear mixed-effect regression models, adjusted for confounders. In the adjusted models, positive associations were found between several PFASs and cholesterol concentrations in large to medium sized HDL and medium sized LDL particles. We found a 4–12% increase in HDL cholesterol per interquartile range (IQR) increase for several PFASs. In women the associations with PFNA, PFUnDA, PFDoDA and PFOS were significant after adjustment for multiple comparisons. Similar magnitude of change was observed between longer chained PFASs and LDL cholesterol, and a few of these associations reached significance for cholesterol in large to medium LDL particle sizes in women. No significant associations with plasma triglycerides were observed. However, most PFASs tended to be associated with reduction in VLDL (very low-density lipoproteins) particle number and VLDL triglyceride. Findings from this exploratory study, suggest that background PFAS exposures influence particle size distributions and lipid composition of plasma lipoprotein subclasses, and that these effects may be more prominent in women. A two-points lipoprofiling for all subjects indicated both low intra-individual variability and good analytical reproducibility.

Prolonged Fasting Alters the Size, Function, and Glycoproteomic Profile of HDL Particles

ObjectivesTo investigate the effects of a single 36-hour fast on HDL glycoproteomic composition on isolated HDL particles. MethodsWe obtained plasma from a previous study where 20 healthy subjects, age 20–40, fasted for 36 hours. HDL was isolated using density-based ultracentrifugation steps, followed by size-exclusion chromatography. Glycoproteomic was analyzed using a targeted LC-MS/MS method, and lipoprotein particle size distribution analysis using nuclear magnetic resonance (NMR) spectroscopy. ResultsHDL-associated apolipoprotein A-IV (ApoA-IV) content was significantly reduced (8918.39 +/– 3823.39 normalized ion counts vs 3690.82 +/– 2147.29 normalized ion count, p adjusted < 0.0001), suggesting a reduction in intestinally-derived HDL after a 36-hour fast. HDL associated apolipoprotein C-III (ApoC-III) di-sialylated glycopeptides decreased in HDL following a 36-hour fast compared to an overnight 12-hour fast (0.1680 +/– 0.0342 normalized ion counts vs 0.1315 +/– 0.0373 normalized ion counts, p adjusted = 0.041). Additionally, particle size distribution analysis showed an increase in abundance of calibrated large HDL of size 9.6–13nm (3.42 +/– 2.218 μmol/L vs 3.885 +/– 2.134 μmol/L, p adjusted = 0.011) and a decrease in abundance of medium HDL of size 8.1–9.5nm (6.88 +/– 1.86 μmol/L vs 5.82 +/– 2.048 μmol/L, p adjusted = 0.019) after a 36-hour fast. There were no significant changes in LDL particle size (21.115 +/– nm s 21.205 +/– 0.458 nm, p adjusted = 0.655) but there was a significant increase in overall calibrated LDL particle concentration (1138.05 +/– 357.94 μmol/L vs 1262.3 +/– 313.33 μmol/L, p adjusted = 0.011) and calibrated small LDL particle concentration (454.85 +/– 187.76 μmol/L vs 598.8 +/– 190.84 μmol/L, p adjusted = 0.025). ConclusionsOur findings indicate that prolonged fasting alters lipoprotein profiles by affecting the proportions of large and small HDL and LDL particles, as well as altering the protein composition of HDL particles, specifically by reducing the abundance of ApoA-IV, which suggests a reduction in the contribution of intestinally-derived HDL particles to the circulating HDL pool. Future studies are needed to determine the long-term effects of multiple bouts of prolonged fasting. Funding SourcesUniversity of California Davis, National Institute on Aging.

1096-P: The LDL-C/apoB Ratio Predicts Future Cardiovascular Events in Cardiovascular Disease Patients with Nonalcoholic Fatty Liver Disease as Well as in Those without Nonalcoholic Fatty Liver Disease

A low LDL-C / apoB ratio reflects small LDL particle size and is associated with insulin resistance. Nonalcoholic fatty liver disease (NALFD) is an important feature of the insulin resistance syndrome and confers an increased cardiovascular risk. The impact of the LDL-C / apoB ratio on the risk of cardiovascular events in patients with NAFLD is unclear and is addressed in the present study. We enrolled a large high risk cohohort of 1515 patients with established cardiovascular disease (1272 patients with angiographically proven stable CAD and 243 patients with sonographically proven peripheral artery disease) . NAFLD was diagnosed using the validated fatty liver index. Prospectively, cardiovascular events were recorded over a mean follow-up period of 7.6±4.9 years. At baseline, the LDL-C / apoB ratio was significantly lower in patients with NAFLD (n=709) than in subjects who did not have NAFLD (1.34±0.29 vs. 1.39±0.26 mg/dl; p=0.001) . During follow-up, 755 patients suffered cardiovascular events. The event rate was higher in patients with than in those without NAFLD (53.6 vs. 47.6%; p=0.020) . The LDL-C/ApoB ratio significantly predicted cardiovascular events in the total study cohort, with a standardized adjusted hazard ratio (HR) of 0.86 [0.80-0.94]; p&amp;lt;0.0 and both in patients with NAFLD (HR 0.87 [0.78-0.97]; p=0.013) and in subjects who did not have NAFLD (HR 0.87 [0.77-0.97]; p=0.013, respectively) . We conclude that in subjects with established cardiovascular disease the LDL-C / apoB ratio predicts cardiovascular events both among patients with NAFLD and in those who do not have NAFLD. Disclosure M.Maechler: None. L.Sprenger: None. A.Mader: None. B.Larcher: None. A.Vonbank: None. A.Leiherer: None. A.Muendlein: None. H.Drexel: None. C.H.Saely: None.

Atherogenicity of low-density lipoproteins after switching from a protease inhibitor to dolutegravir: a substudy of the NEAT022 study.

The aim of this study was to investigate whether switching from a ritonavir-boosted PI-based regimen to a dolutegravir-based regimen improved the atherogenic properties of LDL particles in patients with HIV. This was a substudy of the NEAT022 study (ClinicalTrials.gov NCT02098837). Adults with HIV with a Framingham score >10% or aged >50 years and being treated with a stable boosted PI-based regimen were randomized to either switch to dolutegravir or continue with boosted PI. At baseline and Week 48, we assessed atherogenic LDL properties: LDL particle size and phenotype (A, intermediate, B), oxidized LDL (ox-LDL) and lipoprotein-associated phospholipase A2 (Lp-PLA2) activity. Eighty-six participants (dolutegravir 44; PI 42) were included. Participants had a median (IQR) age of 54 (51-57) years and 79.1% were male. In the dolutegravir arm, after 48 weeks, we observed: (1) an increase in LDL size [median 1.65 Å (IQR -0.60 to 4.20); P = 0.007], correlated with the decrease in triglyceride concentration [Spearman correlation = -0.352 (P = 0.001)], with a corresponding decrease of subjects with atherogenic LDL phenotype B (36.4% to 20.5%; P = 0.039); (2) a decrease in Lp-PLA2 activity [median 1.39 μmol/min/mL (IQR -2.3 to 0.54); P = 0.002]; and (3) a decrease in ox-LDL [median 14 U/L (IQR -102 to 13); P = 0.006]. In the PI arm, none of these favourable lipid modifications was observed. Forty-eight weeks after switching from a PI-based to a dolutegravir-based regimen, patients with Framingham score >10% or aged >50 years showed improvement of several atherogenic lipid features, including LDL particle phenotype, ox-LDL and Lp-PLA2.

Circulating Metabolic Biomarkers Are Consistently Associated With Type 2 Diabetes Risk in Asian and European Populations.

While Asians have a higher risk of type 2 diabetes (T2D) than Europeans for a given body mass index (BMI), it remains unclear whether the same markers of metabolic pathways are associated with diabetes. We evaluated associations between metabolic biomarkers and incidence of T2D in 3 major Asian ethnic groups (Chinese, Malay, and Indian) and a European population. We analyzed data from adult males and females of 2 cohorts from Singapore (n = 6393) consisting of Chinese, Malays, and Indians and 3 cohorts of European-origin participants from Finland (n = 14 558). We used nuclear magnetic resonance to quantify 154 circulating metabolic biomarkers at baseline and performed logistic regression to assess associations with T2D risk adjusted for age, sex, BMI and glycemic markers. Of the 154 metabolic biomarkers, 59 were associated with higher risk of T2D in both Asians and Europeans (P < 0.0003, Bonferroni-corrected). These included branched chain and aromatic amino acids, the inflammatory marker glycoprotein acetyls, total fatty acids, monounsaturated fatty acids, apolipoprotein B, larger very low-density lipoprotein particle sizes, and triglycerides. In addition, 13 metabolites were associated with a lower T2D risk in both populations, including omega-6 polyunsaturated fatty acids and larger high-density lipoprotein particle sizes. Associations were consistent within the Asian ethnic groups (all Phet ≥ 0.05) and largely consistent for the Asian and European populations (Phet ≥ 0.05 for 128 of 154 metabolic biomarkers). Metabolic biomarkers across several biological pathways were consistently associated with T2D risk in Asians and Europeans.

Nutrigenetics, omega-3 and plasma lipids/lipoproteins/apolipoproteins with evidence evaluation using the GRADE approach: a systematic review

ObjectivesDespite the uptake of nutrigenetic testing through direct-to-consumer services and healthcare professionals, systematic reviews determining scientific validity are limited in this field. The objective of this review was to: retrieve,...

Colonic Microbiota Profile Characterization of the Responsiveness to Dietary Fibre Treatment in Hypercholesterolemia.

This study aimed to determine how the microbiota profile might be predisposed to a better response in blood lipid profiles due to dietary fibre supplementation. A three-arm intervention study that included three different fibre types (mainly insoluble, soluble, and antioxidant fibre) supplemented (19.2 g/day) during 2 months in individuals with hypercholesterolemia was developed. Changes in faecal microbiota and blood lipid profile after fibre supplementation were determined. In all volunteers, regardless of fibre type, an increase in the abundance of Bifidobacterium was observed, and similarly, an inverse relationship between faecal propionic acid and blood LDL-cholesterol, LDL particle size, and LDL/HDL particle ratio (p-values 0.0067, 0.0002, and 0.0067, respectively) was observed. However, not all volunteers presented an improvement in lipid profile. The non-responders to fibre treatment showed a decrease in microbiota diversity (Shannon and Simpson diversity index p-values of 0.0110 and 0.0255, respectively) after the intervention; where the reduction in short-chain fatty acids (SCFAs) producing bacterial genera such as Clostridium XIVa and Ruminococcus after dietary fibre treatment was the main difference. It was concluded that the non-responsiveness to dietary fibre treatment might be mediated by the lack of ability to maintain a stable SCFA producing bacteria diversity and composition after extra fibre intake.

Perfil lipoproteico por espectroscopia nuclear magnética en pacientes con insuficiencia cardiaca crónica comparado con controles emparejados

Introduction and objectivesAdvanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. MethodsThis cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. ResultsThe 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P<.001) and HDL (25.7 vs 27.9μmol/L; P <.001) particle concentrations, with this last difference being mediated by a significantly lower concentration of the small subfraction of HDL (15.2 vs 18.6μmol/L; P <.001). Mean very low-density lipoprotein, LDL, and HDL particle size was significantly higher in patients with HF vs controls. All HDL-related differences from controls persisted after adjustment for New York Heart Association functional class or body mass index. We found strong negative correlations of known cardiac biomarkers (N-terminal pro-brain natriuretic peptide and interleukin-1 receptor-like 1) with total and small LDL and HDL fractions and HDL particle size. ConclusionsPatients with chronic HF significantly differ in their lipoprotein profile compared with unaffected controls. Further research is needed to better understand the pathogenic relevance of this difference.

Phytonutrients of Bitter Apricot Seeds Modulate Human Lipid Profile and LDL Subfractions in Adults with Elevated Cholesterol Levels.

The objective of the present study was to evaluate the effect of short-term consumption of bitter apricot seeds phytonutrients on cardiovascular risk factors with a special focus on LDL cholesterol subfractions using the Lipoprint system. A group of 34 adult volunteers (21 female/13 male) consumed 60 mg kg−1 of body weight of bitter apricot seeds daily for 42 days. Subjects were divided into two groups: one with normal cholesterol levels (NTC) and one with elevated total cholesterol levels (ETC). Blood serum levels of total cholesterol (T-C), low-density cholesterol (LDL-C), high-density cholesterol (HDL-C), and triglycerides (TG) did not change significantly (p > 0.05) in NTC group. However, there were significant decreasing of T-C (p ˂ 0.05) and LDL-C (p < 0.01) in ETC group. The LDL1, LDL2, and atherogenic LDL3−7 subfractions progressively decreased after 42 days of apricot seeds consumption in ETC group (p < 0.05). Apricot seeds consumption was associated with a significant increase in the mean LDL particle size especially in ETC group (p ˂ 0.01). The results of the present study support the hypothesis that daily consumption of bitter apricot seeds for 42 days positively modified the lipoprotein profile in the group with elevated total cholesterol.

Apolipoprotein F concentration, activity, and the properties of LDL controlling ApoF activation in hyperlipidemic plasma

Apolipoprotein F (ApoF) modulates lipoprotein metabolism by selectively inhibiting cholesteryl ester transfer protein activity on LDL. This ApoF activity requires that it is bound to LDL. How hyperlipidemia alters total plasma ApoF and its binding to LDL are poorly understood. In this study, total plasma ApoF and LDL-bound ApoF were quantified by ELISA (n = 200). Plasma ApoF was increased 31% in hypercholesterolemic plasma but decreased 20% in hypertriglyceridemia. However, in donors with combined hypercholesterolemia and hypertriglyceridemia, the elevated triglyceride ameliorated the rise in ApoF caused by hypercholesterolemia alone. Compared with normolipidemic LDL, hypercholesterolemic LDL contained ∼2-fold more ApoF per LDL particle, whereas ApoF bound to LDL in hypertriglyceridemia plasma was <20% of control. To understand the basis for altered association of ApoF with hyperlipidemic LDL, the physiochemical properties of LDL were modified in vitro by cholesteryl ester transfer protein ± LCAT activities. The time-dependent change in LDL lipid composition, proteome, core and surface lipid packing, LDL surface charge, and LDL size caused by these factors were compared with the ApoF binding capacity of these LDLs. Only LDL particle size correlated with ApoF binding capacity. This positive association between LDL size and ApoF content was confirmed in hyperlipidemic plasmas. Similarly, when in vitro produced and enlarged LDLs with elevated ApoF binding capacity were incubated with LPL to reduce their size, ApoF binding was reduced by 90%. Thus, plasma ApoF levels and the activation status of this ApoF are differentially altered by hypercholesterolemia and hypertriglyceridemia. LDL size is a key determinate of ApoF binding and activation.

Relationship between Adiposity, Low-Density Lipoprotein Particles Size and Cardiovascular Risk among Adult Obese Cameroonians

Relationship between Adiposity, Low-Density Lipoprotein Particles Size and Cardiovascular Risk among Adult Obese Cameroonians

Effects of a low-carbohydrate diet on insulin-resistant dyslipoproteinemia—a randomized controlled feeding trial

ABSTRACTBackgroundCarbohydrate restriction shows promise for diabetes, but concerns regarding high saturated fat content of low-carbohydrate diets limit widespread adoption.ObjectivesThis preplanned ancillary study aimed to determine how diets varying widely in carbohydrate and saturated fat affect cardiovascular disease (CVD) risk factors during weight-loss maintenance.MethodsAfter 10–14% weight loss on a run-in diet, 164 participants (70% female; BMI = 32.4 ± 4.8 kg/m2) were randomly assigned to 3 weight-loss maintenance diets for 20 wk. The prepared diets contained 20% protein and differed 3-fold in carbohydrate (Carb) and saturated fat as a proportion of energy (Low-Carb: 20% carbohydrate, 21% saturated fat; Moderate-Carb: 40%, 14%; High-Carb: 60%, 7%). Fasting plasma samples were collected prerandomization and at 20 wk. Lipoprotein insulin resistance (LPIR) score was calculated from triglyceride-rich, high-density, and low-density lipoprotein particle (TRL-P, HDL-P, LDL-P) sizes and subfraction concentrations (large/very large TRL-P, large HDL-P, small LDL-P). Other outcomes included lipoprotein(a), triglycerides, HDL cholesterol, LDL cholesterol, adiponectin, and inflammatory markers. Repeated measures ANOVA was used for intention-to-treat analysis.ResultsRetention was 90%. Mean change in LPIR (scale 0–100) differed by diet in a dose-dependent fashion: Low-Carb (–5.3; 95% CI: –9.2, –1.5), Moderate-Carb (–0.02; 95% CI: –4.1, 4.1), High-Carb (3.6; 95% CI: –0.6, 7.7), P = 0.009. Low-Carb also favorably affected lipoprotein(a) [–14.7% (95% CI: –19.5, –9.5), –2.1 (95% CI: –8.2, 4.3), and 0.2 (95% CI: –6.0, 6.8), respectively; P = 0.0005], triglycerides, HDL cholesterol, large/very large TRL-P, large HDL-P, and adiponectin. LDL cholesterol, LDL-P, and inflammatory markers did not differ by diet.ConclusionsA low-carbohydrate diet, high in saturated fat, improved insulin-resistant dyslipoproteinemia and lipoprotein(a), without adverse effect on LDL cholesterol. Carbohydrate restriction might lower CVD risk independently of body weight, a possibility that warrants study in major multicentered trials powered on hard outcomes. The registry is available through ClinicialTrials.gov: https://clinicaltrials.gov/ct2/show/NCT02068885.

Moderate Alcohol Consumption and Lipoprotein Subfractions: A Systematic Review of Intervention and Observational Studies

<h3>Lead Author's Financial Disclosures</h3> T.W. has received a Ph.D. scholarship partly sponsored by Carlsberg Foundation Semper Ardens grant Remaining Ph.D. scholarship sponsored by National Institute of Alcohol Abuse and Alcoholism (NIAAA). <h3>Study Funding</h3> Ph.D. scholarship sponsored in part by a Carlsberg Foundation Semper Ardens grant on biomarkers to L.O.D., and in part by National Institute of Alcohol Abuse and Alcoholism [grant number U10AA025286 to L.O.D.]. <h3>Background/Synopsis</h3> Moderate alcohol consumption is associated with decreased risk of cardiovascular disease and improvement in cardiovascular risk markers, including lipoproteins1, 2, and lipoprotein subfractions. Changes in lipoprotein subclasses could mediate the potential beneficial effects of moderate drinking on cardiovascular health. <h3>Objective/Purpose</h3> This study aimed to systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms. Secondarily, to investigate whether results differed by study design and subject health status. <h3>Methods</h3> The review followed the PRISMA guidelines. Studies with alcohol intake at doses up to 60 g/d were included from nine scientific databases. Lipoprotein subfractions and related mechanisms were examined. Eligible studies were human and ex vivo studies in all kinds of study designs, populations, and publication years. The last search was performed in March 2021, and clinicaltrials.gov was screened for unpublished literature. Risk of bias was assessed with The Cochrane Collaboration tool for assessing the risk of bias, The Risk of Bias Assessment tool for non-randomized Studies, and The JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies. <h3>Results</h3> We included 37 intervention trials and 77 observational studies with a total of 20,510 and 104,773 participants, respectively. Most intervention studies provided an alcohol dose between 20 to 40 g per day. Alcohol intake was positively related to all HDL subfractions measured, independent of study design. Studies on the effects of alcohol on LDL and VLDL subfractions were limited, especially intervention studies. However, some studies of varying design found lower levels of small LDL particles, increased LDL particle size, and complex, non-linear relationships to apoB-containing particles. Hypothesis generating results on the associations of alcohol with lipoprotein subfractions defined by the content of the pro-atherogenic apoC-III were also identified. As for the mechanisms investigated, cholesterol efflux capacity and paraoxonase activity were consistently increased. Most studies included healthy subjects or populations of mixed health status. Several studies were graded to have unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies. <h3>Conclusions</h3> Alcohol intake in doses up to 60 g/day can cause changes in lipoprotein subfractions, such as increased HDL subfractions and decreased smaller LDL particles, which may relate to cardiovascular health. Future studies should investigate effects on apoB-containing lipoproteins and novel biomarkers such as HDL subfractions defined by apolipoproteins like apoC-III. This review is registered at http://www.crd.york.ac.uk/prospero/, no.: 98955.

Moderate alcohol consumption and lipoprotein subfractions: a systematic review of intervention and observational studies.

Moderate alcohol consumption is associated with decreased risk of cardiovascular disease (CVD) and improvement in cardiovascular risk markers, including lipoproteins and lipoprotein subfractions. To systematically review the relationship between moderate alcohol intake, lipoprotein subfractions, and related mechanisms. Following PRISMA, all human and ex vivo studies with an alcohol intake up to 60 g/d were included from 8 databases. A total of 17 478 studies were screened, and data were extracted from 37 intervention and 77 observational studies. Alcohol intake was positively associated with all HDL subfractions. A few studies found lower levels of small LDLs, increased average LDL particle size, and nonlinear relationships to apolipoprotein B-containing lipoproteins. Cholesterol efflux capacity and paraoxonase activity were consistently increased. Several studies had unclear or high risk of bias, and heterogeneous laboratory methods restricted comparability between studies. Up to 60 g/d alcohol can cause changes in lipoprotein subfractions and related mechanisms that could influence cardiovascular health. PROSPERO registration no. 98955.

Abstract 13992: Cardiovascular Disease Risk of Abnormal Glucose Tolerance Depends on Etiology: Insulin Resistance versus Beta-Cell Failure

Background: Cardiovascular disease (CVD) and abnormal glucose tolerance (Abnl-GT) are rapidly increasing in sub-Saharan Africa. Abnl-GT is a primary risk factor for CVD. Yet, different Abnl-GT etiologies, insulin resistance (IR) or β-cell failure, may have different CVD risk profiles. Therefore, in 493 African-born Blacks living in the United States [male: 64%, age: 38±10y (mean±SD)], we evaluated the CVD risk profile within each Abnl-GT etiology. Methods: OGTT were performed. Abnl-GT, a term combining diabetes and prediabetes, was defined as fasting plasma glucose (FPG)≥100 mg/dL and/or glucose at 2h≥140 mg/dL. IR was defined by the upper quartile of HOMA-IR (≥2.03). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Fasting lipids, including high-density lipoprotein (HDL), low-density lipoprotein (LDL) particle sizes, were measured. Dyslipidemia was defined as total cholesterol, TC&gt;200mg/dL, LDL&gt;130mg/dL, HDL&lt;35mg/dL and triglycerides, TG&gt;150mg/dL or any combination thereof. CVD risk was determined by the Pooled-Cohort Equation (PCE) [age, TC, HDL, SBP, diabetes, smoking status], as developed in the ARIC cohort. Results: Abnl-GT occurred in 37% (183/493) of participants, with Abnl-GT due to IR in 28% (69/183) and β-cell-failure in 62% (114/183). Neither systolic nor diastolic BP differed between the Abnl-GT groups (both P &gt;0.05). HDL, HDL-size and LDL-size were lower and TG higher in the IR group compared to the β-cell-failure group (all P &lt;0.01). The prevalence of dyslipidemia was higher in the IR than the β-cell-failure group at 49% (34/69) vs 28% (32/114) ( P &lt;0.05). The IR had a higher PCE score versus the β-cell failure group [26.5±2.7 vs 18.8.0±1.9 ( P =0.001)]. Conclusions: Although IR was a less common cause of Abnl-GT than β-cell failure, the IR group had a more adverse lipid profile and therefore a higher CVD risk compared to the β-cell failure group. Thus, the etiology of Abnl-GT should be taken into account when developing treatment strategies for patients at higher CVD risk.

1H-magnetic resonance spectroscopy lipoprotein profile in patients with chronic heart failure versus matched controls

Introduction and objectivesAdvanced lipoprotein phenotyping is a better predictor of atherosclerotic cardiovascular risk than cholesterol concentration alone. Lipoprotein profiling in heart failure (HF) is incompletely characterized. We aimed to describe the lipoprotein profile in patients with chronic HF compared with a matched control population. MethodsThis cross-sectional study was performed from May 2006 to April 2014 and included ambulatory patients with chronic HF. Lipid concentrations and the size of main lipoprotein fractions (high-density lipoprotein [HDL], low-density lipoprotein [LDL], and very low-density lipoprotein) and the particle concentration of their 3 subfractions (large, medium and small) were assessed using 1H magnetic resonance spectroscopy. ResultsThe 429 included patients with chronic HF were compared with 428 matched controls. Patients with chronic HF had lower total cholesterol and lower mean LDL (1115 vs 1352 nmol/L; P<.001) and HDL (25.7 vs 27.9μmol/L; P <.001) particle concentrations, with this last difference being mediated by a significantly lower concentration of the small subfraction of HDL (15.2 vs 18.6μmol/L; P <.001). Mean very low-density lipoprotein, LDL, and HDL particle size was significantly higher in patients with HF vs controls. All HDL-related differences from controls persisted after adjustment for New York Heart Association functional class or body mass index. We found strong negative correlations of known cardiac biomarkers (N-terminal pro-brain natriuretic peptide and interleukin-1 receptor-like 1) with total and small LDL and HDL fractions and HDL particle size. ConclusionsPatients with chronic HF significantly differ in their lipoprotein profile compared with unaffected controls. Further research is needed to better understand the pathogenic relevance of this difference.

Effect of carbohydrate-restricted dietary interventions on LDL particle size and number in adults in the context of weight loss or weight maintenance: a systematic review and meta-analysis

LDL particle size and number (LDL-P) are emerging lipid risk factors. Nonsystematic reviews have suggested that diets lower in carbohydrates and higher in fats may result in increased LDL particle size when compared with higher-carbohydrate diets. This study aimed to systematically review available evidence and conduct meta-analyses of studies addressing the association of carbohydrate restriction with LDL particle size and LDL-P. We searched 6 electronic databases on 4 January, 2021 for randomized trials of any length that reported on dietary carbohydrate restriction (intervention) compared with higher carbohydrate intake (control). We calculated standardized mean differences (SMDs) in LDL particle size and LDL-P between the intervention and control groups of eligible studies, and pooled effect sizes using random-effects models. We performed prespecified subgroup analyses and examined the effect of potential explanatory factors. Internal validity and publication bias were assessed using Cochrane's risk-of-bias tool and funnel plots, respectively. Studies that could not be meta-analyzed were summarized qualitatively. This review summarizes findings from 38 randomized trials including a total of 1785 participants. Carbohydrate-restricted dietary interventions were associated with an increase in LDL peak particle size (SMD=0.50; 95% CI: 0.15, 0.86; P<0.01) and a reduction in LDL-P (SMD = -0.24; 95% CI: -0.43, -0.06; P=0.02). The effect of carbohydrate-restricted dietary interventions on LDL peak particle size appeared to be partially explained by differences in weight loss between intervention groups and exploratory analysis revealed a shift from small dense to larger LDL subclasses. No statistically significant association was found between carbohydrate-restricted dietary interventions and mean LDL particle size (SMD=0.20; 95% CI: -0.29, 0.69; P=0.37). The available evidence indicates that dietary interventions restricted in carbohydrates increase LDL peak particle size and decrease the numbers of total and small LDL particles.This review was registered at www.crd.york.ac.uk/prospero/ as CRD42020188745.

Beta-cell failure rather than insulin resistance is the major cause of abnormal glucose tolerance in Africans: insight from the Africans in America study

IntroductionUncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of...

Triglyceride-rich lipoprotein and LDL particle subfractions and their association with incident type 2 diabetes: the PREVEND study

BackgroundTriglyceride-rich lipoproteins particles (TRLP) and low density lipoprotein particles (LDLP) vary in size. Their association with β-cell function is not well described. We determined associations of TRLP and LDLP subfractions with β-cell function, estimated as HOMA-β, and evaluated their associations with incident T2D in the general population.MethodsWe included 4818 subjects of the Prevention of Renal and Vascular End-Stage Disease (PREVEND) study without T2D at baseline. TRLP and LDLP subfraction concentrations and their average sizes were measured using the LP4 algorithm of the Vantera nuclear magnetic resonance platform. HOMA-IR was used as measure of insulin resistance. HOMA-β was used as a proxy of β-cell function.ResultsIn subjects without T2D at baseline, very large TRLP, and LDL size were inversely associated with HOMA-β, whereas large TRLP were positively associated with HOMA-β when taking account of HOMA-IR. During a median follow-up of 7.3 years, 263 participants developed T2D. In multivariable-adjusted Cox regression models, higher concentrations of total, very large, large, and very small TRLP (reflecting remnants lipoproteins) and greater TRL size were associated with an increased T2D risk after adjustment for relevant covariates, including age, sex, BMI, HDL-C, HOMA-β, and HOMA-IR. On the contrary, higher concentrations of large LDLP and greater LDL size were associated with a lower risk of developing T2D.ConclusionsSpecific TRL and LDL particle characteristics are associated with β-cell function taking account of HOMA-IR. Moreover, TRL and LDL particle characteristics are differently associated with incident T2D, even when taking account of HOMA-β and HOMA-IR.

Association of Kidney Function With NMR-Quantified Lipids, Lipoproteins, and Metabolic Measures in Mexican Adults.

ContextChronic kidney disease (CKD) and diabetes are associated with dyslipidemia, metabolic abnormalities, and atherosclerotic risk. Nuclear magnetic resonance (NMR) spectroscopy provides much more detail on lipoproteins than traditional assays.MethodsIn about 38 000 participants from the Mexico City Prospective Study, aged 35 to 84 years and not using lipid-lowering medication, NMR spectroscopy quantified plasma concentrations of lipoprotein particles, their lipidic compositions, and other metabolic measures. Linear regression related low estimated glomerular filtration rate (eGFR; <60 mL/min/1.73 m2) to each NMR measure after adjustment for confounders and for multiplicity. Analyses were done separately for those with and without diabetes.ResultsAmong the 38 081 participants (mean age 52 years, 64% women), low eGFR was present for 4.8% (306/6403) of those with diabetes and 1.2% (365/31 678) of those without diabetes. Among both those with and without diabetes, low eGFR was significantly associated with higher levels of 58 NMR measures, including apolipoprotein B (Apo-B), the particle numbers of most Apo-B containing lipoproteins, the cholesterol and triglycerides carried in these lipoproteins, several fatty acids, total cholines and phosphatidylcholine, citrate, glutamine, phenylalanine, β-OH-butyrate, and the inflammatory measure glycoprotein-A, and significantly lower levels of 13 NMR measures, including medium and small high-density lipoprotein particle measures, very low-density lipoprotein particle size, the ratio of saturated:total fatty acids, valine, tyrosine, and aceto-acetate.ConclusionsIn this Mexican population with high levels of adiposity and diabetes, low kidney function was associated with widespread alterations in lipidic and metabolic profiles, both in those with and without diabetes. These alterations may help explain the higher atherosclerotic risk experienced by people with CKD.