LDL Particle Size Research Articles

The LDL-C/ApoB ratio predicts major cardiovascular events in patients with established atherosclerotic cardiovascular disease

Background and aimsThe low density lipoprotein cholesterol to Apolipoprotein B (LDL-C/ApoB) ratio is a validated proxy for low density lipoprotein (LDL) particle size that can be easily calculated from a standard lipid/apolipoprotein profile. Whether it is predictive of cardiovascular events in patients with established atherosclerosis is not known and is addressed in the present investigation. MethodsWe determined the LDL-C/ApoB ratio in a cohort of 1687 subjects with established atherosclerosis. Prospectively, major cardiovascular events (MACE) including cardiovascular death, non-fatal myocardial infarction and non-fatal stroke were recorded over a period of 9.9 ± 4.6 years. The study covers >16,000 patient-years. ResultsAt baseline, the LDL-C/ApoB ratio was 1.36 ± 0.28 in our cohort. During follow up, a total of 558 first MACE were recorded. The LDL-C/ApoB ratio predicted MACE in univariate Cox proportional hazard analysis (HR 0.90 [0.82–0.98]; p = 0.014); this finding was confirmed after adjustment for age, gender, intensity of statin treatment, hypertension, history of smoking, type 2 diabetes, body mass index and ApoB (HR 0.87 [0.78–0.97]; p = 0.013). ConclusionsThe LDL-C/ApoB ratio is independently predictive of MACE in subjects with established atherosclerosis.

Low-density lipoprotein cholesterol-to-apolipoprotein B ratio as a potential indicator of LDL particle size and plasma atherogenicity in type 2 diabetes

AimsAtherogenic dyslipidemia, associated with small, dense low-density lipoprotein-cholesterol (S-LDL) particles and impaired metabolism of triglycerides (TGs) and high-density lipoprotein-cholesterol (HDL-c), leads to the development of atherosclerosis-related complications of type 2 diabetes mellitus. Based on the hypothesis that an LDL-c-to-apolipoprotein B ratio (LDL/ApoB) < 1.2 may predict the prevalence of S-LDL, this study aimed to evaluate the LDL/ApoB ratio in patients with type 2 diabetes with moderately elevated TG levels. MethodsThe study population consisted of 121 outpatients with type 2 diabetes (S-LDL group, LDL/ApoB < 1.2, n = 79; L-LDL group, LDL/ApoB > 1.2, n = 42) and 58 healthy subjects. The LDL/ApoB ratio was calculated from the measured LDL-c and ApoB levels in participants with TG levels lower than 4.5 mmol/L. Since TGs and HDL-c are included in the atherogenic index of plasma (AIP), we evaluated the relationship between LDL/ApoB and the AIP. ResultsHigher levels of AIP, TG (both P < 0.0001), and lipid hydroperoxides (LOOH) (P < 0.001) and lower levels of HDL-c, total cholesterol, and non-HDL-c (P < 0.001, <0.01, <0.05, respectively) were found in the S-LDL group compared to the L-LDL group. There were significant relationships between the LDL/ApoB ratio and the AIP, TG (both P < 0.0001), LOOH (P < 0.0005), and HDL-c levels (P < 0.05) in the S-LDL group. ConclusionsThe prevalence of S-LDL particles (65%) and the close association of LDL/ApoB with the AIP suggest that this ratio may be a potential indicator of increased cardiovascular risk in patients with type 2 diabetes.

Clinical Importance of the LDL-C/Apolipoprotein B Ratio for Neointimal Formation after Everolimus-Eluting Stent Implantations.

Aims: Smaller low-density lipoprotein (LDL) particle size has been suggested to result in the development of endothelial dysfunction, atherosclerosis, and in-stent restenosis (ISR); however, little is known regarding the impact of the LDL particle size on the neointima formation leading to ISR after everolimus-eluting stent (EES) implantation. Methods: In this study, we have included 100 patients to examine the relationship between an LDL-C/apolipoprotein B (Apo B) ≤ 1.2, reportedly representing the LDL particle size, and the neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during the follow-up coronary angiography (CAG) period (8.8±2.5 months) after EES implantation. We divided them into two groups: LDL-C/Apo B ≤ 1.2 group (low LDL-C/Apo B group, n =53) and LDL-C/Apo B ＞1.2 group (high LDL-C/Apo B group, n =47). Results: The low LDL-C/Apo B group had a significantly larger neointimal volume (12.8±5.3 vs. 10.3±4.9 mm 3 , p =0.021) and lower incidence of a neointimal homogeneous pattern (71 vs. 89 %), higher incidence of a neointimal heterogeneous pattern (25 vs. 9 %) ( p =0.006) and higher prevalence of macrophage accumulation (9 vs. 2 %) ( p =0.030) as assessed via OCT, and, as per the CAS findings, a higher prevalence of yellow grade ≥ 2 (grade 2; adjusted residual: 2.94, grade 3; adjusted residual: 2.00, p =0.017) than the high LDL-C/Apo B group. Conclusions: A low LDL-C/Apo B ratio was found to be strongly associated with neointimal proliferation and neointimal instability evidenced chronically by OCT and CAS. An LDL-C/Apo B ≤ 1.2 will be of aid in terms of identifying high-risk patients after EES implantation.

Achievement of the Targets of the 20-Year Infancy-Onset Dietary Intervention-Association with Metabolic Profile from Childhood to Adulthood.

The Special Turku Coronary Risk Factor Intervention Project (STRIP) is a prospective infancy-onset randomized dietary intervention trial targeting dietary fat quality and cholesterol intake, and favoring consumption of vegetables, fruit, and whole-grains. Diet (food records) and circulating metabolites were studied at six time points between the ages of 9–19 years (n = 549–338). Dietary targets for this study were defined as (1) the ratio of saturated fat (SAFA) to monounsaturated and polyunsaturated fatty acids (MUFA + PUFA) < 1:2, (2) intake of SAFA < 10% of total energy intake, (3) fiber intake ≥ 80th age-specific percentile, and (4) sucrose intake ≤ 20th age-specific percentile. Metabolic biomarkers were quantified by high-throughput nuclear magnetic resonance metabolomics. Better adherence to the dietary targets, regardless of study group allocation, was assoiated with higher serum proportion of PUFAs, lower serum proportion of SAFAs, and a higher degree of unsaturation of fatty acids. Achieving ≥ 1 dietary target resulted in higher low-density lipoprotein (LDL) particle size, lower circulating LDL subclass lipid concentrations, and lower circulating lipid concentrations in medium and small high-density lipoprotein subclasses compared to meeting 0 targets. Attaining more dietary targets (≥2) was associated with a tendency to lower lipid concentrations of intermediate-density lipoprotein and very low-density lipoprotein subclasses. Thus, adherence to dietary targets is favorably associated with multiple circulating fatty acids and lipoprotein subclass lipid concentrations, indicative of better cardio-metabolic health.

The Relationship between Daily Fructose Consumption and Oxidized Low-Density Lipoprotein and Low-Density Lipoprotein Particle Size in Children with Obesity.

PurposeObesity has become a very significant health problem in childhood. Fructose taken in an uncontrolled manner and consumed in excessive amounts is rapidly metabolized in the body and gets converted into fatty acids. This single center prospective case-control study aims to investigate the relationship between fructose consumption and obesity and the role of fructose consumption in development of atherosclerotic diseases.MethodsA total of 40 obese and 40 healthy children who were of similar ages (between 8 and 18 years) and sexes were included in the study. In the patient and control groups, the urine fructose levels, as well as the levels of oxidized low-density lipoprotein (LDL), small dense LDL, Apolipoprotein A and Apolipoprotein B values, which have been shown to play a role in development of atherosclerotic diseases, were measured.ResultsThe levels of oxidized LDL and small dense LDL and the ratio of Apolipoprotein A/Apolipoprotein B were found to be significantly higher in the patient group.ConclusionWe found that urinary fructose levels were higher in the obese children than the healthy children. Our results suggest that overconsumption of fructose in children triggers atherogenic diseases by increasing the levels of small dense LDL and oxidized LDL and the ratio of Apolipoprotein B/Apolipoprotein A.

LDL-particle size is a predictor of cardiovascular events in cardiovascular disease patients with nonalcoholic fatty-liver disease as well as in those without nonalcoholic fatty-liver disease

Background and Aims: Nonalcoholic fatty liver disease (NAFLD) is associated with atherogenic dyslipidemia, in particular with a small LDL particle size. However, there are no data on the association between LDL particle size and cardiovascular events in cardiovascular disease patients with NAFLD. This issue is addressed in the present study.

Novel plasma biomarkers improve discrimination of metabolic health independent of weight

We sought to determine if novel plasma biomarkers improve traditionally defined metabolic health (MH) in predicting risk of cardiovascular disease (CVD) events irrespective of weight. Poor MH was defined in CATHGEN biorepository participants (n > 9300), a follow-up cohort (> 5600 days) comprising participants undergoing evaluation for possible ischemic heart disease. Lipoprotein subparticles, lipoprotein-insulin resistance (LP-IR), and GlycA were measured using NMR spectroscopy (n = 8385), while acylcarnitines and amino acids were measured using flow-injection, tandem mass spectrometry (n = 3592). Multivariable Cox proportional hazards models determined association of poor MH and plasma biomarkers with time-to-all-cause mortality or incident myocardial infarction. Low-density lipoprotein particle size and high-density lipoprotein, small and medium particle size (HMSP), GlycA, LP-IR, short-chain dicarboxylacylcarnitines (SCDA), and branched-chain amino acid plasma biomarkers were independently associated with CVD events after adjustment for traditionally defined MH in the overall cohort (p = 3.3 × 10−4–3.6 × 10−123), as well as within most of the individual BMI categories (p = 8.1 × 10−3–1.4 × 10−49). LP-IR, GlycA, HMSP, and SCDA improved metrics of model fit analyses beyond that of traditionally defined MH. We found that LP-IR, GlycA, HMSP, and SCDA improve traditionally defined MH models in prediction of adverse CVD events irrespective of BMI.

Abstract 13420: The LDL/apolipoprotein B Ratio Which is an Index for LDL Particle Size is a Strong Predictor for Neointimal Characteristics and In-stent Restenosis After Everolimus-eluting Stent Implantation

Introduction: The smaller size of LDL particle has suggested the development of endothelial dysfunction, atherosclerosis and in-stent restenosis (ISR), but little is known regarding the impact of LDL particle size on neointimal formation leading to ISR. Hypothesis: The LDL-C/Apolipoprotein B (Apo B) ratio &amp;lt; 1.2 has been reported to indirectly represent a high proportion of sdLDL. It was hypothesized that in-stent neointimal proliferation in LDL/ApoB &amp;lt; 1.2 patients may be excessive and unstable. Methods: In 135 patients, we investigated the relationship between the LDL particle size and neointimal characteristics using optical coherence tomography (OCT) and coronary angioscopy (CAS) during follow-up angiography after stent implantation. Results: ISR was identified in 35 patients, who had a significantly lower LDL/ApoB ratio (0.99±0.25 vs. 1.17±0.25; p &amp;lt; 0.01) and higher proportion of yellow grade 2 and 3 by CAS than non-ISR group (n=100). Among the non-ISR group, LDL/ApoB &amp;lt; 1.2 group (n=59) had a significantly larger neointimal volume by OCT, and higher proportion of yellow grade 2 and 3 by CAS compared with LDL/ApoB &amp;gt; 1.2 group (n=41) (Figure). Conclusions: Smaller size of LDL strongly associated with the neointimal proliferation, the neointimal instability and ISR evidenced by multimodalities, suggesting that smaller ratio of LDL/ApoB could be a surrogate marker for the neointimal characteristics after stent implantation.

Pasta Supplemented with Opuntia ficus-indica Extract Improves Metabolic Parameters and Reduces Atherogenic Small Dense Low-Density Lipoproteins in Patients with Risk Factors for the Metabolic Syndrome: A Four-Week Intervention Study.

Food supplementation with Opuntia ficus-indica (OFI) has been associated with a significant reduction in total cholesterol, body fat, hyperglycemia and blood pressure. Since OFI may also have antioxidant and anti-atherogenic properties, we hypothesized that its supplementation might reduce atherogenic lipoproteins, including small, dense low-density lipoproteins (sdLDL). Forty-nine patients (13 men and 36 women, mean age: 56 ± 5 years) with one or two criteria for the metabolic syndrome weekly consumed 500 g of pasta supplemented with 3% OFI extract (30% of insoluble polysaccharides with high antioxidant power) for 1 month. The full LDL subclass profile was assessed by gel electrophoresis (Lipoprint, Quantimetrix, Redondo Beach, CA, USA). After 1 month of pasta supplementation, waist circumference (p = 0.0297), plasma glucose (p < 0.0001), triglycerides (p = 0.0137), plasma creatinine (p = 0.0244), urea and aspartate transaminase (p < 0.0001 for each) significantly decreased. A percentage increase in larger, less atherogenic LDL-1 (p = 0.0002), with a concomitant reduction in smaller, denser LDL-2 (p < 0.0001) and LDL-3 (p = 0.0004), were found. LDL-4 and-5 decreased, although not significantly. This is the first intervention study suggesting that pasta enriched with an OFI extract may have beneficial effects on some metabolic parameters and the LDL particle sizes, reducing atherogenic sdLDL. Future studies will help to establish if these findings impact cardiovascular outcomes.

Identification of a TMEM182 rs141764639 polymorphism associated with central obesity by regulating tumor necrosis factor-α in a Korean population.

To investigate the effect of a single nucleotide polymorphism (SNP) in transmembrane protein 182 (TMEM182) on the risk of having central obesity and the related phenotype. In total, 2141 subjects with central obesity (n = 827) and normal controls (n = 1314) were included. The most strongly associated SNPs were related to waist circumference, and one SNP, rs141764639, was identified in TMEM182 (p = 7.30E-06, q = 0.0326). The TC genotype was associated with more central obesity; higher levels of blood pressure, glucose-related parameters, and inflammatory markers; abnormal lipid profiles; and smaller LDL particle sizes than the major allele homozygotes in the total population. TNF-α in the TC genotype showed extremely high levels compared to the TT genotype. There were significant interactions between the genotypes and waist circumference in relation to LDL particle size, TNF-α level, and IL-6 level. Compared with the reference group, the odds ratio for central obesity in C allele carriers was significantly increased by 2-fold. The polymorphism of TMEM182 rs141764639 might have an effect on the incidence of central obesity in the Korean population by interacting with the upregulation of TNF-α, a proinflammatory cytokine. Moreover, LDL particle size, which is an atherogenic lipid profile trait, was associated with the TMEM182 rs141764639 genotype.

Lipids, biomarkers, and subclinical atherosclerosis in treatment-naive HIV patients starting or not starting antiretroviral therapy: Comparison with a healthy control group in a 2-year prospective study.

ObjectiveTo assess the effect of HIV infection and combined antiretroviral therapy (c-ART) on various proatherogenic biomarkers and lipids and to investigate their relationship with subclinical atherosclerosis in a cohort of treatment-naive HIV-infected patients.MethodsWe performed a prospective, comparative, multicenter study of 2 groups of treatment-naive HIV-infected patients (group A, CD4>500 cells/μL, not starting c-ART; and group B, CD4<500 cells/μL, starting c-ART at baseline) and a healthy control group. Laboratory analyses and carotid ultrasound were performed at baseline and at months 12 and 24. The parameters measured were low-density lipoprotein (LDL) particle phenotype, lipoprotein-associated phospholipase A2 (Lp-PLA2), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP), sCD14, sCD163, monocyte chemoattractant protein-1(MCP-1), and asymmetric dimethylarginine (ADMA). A linear mixed model based on patient clusters was used to assess differences in biomarkers between the study groups and over time.ResultsThe study population comprised 62 HIV-infected patients (group A, n = 31; group B, n = 31) and 22 controls. Age was 37 (30–43) years, and 81% were men. At baseline, the HIV-infected patients had a worse LDL particle phenotype and higher plasma concentration of sCD14, sCD163, hs-CRP, and LDL-Lp-PLA2 than the controls. At month 12, there was an increase in total cholesterol (p = 0.002), HDL-c (p = 0.003), and Apo A-I (p = 0.049) and a decrease in sCD14 (p = <0.001) and sCD163 (p<0.001), although only in group B. LDL particle size increased in group B at month 24 (p = 0.038). No changes were observed in group A or in the healthy controls. Common carotid intima-media thickness increased in HIV-infected patients at month 24 (Group A p = 0.053; group B p = 0.048). Plasma levels of sCD14, sCD163, and hs-CRP correlated with lipid values.ConclusionsIn treatment-naive HIV-infected patients, initiation of c-ART was associated with an improvement in LDL particle phenotype and inflammatory/immune biomarkers, reaching values similar to those of the controls. HIV infection was associated with progression of carotid intima-media thickness.

Maternal hypercholesterolemia programs dyslipidemia in adult male mouse progeny.

As a collection of metabolic abnormalities including inflammation, insulin resistance, hypertension, hormone imbalance, and dyslipidemia, maternal obesity has been well-documented to program disease risk in adult offspring. Although hypercholesterolemia is strongly associated with obesity, less work has examined the programming influence of maternal hypercholesterolemia (MHC) independent of maternal obesity or high-fat feeding. This study was conducted to characterize how MHC per se impacts lipid metabolism in offspring. Female (n = 6/group) C57BL/6J mice were randomly assigned to: (1.) a standard chow diet (Control, CON) or (2.) the CON diet supplemented with exogenous cholesterol (CH) (0.15%, w/w) throughout mating and the gestation and lactation periods. At weaning (postnatal day (PND) 21) and adulthood (PND 84), male offspring were characterized for blood lipid and lipoprotein profile and hepatic lipid endpoints, namely cholesterol and triglyceride (TG) accumulation, fatty acid profile, TG production, and mRNA expression of lipid-regulatory genes. Both newly weaned and adult offspring from CH mothers demonstrated increased very low-density lipoprotein (VLDL) particle number and size and hepatic TG and n-6 polyunsaturated fatty acid accumulation. Further, adult CH offspring exhibited reduced fatty acid synthase (Fasn) and increased diglyceride acyltransferase (Dgat1) mRNA expression. These programming effects appear to be independent of changes in hepatic TG production and postprandial lipid clearance. Study results suggest that MHC, independent of obesity or high-fat feeding, can induce early changes to serum VLDL distribution and hepatic lipid profile that persist into adulthood.

59-OR: Lipoprotein Particle Distribution by NMR in Youth with Type 2 Diabetes (T2D) in the TODAY Study

T2D in adolescents is associated with an unfavorable lipid profile, but data on lipoprotein particle size and distribution in this population have yet to be published. The TODAY Study, a randomized treatment trial of T2D in youth, provided the opportunity to evaluate lipoprotein particle distribution and relate lipoprotein particle number and size to HbA1C, need for insulin treatment, gender, race/ethnicity, BMI, and blood pressure (BP). TODAY participants (n=348) with yearly samples available for NMR Lipoprofile assessments (baseline, 12, 24, 36 mos) were included. Baseline participant characteristics (mean±SD) were: age 13.7±2.0 yrs; BMI 34.3±7.6 kg/m2; 62.4% female; 20.7% White, 32.2% Non-Hispanic Black (NHB), 43.7% Hispanic. Analysis demonstrated increasing numbers of LDL, HDL, and VLDL particles over the three yrs (all ps&amp;lt;0.0001) with somewhat weaker trends for decreasing particle size (LDL p=0.0009, HDL p=0.02). HbA1c showed a strong positive correlation with LDL, VLDL, and HDL particle number (all ps&amp;lt;0.005). HbA1c was negatively associated with LDL (p&amp;lt;0.0001) and HDL size (p=0.001) but positively associated with VLDL size (p&amp;lt;0.0001). Need for insulin treatment did not impact these associations. Female subjects had larger HDL particle size than males at baseline (p=0.0004) and throughout (p&amp;lt;0.0001). NHBs had the largest LDL and HDL particle size and smallest VLDL particle size. BMI% and BP showed positive association with LDL, HDL, and VLDL particle numbers but negative association with LDL and HDL size. The preponderance of lipoprotein parameters were strongly associated with TG/HDL ratio and non-HDL-C after adjusting for baseline age, race, gender, BMI%, BP, and need for insulin treatment (p&amp;lt;0.0001). In conclusion, these data demonstrate an atherogenic lipoprotein phenotype in youth with T2D and strong relationships with glycemic control and other cardiac risk factors. Concern regarding premature development of atherosclerosis in youth with T2D is warranted. Disclosure L.E. Katz: None. J.D. Otvos: Employee; Self; LabCorp. K. Drews: None. B. Tesfaldet: None. F. Bacha: Research Support; Self; AstraZeneca, Takeda Development Center Americas, Inc. S.M. Willi: Advisory Panel; Self; Boehringer Ingelheim International GmbH. Research Support; Self; Eli Lilly and Company, Janssen Pharmaceuticals, Inc., Tolerion, Inc. Other Relationship; Self; Caladrius Biosciences, Inc. S.M. Marcovina: None. S. Mckay: None. R.S. Weinstock: Board Member; Self; JDRF. Consultant; Self; Insulogic LLC. Research Support; Self; Boehringer Ingelheim International GmbH, Diasome Pharmaceuticals, Inc., Eli Lilly and Company, Insulet Corporation, Jaeb Center for Health Research, Kowa Research Institute, Inc., Medtronic, Tolerion, Inc. Funding National Institute of Diabetes and Digestive and Kidney Diseases (U01DK61212)

An Algorithmic Approach for Lipid Metabolism and Management of Patients with Xanthelasma Palpebrarum (XP)

Abstract Objectives XP (flat, yellowish plaques around the eyes) is difficult to treat and often recurs. We describe an algorithmic approach to explore the lipid metabolism and management of XP. Methods A 64 yo female with hypothyroidism, obesity, and metabolic syndrome was successful with weight loss and glycemia but noted recurrence of XP after a surgical excision. Her lipid profile (on rosuvastatin) revealed: total cholesterol 150 mg/dL, LDL 54 mg/dL, triglycerides 74 mg/dL, HDL 81 mg/dL. Apolipoprotein (Apo) A1 was 213 mg/dL (nl female &amp;gt; 140). Apo B100 was 63 mg/dL (nl &amp;lt; 130). Lp(a) was 29 mg/dL (nl &amp;lt; 30). LDL particles were 958 nmol/L (nl &amp;lt; 1000). LDL particle size was 20.9 nm (nl &amp;gt; 20.5). Small dense LDL particles were 598 nmol/L (nl &amp;lt; 528). There was presence of serum campesterol (3.7 mg/L; nl 0–7.0) and sitosterol (2.1 mg/L; nl 0–5.0), but not desmosterol or lathosterol. Oral ezetimibe (EZ), 10 mg/day was administered. After 8 months of therapy, campesterol and sitosterol dropped significantly (campesterol: 2.1, - 44%; sitosterol: 1.3, - 39%). XP lesions resolved completely. Results We developed an algorithmic approach to XP management. The sequence is as follows: 1) examine standard lipid levels, 2) examine levels of pro-atherogenic particles, 3) explore net cholesterol tissue transport, 4) confirm hepatic cholesterol synthesis suppression, 5) examine plant sterols, 6) treat the abnormalities detected. In this example case phytosterols were responsible for XP recurrence. Sitosterol and campesterol should be minimally absorbed by the gut through the Nieman Pick C1 Like 1 (NPC1L1) sterol influx transporter and eliminated by the sterol efflux transporters, adenosine triphosphate-binding cassette (ABC) ABCG5/ABCG8. If phytosterols are retained in the body, they may predispose to resistant XP. An algorithmic approach to XP suggested that hyper-absorption of plant sterols by the NPC1L1 transporter was present. This was clinically confirmed because inhibition of NPC1L1 transport (by EZ) significantly reduced plant sterol levels. Plant sterols were also clinically confirmed as the cause of her XP, since their reduction and led to XP resolution. Conclusions We present an algorithmic approach to help detail the metabolic etiology of XP and direct its management. The example case demonstrates its value to reduce XP recurrence and resolve XP in selected cases. Funding Sources None.

Effects of a Low-Carbohydrate Diet on Cardiometabolic Risk Factors During Weight-Loss Maintenance: A Randomized Controlled Feeding Trial

Abstract Objectives To compare effects of diets varying in carbohydrate (carb) and fat on plasma lipids and lipoprotein subfractions. Methods Participants (N = 164, 70% female, 18–65 y, BMI ≥ 25 kg/m2) achieved 10–14% weight loss on a run-in diet and then were randomized to 3 test diets for 20 weeks of weight-loss maintenance. Percentages of total energy from carb-fat-protein for high-, moderate-, and low-carb diets were 60-20-20 (HI), 40-40-20 (MOD), and 20–60-20 (LO). Relative amounts of added sugar (15% total carb) and saturated fat (35% total fat) were fixed across diets. Plasma was collected at START (post-weight loss) and END of trial. The primary outcome for this ancillary study was lipoprotein insulin resistance (LPIR) – a 6-component weighted score of 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) (NMR spectroscopy, LabCorp). Other outcomes included large LDL-P concentration, triglycerides (TG), and cholesterol (HDL-C, LDL-C). Means (±SE) and END–START changes (mean [95% CI]) were constructed and compared from repeated measures ANOVA. Results Retention was 90% and 147 participants provided evaluable data, with no difference in body weight by diet after randomization. LPIR was 32.6 ± 1.5 at START. Change in LPIR differed by diet (P = 0.009): LO (−5.3 [−9.2, −1.5]), MOD (−0.02 [−4.1, 4.1]), HI (3.6 [−0.6, 7.7]). Diet effects favoring LO compared to HI were observed for large/very large TRL-P (P = 0.005), large HDL-P (P = 0.045), TG (P = 0.006), and HDL-C (P = 0.04). There were no mean differences between diets for particle sizes, LDL-P subfraction concentrations, and LDL-C (START: 79.3 ± 1.8 mg/dL; END–START: HI, 8.2 [4.2, 12.2]; MOD, 11.7 [7.8, 15.7]; LO, 10.0 [6.3, 13.7]). Conclusions With 3-fold higher saturated fat content (21% vs 7% total energy), a low- vs high-carb diet improved LPIR, a biomarker of diabetes risk, and several other components of the metabolic syndrome, with no adverse effects on LDL-P or LDL-C. These results from a large feeding study suggest that carb restriction may help prevent cardiometabolic disease independent of body weight. Funding Sources Nutrition Science Initiative (gifts from Arnold Ventures and Robert Lloyd Corkin Charitable Foundation), New Balance Foundation, Many Voices Foundation, Blue Cross Blue Shield.

2019 ESC Guidelines on diabetes, pre-diabetes, and cardiovascular diseases developed in collaboration with the EASD: The Task Force for diabetes, pre-diabetes, and cardiovascular diseases of the European Society of Cardiology (ESC) and the European Association for the Study of Diabetes (EASD)

It has been demonstrated that diabetic dyslipidaemia is the chief bridge between diabetes and incremental risk of cardiovascular disease in patients with diabetes. However, the characteristics of lipoprotein subfractions distribution in patients with type 2 diabetes (T2D) have not been fully investigated. The aim of present study was to evaluate the distributions of lipoprotein subfractions in T2D patients.A total of 920 patients, who have not received lipid-lowering drug treatment previously, were consecutively enrolled in this study. Based on the evidence of diabetes, patients were divided into T2D group (n=204) and non-T2D group (n=716). Both low- and high-density lipoprotein cholesterol (LDL- and HDL-C) subfractions were analysed using the Quantimetrix Lipoprint System. The distributions of lipoprotein subfractions were evaluated in patients with and without T2D.Compared with non-T2D individuals, the T2D group manifested significantly lower large HDL-C concentration/HDL subfraction percentage, smaller mean LDL particle size but higher small HDL-C and LDL-C concentrations as well as small HDL and LDL subfraction percentages. Moreover, the data indicated that the small HDL-C/ LDL-C concentrations, the small and large HDL subfraction percentages along with the mean LDL particle size were independently related to the existence of T2D (95% CI=1.009–1.067, p=0.009; 95% CI=0.938-0.983, p=0.001; 95% CI=1.023–1.135, p=0.005; 95% CI= 1.005–1.048, p=0.014; 95% CI=0.940-0.999, p=0.040; respectively) assessed by logistic regression analysis.The present study indicated that the changes of lipid profile in patients with T2D are characterised by abnormal distributions of lipoprotein subfractions apart from clinically atherogenic dyslipidaemia.

2D Diffusion-Ordered 1 H-NMR Spectroscopy Lipidomic Profiling after Oral Single Macronutrient Loads: Influence of Obesity, Sex, and Female Androgen Excess.

Postprandial dysmetabolism plays a major role in the pathogenesis of metabolic disorders such as obesity and the polycystic ovary syndrome (PCOS). The aim is to characterize the circulating lipoprotein particle profiles in response to oral glucose, lipid, and protein challenges. 17 women with PCOS, 17 control women, and 19 healthy men selected to have similar age and body mass index are studied. Blood samples are collected following the ingestion of 300kcal in the form of glucose, lipids, or proteins, and they are submitted to two-dimensional (2D) diffusion-ordered 1 H-NMR spectroscopy. Regardless of macronutrient administered, the number of very low-density (VLDL) particles increases whereas low density-lipoprotein (LDL) decreases. High density-lipoprotein (HDL) particles increase only after lipid ingestion. Obese subjects show an increase in the number of large VLDL particles and a decrease in large LDL particles, with a significant reduction in the average particle size of LDL. Patients with PCOS show a particularly unfavorably smaller LDL particle size response to oral lipid intake, regardless of obesity. Oral macronutrient challenges induce immediate class-specific postprandial changes in particle number and size of lipoproteins, with lipids inducing a more pro-atherogenic lipoprotein profile compared to glucose and proteins, particularly in obese subjects and women with PCOS.

Precipitated sdLDL: An easy method to estimate LDL particle size.

BackgroundLDL‐C lowering is the main measure in cardiovascular disease prevention but a residual risk of ischemic events still remains. Alterations of lipoproteins, specially, increase in small dense LDL (sdLDL) particles are related to this risk.ObjectiveTo investigate the potential use of sdLDL cholesterol concentration (sdLDL‐C) isolated by an easy precipitation method and to assess the impact of a set of clinical and biochemical variables determined by NMR on sdLDL concentration.MethodssdLDL‐C and NMR lipid profile were performed in 85 men samples. Association among them was evaluated using Pearson coefficients (r xy). A multivariate regression was performed to identify the influence of NMR variables on sdLDL‐C.ResultsA strong association between sdLDL‐C and LDLLDL‐P (r xy = 0.687) and with LDL‐Z (r xy = −0.603) was found. The multivariate regression explained a 56.8% in sdLDL‐C variation (P = 8.77.10‐12). BMI, ApoB, triglycerides, FFA, and LDL‐Z showed a significant contribution. The most important ones were ApoB and LDL‐Z; a 1nm increase (LDL‐Z) leads to decrease 126 nmol/L in sdLDL‐C.ConclusionThe association between sdLDL‐C, LDL‐Z, and LDL‐P is clear. From a large number of variables, especially LDL‐Z and apoB influence on sdLDL‐C. Results show that the smaller the LDL size, the higher their cholesterol concentration. Therefore, sdLDL‐C determination by using this easy method would be useful to risk stratification and to uncover cardiovascular residual risk.

THE LDL/APOLIPOPROTEIN B RATIO, AN INDEX FOR LDL PARTICLE SIZE, IS A STRONG PREDICTOR FOR NEOINTIMAL CHARACTERISTICS AND IN-STENT RESTENOSIS AFTER EVEROLIMUS-ELUTING STENT IMPLANTATION

The smaller size of LDL particle has suggested the development of endothelial dysfunction, atherosclerosis and in-stent restenosis (ISR), but little is known regarding the impact of LDL particle size on neointimal formation leading to ISR. In 135 patients, we investigated the relationship between

Effect of propolis and N-acetylcysteine supplementation on lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection.

Propolis and N-acetylcysteine have positive impact on respiratory tract health. Also, it has been suggested that they have beneficial effects on serum lipid and oxidative stress status, but the available data are limited and mostly gained from animal models. In this study we evaluated the effects of propolis and N-acetylcysteine supplementation (PropoMucil®) on lipid status, lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection. Twenty subjects with acute respiratory infection were included. PropoMucil® granules for oral solution (80 mg of dry propolis extract and 200 mg of N-acetylcysteine) were administered tree times per day for ten days. Serum lipid profile, paraoxonase 1 activity and low-density and high-density lipoprotein size and subclasses distribution were assessed at baseline and after supplementation. Following ten days of supplementation lipid status remained unchanged, but a significant increase of low-density lipoprotein particle size and proportion of high-density lipoprotein 3a particles were found (P<0.05). Moreover, supplementation with PropoMucil® significantly improved high-density lipoprotein particles distribution, particularly in those who smoke. There was a moderate increase of paraoxonase 1 activity, but without statistical significance. The presented study demonstrated that short-term supplementation with PropoMucil® has beneficial effects on low-density and high-density lipoprotein subclasses distribution and paraoxonase 1 activity in subjects with acute respiratory infection particularly in those who smoke.