Small Low-density Lipoprotein Research Articles

Small LDL subfractions are associated with coronary atherosclerosis despite no differences in conventional lipids.

Lipoprotein subfractions currently represent a new source of cardiovascular disease (CVD) risk markers that may provide more information than conventional lipid measures. We aimed to investigate whether lipoprotein subfractions are associated with coronary atherosclerosis in patients without prior known CVD. Fasting serum samples from 60 patients with suspected coronary artery disease (CAD) were collected before coronary angiography and analyzed by nuclear magnetic resonance (NMR) spectroscopy. The severity of coronary atherosclerosis was quantified by the Gensini score (≤20.5 = nonsignificant coronary atherosclerosis, 20.6-30.0 = intermediate coronary atherosclerosis, ≥30.1 = significant CAD). Differences in lipoprotein subfractions between the three Gensini groups were assessed by two-way ANOVA, adjusted for statin use. Despite no differences in conventional lipid measures between the three Gensini groups, patients with significant CAD had higher apolipoprotein-B/apolipoprotein-A1 ratio, 30% more small and dense low-density lipoprotein 5 (LDL-5) particles, and increased levels of cholesterol, triglycerides, and phospholipids within LDL-5 compared with patients with nonsignificant coronary atherosclerosis and intermediate coronary atherosclerosis (P ≤ 0.001). In addition, the low-density lipoprotein (LDL) cholesterol/high-density lipoprotein cholesterol ratio, and triglyceride levels of LDL 4 were significantly increased in patients with significant CAD compared with patients with nonsignificant coronary atherosclerosis. In conclusion, small and dense lipoprotein subfractions were associated with coronary atherosclerosis in patients without prior CVD. Additional studies are needed to explore whether lipoprotein subfractions may represent biomarkers offering a clinically meaningful improvement in the risk prediction of CAD.

Effects of Gestational Diabetes Mellitus on Cholesterol Metabolism in Women with High-Risk Pregnancies: Possible Implications for Neonatal Outcome.

Metabolic disorders in pregnancy, particularly gestational diabetes mellitus (GDM), are associated with an increased risk for adverse pregnancy outcome and long-term cardiometabolic health of mother and child. This study analyzed changes of serum cholesterol synthesis and absorption markers during the course of high-risk pregnancies, with respect to the development of GDM. Possible associations of maternal lipid biomarkers with neonatal characteristics were also investigated. The study included 63 women with high risk for development of pregnancy complications. Size and proportions of small low-density (LDL) and high-density lipoprotein (HDL) particles were assessed across trimesters (T1–T3), as well as concentrations of cholesterol synthesis (lathosterol, desmosterol) and absorption markers (campesterol, β-sitosterol). During the study, 15 women developed GDM, while 48 had no complications (non-GDM). As compared to the non-GDM group, women with GDM had significantly higher triglycerides in each trimester, while having a lower HDL-C level in T3. In addition, they had significantly lower levels of β-sitosterol in T3 (p < 0.05). Cholesterol synthesis markers increased across trimesters in both groups. A decrease in serum β-sitosterol levels during the course of pregnancies affected by GDM was observed. The prevalence of small-sized HDL decreased in non-GDM, while in the GDM group remained unchanged across trimesters. Newborn’s size in the non-GDM group was significantly higher (p < 0.01) and inversely associated with proportions of both small, dense LDL and HDL particles (p < 0.05) in maternal plasma in T1. In conclusion, high-risk pregnancies affected by GDM are characterized by altered cholesterol absorption and HDL maturation. Advanced lipid testing may indicate disturbed lipid homeostasis in GDM.

Genetic determinants of circulating metabolites and the risk of stroke and its subtypes.

Circulating metabolites have been implicated in stroke pathogenesis, but their genetic determinants are understudied. Using a Mendelian randomization approach, our aim was to provide evidence for the relationship of circulating metabolites and the risk of stroke and its subtypes. Genetic instruments of 102 circulating metabolites were obtained from a genome-wide association study, including 24,925 European individuals. Stroke was extracted from the MEGASTROKE dataset (67,162 cases; 454,450 controls) and a lacunar stroke dataset (7338 cases; 254,798 controls). The magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury were evaluated by a genome-wide association study of white matter hyperintensities (N=18,381), fractional anisotropy (N=17,663), mean diffusivity (N=17,467) and brain microbleeds (N=25,862). The inverse-variance weighted method Mendelian randomization was used as the primary analytical method, and directional pleiotropy and heterogeneity were examined in sensitivity analyses. A genetic predisposition to a higher level of cholesterol in small and low-density lipoprotein (LDL) was associated with risk of stroke (odds ratio [OR] 1.14, 95% confidence interval [CI]1.08-1.21, p=5.98 × 10-7 ), especially for large-artery atherosclerotic stroke (OR 1.34, 95% CI 1.19-1.52, p=1.90 × 10-6 ). Total lipids in LDL particles were also associated with risk of stroke. A genetically determined higher cholesterol level in high-density lipoprotein (HDL-C) was associated with risk of intracerebral haemorrhage (OR 1.74, 95% CI 1.23-2.45, p=1.66 × 10-3 ). No statistically significant association was found between genetic predisposition to circulating metabolites and magnetic resonance imaging markers of cerebral small vessel disease and microstructural injury. Genetically determined levels of lipids in small LDL were associated with the risk of stroke, suggesting that a therapeutic strategy targeting small LDL levels may be crucial for stroke prevention. HDL-C was positively associated with the risk of intracerebral haemorrhage.

Cord Blood Advanced Lipoprotein Testing Reveals an Interaction between Gestational Diabetes and Birth-Weight and Suggests a New Early Biomarker of Infant Obesity.

Abnormal lipid metabolism is associated with gestational diabetes mellitus (GDM) and is observed in neonates with abnormal fetal growth. However, the underlying specific changes in the lipoprotein profile remain poorly understood. Thus, in the present study we used a novel nuclear magnetic resonance (NMR)-based approach to profile the umbilical cord serum lipoproteins. Two-dimensional diffusion-ordered 1H-NMR spectroscopy showed that size, lipid content, number and concentration of particles within their subclasses were similar between offspring born to control (n = 74) and GDM (n = 62) mothers. Subsequent data stratification according to newborn birth-weight categories, i.e., small (n = 39), appropriate (n = 50) or large (n = 49) for gestational age (SGA, AGA and LGA, respectively), showed an interaction between GDM and birth-weight categories for intermediate-density lipoproteins (IDL)-cholesterol content and IDL- and low-density lipoproteins (LDL)-triglyceride content, and the number of medium very low-density lipoproteins (VLDL) and LDL particles specifically in AGA neonates. Moreover, in a 2-year follow-up study, we observed that small LDL particles were independently associated with offspring obesity at 2 years (n = 103). Collectively, our data demonstrate that GDM disturbs triglyceride and cholesterol lipoprotein content across birth-weight categories, with AGA neonates born to GDM mothers displaying a profile more similar to that of adults with dyslipidemia. Furthermore, an altered fetal lipoprotein pattern was associated with the development of obesity at 2 years.

Anorexia Nervosa Is Associated with a Shift to Pro-Atherogenic Low-Density Lipoprotein Subclasses.

Anorexia nervosa (AN) is a severe eating disorder affecting primarily female adolescents and younger adults. The energy deprivation associated with AN has been shown to alter lipoprotein metabolism, which may affect cardiovascular risk. However, the mechanisms leading to alterations in the composition, structure, and function of lipoproteins in AN patients are not well-understood yet. Here, we investigated the lipid abnormalities associated with AN, particularly changes in the distribution, composition, metabolism, and function of lipoprotein subclasses. In this exploratory study, we analyzed serum samples of 18 women diagnosed with AN (BMI < 17.5 kg/m2) and 24 normal-weight women (BMI from 18.5–24.9 kg/m2). Using the Quantimetrix Lipoprint® system, we determined low-density lipoprotein (LDL) subclass distribution, including quantitative measurements of very low-density lipoprotein (VLDL), intermediate density lipoprotein (IDL) and high-density lipoprotein (HDL) subclass distribution. We quantified the most abundant apolipoproteins of HDL and assessed lecithin-cholesterol acyltransferase (LCAT) and cholesteryl-ester transfer protein (CETP) activities. In addition, anti-oxidative capacity of apoB-depleted serum and functional metrics of HDL, including cholesterol efflux capacity and paraoxonase activity were assessed. The atherogenic lipoprotein subclasses VLDL and small LDL particles were increased in AN. Levels of VLDL correlated significantly with CETP activity (rs = 0.432, p = 0.005). AN was accompanied by changes in the content of HDL-associated apolipoproteins involved in triglyceride catabolism, such as apolipoprotein C-II (+24%) and apoA-II (−27%), whereas HDL-associated cholesterol, phospholipids, and triglycerides were not altered. Moreover, AN did not affect HDL subclass distribution, cholesterol efflux capacity, and paraoxonase activity. We observed a shift to more atherogenic lipoprotein subclasses in AN patients, whereas HDL functionality and subclass distribution were not altered. This finding underpins potential detrimental effects of AN on lipid metabolism and the cardiovascular system by increasing atherosclerotic risk factors.

Relationship between Apolipoprotein E Genotype and Lipoprotein Profile in Patients with Coronary Heart Disease.

(1) Background: Apolipoprotein E(ApoE) plays a critical role in lipid transport. The specific allele of APOE being expressed is associated with the development of coronary heart disease (CHD), however the specific mechanisms by which ApoE drives disease are unclear. In this study, we investigated the relationship between APOE allele, lipoprotein metabolome, and CHD severity to provide evidence for the efficacy of clinical cholesterol-lowering therapy; (2) Methods: Blood samples were collected from 360 patients with CHD that were actively being treated with statins. The lipoprotein profile, including particle numbers, particle size, and lipoprotein composition concentrates, was measured by nuclear magnetic resonance (NMR) spectroscopy. The severity of CHD was determined by quantifying coronary angiography results using the Gensini scoring system; (3) Results: We found there was no significant difference in low-density lipoprotein cholesterol (LDL-C) levels among ε2+ (ε2 allele carriers, consisting of ε2/ε2 and ε2/ε3 genotypes), ε3 (consisting of ε3/ε3 and ε2/ε4 genotypes), and ε4+ (ε4 allele carriers, consisting of ε3/ε4 and ε4/ε4 genotypes) participants receiving statin treatment. Compared with the ε3 group, patients with the ε2+ genotype showed lower concentrations of total low-density lipoprotein (LDL), small-LDL, and middle-LDL particles, as well as a larger LDL size, higher very low-density lipoprotein (VLDL) composition concentrates, and higher intermediate density lipoprotein (IDL) composition concentrates. The ε4+ group showed higher concentrations of total LDL, small LDL particles, and LDL compositions with smaller LDL size. The higher level of small LDL concentration was associated with a high Gensini score (B = 0.058, p = 0.024). Compared with the ε3 group, the risk of increased branch lesions in the ε2+ group was lower (OR = 0.416, p = 0.027); (4) Conclusions: The specific allele of APOE being expressed can affect the severity of CHD by altering components of the lipoprotein profile, such as the concentration of small LDL and LDL size.

Atherogenic lipidomics profile in healthy individuals with low cardiorespiratory fitness: The HUNT3 fitness study

Background and aimsLow cardiorespiratory fitness is a strong and independent risk factor for cardiovascular disease (CVD). Serum profiling of healthy individuals with large differences in cardiorespiratory fitness may therefore reveal early biomarkers of CVD development. Thus, we aimed to identify circulating lipoprotein subfractions differentially expressed between groups of individuals with large differences in cardiorespiratory fitness, measured as maximal oxygen uptake (VO2max). MethodsHealthy subjects (40–59 years) were selected from the third wave of the Trøndelag health study (HUNT3) based on having an age-dependent high VO2max (47.1 ± 7.7 mL kg−1·min−1, n = 103) or low VO2max (31.4 ± 4.9 mL kg−1·min−1, n = 108). The individuals were matched on gender, age, physical activity level and fasting status. Results99 lipoprotein subfractions were quantified in serum samples using nuclear magnetic resonance (NMR) lipidomics. Standard clinical analyses showed similar levels of total cholesterol, low-density lipoprotein (LDL)-cholesterol and high-density lipoprotein (HDL)-cholesterol between the groups, and slightly higher levels of triglycerides in participants with low VO2max. Thirteen lipoprotein subfractions were increased in the low VO2max group compared to the high VO2max group (p < 0.005), including mainly large very low-density lipoprotein (VLDL) subfractions. In addition, triglyceride levels in small-sized HDL and LDL particles were increased in participants with low VO2max. Correlation analyses between VO2max and lipoproteins subfractions displayed a negative correlation between VO2max and the levels of cholesterol and phospholipids in the small HDL particles. The lipoprotein profile of individuals with low VO2max is similar to the profile of insulin resistant individuals. ConclusionsLow VO2max was associated with enrichment of large VLDL particles, as well as an increased triglycerides content in the small and dense HDL and LDL particles. This unfavorable lipid profile is likely to be involved in the strong associations between VO2max and CVD.

Assessment of Reliability of Advanced Lipid Parameters for Premature Coronary Artery Disease in Young Indians: A Case-control Study

Introduction: Coronary Artery Disease (CAD) appears even in patients with normal level of conventional lipid parameters. But due to lack of specific guidelines on Indian population, involving detection of advanced lipid indices, has resulted in inadequate finding, management, and control of cardiovascular disease risks. This emphasises the need of advanced lipid indices for prediction of CAD at younger age. Aim: To evaluate the reliability of advanced lipid indices compared to conventional lipid parameters for diagnosis of CAD. Also, to determine the effectiveness of advanced lipid indices in screening young Indian for the risk of Premature CAD (PCAD). Materials and Methods: A case-control study was conducted at a tertiary care centre in Bengaluru, Karnataka, India, between January 2020 to January 2022. The study enrolled total 983 subjects which were divided into cases and controls. The estimation of usual lipid profile (Triglycerides (TG), High Density Lipoprotein (HDL), Low Density Lipoprotein (LDL), and Total Cholesterol (TC)) and advanced lipid parameters, oxidized LDL, Apolipoprotein A1 (Apo A1), lipoprotein (a), small density LDL (Sd-LDL), and Apolipoprotein B-100 (Apo B) was studied for each enrolled individual. These lipid parameters were used to calculate various lipid indices like Lipid Pentad Index (LPI), Lipid Tetrad Index (LTI), Atherosclerotic Index (AI), and Advanced Atherosclerotic Index (AAI); and TC/HDL ratio. Statistical analysis was performed using Chi-square test, Fisher’s exact test, multivariate logistic regression, and Student’s t-test/ Analysis of Variance (ANOVA) test. Results: Mean age of patient in case group was 32.31±5.42 years and individuals in control group was 32.13±5.21 years. Among case group, 427 (88.04%) enrolled males had PCAD. In case group, total 45 (9.28%) had diabetes, 51 (10.51%) had family history of PCAD and 230 (47.42%) patients were smokers. The values of TC (p=0.009), LDL (p&lt;0.001), Apo A1 (p&lt;0.001), HDL (p&lt;0.001) were significantly lower among cases compared to controls, lipoprotein (a) (p=0.04), Sd-LDL (p&lt;0.001), TG (p&lt;0.001) were significantly higher among cases compared to controls. Among the calculated lipid indices, the values of AI (p&lt;0.001), LTI (p&lt;0.001), LPI (p=0.001) and AAI (p=0.01) were significantly higher among cases as compared to controls. Conclusion: Advanced lipid indices are statistically more reliable than conventional lipid parameters. Newer advanced lipid indices are effective in screening young Indian individuals for the risk of PCAD.

Lipoprotein subtypes after testosterone therapy in transmasculine adolescents

Differences in lipoprotein-particle subclasses between men and women start in puberty and narrow after menopause, suggesting a role for sex steroids. In this cross-sectional cohort study, we examined lipoprotein subtype profiles in transmasculine adolescents treated with testosterone. Transmasculine adolescents (n = 17) had lipoprotein profiles that were similar to those of cisgender males (n = 33) and more atherogenic than those of cisgender females (n = 32), with higher concentrations of small low-density lipoprotein (LDL) particles (435 ± 222 nmol/L vs. 244 ± 163 nmol/L, p = 0.008) and lower concentrations of large high-density lipoprotein (HDL) particles (1.5 ± 1.3 μmol/L vs 2.7 ± 1.2 μmol/L, p = 0.003) when compared to cisgender females. Thus, testosterone appears to be a major contributor to differences in lipoprotein profiles, a surrogate for cardiovascular disease risk, between cisgender women and both transgender and cisgender men.

Per particle triglyceride-rich lipoproteins imply higher myocardial infarction risk than low-density lipoproteins: Copenhagen general population study

Background and Aims: Apolipoprotein B (apoB)-containing triglyceride-rich lipoproteins and low-density lipoproteins (LDL) are each causal for myocardial infarction and atherosclerotic cardiovascular disease; however, the relative importance is unknown. We tested the hypothesis that for the same number of apoB-containing particles from smaller LDL through to larger triglyceride-rich lipoproteins, the risk of myocardial infarction is similar.

A metabolomic index based on lipoprotein subfractions and branched chain amino acids is associated with incident hypertension

ObjectiveThe present study aims to evaluate the performance of the Diabetes Risk Index (DRI), a metabolomic index based on lipoprotein particles and branched chain amino acids, on the incidence of newly developed hypertension in a large community dwelling cohort. MethodsThe DRI was calculated by combining 6 lipoprotein parameters [sizes of very-low-density lipoprotein (VLDL), low-density lipoprotein (LDL) and high-density lipoprotein (HDL), concentrations of large VLDL, small LDL, and large HDL particles], and the concentrations of valine and leucine. DRI scores were estimated in 4169 participants from the PREVEND prospective cohort. Cox proportional hazards regression was used to evaluate the association of DRI scores with incident hypertension. ResultsDuring a median follow-up of 8.6 years, 924 new hypertension cases were ascertained. In analyses adjusted for age and sex, there was a significant association between DRI and incident hypertension with a hazard ratio (HR) per 1 SD increase of 1.45 (95% CI 1.36,1.54; p < 0.001). After additional adjustment for traditional risk factors, the HR remained significant (HRadj 1.21, 95% CI 1.10, 1.33, p <0.001). Likewise, subjects in the top quartile of DRI presented with a higher risk of hypertension (HRadj 1.64, 95% CI 1.28, 2.10, p <0.001). Furthermore, the net reclassification improvement assessment improved after the addition of DRI to a traditional risk model (p <0.001), allowing proper reclassification of 34% of the participants. ConclusionHigher DRI scores were associated with an increased risk of incident hypertension. Such association was independent of traditional clinical risk factors for hypertension.

COVID-19 AMONG DIABETES PATIENTS TYPE 2

A total of 74 COVID-19 diabetic patients were enrolled in the study. Twenty-seven patients (36.5%) were severely ill, and ten patients (13.5%) died. Severe patients had higher blood glucose, serum amyloid A (SAA), C reactive protein, and interleukin 6 levels than non-severe patients (P&gt; 0.05). Severe patients had lower levels of albumin, cholesterol, high density lipoprotein, small and dense low density lipoprotein, and CD4 T lymphocyte counts than non-severe patients (P &gt; 0.05). Reduced CD4 21 + T lymphocyte counts (OR = 0.988, 95 percent confidence interval [95 percent CI] 0.979–0.997) and elevated SAA levels (OR = 1.029, 95 percent CI 1.002–1.058) were found as risk variables for COVID- 19 severity with diabetes in a logistic regression analysis (P &gt; 0.05).&#x0D; Keywords: COVID-19, Diabetes, Hyperglycemia, Dislipidemia, CD4+ T lymphocyte , follow up symptoms.

Cardiometabolic Associations between Physical Activity, Adiposity, and Lipoprotein Subclasses in Prepubertal Norwegian Children.

Lipoprotein subclasses possess crucial cardiometabolic information. Due to strong multicollinearity among variables, little is known about the strength of influence of physical activity (PA) and adiposity upon this cardiometabolic pattern. Using a novel approach to adjust for covariates, we aimed at determining the “net” patterns and strength for PA and adiposity to the lipoprotein profile. Principal component and multivariate pattern analysis were used for the analysis of 841 prepubertal children characterized by 26 lipoprotein features determined by proton nuclear magnetic resonance spectroscopy, a high-resolution PA descriptor derived from accelerometry, and three adiposity measures: body mass index, waist circumference to height, and skinfold thickness. Our approach focuses on revealing and validating the underlying predictive association patterns in the metabolic, anthropologic, and PA data to acknowledge the inherent multicollinear nature of such data. PA associates to a favorable cardiometabolic pattern of increased high-density lipoproteins (HDL), very large and large HDL particles, and large size of HDL particles, and decreasedtriglyceride, chylomicrons, very low-density lipoproteins (VLDL), and their subclasses, and to low size of VLDL particles. Although weakened in strength, this pattern resists adjustment for adiposity. Adiposity is inversely associated to this pattern and exhibits unfavorable associations to low-density lipoprotein (LDL) features, including atherogenic small and very small LDL particles. The observed associations are still strong after adjustment for PA. Thus, lipoproteins explain 26.0% in adiposity after adjustment for PA compared to 2.3% in PA after adjustment for adiposity.

Long-term fasting improves lipoprotein-associated atherogenic risk in humans

PurposeDyslipidemia is a major health concern associated with an increased risk of cardiovascular mortality. Long-term fasting (LF) has been shown to improve plasma lipid profile. We performed an in-depth investigation of lipoprotein composition.MethodsThis observational study included 40 volunteers (50% men, aged 32–65 years), who underwent a medically supervised fast of 14 days (250 kcal/day). Changes in lipid and lipoprotein levels, as well as in lipoprotein subclasses and particles, were measured by ultracentrifugation and nuclear magnetic resonance (NMR) at baseline, and after 7 and 14 fasting days.ResultsThe largest changes were found after 14 fasting days. There were significant reductions in triglycerides (TG, − 0.35 ± 0.1 mmol/L), very low-density lipoprotein (VLDL)-TG (− 0.46 ± 0.08 mmol/L), VLDL-cholesterol (VLDL-C, − 0.16 ± 0.03 mmol/L) and low-density lipoprotein (LDL)-C (− 0.72 ± 0.14 mmol/L). Analysis of LDL subclasses showed a significant decrease in LDL1-C (− 0.16 ± 0.05 mmol/L), LDL2-C (− 0.30 ± 0.06 mmol/L) and LDL3-C (− 0.27 ± 0.05 mmol/L). NMR spectroscopy showed a significant reduction in large VLDL particles (− 5.18 ± 1.26 nmol/L), as well as large (− 244.13 ± 39.45 nmol/L) and small LDL particles (− 38.45 ± 44.04 nmol/L). A significant decrease in high-density lipoprotein (HDL)-C (− 0.16 ± 0.04 mmol/L) was observed. By contrast, the concentration in large HDL particles was significantly raised. Apolipoprotein A1 decreased significantly whereas apolipoprotein B, lipoprotein(a), fibrinogen and high-sensitivity C-reactive protein were unchanged.ConclusionOur results suggest that LF improves lipoprotein levels and lipoprotein subclasses and ameliorates the lipoprotein-associated atherogenic risk profile, suggesting a reduction in the cardiovascular risk linked to dyslipidemia.Trial RegistrationStudy registration number: DRKS-ID: DRKS00010111 Date of registration: 03/06/2016 “retrospectively registered”.

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.

Regular exercise and patterns of response across multiple cardiometabolic traits: the HERITAGE family study

ObjectivesWe investigated whether high responsiveness or low responsiveness to exercise training aggregates in the same individuals across seven cardiometabolic traits.MethodsA total of 564 adults (29.2% black, 53.7% female) from the...

Association of Coronary Calcium, Carotid Wall Thickness, and Carotid Plaque Progression With Low-Density Lipoprotein and High-Density Lipoprotein Particle Concentration Measured by Ion Mobility (From Multiethnic Study of Atherosclerosis [MESA

Current risk stratification strategies do not fully explain cardiovascular disease (CVD) risk. We aimed to evaluate the association of low-density lipoprotein (LDL-P) and high-density lipoprotein (HDL-P) particles with progression of coronary artery calcium and carotid wall injury. All participants in the Multi-Ethnic Study Atherosclerosis (MESA) with LDL-P and HDL-P measured by ion mobility, coronary artery calcium score (CAC), carotid intima-media thickness (IMT), and carotid plaque data available at Exam 1 and 5 were included in the study. CAC progression was annualized and treated as a categorical or continuous variable. Carotid IMT and plaque progression were treated as continuous variables. Fully adjusted regression models included established CVD risk factors, as well as traditional lipids. Mean (±SD) follow-up duration was 9.6 ± 0.6 years. All LDL-P subclasses as well as large HDL-P at baseline were positively and significantly associated with annualized CAC progression, however, after adjustment for established risk factors and traditional lipids, only the association with medium and very small LDL-P remained significant (β -0.02, p = 0.019 and β 0.01, p = 0.003, per 1 nmol/l increase, respectively). Carotid plaque score progression was positively associated with small and very small LDL-P (p <0.01 for all) and non-HDL-P (p = 0.013). Only the association with very small LDL-P remained significant in a fully adjusted model (p = 0.035). Mean IMT progression was not associated with any of the lipid particles. In conclusion, in the MESA cohort, LDL-P measured by ion mobility was significantly associated with CAC progression as well as carotid plaque progression beyond the effect of traditional lipids.

Lipoprotein subfraction LDL-5 and the presence of coronary atherosclerosis

Abstract Background Coronary artery disease (CAD) has high mortality rates and is a frequent cause of death globally. Serum lipids play a pivotal role in the development of atherosclerosis, and elevated levels of total cholesterol, low density lipoprotein (LDL) cholesterol, and triglycerides are well known risk factors of cardiovascular disease (CVD). However, there are limitations in the ability to predict CVD risk, which has led to an increased clinical interest in identifying novel risk markers. With the advances in lipidomic technology, lipoprotein subfractions may provide additional information that is missing in today's evaluation of CVD risk. Lipoprotein subfractions differ in size and density, and recent studies suggest that high density of small LDL particles provide a greater risk for CVD. Purpose To investigate whether lipoprotein subfractions are associated with the presence and extent of coronary atherosclerosis. Methods Fasting serum samples from 60 participants with suspected stable CAD were collected before scheduled coronary angiography, and analysed by nuclear magnetic resonance (NMR). The presence and extent of atherosclerosis were quantified by the Gensini Score. Participants were classified into one of three Gensini groups based on severity (&amp;lt;20.5, normal; 20.6–30, non-significant CAD; &amp;gt;30.1, significant CAD). Results A three-way ANOVA, adjusted for statin-use and sex, revealed statistically significant differences (p&amp;lt;0.005) in LDL-5 particle number, LDL-5 triglycerides, and LDL-5 phospholipids between the Gensini groups. In addition, significant differences (p&amp;lt;0.005) were found in the ratios apolipoprotein A/apolipoprotein B and LDL cholesterol/HDL cholesterol between the Gensini groups. All significant variables, identified by the three-way ANOVA, displayed the highest levels in the Gensini group with significant CAD. Conclusion Despite no difference in the traditional clinical measurements (total cholesterol, LDL cholesterol, HDL cholesterol and triglycerides), NMR-lipidomics revealed significant differences in LDL-5 between the Gensini groups. Interestingly, our results reveal that those with significant CAD have a higher density of small LDL subfractions. Funding Acknowledgement Type of funding source: Foundation. Main funding source(s): Norwegian Health Association, The Liaison Committee for Education, Research and Innovation in Central Norway

Randomized nutrient bar supplementation improves exercise-associated changes in plasma metabolome in adolescents and adult family members at cardiometabolic risk.

Poor diets contribute to metabolic complications of obesity, insulin resistance and dyslipidemia. Metabolomic biomarkers may serve as early nutrition-sensitive health indicators. This family-based lifestyle change program compared metabolic outcomes in an intervention group (INT) that consumed 2 nutrient bars daily for 2-months and a control group (CONT). Overweight, predominantly minority and female adolescent (Teen)/parent adult caretaker (PAC) family units were recruited from a pediatric obesity clinic. CONT (8 Teen, 8 PAC) and INT (10 Teen, 10 PAC) groups randomized to nutrient bar supplementation attended weekly classes that included group nutrition counseling and supervised exercise. Pre-post physical and behavioral parameters, fasting traditional biomarkers, plasma sphingolipids and amino acid metabolites were measured. In the full cohort, a baseline sphingolipid ceramide principal component composite score correlated with adiponectin, triglycerides, triglyceride-rich very low density lipoproteins, and atherogenic small low density lipoprotein (LDL) sublasses. Inverse associations were seen between a sphingomyelin composite score and C-reactive protein, a dihydroceramide composite score and diastolic blood pressure, and the final principal component that included glutathionone with fasting insulin and the homeostatic model of insulin resistance. In CONT, plasma ceramides, sphinganine, sphingosine and amino acid metabolites increased, presumably due to increased physical activity. Nutrient bar supplementation (INT) blunted this rise and significantly decreased ureagenic, aromatic and gluconeogenic amino acid metabolites. Metabolomic changes were positively correlated with improvements in clinical biomarkers of dyslipidemia. Nutrient bar supplementation with increased physical activity in obese Teens and PAC elicits favorable metabolomic changes that correlate with improved dyslipidemia. The trial from which the analyses reported upon herein was part of a series of nutrient bar clinical trials registered at clinicaltrials.gov as NCT02239198.

Protective lifestyle behaviours and lipoprotein particle subclass profiles in a middle-to older-aged population

Background and aimsLipoprotein particle size is associated with increased atherosclerosis and cardiovascular disease risk. Certain lifestyle behaviours may be cardioprotective. We examined lipoprotein particle size and concentration relationships with a protective lifestyle behaviour (PLB) score. MethodsThis was a cross-sectional analysis of 2045 middle-to older-aged adults. Lipoprotein particle subclass size and concentrations were determined using nuclear magnetic resonance spectroscopy. Five protective behaviours included never smoking, moderate alcohol intake, moderate to vigorous physical activity, a high-quality diet (upper 40% Dietary Approaches to Stop Hypertension score) and a normal body mass index (BMI) (18.5–24.9 kg/m2). Linear and logistic regression analyses tested individual protective behaviour and PLB score associations with lipoprotein subclasses. ResultsIndividual behaviour associations varied according to lipoprotein subclass, with normal BMI showing the greatest number of significant relationships. Logistic regression analyses revealed that subjects with the fewest number of protective behaviours had 1.4–2.8 increased odds of having less favourable lipoprotein profiles defined as above or below median level lipoprotein particle subclass size or concentration. Following additional adjustment for BMI, significant trend relationships were observed between the PLB score and large and medium very low-density lipoprotein (p = 0.001 and p < 0.001), total and smaller low-density lipoprotein (LDL) concentrations (p = 0.008 and p < 0.001), LDL size (p = 0.003) and a lipoprotein insulin resistance score (p = 0.003). ConclusionsResults show a cumulative protective effect of healthy lifestyle behaviours against an unfavourable potentially pro-atherogenic lipoprotein profile in middle-to older-aged adults, highlighting the importance of lifestyle promotion in healthy ageing.