Hypercholesterolemic Subjects Research Articles

Lipid-lowering response in subjects with the p.(Leu167del) mutation in the APOE gene

Background and aimsThe aim of this work was to compared the effect of lipid lowering drugs among familial hypercholesterolemia (FH) subjects with a functional mutation in LDLR (LDLR FH) and FH with the p.(Leu167del) mutation in APOE. MethodsWe retrospectively selected all adults with the p.(Leu167del) mutation on lipid-lowering treatment (n = 22) attending the Lipid Unit at the Hospital Miguel Servet. Age and sex matched LDLR FH from the same Unit were randomly selected as a control group (n = 44). ResultsThe mean percentage reduction in LDLc was significantly higher in the p.(Leu167del) carriers (−52.1%) than in the LDLR FH (−39.7%) (p = 0.040) when on high intensity statins. Similar differences between groups were observed in non-HDLc −49.4% and −36.4%, respectively (p = 0.030). ConclusionsSubjects with p.(Leu167del) mutation have a higher lipid-lowering response to statins with or without ezetimibe than LDLR FH. This supports the use of genetics for a more efficient management of FH.

The effects of nattokinase supplementation on collagen-epinephrine closure time, prothrombin time and activated partial thromboplastin time in nondiabetic and hypercholesterolemic subjects.

The aim of this study was to investigate whether supplementation with nattokinase, which is considered one of the most active functional ingredients found in natto, alters hemostatic factors. Subjects presenting with hypercholesterolemia (serum cholesterol: 200-280 mg dL-1) were randomly divided into nattokinase and placebo groups (n = 50, respectively). No significant between-group differences were found at baseline in collagen-epinephrine closure time (C-EPI CT), prothrombin time (PT), or activated partial thromboplastin time (aPTT). After 8 weeks of treatment, the nattokinase group exhibited significant increases in C-EPI CT, PT, and aPTT. The nattokinase group showed significantly greater increases in C-EPI CT (P = 0.001) and aPTT (P = 0.016) than the placebo group. Moreover, at 8 weeks, the nattokinase group showed a significantly higher C-EPI CT than the placebo group (P = 0.001). Additionally, a significant correlation between PT and aPTT was observed (r = 0.491, P < 0.001). In conclusion, nattokinase supplementation was associated with prolonged C-EPI CT and aPTT in nondiabetic and borderline-to-moderate hypercholesterolemic subjects.

Coenzyme Q10 Attenuates Platelet Integrin αIIbβ3 Outside-in Signaling through Targeting cAMP/PKA Pathway and Inhibits Atherosclerosis

Introduction: Platelet integrin αIIbβ3 outside-in signaling is crucial for platelet adhesion and aggregation, and contributes to atherogenesis. Coenzyme Q10 (CoQ10) has been implicated as a protective factor against cardiovascular diseases (CVDs), particularly atherosclerosis. However, whether CoQ10 attenuates atherosclerosis through inhibiting platelet function and αIIbβ3 outside-in signaling is unknown. The aim of this study was to explore whether CoQ10 affects platelet function and αIIbβ3 outside-in signalling and thus inhibiting the progress of atherosclerosis in vivo and the underlying mechanisms in vitro.Methods:In vitro study, The murine platelet rich plasma (PRP) from C57BL/6J wild-type (WT) mice or human PRP and gel-filtered platelets were incubated with different concentrations (1, 10 or 100 μM) of CoQ10 or the vehicle control for 50 min. Platelet aggregation, spreading on fibrinogen (Fg) and clot retraction were determined. In addition, the effects of CoQ10 on platelet integrin αIIbβ3 inside-out signalling (e.g., talin-1 and kindlin-3 binding to integrin β3) were determined by immunoprecipitation, and outside-in signalling (e.g., phosphorylation of sarcoma tyrosine-protein kinase (c-Src), focal adhesion kinase (FAK), and β3 cytoplasmic tail, myosin light chain (MLC)) were determined by Western blotting. The levels of platelet ATP and cAMP were measured by ELISA assays. In vivo study, male homozygous apolipoprotein E-deficient (apoE-/-) mice (C57BL/6 genetic background) were fed either a standard normal AIN-93G diet (NC group), a Western-type diet (HFD group) or a Western-type diet supplemented with CoQ10 (1800 mg/kg diet) (CoQ10 group) for 12 weeks. Platelet aggregation, granule secretion, platelet spreading, clot retraction, integrin αIIbβ3 outside-in signalling, platelet-leukocyte interactions and carotid artery plaque area were also examined. In our randomized, double-blind, placebo-controlled trial, 101 hypercholesterolemic subjects were randomly administrated to 120 mg CoQ10 or placebo daily for 24 weeks. Platelet intracellular CoQ10 levels, platelet aggregation in PRP, platelet platelet factor 4 (PF-4) and C-C motif ligand 5 (CCL5) release, and platelet integrin αIIbβ3 outside-in signalling were also evaluated before and after 24 weeks of intervention.Results: We found that CoQ10 inhibited human and WT mouse platelet aggregation, platelet spreading, granule secretion, and clot retraction in vitro and apoE-/- mice on a high fat diet. CoQ10 also reduced atherosclerosis and platelet-monocyte aggregation in apoE-/- mice. The inhibitory effects of CoQ10 is mediated by attenuated αIIbβ3 outside-in signalling pathway (e.g., attenuation of phosphorylation of c-Src, FAK, and β3 cytoplasmic tail, and MLC in thrombin-activated platelets or platelets exposed to immobilized Fg), which requires up-regulation of the cAMP/PKA pathway, where CoQ10 inhibited phosphodiesterase 3A activity and activated the A2A adenosine receptor. However, CoQ10 did not affect platelet integrin αIIbβ3 inside-out signalling pathway, platelet cellular ATP, or platelet apoptosis (the mitochondrial membrane potential and phosphatidylserine exposure). Moreover, our clinical trial in dyslipidemic patients demonstrated that CoQ10 supplementation attenuated platelet aggregation, which was positively correlated with the increased platelet CoQ10 concentrations, inhibited αIIbβ3 outside-in signalling and decreased platelet PF-4 and CCL5 secretion.Conclusions: We present new data to suggest that CoQ10 plays a novel role in attenuating platelet function and integrin αIIbβ3 outside-in signalling though targeting cAMP/PKA signalling cascade and thus inhibiting the progress of atherosclerosis. CoQ10 is therefore a promising agent for the prevention and/or treatment for cardiovascular disease. DisclosuresNo relevant conflicts of interest to declare.

Design of the randomized, placebo-controlled evolocumab for early reduction of LDL-cholesterol levels in patients with acute coronary syndromes (EVOPACS) trial.

Statins lower low-density lipoprotein cholesterol (LDL-C) and improve clinical outcomes in patients with atherosclerotic cardiovascular disease (CVD). Patients with acute coronary syndromes (ACS) often do not achieve LDL-C targets despite potent statin treatment, and have a particularly high risk of early recurrent events. Evolocumab, a proprotein convertase subtilisin/kexin type (PCSK9)-inhibitor resulting in rapid, marked LDL-C reduction, has been studied in hypercholesterolemic subjects without CVD and stabilized patients with CVD; the feasibility, safety, and efficacy of this treatment initiated in the acute phase of ACS remain unknown. We report the design of evolocumab for early reduction of LDL-cholesterol levels in patients with ACS (EVOPACS), a phase-3, multicenter, randomized, double-blind, placebo-controlled trial to assess the feasibility, safety, and LDL-C-lowering efficacy of evolocumab on top of atorvastatin 40 mg in patients with ACS. The primary endpoint is percent change in LDL-C from baseline to 8 weeks. Secondary endpoints are adverse events and serious adverse events. Against a background of beneficial cardiovascular effects of statins beyond LDL-C lowering and in view of preclinical evidence of similar effects of PCSK9 inhibition, the study will also address a variety of exploratory endpoints including the change in C-reactive protein and other inflammatory biomarkers; platelet reactivity; and occurrence of contrast-induced acute kidney injury and myocardial injury in patients undergoing cardiac catheterization. An intracoronary imaging sub-study will investigate the change from baseline in the lipid core burden index in non-culprit lesions, as assessed by serial near-infrared spectroscopy. Recruitment began in January 2018 and enrollment of 308 patients is planned.

Different age-independent effects of nutraceutical combinations on endothelium-mediated coronary flow reserve

BackgroundSome components of Nutraceuticals (NUT) such as red yeast rice and Morus alba have demonstrated positive effects on the endothelial function in hypercholesterolemic subjects. Our aim was to compare the effects of two different NUT combinations on cold pressure test (CPT) derived coronary flow reserve (CFR) assessed by transthoracic echo-Doppler.ResultsIn a randomized, single-blind study, 28 consecutive patients with a variety of cardiovascular risk factors received NUT A (LopiGLIK®: berberine, red yeast rice powder, and leaf extract of Morus alba) or B (Armolipid Plus®: policosanol, red yeast rice, berberine, astaxantine, folic acidandcoenzyme Q10). An echo-Doppler exam with evaluation of CFR was performed at baseline, 2 h (acute test) and 30 days after daily NUT assumption. Blood sampling for metabolic profile and platelet aggregometry was performed at baseline and after 30 days of daily NUT assumption. CFR was not significantly modified at the acute test. After 30 days, CFR improved with NUT A (p < 0.0001), because of the increase of hyperemic flow velocity (p = 0.007), but not with NUT B. CFR was comparable between the two groups at baseline but became significantly higher after 30 days in NUT A (p < 0.02), with a higher CFR percent variation versus baseline (p = 0.008). Total cholesterol and LDL-cholesterol were reduced with both NUT A (p < 0.001 and p < 0.002, respectively) and B (both p < 0.02), whereas platelet aggregation did not significantly change. In the pooled group of patients, after adjusting for age and percent changes of systolic blood pressure, heart rate, LDL-cholesterol and glycemia, NUT A – but not NUT B - was independently associated with CFR changes (β = 0.599, p = 0.003).ConclusionsLopiGLIK® improved endothelial-derived CFR, independently of the beneficial effects exerted on the lipid profile. These findings can have clinical reflections on the prevention of age-related inflammatory diseases including coronary artery disease.Trial registration(NUTRENDO)″(ClinicalTrials.gov, NCT02969070).

Effect of probiotics on lipid profiles in hypercholesterolaemic adults: A meta-analysis of randomized controlled trials

BackgroundRecent clinical studies have yielded controversial results regarding the effect of probiotics on lipid profiles. To assess the efficacy of probiotics in lowering serum lipid concentrations, we conducted a meta-analysis of randomized controlled trials (RCTs). MethodsLiterature from the PubMed, Embase and Cochrane databases were searched and screened. The effects of probiotics on lipid profiles were assessed by mean difference (MD) and 95% confidence interval (CI). All included studies were analyzed using Review Manager 5.3 (Cochrane Collaboration, 2014). ResultsA total of 19 RCTs, including 967 participants, met the inclusion criteria. Probiotic interventions reduced total cholesterol (TC) and low-density lipoprotein cholesterol (LDL-C) compared to controls (placebo or no treatment) by −0.25mmol/L (95% CI: −0.39, −0.12) and −0.17mmol/L (95% CI: −0.25, −0.09), respectively. No significant effects of probiotics on triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) levels were found. The effects of probiotics on decreasing TC and LDL-C levels were greater for longer intervention times, certain probiotic strains, and in younger mildly hypercholesterolaemic subjects. ConclusionThis meta-analysis revealed that the use of probiotics can significantly lower TC and LDL-C levels in hypercholesterolaemic adults, which brings hope for reducing the risk factors for developing cardiovascular disease.

Coronary Artery Calcium and Cardiovascular Events in Patients With Familial Hypercholesterolemia Receiving Standard Lipid-Lowering Therapy

ObjectivesThe aim of this study was to evaluate the role of coronary artery calcium (CAC) as a predictor of atherosclerotic cardiovascular disease (ASCVD) (fatal or not myocardial infarction, stroke, unstable angina requiring revascularization, and elective myocardial revascularization) events in asymptomatic primary prevention molecularly proven heterozygous familial hypercholesterolemia (FH) subjects receiving standard lipid-lowering therapy. BackgroundFH is associated with premature ASCVD. However, the clinical course of ASCVD in subjects with FH is heterogeneous. CAC score, a marker of subclinical atherosclerosis burden, may optimize ASCVD risk stratification in FH. MethodsSubjects with FH underwent CAC measurement and were followed prospectively. The association of CAC with ASCVD was evaluated using multivariate analysis. ResultsA total of 206 subjects (mean age 45 ± 14 years, 36.4% men, baseline and on-treatment low-density lipoprotein cholesterol 269 ± 70 mg/dl and 150 ± 56 mg/dl, respectively) were followed for a median of 3.7 years (interquartile range: 2.7 to 6.8 years). CAC was present in 105 (51%), and 15 ASCVD events (7.2%) were documented. Almost one-half of events were hard outcomes, and the others were elective myocardial revascularizations. The annualized rates of events per 1,000 patients for CAC scores of 0 (n = 101 [49%]), 1 to 100 (n = 62 [30%]) and >100 (n = 43 [21%]) were, respectively, 0, 26.4 (95% confidence interval: 12.9 to 51.8), and 44.1 (95% confidence interval, 26.0 to 104.1). In multivariate Cox regression analysis, log(CAC score + 1) was independently associated with incident ASCVD events (hazard ratio: 3.33; 95% CI: 1.635 to 6.790; p = 0.001). ConclusionsCAC was independently associated with ASCVD events in patients with FH receiving standard lipid-lowering therapy. This may help further stratify near-term risk in patients who might be candidates for further treatment with newer therapies.

An evaluation of the serum biomarkers of Endothelial dysfunction in hypertensive and hypercholesterolemic subjects: A case-control study

An evaluation of the serum biomarkers of Endothelial dysfunction in hypertensive and hypercholesterolemic subjects: A case-control study

Use of plasma metabolomics to analyze phenotype-genotype relationships in young hypercholesterolemic females

Hypercholesterolemia is characterized by high plasma LDL cholesterol and often caused by genetic mutations in LDL receptor (LDLR), APOB, or proprotein convertase subtilisin/kexin type 9 (PCSK9). However, a substantial proportion of hypercholesterolemic subjects do not have any mutations in these canonical genes, leaving the underlying pathobiology to be determined. In this study, we investigated to determine whether combining plasma metabolomics with genetic information increases insight in the biology of hypercholesterolemia. For this proof of concept study, we combined plasma metabolites from 119 hypercholesterolemic females with genetic information on the LDL canonical genes. Using hierarchical clustering, we identified four subtypes of hypercholesterolemia, which could be distinguished along two axes represented by triglyceride and large LDL particle concentration. Subjects with mutations in LDLR or APOB preferentially clustered together, suggesting that patients with defects in the LDLR pathway show a distinctive metabolomics profile. In conclusion, we show the potential of using metabolomics to segregate hypercholesterolemic subjects into different clusters, which may help in targeting genetic analysis.

Predicting cardiovascular disease in familial hypercholesterolemia.

Familial hypercholesterolemia is a frequent genetic disease associated with a high lifetime risk of cardiovascular disease (CVD). Statins are the cornerstone of treatment of familial hypercholesterolemia; however, with the advent of novel LDL-cholesterol lowering therapies, it has become necessary to identify familial hypercholesterolemia subjects presenting a significant residual CVD risk. The aim of this review is to provide an update on the recent literature concerning cardiovascular risk stratification in familial hypercholesterolemia. Recently, several clinical and genetic factors have been shown to be independent predictors of CVD in familial hypercholesterolemia. These include clinical scores such as the Montreal-FH-SCORE, novel protein biomarkers, carotid plaque score and genetic predictors such as genetic risk scores as well as single-nucleotide polymorphisms. Although there has been recent progress in cardiovascular risk stratification in familial hypercholesterolemia, there is still a need to further refine our knowledge concerning phenotype modifiers in this disease. Indeed, current known predictors do not explain the entirety of cardiovascular risk. More precise individual risk stratification in familial hypercholesterolemia could help to better tailor the proper therapy for each patient.

Genotyping and Frequency of PCSK9 Variations Among Hypercholesterolemic and Diabetic Subjects.

Non-synonymous single-nucleotide polymorphism (SNPs) in the gene for proprotein convertase subtilisin/kexin type 9 (PCSK9) can influence cholesterol and glucose metabolism, leading to increased risk of cardiovascular disease and diabetes. To determine the frequency of four common PCSK9 SNPs, L10Ins, A56V, I474V, and E670G, in a population sample (n = 98) of the Hail region of Kingdom of Saudi Arabia. Blood was collected from participants; serum cholesterol, blood glucose and glycated hemoglobin were determined; genomic DNA was extracted and PCR amplicons from SNP-containing PCSK9 exons were subjected to Sanger sequencing. Out of 98 participants. 10 (10.20%) carried none of the SNPs, 2 (2.04%) the L10ins/A56V linked SNPs, 35 (35.71%) the I474V SNP, 22 (22.45%) both the I474V and E670G SNPs, and 29 (29.59%) the E670G SNP. Of the 30 eucholesterolemic diabetics patients, 11 (36.66%) carried the I474V SNP, 10 (33.33%) the E679G SNP and 6 (20%) the I474V/E679G. SNPs. Of 63 diabetic patients, 26 (41.26%) carry I474V SNP and 22 (34.92%) carry E670G SNP. Our data demonstrated that the I474V and E670G PCSK9 variants are very frequent in the Hail region of Saudi Arabia and are found at even higher frequency among diabetics. Further investigations are needed to determine whether these variations or another variant segregating with them can explain its apparent association with diabetes in this population.

Cardiovascular Benefits of Phenol-Enriched Virgin Olive Oils: New Insights from the Virgin Olive Oil and HDL Functionality (VOHF) Study.

The main findings of the "Virgin Olive Oil and HDL Functionality" (VOHF) study and other related studies on the effect of phenol-enriched virgin olive oil (VOO) supplementation on cardiovascular disease are integrated in the present work. VOHF assessed whether VOOs, enriched with their own phenolic compounds (FVOO) or with those from thyme (FVOOT), improve quantity and functionality of HDL. In this randomized, double-blind, crossover, and controlled trial, 33 hypercholesterolemic subjects received a control VOO (80mg kg-1 ), FVOO (500mg kg-1 ), and FVOOT (500mg kg-1 ; 1:1) for 3 weeks. Both functional VOOs promoted cardioprotective changes, modulating HDL proteome, increasing fat-soluble antioxidants, improving HDL subclasses distribution, reducing the lipoprotein insulin resistance index, increasing endogenous antioxidant enzymes, protecting DNA from oxidation, ameliorating endothelial function, and increasing fecal microbial metabolic activity. Additional cardioprotective benefits were observed according to phenol source and content in the phenol-enriched VOOs. These insights support the beneficial effects of OO and PC from different sources. Novel therapeutic strategies should increase HDL-cholesterol levels and enhance HDL functionality. The tailoring of phenol-enriched VOOs is an interesting and useful strategy for enhancing the functional quality of HDL, and thus, it can be used as a complementary tool for the management of hypercholesterolemic individuals.

Roles of Spicy Foods and Their Bioactive Compounds in Management of Hypercholesterolemia.

Hypercholesterolemia, as one of the major risk factors in development of cardiovascular diseases, is of mounting prevalence worldwide in recent years. Many nutraceuticals and phytochemical supplements serve as a promising complementary therapy in the management of hypercholesterolemia. Among them, spicy foods have attracted special attention. Plasma lipid-lowering activity of garlic, ginger, and turmeric have been well-studied in both humans and animals. Consumption of either 3 g/day of ginger or 2 g/day of curcumin for over 4 weeks effectively reduced blood cholesterol in hypercholesterolemia subjects. However, effects of chili and black peppers on blood cholesterol are studied little clinically. The present review is to summarize the findings of recent studies on the efficacy and mechanism of spicy foods and their primary bioactive components in management of hypercholesterolemia from preclinical studies to clinical trials.

Effect of Monacolin K and COQ10 supplementation in hypertensive and hypercholesterolemic subjects with metabolic syndrome.

Metabolic syndrome (MetS) is a world-wide epidemic disease with an increased risk of morbidity and mortality. Treatment strategies of MetS include pharmacologic and non-pharmacologic interventions and in this respect a relevant role has been shown for nutraceutical compounds (NCs). The aim of this study was to investigate the efficacy and safety of NCs incorporated with diet and lifestyle management versus diet alone, in lowering blood pressure (BP) values and improving lipid and glucose profile, in a group of hypertensives and hyper-cholesterolemic patients with MetS. 104 subjects with MetS (mean age 57.4 ± 8.8 years, 51% males) without history of cardio-vascular (CV) diseases were enrolled in the study. 52 subjects were treated with a once-daily oral formulation of a NCs containing red yeast rice and coenzyme Q10 added to their diet for 2 months and were compared with the 52 patients following a diet program. Differences in BP, serum total cholesterol (TC), low- and high-density-lipoprotein cholesterol (LDLC and HDLC), triglycerides (TG) and glucose values were compared by analysis of variance. A significant reduction of BP, TC, TG, LDLC and glucose levels was observed in both treatment groups. However, a greater reduction of systolic BP (-5.2 vs. -3.0 mmHg), diastolic BP (-4.9 vs. 2.9 mmHg), total cholesterol (-17.2%), LDLC (-21.8%), TG (-16.0%) and serum glucose (-3.4%) was observed in the treatment group relative to the control (p < 0.001 for all); HDLC remained unchanged (p = N.S.). Gender difference was not found in either group (p = N.S.). In patients with MetS, NC supplementation was safe, well tolerated and effective in improving clinic BP, lipid and glucose profile.

Moderate consumption of a soluble green/roasted coffee rich in caffeoylquinic acids reduces cardiovascular risk markers: results from a randomized, cross-over, controlled trial in healthy and hypercholesterolemic subjects.

Coffee is rich in bioactive compounds with health beneficial properties, with green coffee presenting higher phenol content than roasted. We evaluated the effects of regularly consuming realistic amounts of a green/roasted coffee blend on cardiovascular health-related biomarkers. A randomized, cross-over, controlled study was carried out in 25 normocholesterolemic [total cholesterol (TC) < 200mg/dL] and 27 hypercholesterolemic (TC 200-240mg/dL) subjects. During 8 weeks, volunteers consumed 6g/day of soluble green/roasted (35:65) coffee or a control beverage (water or an isotonic drink). Blood pressure, heart rate and body weight were monitored at the end of each intervention, and serum lipids [TC, HDL-C, LDL-C, VLDL-C, triglycerides and phospholipids], cytokines and chemokines (IL-1β, IL-2, IL-4, IL-5, IL-6, IL-7, IL-10, IL-12, IL-13, IL-17, G-CSF, GM-CSF, MCP-1, MIP-1β, TNF-α, INF-γ), adhesion molecules (ICAM-1, VCAM-1), and C-reactive protein were measured. Plasma antioxidant capacity (FRAP, ORAC and ABTS methods), and lipid (malondialdehyde, MDA) and protein (carbonyl groups, CG) oxidation were also determined. Attending to the general lineal model of variance for repeated measures, after the green/roasted coffee intervention significant reductions in TC, LDL-C, VLDL-C and triglycerides levels (p = 0.006, 0.001, 0.003 and 0.017, respectively), and a significant group effect were observed (0.001, < 0.001, 0.019 and 0.027, respectively). Only within the hypercholesterolemic group, attending to the Bonferroni test, the aforementioned lipid parameters were significantly lower after regular green/roasted coffee intake compared to baseline values. Moreover, after the coffee stage, plasma antioxidant capacity improved, according to the increase in ORAC and FRAP values (p < 0.001 and p < 0.001, respectively) and decrease of MDA (p = 0.015) and CG (p < 0.001) levels, without differences between groups. Systolic (p = 0.001) and diastolic (p < 0.001) blood pressure, heart rate (p = 0.035), and body weight (p = 0.017) were reduced in both normo- and hypercholesterolemic groups. Regular consumption of moderate amounts of a soluble green/roasted (35:65) coffee blend may contribute to improve cardiovascular health in moderately hypercholesterolemic people, as reducing serum lipids, blood pressure and body weight effects, as well as increasing plasma antioxidant capacity, have been observed. Moreover, positive influences on blood pressure, body weight, and plasma antioxidant capacity were obtained in the healthy group. Therefore, incorporation of green coffee beans into the coffee brew can be recommended as part of a dietary strategy to protect from cardiovascular disease.

Down-regulation of partial substitution for staple food by oat noodles on blood lipid levels: A randomized, double-blind, clinical trial

This clinical trial was conducted to assess the lipid-lowering activity of oat noodles by replacing partial staple food (wheat or rice noodle) in normal and mildly hypercholesterolemic subjects. Totally 84 healthy and mild hypercholesterolemic subjects were recruited and divided into 2 groups as experimental (oat noodles) and placebo (wheat noodles) and instructed to consume 100 g of oat noodles or wheat noodles (replacing one or two meals/day) for 10 weeks and followed by 2 weeks of follow up (without noodle consumption). Various anthropometric measurements and biochemical analysis were carried out during initial (baseline), 2nd, 6th, 10th and 12th week (follow-up). Consumption of oat noodles by replacing staple food for 10 weeks significantly reduced (**p < 0.01) the levels of total cholesterol (TC; 17.46%) and low-density lipoprotein LDL-c (19.03%) in both healthy and mildly hypercholesterolemic subjects. However, the hypocholesterolemic effect is significantly higher in mildly hypercholesterolemic subjects as compared with normal subjects. A pronounced decline (*p < 0.05) in the levels of various cardiovascular diseases (CVDs) markers including TC/HDL and LDL/HDL ratios and blood pressure (SBP; 11.09% and DBP; 7.48%) were observed in oat noodles supplemented subjects as equivalence with the placebo group. The partial replacement of staple food with oat noodle could considerably improve the health status of all subjects especially in hypercholesterolemic subjects and thus lower the risk of CVDs.

Delayed postprandial TAG peak after intake of SFA compared with PUFA in subjects with and without familial hypercholesterolaemia: a randomised controlled trial.

Postprandial hypertriacylglycerolaemia is associated with an increased risk of developing CVD. How fat quality influences postprandial lipid response is scarcely explored in subjects with familial hypercholesterolaemia (FH). The aim of this study was to investigate the postprandial response of TAG and lipid sub-classes after consumption of high-fat meals with different fat quality in subjects with FH compared with normolipidaemic controls. A randomised controlled double-blind cross-over study with two meals and two groups was performed. A total of thirteen hypercholesterolaemic subjects with FH who discontinued lipid-lowering treatment 4 weeks before and during the study, and fourteen normolipidaemic controls, were included. Subjects were aged 18-30 years and had a BMI of 18·5-30·0 kg/m2. Each meal consisted of a muffin containing 60 g (70 E%) of fat, either mainly SFA (40 E%) or PUFA (40 E%), eaten in a random order with a wash-out period of 3-5 weeks between the meals. Blood samples were collected at baseline (fasting) and 2, 4 and 6 h after intake of the meals. In both FH and control subjects, the level of TAG and the largest VLDL sub-classes peaked at 2 h after intake of PUFA and at 4 h after intake of SFA. No significant differences were found in TAG levels between meals or between groups (0·25≤P≤0·72). The distinct TAG peaks may reflect differences in the postprandial lipid metabolism after intake of fatty acids with different chain lengths and degrees of saturation. The clinical impact of these findings remains to be determined.

Cereal-Based Snack Bar with Added Plant Stanol Ester (Benecol®) Consumed between Meals Lowers Serum Total and LDL Cholesterol Effectively in Mildly to Moderately Hypercholesterolemic Subjects.

The cholesterol-lowering effect of foods with added plant sterols or stanols consumed as snacks might be compromised. The purpose of this study was to confirm the cholesterol-lowering efficacy of a specially formulated cereal-based snack bar with added plant stanol ester (1.6 g plant stanols/day) when consumed between meals twice a day. In a double-blind, placebo-controlled, 4-week parallel-design study, 71 mildly to moderately hypercholesterolemic subjects were randomized into one of two groups, stanol or placebo group. Subjects were advised to replace their ordinary snacks with test products in an isocaloric manner and otherwise keep their habitual diet unchanged. The study showed that a snack bar product with added plant stanol ester lowered LDL and non-HDL cholesterol by 8.6% and 9.2% (mean%-change), respectively, as compared to the placebo product. The change in LDL cholesterol was statistically significantly different (P = 0.001) between the groups while the change in HDL cholesterol or triglycerides did not differ between the groups. In conclusion, the cereal-based snack bar with added plant stanol ester ingested without a meal reduced LDL cholesterol significantly without affecting HDL cholesterol or triglyceride concentrations in mildly hypercholesterolemic men and women. The study is registered as NCT03284918.

Abstract 553: Scavenging Reactive Aldehydes With 5'-o-pentyl-pyridoxamine (PPM) Improves HDL Function and Reduces Atherosclerosis in Ldlr Deficient Mice

Background: Lipid peroxidation products impair the cholesterol efflux capacity of high-density lipoprotein (HDL) and contribute to the development of atherosclerosis. The effect of inhibition of HDL dysfunction by scavengers on HDL function and whether scavenging reactive aldehydes with PPM protects against the development of atherosclerosis was examined. Methods and Results: HDL of familial hypercholesterolemia (FH) subjects have impaired ability to promote cholesterol efflux and FH-HDL contain 5-fold more malondialdehyde adducts (MDA) than control HDL. In vitro studies revealed that reactive aldehyde MDA crosslinks apolipoprotein AI (apoAI) and impairs the ability of HDL to promote cholesterol efflux from Apoe -/- macrophages. 5'-O-pentyl-pyridoxamine (PPM), a potent scavenger of reactive aldehydes, abolished MDA-mediated crosslinking of apoA-I in HDL by 80 % (P&lt;0.05). PPM prevents the reduction in cholesterol efflux capacity of MDA treated HDL in Apoe-/- macrophages. Furthermore, PPM significantly improved the cholesterol efflux capacity of HDL from Ldlr -/- mice fed a Western diet (WD) for 16 weeks (P&lt;0.05), indicating that PPM protects HDL from modifications by reactive aldehydes and maintains HDL function in vivo. Importantly, administration of 1 mg/mL of the reactive aldehyde scavenger PPM, versus 1 mg/mL of the nonreactive analogue PPO, to Ldlr -/- mice consuming a WD for 16 weeks reduced the extent of proximal aortic atherosclerosis by 45% (P&lt;0.05). Immunohistochemistry studies revealed that PPM reduced the macrophage content and the number of TUNEL positive cells by 55% (P&lt;0.05) and by 60% (P&lt;0.01) in advanced atherosclerotic lesions of Ldlr -/- mice, respectively. In addition, the necrotic core area was reduced by 52% (P&lt;0.05) in advanced atherosclerotic lesions in Ldlr -/- mice treated with PPM compared to the control group. Conclusions: Treatment with PPM, a reactive aldehyde scavenger: 1) inhibits MDA-ApoA1 adduct formation thereby preserving HDL cholesterol efflux capacity in Ldlr -/- mice; 2) reduces the number of apoptotic cells in atherosclerotic lesions and the necrotic core area in lesions of Ldlr -/- mice. These results support the therapeutic potential of PPM in the treatment of atherosclerotic cardiovascular disease.

Effect of Amaranth Grain Consumption on Lipid Profile of Hypercholesterolemic Subjects

1. Abstract Introduction: An increase in Obesity and increased risk for chronic diseases has sparked global interest in less consumed traditional foods such as Quinoa and Amaranth. Amaranth grain is a pseudo-cereal with high quality gluten-free protein. It is consumed as a cereal, popped or in the form of a sweet preparation for religious fasting occasions in India. Animal studies suggest that amaranth seed consumption improves blood glucose and lipid profile. The present study was carried out in India with the objective of assessing the impact of amaranth grain consumption on fasting lipid profile and glucose concentration of hypercholesterolemic subjects. Materials and Methods : Nineteen subjects aged between 40-65yrs with hypercholestrolemia, fasting plasma cholesterol ≥ 200mg/dl were recruited. Informed consent was taken from the willing subjects, and popped amaranth grain 60g/day were provided for a period of eight weeks to replace regularly-consumed cereals in their diet. Before and after 8 weeks of amaranth grain consumption anthropometric parameters, fasting blood glucose and body composition by bio impedance method were measured. Results <span lang=EN-IN style=font-size: 10.0pt;font-family: times= new= roman,serif;mso-ascii-theme-font:major-latin;= mso-hansi-theme-font:major-latin;mso-bidi-theme-font:major-latin;color:black=>: No significant changes in weight and body composition were observed. However, plasma total and LDL-cholesterol and fasting plasma glucose concentrations showed significant increases after 8 weeks of amaranth grain consumption. Conclusion: Consumption of popped amaranth grain for 8 weeks in humans did not decrease blood lipid levels, <span lang=EN-IN style=font-size:10.0pt; font-family: times= new= roman,serif;mso-ascii-theme-font:major-latin;= mso-hansi-theme-font:major-latin;mso-bidi-theme-font:major-latin;color:black;= mso-themecolor:text1=>however a small increase in female subjects was observed. The significance of this observation is not known. 2. Keywords: <span lang=EN-IN style=font-size: 10.0pt;font-family: times= new= roman,serif;mso-ascii-theme-font:major-latin;= mso-hansi-theme-font:major-latin;mso-bidi-theme-font:major-latin;color:black=> Amaranth Seeds; Fasting Plasma Glucose; Total Cholesterol; HDL-Cholesterol