Plasma LDL-C Levels Research Articles

Screening for subclinical atherosclerosis in patients clinically diagnosed with familial hypercholesterolemia and determination of imaging-guided patient management strategy

Abstract Introduction Familial hypercholesterolemia (FH) is a monogenic dyslipidemia characterized by elevated plasma LDL-C levels, leading to early cardiovascular disease. The Dutch Lipid Clinic Network (DLCN) score is the most widely used clinical scoring system in current practice. Subclinical atherosclerosis is defined as the detection of atheromatous plaques in arterial territories, such as coronary, carotid or iliofemoral, before a symptom or event occurs. It is an early indicator of atherosclerotic burden. In this study, we investigated the presence of subclinical atherosclerosis in FH patients with a definite or probable clinical diagnosis according to DLCN score. We also tried to identify independent predictors of subclinical atherosclerosis. Methods This study is a single-center, prospective, and cross-sectional investigation involving a cohort of 215 FH patients. These patients are primary prevention patients and among them, 120 patients received a definite clinical diagnosis, while 95 patients received a probable clinical diagnosis based on the DLCN score. Carotid USG and Femoral USG were performed to screen for subclinical atherosclerosis and CAC score was calculated by non-contrast CT. Apo A-I, Apo B and Lp (a) measurements were analyzed by immunonephelometric method. Results The study population consisted of 136 (63%) women and 79 (37%) men. The mean age was 54 years (43-62) and the stigmata rate was 18%. Initially, 17% of patients were on aspirin, and 32% were receiving statin treatment; however, following subclinical atherosclerosis screening, these proportions significantly increased (aspirin usage to %32 and statin usage to %96) within the population. 148 patients (69%) had subclinical atherosclerosis in at least one site. Upon regional analysis, subclinical atherosclerosis rates were 48% in the coronary arteries, 47.5% in the carotid bifurcation region, and 40.5% in the femoral bifurcation region. Additionally, 25% of patients had atherosclerosis at one site, 27% at two sites, and 17% at all three sites. Age, male gender, pretreatment LDL-C level, Apo A-I/Apo B ratio and DM were identified as independent predictors of the presence of subclinical atherosclerosis in the FH patients. Furthermore age, male gender, pretreatment nonHDL-C level, Lp (a) ≥ 30 mg/dl and presence of femoral plaque were identified as independent predictors of coronary atherosclerosis. Conclusion Subclinical atherosclerosis is prevalent among FH patients, and this study has identified independent predictors associated with presence of subclinical atherosclerosis. However, despite this heightened risk, medication utilization among these patients remains below optimal levels and only a small proportion of the population has achieved their treatment goals. Our study highlights the influence of subclinical atherosclerosis on treatment approaches, as demonstrated by the notable rise in statin and aspirin utilization observed after screening.Clinical and biochemical characteristicsSubclinical Atherosclerosis Rates

Influence of Varied Dietary Cholesterol Levels on Lipid Metabolism in Hamsters.

Syrian hamsters are valuable models for studying lipid metabolism due to their sensitivity to dietary cholesterol, yet the precise impact of varying cholesterol levels has not been comprehensively assessed. This study examined the impact of varying dietary cholesterol levels on lipid metabolism in Syrian hamsters. Diets ranging from 0% to 1% cholesterol were administered to assess lipid profiles and oxidative stress markers. Key findings indicate specific cholesterol thresholds for inducing distinct lipid profiles: below 0.13% for normal lipids, 0.97% for elevated LDL-C, 0.43% for increased VLDL-C, and above 0.85% for heightened hepatic lipid accumulation. A cholesterol supplementation of 0.43% induced hypercholesterolemia without adverse liver effects or abnormal lipoprotein expression. Furthermore, cholesterol supplementation significantly increased liver weight, plasma total cholesterol, LDL-C, and VLDL-C levels while reducing the HDL-C/LDL-C ratio. Fecal cholesterol excretion increased, with stable bile acid levels. High cholesterol diets correlated with elevated plasma ALT activities, reduced hepatic lipid peroxidation, and altered leptin and CETP levels. These findings underscore Syrian hamsters as robust models for hyperlipidemia research, offering insights into experimental methodologies. The identified cholesterol thresholds facilitate precise lipid profile manipulation, enhancing the hamster's utility in lipid metabolism studies and potentially informing clinical approaches to managing lipid disorders.

Inhibition of hepatic bile salt uptake by Bulevirtide reduces atherosclerosis in Oatp1a1−/−Ldlr−/− mice

Bile salts can strongly influence energy metabolism through systemic signaling, which can be enhanced by inhibiting the hepatic bile salt transporter Na+ taurocholate cotransporting polypeptide (NTCP), thereby delaying hepatic reuptake of bile salts to increase systemic bile salt levels. Bulevirtide is an NTCP inhibitor and was originally developed to prevent NTCP-mediated entry of Hepatitis B and D into hepatocytes. We previously demonstrated that NTCP inhibition lowers body weight, induces glucagon-like peptide-1 (GLP1) secretion, and lowers plasma cholesterol levels in murine obesity models. In humans, a genetic loss-of-function variant of NTCP has been associated with reduced plasma cholesterol levels. Here, we aimed to assess if Bulevirtide treatment attenuates atherosclerosis development by treating female Ldlr−/− mice with Bulevirtide or vehicle for 11 weeks. Since this did not result in the expected increase in plasma bile salt levels, we generated Oatp1a1−/−Ldlr−/− mice, an atherosclerosis-prone model with human-like hepatic bile salt uptake characteristics. These mice showed delayed plasma clearance of bile salts and elevated bile salt levels upon Bulevirtide treatment. At the study endpoint, Bulevirtide-treated female Oatp1a1−/−Ldlr−/− mice had reduced atherosclerotic lesion area in the aortic root that coincided with lowered plasma LDL-c levels, independent of intestinal cholesterol absorption. In conclusion, Bulevirtide, which is considered safe and is EMA-approved for the treatment of Hepatitis D, reduces atherosclerotic lesion area by reducing plasma LDL-c levels. We anticipate that its application may extend to atherosclerotic cardiovascular diseases, which warrants clinical trials.

Sulforaphane upregulates the mRNA expression of NRF2 and NQO1 in non-dialysis patients with chronic kidney disease

Sulforaphane (SFN), found in cruciferous vegetables, is a known activator of NRF2 (master regulator of cellular antioxidant responses). Patients with chronic kidney disease (CKD) present an imbalance in the redox state, presenting reduced expression of NRF2 and increased expression of NF-κB. Therefore, this study aimed to evaluate the effects of SFN on the mRNA expression of NRF2, NF-κB and markers of oxidative stress in patients with CKD. Here, we observed a significant increase in the mRNA expression of NRF2 (p = 0.02) and NQO1 (p = 0.04) in the group that received 400 μg/day of SFN for 1 month. Furthermore, we observed an improvement in the levels of phosphate (p = 0.02), glucose (p = 0.05) and triglycerides (p = 0.02) also in this group. On the other hand, plasma levels of LDL-c (p = 0.04) and total cholesterol (p = 0.03) increased in the placebo group during the study period. In conclusion, 400 μg/day of SFN for one month improves the antioxidant system and serum glucose and phosphate levels in non-dialysis CKD patients.

Assessment of Serum Atherogenic Indices and Insulin Resistance in Retinal Vein Occlusion.

This study aimed to investigate serum atherogenic indices as novel cardiovascular risk factors associated with retinal vein occlusion (RVO). This retrospective case-control study included 57 patients with newly diagnosed RVO whose plasma lipid profile (low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], total cholesterol [TC], and triglycerides [TG]) and insulin resistance were examined. Serum atherogenic indices (LDL-C/HDL-C, TC/HDL-C, TG/HDL-C, and non-HDL-C/HDL-C ratios) and presence of insulin resistance were compared between the patients and 63 healthy subjects. Cut-off values were determined by receiver operating characteristic curve analysis. The mean age of the RVO patients was 63.7±9.4 years. Plasma levels of LDL-C, HDL-C, TC, and TG showed no significant difference between the patient and control groups (p>0.05). However, LDL-C/HDL-C, non-HDL-C/HDL-C, and TC/HDL-C ratios were higher in the RVO group compared to healthy subjects (p=0.015, p=0.036, and p=0.015, respectively). Fasting insulin concentrations, plasma insulin, and homeostasis model assessment of insulin resistance (HOMA-IR) index were higher in the RVO patients compared to controls (p=0.003, p=0.001, and p=0.001, respectively). LDL-C/HDL-C, TC/HDL-C, and non-HDL-C/HDL-C ratios were found to be increased in RVO. Compared to the traditional plasma lipid profile, serum atherogenic indices were found to be superior predictors of RVO development. Measurement of HOMA-IR index should be taken into consideration in the evaluation of insulin resistance. High serum atherogenic indexes in RVO patients reveal the need to take precautions against the risk of cardiovascular disease and stroke.

The Lipid-Lowering Efficacy of a Nutraceutical Combination Including Leucoselect Phytosome, Red Yeast Rice, Policosanol and Folic Acid in Dyslipidaemia Patients: Real-World Insights.

Cardiovascular disease is a global health concern and reducing plasma LDL-C levels is a major goal in cardiovascular prevention. Our study aimed to evaluate the effectiveness of a nutraceutical formulation including leucoselect® phytosome®, red yeast rice, policosanol and folic acid on LDL-c levels in patients at low cardiovascular risk with dyslipidemia. We prospectively enrolled all consecutive patients with dyslipidemia at low cardiovascular risk who were unresponsive to diet and physical activity. Clinical assessments and laboratory analyses, encompassing lipid profile, hepatic function, and CPK levels, were performed at baseline prior to initiating treatment and repeated at the 12-week mark following administration of the study nutraceutical. Sixty (60) consecutive patients (mean age 48.02 ± 10.1 years; 60% male) were included. At the 12-week follow-up, a statistically significant reduction in Total Cholesterol (13.1%) and LDL-c serum level (20.4%) was observed. Hepatic and muscular function remain stable over the time. The adherence to therapy was 99% and the persistence was maximum. The nutraceutical formulation including leucoselect® phytosome® red yeast rice, policosanol and folic acid significantly reduced the LDL-c plasma levels, consistent with previous research showing that the bioactive component in red yeast rice-lovastatin-is effective in addressing problems with lipid metabolism. Importantly, it was safe and well-tolerated among patients with dyslipidemia in a real-world setting.

Oral PCSK9 Inhibitors.

In this review, we will discuss the data from early clinical studies of MK-0616 and summarize clinical trials of other oral proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. The success of PCSK9 inhibition with monoclonal antibody injections has fueled the development of additional therapies targeting PCSK9, including oral formulations, the most advanced of which is MK-0616. MK-0616 is a novel, orally administered macrocyclic peptide that binds to PCSK9 and inhibits binding of PCSK9 to the LDL receptor, thereby decreasing plasma levels of LDL-C. Clinical trial data on the safety and efficacy of MK-0616 are promising and report LDL-C-lowering efficacy comparable to that provided by injectable PCSK9 inhibitors. Ongoing and future studies of oral PCSK9 inhibitors in development will evaluate the safety, efficacy, and effectiveness of these agents and their potential role in preventing cardiovascular disease events.

Atherosclerotic plaque stabilization and regression: a review of clinical evidence.

Atherosclerotic plaque results from a complex interplay between lipid deposition, inflammatory changes, cell migration and arterial wall injury. Over the past two decades, clinical trials utilizing invasive arterial imaging modalities, such as intravascular ultrasonography, have shown that reducing levels of atherogenic lipoproteins, mainly serum LDL-cholesterol (LDL-C), to very low levels can safely reduce overall atherosclerotic plaque burden and favourably modify plaque composition. Classically, this outcome has been achieved with intensive statin therapy. Since 2016, newer and potent lipid-lowering strategies, such as proprotein convertase subtilisin-kexin type 9 inhibition, have shown incremental effects on plaque regression and risk of clinical events. Despite maximal reduction in plasma LDL-C levels, considerable residual cardiovascular risk remains in some patients. Therefore, there is a need to study therapeutic approaches that address residual risk beyond LDL-C reduction to promote plaque stabilization or regression. Contemporary imaging modalities, such as coronary computed tomography angiography, enable non-invasive assessment of the overall atherosclerotic plaque burden as well as of certain local plaque characteristics. This technology could allow further study of plaque stabilization and regression using novel therapeutic approaches. Non-invasive plaque assessment might also offer the potential to guide personalized management strategies if validated for this purpose.

Sirtuin-1 directly binds and deacetylates hepatic PCSK9 to inhibit low-density lipoprotein receptor degradation

Abstract Background Low-density lipoprotein cholesterol (LDL-C) is causally involved in atherosclerotic cardiovascular disease (ASCVD). We have previously shown that pharmacological activation of Sirtuin-1 (SIRT1), a NAD+-dependent deacetylase, reduces plasma LDL-C levels by decreasing PCSK9 and increasing hepatic LDLR expression, thus exerts atheroprotective effects in mice; however, the mechanism of SIRT1 action remains elusive. Purpose We found diminished levels of circulating SIRT1 in atherosclerotic mice compared to wild-type healthy controls. We hypothesized that this decrease in SIRT1 levels may promote dysregulated lipid metabolism and ASCVD in humans. Herein, we aimed to restore the reduced systemic Sirtuin-1 plasma levels in ASCVD by injecting recombinant murine Sirtuin-1 (rmSIRT1) in atherosclerotic mice. Methods Twelve-week-old apolipoprotein E-deficient (ApoE-/-) male mice fed a high-cholesterol diet (1.25% w/w) were randomized to receive rmSIRT1 (n=6; 0.3mg/kg BW i.p.) or vehicle treatment (n=6) every third day over 4-weeks. Mice were euthanized and organs were harvested to study lipid metabolism and ASCVD progression. Human hepatocytes (Huh7) cells were used to perform radioactive assays to study cellular uptake of radioiodinated LDL, surface plasmon resonance to study binding and site-directed mutagenesis to dissect the underlying molecular mechanism exerted by circulating SIRT1. Results Boosting circulating SIRT1 levels increased hepatic LDLR expression, reduced plasma LDL-C levels and progression of plaques in ApoE-/- mice (Figure 1). rmSIRT1 treatment did not change hepatic expression of total PCSK9 but increased its deacetylated status. Mechanistically, rmSIRT1 directly bound to hepatic PCSK9 and deacetylated PCSK9 at 3 sites: Lys243, Lys421 and Lys506 as shown by Surface Plasmon Resonance and mass spectrometry, respectively. In vitro mutagenesis to triple deacetylation mimetic (3KR) in hepatocytes (Huh7 cells) reduced SIRT1-induced PCSK9 activity, as evidenced by increased cellular binding and association of 125I-LDL through LDLR in Huh7cells. Finally, plasma levels of SIRT1 and PCSK9 were assessed at baseline in patients with acute coronary syndromes (ACS) where plasma SIRT1 showed an inverse correlation with PCSK9 and conferred a reduced risk of major adverse cardiovascular events. Conclusion SIRT1 directly binds PCSK9 and decreases its activity by deacetylation, thereby enhancing LDL-C clearance by hepatic LDLR upregulation. Increased circulating SIRT1 exerts atheroprotective effects and is associated with improved prognosis in patients with ACS.Figure 1

Assessment of virgin coconut oil in a balanced diet on indicators of cardiovascular health in non-obese volunteers: A human metabolic study

Background and aimsConsumption of coconut oil is implicated in cardiovascular disease risk. On the contrary, virgin coconut oil (VCO) is believed to offer better health benefits, however, the evidence to support such claims is lacking, particularly in humans. Therefore, this study aimed at assessing the impact of VCO in a balanced diet on HDL-C and some of the anthropometric and biochemical parameters associated with human cardiovascular health before and after the feeding experiment. MethodsIn a crossover observational study, apparently healthy non-obese male volunteers (n = 22) aged between 28 and 50years with a mean body weight of 67.5 kg were inducted into a two-arm controlled feeding experiment one after another for eight weeks with a six-week washout period. In the first arm, the diets were prepared with VCO, whereas peanut oil was used in the second arm (∼35g/day) as the control. ResultsCompared to baseline, the consumption of VCO did not affect HDL-C and anthropometric measures at the end of the 8th week, whereas plasma total cholesterol (TC) and LDL-C levels (Means±standard error; 172 ± 5.6 mg/dL versus 186 ± 5.9 mg/dL and 113 ± 4.29 mg/dL versus 126 ± 4.17 mg/dL respectively) increased significantly. However, plasma triglycerides and some of the cardiovascular risk markers (namely, vascular cell-adhesion molecules, serum amyloid proteins and C-reactive protein) remained unaltered. Further, most of the changes in the VCO arm were comparable to the peanut oil regimen. ConclusionThe consumption of VCO in a balanced diet displayed neutral effects on most parameters related to cardiovascular risk. However, the rise in TC and LDL-C must be tested in a larger sample size over longer periods.

Stabilization of vulnerable plaque in the ACS patient: evidence from HUYGENS studies.

The introduction of PCSK9 inhibitors in addition to statin therapy allowed better control of LDL-C plasma levels with a subsequent reduction of cardiovascular events. Human atherosclerosis has been previously considered an irreversible condition; studies firstly based on angiography imaging and secondly with intra-coronary imaging-mainly IVUS based-have demonstrated that lipid-lowering therapy based on statins can stabilize and even reduce atherosclerotic burden of coronary circulation. While plaque stabilization and/or reduction with PCSK9 inhibitors have already been demonstrated in the GLAGOV study, the HUYGENS study showed a positive effect not only on atherosclerotic burden but also on plaque phenotype, with an increased FCT, decrease in maximum lipid arch, and reduction of macrophages infiltration. Further studies need to assess the clinical impact of the reduction of plaques displaying high-risk features with PCSK9 inhibitors.

Small Intestinal Digestive Functions and Feed Efficiency Differ in Different Pig Breeds

Small intestinal growth and health affect its digestion and absorption ability, while little information exists about the small intestinal morphology and function differences among the different pig breeds. Therefore, 90 healthy 35 days of age Taoyuan black (TB), Xiangcun black (XB), and Duroc (DR) pigs (30 pigs per breed) with similar body weight (BW) of the same breed were reared to 185 days of age to evaluate the potential relationship between feed efficiency and small intestinal morphology and function at 80, 125, and 185 days of age. The results show that the TB and XB pigs had lower initial and final BW, ADG, and ADFI and plasma CHO and LDL-C levels, whereas they had higher plasma LIP levels and jejunal trypsin, invertase, lactase, and maltase activities and higher DM, ADF, Tyr, Arg, and His digestibility at 80 days of age compared with the DR pigs. At 125 days of age, TB and XB pigs had lower apparent total tract digestibility and plasma CHO, HDL-C, LDL-C, and NH3 levels; XB pigs had lower DM and NDF digestibility, and TB pigs had higher jejunal lactase and maltase activities. At 185 days of age, TB and XB pigs had lower DM, EE, ADF, and GE digestibility, while having higher plasma ALT and UN levels; TB pigs had higher plasma AST level and jejunal chymase activity. Furthermore, the plasma free amino acid contents, small intestinal VH, and nutrient transporter expression levels differed at different ages. Therefore, the different pig breeds exhibited significantly different growth performance and small intestinal growth, mainly resulting from the differences in digestive enzymes and nutrient transporters in the small intestine.

Antidiabetic and Antidyslipidemic Effects of Artemisia mesatlantica, an Endemic Plant from Morocco.

The study aimed to assess the antihyperglycemic and antidyslipidemic activities of Artemisia mesatlantica. Artemisia mesatlantica is an endemic plant of Morocco used in traditional medicine as an alternative treatment for diabetes. The study was designed to examine the antihyperglycemic and antidyslipidemicability of aqueous extract of Artemisia mesatlantica (AMAE) in experimental animal models. The effect of the single and repeated oral administration (7 days of treatment) of AMAE (60 mg/kg) on blood glucose and lipid profile were assessed in normal and streptozotocin-induced diabetic rats. Furthermore, to confirm the antidyslipidemic effect of Artemisia mesatlantica, a model of hyperlipidemia induced by tyloxapol (Triton WR-1339) in rats was used. The AMAE (60 mg/kg) was able to significantly reduce glycaemia, improve lipid profile and increase hepatic glycogen content in STZ-induced diabetic rats. In addition, pretreatment of rats for 7 consecutive days with an aqueous extract of Artemisia mesatlantica (600 mg/kg) prior to tyloxapol injection prevented increases in plasma levels of total cholesterol, triglycerides and LDL-c. From these observed results, it can be deduced that Artemisia mesatlantica possesses remarkable antidiabetic and antihyperlipidemic properties.

Evaluating the toxicity of the antiPCSK9 vaccine in the animal model

Abstract Background Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition is a novel cholesterol-lowering treatment for decreasing the risk of atherosclerosis. We have previously shown that active immunization using the antiPCSK9 vaccine could decrease hypercholesterolemia and impede the development of atherosclerotic lesions in the experimental model of atherosclerosis. Purpose Here, we intended to evaluate the toxicity of the vaccine in healthy mice. Methods Forty male and female mice were divided into 4 experimental groups, including vaccine female (10 mice) and male (10 mice) groups receiving the antiPCSK9 vaccine as well as corresponding control female (10 mice) and male (10 mice) groups receiving the phosphate buffer. Vaccination was planned based on 4 subcutaneous injections of the vaccine formulation (10 μg/mouse) in bi-weekly intervals. The toxicity study was performed by the sub-acute protocol, 28 days after the last vaccine injection. To this end, the plasma levels of lipid indexes, urea, creatinine, AST, ALT, ALP, and fasting plasma glucose (FPG), as well as the CBC test were measured using commercial kits. To evaluate histopathological alterations, various tissues including the heart, liver, kidneys, spleen, and brain were studied using hematoxylin & eosin (H&E) staining by an expert pathologist. The severity of damage to the tissue was considered based on the standard classification; grade 1 as light damage, grade 2 as moderate damage, grade 3 as the bit-intense damage, and grade 4 as the intense damage. Results The results showed the non-significant changes of total cholesterol, triglyceride, HDL-C, FBS, creatinine, urea, AST, ALP, ALT, and PAB in the vaccinated mice when compared with control mice. However, plasma levels of LDL-C were significantly decreased in vaccinated male (by16.93±2.5 mg/dL, p=0.001) and female mice (by 22±2.7 mg/dL, p=0.001) when compared with corresponding control mice. CBS test indicated that there were no significant changes in the levels of WBC, RBC, HGB, HCT, MCH, MCHC, PLT, LYM, NEUT, PDW, and MPV in the vaccinated mice when compared with control mice. However, the levels of MCV, RDW-SD, and P-LCR were significantly decreased by (4.6±1.2 fL, p=0.02), (4±0.6 fL, p=0.001), and (0.13±0.01%, p=0.001), respectively, in vaccinated male mice when compared with control male mice. Evaluating histopathological alterations in various tissues indicated no significant adverse effects in vaccinated mice when compared to control mice. Conclusions The findings of the present study indicate that the antiPCSK9 is safe and exerts no adverse effects on the function of different organs and blood levels of the cellular and biochemical biomarkers in healthy mice. Funding Acknowledgement Type of funding sources: None.

Maternal probiotics supplementation improves immune and antioxidant function in suckling piglets via modifying gut microbiota.

Probiotics could improve the health, growth, and development of host or their foetuses/offspring via regulating gut microbiota. The present study was conducted to determine the effects of maternal probiotics supplementation on gut microbiota and metabolites of sows and their suckling piglets, as well as plasma biochemical parameters, oxidative/anti-oxidative indexes, and inflammatory cytokine levels of suckling piglets. A total of 32 pregnant Bama mini-pigs were selected and randomly divided into two groups. The sows were fed a basal diet (control group) or a basal diet supplemented with probiotics (probiotics group) from mating to day 21 of lactation. Samples from sows were collected on day 105 of pregnancy and day 21 of lactation and from piglets on day 21 of lactation. The results showed that probiotics supplementation increased the faecal abundances of Ruminococcus, Bacteroides, and Anaeroplasma and decreased Tenericutes on day 105 of pregnancy while increased the abundances of Actinobacteria and Anaerostipes and decreased Proteobacteria and Desulfovibrio on day 21 of lactation. In addition, probiotics supplementation decreased the faecal levels of tryptamine, putrescine, and cadaverine on day 105 of pregnancy and isovalerate and skatole on day 21 of lactation while increased butyrate level on day 21 of lactation. Further studies showed that maternal probiotics supplementation decreased the plasma levels of AMM, TC, LDL-C, Ala, Tau, MDA, H2 O2 , IL-1β, IL-2, IL-6, and IFN-α of suckling piglets. Moreover, maternal probiotics supplementation increased the abundances of Deferribacteres, Fusobacteria, and Fusobacterium while decreased Anaerostipes in piglet's colon. Spearman's correlation analysis revealed a potential link between gut microbiota alterations and their metabolites. Dietary probiotics supplementation during pregnancy and lactation periods could improve sow status, alleviate oxidative stress and inflammation response, and improve nutrient metabolism of piglets by altering the gut microbiota. The probiotics alter maternal and offspring's gut microbiota involving in offspring's physiological and metabolic changes, and present a new perspective that the effects of gut microbiota changes induced by probiotics supplementation will help in addressing the growth and development and health problem of their foetuses/offspring.

APO E mutations as a cause of familiar hypercholesterolemia in North-East Moravia region

Background and Aims : Familiar hypercholesterolemia (FH) is a collective term for a set of genetically linked diseases that cause increased plasma LDL-C levels by various mechanisms, thereby increasing an individual's cardiovascular risk. FH is most frequently caused by one of the three following mechanisms: the absence or reduction of the number and thereby decreased function of LDL-receptors, the defect in apolipoprotein B or increased function of the PCSK9 enzyme.We recently encountered a remarkable occurrence of patients with mutations in Apo E lipoprotein.

Association of cytochromes P450 3A4*22 and 3A5*3 genotypes and polymorphism with response to simvastatin in hypercholesterolemia patients.

BackgroundsInter-individual variability in response to statin was mainly due to genetic differences. This study aimed to investigate the association of CYP3A4*22 (rs35599367), CYP3A5*3 (rs776746) single nucleotide polymorphism (SNP) with response to simvastatin in hypercholesterolemia patients conducted at King Abdulaziz University hospital (KAUH) in Jeddah, Saudi Arabia.Patients and methodsA total of 274 participants were registered in the current study. Hypercholesterolemic patients taking simvastatin 20 mg (n = 148) and control subjects (n = 126) were tested for rs35599367 and rs776746 genotypes using Custom Taqman ® Assay Probes. Response to simvastatin in these patients was assessed by determination of low density lipoprotein (LDL-C), total cholesterol (TC) and by measuring statin plasma levels using Liquid Chromatography-Mass Spectrometry (LC-MS).ResultsNone of the participants carried a homozygous CYP3A4*22 mutant genotype, while 12 (4.4%) individuals had a heterozygous genotype and 262 (95.6%) had a wild homozygous genotype. The CYP3A5*3 allele was detected in the homozygous mutant form in 16 (5.8%) individuals, while 74 (27.0%) individuals carried the heterozygous genotype and 184 (67.2%) carried the wildtype homozygous genotype. Of the patient group, 15 (11%) were classified as intermediate metabolizers (IMs) and 133 (89%) as extensive metabolizers (EMs). Plasma simvastatin concentrations for the combined CYP3A4/5 genotypes were significantly (P<0.05) higher in the IMs group than in the EMs group. TC and plasma LDL-C levels were also significantly (P<0.05) higher in IMs than in EMs.ConclusionThe present study showed associations between CYP3A4*22 (rs35599367) and CYP3A5*3 (rs776746) SNP combination genotypes with response to statins in hypercholesterolemia. Patients who had either a mutant homozygous allele for CYP3A5*3 or mutant homozygous and heterozygous alleles for CYP3A4*22 showed increased response to lower TC and LDL-C levels.

The pharmacology of cholesterol-lowering drugs: The pharmacology of cholesterol-lowering drugs

The causal role of low-density lipoprotein cholesterol LDL-C in atherosclerotic-related cardiovascular disease (ASCVD) has been undoubtedly established over the last decades, and lowering plasma LDL-C levels represents the main approach to reduce the risk of cardiovascular (CV) events. A large number of observations has definitely proven that the protective effect is independent of the drug used to lower LDL-C, with a continuous linear reduction of CV risk with further LDL-C reductions. Although high-intensity statin therapy may significantly reduce CV event incidence, frequently statins are insufficient to achieve the large reductions recommended by current guidelines for high and very high risk patients. Several non-statin drugs, having mechanisms of action complementary to that of statins, are now available, and include ezetimibe, monoclonal antibodies targeting PCSK9, and, more recently, inclisiran, bempedoic acid, and evinacumab. Combining these drugs based on the recommendations by current and future guidelines should be considered for optimal risk reduction, although several gaps in clinical practice remain to be filled.

Plasma Calcium and Phosphorus Levels and Cardiovascular Disease Risks in Egyptian Type 2 Diabetic Patients

Background: Cardiovascular complication of diabetes is considered an important issue that needs deep investigations. The levels of plasma calcium (Ca) and phosphorus (P) have been implicated as having an association to cardiovascular diseases.&#x0D; AIM: The objective of the present research was to study the plasma levels of both Ca and P and their association to the atherogenic ratio; total cholesterol: high density lipoprotein-cholesterol and the plasma albumin in male and female patients with type 2-diabetes. The interrelation between anthropometric parameters represented by body mass index (BMI), waist circumference and waist/hip ratio with Ca and P were studied. Also, the association between plasma Ca and P with their dietary intake were investigated.&#x0D; Subjects and METODS: Thirty-one type 2-diabetic male and female patients participated in the study, in addition of ten healthy subjects. Biochemical parameters, anthropometric measurements and nutrients′ intake were assessed. Biochemical parameters include plasma Ca, P, lipid profile, albumin, liver function tests and creatinine.&#x0D; RESULTS: Plasma Ca levels of female patients of BMI&gt; 30 kg/m2 demonstrated significant increase compared to the control group. All male and female patients showed significant increase in plasma P compared to the control group. Glycosylated hemoglobin of male and females showed significant high values compared to the control group except for diabetic male of BMI&gt;30 kg/m2 that showed insignificant increase. No significant changes in plasma TG and LDL-C levels were noticed compared to the control. Plasma TC of patients showed significant high levels compared to the control group. The levels of HDL-C of patients were significantly lower than that of the control. The ratios of TC/HDL-C diabetic patients either male or female and whatever their BMI were significantly higher than that of the control. No significant changes in plasma activities of ALT and AST and bilirubin levels were observed among the different groups including the control. Plasma albumin levels demonstrated significant reduction compared to the control group whatever their sexes or BMI. Plasma creatinine levels of the different diabetic groups showed insignificant change from the control group except for the male group of BMI&lt;30 kg/m2 that showed significant elevation. In male, plasma Ca showed significant negative correlation with albumin and positive correlation with creatinine and dietary vitamin D. In female, a significant positive correlation was noticed between plasma and dietary P while a negative correlation was observed between plasma Ca and dietary iron.&#x0D; CONCLUSION: Elevated of plasma P together with reduced plasma albumin and elevated TC/HDL-C may reflect an association of plasma P to CVD in male and female diabetic subjects while high plasma Ca might predict CVD in only female diabetic patients of BMI &gt; 30 kg/m2.

Preliminary Evidence of Efficacy for Policol&amp;lt;sup&amp;gt;®&amp;lt;/sup&amp;gt; One Cholesterol Lowering Effect from Week 4, Adapted to the Upcoming Restrictions for Monacolins in Food in the EU

Cholesterol is necessary for many cell functions but it can also be harmful if it is allowed to reach high blood concentrations, as the risk for premature atherosclerotic cardiovascular diseases increases. Many food supplements contain currently 10 mg of monacolin K in order to benefit of the approved claim to maintain normal blood LDL-cholesterol levels. However, the EFSA has considered that cases of adverse reactions have been reported for monacolins from red yeast rice at intake levels as low as 3 mg/day. That is the reason why the main aim of the present study was to show the effect of Policol^® One new formula in patients with non-desirable lipidic profile levels. Policol^® One new formula contains a wide range of plant extracts with not only a traditional use, but also a proven effect on plasma lipids. The consumption of one capsule of new Policol^® One during dinner for only 4 weeks favorably affected plasma LDL-C (-39.52%) and TC (-40.52%) levels in healthy volunteers. No significant effect on TG and HDL-C was shown after 4 weeks. However, after 12 weeks TG biomarker exhibited a significant reduction (-19.91%) and HDL-C (+9.84%) also improved. No adverse effects were reported during the study. Lower lipid properties may be associated with a synergistic effect of the ingredients which allow us to formulate with a lower and safer dosage of monacolin K.