Serum Low-density Lipoprotein Cholesterol Research Articles

FNDC5 Attenuates Atherosclerotic Plaque Formation and Regulates PPARα/HO-1 in ApoE−/− Mice

Introduction: This study attempted to observe the role of fibronectin type III domain-containing protein 5 (FNDC5) in atherosclerosis development and the underlying mechanism. Methods: After being fed a high-fat diet (HFD), ApoE^−/− mice were injected with saline, control adenovirus (Ad-vector), or FNDC5 overexpressing adenovirus (Ad-FNDC5). ApoE^−/− mice fed with a chow diet were considered the control. After 12 weeks of treatment, the levels of serum high-density lipoprotein cholesterol (HDL-C), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), and irisin were detected by commercial kits. Results: Compared with the control, the serum TG, TC, and LDL-C levels, aortic plaque area, and weight were significantly increased, while serum HDL-C and irisin levels were reduced in HFD mice. Treating with Ad-FNDC5 could alleviate these changes in HFD mice and cause the activation of PPARα/HO-1 signaling in aortic tissue. After co-treating with GW6471, a PPARα antagonist, the effects of Ad-FNDC5 on the weight, serum LDL-C, TC, TG, and HDL-C levels, and aortic plaque of HFD mice were partly blocked. Conclusion: Elevated FNDC5 has a delaying effect on atherosclerotic plaque formation, which may be related to the upregulation of PPARα/HO-1 signaling.

Adenosine Triphosphate Citrate Lyase and Fatty Acid Synthesis Inhibition

Adenosine triphosphate citrate lyase (ACLY) is a key regulatory enzyme of glucose metabolism, cholesterol and fatty acid synthesis, and the inflammatory cascade. Bempedoic acid, an ACLY inhibitor, significantly reduces atherogenic lipid markers, including low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol, and apolipoprotein B. Additional effects of ACLY inhibition include antitumor growth; reduction of triglycerides and proinflammatory molecules such as high-sensitivity C-reactive protein; less insulin resistance; reduction of hepatic lipogenesis; and weight loss. While numerous ACLY inhibitors have been identified, most of the clinical data have focused on bempedoic acid. The Cholesterol Lowering via Bempedoic Acid, an ACL-Inhibiting Regimen (CLEAR) program was a series of phase 3 clinical trials that evaluated its effects on lipid parameters and safety, leading to US Food and Drug Administration approval in 2020. CLEAR Outcomes was a phase 3, double-blind, randomized, placebo-controlled trial in individuals with a history of statin intolerance, serum LDL-C level of 100 mg/dL or higher, and a history of, or at high risk for, cardiovascular disease. Bempedoic acid modestly reduced the primary 4-way cardiovascular composite end point as well as the individual components of myocardial infarction and coronary revascularization but did not reduce stroke, cardiovascular death, or all-cause mortality. Rates of gout and cholelithiasis were higher with bempedoic acid, and small increases in serum creatinine, uric acid, and hepatic-enzyme levels were also observed. ACLY inhibition with bempedoic acid has been established as a safe and effective therapy in high-risk patients who require further LDL-C lowering, particularly for those with a history of statin intolerance. The recently published CLEAR Outcomes trial revealed modest reductions in cardiovascular events with bempedoic acid, proportional to its LDL-C lowering, in high-risk individuals with statin intolerance and LDL-C levels of 100 mg/dL or higher. The additional effects of ACLY inhibition have prompted a more thorough search for novel ACLY inhibitors for conditions such as cancer, hypertriglyceridemia, chronic inflammation, type 2 diabetes, fatty liver disease, obesity, and metabolic syndrome. Similarly, therapies that reduce fatty acid synthesis are being explored for their use in cardiometabolic conditions.

Timing of hormone therapy and its association with cardiovascular risk and metabolic parameters in 4-vinylcyclohexene diepoxide-induced primary ovarian insufficiency mouse model

Objective To evaluate the effects of various initiation time points and durations of hormone therapy (HT) on cardiovascular and metabolic parameters of premenarche, primary ovarian insufficiency (POI) mouse model, induced by 4-vinylcyclohexene diepoxide. Methods A total of 50 mice at 4 weeks of age were developed into POI mouse model, further randomly categorized into 5 groups: control group without any intervention; no HT group with only high-fat diet (NT); group 1 with delayed estradiol treatment (T1); group 2 with on-time, continuous estradiol treatment (T2); and group 3 with on-time estradiol treatment but early stop (T3). Cardiovascular risk and metabolic parameters were measured. Results Presenting with similar body weights, blood glucose levels of T1, T2, and T3 were all significantly lower than NT (p < .001). Serum total cholesterol and insulin were also significantly lower in all HT groups than in NT, especially in T2 (p < .001). For serum low-density lipoprotein-cholesterol, only T2 resulted in the statically lower level than those of NT, T1, and T3 (p < .001). Aortic thickness was significantly increased with aggravated fibrotic change of the intima in NT, and such consequence was significantly ameliorated in HT groups, mostly lowered in T2 (p < .05). Last, serum pro-inflammatory cytokines were significantly low in the HT groups than in NT, especially in T2 with the lowest level (p < .05). Conclusions On-time, continuous E2 treatment immediately after a biologic estrogen deprivation event significantly reduced metabolic and cardiovascular risks in young, pre-menarche female mouse models of POI, confirming decreased serum levels of pro-inflammatory cytokines.

The Role of Proton-Coupled Amino Acid Transporter 2 (SLC36A2) in Cold-Induced Thermogenesis of Mice.

Brown adipocytes mainly utilize glucose and fatty acids to produce energy, which play key roles in thermogenesis. Furthermore, brown adipocytes also utilize other substrates, such as amino acids, for energy expenditure in various conditions. Here, we report the new physiological roles of proton-coupled amino acid transporters, SLC36A2 and SLC36A3, on global energy metabolism. The relative mRNA expression levels of both Slc36a2 and Slc36a3 were all highest in brown adipose tissue. We then generated global Slc36a2 and Slc36a3 knockout mice to investigate their functions in metabolism. Neither loss of Slc36a2 nor Slc36a3 affected the body weight and body composition of the mice. Slc36a2 knockout mice exhibited increased oxygen consumption during the daytime. After cold treatment, inhibition of Slc36a2 significantly decreased the mass of brown adipose tissue compared to wildtype mice, while it lowered the expression level of Cpt1a. Moreover, the serum lipid levels and liver mass were also decreased in Slc36a2 knockout mice after cold treatment. On the contrary, Slc36a3 knockout impaired glucose tolerance and up-regulated serum LDL-cholesterol concentration. Thus, SLC36A2 and SLC36A3 play central and different roles in the energy metabolism of the mice.

Abstract P3111: Sex Differences In The Proteomic Response To Chronic Myocardial Ischemia In Swine

Intro: There are known sex differences in response to ischemic insult yet the mechanisms behind these differences have not been fully elucidated. Previous work in our lab has demonstrated female sex confers a relative protective effect on CO in the setting of chronic ischemia. The aim of this study was to use total proteomic analysis in order to uncover the mechanisms behind sex specific responses to myocardial ischemia in a porcine model. Methods: Eight 11-week old pigs (3 female, 5 male) underwent surgical placement of an ameroid constrictor to the left circumflex artery via left thoracotomy in order to induce chronic myocardial ischemia. After seven weeks, pigs were euthanized and myocardial tissue was harvested for total proteomic analysis. Results: When compared with non-ischemic male tissue non-ischemic female tissue demonstrated upregulation of two variants of LMOD2 and down regulation of five variants of ACADS (Figure 1A). However, when comparing ischemic female tissue with ischemic male tissue there were 626 upregulated proteins and 194 down regulated proteins (Figure 1B). Enrichment analysis revealed upregulation of certain metabolic pathways including the citric acid cycle and glycolysis/gluconeogenesis (Figure 1C) while there was down regulation in pathways involved in cardiac muscle contraction and dilated cardiomyopathy (Figure 1D). There was no difference in serum glucose, HDL, LDL, or total cholesterol (P &gt; 0.05 for all) (Figure 1E). Conclusion: There were clear sex differences in response to chronic cardiac ischemia. Proteins involved in metabolic pathways and myocyte function appear to be particularly affected.

A herb mixture to ameliorate non-alcoholic fatty liver in rats fed a high-fat diet

This study was performed to investigate the effects of an herb extract mixture (HM) in ameliorating non-alcoholic fatty liver disease (NAFLD). The HM contained equal amounts of 70% ethanol extracts from Zingiber officinale, Centella asiatica, and Boehmeria nivea. In vitro, the HM significantly inhibited lipid accumulation in oleic acid-stimulated HepG2 cells. We further evaluated the anti-NAFLD activities of the HM in vivo in an animal model. Rats were fed two different amounts of the HM (50 and 200 mg/kg body weight) along with a high-fat diet for 6 weeks. HM supplementation reduced liver weight; epididymal, peri-renal, and intra-abdominal fat content; and serum triglyceride, total cholesterol, and low-density lipoprotein cholesterol levels as well as increased high-density lipoprotein cholesterol levels in a dose-dependent manner. Histological evaluation of liver specimens further demonstrated that administration of HM significantly prevented hepatic lipid accumulation and subsequent development of hepatic steatosis. These findings suggest that HM can be used as an alternative nutraceutical for ameliorating NAFLD.

Salvianolic acid B inhibits atherosclerosis and TNF-α-induced inflammation by regulating NF-κB/NLRP3 signaling pathway

BackgroundInflammation is critical in the pathophysiology of atherosclerosis (AS). The aim of this study was to investigate the protective effect of salvianolic acid B (Sal B) on AS and to explore the molecular mechanism of tumor necrosis factor-α (TNF-α)-induced damage in human umbilical vein endothelial cells (HUVECs). MethodsIn vivo studies, LDLR−/− mice were fed a high-fat diet (HFD) for 14 weeks to establish an AS model to evaluate the protective effect of Sal B on the development of AS. Total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C) levels were determined in the blood serum. En face and cross section lipid deposits were measured and quantified with Oil Red O staining. Hematoxylin and eosin (H&E) and Masson's trichrome staining were used to quantify atherosclerotic plaque size and collagen fiber content in aortic root sections. Reactive oxygen species (ROS) were detected in aortic root using dihydroethylenediamine (DHE) staining. Apoptosis rate was determined by TdT-mediated dUTP nick end labeling (TUNEL) staining. Immunofluorescence (IF) staining was used to detect the expression of the nuclear factor kappa-B (NF-κB) p65 and NOD-like receptor family pyrin domain containing 3 (NLRP3). To further investigate the protective effect of Sal B, we used TNF-α induced HUVECs inflammation model. We examined cell viability, lactate dehydrogenase (LDH) content, and ROS production. The transcription of NF-κB was evaluated by immunofluorescence. The mRNA levels of NLRP3, caspase-1, and IL-1β were detected by RT-PCR. Pyroptosis related proteins were detected by Western blot. ResultsThe change in the weight of the mice over time was an indication that Sal B had an effect on weight gain. In vivo studies: we were able to show that the serum lipids TC, TG and LDL-C were increased in the model group and that the treatment with Sal B reduced the levels of serum lipids. Histological staining showed that the LDLR−/− mice had a large amount of foam cell deposition accompanied by inflammatory cell infiltration and the formation of atherosclerotic plaques in theMOD group. The pathological abnormalities were significantly improved by Sal B treatment. ROS release and apoptosis were significantly increased after HFD in aortic root, which was attenuated by Sal B. IF results showed that the expression of NF-κB p65 and NLRP3 was significantly increased in the MOD group and significantly decreased in the Sal B group, suggesting that Sal B may act through the NF-κB/NLRP3 pathway. And in vitro studies: inflammatory damage of HUEVCs was induced by TNF-α, and Sal B treatmented significantly increased cell viability and reduced LDH release. It was also found that Sal B inhibited ROS level increase after TNF-α-induced HUEVCs. Activation of NF-κB p65 by TNF-α stimulation, NF-κB p65 is transferred to the nucleus. Sal B treatment could reverse this effect. RT-PCR and Western blot showed that Sal B affected NF-κB transcription and NLRP3 inflammasome activation and could significantly inhibit TNF-α-induced NLRP3 inflammasome activation. These results suggest that Sal B may participate in antiatherosclerotic and inflammatory responses through the NF-κB/NLRP3 pathway. ConclusionsThis study shows that Sal B ameliorates the development of AS lesions in HFD-induced LDLR−/− mice. Furthermore, under TNF-α conditions, Sal B reduced ROS release and reversed nuclear translocation of NF-κB, and inhibited atherosclerosis and inflammation by modulating the NF-κB/NLRP3 pathway.

ARO-ANG3, an investigational RNAI therapeutic, decreases serum LDL-cholesterol, apolipoprotein B, and angiopoietin-like protein 3 in patients with homozygous familial hypercholesterolaemia

ARO-ANG3, an investigational RNAI therapeutic, decreases serum LDL-cholesterol, apolipoprotein B, and angiopoietin-like protein 3 in patients with homozygous familial hypercholesterolaemia

The prognostic role of the low and very low baseline LDL-C level in outcomes of patients with cardiac revascularization; comparative registry-based cohort design

BackgroundAlthough low-density lipoprotein-cholesterol (LDL-C) level is considered one of the main prognostic factors in patients with coronary artery bypass grafting (CABG), the question about “the lower the better” is still unanswered. We aimed to evaluate and compare the outcomes of patients with CABG and low or very low baseline LDL-C, regardless of statin usage.MethodsIn this registry-based cohort study, 10,218 patients with low/very low (70–100 and ≤ 70 mg/dL) baseline LDL-C who underwent isolated and the first-time CABG without known previous history of cardio-cerebrovascular events, were included and compared. The median follow-up was 73.33 (72.15–74.51) months. Primary outcomes were all-cause mortality and major adverse cardio-cerebrovascular events (MACCE) (consisted of all-cause mortality, acute coronary syndrome, stroke or transient ischemic attack, and the need for repeat revascularization [percutaneous coronary intervention or redo-CABG]). Cox regression analyses before and after the propensity score matching (PSM) model were applied to evaluate and compare outcomes.ResultsThe mean age of the study population was 66.17 ± 9.98 years old and 2506 (24.5%) were women. Diabetes mellitus and a history of cigarette smoking were significantly higher in the very low LDL group (P-value ≤ 0.001). In Cox regression analyses before applying PSM model, both all-cause mortality (14.2% vs. 11.9%, P-value = 0.004 and MACCE (26.0% vs. 23.6%, P-value = 0.006) were significantly higher in the very low LDL group compared to low LDL. However, these results were no longer significant after applying the PSM model (all-cause mortality HR: 1.115 [95% CI: 0.986–1.262], P = 0.083 and MACCE HR: 1.077 [95%CI: 0.984–1.177], P = 0.095). The sensitivity analysis to remove the statin effect demonstrated that very low LDL-C level was correlated to higher risk of all-cause mortality in both unmatched and PSM analyses.ConclusionVery low serum LDL-C levels (≤ 70 mg/dl) could increase long-term all-cause mortality and cardiovascular events in patients who have undergone isolated CABG.

Association between serum LDL-C concentrations and risk of diabetes: A prospective cohort study.

Low-density lipoprotein cholesterol (LDL-C) and diabetes mellitus are both modifiable risk factors for cardiovascular disease; however, whether elevated LDL-C levels confer a risk for diabetes remains unclear. We aimed to examine the association between serum LDL-C concentrations at baseline and the risk of developing diabetes at follow-up in the general population of Chinese adults. This study included 5274 adults aged ≥ 40 years from a community cohort who were without diabetes and followed for a median of 4.4 years. A standard 75-g oral glucose tolerance test was conducted at baseline and follow-up visits to diagnose diabetes. Logistic regression models and a restricted cubic spline were used to examine the association between baseline serum LDL-C levels and the risk of diabetes development. Subgroup analyses were conducted stratifying on age, sex, body mass index, hypertension, family history of diabetes, and LDL-C levels. A total of 652 participants (12%) developed diabetes during the follow-up period. Compared to quartile 1 of serum LDL-C, quartiles 2, 3, and 4 were associated with a 30%, 33%, and 30% significantly higher risk of diabetes, respectively after adjustment for confounders including homeostatic model assessment for insulin resistance. The linear relationship between baseline LDL-C down to 30.1 mg/dL and incident diabetes was demonstrated by restricted cubic spline analysis, and each 1-SD increase in LDL-C concentration (28.5 mg/dL) was associated with a 12% increase in the risk of diabetes (odds ratio 1.12, 95% confidence interval 1.03-1.22). In this community-based general population, higher serum LDL-C levels were linearly associated with an elevated risk of incident diabetes.

Extract of Isatidis Radix Inhibits Lipid Accumulation in In Vitro and In Vivo by Regulating Oxidative Stress.

Isatidis Radix (IR), the root of Isatis tinctoria L. belonging to Brassicaceae, has been traditionally used as a fever reducer. Although some pharmacological effects, such as anti-diabetes, anti-virus, and anti-inflammatory, have been reported, there is no study on the anti-obesity effect of IR. This study used 3T3-L1 cells, human mesenchymal adipose stem cells (hAMSCs), and a high-fat diet (HFD)-induced obese mouse model to confirm the anti-adipogenic effect of IR. Intracellular lipid accumulation in 3T3-L1 cells and hAMSCs was decreased by IR treatment.IR extract especially suppressed reactive oxygen species (ROS) production through a cluster of differentiation 36 (CD36)-AMP-activated protein kinase (AMPK) pathway. Consequently, the expressions of peroxisome proliferator-activated receptor gamma (PPARγ), CCAAT-enhancer-binding proteins alpha (C/EBPα), and fatty acid synthesis (FAS) were inhibited by IR extract. In addition, β-oxidation-related genes were also decreased by treatment of IR extract. IR inhibited weight gain through this cascade in the HFD-induced obese mouse model. IR significantly suppressed lipid accumulation in epididymal white adipose tissue (eWAT). Furthermore, the administration of IR extract decreased serum free fatty acid (FFA), total cholesterol (TC), and LDL cholesterol, suggesting that it could be a potential drug for obesity by inhibiting lipid accumulation.

Impact of Liver Transplantation on Adipose Tissue Compartments and Its Association With Metabolic Sequela.

Loss of skeletal muscle can be accompanied by an increase in adipose tissue leading to sarcopenic obesity. There are limited data on how liver transplantation (LT) might impact adipose tissue compartments, particularly among patients with metabolically active disease, such as nonalcoholic steatohepatitis (NASH) and subsequent metabolic sequela. Skeletal muscle, visceral adipose tissue (VAT), and subcutaneous adipose tissue (SAT) were measured using cross-sectional imaging performed in 190 patients pre-LT, 6 mo post-LT and 12 mo post-LT. Changes in adipose tissue and their impact on metabolic diseases were determined in patients transplanted for NASH versus non-NASH. Skeletal muscle, VAT, and SAT were similar in patients with NASH and non-NASH pre-LT despite a higher burden of metabolic diseases in patients with NASH. Following LT, no significant differences between skeletal muscle and SAT were observed in the entire cohort and among patients with NASH (versus non-NASH). LT recipients with the highest muscle mass pre-LT were at the greatest risk for muscle loss post-LT. A time-dependent increase in VAT was noted post-LT, which was more robust among patients with a history of NASH cirrhosis. In adjusted multivariate analysis, NASH versus non-NASH was a strong predictor of post-LT increase in VAT (β-coefficient 3.00, P = 0.04). Pre-LT VAT was an independent predictor of post-LT serum triglycerides (β-coefficient 5.49 ± 2.78, P = 0.05) and low-density lipoprotein cholesterol (β-coefficient 1.80 ± 0.75, P = 0.02). A trend between pre-LT VAT and diabetes was noted but did not reach statistical significance. VAT but not SAT increases rapidly after LT, especially among patients transplanted for NASH cirrhosis and predicts future metabolic burden.

Association between blood lipid levels and risk of gastric cancer: A systematic review and meta-analysis.

The association between blood lipid levels and the risk of gastric cancer (GC) is well known. Therefore, to clarify this association, all relevant prospective cohort studies were included in this meta-analysis. Our study was registered in PROSPERO (CRD42022354899) prior to its commencement. A systematic review and meta-analysis were conducted in accordance with the PRISMA recommendations. Chinese databases (CNKI, CBM, Wanfang, and VIP) and English databases (PubMed, Embase, Web of Science, and the Cochrane Library) were systematically searched up to October 2022. This study included all relevant cohort studies that reported hazard ratios (HRs) or relative risks (RRs) and their corresponding 95% confidence intervals (95% CIs) to examine the association between various lipid profiles (e.g., total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol) and the risk of developing gastric cancer (GC). Fixed effects or random effects models were used based on the level of heterogeneity among the studies, and these models were employed to obtain pooled hazard ratios. Additionally, sensitivity analysis and publication bias analysis were conducted to ensure the robustness and reliability of the findings. After conducting a systematic search, a total of 10 studies were selected out of 10,525 papers involving a total of 5,564,520 individuals. Among these individuals, there were 41,408 GC cases. The analysis revealed that the highest versus lowest serum total cholesterol (TC) concentration was associated with a pooled hazard ratio of 0.89 (95% CI = 0.87-0.92, I2 = 15%). For triglycerides (TGs), the hazard ratio was 1.00 (95% CI = 0.96-1.04, I2 = 37%), while for high-density lipoprotein cholesterol (HDL-C), the hazard ratio was 0.90 (95% CI = 0.86-0.93, I2 = 0%). The hazard ratio for low-density lipoprotein cholesterol (LDL-C) was 0.96 (95% CI = 0.91-1.00, I2 = 0%). Based on the results of this meta-analysis, it was found that serum TC and HDL-C levels were inversely correlated with the risk of GC. No association was observed between serum TG levels and the risk of GC. Similarly, no association was found between serum LDL-C levels and the risk of GC.

The efficacy of dietary approaches to stop hypertension (DASH) diet on lipid profile: A systematic review and meta-analysis of clinical controlled trials.

Dyslipidemia is considered a causal risk factor for coronary heart disease and stroke. Plant-based diets such as dietary approaches to stop hypertension (DASH) have beneficial effects on cardiovascular health. This meta-analysis was conducted to assess the effects of the DASH diet on lipid profiles based on clinical controlled trials. An inclusive online search was performed in medical databases including Web of Science, PubMed, Scopus, and Google Scholar up to October 2021 to identify trials assessing the effect of the DASH diet on lipid profiles. Seventeen studies comprising 2218 individuals were included in this meta-analysis. In comparison to the control group, following the DASH diet resulted in a significant reduction in serum triglycerides (WMD: -5.539 mg/dl; 95% CI: -8.806, -2.272) and low-density lipoprotein cholesterol (WMD: -6.387 mg/dl; 95% CI: -12.272, -0.501). However, DASH diet could not reduce serum total cholesterol (WMD: -5.793 mg/dl; 95% CI: -12.84, 1.254), high-density lipoprotein cholesterol (WMD: 0.631 mg/dl; 95% CI: -0.749, 2.011), and total cholesterol/high-density lipoprotein cholesterol ratio (WMD: -0.11 mg/dl; 95% CI: -0.27, 0.05). Findings of this meta-analysis showed that following the DASH diet had beneficial effects on serum triglycerides and low-density lipoprotein cholesterol, however, it had no effect on serum total cholesterol and high-density lipoprotein cholesterol levels. Based on these results, the DASH diet can be considered a strategy for the prevention and complementary management of dyslipidemia.

Association of ADP-Induced Whole-Blood Platelet Aggregation with Serum Low-Density Lipoprotein Cholesterol in Patients with Coronary Artery Disease When Receiving Maintenance Ticagrelor-Based Dual Antiplatelet Therapy.

The degree of platelet inhibition in patients undergoing dual antiplatelet therapy (DAPT) affects cardiovascular outcomes after acute coronary syndromes (ACS) and/or percutaneous coronary intervention. Our aim was to search for correlates of residual ex vivo platelet reactivity and circulating soluble P-selectin (sP-selectin), an index of in vivo platelet activation, in patients being treated by DAPT with ticagrelor. Adenosine diphosphate (ADP)-induced platelet aggregability (by multiple electrode aggregometry) and plasma sP-selectin were estimated in 62 stable post-ACS subjects (46 men and 16 women; mean age: 64 ± 10 years; 30 with type 2 diabetes (T2DM)) undergoing maintenance DAPT with ticagrelor and aspirin. These patients did not exhibit heart failure or other relevant coexistent diseases except for properly controlled T2DM, mild renal insufficiency, and hypertension. We also assessed this in 64 subjects on clopidogrel-based DAPT matched for age, sex, and T2DM status. ADP-induced platelet aggregation was below the optimal levels (190-460 arbitrary units (AU) * min) in most patients receiving ticagrelor-based DAPT, especially in those with below-median (<1.9 mmol/L) serum concentrations of low-density lipoprotein cholesterol (LDL-c) (128 ± 61 vs. 167 ± 73 AU * min for below-median and above-median LDL-c, respectively, p = 0.025). In contrast, platelet reactivity did not differ by LDL-c on clopidogrel-based DAPT (246 ± 101 vs. 268 ± 108 AU * min for below-median and above-median LDL-c, respectively, p > 0.4). Plasma sP-selectin was found to be unrelated to serum LDL-c when receiving DAPT with ticagrelor (p > 0.4) or clopidogrel (p > 0.8). In conclusion, our preliminary observational study suggests the association of lower residual ex vivo platelet aggregability with better LDL-c control in patients undergoing ticagrelor-based maintenance DAPT, which does not appear to be reflected by plasma sP-selectin. Whether the serum LDL-c level should be considered among the factors affecting the degree of platelet inhibition for those treated with ticagrelor-based DAPT needs to be investigated in larger studies.

Coronary Artery Bypass Grafting in advance aged patients.

This study aimed to assess the impact of coronary artery bypass grafting (CABG) on outcomes in elderly patients compared to younger patients. An observational case-control study was conducted involving 535 patients, divided into two groups: older adults (≥75 years) and younger adults (<75 years). All patients underwent CABG following a similar protocol. The primary endpoints focused on early post-procedure outcomes, including in-hospital mortality and the duration of ICU or hospital stay. Patients were followed up for six months, and secondary study endpoints included long-term mortality, left ventricular ejection fraction, re-hospitalization rates, and repeated revascularization. 535 patients who underwent CABG were enrolled in this study. The smoking habit was significantly higher among younger adults (38.2% vs. 12.5%, P=0.001). Hypertension was more prevalent among older adults than younger adults (75% vs. 60%, P=0.044). LDL cholesterol serum levels were higher among younger adult patients (94.9±32.5 vs. 80.9±32.9, P=0.028). In-hospital death was not significantly different between younger and older adults (2.8% vs. 5.0%, P=0.34). Mortality in the six-month follow-up was non-significantly higher in the elderly (2.1% vs. 8.1%, P=0.06).A significant proportion of patients in both groups (46.9% in younger patients vs. 40% in older ones, P=0.40) received dual antiplatelet therapy (DAPT) prior to CABG due to a recent myocardial infarction and receipt of a new stent, but without increased major bleeding in both groups. CABG should be considered a viable treatment option for elderly patients with acceptable operative risk in current clinical practice.

Prognostic value of perioperative serum low-density lipoprotein cholesterol level for postoperative prognosis of pancreatic cancer: a retrospective study

BackgroundAs a common malignant tumour, pancreatic cancer (PC) has the worst clinical outcome. Early evaluation of the postoperative prognosis has certain clinical value. Low-density lipoprotein cholesterol (LDL-c), which is mainly composed of cholesteryl esters, phospholipids, and proteins, plays an important role in transporting cholesterol into peripheral tissues. LDL-c has also been reported to be correlated with the occurrence and progression of malignant tumours and can predict postoperative prognosis in various tumours.AimsTo determine correlation between serum LDL-c level and clinical outcome in PC patients after surgery.MethodsData of PC patients that received surgery at our department from January 2015 to December 2021 were retrospectively analysed. Receiver operating characteristic (ROC) curves between perioperative serum LDL-c at different timepoints and survival rate at postoperative 1-year were drawn, and the optimal cut-off value was calculated. Patients were categorized into low and high LDL-c groups, and their clinical data and outcome were compared. Univariate and multivariate analyses were applied to screen out risk markers for poor prognosis of PC patients after surgery.ResultsThe area under the ROC curve of serum LDL-c at 4 weeks after surgery and prognosis was 0.669 (95% CI: 0.581–0.757), and the optimal cut-off value was 1.515 mmol/L. The median disease-free survival (DFS) rates of low and high LDL-c groups were 9 months and 16 months, respectively, and the 1-, 2- and 3-year DFS rates were 42.6%, 21.1% and 11.7% in low LDL-c group, respectively, and, 60.2%, 35.3% and 26.2% in high LDL-c group, respectively (P = 0.005). The median overall survival (OS) rates of low and high LDL-c groups were 12 months and 22 months, respectively, and the 1-, 2- and 3-year OS rates were 46.8%, 22.6% and 15.8% in low LDL-c group, respectively, and 77.9%, 46.8% and 30.4% in high LDL-c group, respectively (P = 0.004). Multivariate analysis confirmed low postoperative 4-week serum LDL-c as independent risk marker for early tumour recrudesce and poor clinical outcome in PC patients.ConclusionHigh postoperative 4-week serum LDL-c is a prognostic marker for prolonged DFS and OS time in PC patients.

Antihyperglycemic and antihyperlipidemic effects of Cymbopogon citratus leaves in dexamethasone-induced diabetic rats

Background: In sub-Saharan Africa, especially in Cameroon, different parts of Cymbopogon citrarus (C. citratus) are prescribed as remedies for diabetes mellitus and dyslipidemia. This study was designed to investigate the effects of hydroalcoholic extract of C. citratus (HACC) leaves in dexamethasone-induced-diabetic (Dex-db) rats. Materials and Methods: The HACC was obtained by decoction for 15 min by mixing 250 g of dry powder of the leaves of C. citratus by completing the total volume to 1L with a hydroalcoholic solution (water-ethanol, 30:70). After cooling to room temperature and filtration using Whatman No. 4 filter paper, the extract was concentrated using a rotary evaporator at 45 °C. Moderate diabetes was induced by daily subcutaneous injection of dexamethasone (5 mg/kg) once daily for 7 days. On the 8th day, the animals which have a blood glucose level greater than 120 mg/dL were selected and randomized into 5 groups of 5 animals each who received the different treatments for two weeks as follows: two negative control groups, negative normal control (NNC) and negative dexamethasone control (NDC) received only vehicle (distilled water); one positive control group received glibenclamide (5 mg/kg) and two groups received HACC at doses of 50 and 100 mg/kg respectively. On the other hand, compared to the NDC group, we observed a significant (P&lt;0.001) dose-response after 14 days of treatment a decrease in serum concentrations of TC, LDLc, and AI, and an increase in HDLc. A highly significant decrease (P&lt;0.001) was also observed in serum TG concentration but with a more pronounced action at the lowest dose of HACC (50 mg/kg). Results: After two weeks of administration of the HACC, we observed during the oral glucose tolerance test (OGTT) a highly significant rate of reduction in glycemia (%) at the two doses tested (50 and 100 mg/kg) compared to the NNC group (P&lt;0.001) 2 hours after glucose load, no significant difference was observed (P&gt;0.05). With regard to the serum lipid profile (total cholesterol (TC), HDL cholesterol (HDLc), triglycerides (TG), LDL cholesterol (LDLc) and atherogenicity index (AI)), after 14 days of administration of the various treatments, with the exception of the TC which decreased significantly (P&lt;0.001), no significant difference (P&gt;0.05) was observed on the other parameters in the animals having received the HACC only at the dose of 100 mg/kg compared to the NNC group. Conclusion: This finding suggests that the leaves of C. citratus have a highly significant antihyperglycemic and antihyperlipidemic activity in diabetic rats by preventing the postprandial glycemia peak and by readjusting the lipid profile, in particular by lowering serum LDL-cholesterol, triglycerides and the atherogenicity index.

The Impacts of Animal-Based Diets in Cardiovascular Disease Development: A Cellular and Physiological Overview.

Cardiovascular disease (CVD) is the leading cause of death in the United States, and diet plays an instrumental role in CVD development. Plant-based diets have been strongly tied to a reduction in CVD incidence. In contrast, animal food consumption may increase CVD risk. While increased serum low-density lipoprotein (LDL) cholesterol concentrations are an established risk factor which may partially explain the positive association with animal foods and CVD, numerous other biochemical factors are also at play. Thus, the aim of this review is to summarize the major cellular and molecular effects of animal food consumption in relation to CVD development. Animal-food-centered diets may (1) increase cardiovascular toll-like receptor (TLR) signaling, due to increased serum endotoxins and oxidized LDL cholesterol, (2) increase cardiovascular lipotoxicity, (3) increase renin-angiotensin system components and subsequent angiotensin II type-1 receptor (AT1R) signaling and (4) increase serum trimethylamine-N-oxide concentrations. These nutritionally mediated factors independently increase cardiovascular oxidative stress and inflammation and are all independently tied to CVD development. Public policy efforts should continue to advocate for the consumption of a mostly plant-based diet, with the minimization of animal-based foods.

Association of Non-Genetic Risk Factors with Prostate Cancer in the Population of Jammu Region of J and K, India

ABSTRACT: The rising incidence rates of prostate cancer (CAP) have become a global health disorder. It has a complex etiology and includes both potentially modifiable environmental factors and non-modifiable genetic components. In this study, we aimed to identify the potential and significant non-genetic risk factors associated with CAP in the population of Jammu and Kashmir. A total of 320 study subjects (120 clinically confirmed CAP patients and 200 healthy age-matched unrelated participants) were registered for this investigation after obtaining their prior consent. A predesigned health questionnaire and hospital-based patient history were used to collect data pertaining to clinical variables, sociodemographic characteristics, anthropometric parameters, and biochemical indices. The result revealed that diet patterns (non-vegetarianism, p=0.01), lack of physical activity (p=0.0007), dwelling (urban residents, p=0.0105), higher levels of serum LDL-cholesterol (p=&lt;0.0001), triglyceride (p=0.01), VLDL-cholesterol (p=0.02), total cholesterol (p=0.0527), creatinine (p=0.0006), sodium (p=0.0429), urea (p=0.0006), and PSA (p=&lt;0.0001) were significantly associated with CAP. Moreover, higher mean age (69.82±15.5), the extent/duration of diabetes mellitus (DM) (p=0.0007), lack of physical activity (p=0.0007), high intake of red meat (p=0.0005), LDL-Cholesterol (p=&lt;0.0001) and positive family history (p=&lt;0.0001) were found to be the most significant risk factors for CAP. The study notably identified the most significant and novel (extent/duration of diabetes and serum levels of LDL, VLDL) non-genetic risk factors associated with prostate cancer in the population of the Jammu region thus helping to target the high-risk populations and informing preventive interventions.