Risultati per: Livelli molto elevati di Colesterolo HDL-C associati al rischio di demenza

Oncologi, ‘subito un piano di recupero per la prevenzione’

I sindacati contestano mancate assunzioni.’Abuso di precettazioni’

Sindacati: ‘Anche 15mila interventi. Garantita l’urgenza’

Araldi, ‘con MedMal Report identifichiamo aree più a rischio’

Cherubini (Siedp) “evitabili in oltre 450 bimbi ogni anno”

Circulation, Volume 150, Issue Suppl_1, Page A4141522-A4141522, November 12, 2024. Background:Maternal nutritional status and periconceptional environmental conditions have been previously linked to the methylation of the vtRNA 2-1 promoter. Bariatric surgery is an effective treatment for morbid obesity, with most patients achieving significant weight control within 1-2 years post-surgery. However, some patients do not experience the desired weight loss. The clinical correlation between the methylation of the vtRNA 2-1 promoter and postoperative outcomes in obese patients remains unclear. This study aims to elucidate the relationship between the methylation of the vtRNA 2-1 promoter and the effectiveness of bariatric surgery.Hypothesis:The degree of methylation of the vtRNA 2-1 promoter is related to excess weight loss (EWL) after bariatric surgery.Methods:The OCEAN registry (Obesity and Clock for Elegant AgiNg) is a prospective cohort study collecting data from 2011 to 2017, including 381 obese patients, 179 of whom underwent bariatric surgery. Quantitative pyrosequencing was performed on all patients. Postoperative weight and EWL were tracked and recorded at 3, 6, 12, and 24 months. Statistical analyses were conducted using SPSS.26.Results:The degree of methylation of the vtRNA 2-1 promoter shows a bimodal distribution. Compared to the normal group from the Taiwan Biobank, the methylation distribution between the two groups differs significantly. Patients were categorized into hypomethylation (≤10%), intermediate-methylation (10-40%), and hypermethylation (≥40%) groups. Statistics indicate that hypermethylation is associated with higher EWL at one year (p=0 .047) and two years (p=0.04) post-surgery compared to the hypomethylation group. In the linear regression model, after controlling for variables including age, creatinine, cholesterol, TG, LDL, AC sugar and HbA1c, our analysis revealed a positive correlation between HDL and one year EWL.Conclusion:Obese patients who have hypermethylation of the vtRNA 2-1 promoter demonstrate improved EWL one and two years following bariatric surgery. Given the previous links between the methylation of the vtRNA 2-1 promoter and maternal nutritional status, these findings suggest that early life nutritional factors may influence the effectiveness of bariatric surgery outcomes. Further comprehensive and long-term studies are needed to confirm the methylation of the vtRNA 2-1 promoter as a viable indicator for predicting bariatric surgery outcomes and improving cardiovascular health.

Circulation, Volume 150, Issue Suppl_1, Page A4141657-A4141657, November 12, 2024. Background:The prevalence of calcific valve stenosis (CAVS) in familial hypercholesterolemia (FH) is 30-40%. Eleveated Lp(a) levels independently promotes faster progression of CAVS. Low HDL particles (HDL-P), increase apoC3 and serum amyloid A (SAA)-bound HDL are associated with long-term incidence and progression of CAVS.Aim:Dextran-sulfate-adsorption lipoprotein-apheresis (LA), the only LA device available in the United States, reduces LDL-C and Lp(a) by an average of 60%-80% via binding positive-charged apolipoprotein B to a negative-changed environment. Despite the negative charge of HDL-C, it is acutely reduced by 10%-20%. However, the total HDL-P number, as measured by nuclear magnetic resonance testing, is increased by an average of 16% following LA therapy. We hypothesized that regular LA may improve cardiovascular outcomes and slow the progression of CAVS via its effects on HDL functionality and Lp(a) levels.Methods:This case series describes 39 Caucasian patients (mean age 61 years, 70% female, 80% statin intolerant) with FH and/or elevated Lp(a) (Liposorber LA-15, Kaneka) over a mean treatment period of 4.8 years, as compared to an average of 5.3 years pre-treatment. Pre-treatment LDL-C and Lp(a) levels were 144 mg/dL (range, 35-314) and 167 nmol/L (range 2-530). HDL proteomic analysis was performed to identify numerous proteins and lipids segregated into distinct subclasses. Major adverse cardiovascular events were defined as: MI=myocardial event, PCI=percutaneous cornary intervention, CABG=coronary artery bypass surgery, TIA=transient ischemic attack, CAVS=calcific artic stenosis.Results:LA therapy reduced mean LDL-C to an average of 40 mg/dL and Lp(a) to 24nmol/L, while total HDL-C was lowered by 14%. Extra small and small-sized HDL-P was reduced by 42% and 20%, respectively (P

Circulation, Volume 150, Issue Suppl_1, Page A4148181-A4148181, November 12, 2024. Background:Following an ischemic stroke, a serious complication known as hemorrhagic transformation (HT) might jeopardize patient outcomes. Inflammatory indicators, such as the neutrophil-to-leukocyte ratio (NRR), and lipid markers, such as the low-density lipoprotein (LDL) to high-density lipoprotein (HDL) ratio, have been investigated as HT predictors. Recent research has delved further into the predictive significance of these biomarkers for ischemic stroke outcomes.Objectives:To systematically review the literature on the predictive value of NLR and LDL to HDL ratios for HT in ischemic stroke patients, incorporating recent findings that enhance our understanding of these biomarkers.Methods:A detailed search of electronic databases was conducted to gather studies focusing on NLR and LDL to HDL ratios as predictors for HT in ischemic stroke. The selection process followed strict inclusion criteria, and the quality of studies was rigorously assessed.Results:The paper discusses new findings that emphasize the impact LDL and NLR play in influencing HDL ratios and, hence, HT prediction. Following an ischemic stroke, an increased incidence of HT, especially parenchymal hematoma (PH), has been associated with greater NLR. A high neutrophil-to-HDL ratio (NHR) has also been identified as a possible predictor of poor prognosis in ischemic stroke, underscoring its significance in predicting HT. Furthermore, the LDL-to-HDL ratio has been connected to long-term clinical outcomes like death and recurrent myocardial infarction, which may be associated with HT risk.Conclusions:In individuals with ischemic stroke, NLR and LDL-to-HDL ratios are potential HT indicators. The addition of current data underscores the potential of these ratios not just as HT indicators but also as markers for broader stroke-related effects. More studies are needed to validate these results and provide consistent recommendations for their use in clinical practice.

Circulation, Volume 150, Issue Suppl_1, Page A4138698-A4138698, November 12, 2024. Background:Mitochondrial aldehyde dehydrogenase 2 (ALDH2) is responsible for acetaldehyde metabolism with alcohol consumption. ALDH2 deficiency is a common enzymopathy – afflicting ~540 million East Asians. The ALDH2*2 variant, a missense mutation, significantly decreases enzyme activity. Recent studies suggest a potential link between ALDH2 deficiency and increased cardiovascular disease (CVD) risk. High-Density Lipoprotein cholesterol (HDL-C) is inversely associated with CVD and is known to increase with alcohol consumption. However, the impact of ALDH2*2 on HDL-C levels in East Asians remain unclear.Methods:Using the NIHAll of Uscohort, we assessed HDL-C levels and reported alcohol consumption habits (never, < once/week, > once/week) at enrollment, as well as ALDH2 variant status among East Asian participants. Differences in HDL-C values were analyzed with Mann-Whitney U-tests.Results:Among 3,289 US Asian adults (age 46.8 ± 16.1 years; 58.8% female), median HDL-C was 54mg/dL [IQR 45, 67]. Of these, 2809 (85.4%) had wildtype ALDH2, and 480 (14.6%) had ALDH2*2.Individuals with ALDH2*2 reported lower alcohol consumption (Figure A) but exhibited higher HDL-C levels (p=0.0002). The association was similar regardless of sex (Figure B).Conclusion:The ALDH2*2 variant is associated with higher HDL-C levels, despite lower alcohol consumption, indicating a possible independent influence on HDL-C levels. In the context of previous studies linking ALDH2 deficiency to adverse CVD outcomes, this suggests that ALDH2 may have a role independent of HDL-C levels, or it could affect HDL function rather than the HDL-C level itself.

Circulation, Volume 150, Issue Suppl_1, Page A4142394-A4142394, November 12, 2024. Background:Ferroptosis is a novel type of programmed cell death characterized by excessive lipid peroxides and iron overload inside the cell. SLC7A11/GSH is one of the most important anti-ferroptotic pathways. Macrophage ferroptosis contributes to the progression of atherosclerosis. HDL exerts anti-atherosclerotic effects primarily by promoting cholesterol efflux. Whether HDL also inhibits macrophage ferroptosis is unknown.Research Questions:This research was aimed to explore the effects and mechanisms of HDL on macrophage ferroptosis.Methods:Macrophage ferroptosis was detected in plaques from patients with coronary artery disease. In vitro, macrophage was induced ferroptosis by multiple inducers and then the cells were treated with either vehicle or HDL or ApoA1. Ferroptosis was measured by detecting multiple ferroptosis markers (lipid peroxide, LDH release, ROS production, and cellular ferrous ion level).Results:Compared to controls, iron, lipid peroxide and macrophages were co-localized and significantly increased in coronary plaques, suggesting increased macrophage ferroptosis in atherosclerosis. In mouse macrophages, ferroptosis-inducers increased ferroptosis significantly, which was inhibited by HDL and ferroptosis inhibitors, but not neither by inhibitors of apoptosis, necroptosis, or autophagy. ApoA1, the main apolipoprotein on HDL, may account for HDL’s anti-ferroptotic effect. Mechanically, ApoA1 upregulated System Xc- (encoded by SLC7A11), an amino acid antiporter that exchanges intracellular glutamate and extracellular cysteine, thus elevating intracellular GSH and reducing ferroptosis. We further elucidated that ApoA1 activated NRF2, the transcription factor of SLC7A11, by promoting its nuclear translocation.Conclusion:Our results imply that HDL/ApoA1 inhibits macrophage ferroptosis via upregulating NRF2/SLC7A11/GSH pathway, enriching the regulation and mechanisms of HDL/ApoA1’s anti-atherosclerotic effects.

Circulation, Volume 150, Issue Suppl_1, Page A4147750-A4147750, November 12, 2024. Introduction:It is now recognized that the quality of lipoprotein particles may impact atherogenesis more than their plasma concentration. HDL and LDL can be separated into five subfractions increasingly electronegative subfractions (H1 to H5 and L1 to L5), with H1 and L1 being beneficial and H5 and L5 being dysfunctional. This study examines the effects of H5 and L5 on the viability of endothelial cells (ECs) and monocytes, key components of vascular immunity.Hypothesis:We hypothesize that L5 induces cytotoxic responses in monocytes (THP-1 cells) and bovine aortic ECs (BAECs), with H5 exacerbating these effects, thereby promoting inflammatory and atherogenic processes in atherosclerosis.Methods:H5 and L5 were fractionated by anion-exchange chromatography. Cells were treated with 50 µg/mL of L1, L5, H1, and H5 for 24 hours. Cell viability was assessed using a fluorescence-based viability detection method after trypan blue exclusion staining. Image-based cytometric quantification was performed using the Nexcelom Cellometer. Lipidomics was used to characterize L5 and H5, and transcriptomic analysis was performed on BAECs treated with H1 and H5 to identify differentially expressed genes.Results:H5 slightly and L5 moderately reduced cell viability, while their combination significantly decreased both cell numbers and viability (Figures A and B). In contrast, H1 and L1 increased cell numbers compared to PBS control (Figure C). Lipidomic analysis revealed that H5 and L5 have higher triglyceride and lower phosphatidylcholine content than H1 and L1. Transcriptomic analysis indicated that H5 is associated with changes in cell cycle regulation and cellular senescence, affecting DNA damage response and chromosome organization.Conclusion:L5 and H5, particularly in a synergistic manner, significantly impact EC and monocyte viability, impairing vascular innate immunity and contributing to atherosclerosis pathogenesis. Conversely, H1 and L1 increase cell proliferation, indicating their non-cytotoxic role and potential nutrient provision. Lipidomic and transcriptomic analyses further support the distinct roles of these lipoprotein subclasses in impaired vascular innate immunity and their contribution to atherogenic processes.

Circulation, Volume 150, Issue Suppl_1, Page A4120854-A4120854, November 12, 2024. Introduction:Familial hyper-alpha-lipoproteinemia (HALP) is a heterogenous genetic lipid disorder that is found in only 8% of the population and manifests as elevated HDL levels above the 90thpercentile. HALP is due to mutations in various genes including cholesteryl ester transfer protein (CETP), hepatic lipase, or apolipoprotein C-III (APOC3). While epidemiological studies have noted an inverse relationship between high HDL and the development of coronary artery disease, recent data have shown a lack of causal atheroprotective effects. We present a case of a patient with significantly elevated HDL and peripheral vascular disease.Case Description:Patient is a 64-year-old female with past medical history of peripheral artery disease with occlusion of the left femoral artery and popliteal arteries status post angioplasty, hypertension, type 2 diabetes, alcohol use, and CKD Stage 4 who presented to the advanced lipid clinic for management of elevated lipoproteins. Patient’s laboratory data was significant for total cholesterol (TC) of 375 mg/dL, a high-density lipoprotein (HDL) of >200 mg/dL, triglycerides (TG) of 66 mg/dL, and a low-density lipoprotein (LDL) of 175 mg/dL. Further testing revealed elevated apolipoprotein A-I of 231 mg/dL. Patient was subsequently initiated on a high intensity statin with improvement in her lipid panel with a TC of 247 mg/dL, HDL of 133 mg/dL, TG of 50 mg/dL, and LDL of 106 mg/dL, with plan for further uptitration of lipid therapy to target LDL

Circulation, Volume 150, Issue Suppl_1, Page A4142609-A4142609, November 12, 2024. Introduction:Lifestyle habits are considered to be significant determinants of serum lipoprotein concentration. There have been many studies on the factors affecting serum LDL cholesterol(LDL-C) or HDL cholesterol(HDL-C) levels, however, most studies have been conducted in unrelated individuals who had different genetic backgrounds, making it difficult to determine which factors affecting lipid profile might be genetic or environmental.Research Questions:Monozygotic(MZ) twins share almost the same genes, so we hypothesize that twin research may allow us to determine factors associated with lipid profile.Aim:The aim is to examine factors that affect LDL-C and HDL-C levels using data of monozygotic twins database including nutrition survey data, anthropometric and biochemical parameters and to identify genes whose expression levels changed in pairs with large within-pair difference of LDL-C or HDL-C.Methods:The database of 263 pairs of MZ twins in the Osaka University Twin Research Center was analyzed. 1. As for the dietary, smoking, exercise, and drinking habits, we confirmed their influences on LDL-C or HDL-C by Wilcoxon’s signed-rank test in the MZ pairs with the different lifestyle habits. 2. We performed a linear regression analysis of 263 pairs to identfy anthropometric and biochemical parameters(BMI, serum TG, TP and HbA1c etc) associated with the difference in LDL-C(ΔLDL-C) and HDL-C(ΔHDL-C). 3. RNA-seq data derived from peripheral blood mononuclear cells of 59 pairs were examined in the group of large ΔLDL-C or ΔHDL-C.Result:1. LDL-C increased with increased cholesterol intake(n=65 pairs, p

Circulation, Volume 150, Issue Suppl_1, Page A4141018-A4141018, November 12, 2024. Background:It is unclear if the novel, functionally unidentified HDL cholesterol subtypes HDL-2b and HDL-3 can be used to predict acute myocardial infarction (AMI).Methods:This cross-sectional study comprised 1,200 hospitalized patients with AMI identified using ICD-9 coding. The Gensini score was used to assess stenosis severity, defining patients as severe (score ≥50) or mild to moderate (score

Circulation, Volume 150, Issue Suppl_1, Page A4142200-A4142200, November 12, 2024. Introduction:Apolipoprotein B (ApoB) is a better marker of residual risk for cardiovascular disease in patients treated with lipid-lowering therapy (LLT) than low-density lipoprotein cholesterol (LDL-C) and non-high-density lipoprotein cholesterol (non-HDL-C). However, it is unclear if treating to an apoB target is more cost-effective than treating to an LDL-C or non-HDL-C target.Methods:We used the CVD Policy Model, a validated computer simulation model, to estimate the clinical and economic outcomes associated with atherogenic lipid targets for LLT in a cohort of statin-eligible and ASCVD-free U.S. adults. We considered non-HDL-C, and apoB targets for intensification of LLT. Treatments considered were intermediate-intensity statin therapy, high-intensity statin therapy, and ezetimibe, intensified in that order. Upon entering the model, all individuals commenced statin therapy. Under ‘usual care,’ patients with LDL-C ≥100 mg/dL after three months of treatment were escalated to higher-intensity treatment. Under non-HDL-C and apoB testing strategies, LLT was escalated if patients had non-HDL-C ≥119 mg/dL and apoB ≥78.7 mg/dL, respectively, based on percentile equivalence to the LDL-C target. The primary outcomes for our study were healthcare costs (2023 U.S. dollars) and quality-adjusted life years (QALYs). Secondary outcomes were CVD events prevented and life years gained. A lifetime horizon was adopted with a health sector perspective. Future costs and QALYs were discounted at 3% annually.Results:In a sex-balanced simulated cohort of 500,000 individuals, both non-HDL-C and apoB testing produced more QALYs and fewer costs than usual care (LDL-C target). Intensification based on apoB, produced 1,416 more QALYs than non-HDL-C-guided intensification, saving around $29,300,000 over the lifecourse of the simulated cohort. Compared to non-HDL-C testing, apoB testing would lead to 1,233 fewer CVD events and 3,800 more life years. Health gains were greater for men, though apoB screening was cost-saving (i.e., higher QALYs, lower cost) when compared to LDL-C and non-HDL-C testing for men and women.Conclusion:Making LLT intensification decisions based on apoB instead of LDL-C or non-HDL-C would save costs while improving population health.