Insights Into Causal Effects of Genetically Proxied Lipids and Lipid‐Modifying Drug Targets on Cardiometabolic Diseases

Journal of the American Heart Association, Год журнала: 2025, Номер unknown

Опубликована: Янв. 27, 2025

Background The differential impact of serum lipids and their targets for lipid modification on cardiometabolic disease risk is debated. This study used Mendelian randomization to investigate the causal relationships underlying mechanisms. Methods Genetic variants related profiles were sourced from Global Lipids Genetics Consortium. Summary data 10 diseases compiled both discovery replication sets. Expression quantitative trait loci relevant tissues employed evaluate significant lipid‐modifying drug targets. Comprehensive analyses including colocalization, mediation, bioinformatics conducted validate results potential mediators Results Significant associations identified between lipids, targets, various diseases. Notably, genetic enhancement LPL (lipoprotein lipase) was linked reduced risks myocardial infarction (odds ratio [OR] 1 , 0.65 [95% CI, 0.57–0.75], P =2.60×10 −9 ; OR 2 0.59 0.49–0.72], =1.52×10 −7 ), ischemic heart (OR 0.968 0.962–0.975], =5.50×10 −23 0.64 0.55–0.73], =1.72×10 −10 coronary 0.980 0.975–0.985], =3.63×10 −14 0.54–0.75], =6.62×10 −8 ) across Moreover, strong colocalization expression in blood subcutaneous adipose tissue with (OR, 0.918 0.872–0.967], =1.24×10 −3 PP.H4, 0.99) 0.991 0.983–0.999], =0.041; PP.H4=0.92). Glucose levels pressure as total effect outcomes. Conclusions substantiates role specific diseases, highlighting a potent target. effects are suggested be influenced by changes glucose pressure, providing insights into its mechanism action.

Язык: Английский

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Remnant cholesterol and low-grade inflammation jointly in atherosclerotic cardiovascular disease: implications for clinical trials

Current Opinion in Clinical Nutrition & Metabolic Care, Год журнала: 2023, Номер 27(2), С. 125 - 135

Опубликована: Ноя. 21, 2023

Purpose of review Atherosclerotic cardiovascular disease (ASCVD) is the leading cause death despite development effective treatments. Recently, elevated remnant cholesterol and low-grade inflammation have emerged as factors explaining part residual ASCVD risk. Interestingly, coexistence both high can further increase risk ASCVD. The aim this to describe role inflammation, separately combined, in Recent findings Results from recently published studies, including observational genetic Mendelian randomization support a causal relationship between on primary secondary prevention settings. In addition, current evidence studies suggests that increases Summary suggest combined with may confer particular for Attention dual threat necessary, research field warranted. effect cholesterol-lowering drugs anti-inflammatory alone remains be elucidated. Video abstract http://links.lww.com/COCN/A20

Язык: Английский

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Remnant cholesterol, LDL cholesterol, and apoB absolute mass changes explain results of the PROMINENT trial

Atherosclerosis, Год журнала: 2024, Номер 393, С. 117556 - 117556

Опубликована: Апрель 20, 2024

The PROMINENT trial, a cardiovascular outcome trial of the triglyceride- and remnant cholesterol-lowering agent pemafibrate, has shown neutral results despite reduction in plasma triglycerides cholesterol. We tested hypothesis that absolute mass changes cholesterol, LDL apolipoprotein B explain trial.

Язык: Английский

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Cardiovascular disease lipids and lipoproteins biomarker standardization

Critical Reviews in Clinical Laboratory Sciences, Год журнала: 2025, Номер unknown, С. 1 - 22

Опубликована: Март 1, 2025

Cardiovascular disease (CVD) is the leading cause of mortality in United States and globally. This review describes changes CVD lipid lipoprotein biomarker measurements that occurred line with evolution clinical practice guidelines for risk assessment treatment. It also discusses level comparability these practice. Comparable reliable are achieved through assay standardization, which not only depends on correct test calibration but factors such as analytical sensitivity, selectivity, susceptibility to can affect measurement process, stability system over time. The current status standardization traditional newer biomarkers discussed, approaches setting achieving goals low-density cholesterol (LDL-C), high-density (HDL-C), total (TC), triglycerides (TG), lipoprotein(a) (Lp(a)), apolipoproteins (apo) A-I B, non-HDL-C. Appropriate levels blood lipids maintained by Centers Disease Control Prevention's (CDC) Biomarkers Standardization Program (CDC BSP) using performance recommended National Cholesterol Education Program. agreement be dependent characteristics analytes differences principles between reference procedures assays. technical limitations observed apolipoproteins. Additionally, apoB Lp(a) may more accurately capture residual risk, respectively, than lipids, thus prompting recommend apolipoprotein measurements. further CDC's approach apoA-I B past 11 years. systems previously a single laboratory, no longer exist, requiring creation new systems, currently underway. situation emphasizes importance collaborative network laboratories, Reference Methods Laboratory Network (CRMLN), ensure sustainability. CDC supporting International Federation Clinical Chemistry Medicine's (IFCC) work establish lipoproteins. Ensuring reliability remains critical effective implementation improving patient care. Utilizing experience gained three decades, BSP will continue improve emerging together stakeholders.

Язык: Английский

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Metabolic diseases in the East Asian populations

Nature Reviews Gastroenterology & Hepatology, Год журнала: 2025, Номер unknown

Опубликована: Апрель 8, 2025

Язык: Английский

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Machine-learning models to predict serious adverse hospitalization events after ACS

Postgraduate Medical Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 3, 2025

We developed a risk stratification model to predict serious adverse hospitalization events (mortality, cardiac shock, arrest) (SAHE) after acute coronary syndrome (ACS) based on machine-learning models and logistic regression model. This cohort study is the CCC-ACS project. The primary efficacy outcomes were SAHE. Clinical prediction established five (XGBoost, RF, MLP, KNN, stacking model) models. Among 112 363 patients in study, age (55-65 years: OR: 1.392; 95%CI: 1.212-1.600; 65-75 1.878; 1.647-2.144; ≥75 year: 2.976; 2.615-3.393), history of diabetes mellitus (OR: 1.188; 1.083-1.302), renal failure 1.645; 1.311-2.044), heart rate (60-100 beats/min: 0.468; 0.409-0.536; ≥100 0.540; 0.454-0.643), shock index (0.4-0.8: 1.796; 1.440-2.264; ≥0.8: 5.883; 4.619-7.561), KILLIP (II: 1.171; 1.048-1.306; III: 1.696; 1.469-1.952; IV: 7.811; 7.023-8.684), arrest at admission 12.507; 10.757-14.530) independent predictors severe for ACS patients. In several models, RF (AUC: 0.817; 0.808-0.826) XGBoost 0.816; 0.807-0.825) also showed good discrimination training set, which ranked first two positions. They presented accuracy best clinical benefits decision curve analysis. addition, was able discriminate SAHE performed (0.822; 0.822-0.822) compared Model calibration analysis these have similar predictive performance. Based findings, we In-hospital Major Adverse Events Risk Scores its online calculator. One (https://ccc-acs-sae-3-xcnjsvoccusjwkfhfthh44.streamlit.app/), another (https://ccc-acs-sae-logistic-9te57ylnq3kazkeuyc7dub.streamlit.app/), offering validated tool survival with during hospitalization. Machine-learning-based approaches identifying an feasible practical. this, websites clinicians' decision-making. CCC-ACS-MSAE score accurate discriminative capabilities predicting might help guide Key messages: Three research questions three bullet points What already known this topic? Observational studies identified factors in-hospital death syndromes (ACS). However, real-world results large sample China still need be further explored. does add? How affect research, practice, or policy? Early identification high-risk will reduce deaths improve prognosis

Язык: Английский

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Mass changes in remnant cholesterol and LDL cholesterol explain part of the results of gemfibrozil and non‐gemfibrozil fibrate trials

Journal of Internal Medicine, Год журнала: 2024, Номер 295(5), С. 707 - 710

Опубликована: Фев. 11, 2024

Table S1. Absolute changes of lipid traits in PROMINENT, ACCORD, FIELD, BIP, VA-HIT, and HHS. S2. Comparison different gemfibrozil non-gemfibrozil fibrate trials CGPS mimicking corresponding trial. Figure Copenhagen General Population Study using calculated LDL cholesterol remnant by the Martin-Hopkins equation. non-HDL cholesterol. Please note: The publisher is not responsible for content or functionality any supporting information supplied authors. Any queries (other than missing content) should be directed to author article.

Язык: Английский

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Effect of Adding Apolipoprotein B Testing on the Prevalence of Dyslipidemia and Risk of Cardiovascular Disease in the Korean Adult Population

Metabolites, Год журнала: 2024, Номер 14(3), С. 169 - 169

Опубликована: Март 18, 2024

Traditional lipid parameters—including total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), high-density (HDL-C), and non-HDL-C (calculated as TC minus HDL-C)—have long been used indicators of cardiovascular disease (CVD) risk. The laboratory records 9604 Korean adults who underwent traditional panel tests (TC, TG, HDL), well ApoB testing, were analyzed to evaluate the prevalence dyslipidemia high CVD risk (utilizing NCEP ATP III criteria for panels various test cutoffs recommended by international guidelines (145 mg/dL, 130 100 mg/dL)). overall dyslipidemia, determined criteria, was 27.4%. Utilizing 145 mg/dL resulted in figures 5.3%, 11.0%, 36.3%, respectively. concordance classification between at 78.4%, 81.3%, 74.7%, Up 17.5% participants, based on an cutoff ≥100 exhibited isolated absence anomalies. Incorporating testing could enhance identification Koreans

Язык: Английский

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Monoglucosyl rutin, a flavonoid glycoside, improves low-density lipoprotein-cholesterol levels in healthy adults: A randomized controlled trial

Functional Foods in Health and Disease, Год журнала: 2024, Номер 14(6), С. 222 - 235

Опубликована: Июнь 3, 2024

Background: Atherosclerotic cardiovascular disease (ASCVD) continues to be a significant contributor global mortality, impacting over 523 million individuals worldwide. Dyslipidemia stands as one of the foremost risk factors for ASCVD. Thus, prioritizing reduction low-density lipoprotein cholesterol (LDL-C) levels is essential in mitigating complications. Objective: This study aimed evaluate lipid-lowering activity dietary supplement containing monoglucosyl rutin (MR) with low mild hypercholesterolemia. Methods: was randomized, placebo-controlled, double-blind, parallel-group conducted from April 20 December 24, 2022. The population included 56 healthy Japanese adult participants LDL-C between 120–139 mg/dL who were randomly allocated either MR or placebo groups (n = 28/group) using computerized random number generator. 200 mg divided into 3 tablets given daily; instructed take 1 tablet water after each meal 12 weeks. main focus on measuring serum level primary outcome, additional attention secondary outcomes such high-density (HDL-C), total cholesterol, and nonHDL-C levels. also evaluated percentage achieving below 120 12-week intervention. Assessments 4, 8, weeks Results: There 54 (27 group) per-protocol set (PPS) 53 (placebo group, 26; 27) modified PPS (mPPS). A statistically group difference observed (P < 0.05), 5.0% decrease preintervention coincided (statistically significant?) decreases levels, LDL-C/HDL-C ratio. During period, there no adverse event concern about safety MR. Conclusions: has potential preventive therapeutic tool improving improve long-term health reducing morbidity. Keywords: rutin, flavonoid glycoside, hyperlipidemia, lipid profile Trial registration number: UMIN000047790

Язык: Английский

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The 10 essential questions regarding lipoprotein(a)

Current Opinion in Clinical Nutrition & Metabolic Care, Год журнала: 2023, Номер 27(2), С. 136 - 143

Опубликована: Ноя. 14, 2023

Purpose of review Lp(a) is one the most atherogenic lipoproteins, and significant progress has been made to understand its pathophysiology over last 20 years. There are now selective therapies in late-stage clinical trials lower Lp(a). Yet there many outstanding questions about This outlines 10 burning tries answer some them. Recent findings Antisense oligonucleotide (ASO) treatment currently advanced therapy plasma by 60–80%. are, however, also two small molecule medications early stage development with similar efficacy. Summary aims important preclinical metabolism physiological role possible therapeutic approaches nutraceuticals, available lipid-lowering new medications. In addition, ways illustrated use as a marker better predict cardiovascular risk.

Язык: Английский

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