Cardiovascular Protective Properties of GLP-1 Receptor Agonists: More than Just Diabetic and Weight Loss Drugs

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(16), P. 4674 - 4674

Published: Aug. 9, 2024

Owing to their potent glucose-lowering efficacy and substantial weight loss effects, glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are now considered part of the frontline therapeutic options treat both type 2 diabetes mellitus nondiabetic overweight/obesity. Stemming from successful demonstration cardiometabolic modulation reduction major adverse cardiovascular events in clinical outcome trials, GLP-1 RAs have since been validated as agents with compelling protective properties. Studies spanning bench preclinical large-scale randomised controlled trials consistently corroborated benefits this pharmacological class. Most notably, there is converging evidence that they exert favourable effects on atherosclerotic ischaemic endpoints, data indicating may do so by directly modifying burden composition plaques. This narrative review examines underlying pharmacology behind RAs, particular focus disease. It also delves into mechanisms underpin putative plaque-modifying actions, addresses existing knowledge gaps challenges looks future developments field, including use combination incretin for management.

Language: Английский

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The Polypill: A New Alternative in the Prevention and Treatment of Cardiovascular Disease

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(11), P. 3179 - 3179

Published: May 29, 2024

Cardiovascular disease (CVD) is the primary cause of death and disability worldwide. Although age-standardized CVD mortality rates decreased globally by 14.5% between 2006 2016, burden remains disproportionately higher in low- middle-income countries compared to high-income countries. Even though proven, effective approaches based on multiple-drug intake aimed at prevention treatment are currently available, poor adherence, early discontinuation treatment, suboptimal daily execution prescribed therapeutic regimes give rise shortfalls drug exposure, leading high variability responses medications. Wald Law, their landmark paper published BMJ 2003, hypothesized that use a fixed-dose combination statins, β-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, aspirin (classic Polypill composition) may increase adherence decrease up 80% when as or substitution traditional protocols. Since then, many clinical trials have tested this hypothesis, with comparable results. This review aims describe available performed assess impact combinations cost-effectiveness, risk factors critical onset CVD.

Language: Английский

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Changes in Phenylacetylglutamine Levels Provide Add-On Value in Risk Stratification of Hypertensive Patients: A Longitudinal Cohort Study

Metabolites, Journal Year: 2025, Volume and Issue: 15(1), P. 64 - 64

Published: Jan. 20, 2025

Background: Despite antihypertensive treatment, some high-risk hypertensive patients still experience major adverse cardiovascular events (MACEs). Current risk stratification tools may underestimate the presence of metabolites in hypertension and thereby MACEs. Objectives: We aimed to explore potential value gut microbiota-derived metabolite phenylacetylglutamine (PAGln) hypertension. Methods: measured plasma PAGln levels using liquid chromatography tandem mass spectrometry 1543 patients, dividing them into a discovery cohort (n = 792) validation 751). After follow-up, Kaplan–Meier curve Cox regression model were utilized determine correlation between MACEs (death, non-fatal ischemic stroke hemorrhagic stroke, acute coronary syndrome unplanned revascularization). examined predictive performance different subgroups evaluated incremental as an addition ASCVD assessment model. Results: Among all 148 experienced after mean follow-up 3.02 years. In both cohorts, adjusting other confounding factors, remained independent factor patients. Patients with ≥ 1.047 μmol/L have higher concentration provided model, better cohort. It was most effective female, systolic blood pressure (SBP) 130 mmHg taking angiotensin-converting enzyme inhibitors (ACEIs). Conclusions: associated increased hypertension, especially women or SBP ACEIs. should be considered predictor improve prognosis.

Language: Английский

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Empagliflozin Plays Vasoprotective Role in Spontaneously Hypertensive Rats via Activation of the SIRT1/AMPK Pathway

Cells, Journal Year: 2025, Volume and Issue: 14(7), P. 507 - 507

Published: March 29, 2025

Empagliflozin (EMPA), a sodium-glucose co-transporter 2 (SGLT2) inhibitor, prevents endothelial dysfunction, but its effects on vascular tone in hypertension remain unclear. This study investigated whether EMPA modulates vasomotor via sirtuin 1 (SIRT1) and AMP-activated protein kinase (AMPK) pathways spontaneously hypertensive rats (SHR) controls (Wistar Kyoto rats, WKY). Functional (wire myography, organ bath) biochemical (Western blot) studies were conducted the third-order of superior mesenteric arteries (sMAs) and/or aortas. induced concentration-dependent relaxation preconstricted sMAs both groups. In SHR, enhanced acetylcholine (Ach)-induced aortas reduced constriction by phenylephrine (Phe) U46619 sMAs. The SIRT1 inhibitor (EX527) abolished EMPA’s Ach-mediated U46619-induced vasoconstriction, while AMPK inhibition Phe-induced vasoconstriction. SHR showed increased SGLT2 expression decreased pAMPK/AMPK levels conclusion, might exert vasoprotective enhancing endothelium-dependent reducing AMPK/SIRT1 pathways. These properties could improve health patients with related conditions. Further are needed to explore new indications for inhibitors.

Language: Английский

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Novel Metabolites Genetically Linked to Salt Sensitivity of Blood Pressure: Evidence from mGWAS in Chinese Population

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(10), P. 4538 - 4538

Published: May 9, 2025

This study aims to identify genetically influenced metabolites (GIMs) associated with SSBP and elucidate their regulatory pathways through metabolome genome-wide association studies (mGWASs). Untargeted metabolomics genotyping were performed on 54 participants from the Systematic Epidemiological Study of Salt Sensitivity (EpiSS). The mGWAS was conducted 970 plasma metabolites, potential biological mechanisms explored. multivariable logistic regression model mendelian randomization (MR) employed investigate causal relationship between GIMs SSBP. Metabolomic analysis 100 subjects in replication validate identified discovery set revealed associations 1485 loci 18 metabolites. After performing linkage disequilibrium analysis, 368 independent mQTLs annotated 141 genes. These functional genes primarily implicated signal transduction sinoatrial node atrial cardiac muscle cells. Five key using CytoHubba, including CAMK2A, TIAM1, RYR2, RBFOX1, NRXN3. One-sample MR 14 SSBP, LysoPC (0:0/22:5n-3) positively (p < 0.05). Phe-lle validated analysis. elucidates genetic underlying identifies that are causally findings provide insights into identifying metabolic biomarkers characterizing its regulation mechanisms.

Language: Английский

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Is Targeting LDL-C Levels Below 70 mg/dL Beneficial for Cardiovascular and Overall Health? A Critical Examination of the Evidence

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(10), P. 3569 - 3569

Published: May 20, 2025

Over the past two decades, cardiovascular disease (CVD) prevention guidelines have progressively lowered LDL-C targets to <70 mg/dL for high-risk individuals based on assumption of a linear relationship between levels and CVD risk. However, available evidence challenges this premise. Multiple studies demonstrate weak or inconsistent association atherosclerosis progression at individual patient-level. Systematic reviews supporting linearity notable limitations, including extrapolation beyond observed ranges potential ecological fallacy, as meta-regression analyses rely study-level data, while patient-level data within same trials often show no reduction outcomes. Moreover, randomized controlled explicitly designed assess yielded inconclusive biased results. itself is heterogeneous marker, with particle size composition influencing its atherogenicity. The benefits lipid-lowering therapies may arise in part from pleiotropic effects unrelated lowering. Additionally, several indicate that higher are paradoxically associated longevity elderly populations equal even greater than general population. Collectively, body raises questions about validity current < 70 patients.

Language: Английский

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Depression in Cardiac Patients Is a Major Cardiovascular Event Risk Factor: A 12-Month Observational Study

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(22), P. 6911 - 6911

Published: Nov. 16, 2024

: Depression is a known factor in poor cardiovascular outcomes but often underassessed cardiac units. This study evaluates the impact of depression on patients undergoing interventions.

Language: Английский

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Hypertension: A Continuing Public Healthcare Issue

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 26(1), P. 123 - 123

Published: Dec. 26, 2024

Hypertension is a cardiovascular disease defined by an elevated systemic blood pressure. This devastating afflicts 30–40% of the adult population worldwide. The burden for hypertension great, and it greatly increases risk morbidity mortality. Unfortunately, there are myriad factors that result in These include genetic factors, sedentary lifestyle, obesity, salt intake, aging, stress. Although lifestyle modifications have had limited success, anti-hypertensive drugs been moderately effective lowering New approaches to control treat digital health tools compounds activate angiotensin receptor type 2 (AT2), which can promote health. Nonetheless, research on its management vital lessening significant economic this condition.

Language: Английский

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