Effects of Time-Restricted Eating on Cardiometabolic and Cardiovascular Health: Study Protocol (TRES)

This study aims to assess the safety, feasibility, and effectiveness of 10-hr Time-Restricted Eating (TRE) compared to ad libitum eating on anthropometric measurements, cardiometabolic and cardiovascular health in patients with Acute Coronary Syndrome (ACS). The Time-Restricted Eating Study (TRES) is a single-centre, pragmatic, prospective, randomised controlled trial that will include 48 patients with ACS. Participants will be randomised in a 1:1 ratio to the intervention group where eating duration is restricted to 10 hours per day or control group with no limitation of eating duration imposed. Testing is scheduled at baseline and after four weeks of intervention. The primary outcome is change in body weight after four weeks of intervention. Secondary outcomes include changes in body composition, glycaemic and lipid profiles, inflammatory markers, oxidative stress, endothelial function, arterial stiffness, blood pressure, heart rate, safety, and feasibility of TRE on patients with ACS. The study was approved by the UiTM Research Ethics Committee. Findings will be disseminated through manuscripts, reports, and presentations. Findings on the feasibility and effectiveness of TRE in patients with ACS may broaden the body of evidence for implementing TRE as a dietary intervention to prevent secondary cardiovascular diseases

A case report of heterozygous familial hypercholesterolaemia with LDLR gene mutation complicated by premature coronary artery disease detected in primary care

BackgroundFamilial Hypercholesterolemia (FH) is an autosomal dominant genetic condition predominantly caused by the low-density lipoprotein receptor (LDLR) gene mutation.Case SummaryThis is the case of a 54-year-old Malay woman with genetically confirmed FH complicated by premature coronary artery disease (PCAD). She was clinically diagnosed in primary care at 52 years old, fulfilling the Simon Broome Criteria (possible FH), Dutch Lipid Clinic Criteria (score of 8: probable FH) and Familial Hypercholesterolemia Case Ascertainment Tool (FAMCAT relative risk score of 9.51). Subsequently, she was confirmed to have a heterozygous LDLR c.190+4A>T intron 2 pathogenic variant at the age of 53 years. She was known to have hypercholesterolemia and was treated with statin since the age of 25. However, the lipid-lowering agent was not intensified to achieve the recommended treatment target. The delayed FH diagnosis has caused this patient to have PCAD and percutaneous coronary intervention (PCI) at the age of 29 years and a second PCI at the age of 49 years. She also has a very strong family history of hypercholesterolemia and PCAD, where seven out of eight of her siblings were affected. Despite this, FH was not diagnosed early and cascade screening of family members was not conducted, resulting in a missed opportunity to prevent PCAD.DiscussionFH can be clinically diagnosed in primary care to identify those who may require genetic testing. Multidisciplinary care focuses on improving identification, cascade screening and management of FH is vital to improving prognosis and ultimately preventing PCAD

Current insights on dyslipidaemia management for prevention of atherosclerotic cardiovascular disease: a malaysian perspective

Dyslipidaemia is highly prevalent in the Malaysian population and is one of the main risk factors for atherosclerotic cardiovascular disease (ASCVD). Low-density lipoprotein cholesterol (LDL-C) is recognised as the primary target of lipid-lowering therapy to reduce the disease burden of ASCVD. Framingham General CV Risk Score has been validated in the Malaysian population for CV risk assessment. The Clinical Practice Guidelines (CPG) on the management of dyslipidaemia were last updated in 2017. Since its publication, several newer randomised clinical trials have been conducted with their results published in research articles and compared in meta-analysis. This underscores a need to update the previous guidelines to ensure good quality care and treatment for the patients. This review summarises the benefits of achieving LDL-C levels lower than the currently recommended target of < 1.8mmol/L without any safety concerns. In most high and very high-risk individuals, statins are the first line of therapy for dyslipidaemia management. However, certain high-risk individuals are not able to achieve the LDL-C goal as recommended in the guideline even with high-intensity statin therapy. In such individuals, lower LDL-C levels can be achieved by combining the statins with non-statin agents such as ezetimibe and PCSK9 inhibitors. Emerging non-statin lipid-lowering therapies and challenges in dyslipidaemia management are discussed in this article. The review also summarises the recent updates on local and international guidelines for dyslipidaemia management

Semaglutide and cardiovascular outcomes in patients with obesity and prevalent heart failure: a prespecified analysis of the SELECT trial

Background: Semaglutide, a GLP-1 receptor agonist, reduces the risk of major adverse cardiovascular events (MACE) in people with overweight or obesity, but the effects of this drug on outcomes in patients with atherosclerotic cardiovascular disease and heart failure are unknown. We report a prespecified analysis of the effect of once-weekly subcutaneous semaglutide 2·4 mg on ischaemic and heart failure cardiovascular outcomes. We aimed to investigate if semaglutide was beneficial in patients with atherosclerotic cardiovascular disease with a history of heart failure compared with placebo; if there was a difference in outcome in patients designated as having heart failure with preserved ejection fraction compared with heart failure with reduced ejection fraction; and if the efficacy and safety of semaglutide in patients with heart failure was related to baseline characteristics or subtype of heart failure. Methods: The SELECT trial was a randomised, double-blind, multicentre, placebo-controlled, event-driven phase 3 trial in 41 countries. Adults aged 45 years and older, with a BMI of 27 kg/m2 or greater and established cardiovascular disease were eligible for the study. Patients were randomly assigned (1:1) with a block size of four using an interactive web response system in a double-blind manner to escalating doses of once-weekly subcutaneous semaglutide over 16 weeks to a target dose of 2·4 mg, or placebo. In a prespecified analysis, we examined the effect of semaglutide compared with placebo in patients with and without a history of heart failure at enrolment, subclassified as heart failure with preserved ejection fraction, heart failure with reduced ejection fraction, or unclassified heart failure. Endpoints comprised MACE (a composite of non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death); a composite heart failure outcome (cardiovascular death or hospitalisation or urgent hospital visit for heart failure); cardiovascular death; and all-cause death. The study is registered with ClinicalTrials.gov, NCT03574597. Findings: Between Oct 31, 2018, and March 31, 2021, 17 604 patients with a mean age of 61·6 years (SD 8·9) and a mean BMI of 33·4 kg/m2 (5·0) were randomly assigned to receive semaglutide (8803 [50·0%] patients) or placebo (8801 [50·0%] patients). 4286 (24·3%) of 17 604 patients had a history of investigator-defined heart failure at enrolment: 2273 (53·0%) of 4286 patients had heart failure with preserved ejection fraction, 1347 (31·4%) had heart failure with reduced ejection fraction, and 666 (15·5%) had unclassified heart failure. Baseline characteristics were similar between patients with and without heart failure. Patients with heart failure had a higher incidence of clinical events. Semaglutide improved all outcome measures in patients with heart failure at random assignment compared with those without heart failure (hazard ratio [HR] 0·72, 95% CI 0·60-0·87 for MACE; 0·79, 0·64-0·98 for the heart failure composite endpoint; 0·76, 0·59-0·97 for cardiovascular death; and 0·81, 0·66-1·00 for all-cause death; all pinteraction>0·19). Treatment with semaglutide resulted in improved outcomes in both the heart failure with reduced ejection fraction (HR 0·65, 95% CI 0·49-0·87 for MACE; 0·79, 0·58-1·08 for the composite heart failure endpoint) and heart failure with preserved ejection fraction groups (0·69, 0·51-0·91 for MACE; 0·75, 0·52-1·07 for the composite heart failure endpoint), although patients with heart failure with reduced ejection fraction had higher absolute event rates than those with heart failure with preserved ejection fraction. For MACE and the heart failure composite, there were no significant differences in benefits across baseline age, sex, BMI, New York Heart Association status, and diuretic use. Serious adverse events were less frequent with semaglutide versus placebo, regardless of heart failure subtype. Interpretation: In patients with atherosclerotic cardiovascular diease and overweight or obesity, treatment with semaglutide 2·4 mg reduced MACE and composite heart failure endpoints compared with placebo in those with and without clinical heart failure, regardless of heart failure subtype. Our findings could facilitate prescribing and result in improved clinical outcomes for this patient group. Funding: Novo Nordisk

Cocaine-Associated Myocardial Infarction: Should They All Be Stented?

Cocaine use is a known cause of chest pain and acute myocardial infarction and frequently leads to cardiac catheterization procedure. The treatment of cocaine-related acute coronary syndromes presents unique challenges because a variety of mechanisms including atherosclerotic plaque rupture, platelet activation, and coronary vasospasm may contribute to the pathogenesis. Our case highlights important considerations taken in dealing with this acute scenari

Anaphylaxis from Wasp Stings Inducing Coronary Thrombus

Myocardial infarction as a result of wasp stings is a rare manifestation of acute coronary syndromes. It has been ascribed to kounis syndrome or allergic angina whose triggers include mast cell degranulation leading to coronary vasospasm and/or local plaque destabilisation. Its exact pathophysiology is still not clearly defined. We present a case of an acute coronary syndrome as a consequence of wasp stings and discuss its possible aetiology

Vulnerable plaque: From bench to bedside; local pacification versus systemic therapy

Critical coronary stenoses accounts for a small proportion of acute coronary syndromes and sudden death. The majority are caused by coronary thromboses that arise from a nonangiographically obstructive atheroma. Recent developments in noninvasive imaging of so-called vulnerable plaques created opportunities to direct treatment to prevent morbidity and mortality associated with these high-risk lesions. This review covers therapy employed in the past, present, and potentially in the future as the natural history of plaque assessment unfolds

Predicting 30-day mortality after an acute coronary syndrome (ACS) using machine learning methods for feature selection, classification and visualization

Hybrid combinations of feature selection, classification and visualisation using machine learning (ML) methods have the potential for enhanced understanding and 30-day mortality prediction of patients with cardiovascular disease using population-specific data. Identifying a feature selection method with a classifier algorithm that produces high performance in mortality studies is essential and has not been reported before. Feature selection methods such as Boruta, Random Forest (RF), Elastic Net (EN), Recursive Feature Elimination (RFE), learning vector quantization (LVQ), Genetic Algorithm (GA), Cluster Dendrogram (CD), Support Vector Machine (SVM) and Logistic Regression (LR) were combined with RF, SVM, LR, and EN classifiers for 30-day mortality prediction. ML models were constructed using 302 patients and 54 input variables from the Malaysian National Cardiovascular Disease Database. Validation of the best ML model was performed against Thrombolysis in Myocardial Infarction (TIMI) using an additional dataset of 102 patients. The Self-Organising Feature Map (SOM) was used to visualise mortality-related factors post-ACS. The performance of ML models using the area under the curve (AUC) ranged from 0.48 to 0.80. The best-performing model (AUC = 0.80) was a hybrid combination of the RF variable importance method, the sequential backward selection and the RF classifier using five predictors (age, triglyceride, creatinine, troponin, and total cholesterol). Comparison with TIMI using an additional dataset resulted in the best ML model outperforming the TIMI score (AUC = 0.75 vs. AUC = 0.60). The findings of this study will provide a basis for developing an online ML-based population-specific risk scoring calculator