The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

AIM: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined. METHODS: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore. MASLD was defined as hepatic steatosis, with at least one of five metabolic criteria. Hepatic steatosis was determined using the Hepatic Steatosis Index. Propensity score matching was performed to adjust for age and sex. The Kaplan-Meier curve was constructed for long-term all-cause mortality. Cox regression analysis was used to investigate independent predictors of long-term all-cause mortality. RESULTS: In this study of 4446 patients with AMI, 2223 patients with MASLD were matched with patients without MASLD using propensity scores. The mean follow-up duration was 3.4 ± 2.4 years. The MASLD group had higher rates of obesity, diabetes and chronic kidney disease than their counterparts. Patients with MASLD had early excess all-cause mortality (6.8% vs. 3.6%, p < .001) at 30 days, with unfavourable mortality rates sustained in the long-term (18.3% vs. 14.5%, p = .001) compared with those without MASLD. After adjustment, MASLD remained independently associated with higher long-term all-cause mortality (hazard ratio 1.330, 95% confidence interval 1.106-1.598, p = .002). CONCLUSION: MASLD embodies a higher burden of metabolic dysfunction and is an independent predictor of long-term mortality in the AMI population. Its early identification may be beneficial for risk stratification and provide therapeutic targets for secondary preventive strategies in AMI.

The Global Epidemic of Metabolic Fatty Liver Disease.

PURPOSE OF REVIEW: The objective of this manuscript is to examine the current literature on the epidemiology of metabolic dysfunction-associated steatotic liver disease (MASLD), its correlation with cardiovascular disease (CVD) outcomes, as well as to evaluate the update in nomenclature from non-alcoholic liver disease (NAFLD). RECENT FINDINGS: The update of diagnostic criteria from NAFLD to MASLD reduces the stigma associated with alcohol consumption and poor health choices. It also shines a light on the crucial role of cardiometabolic risk factors in disease pathophysiology. The incidence and prevalence of MASLD are projected to increase significantly in the future as the population burden of cardiometabolic risk factors rises. MASLD is also a potent risk factor for developing CVD that should be tackled by using a multi-disciplinary team with a holistic approach. As the new nomenclature for metabolic liver disease is adopted on a global scale, more research is needed to investigate the applicability of findings from previous trials focusing on NAFLD. It is anticipated that the epidemic of MASLD will continue to increase globally, hence the urgent need for therapeutic approaches to reverse this trend.

Type 2 diabetes mellitus and cardiometabolic outcomes in metabolic dysfunction-associated steatotic liver disease population.

The metabolic syndrome, characterized by type 2 diabetes mellitus (T2DM), hypertension, hyperlipidemia, and obesity, collectively increases the risk of cardiovascular diseases. Nonalcoholic fatty liver disease (NAFLD) is a prominent manifestation, affecting over a third of the global population with a concerning annual increase in prevalence. Nearly 70 % of overweight individuals have NAFLD, and NAFLD-related deaths are predicted to rise, especially among young adults. The association of T2DM and NAFLD has led to the proposal of "metabolic dysfunction-associated steatotic liver disease" (MASLD) terminology, encompassing individuals with T2DM, overweight/obesity, hypertension, hypertriglyceridemia, or low HDL-cholesterol. Patients with MASLD will likely have double the risk of developing T2DM, and the combination of insulin resistance, overweight/obesity, and MASLD significantly elevates the risk of T2DM. Cardiovascular diseases remain the leading cause of mortality in the MASLD and T2DM population, with MASLD directly associated with coronary artery disease, compounded by coexisting insulin resistance and T2DM. Urgency lies in early detection of subclinical cardiovascular diseases among patients with T2DM and MASLD. Novel strategies targeting multiple pathways offer hope for effectively improving cardiometabolic health. Understanding and addressing the intertwined factors contributing to these disorders can pave the way towards better management and prevention of cardiometabolic complications.

Gut-liver axis: Potential mechanisms of action of food-derived extracellular vesicles.

Food-derived extracellular vesicles (FEVs) are nanoscale membrane vesicles obtained from dietary materials such as breast milk, plants and probiotics. Distinct from other EVs, FEVs can survive the harsh degrading conditions in the gastrointestinal tract and reach the intestines. This unique feature allows FEVs to be promising prebiotics in health and oral nanomedicine for gut disorders, such as inflammatory bowel disease. Interestingly, therapeutic effects of FEVs have recently also been observed in non-gastrointestinal diseases. However, the mechanisms remain unclear or even mysterious. It is speculated that orally administered FEVs could enter the bloodstream, reach remote organs, and thus exert therapeutic effects therein. However, emerging evidence suggests that the amount of FEVs reaching organs beyond the gastrointestinal tract is marginal and may be insufficient to account for the significant therapeutic effects achieved regarding diseases involving remote organs such as the liver. Thus, we herein propose that FEVs primarily act locally in the intestine by modulating intestinal microenvironments such as barrier integrity and microbiota, thereby eliciting therapeutic impact remotely on the liver in non-gastrointestinal diseases via the gut-liver axis. Likewise, drugs delivered to the gastrointestinal system through FEVs may act via the gut-liver axis. As the liver is the main metabolic hub, the intestinal microenvironment may be implicated in other metabolic diseases. In fact, many patients with non-alcoholic fatty liver disease, obesity, diabetes and cardiovascular disease suffer from a leaky gut and dysbiosis. In this review, we provide an overview of the recent progress in FEVs and discuss their biomedical applications as therapeutic agents and drug delivery systems, highlighting the pivotal role of the gut-liver axis in the mechanisms of action of FEVs for the treatment of gut disorders and metabolic diseases.

Impact of Chronic Kidney Disease on the Processes of Care and Long-Term Mortality of Non-ST-Segment-Elevation Myocardial Infarction: A Nationwide Cohort Study and Long-Term Follow-Up.

BACKGROUND: A growing population of patients with chronic kidney disease (CKD) presents with non-ST-segment-elevation myocardial infarction, although little is known about their longer-term mortality. METHODS AND RESULTS: Using the MINAP (Myocardial Ischaemia National Audit Project) registry, linked to Office for National Statistics mortality data, we analyzed 363 559 UK patients with non-ST-segment-elevation myocardial infarction, with or without CKD. Cox regression models were fitted, adjusting for baseline demographics. Compared with patients without CKD, patients with CKD were less frequently prescribed P2Y12 inhibitors (89% versus 86%, P<0.001) less likely to undergo invasive angiography (67% versus 41%, P<0.001) or percutaneous coronary intervention (41% versus 25%, P<0.001), and were less often referred to cardiac rehabilitation (80% versus 66%, P<0.001). Following non-ST-segment-elevation myocardial infarction, patients with CKD had higher risk of 30-day (adjusted hazard ratio [HR], 1.24 [95% CI, 1.20-1.29], 1-year 1.47 [95% CI, 1.44-1.51]) and 5-year mortality 1.55 (95% CI, 1.53-1.58) than patients without CKD (all P<0.001). Risk of mortality over the entire study period was highest in CKD Stage 5 (HR, 2.98 [95% CI, 2.87-3.10]), even after excluding mortality ≤30 days (HR, 3.03 [95% CI, 2.90-3.17]) (P<0.001). There was no significant difference in proportion of deaths attributable to cardiovascular disease at 30 days (CKD; 76% versus no CKD; 76%), or 1 -year (CKD; 62% versus no CKD; 62%). CONCLUSIONS: Patients with CKD were significantly less likely to receive invasive investigation or undergo percutaneous coronary intervention and had significantly higher risk of short- and longer-term mortality. Risk of mortality increased with reducing CKD stage. Cardiovascular disease was the main cause of mortality in patients with CKD, but at comparable rates to the general population with non-ST-segment-elevation myocardial infarction.

Anthropometric and cardiometabolic effects of polyphenols in people with overweight and obesity: an umbrella review.

CONTEXT: Polyphenols are plant-based compounds with potential anti-inflammatory, antioxidant, and anti-obesogenic properties. However, their effects on health outcomes remain unclear. OBJECTIVE: To evaluate the effects of polyphenols on anthropometric and cardiometabolic markers. DATA SOURCES: Six electronic databases-namely, EMBASE, CINAHL, PubMed, Scopus, The Cochrane Library (reviews only), and Web of Science-were searched for relevant systematic reviews with meta-analyses (SRMAs). DATA EXTRACTION: Three reviewers performed the data extraction via a data-extraction Microsoft Excel spreadsheet. DATA ANALYSIS: An umbrella review and meta-analysis of existing SRMAs was conducted. Eighteen SRMAs published from 2015 to 2023, representing 445 primary studies and 838 unique effect sizes, were identified. Meta-analyses were conducted using random-effects models with general inverse variance. Polyphenol-containing foods were found to significantly improve weight (-0.36 kg; 95% confidence interval [CI]: -0.62, 0.77 kg; P < 0.01, I2 = 64.9%), body mass index (-0.25 kg/m2; 95% CI: -0.34, -0.17 kg/m2; P < 0.001, I2 = 82.4%), waist circumference (-0.74 cm; 95% CI: -1.34, -0.15 cm; P < 0.01, I2 = 99.3%), low-density-lipoprotein cholesterol (-1.75 mg/dL; 95% CI: -2.56, -0.94; P < 0.001, I2 = 98.6%), total cholesterol (-1.23 mg/dL; 95% CI: -2.00, -0.46; P = 0.002, I2 = 94.6%), systolic blood pressure (-1.77 mmHg; 95% CI: -1.77, -0.93 mmHg; P < 0.001, I2 = 72.4%), diastolic blood pressure (-1.45 mmHg; 95% CI: -2.09, -0.80 mmHg; P < 0.001, I2 = 61.0%), fat percentage (-0.70%; 95% CI: -1.03, -0.36%; P < 0.001, I2 = 52.6%), fasting blood glucose (-0.18 mg/dL; 95% CI: -0.35, -0.01 mg/dL; P = 0.04, I2 = 62.0%), and C-reactive protein (CRP; including high-sensitivity-CRP [hs-CRP]) (-0.2972 mg/dL; 95% CI: -0.52, -0.08 mg/dL; P = 0.01, I2 = 87.9%). No significant changes were found for high-density-lipoprotein cholesterol (-0.12 mg/dL; 95% CI: -1.44, 0.69; P = 0.67, I2 = 89.4%) and triglycerides (-1.29 mg/dL; 95% CI: -2.74, 0.16; P = 0.08, I2 = 85.4%). Between-study heterogeneity could be explained by polyphenol subclass differences. CONCLUSION: The findings of this umbrella review support the beneficial effects of polyphenols on anthropometric and metabolic markers, but discretion is warranted to determine the clinical significance of the magnitude of the biomarker improvements. SYSTEMATIC REVIEW REGISTRATION: International Prospective Register of Systematic Reviews no. CRD42023420206.

Public acceptance of using artificial intelligence-assisted weight management apps in high-income southeast Asian adults with overweight and obesity: a cross-sectional study.

Introduction: With in increase in interest to incorporate artificial intelligence (AI) into weight management programs, we aimed to examine user perceptions of AI-based mobile apps for weight management in adults with overweight and obesity. Methods: 280 participants were recruited between May and November 2022. Participants completed a questionnaire on sociodemographic profiles, Unified Theory of Acceptance and Use of Technology 2 (UTAUT2), and Self-Regulation of Eating Behavior Questionnaire. Structural equation modeling was performed using R. Model fit was tested using maximum-likelihood generalized unweighted least squares. Associations between influencing factors were analyzed using correlation and linear regression. Results: 271 participant responses were analyzed, representing participants with a mean age of 31.56 ± 10.75 years, median (interquartile range) BMI, and waist circumference of 27.2 kg/m2 (24.2-28.4 kg/m2) and 86.4 (80.0-94.0) cm, respectively. In total, 188 (69.4%) participants intended to use AI-assisted weight loss apps. UTAUT2 explained 63.3% of the variance in our intention of the sample to use AI-assisted weight management apps with satisfactory model fit: CMIN/df = 1.932, GFI = 0.966, AGFI = 0.954, NFI = 0.909, CFI = 0.954, RMSEA = 0.059, SRMR = 0.050. Only performance expectancy, hedonic motivation, and the habit of using AI-assisted apps were significant predictors of intention. Comparison with existing literature revealed vast variabilities in the determinants of AI- and non-AI weight loss app acceptability in adults with and without overweight and obesity. UTAUT2 produced a good fit in explaining the acceptability of AI-assisted apps among a multi-ethnic, developed, southeast Asian sample with overweight and obesity. Conclusion: UTAUT2 model is recommended to guide the development of AI-assisted weight management apps among people with overweight and obesity.

Medication and supplement pharmacokinetic changes following bariatric surgery: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. METHODS: Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model. RESULTS: Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I2 = 67%), increased maximal concentration (MD = 6.90 µg/ml, p = 0.006, I2 = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I2 = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters. CONCLUSION: This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.

Efficacy and safety of tirzepatide, GLP-1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta-analysis.

OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of tirzepatide compared to glucagon-like peptide-1 receptor agonists (GLP-1 RA) and other weight loss drugs in the treatment of overweight and obesity. METHODS: MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP-1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta-analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects. RESULTS: Thirty-one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight-related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42-16.34). As compared to placebo, tirzepatide and GLP-1 RA across all doses had significant increases in gastrointestinal adverse effects. CONCLUSIONS: The superiority of tirzepatide and GLP-1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity.

Cardiovascular Outcomes in Acute Coronary Syndrome and Malnutrition: A Meta-Analysis of Nutritional Assessment Tools.

Background: There is emerging evidence that malnutrition is associated with poor prognosis among patients with acute coronary syndrome (ACS). Objectives: This study seeks to elucidate the prognostic impact of malnutrition in patients with ACS and provide a quantitative review of most commonly used nutritional assessment tools. Methods: Medline and Embase were searched for studies reporting outcomes in patients with malnutrition and ACS. Nutritional screening tools of interest included the Prognostic Nutrition Index, Geriatric Nutritional Risk Index, and Controlling Nutritional Status. A comparative meta-analysis was used to estimate the risk of all-cause mortality and cardiovascular events based on the presence of malnutrition and stratified according to ACS type, ACS intervention, ethnicity, and income. Results: Thirty studies comprising 37,303 patients with ACS were included, of whom 33.5% had malnutrition. In the population with malnutrition, the pooled mortality rate was 20.59% (95% CI: 14.95%-27.67%). Malnutrition was significantly associated with all-cause mortality risk after adjusting for confounders including age and left ventricular ejection fraction (adjusted HR: 2.66, 95% CI: 1.78-3.96, P = 0.004). There was excess mortality in the group with malnutrition regardless of ACS type (P = 0.132), ethnicity (P = 0.245), and income status (P = 0.058). Subgroup analysis demonstrated no statistically significant difference in mortality risk between individuals with and without malnutrition (P = 0.499) when using Controlling Nutritional Status (OR: 7.80, 95% CI: 2.17-28.07, P = 0.011), Geriatric Nutritional Risk Index (OR: 4.30, 95% CI: 2.78-6.66, P < 0.001), and Prognostic Nutrition Index (OR: 4.67, 95% CI: 2.38-9.17, P = 0.023). Conclusions: Malnutrition was significantly associated with all-cause mortality risk following ACS, regardless of ACS type, ethnicity, and income status, underscoring the importance of screening and interventional strategies for patients with malnutrition.