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.

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.

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort.

Background: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. Methods: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. Findings: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. Interpretation: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. Funding: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore.

General Public's knowledge, awareness, and perception of Cardiometabolic diseases: data from a Singapore study population.

Background: Health literacy and illness perception play crucial roles in tackling the cardiometabolic disease epidemic. We aim to compare the attitudes, knowledge, self-perceived risks and actions taken, between individuals with and without metabolic risk factors (MFs). Methods: From 5 June to 5 October 2022, participants of the general public were invited to complete a self-administered questionnaire. MF status was defined as the presence of hypertension, hyperlipidemia, diabetes mellitus and/or current/previous smoking. Participants were assessed based on four categories (knowledge-based, attitude-based, perceived risk, and action-based) of questions pertaining to four cardiometabolic diseases - diabetes mellitus, hypertension, hyperlipidemia, and non-alcoholic fatty liver disease. Results: A total of 345 participants were enrolled, of whom 34.5% had at least one MF. Compared to those without MFs, participants with MFs had lower knowledge scores, but higher perceived risk scores across all cardiometabolic diseases. The largest knowledge gap pertained to hypertension-related questions. After adjustment, linear regression demonstrated that the presence of MFs (ß:2.752, 95%CI: 0.772-4.733, p = 0.007) and higher knowledge scores (ß:0.418, 95%CI: 0.236-0.600, p < 0.001) were associated with higher perceived risk. Despite increased perceived risk in those with MFs, this translated to only few increased self-reported preventive actions, when compared to those without MFs, namely the reduction in red meat/processed food consumption (p = 0.045) and increase in fruits/vegetables consumption (p = 0.009). Conclusion: This study identified a vulnerable subpopulation living with MFs, with high perceived risks, and discordant levels of knowledge and preventive actions taken. Nationwide efforts should be channeled into addressing the knowledge-to-action gap.

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity. METHODS: Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, ≥5%, ≥10%, and ≥15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively. RESULTS: RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved ≥5%, ≥10%, and ≥15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide. CONCLUSION: Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies.

Epicardial Adipose Tissue Assessed by Computed Tomography and Echocardiography Are Associated With Adverse Cardiovascular Outcomes: A Systematic Review and Meta-Analysis.

BACKGROUND: Epicardial adipose tissue (EAT) has garnered attention as a prognostic and risk stratification factor for cardiovascular disease. This study, via meta-analyses, evaluates the associations between EAT and cardiovascular outcomes stratified across imaging modalities, ethnic groups, and study protocols. METHODS: Medline and Embase databases were searched without date restriction on May 2022 for articles that examined EAT and cardiovascular outcomes. The inclusion criteria were (1) studies measuring EAT of adult patients at baseline and (2) reporting follow-up data on study outcomes of interest. The primary study outcome was major adverse cardiovascular events. Secondary study outcomes included cardiac death, myocardial infarction, coronary revascularization, and atrial fibrillation. RESULTS: Twenty-nine articles published between 2012 and 2022, comprising 19 709 patients, were included in our analysis. Increased EAT thickness and volume were associated with higher risks of cardiac death (odds ratio, 2.53 [95% CI, 1.17-5.44]; P=0.020; n=4), myocardial infarction (odds ratio, 2.63 [95% CI, 1.39-4.96]; P=0.003; n=5), coronary revascularization (odds ratio, 2.99 [95% CI, 1.64-5.44]; P<0.001; n=5), and atrial fibrillation (adjusted odds ratio, 4.04 [95% CI, 3.06-5.32]; P<0.001; n=3). For 1 unit increment in the continuous measure of EAT, computed tomography volumetric quantification (adjusted hazard ratio, 1.74 [95% CI, 1.42-2.13]; P<0.001) and echocardiographic thickness quantification (adjusted hazard ratio, 1.20 [95% CI, 1.09-1.32]; P<0.001) conferred an increased risk of major adverse cardiovascular events. CONCLUSIONS: The utility of EAT as an imaging biomarker for predicting and prognosticating cardiovascular disease is promising, with increased EAT thickness and volume being identified as independent predictors of major adverse cardiovascular events. REGISTRATION: URL: https://www.crd.york.ac.uk/prospero; Unique identifier: CRD42022338075.

Higher risk of adverse cardiovascular outcomes in females with type 2 diabetes Mellitus: an Umbrella review of systematic reviews.

BACKGROUND: Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have excess mortality risk compared to their male counterparts. An important next step to address the high global burden of T2DM and cardiovascular disease (CVD) is an umbrella review to summarize data on sex differences in cardiovascular outcomes for patients with T2DM and assess the strength of the evidence observed. METHODS AND RESULTS: Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32-1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25-1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05-1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07-1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11-2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20-1.73, P < 0.001) as compared to males. CONCLUSIONS: This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities.

This umbrella review highlights the sex differences in adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM), with females at a higher risk than males. This is contributed by both biological and healthcare disparities and underscores the need for equitable care and personalized medical therapy.Females with T2DM have a higher risk of coronary heart disease, acute coronary syndrome, heart failure, and cardiac mortality compared to males.Clinicians need to be aware of the substantial heterogeneity across the current T2DM studies, and future meta-analysis and large-scale studies examining sex differences in outcomes should attempt to address the heterogeneity and epidemiological factors for a better quality of evidence.

Socioeconomic deprivation and prognostic outcomes in acute coronary syndrome: A meta-analysis using multidimensional socioeconomic status indices.

BACKGROUND: Low socioeconomic status (SES) is an important prognosticator amongst patients with acute coronary syndrome (ACS). This paper analysed the effects of SES on ACS outcomes. METHODS: Medline and Embase were searched for articles reporting outcomes of ACS patients stratified by SES using a multidimensional index, comprising at least 2 of the following components: Income, Education and Employment. A comparative meta-analysis was conducted using random-effects models to estimate the risk ratio of all-cause mortality in low SES vs high SES populations, stratified according to geographical region, study year, follow-up duration and SES index. RESULTS: A total of 29 studies comprising of 301,340 individuals were included, of whom 43.7% were classified as low SES. While patients of both SES groups had similar cardiovascular risk profiles, ACS patients of low SES had significantly higher risk of all-cause mortality (adjusted HR:1.19, 95%CI: 1.10-1.1.29, p < 0.001) compared to patients of high SES, with higher 1-year mortality (RR:1.08, 95%CI:1.03-1.13, p = 0.0057) but not 30-day mortality (RR:1.07, 95%CI:0.98-1.16, p = 0.1003). Despite having similar rates of ST-elevation myocardial infarction and non-ST-elevation ACS, individuals with low SES had lower rates of coronary revascularisation (RR:0.95, 95%CI:0.91-0.99, p = 0.0115) and had higher cerebrovascular accident risk (RR:1.25, 95%CI:1.01-1.55, p = 0.0469). Excess mortality risk was independent of region (p = 0.2636), study year (p = 0.7271) and duration of follow-up (p = 0.0604) but was dependent on the SES index used (p < 0.0001). CONCLUSION: Low SES is associated with increased mortality post-ACS, with suboptimal coronary revascularisation rates compared to those of high SES. Concerted efforts are needed to address the global ACS-related socioeconomic inequity. REGISTRATION AND PROTOCOL: The current study was registered with PROSPERO, ID: CRD42022347987.

Mortality, Cardiovascular, and Medication Outcomes in Patients With Myocardial Infarction and Underweight in a Meta-Analysis of 6.3 Million Patients.

Although most of the current evidence on myocardial infarction focuses on obesity, there is growing evidence that patients who are underweight have unfavorable prognosis. This study aimed to explore the prevalence, clinical characteristics, and prognosis of this population at risk. Embase and Medline were searched for studies reporting outcomes in populations who were underweight with myocardial infarction. Underweight and normal weight were defined according to the World Health Organization criteria. A single-arm meta-analysis of proportions was used to estimate the prevalence of underweight in patients with myocardial infarction, whereas a meta-analysis of proportions was used to estimate the odds ratio of all-cause mortality, medications prescribed, and cardiovascular outcomes. Twenty-one studies involving 6,368,225 patients were included, of whom 47,866 were underweight. The prevalence of underweight in patients with myocardial infarction was 2.96% (95% confidence interval 1.96% to 4.47%). Despite having fewer classical cardiovascular risk factors, patients who were underweight had 66% greater hazard for mortality (hazard ratio 1.66, 95% confidence interval 1.44 to 1.92, p <0.0001). The mortality of patients who were underweight increased from 14.1% at 30 days to 52.6% at 5 years. Nevertheless, they were less likely to receive guideline-directed medical therapy. Relative to subjects with normal weight, Asian populations who were underweight had greater mortality risks than those of their Caucasian counterparts (p = 0.0062). In conclusion, in patients with myocardial infarction, those who were underweight tend to have poorer prognostic outcomes. A lower body mass index is an independent predictor of mortality, which calls for global efforts in addressing this modifiable risk factor in clinical practice guidelines.

Trends and predictions of malnutrition and obesity in 204 countries and territories: an analysis of the Global Burden of Disease Study 2019.

Background: Malnutrition and obesity are interdependent pathologies along the same spectrum. We examined global trends and projections of disability-adjusted life years (DALYs) and deaths from malnutrition and obesity until 2030. Methods: Using data from the 2019 Global Burden of Disease study involving 204 countries and territories, trends in DALYs and deaths were described for obesity and malnutrition from 2000 to 2019, stratified by geographical regions (as defined by WHO) and Socio-Demographic Index (SDI). Malnutrition was defined according to the 10th revision of International Classification of Diseases codes for nutritional deficiencies, stratified by malnutrition type. Obesity was measured via body mass index (BMI) using metrics related to national and subnational estimates, defined as BMI ≥25 kg/m2. Countries were stratified into low, low-middle, middle, high-middle, and high SDI bands. Regression models were constructed to predict DALYs and mortality up to 2030. Association between age-standardised prevalence of the diseases and mortality was also assessed. Findings: In 2019, age-standardised malnutrition-related DALYs was 680 (95% UI: 507-895) per 100,000 population. DALY rates decreased from 2000 to 2019 (-2.86% annually), projected to fall 8.4% from 2020 to 2030. Africa and low SDI countries observed highest malnutrition-related DALYs. Age-standardised obesity-related DALY estimates were 1933 (95% UI: 1277-2640). Obesity-related DALYs rose 0.48% annually from 2000 to 2019, predicted to increase by 39.8% from 2020 to 2030. Highest obesity-related DALYs were in Eastern Mediterranean and middle SDI countries. Interpretation: The ever-increasing obesity burden, on the backdrop of curbing the malnutrition burden, is predicted to rise further. Funding: None.

The global burden of metabolic disease: Data from 2000 to 2019.

Global estimates of prevalence, deaths, and disability-adjusted life years (DALYs) from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019 were examined for metabolic diseases (type 2 diabetes mellitus [T2DM], hypertension, and non-alcoholic fatty liver disease [NAFLD]). For metabolic risk factors (hyperlipidemia and obesity), estimates were limited to mortality and DALYs. From 2000 to 2019, prevalence rates increased for all metabolic diseases, with the greatest increase in high socio-demographic index (SDI) countries. Mortality rates decreased over time in hyperlipidemia, hypertension, and NAFLD, but not in T2DM and obesity. The highest mortality was found in the World Health Organization Eastern Mediterranean region, and low to low-middle SDI countries. The global prevalence of metabolic diseases has risen over the past two decades regardless of SDI. Urgent attention is needed to address the unchanging mortality rates attributed to metabolic disease and the entrenched sex-regional-socioeconomic disparities in mortality.

Long-Term Prognosis of Patients With Coexisting Obesity and Malnutrition After Acute Myocardial Infarction: A Cohort Study.

BACKGROUND: The double burden of malnutrition, described as the coexistence of malnutrition and obesity, is a growing global health issue. This study examines the combined effects of obesity and malnutrition on patients with acute myocardial infarction (AMI). METHODS: Patients presenting with AMI to a percutaneous coronary intervention-capable hospital in Singapore between January 2014 and March 2021 were retrospectively studied. Patients were stratified into the following: (1) nourished nonobese, (2) malnourished nonobese, (3) nourished obese, and (4) malnourished obese. Obesity and malnutrition were defined according to the World Health Organization definition (body mass index ≥27.5 kg/m2) and Controlling Nutritional Status score, respectively. The primary outcome was all-cause mortality. The association between combined obesity and nutritional status with mortality was examined using Cox regression, adjusted for age, sex, AMI type, previous AMI, ejection fraction, and chronic kidney disease. Kaplan-Meier curves for all-cause mortality were constructed. RESULTS: The study included 1829 AMI patients, of which 75.7% were male and mean age was 66 years. Over 75% of patients were malnourished. Majority were malnourished nonobese (57.7%), followed by malnourished obese (18.8%), nourished nonobese (16.9%), and nourished obese (6.6%). Malnourished nonobese had highest all-cause mortality (38.6%), followed by the malnourished obese (35.8%), nourished nonobese (21.4%), and nourished obese (9.9%, P<0.001). Kaplan-Meier curves demonstrated least favorable survival in malnourished nonobese group, followed by malnourished obese, nourished nonobese, and nourished obese. With nourished nonobese group as the reference, malnourished nonobese had higher all-cause mortality (hazard ratio, 1.46 [95% CI, 1.10-1.96], P=0.010), but only a nonsignificant increase in mortality was observed in the malnourished obese (hazard ratio, 1.31 [95% CI, 0.94-1.83], P=0.112). CONCLUSIONS: Among AMI patients, malnutrition is prevalent even in the obese. Compared to nourished patients, malnourished AMI patients have a more unfavorable prognosis especially in those with severe malnutrition regardless of obesity status, but long-term survival is the most favorable among nourished obese patients.

A two-decade population-based study on the effect of hypertension in the general population with obesity in the United States.

OBJECTIVE: With rising prevalence of hypertension and obesity, the effect of hypertension in obesity remains an important global issue. The prognosis of the US general population with obesity based on hypertension control was examined. METHODS: This study examined participants from the National Health and Nutrition Examination Survey between 1999 and 2018. Individuals with obesity were stratified into no hypertension, controlled hypertension, and uncontrolled hypertension. The study outcome was all-cause mortality. Cox regression of all-cause mortality was adjusted for age, sex, ethnicity, diabetes, and previous myocardial infarction. RESULTS: Of 16,386 individuals with obesity, 53.1% had no hypertension, 24.7% had controlled hypertension, and 22.2% had uncontrolled hypertension. All-cause mortality was significantly higher in uncontrolled hypertension (17.1%), followed by controlled hypertension (14.8%) and no hypertension (4.0%). Uncontrolled hypertension had the highest mortality risk (hazard ratio [HR] 1.34, 95% CI: 1.13-1.59, p = 0.001), followed by controlled hypertension (HR 1.21, 95% CI: 1.10-1.34, p < 0.001), compared with no hypertension after adjustment. The excess mortality trend was more pronounced in females, those with diabetes, and those older than age 65 years. CONCLUSIONS: The incremental mortality risk in controlled and uncontrolled hypertension, compared with the normotensive counterparts, irrespective of sex, age, and diabetes status, urges health care providers to optimize hypertension control and advocate weight loss to achieve better outcomes in obesity.

The global syndemic of metabolic diseases in the young adult population: A consortium of trends and projections from the Global Burden of Disease 2000-2019.

BACKGROUND: A significant proportion of premature deaths globally are related to metabolic diseases in young adults. We examined the global trends and mortality of metabolic diseases in individuals aged below 40 years using data from the Global Burden of Diseases, Injuries and Risk Factors Study (GBD) 2019. METHODS: From 2000 to 2019, global estimates of deaths and disability-adjusted life years (DALYs) were described for metabolic diseases (type 2 diabetes mellitus [T2DM], hyperlipidemia, hypertension, obesity, non-alcoholic fatty liver disease [NAFLD]). Subgroup analyses were performed based on sex, geographical regions and Socio-Demographic Index (SDI). Age-standardised death and DALYs were presented per 100,000 population with 95 % uncertainty intervals (UI). Projections of mortality and DALYs were estimated using regression models based on the GBD 2019 data and combining them with Institute for Health Metrics and Evaluation projection counts for years up to 2050. RESULTS: In 2019, the highest age-standardised death rates were observed in hypertension (133·88 [121·25-155·73]), followed by obesity (62·59 [39·92-89·13]), hyperlipidemia (56·51 [41·83-73·62]), T2DM (18·49 [17·18-19·66]) and NAFLD (2·09 [1·61-2·60]). Similarly, obesity (1932·54 [1276·61-2639·74]) had the highest age-standardised DALYs, followed by hypertension (2885·57 [2580·75-3201·05]), hyperlipidemia (1207·15 [975·07-1461·11]), T2DM (801·55 [670·58-954·43]) and NAFLD (53·33 [40·73-68·29]). Mortality rates decreased over time in hyperlipidemia (-0·6 %), hypertension (-0·47 %), NAFLD (-0·31 %) and T2DM (-0·20 %), but not in obesity (1·07 % increase). The highest metabolic-related mortality was observed in Eastern Mediterranean and low SDI countries. By 2050, obesity is projected to contribute to the largest number of deaths (102·8 % increase from 2019), followed by hypertension (61·4 % increase), hyperlipidemia (60·8 % increase), T2DM (158·6 % increase) and NAFLD (158·4 % increase), with males continuing to bear the greatest burden across all metabolic diseases. CONCLUSION: The growing burden of metabolic diseases, increasing obesity-related mortality trends, and the sex-regional-socioeconomic disparities evident in young adulthood, underlie the concerning growing global burden of metabolic diseases now and in future.

The prognostic value of including non-alcoholic fatty liver disease in the definition of metabolic syndrome.

BACKGROUND/AIMS: Metabolic syndrome (MetS) affects over one third of the US adult population. Despite its close association with non-alcoholic fatty liver disease (NAFLD), the traditional definition of MetS does not account for the presence of NAFLD. The present study thus aims to evaluate the inclusion of NAFLD in the diagnostic criteria of metabolic syndrome on its accuracy of capturing individuals with metabolic dysregulation and its prediction of adverse events. METHODS: Data collected from NHANES between 1999 and 2018 was analysed. Clinical characteristics and outcomes between individuals with metabolic syndrome from both the American Heart Association/National Heart, Lung, and Blood Institute (MetS) and the study's proposed diagnostic criteria (MetS2) were evaluated. Outcomes in both groups were evaluated with multivariate analyses, and further subgroup analysis on individuals matched with Coarsened Exact Matching was performed. RESULTS: Of 46,184 individuals included, 32.54% and 40.54% fulfilled MetS and MetS2 criteria respectively. Considering NAFLD in the definition of metabolic syndrome, a further 8.00% (n = 3694) were included. MetS was significantly associated with all-cause (HR: 1.184, 95% CI: 1.110-1.263, p < 0.001) and cardiovascular disease (CVD) mortality (SHR: 1.288, 95% CI: 1.233-1.347, p < 0.001), and major adverse cardiovascular events (MACE). MetS2 was similarly associated with all-cause (HR: 1.175, 95% CI: 1.088-1.269, p < 0.001), CVD mortality (SHR: 1.283, 95% CI: 1.245-1.323, p < 0.001) and MACE. CONCLUSION: Inclusion of NAFLD allows for identification a greater proportion of the population with metabolic risk. This allows for early intervention and potential to lift some burden off the global healthcare system.

Higher mortality in acute coronary syndrome patients without standard modifiable risk factors: Results from a global meta-analysis of 1,285,722 patients.

BACKGROUND: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes, hyperlipidemia, hypertension, and smoking, are used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. METHODS: Embase, Medline and Pubmed were searched for studies comparing SMuRF-less and SMuRF patients with first presentation of ACS. We conducted single-arm analyses to determine the proportion of SMuRF-less patients in the ACS cohort, and compared the clinical presentation and outcomes of these patients. RESULTS: Of 1,285,722 patients from 15 studies, 11.56% were SMuRF-less. A total of 7.44% of non-ST-segment-elevation ACS patients and 12.87% of ST-segment-elevation myocardial infarction (STEMI) patients were SMuRF-less. The proportion of SMuRF-less patients presenting with STEMI (60.71%) tended to be higher than those with SMuRFs (49.21%). Despite lower body mass index and fewer comorbidities such as chronic kidney disease, peripheral arterial disease, stroke and heart failure, SMuRF-less patients had increased in-hospital mortality (RR:1.57, 95%CI:1.38 to 1.80) and cardiogenic shock (RR:1.39, 95%CI:1.18 to 1.65), but lower risk of heart failure (RR:0.91, 95%CI:0.83 to 0.99). On discharge, SMuRF-less patients were prescribed less statins (RR:0.93, 95%CI:0.91 to 0.95), beta-blockers (RR:0.94, 95%CI:0.92 to 0.96), P2Y12 inhibitors (RR: 0.98, 95%CI: 0.96 to 0.99), and angiotensin-converting-enzyme inhibitor or angiotensin-receptor blocker (RR:0.92, 95%CI:0.75 to 0.91). CONCLUSION: In this study level meta-analysis, SMuRF-less ACS patients demonstrate higher mortality compared with patients with at least one traditional atherosclerotic risk factor. Underuse of guideline-directed medical therapy amongst SMuRF-less patients is concerning. Unraveling novel risk factors amongst SMuRF-less individuals is the next important step. SUMMARY: Standard modifiable cardiovascular risk factors (SMuRF), comprising diabetes mellitus, hyperlipidemia, hypertension, and smoking, are often used for risk stratification in acute coronary syndrome (ACS). Recent studies showed an increasing proportion of SMuRF-less ACS patients. Of 1,285,722 ACS patients, 11.56% were SMuRF-less. Despite lower body mass index and fewer comorbidities, SMuRF-less patients had increased in-hospital mortality and cardiogenic shock. However, despite worse outcomes, SMuRF-less patients were prescribed less guideline-directed medical therapies on discharge.

Hepatic steatosis and advanced hepatic fibrosis are independent predictors of long-term mortality in acute myocardial infarction.

AIM: To examine the prevalence and prognosis of hepatic steatosis and fibrosis in post-acute myocardial infarction (AMI) patients. METHODS: Patients presenting with AMI to a tertiary hospital were examined from 2014 to 2021. Hepatic steatosis and advanced hepatic fibrosis were determined using the Hepatic Steatosis Index and fibrosis-4 index, respectively. The primary outcome was all-cause mortality. Cox regression models identified determinants of mortality after adjustments and Kaplan-Meier curves were constructed for all-cause mortality, stratified by hepatic steatosis and advanced fibrosis. RESULTS: Of 5765 patients included, 24.8% had hepatic steatosis, of whom 41.7% were diagnosed with advanced fibrosis. The median follow-up duration was 2.7 years. Patients with hepatic steatosis tended to be younger, female, with elevated body mass index and an increased metabolic burden of diabetes, hypertension and hyperlipidaemia. Patients with hepatic steatosis (24.6% vs. 20.9% mortality, P < .001) and advanced fibrosis (45.6% vs. 32.9% mortality, P < .001) had higher all-cause mortality rates compared with their respective counterparts. Hepatic steatosis (adjusted hazard ratio 1.364, 95% CI 1.145-1.625, P = .001) was associated with all-cause mortality after adjustment for confounders. Survival curves showed excess mortality in patients with hepatic steatosis compared with those without (P = .002). CONCLUSIONS: Hepatic steatosis and advanced fibrosis have a substantial prevalence among patients with AMI. Both are associated with mortality, with an incrementally higher risk when advanced fibrosis ensues. Hepatic steatosis and fibrosis could help risk stratification of AMI patients beyond conventional risk factors.

Barriers and Facilitators to Engagement With a Weight Management Intervention in Asian Patients With Overweight or Obesity: A Systematic Review.

OBJECTIVE: The obesity epidemic is a global health concern with Asian countries facing one of the most rapid rises in obesity rates. However, given the underwhelming long-term efficacy of weight loss strategies, especially in Asia, this review aimed to explore barriers and facilitators to weight management of patients with overweight and obesity in Asia. METHODS: Medline, CINAHL, PsycINFO, and Web of Science were searched for articles discussing barriers and facilitators of treatment to obesity from the perspectives of both health care professionals (HCPs) and patients. Qualitative and mixed method studies from Asia were included. Key quotes were extracted, coded, and thematically analyzed according to the methodology of Thomas and Harden. RESULTS: A total of 26 articles were included in this review. From patient perspectives, 3 main themes were identified: factors influencing poor eating behavior, inhibiting lifestyle modifications, and facilitating lifestyle modifications. Patients highlighted several barriers including the lack of social support, physiologic limitations to exercise, and low health literacy. Rigid sociocultural norms and lack of accessible health care services, exercise facilities, and healthy food exacerbated the barriers. Facilitators to lifestyle modifications consisted of strong support systems and high health literacy. HCPs agreed that low health literacy, lack of social support, and patient motivation impeded patients' weight loss attempts but were unaware of the other barriers they faced. CONCLUSION: There are discrepancies between ideas of barriers and facilitators of HCPs and patients. A mixture of population level, primary care, and personal interventions are required to address this disparity, and enhanced health literacy can improve weight loss outcomes.