Lee, Kwan

ABSTRACT Background & Aims Metabolic dysfunction‐associated steatotic liver disease (MASLD) is highly prevalent and increasingly recognized as a multisystem cardiometabolic disorder. The global burden, incidence and prognostic implications of coexisting chronic kidney disease (CKD) in MASLD remain uncertain. Methods In this meta‐analysis, we searched MEDLINE and EMBASE from inception through September 25, 2025, for observational studies reporting CKD prevalence and/or incidence among adults (≥ 18 years) with MASLD. The primary outcomes were pooled CKD prevalence, estimated using random‐effects models on the logit scale with the Hartung–Knapp adjustment, and pooled CKD incidence (per 1000 person‐years), estimated using random‐effects models with exact Poisson confidence intervals. Secondary outcomes included all‐cause mortality and cardiovascular, renal and cancer outcomes. Results From 2811 records, 36 observational studies met the inclusion criteria. Twenty‐three studies contributed prevalence estimates (575 615 participants; 56 248 CKD cases) and thirteen studies contributed incidence estimates (27 996 new events). The pooled global CKD prevalence among individuals with MASLD was 15.22% (95% CI 9.69–23.12). The pooled CKD incidence was 22.17 per 1000 person‐years (95% CI 11.44–32.89) in the MASLD population. Hypertension (OR 1.49, 95% CI 1.29–1.72), dyslipidaemia (OR 1.22, 95% CI 1.20–1.24) and diabetes (OR 1.94, 95% CI 1.69–2.22) were associated with higher odds of CKD in the MASLD population. All‐cause mortality rates were 18.28 per 1000 person‐years (95% CI 3.45–33.11) in coexistent MASLD and CKD, more than double those in the MASLD‐only population (7.26 per 1000 person‐years (95% CI 2.97–11.56)). Conclusions Coexistent CKD affects one in seven individuals with MASLD worldwide, conferring a more than two‐fold increased risk of all‐cause mortality compared with individuals with MASLD alone.

Background: Disparities exist in the representation of genders in cardiovascular clinical trials. Atrial fibrillation (AF) is associated with significant morbidity and mortality; however, understanding regarding the representation of women in AF-related clinical trials remains limited. Therefore, this systematic review sought to evaluate the representation of women in AF-related clinical trials. Methods: We conducted a systematic review of clinical trials using the PubMed, Scopus, and EMBASE databases from 1996 to January 1st, 2024, focusing on AF-related lifestyle interventions, pharmacological treatments, catheter ablation, and device therapies for AF. Data extraction and analysis encompassed trial characteristics, participant demographics, and funding sources. The primary outcome was the prevalence of female enrollees, quantified through participation-to-prevalence ratios (PPRs). This was estimated overall and stratified by funding source, intervention type, and enrollment region. Results: Of the 103 clinical trials involving 218,322 participants (39.5% female), the PPR ranged from 0.00 to 1.73, with an average PPR of 1.03. Meanwhile, 43% of the trials exhibited female under-representation (PPR, <0.8). University-funded trials showed higher female enrollment (mean PPR, 0.951) compared to industry/government-funded trials (mean PPR, 0.800). No differences were observed in the representation of women when comparing enrollment regions or intervention types. Conclusions: Despite advancements in AF management, gender disparities persist in AF-related clinical trial representation, particularly in industry/government-funded studies compared to university-funded trials. Thus, addressing implicit biases and enforcing sex equality guidelines are critical steps toward more inclusive cardiovascular research.

Abstract Background The incidence of type 2 diabetes mellitus among young adults has been increasing over the past few decades. There are limited data on contemporary national cardiovascular mortality rates in young adults with diabetes mellitus (DM). Methods We queried the Centers for Disease Control and Prevention's Wide‐Ranging Online Data for Epidemiologic Research database for patients aged 15 to 44 years from 1999 to 2019 in the primary analysis. A secondary analysis included data from 2020 to 2022 to examine the effect of the COVID‐19 pandemic. We analysed patients in whom cardiovascular diseases (CVD) were listed as the main cause of death and DM as a contributing cause of death. In calculating age‐adjusted mortality rates (AAMR) per 100 000 individuals, we used CVD mortality in young adults with comorbid diabetes as the numerator and the overall population as the denominator. We determined temporal trends by estimating the average annual percent change (AAPC) using the Joinpoint regression program. Results Among 3 309 079 individuals aged 15–44 years who died, 30 978 deaths were due to CVD with comorbid DM listed as a contributing cause. The overall AAMR increased from 1.08 per 100 000 individuals in 1999 to 1.23 per 100 000 individuals in 2019, with an average APC of 0.75 (95% CI, 0.31–1.20). Compared with 1999, the percentage increase in CVD deaths in 2019 among young adults with comorbid DM was +6.2%, whereas a decrease of 19.9% was observed among those without comorbid DM. Males had a higher AAMR than females (1.60 vs. 0.97). Non‐Hispanic Black individuals and non‐Hispanic American Indian/Alaska Native individuals had the highest AAMRs of 2.99 and 2.89, respectively. The AAMR was higher in rural regions compared to urban areas (1.63 vs. 1.23). The overall AAMR increased markedly from 1.23 in 2019 to 1.60 in 2022, with a similar pattern observed across demographic subgroups. Conclusion Our study reveals a rising trend in CVD mortality in young adults with DM as a contributing cause. Males, non‐Hispanic Black individuals, and individuals from rural regions had higher AAMR than their counterparts. This warrants the development of specific healthcare policies aimed at these at‐risk populations. Lay summary Our study shows that cardiovascular disease (CVD) deaths are increasing in young adults with diabetes mellitus listed as a contributing cause.

Background To compare the effectiveness of glucagon‐like peptide‐1 receptor agonists (GLP‐1 RAs) versus bariatric surgery on cardiovascular outcomes in patients with heart failure (HF) with preserved ejection fraction and obesity. Methods Using the TriNetX research network, we conducted a retrospective cohort study of adults (aged ≥18 years) with HF with preserved ejection fraction and obesity (body mass index >30 kg/m 2 ) from 2017 to 2022. Patients were categorized into 2 cohorts: those receiving GLP‐1 RAs (semaglutide or tirzepatide) and those who underwent bariatric surgery. Propensity score matching (1:1) was used to balance baseline characteristics. Primary outcomes included acute HF events and all‐cause hospitalizations. Secondary outcomes included all‐cause death, myocardial infarction, stroke, and follow‐up body mass index. Cox proportional hazard models were used to estimate hazard ratios (HRs). Results A total of 2747 patients were included per cohort (mean age, 68 years). GLP‐1 RA therapy was associated with lower incidence of acute HF events (38.9% versus 44.6%; HR, 0.78 [95% CI, 0.72–0.85]), all‐cause death (11.1% versus 14.8%; HR, 0.71 [95% CI, 0.61–0.82]), and all‐cause hospitalizations (66.4% versus 77.3%; HR, 0.62 [95% CI, 0.58–0.66]). Rates of myocardial infarction (13.8% versus 13.4%; HR 0.99 [0.86–1.14]) and stroke (9.7% versus 10.7%; HR, 0.87 [0.74–1.02]) were similar between groups. Mean body mass index at follow‐up was 38.0 in the GLP‐1 RA cohort versus 37.7 after bariatric surgery ( P =0.34). Hemoglobin A 1c at follow‐up was higher in the GLP‐1 RA group (7.4 versus 6.8; P <0.001). Conclusions In patients with HF with preserved ejection fraction and obesity, GLP‐1 RA therapy was associated with improved outcomes compared with bariatric surgery, supporting the need for prospective trials to evaluate GLP‐1 RAs as a therapeutic alternative.

Background Immune‐checkpoint inhibitors (ICI) are associated with adverse cardiac events. Although troponin elevation is a diagnostic criterion for ICI‐related myocarditis (ICIrM) and myocardial infarction, data on other causes of troponin elevation and their outcomes in ICI‐treated patients are limited. Methods All patients treated with ICI who had hs‐TnT (high‐sensitivity troponin T) measured at a multicenter institution from 2011 to 2022 were included. Clinical data, outcomes (cardiac death, heart failure (HF), major adverse cardiovascular events [myocardial infarction, stroke, heart failure]), and cause of hs‐TnT elevation were assessed. Risks of cardiac events were compared across hs‐TnT elevation causes. Results Of 5423 patients treated with ICI, 1669 had post‐ICI hs‐TnT measurement (mean age 68.7±11.3 years, 58.3% male), with 1‐year follow‐up. Hs‐TnT elevation in patients with ICIrM (n=59) was associated with the highest risk for cardiac death (hazard ratio [HR], 52.7 [95% CI, 11.7–238.0], P <0.001), followed by hs‐TnT elevation due to heart failure (HR, 15.9), myocardial infarction/type 2 ischemia (HR, 11.6), and infection/sepsis (HR, 5.7), compared with those with no hs‐TnT elevation. ICIrM also carried highest risk for major adverse cardiovascular events (HR, 8.2, [95% CI, 4.4–15.3], P <0.001), followed by myocardial infarction/type 2 ischemia (HR, 8.1), heart failure (HR, 7.6), pulmonary embolus (HR, 5.1), infection/sepsis (HR, 4.1), and indeterminate cause (HR, 2.4). Among ICIrM, HsTnT value >576 ng/L best predicted risk for cardiac death and >319 ng/L for major adverse cardiovascular events. Conclusions Hs‐TnT elevation after ICI therapy is associated with increased risk of cardiac events, particularly in ICIrM, and a graded prognostic association depending on the cause of hs‐TnT elevation. Identifying the underlying cause and troponin thresholds may guide risk stratification and management.

Abstract Aims We evaluated clinical outcomes with GLP-1 RA use post-TAVI in patients with T2D. GLP-1 receptor agonists (GLP1-RAs) lower cardiovascular risk in type 2 diabetes (T2D), but their impact in patients with valvular heart disease, including those undergoing transcatheter aortic-valve implantation (TAVI), remained unexplored. Methods and results We conducted a retrospective cohort study using the TriNetX network, including 25 184 adults (≥18 years) with T2D who underwent TAVI (2015–2023). Patients were stratified based on GLP1-RA initiation within 14 days post-TAVI. Baseline characteristics, comorbidities, medications, and laboratory data were balanced using 1:1 propensity score matching (PSM). Cox models estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for events from one-month post-TAVI until the most recent follow-up. PSM yielded 1101 patients per group, with a mean age of 73 years and 39% female. Mean follow-up duration was 2.2 ± 1.1 and 2.6 ± 1.8 years for GLP1-RA users and non-users, respectively. GLP1-RA use was also associated higher survival probability (HR: 0.708 [95% CI: 0.583–0.859]), and lower rates of all-cause hospitalization (HR: 0.790 [95% CI, 0.706–0.885]), major cardiovascular events (HR: 0.849 [95% CI: 0.749–0.963]), and acute heart failure exacerbation (HR: 0.785 [95% CI: 0.677–0.909]), acute kidney injury (HR: 0.843 [95% CI: 0.719–0.988]), and major kidney events (HR: 0.665 [95% CI: 0.510–0.866]). No differences were observed in acute myocardial infarction, cerebral infarction, or cardiac arrest. Conclusion In patients with T2D undergoing TAVI, GLP1-RA use is associated with significant survival benefits and improved cardiorenal outcomes. However, these findings are limited by the observational design, high comorbidity burden, lack of data on medication compliance, and specific cause of death. Prospective trials are warranted to confirm these benefits.

Despite advances in lipid-lowering and antithrombotic therapy, patients with acute coronary syndromes remain at elevated risk for recurrent events due to persistent atherosclerotic inflammation. This review evaluates inflammation as a therapeutic target in secondary prevention and discusses established, investigational, and emerging strategies. Colchicine, now FDA-approved for cardiovascular risk reduction, lowered major adverse cardiovascular events in COLCOT and LoDoCo2. Canakinumab (IL-1β inhibition) reduced recurrent events in proportion to IL-6 and hsCRP suppression, while ziltivekimab (IL-6 inhibition) achieved profound biomarker reductions but remains investigational. Early-phase studies of anakinra (IL-1 receptor antagonist) and dapansutrile (oral NLRP3 inhibitor) showed anti-inflammatory effects in early trials, whereas varespladib and darapladib illustrated the challenges of targeting lipid-associated pathways. Beyond direct immunomodulators, GLP-1 receptor agonists and SGLT2 inhibitors provide both cardioprotective and anti-inflammatory benefits, reinforcing their expanding role post-ACS. Additional emerging avenues include triptolidiol, dasatinib, and BTK or JAK/STAT inhibitors, while novel approaches, such as nanozyme delivery systems and CRISPR-based editing, extend the therapeutic horizon. This review highlights the potential of inflammation-targeted therapies to advance secondary prevention in ACS by integrating current evidence and perspectives on future therapeutic developments.

Background: Glucagon-like peptide-1 (GLP-1) agonists have been shown to improve outcomes across various cardiovascular diseases. However, data regarding the effects of GLP-1 agonists in obstructive hypertrophic cardiomyopathy (HCM) is limited. Objective: This study aimed to evaluate the 5-year outcomes of GLP-1 agonists in patients with HCM. Methods: Using TriNetX Analytics Network, we identified patients aged ≥18 years with a diagnosis of obstructive hypertrophic cardiomyopathy between 1/1/2014 and 1/1/2019. Patients were divided into two groups: those treated with GLP-1 agonists for ≥ 1 year and those who were not. Propensity score matching (PSM) was performed using demographics, cardiac medications, and comorbidities. The study outcomes were 5-year all-cause mortality and cardiac adverse events. Results: A total of 52,978 patients with HCM were identified, including 2,654 (5.0%) patients treated with GLP-1 agonists. After PSM, 2,588 patients in each group were analyzed. Patients on GLP-1 agonists were associated with lower odds of all-cause mortality (5.0% vs. 15.6%, p<0.01), all-cause hospitalization (46.3% vs. 67.8%, p<0.01), acute decompensated heart failure ((9.4% vs. 21.4%, p<0.01), cardiac arrest (3.6% vs. 5.4%, p<0.01), cerebrovascular accidents (9.5% vs. 14.1%, p<0.01), and cardiogenic shock (1.4% vs. 3.6%, p<0.01). Additionally, reduced rates of new ICD implantation (3.5% vs. 7.9%, p<0.01) and septal reduction therapy (1.7% vs. 3.5%, p<0.01) were observed in the GLP-1 agonists group. Conclusion: The use of GLP-1 agonists in HCM was associated with improved cardiovascular outcomes. Future clinical trials are needed to validate these potential benefits.

Background: Spontaneous coronary artery dissection (SCAD) is increasingly recognized as a cause of acute coronary syndrome, particularly in young to middle-aged women. While most presentations are associated with preserved left ventricular ejection fraction (LVEF), a subset of patients present with acute systolic dysfunction. The characteristics of patients who recover their LVEF are not clearly defined. Methods: We retrospectively analyzed 495 patients with angiographically confirmed SCAD treated at three Mayo Clinic sites (Arizona, Rochester, and Florida) from 1994 to 2023. Patients with a prior history of myocardial infarction, coronary artery disease, and congenital heart disease were excluded. Baseline LVEF at SCAD presentation was categorized into <35%, 35–39%, 40–49%, and ≥50%. Follow-up LVEF was assessed by echocardiography performed between 30 days and 1 year post-SCAD. The primary outcome was improvement in LVEF to ≥50% at follow-up. Results: A total of 495 SCAD patients were included. At presentation, 26% had reduced LVEF: 6% had LVEF <35%, 5% had LVEF between 35–39%, and 15% had LVEF between 40–49%. Patients who did not normalize their EF at follow-up were slightly younger (45 vs. 48 years, p=0.04), were more likely to have had an in-hospital cardiac arrest (13% vs. 4%, p=0.01), required mechanical circulatory support during their care, and had SCAD involving the left main artery (11% vs. 2%, p=0.01). Predictors of EF normalization included SCAD which involved the obtuse marginals (15% vs. 4%, p<0.05). The group with the lowest EF at presentation had the highest probability of persistent EF <50% at follow-up (32% for those with LVEF <35%) while patients who had normal EF at presentation had a 6% chance of having EF <50% at follow-up (Figure 1). Conclusions: Our study shows that the majority of SCAD patients have normal EF at presentation. 80% of those with reduced EF at presentation will normalize at follow-up. Predictors of low EF at follow-up included dissection involving the left main artery, lower EF at SCAD presentation, in-hospital arrest and use of mechanical circulatory support.