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Aims: The aim of this study was determine the incidence of major adverse cardiac events within 30 and 365-days among patients discharged from emergency departments (EDs), following a single high-sensitivity cardiac troponin I test result below or close to the limits of detection (LoD)., Methods and Results: Patients ≥20 years old who presented to four EDs from mid-2014 to end-2015, underwent a single high-sensitivity troponin test and were discharged were included. Data from ED presentations, hospital admissions, mortality records, and pathology laboratories were linked and harmonized. High-sensitivity troponin levels were categorized as below (<2 ng/L) or close to (<5 ng/L) the LoD. The primary outcome was cardiovascular death and myocardial infarction (MI), identified using ICD-10-AM codes. In a cohort of 6633 patients, 49% had high-sensitivity troponin levels below the LoD (<2 ng/L), and 79% had levels <5 ng/L. There were no primary outcome events at 30-day follow-up among patients with high-sensitivity troponin results below 2 or 5 ng/L. At 365-days, there were 5 (0.15%) and 11 (0.21%) primary outcome events for patients with high-sensitivity troponin results below 2 and 5 ng/L, indicating negative predictive values of 99.85% and 99.79%., Conclusion: These findings confirm that patients with a single very low level of high-sensitivity troponin on presentation to EDs are at low risk of MI and cardiovascular death at 30 and 365 days, supporting the safety of a triage strategy incorporating a single high-sensitivity troponin result below the LoD to identify patients at low-risk, who may be suitable for expedited discharge., Competing Interests: Conflict of interest: Derek Chew has received research support from Roche Diagnostics and Siemens Healthineers. All other authors have no competing interests to declare., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Sodium-glucose co-transporter inhibitors (SGLTis) have cardiovascular protective effects. We aimed to assess the effects of SGLTis on individual hard clinical endpoints and quality of life (QoL) in patients with cardiovascular risk factors., Methods and Results: Data was searched in PubMed, Embase, Cochrane Library and clinicaltrials.gov databases up to February 2024. Randomized controlled trials (RCTs) comparing SGLTis with placebo were included. The primary outcomes were individual hard clinical endpoints (Subset A) and QoL (Subset B). For Subset A, 13 RCTs including 90 413 patients were enrolled (age 66 ± 10.1 years, 35.7% female, follow-up 2.4 ± 0.3 years); as compared with placebo, SGLTis were associated with significantly lower risk of all-cause mortality [risk ratio (RR): 0.90, 95% confidence interval (CI): 0.86-0.94, P < 0.01], cardiovascular mortality (RR: 0.87, 95% CI: 0.82-0.92, P < 0.01), hospitalization for heart failure (HF) (RR: 0.72, 95% CI: 0.68-0.76, P < 0.01), HF events (RR: 0.72, 95% CI: 0.68-0.75, P < 0.01), hospitalization for any cause (RR: 0.91, 95% CI: 0.88-0.93, P < 0.01) and myocardial infarction (MI) (RR: 0.92, 95% CI: 0.85-0.99, P = 0.03). Notably, the favourable effect of SGLTis on all-cause mortality was more pronounced in younger (<65 years) patients (RR: 0.86, 95% CI: 0.81-0.92) and in studies with less female (RR: 0.84, 95% CI: 0.79-0.90). The favourable effect of SGLTis on MI was only observed in patients who received sotagliflozin (RR: 0.47, 95% CI: 0.31-0.73). For Subset B, nine RCTs including 2552 HF patients were enrolled (age 67.8 ± 12.4 years, 36.4% female, follow-up 3.4 ± 1.9 months); SGLTis were associated with significant improvement in QoL as compared with placebo., Conclusions: In patients with a broad spectrum of cardiovascular risk factors, SGLTis substantially improve individual hard clinical outcomes and QoL., (© 2024 The Author(s). ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Context: Thyroid-stimulating hormone (TSH) trajectory classification represents a novel approach to defining the adequacy of levothyroxine (LT4) treatment for hypothyroidism over time., Objective: This is a proof of principle study that uses longitudinal clinical data, including thyroid hormone levels from a large prospective study to define classes of TSH trajectories and examine changes in cardiovascular (CV) health markers over the study period., Methods: Growth mixture modeling (GMM), including latent class growth analysis (LCGA), was used to classify LT4-treated individuals participating in the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil) based on serial TSH levels. Repeated measure analyses were then utilized to assess within-class changes in blood pressure, lipid levels, hemoglobin A1c, and CV-related medication utilization., Results: From the 621 LT4-treated study participants, the best-fit GMM approach identified 4 TSH trajectory classes, as defined by their relationship to the normal TSH range: (1) high-high normal TSH, (2) normal TSH, (3) normal to low TSH, and (4) low to normal TSH. Notably, the average baseline LT4 dose was lowest in the high-high normal TSH group (77.7 µg, P < .001). There were no significant differences in CV health markers between the classes at baseline. At least 1 significant difference in CV markers occurred in all classes, highlighted by the low to normal class, in which total and high-density lipoprotein cholesterol, triglycerides, and A1c all increased significantly (P = .049, P < .001, P < .001, and P = .001, respectively). Utilization of antihypertensive, antihyperlipidemic, and antidiabetes medications increased in all classes., Conclusion: GMM/LCGA represents a viable approach to define and examine LT4 treatment by TSH trajectory. More comprehensive datasets should allow for more complex trajectory modeling and analysis of clinical outcome differences between trajectory classes., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Giant cell myocarditis (GCM) and cardiac sarcoidosis (CS) are rare inflammatory diseases of the myocardium with poor prognosis. Cardiovascular disease outcomes among both diseases have not been well studied with limited literature., Objective: This study aims to investigate the cardiovascular outcomes among patients with GCM and CS., Method: We queried the TriNeTX Global Collaborative Network for adult patients with giant cell myocarditis and cardiac sarcoidosis between January 2000 to May 2023 and created two groups: one with giant cell myocarditis and second with cardiac sarcoidosis. Both the groups were followed for 6 months and 12 months., Result: After propensity score matched analysis (PSM), among the 4804 patients (2402 patients in each group), the mean age of patients was 57.1 and 57.6 years in GCM and CS groups, respectively. PSM analysis showed that primary outcome i.e., all-cause mortality was significantly higher in GCM group both after 6 months [relative risk (RR) 2.33, 95 % confidence interval (CI): 1.64-3.30, p < 0.01] and 1 year follow up [RR, 1.54 (95 % CI: 1.20-1.98), p < 0.01] as compared with CS group. However, secondary outcomes i.e., heart failure (HF) at 6 month (RR 0.66, 95 % CI: 0.52-0.85, p < 0.01), and at 1 year (RR 0.60, 95 % CI: 0.49-0.73, p < 0.01), ventricular tachycardia (VT) at 6 months (RR 0.34, 95 % CI: 0.25-0.46, p < 0.01), and at 1 year (RR 0.32, 95 % CI: 0.25-0.41, p < 0.01), atrioventricular (AV) node block at 6 month (RR 0.45, 95 % CI: 0.33-0.61, p < 0.01), and at 1 year (RR 0.43, 95 % CI: 0.34-0.55, p < 0.01), and atrial flutter and fibrillation (AF) at 6 months (RR 0.67, 95 % CI: 0.48-0.94, p = 0.02), and at 1 year (RR 0.59, 95 % CI: 0.45-0.76, p < 0.01) were found significantly lower in GCM group as compared to CS group. On the other hand, heart transplant incidence was comparable between both the groups., Conclusion: These findings suggest that GCM patients have high risk of mortality and lower risk of HF, VT, AV node block, and AF when compared with CS., Competing Interests: Declaration of competing interest The abstract of this study has been accepted for in-person presentation at the AHA 24., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background and Aims: Frailty is increasingly prevalent in people presenting with acute coronary syndrome (ACS). This high-risk group is typically excluded from trials of interventions in ACS, and there is uncertainty about the risks and benefits of invasive management., Methods: Patients with an ACS diagnosis between 2010 and 2015 in England were identified from Hospital Episode Statistics, with linked Office for National Statistics mortality data. Frailty was defined by the Hospital Frailty Risk Score. Causal inference analysis used regional variation in revascularization as an instrumental variable to estimate average treatment effects of revascularization on cardiovascular mortality up to 5 years in people presenting with ACS and low-, intermediate-, or high-risk frailty., Results: The analysis included 565 378 ACS patients, of whom 11.6% (n = 65 522) were at intermediate risk and 4.7% (n = 26 504) were at high risk of frailty. Intermediate and high frailty risks were associated with reduced likelihood of echocardiography, invasive angiography, or revascularization and increased likelihood of mortality and major adverse cardiovascular events compared with low frailty risk. Cardiovascular death at 5 years was 78.6%, 77.3%, and 75.7% in people at low, intermediate, and high frailty risk, respectively. Instrumental variable analysis suggested that revascularization resulted in a higher absolute reduction in cardiovascular mortality in high and intermediate frail risk patients compared with low risk at 1-year post-ACS., Conclusions: Frailty is common in people presenting with ACS, where cardiovascular causes are the principal mode of death. Revascularization is associated with short- and long-term survival benefits in people at intermediate and high risk of frailty after adjustment for measured and unmeasured confounders., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have emerged as a promising class of medications for type 2 diabetes (T2D) management. While their glucose-lowering effects are well-established, their long-term impact on cardiovascular outcomes remains a subject of ongoing research and debate. This systematic review aims to assess the long-term cardiovascular effects of GLP-1 RAs in adults with T2D compared to placebo, standard care, or other glucose-lowering medications. We systematically searched PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies published from database inception to April 2024. Two independent reviewers screened the studies and extracted the data. The primary outcome was major adverse cardiovascular events (MACE), a composite of cardiovascular death, non-fatal myocardial infarction (MI), and non-fatal stroke. Secondary outcomes included individual components of MACE, hospitalization for heart failure, and all-cause mortality. We included 15 studies (eight RCTs and seven observational studies) involving over 180,000 participants. GLP-1 RAs were associated with a significant reduction in MACE compared to placebo or standard care (risk ratio: 0.88, 95% CI: 0.82-0.94, p<0.001). GLP-1 RAs also demonstrated superior cardiovascular protection compared to DPP-4 inhibitors and sulfonylureas. The benefits were particularly pronounced in reducing the risk of stroke and MI. Notably, some studies found larger cardiovascular benefits in frail patients. The effects on heart failure outcomes were mixed, with potential attenuated benefits in patients with baseline heart failure. GLP-1 RAs also showed promising effects on renal outcomes and metabolic parameters. The quality of evidence ranged from moderate to high across outcomes. This systematic review provides strong evidence that GLP-1 RAs offer significant cardiovascular benefits in adults with T2D, particularly in reducing MACE, stroke, and MI. The findings support current guidelines recommending GLP-1 RAs as preferred agents in patients with established cardiovascular disease or high cardiovascular risk. However, the variability in effects across different patient subgroups underscores the need for personalized treatment approaches. Future research should focus on head-to-head comparisons between different GLP-1 RAs, long-term follow-up studies, and investigation of combination therapies to further optimize the use of these agents in clinical practice., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Tariq et al.)

Purpose: This meta-analysis investigates the sex differences in mortality risk between the acute coronary syndrome (ACS) population without standard modifiable risk factors (SMuRF-less) and those with at least one standard modifiable risk factor (SMuRF), and analyses mortality rates between males and females within the SMuRF-less cohort., Methods: The MEDLINE and Embase databases were searched for cohort studies with sex-stratified outcomes for SMuRF-less versus SMuRF patients with ACS till 15 December 2023. The analysis of variables reported in proportions was carried out by utilizing a meta-analysis with a generalized linear mixed model while continuous variables were analyzed by a meta-analysis of means, using an inverse variance method., Results: Eight studies were included in the current paper, with 82,395 SMuRF-less ACS patients and 607,558 SMuRF ACS patients. Excess in-hospital mortality found in SMuRF-less ACS, compared to those with SMuRFs, were only observed in females (RR 1.56, 95%CI 1.08-2.25, p = 0.029), but not in males (RR 1.59, 95%CI 0.90-2.80, p = 0.088). On longer follow-up, the 1- and 2-year post-ACS mortality rates were similar across the SMuRF-less and SMuRF cohorts, for both sexes. The subgroup analysis of SMuRF-less ACS individuals revealed that SMuRF-less females had higher in-hospital (RR 1.52, 95%CI 1.30-1.78, p = 0.002), 1-year (RR 1.51, 95%CI 1.34-1.71, p = 0.005) and 2-year mortality risks (RR 1.40, 95%CI 1.13-1.75, p = 0.016) compared to the SMuRF-less male counterparts., Conclusion: Paradoxical excess mortality in SMuRF-less ACS, compared to those with SMuRFs, was only observed in females. Females without cardiovascular risk factors are at the highest risk of short- and medium-term mortality following ACS., Competing Interests: Declarations Conflict of interest The authors declare that they have no conflict of interest., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Studies have reported associations between prostate cancer, type II diabetes mellitus (T2DM), and cardiovascular disease in the context of treatment with hormone therapy (HT). This study aimed to assess the role of Sodium-Glucose Cotransporter-2 Inhibitors (SGLT2i) in preventing adverse cardiovascular and renal outcomes in diabetics with prostate cancer., Methods: Patients ≥ 18 years of age with T2DM and prostate cancer who received HT between August 1, 2013, and August 31, 2021, were identified using the TriNetX research network. Patients were divided into two cohorts based on treatment with SGLT2i or alternative antidiabetic therapies. The primary outcome was the composite of all-cause mortality, new-onset heart failure (HF), acute myocardial infarction (MI), and peripheral artery disease over 2 years from HT initiation., Results: After propensity score matching, 2155 patients remained in each cohort. The primary composite outcome occurred in 218 patients (16.1%) in the SGLT2i cohort versus 355 patients (26.3%) in the non-SGLT2i cohort (OR 0.539, 95% CI 0.446-0.651; p < 0.001). Furthermore, SGLT2i were associated with significantly lower odds of HF, HF exacerbation, peripheral artery disease, atrial fibrillation/flutter, cardiac arrest, need for renal replacement therapy, overall emergency room visits/hospitalizations, and all-cause mortality., Conclusions: Use of SGLT2i for the treatment of T2DM among patients with prostate cancer on HT is associated with favorable cardiovascular, renal, and all-cause mortality outcomes. This observation supports the hypothesis that a therapeutically relevant link exists between HT and cardiovascular disease in the context of prostate cancer., Competing Interests: Declarations Ethics Approval This is an observational study. The need for Institutional Review Board (IRB) approval was waived by Lahey Clinic IRB due to the use of deidentified data for the analysis. The study findings are reported per the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines for cohort studies. Consent to Participate Not applicable. Consent for Publication Not applicable. Conflict of Interest EK is supported in part by NIH/NCI 1RO1HL157273 and by CPRIT RP200381. AD is supported in part by the Ting Tsung and Wei Fong Chao Distinguished Chair and is a consultant for Bayer. JB is consultant for Abbott, American Regent, Amgen, Applied Therapeutic, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol Myers Squibb, Cardiac Dimension, Cardior, CVRx, Cytokinetics, Edwards, Element Science, Innolife, Impulse Dynamics, Imbria, Inventiva, Lexicon, Lilly, LivaNova, Janssen, Medtronics, Merck, Occlutech, Novartis, Novo Nordisk, Pfizer, Pharmacosmos, Pharmain, Roche, Sequana, SQ Innovation, and Vifor. AWH is consultant for Janssen, Intellisphere, Exelixis, has received honoraria from Medscape, Binaytara Foundation, travel support from Dava Oncology, and institutional funding from Bayer and Eisai. The remaining authors have nothing to disclose., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Given the limited head-to-head comparison of cardiovascular and renal outcomes between liraglutide and dulaglutide, our study aimed to investigate the clinical outcomes between dulaglutide and liraglutide in a real-world setting. In this new-user design, comparative and retrospective cohort study, patients with type 2 diabetes mellitus with prescription for GLP-1RAs from January 1, 2016 to December 31, 2022 (n = 8,278) were included. Primary outcome was composite cardiovascular outcomes which was composed of cardiovascular death, non-fatal myocardial infarction, and non-fatal ischemic stroke. The composite renal outcome was also interested, including new macroalbuminuria, doubling of serum creatinine, worsening of estimated glomerular filtration rate (eGFR), and progression to dialysis. A total of 3,210 subjects receiving liraglutide and 5,068 subjects receiving dulaglutide were identified. In the adjusted cohort by applying inverse probability of treatment weighting, the incidence of composite cardiovascular outcomes was 18.4 and 18.7 events per 1000 person-years in the liraglutide and dulaglutide groups, respectively. The risk of cardiovascular outcomes did not significantly differ between groups (hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.85-1.15). Moreover, the risk of composite renal outcomes was also comparable between groups (subdistribution HR 1.07, 95% CI 0.995-1.16). Liraglutide and dulaglutide demonstrated comparable cardiovascular and renal outcomes in a real-world setting., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: This meta-analysis was designed to investigate cardio-renal outcomes and safety of sodium-glucose cotransporter-2 inhibitors (SGLT2i) as a therapeutic option among chronic kidney disease(CKD) patients with GFR < 60 mL/min/1.73 m2, regardless of their diabetic status., Method: We conducted a full-scale search from MEDLINE, EMBASE and the Cochrane Library database to identify eligible studies up to Jun 2024. All randomized controlled trials (RCTs) comparing cardio-renal outcomes and/or safety of SGLT2i in CKD patients with eGFR < 60 mL/min/1.73 m 2 were involved. The relative risk (RR) and 95% confidence interval (CI) for primary outcomes and adverse events were computed by random-effects mode. We used I 2 statistic to analyze heterogeneity. Publication bias was assessed by Egger's test., Results: Our study incorporated 17 RCTS, including 27,928 patients. In CKD patients with eGFR < 60 mL/min/1.73 m 2 , SGLT2i decreased risks of cardiovascular events (seven studies, 17,355 participants, RR 0.77, 95% CI 0.70-0.84), hospitalization for heart failure (HHF) (seven studies, 17,869 participants, RR 0.73, 95% CI 0.65-0.82), cardiovascular death (eight studies, 23,079 participants, RR 0.81, 95% CI 0.74 to 0.88) and renal composite outcomes (eight studies, 22,525 participants, RR 0.70, 95% CI 0.61-0.80) with lower risks of any serious adverse effects(fourteen studies, 19,654 participants, RR 0.91, 95% CI 0.87-0.95), hypoglycemia (nine studies, 16,412 participants, RR 0.91, 95% CI 0.84-0.98), hyperkalemia (four studies, 2693 participants, RR 0.68, 95% CI 0.51-0.93) and acute renal injury (five studies, 5424 participants, RR 0.79, 95% CI 0.65-0.95) compared to placebo. SGLT2i also slowed eGFR decline (total slopes: five studies, 10,370 participants, mean difference 1.17, 95%CI 0.86-1.49; chronic slopes: four studies, 8459 participants, mean difference 2.12, 95%CI 1.64-2.61). Further subgroup analyses revealed that SGLT2i decreased relative risks of cardiovascular outcomes(three studies, 1075 participants, RR 0.76, 95% CI 0.54-0.82), HHF(four studies, 1280 participants, RR 0.74, 95% CI 0.55-1.00) and renal composite outcomes (six studies,4375 participants, RR 0.78, 95% CI 0.68-0.88) with no increased adverse events in the CKD 4 patients., Conclusions: SGLT2i significantly improved cardio-renal outcomes and were generally safe in CKD patients with eGFR < 60 mL/min/1.73 m2 and with eGFR < 30 mL/min/1.73 m2. Future large-scale RCTs are needed to confirm the robustness of these results., (© 2024. The Author(s).)

Purpose: To investigate the association between blood pressure (BP) time in range (TIR) and composite cardiovascular outcomes in patients with primary aldosteronism (PA)., Methods: Between January 2019 and December 2021, 47 patients with PA were recruited from the First Affiliated Hospital of Xiamen University. Twenty-four-hour ambulatory BP monitoring (ABPM) and cardiovascular outcomes were assessed in all patients during the first diagnosis of PA., Results: The mean age of the patients was 48.8 ± 11.4 years. Compared to PA without composite cardiovascular outcomes, the nighttime systolic BP TIR [31.2% (6.2%, 81.2%) vs. 11.5% (0.0%, 29.7%), p = 0.02] and defined daily dose (DDDs) of antihypertensive medication [2.0 (1.0, 2.8) vs. 1.0 (1.0, 2.0), p = 0.03] were lower in PA patients with composite cardiovascular outcomes, while higher glucose (5.0 ± 1.0 mmol/L vs. 5.9 ± 1.5 mmol/L) and prevalence of a history of alcohol intake was higher in PA patients with composite cardiovascular outcomes. There were no differences in age, sex, BMI, smoking, duration of hypertension, lipid levels, aldosteronism, clinic BP, 24-hour mean BP, daytime or nighttime BP, percentage of nocturnal SBP or DBP decline, 24-hour BP TIR, daytime BP TIR, or nighttime DBP TIR between the two groups. After adjusting for confounding factors, nighttime systolic BP TIR was significantly associated with composite cardiovascular outcomes (adjusted OR = 0.92 [95% CI 0.86, 0.99]) in multiple logistic regression analysis., Conclusion: Nighttime systolic BP TIR was significantly associated with composite cardiovascular outcomes in patients with PA., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Diabetes is the most common cause of kidney disease in individuals that receive a kidney transplant, and those without pre-existing diabetes are at greater risk of developing diabetes following kidney transplant. A class of diabetes treatment medications called glucagon-like peptide-1 receptor agonists (GLP-1RA) has seen recent widespread use for people with diabetes or obesity, with efficacy for improved glycemic control, weight loss, and reduced risk of cardiovascular events. Given these benefits, and indications for use that often co-occur in kidney transplant recipients, use of GLP-1RAs warrants consideration in this population. Therefore, we sought to review the current literature to better understand the mechanisms of action, clinical application, and person-centred considerations of GLP-1RAs in kidney transplant recipients., Sources of Information: Original articles were identified between December 2023 and July 2024 from electronic databases including the Ovid MEDLINE database, PubMed, and Google Scholar using terms "kidney transplant," "GLP-1," "glucagon-like peptide-1 receptor agonist," and "diabetes.", Methods: A comprehensive review of the literature was conducted to explore the relationship between GLP-1RAs and kidney transplant recipients. We reviewed the current state of evidence across the research disciplines of basic or fundamental science, clinical and health services research, and person-centred equity science, and highlighted important knowledge gaps that offer opportunities for future research., Key Findings: Numerous clinical studies have demonstrated the benefit of GLP-1RAs in people with and without diabetic kidney disease, including decreased risk of cardiovascular events. However, there is a paucity of high-quality randomized controlled trials and observational studies analyzing use of GLP-1RAs in kidney transplant recipients. Evidence of benefit in this population is therefore limited to small studies or inferred from research conducted in nontransplant populations. Growing evidence from preclinical and clinical studies may elucidate renoprotective mechanisms of GLP-1RAs and remove barriers to application of these drugs in the transplant recipient population. Individuals who are female, non-white, have lower socioeconomic status, and live in rural communities are at greater risk of diabetes and have lower uptake of GLP-1RAs. There is a need for clinical trials across diverse kidney transplant populations to estimate the efficacy of GLP-1RAs on important health outcomes., Limitations: The search strategy for this narrative review may not have been sensitive to identify all relevant articles. Our search was limited to English language articles., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

Heart failure is a highly prevalent disease, which courses with frequent readmissions, mainly by Acute Heart Failure (AHF). Reduced renal function is associated with increased mortality in patients with HF. Therefore, an accurate and precise evaluation of renal function in patients with HF is crucial. The error of estimated GFR (eGFR) is wide and common, showing a ± 30% variability compared to measured GFR (mGFR). However, there is no evidence on the error of formulas in reflecting real renal function and particularly the consequences of this error in patients with AHF. This is a prospective study comparing the impact of mGFR versus eGFR in the onset of cardiovascular (CV) outcomes in patients with AHF. This was tested with cox survival analysis. Measured GFR was determined by the plasma clearance of iohexol-dbs and eGFR by Cockroft-Gould, MDRD, CKD-EPI creatinine, CKD-EPI cystatin-C and CKD-EPI creatinine + cystatin-C equations formulas. Also the agreement between mGFR and eGFR was analyzed. A total of 90 patients were included. Average age was 66 (± 12 years) and 52 (58%) were male. Of them 53 patients (59%) had a cardiovascular event during follow-up, 22 fatal (41%). The agreement between mGFR and eGFR indicated moderate precision and accuracy (concordance correlation coefficient of 0.77; CI = 0.73-0.82). In multiple cox survival analysis, mGFR was significantly associated with cardiovascular events together with NTproBNP, BMI, LVEF and previous coronary artery disease (p = 0.037; HR = 0.98, 95% CI = 0.95-0.99). Estimated GFR by formulas was not significant. In patients with AHF the error of formulas is large, frequent and random, also, mGFR and not eGFR predicted future CV events. The error of eGFR may have clinical consequences in specific subpopulations., (© 2024. The Author(s).)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have been shown to provide cardiovascular benefits in patients with type 2 diabetes mellitus (T2DM). However, their cardiovascular protective efficacy in high-risk T2DM patients, particularly those with a history of cardiovascular events or severe chronic kidney disease, remains uncertain., Methods: A comprehensive search was conducted in PubMed, Embase, Web of Science, and The Cochrane Library to identify randomized controlled trials (RCTs) that evaluated the effects of GLP-1 RAs on cardiovascular outcomes in high-risk patients with T2DM. A random-effects model was used to calculate pooled hazard ratios (HRs) for cardiovascular outcomes. Subgroup analyses and GRADE assessment were also performed., Results: Nine RCTs involving 63,613 patients were included. GLP-1 RAs significantly reduced the risk of the primary composite outcome (HR: 0.86, 95% CI: 0.80-0.92), cardiovascular death (HR: 0.85, 95% CI: 0.78-0.93), all-cause death (HR: 0.87, 95% CI: 0.82-0.93), myocardial infarction (HR: 0.90, 95% CI: 0.82-0.98), stroke (HR: 0.85, 95% CI: 0.77-0.95), and heart failure (HF) hospitalization (HR: 0.90, 95% CI: 0.83-0.97). No significant difference in unstable angina (UA) hospitalization was observed (HR: 1.04, 95% CI: 0.95-1.15). Subgroup analyses indicated greater benefits with combination therapy, particularly in patients with chronic kidney disease. The quality of evidence was rated as "High" for six outcomes and "Moderate" for UA hospitalization., Conclusions: GLP-1 RAs significantly reduce cardiovascular risk in high-risk T2DM patients, especially with combination therapy and in those with chronic kidney disease. However, further research is needed to confirm their long-term effects., (© 2024. The Author(s).)

Introduction: The renin-angiotensin-aldosterone system (RAAS) plays a pivotal role in regulating blood pressure (BP), with dysregulation of RAAS resulting in hypertension and potentially heart failure (HF), myocardial infarction (MI), cardio-renal syndrome, and stroke. RAAS inhibitors, such as angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), have advantages beyond BP control. However, differences between these two drug classes need to be considered when choosing a therapy for preventing cardiovascular events., Methods: A panel of 36 Egyptian cardiologists developed consensus statements on RAAS inhibitors for primary and secondary prevention of cardiovascular outcomes and stroke, using a modified three-step Delphi process., Results: The consensus statements highlight the importance of effective BP control and the role of RAAS blockade for prevention and management of various cardiovascular diseases. ACEis and ARBs differ in their mode of action and, thus, clinical effects. On the basis of available evidence, the consensus group recommended the following: ACEis should be considered as first choice (in preference to ARBs) to reduce the risk of MI, for primary prevention of HF, and for secondary prevention of stroke. ACEis and ARBs show equivalent efficacy for the primary prevention of stroke. Evidence also favors the preferential use of ACEis in patients with type 2 diabetes, for BP control, for the primary prevention of diabetic kidney disease, and to reduce the risk of major cardiovascular and renal outcomes. Treatment with an ACEi should be started within 24 h of ST segment elevation MI (and continued long term) in patients with HF, left ventricular systolic dysfunction, and/or diabetes. Angiotensin receptor/neprilysin inhibitors (ARNIs) are the first choice for patients with HF and reduced ejection fraction, with ACEis being the second choice in this group. ARBs are indicated as alternatives in patients who cannot tolerate ACEis. ACEis may be associated with cough development, but the incidence tends to be overestimated, and the risk can be reduced by use of a lipophilic ACEi or combining the ACEi with a calcium channel blocker., Conclusion: RAAS blockade is an essential component of hypertension therapy; however, the protective effects provided by ACEis are superior to those of ARBs. Therefore, an ACEi is indicated in almost all cases, unless not tolerated., (© 2024. The Author(s).)

Background: Depression is associated with major adverse cardiovascular events (MACE). Whether longitudinal changes in depression affect MACE in patients with coronary heart disease (CHD) remains unknown., Objectives: The authors evaluated the hypothesis that increasing or persistent depression predicts MACE in patients with CHD., Methods: At baseline, 3,483 Emory Cardiovascular Biobank participants (median age 65.5 years, 31.6% female) completed the Patient Health Questionnaire 8 (PHQ8) for depression evaluation. At 1 year, 2,639 of these event-free participants repeated the questionnaire. Depression was defined as a PHQ8 score >9 and change in depressive symptoms ( Δ PHQ8) was year 1 score minus baseline PHQ8 scores. We categorized participants into never depression (both PHQ8 <10), new depression (baseline PHQ8 <10; 1-year PHQ8 >9), remitted depression (baseline PHQ8 >9; year 1 PHQ8 <10), and persistent depression (both PHQ8 >9) groups. Fine-Gray models with noncardiovascular death as the competing event and adjusted for demographics, CHD, and depression related factors evaluated how changes in depression affect MACE (cardiovascular death and MI)., Results: Overall, the incidence of MACE was 14%, with 8.7% of those with follow-up PHQ8 having MACE. 2.9% had persistent depression, 4.5% had new depression, 10.8% had remitted depression, and 81.8% never had depression. Increasing depressive symptoms independently predicted MACE ( Δ PHQ8 subdistribution HR: 1.06 [95% CI: 1.02-1.09], P  < 0.001). Correspondingly, the incidence of MACE was higher in those with persistent (20.8%) or new depression (11.9%) than in those with remitted (9.4%) or never depression (8%) ( P  < 0.001). Compared to never depression, persistent depression independently predicted MACE (subdistribution HR: 2.78 [95% CI: 1.2-6.5], P  = 0.017)., Conclusions: Increasing or persistent depression predicts MACE in individuals with CHD., Competing Interests: Dr Vatsa is supported by the 10.13039/100013726Abraham J. & Phyllis Katz Foundation (Atlanta, GA), 10.13039/100000002NIH–10.13039/100000050NHLBI grant 1R01HL157311, and T32 HL130025. Dr Vaccarino is supported by R01 HL109413 and R01 HL163998. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Aim: We aimed to determine whether baseline high-density lipoprotein (HDL) cholesterol efflux capacity (CEC) at the time of coronary angiography (CAG) could serve as a prognostic marker for future major adverse cardiovascular events (MACE) in patients with coronary artery disease (CAD) through a systematic review and meta-analysis., Methods: The MEDLINE, Cochrane, and Embase databases were used for data collection. As of April 2024, 2,871 studies have been identified. Clinical studies comparing MACEs over an observational interval exceeding 12 months in patients with angiographically defined CAD with estimated hazard ratios (HRs) of MACEs in the higher or top-quartile HDL-CEC (H-HDL-CEC) group compared with the lower or bottom-quartile HDL-CEC (L-HDL-CEC) group, after adjusting for six confounding variables, including HDL-C, were included. HRs of 1) overall cardiovascular outcomes, composite of cardiovascular mortality, myocardial infarction, any coronary revascularization, and all-cause mortality (Model-1), and 2) cardiovascular outcomes excluding all-cause mortality from Model-1 (Model-2), compared between the L-HDL-CEC and H-HDL-CEC groups, were estimated using a random-effects model, respectively., Results: In five studies, 5,725 patients with CAD with a mean observational interval of 4.9 years were included. The H-HDL-CEC group had significantly lower risks for both estimates (Model-1: HR: 0.34, 95% confidence interval [CI]: 0.18-0.63 [p=0.0005], and I 2 =59.8% [p=0.04]; Model-2: HR: 0.28, 95% CI: 0.13-0.60 [p=0.0013], and I 2 =64% [p=0.04])., Conclusion: This is the first systematic review and meta-analysis to demonstrate a significant inverse relationship between the baseline HDL-CECs on CAG and long-term MACEs in CAD patients.

Dual agonism of glucagon and glucagon-like peptide-1 (GLP-1) receptors may be more effective than GLP-1 receptor agonism alone in reducing body weight, but the cardiovascular (CV) effects are unknown. The authors describe the rationale and design of SYNCHRONIZE-CVOT, a phase 3, randomized, double-blind, parallel-group, event-driven, CV safety study of survodutide, a dual glucagon and GLP-1 receptor agonist, administered subcutaneously once weekly compared with placebo in adults with a body mass index ≥27 kg/m 2 and established CV disease or chronic kidney disease, and/or at least 2 weight-related complications or risk factors for CV disease. The primary endpoint of SYNCHRONIZE-CVOT is time to first occurrence of the composite adjudicated endpoint of 5-point major adverse CV events. This global CV outcomes trial is currently enrolling, with a target recruitment of 4,935 participants. SYNCHRONIZE-CVOT is the first trial that will determine the CV safety and efficacy of survodutide in people with obesity and increased CV risk. (A Study to Test the Effect of Survodutide [BI 456906] on Cardiovascular Safety in People With Overweight or Obesity [SYNCHRONIZE-CVOT]; NCT06077864)., Competing Interests: Funding Support and Author Disclosures The SYNCHRONIZE-CVOT was funded by Boehringer Ingelheim. Dr Kosiborod has received research grants (payments to institution) from AstraZeneca, Boehringer Ingelheim, and Pfizer; has served as a consultant on advisory boards (payments to institution) for 35Pharma, Alnylam, Amgen, Applied Therapeutics, Arrowhead Pharmaceuticals, AstraZeneca, Bayer, Boehringer Ingelheim, Corcept Therapeutics, Cytokinetics, Dexcom, Eli Lilly, Esperion Therapeutics, Imbria Pharmaceuticals, Janssen, Lexicon Pharmaceuticals, Merck (Diabetes and Cardiovascular), Novo Nordisk, Pfizer, Pharmacosmos, Regeneron, Sanofi, scPharmaceuticals, Structure Therapeutics, Vifor Pharma, and Youngene Therapeutics; has received other research support (Data Analytic Center Fees – payments to institution) from AstraZeneca and Vifor Pharma; has received honoraria (payments to institution) from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk; and has received stock options (personal) from Artera Health and Saghmos Therapeutics. Dr Platz’s employer has received support from Novartis for consulting work; and she has consulted for scPharmaceuticals; has received research support from the National Institutes of Health, American Heart Association, and AstraZeneca; and has served on the clinical trial steering committee of the SYNCHRONIZE 1 and 2 trials and SYNCHRONIZE-CVOT funded by Boehringer Ingelheim. Dr Wharton has received research funding from Novo Nordisk and Bausch Health Canada; and has received honoraria for academic talks and advisory board from Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Regeneron, Bausch Health Canada, Merck, iNova, and Currax. Dr le Roux has received grants from the EU Innovative Medicine Initiative, Irish Research Council, Science Foundation Ireland, Anabio, and the Health Research Board; serves on advisory boards and speakers panels of Novo Nordisk, Roche, Herbalife, GI Dynamics, Eli Lilly, Johnson & Johnson, Glia, Irish Life Health, Boehringer Ingelheim, Currax, Zealand Pharma, Keyron, AstraZeneca, Arrow Pharma, and Rhythm Pharma; is the Chair of the Irish Society for Nutrition and Metabolism; and he provides obesity clinical care in the My Best Weight clinic and Beyond BMI clinic and is a shareholder in these clinics. Drs Brueckmann, Startseva, and Ajaz Hussain are full-time employees of Boehringer Ingelheim International GmbH. Ms Unseld is a full-time employee of Boehringer Ingelheim Pharma GmbH and Co KG. Dr Kaplan has served as a consultant to Altimmune, Amgen, Bain Capital, Boehringer Ingelheim, Cytoki, Gelesis, Gilead Sciences, Glyscend, Intellihealth, Johnson and Johnson, Kallyope, Eli Lilly and Co, Novo Nordisk, Optum Health, Perspectum, Pfizer, Sidekick Health, Skye Bioscience, twenty30.health, and Xeno Biosciences. The authors meet criteria for authorship as recommended by the ICMJE (International Committee of Medical Journal Editors), were fully responsible for all content and editorial decisions, and were involved at all stages of manuscript development. The authors did not receive payment related to the development of this manuscript. Boehringer Ingelheim was given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Cardiovascular disease (CVD) remains a leading cause of morbidity and mortality worldwide, particularly in individuals with obesity and type 2 diabetes mellitus (T2DM). This meta-analysis aimed to compare the effectiveness of bariatric metabolic surgery (BMS) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) on cardiovascular outcomes and mortality in patients with obesity. A comprehensive literature search was conducted in Medline, Embase, and Cochrane CENTRAL from inception to September 15, 2024. Four observational studies meeting the inclusion criteria were analyzed, comprising a total of 247,000 patients. The primary outcomes were major adverse cardiovascular events (MACE) and all-cause mortality. Random effects models were used to calculate pooled risk ratios (RR) with 95% confidence intervals (CI). The results showed that BMS was associated with a significantly lower risk of MACE compared to GLP-1RAs (RR: 0.71, 95% CI: 0.56-0.90, p = 0.004), indicating a 29% reduction in MACE risk. Additionally, BMS demonstrated a 25% reduction in all-cause mortality risk (RR: 0.75, 95% CI: 0.65-0.87, p < 0.0001). These findings suggest that BMS offers superior cardiovascular protection and improved survival outcomes compared to GLP-1RAs in obese patients. The observed benefits may be attributed to more significant reductions in body mass index (BMI) and improvements in metabolic parameters achieved through surgical intervention. However, the limitations of this study, including its observational nature and the limited number of included studies, underscore the need for further research, particularly randomized controlled trials (RCTs), to confirm these findings and guide clinical decision-making in obesity management., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Saeed et al.)

Background and Aims: Cardiovascular diseases (CVD) pose a significant global health burden. Lowering low-density lipoprotein-cholesterol is the primary therapeutic aim for preventing primary and secondary CVD events. While statins are the standard treatments, their limitations, such as side effects and intolerance in certain patient groups, necessitate exploration of alternative lipid-lowering therapies (LLTs). We systematically reviewed randomised controlled trials (RCTs) evaluating cardiovascular outcomes associated with non-statin LLTs (bempedoic acid, alirocumab, evolocumab, ezetimibe, and inclisiran) in adults with CVD or high cardiovascular risk., Methods: EMBASE, Medline, Cochrane Library, and clinical trial registries were systematically searched for eligible studies, from inception until February 08, 2023. Two reviewers independently screened the studies, with discrepancies resolved by a third reviewer. Data extraction and validation were conducted, and the risk of bias was assessed using the Cochrane Risk-of-Bias tool-2 for RCTs., Results: The search strategy yielded 2104 citations. Post screening for eligibility, nine unique trials/studies (84 publications) were identified. Among these, one trial each was identified for bempedoic acid and alirocumab, three for evolocumab, and four for ezetimibe. No published literature documenting the cardiovascular outcomes of inclisiran was identified. Only one trial (CLEAR Outcomes) included statin-intolerant patients at baseline. Most studies evaluated a 3-component, 4-component, or 5-component major adverse cardiovascular events composite as an outcome along with individual components. The quality of the included trials was found to be fair-to-good., Conclusions: The systematic review findings emphasise the significance of considering non-statin LLTs as viable treatment options for individuals with CVD or high cardiovascular risk who cannot tolerate or achieve optimal lipid control with statin therapy alone., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Prof. Gabriella Iannuzzo reports a relationship with SOBI, Daiichi-Sankyo, Novartis that includes: participation in advisory board. Prof. Gabriella Iannuzzo reports a relationship with 10.13039/100004339Sanofi, 10.13039/100002429Amgen, 10.13039/100013220Ultragenyx that includes: support for attending meetings. Prof. Gabriella Iannuzzo reports a relationship with Ultragenyx and Amryt Pharmaceuticals that includes: internal training. Shantanu Jawla reports a relationship with Daiichi-Sankyo that includes: employment. Geetank Kamboj reports a relationship with Skyward Analytics that includes: employment. Geetank Kamboj reports a relationship with Daiichi-Sankyo that includes: consulting or advisory. Parinita Barman reports a relationship with Skyward Analytics that includes: employment. Parinita Barman reports a relationship with Daiichi-Sankyo that includes: consulting or advisory. Shirish Dongare reports a relationship with Skyward Analytics that includes: employment. Shirish Dongare reports a relationship with Daiichi-Sankyo that includes: consulting or advisory. There are no other known competing financial interests or personal relationships that could have influenced the work reported in this paper., (© 2024 The Authors.)

Introduction: GLP-1 receptor agonists provide multiple benefits for patients with type 2 diabetes. Nonetheless, there are also several significant adverse effects associated with these agents. A thorough understanding of both therapeutic and toxicological profiles of GLP-1 receptor agonists is crucial for appropriate utilization of this medication class. A literature search of PubMed and ClinicalTrials.gov was carried out to inform discussion on the topic., Areas Covered: This review article discusses the key advantages and disadvantages derived from the use of GLP-1 receptor agonists in the treatment of type 2 diabetes. Landmark trials which helped characterize the cardiovascular and renal benefits of GLP-1 receptor agonists are highlighted. We also discuss key studies still in progress and new formulations under investigation., Expert Opinion: GLP-1 receptor agonists provide glycemic and complication-risk reduction benefits for individuals with type 2 diabetes. Current data suggests there is a lot of potential for further applications, even outside of type 2 diabetes management. It would be of particular interest to see the range of benefits conferred from GLP-1 receptor agonists in individuals without type 2 diabetes. Broader application of these medications could be expected given the ongoing development of new oral formulations and combination agents.

Introduction: Randomized controlled trials (RCT) have not demonstrated a role for continuous positive airway pressure (CPAP) on the secondary prevention of major cardiovascular events in obstructive sleep apnea (OSA) patients. However, participants in RCTs are substantially different from real-world patients. Therefore, we aimed to assess the effect of CPAP treatment on major cardiovascular events in real-world OSA patients., Methods: Population-based longitudinal observational study including all OSA patients with an active CPAP prescription at the beginning of 2011 in Catalonia, Spain, that terminated CPAP treatment during 2011 and did not have CPAP prescriptions between 2012-2015; and propensity-score-matched OSA patients that continued CPAP treatment until the end of 2015 or death. Adjusted hazard ratios were used to assess the association between CPAP treatment and overall and cardiovascular mortality, cardiovascular hospitalizations, or major adverse cardiovascular events (MACEs)., Results: 3638 CPAP terminators and 10,914 propensity-score-matched continuators were included (median age 67 [57-77] years, 71.4% male). During a median follow-up of 47.9 months CPAP continuators showed a lower risk of cardiovascular death than terminators (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.50-0.75) after adjusting by age, sex and key comorbidities. Similar results were found for cardiovascular hospitalizations (HR: 0.87; 95% CI: 0.76-0.99) and MACEs (HR: 0.84; 95% CI: 0.75-0.95)., Conclusion: CPAP treatment continuation could be associated with a significantly lower risk of major cardiovascular events in real-world OSA patients. This result highlights the importance of including real-world patients in studies on OSA., (Copyright © 2024 SEPAR. Published by Elsevier España, S.L.U. All rights reserved.)

Purpose of Review: To examine the concept of time in target range for blood pressure (BP) management, exploring its calculation methods, implications for patient outcomes, and potential use in patient care., Recent Findings: Recent post-hoc analyses of clinical trials and observational studies highlight the importance of BP time in target range in predicting cardiovascular outcomes. Higher time in target range correlates with reduced risks of major adverse cardiovascular events including heart failure, stroke, myocardial infarction and all-cause mortality. Additionally, longer time in target range decreases the risk of incident atrial fibrillation and risk of developing dementia. BP time in target range is a novel metric offering valuable insights into BP control and its impact on clinical outcomes. Higher time in target range is consistently associated with better cardiovascular outcomes across various patient populations. However, the clinical application of BP time in target range requires further investigation through prospective clinical trials and real-world studies. Integrating wearable devices for continuous BP monitoring could enhance the practical utility of BP time in target range in hypertension management., (© 2024. The Author(s).)

Purpose: Given the increased cardio-metabolic risk in patients with acromegaly, this study compared cardiovascular outcomes, mortality, and in-hospital outcomes between patients with acromegaly and non-functioning pituitary adenoma (NFPA) following pituitary surgery., Methods: This was a nationwide cohort study using data from hospitalized patients with acromegaly or NFPA undergoing pituitary surgery in Switzerland between January 2012 and December 2021. Using 1:3 propensity score matching, eligible acromegaly patients were paired with NFPA patients who underwent pituitary surgery, respectively. The primary outcome comprised a composite of cardiovascular events (myocardial infarction, cardiac arrest, ischemic stroke, hospitalization for heart failure, unstable angina pectoris, cardiac arrhythmias, intracranial hemorrhage, hospitalization for hypertensive crisis) and all-cause mortality. Secondary outcomes included individual components of the primary outcome, surgical re-operation, and various hospital-associated outcomes., Results: Among 231 propensity score-matched patients with acromegaly and 491 with NFPA, the incidence rate of the primary outcome was 8.18 versus 12.73 per 1,000 person-years (hazard ratio [HR], 0.64; [95% confidence interval [CI], 0.31-1.32]). Mortality rates were numerically lower in acromegaly patients (2.43 vs. 7.05 deaths per 1,000 person-years; HR, 0.34; [95% CI, 0.10-1.17]). Individual components of the primary outcome and in-hospital outcomes showed no significant differences between the groups., Conclusion: This cohort study did not find an increased risk of cardiovascular outcomes and mortality in patients with acromegaly undergoing pituitary surgery compared to surgically treated NFPA patients. These findings suggest that there is no legacy effect regarding higher cardio-metabolic risk in individuals with acromegaly once they receive surgical treatment., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose of Review: Analyze current evidence on racial/ethnic disparities in cardiovascular outcomes among cancer survivors, identifying factors and proposing measures to address health inequities., Recent Findings: Existing literature indicates that the Black population experiences worse cardiovascular outcomes following the diagnosis of both initial primary cancer and second primary cancer, with a notably higher prevalence of cardio-toxic events, particularly among breast cancer survivors. Contributing socioeconomic factors to these disparities include unfavorable social determinants of health, inadequate insurance coverage, and structural racism within the healthcare system. Additionally, proinflammatory epigenetic modification is hypothesized to be a contributing genetic variation factor. Addressing these disparities requires a multiperspective approach, encompassing efforts to address racial disparities and social determinants of health within the healthcare system, refine healthcare policies and access, and integrate historically stigmatized racial groups into clinical research. Racial and ethnic disparities persist in cardiovascular outcomes among cancer survivors, driven by multifactorial causes, predominantly associated with social determinants of health. Addressing these healthcare inequities is imperative, and timely efforts must be implemented to narrow the existing gap effectively., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Long COVID is a condition where symptoms or complications persist beyond 3 months after COVID-19 infection. Although most athletes experience mild symptoms, those involved in sports with higher cardiovascular demands can develop long COVID, which can negatively impact sports performance. This narrative review aimed to analyze the long COVID in athletes, especially cardiovascular effects; to alert medical and sporting community for the clinical aftermaths of COVID-19, focusing on physical activity; and to discuss the potential return-to-play strategies for these athletes., Methods: An electronic search in PubMed database for articles published between January/2020 and February/2023 was performed including athletic populations with COVID-19, emphasizing long-term complications, especially the cardiovascular effects., Results and Conclusions: While severe cardiac complications are rare, athletes with long COVID often experience symptoms such as fatigue, dyspnea, palpitations, and exercise intolerance. To manage athletes with long COVID, individualized and structured return-to-play programs with the involvement of multidisciplinary teams are crucial. This underscores the importance of recognizing long COVID in athletes, raising awareness of its potential impacts, and implementing strategies to ensure a safe return to play.

Background: The epidemiology of coronary artery disease (CAD) has shifted, with increasing prevalence of cardiometabolic disease and decreasing findings of obstructive CAD on myocardial perfusion imaging (MPI). Coronary microvascular dysfunction (CMD), defined as impaired myocardial flow reserve (MFR) by positron emission tomography (PET), has emerged as a key mediator of risk. We aimed to assess whether PET MFR provides additive value for risk stratification of cardiometabolic disease patients compared with single-photon emission computed tomography (SPECT) MPI., Methods: We retrospectively followed patients referred for PET, exercise SPECT, or pharmacologic SPECT MPI with cardiometabolic disease (obesity, diabetes, or chronic kidney disease) and without known CAD. We compared rates and hazards of composite major adverse cardiovascular events (MACEs) (annualized cardiac mortality or acute myocardial infarction) among propensity-matched PET and SPECT patients using Poisson and Cox regression. Normal SPECT was defined as a total perfusion deficit (TPD) of <5%, reflecting the absence of obstructive CAD. Normal PET was defined as a TPD of <5% plus an MFR of ≥2.0., Results: Among 21,544 patients referred from 2006 to 2020, cardiometabolic disease was highly prevalent (PET: 2308 [67%], SPECT: 9984 [55%]) and higher among patients referred to PET (P < 0.001). Obstructive CAD findings (TPD > 5%) were uncommon (PET: 21% and SPECT: 11%). Conversely, impaired MFR on PET (<2.0) was common (62%). In a propensity-matched analysis over a median 6.4-year follow-up, normal PET identified low-risk (0.9%/year MACE) patients, and abnormal PET identified high-risk (4.2%/year MACE) patients with cardiometabolic disease; conversely, those with normal pharmacologic SPECT remained moderate-risk (1.6%/year, P < 0.001 compared to normal PET)., Conclusions: Cardiometabolic disease is common among patients referred for MPI and is associated with a heterogenous level of risk. Compared with pharmacologic SPECT, PET with MFR can detect nonobstructive CAD including CMD and can more accurately discriminate low-risk from higher-risk individuals., (Copyright © 2024 American Society of Nuclear Cardiology. Published by Elsevier Inc. All rights reserved.)

Importance: There is uncertainty as to whether treatment of subclinical hypothyroidism (SCH) is associated with cardiovascular outcomes. Objectives: To determine whether levothyroxine replacement therapy decreases the risk of major adverse cardiovascular events (MACE) among individuals with SCH defined as having a thyrotropin (TSH) level between 5 and 10 mU/L. Design: We conducted a population-based cohort study using a prevalent new-user design. Setting: The study utilized data from the United Kingdom Clinical Practice Research Datalink. Participants: We identified a base cohort of individuals aged ≥18 years with incident SCH defined as having at least two TSH levels between 5 and 10 mU/L within one year between 1998 and 2018. We matched 76,946 levothyroxine treated to 76,946 untreated individuals based on age, sex, calendar time, duration of SCH, and time-conditional propensity score. We compared individuals with SCH treated with levothyroxine with individuals with no treatment. Exposure: Levothyroxine treatment versus no treatment. Main Outcome Measures: The primary outcome, MACE, was defined as a composite of nonfatal myocardial infarction, nonfatal ischemic stroke, and cardiovascular-related mortality. Results: The mean age of the study cohort was 62.8 years, and 76.5% were women. During a median follow-up time of 1.6 years (interquartile range: 0.5-4.2), the incidence rate for MACE among individuals treated with levothyroxine was 12.8 per 1000 person-years; confidence interval (CI): 12.2-13.3 and 13.9 per 1000 person-years; CI: 13.4-14.3 among nontreated individuals. Levothyroxine treatment was associated with a small decreased risk of MACE (hazard ratio: 0.88; CI: 0.83-0.93). Conclusions: Levothyroxine treatment of SCH was associated with a small decreased risk of MACE. However, given the observational nature of the study, residual confounding should be considered in the interpretation of this finding.

Background : The role of treadmill stress echocardiography (TSE) in symptomatic patients may be limited. We evaluated whether carotid intima-media thickness (cIMT) and coronary artery calcium (CAC) scores can predict cardiovascular (CV) outcomes in patients with negative TSE. Methods : Patients who had negative TSE and measured cIMT or CAC scoring were enrolled and followed up. The primary CV outcome was defined as a composite of acute coronary syndrome, coronary revascularization, heart failure, stroke, and CV death. Results : Overall, 1095 patients participated. The median follow-up duration was 5.8 years. Patients with increased cIMT and CAC scores experienced a high incidence of primary CV outcomes (normal vs. increased group on cIMT and CAC scoring: 4.4% vs. 20.0% and 0.4% vs. 25.0%, respectively, p < 0.001). In the Cox proportional hazard model, increased cIMT and CAC scores were associated with increased primary CV outcomes (adjusted hazard ratio [95% confidence interval], p -value for increased cIMT and increased CAC scores = 2.939 [1.241-6.960], p = 0.014 and 45.192 [5.497-371.505], p < 0.001, respectively). Conclusions : Patients with increased cIMT and CAC scores have poor CV outcomes even though they have negative TSE results, and therefore, they should be carefully monitored.

Type 2 diabetes mellitus (T2DM) is a significant risk factor for cardiovascular diseases, prompting research into treatments that can mitigate this risk. Sodium-glucose cotransporter 2 (SGLT2) inhibitors, particularly dapagliflozin and empagliflozin, have shown promising cardiovascular benefits in T2DM patients. This meta-analysis aimed to directly compare the cardiovascular outcomes of these two drugs. To achieve this, we conducted a comprehensive literature search across multiple databases up to August 5, 2024, including both randomized controlled trials (RCTs) and observational studies. The primary outcomes of interest were major adverse cardiovascular events (MACE), atrial fibrillation (AF), cardiovascular mortality, myocardial infarction (MI), and hospitalization for heart failure (HF). Twelve studies met the inclusion criteria for this meta-analysis. The pooled analysis revealed several key findings. Notably, dapagliflozin demonstrated superior efficacy in preventing atrial fibrillation compared to empagliflozin. However, no significant differences were observed between the two drugs in terms of MACE, cardiovascular mortality, hospitalization for heart failure (HHF), or myocardial infarction. When compared to placebo, both dapagliflozin and empagliflozin showed greater effectiveness in preventing adverse cardiovascular outcomes in T2DM patients. These results reinforce the cardiovascular benefits of both dapagliflozin and empagliflozin in patients with T2DM. The comparable efficacy in most outcomes suggests that clinicians have flexibility in prescribing either of these SGLT2 inhibitors. However, the lower risk of atrial fibrillation associated with dapagliflozin may be a crucial factor in treatment decisions, especially for patients with a history of or at high risk for atrial fibrillation., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sinha et al.)

Background Coronary artery disease (CAD) is influenced by oxidative stress, which is a critical yet often overlooked factor in disease progression. While traditional biomarkers such as cholesterol levels and blood pressure are commonly used, they do not fully capture oxidative damage. Malondialdehyde (MDA), a byproduct of lipid peroxidation, offers additional insights into oxidative stress and CAD severity. Unlike conventional markers, such as low-density lipoprotein (LDL) cholesterol, which primarily reflects lipid levels, and high-sensitivity C-reactive protein (hs-CRP), which indicates inflammation, MDA directly measures oxidative damage. This makes MDA a potentially valuable complement to these traditional biomarkers, providing a more nuanced understanding of CAD risk. Despite its potential, the role of MDA in clinical assessments remains underexplored. This study aims to address this gap by evaluating MDA's effectiveness as a complementary biomarker, enhancing the assessment of CAD risk and progression beyond what is provided by existing markers. Objective This study aims to assess serum MDA levels in relation to CAD severity to explore its potential as a non-invasive biomarker for disease progression and cardiovascular outcomes. Methodology This cross-sectional study was conducted at the Department of Cardiology, Mardan Medical Complex Teaching Hospital, Pakistan, from June 2023 to May 2024. Patients were divided into different groups with varying severity of CAD. The one-way ANOVA was used to assess differences among groups, and Pearson's correlation coefficient explored relationships between MDA and all study variables. Simple linear regression analyzed associations between MDA levels, patient groups, and other variables, controlling for covariates. MDA's potential as a predictive biomarker was assessed through ROC curve analysis, with statistical significance set at a p-value < 0.05. Results A total of 133 patients were included in the study, categorized based on CAD severity into mild (n=71), moderate (n=39), and severe (n=23) groups. Serum MDA levels significantly increased with the severity of CAD. Specifically, MDA levels were 116.61 ± 41.95 in the mild group, 253.45 ± 180.29 in the moderate group, and peaked at 459.91 ± 149.80 in the severe group. The differences in MDA levels among these groups were statistically significant (p < 0.01), supporting the association between higher MDA levels and increased CAD severity. Factors such as BMI, heart rate, blood pressure, and smoking status also significantly influenced MDA levels. Receiver operating characteristic (ROC) curve analysis demonstrated high diagnostic accuracy of MDA for assessing CAD severity, with area under the curve (AUC) values of 0.81 for moderate and 0.94 for severe CAD. Comorbid conditions such as diabetes mellitus were associated with elevated MDA levels. Conclusion Elevated serum MDA serves as a reliable, non-invasive biomarker for predicting CAD severity, with potential applications in clinical risk assessment and management strategies. By identifying patients with elevated oxidative stress early, clinicians can implement timely interventions, potentially slowing disease progression and improving outcomes., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Bacha Khan Medical College issued approval No 569/ BKMC. This is to certify that Ethical Approval has been granted to Dr. Asfandiyar, Consultant Cardiologist, Department of Cardiology, MTI Bacha Khan Medical College & Mardan Medical Complex, Mardan. The title of his article is “Estimation of Serum Malondialdehyde (MDA) an Oxidative Stress Predictive Biomarker for the Severity of Coronary Artery Disease (CAD) and Their Clinical Outcomes“. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: This study was supported by Pro-Gene Diagnostics and Research Laboratory, which provided funding for the biomarker analysis. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, . et al.)

This meta-analysis evaluated the clinical outcomes of intravascular ultrasound (IVUS)-guided versus angiography-guided percutaneous coronary intervention (PCI) in patients with coronary artery disease (CAD). A comprehensive literature search was conducted across major electronic databases, identifying relevant studies published up to August 15, 2024. Thirteen randomized controlled trials (RCTs) met the inclusion criteria, comparing IVUS-guided and angiography-guided PCI. The primary outcomes were major adverse cardiac events (MACE) and stent thrombosis, while secondary outcomes included all-cause mortality, cardiac mortality, myocardial infarction, and revascularization rates. Pooled analysis revealed that IVUS-guided PCI significantly reduced the risk of MACE (risk ratio (RR): 0.63, 95% CI: 0.50-0.79) and stent thrombosis (RR: 0.52, 95% CI: 0.30-0.90) compared to angiography-guided PCI. Secondary outcomes also favored IVUS guidance, with significant reductions in cardiac mortality, myocardial infarction, target lesion revascularization (TLR), and target vessel revascularization (TVR). While a trend towards reduced all-cause mortality was observed with IVUS guidance, it did not reach statistical significance. Notably, low heterogeneity across studies strengthened the reliability of these findings. Meta-regression analysis indicated that the presence of myocardial infarction did not significantly moderate the effect of IVUS on clinical outcomes, suggesting consistent benefits across patient subgroups. These results highlight the potential of IVUS-guided PCI to improve cardiovascular outcomes and reduce the need for repeat procedures. The findings support the growing body of evidence favoring IVUS use in PCI, particularly in complex lesions and high-risk patients. However, considerations such as cost-effectiveness and the need for specialized training remain important factors in the widespread adoption of IVUS-guided PCI in clinical practice., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Krishna Mohan et al.)

We investigated the risk of cardiovascular events, all-cause mortality, and liver-related mortality according to the presence of metabolic syndrome (MetS) and fatty liver index (FLI). In this retrospective longitudinal population-based cohort study, we used Korean National Health Insurance Service data from 2009 to 2012. Nonalcoholic fatty liver disease (NAFLD) was defined as FLI ≥ 60. Risk of all-cause mortality, liver-related mortality, and major adverse cardiovascular events (MACE) including myocardial infarction (MI), stroke, heart failure (HF), and cardiovascular disease (CVD)-related mortality was assessed according to the presence of MetS and FLI among adults (aged 40 to 80 years) who underwent health examinations (n = 769,422). During a median 8.59 years of follow up, 44,356 (5.8%) cases of MACE, 24,429 (3.2%) cases of all-cause mortality, and 1114 (0.1%) cases of liver-related mortality were detected in the entire cohort. When the FLI < 30 without MetS group was set as a reference, the FLI ≥ 60 with MetS group had the highest risk of MACE (adjusted hazard ratio [aHR] 2.05, 95% confidence interval [CI] 1.98-2.13) and all-cause mortality (aHR 1.96, 95% CI 1.86-2.07). The risk of liver-related mortality (aHR 10.71, 95% CI 8.05-14.25) was highest in the FLI ≥ 60 without MetS group. The FLI ≥ 60 with MetS group had a higher risk of MACE (aHR 1.39, 95%CI 1.28-1.51), a lower risk of liver-related mortality (aHR 0.44, 95%CI 0.33-0.59), and no significant difference in all-cause mortality compared with the FLI ≥ 60 without MetS group. The FLI ≥ 60 with MetS group was associated with the highest risk of MACE and the FLI ≥ 60 without MetS group had the highest risk liver-related mortality, but there was no significant difference in all-cause mortality between two groups. In conclusion, as FLI levels increase, the risk of MACE increases, and the risk increases additively in the presence of MetS. The risk of liver-related mortality increases with higher FLI levels, the effect of high FLI on increased risk is more significant in groups without MetS compared to those with MetS., (© 2024. The Author(s), under exclusive licence to Società Italiana di Medicina Interna (SIMI).)

Purpose of Review: This article summarizes the medical management of obesity with an emphasis on incretin-based therapeutics that target the neuro-hormonal basis of obesity., Recent Findings: Medications that mimic the effect of incretins, a group of peptide hormones released in response to nutrient intake that regulate appetite, result in potent and durable weight loss. Glucagon-like peptide 1 (GLP-1) agonists and glucose-dependent insulinotropic polypeptide (GIP) agonists such as semaglutide and tirzepatide are approved by the United States Food and Drug Administration (FDA) for the management of obesity. The SELECT trial demonstrated that semaglutide led to a reduction in major adverse cardiovascular events in patients without diabetes who were either overweight and had preexisting cardiovascular disease or obese., Summary: The treatment of obesity is critical to prevent the progression of cardiovascular-kidney-metabolic syndrome. Incretin-based therapies offer remarkable weight loss and reduce major cardiovascular adverse events., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Heart failure with preserved ejection fraction (HFpEF) is common in type 2 diabetes mellitus (T2D), leading to high morbidity and mortality. Managing HFpEF in diabetic patients is challenging with limited treatments. Sodium-glucose co-transporter 2 (SGLT2) inhibitors and glucagon-like peptide-1 receptor agonists (GLP1-RA) have shown potential cardiovascular benefits. This meta-analysis compares the effects of GLP1-RA and SGLT2 inhibitors on HFpEF in T2D patients., Methods: We conducted a meta-analysis of randomized controlled trials (RCTs) and observational studies evaluating GLP1-RA and SGLT2 inhibitors' impact on HFpEF in T2D patients. Databases searched included PubMed, MEDLINE, and Cochrane Library up to July 2024. Primary outcomes were changes in left ventricular ejection fraction (LVEF), myocardial fibrosis (extracellular volume fraction, ECV), and functional capacity (6-minute walk test, 6MWT). Secondary outcomes included HbA1c, body weight, and systolic blood pressure (SBP).  RESULTS: Twelve studies with 3,428 patients (GLP1-RA: 1,654; SGLT2 inhibitors: 1,774) were included. Both GLP1-RA and SGLT2 inhibitors significantly improved LVEF compared to placebo (GLP1-RA: mean difference [MD] 2.8%, 95% confidence interval [CI] 1.5 to 4.1, p < 0.001; SGLT2 inhibitors: MD 3.2%, 95% CI 2.0 to 4.4, p < 0.001). SGLT2 inhibitors significantly reduced myocardial fibrosis (MD -3.5%, 95% CI -4.2 to -2.8, p < 0.001) more than GLP1-RA (MD -2.3%, 95% CI -3.0 to -1.6, p < 0.001). Functional capacity improved significantly with both treatments (GLP1-RA: MD 45 m, 95% CI 30 to 60, p < 0.001; SGLT2 inhibitors: MD 50 m, 95% CI 35 to 65, p < 0.001). Secondary outcomes showed reductions in HbA1c (GLP1-RA: MD -1.1%, 95% CI -1.4 to -0.8, p < 0.001; SGLT2 inhibitors: MD -1.0%, 95% CI -1.3 to -0.7, p < 0.001) and body weight (GLP1-RA: MD -2.5 kg, 95% CI -3.1 to -1.9, p < 0.001; SGLT2 inhibitors: MD -2.0 kg, 95% CI -2.6 to -1.4, p < 0.001). Both treatments significantly lowered SBP (GLP1-RA: MD -5.2 mmHg, 95% CI -6.5 to -3.9, p < 0.001; SGLT2 inhibitors: MD -4.8 mmHg, 95% CI -6.0 to -3.6, p < 0.001)., Conclusions: GLP1-RA and SGLT2 inhibitors significantly benefit HFpEF management in T2D patients. SGLT2 inhibitors reduce myocardial fibrosis more effectively, while both improve LVEF, functional capacity, and metabolic parameters. These therapies should be integral to HFpEF management in diabetic patients. Further research is needed on long-term outcomes and potential combined therapy effects., (© 2024. The Author(s).)

Background: Sodium-glucose co-transporter-2 inhibitors (SGLT2i) have cardiovascular (CV) benefits, particularly in reducing the risk of heart failure (HF). Pioglitazone (Pio) has shown potential in decreasing the risks of recurrent stroke, non-fatal myocardial infarction (MI), and all-cause mortality but increasing risks of HF. Our study aimed to examine the synergistic effects on CV outcomes in patients with type 2 diabetes mellitus (T2DM) who received the combined treatment of SGLT2i and Pio., Materials and Methods: A total of 117,850 patients with T2DM and without a history of HF were selected as the observational study cohort from the Chang Gung Research Database (CGRD) in Taiwan between January 1, 2016, and December 31, 2019. The primary composite outcome was 4-point major adverse CV events (4P-MACE), including CV death, non-fatal MI, non-fatal ischemic stroke, and hospitalization for HF. The study was divided into four groups: a combined treatment group in which SGLT2i and Pio were used, two individual groups in which SGLT2i or Pio was used separately, and a reference group (non-study drugs)., Results: Combined treatment of SGLT2i and Pio had the lowest risk of 4P-MACE (adjusted hazard ratio [aHR], 0.66; 95% confidence interval [CI], 0.54-0.80) compared with the reference group after a mean follow-up of 2.2 years. There was no significant difference in risks of hospitalization for HF (adjusted subdistribution hazard ratio, 0.73; 95% CI, 0.49-1.07) compared with the reference group., Conclusions: In T2DM patients without HF, the combined treatment with SGLT2i and Pio may synergistically provide CV benefits without increasing risks of HF., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Wang, Liu, Yen, Wu, Huang, Lee and Hsiao.)

Background and Aims: In the FLOW trial, semaglutide reduced the risks of kidney and cardiovascular (CV) outcomes and death in participants with type 2 diabetes mellitus (T2D) and chronic kidney disease (CKD). These prespecified analyses assessed the effects of semaglutide on CV outcomes and death by CKD severity., Methods: Participants were randomised to subcutaneous semaglutide 1 mg or placebo weekly. The main outcome was a composite of CV death, non-fatal myocardial infarction (MI) ornon-fatal stroke (CV death/MI/stroke) as well as death due to any cause by baseline CKD severity. CKD was categorised by eGFR < or ≥60 mL/min/1.73 m2, UACR < or ≥300 mg/g or KDIGO risk classification., Results: 3533 participants were randomised with a median follow-up of 3.4 years. Low/moderate KDIGO risk was present in 242 (6.9%), while 878 (24.9%) had high and 2412 (68.3%) had very high KDIGO risk. Semaglutide reduced CV death/MI/stroke by 18% (HR 0.82 [95% CI 0.68-0.98]; P = .03), with consistency across eGFR categories, UACR levels and KDIGO risk classification (all P-interaction >.13). Death due to any cause was reduced by 20% (HR 0.80 [0.67-0.95]; P = .01), with consistency across eGFR categories and KDIGO risk class (P-interaction .21 and .23, respectively). The P-interaction treatment effect for death due to any cause by UACR was .01 (<300 mg/g HR 1.17 [0.83-1.65]; ≥300 mg/g HR 0.70 [0.57-0.85])., Conclusions: Semaglutide significantly reduced the risk of CV death/MI/stroke regardless of baseline CKD severity in participants with T2D., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background Acute myocardial infarction (AMI) is a leading cause of morbidity and mortality worldwide, particularly in low- and middle-income countries like Pakistan, where healthcare resources are limited. Early Invasive Strategy (EIS), typically involving percutaneous coronary intervention (PCI), has been shown to improve outcomes in AMI patients. However, the effectiveness of EIS in resource-limited settings, such as Pakistan, remains under-explored. Objective This prospective observational cohort study aimed to assess the impact of an Early Invasive Strategy (EIS) on left ventricular (LV) function recovery in acute myocardial infarction (AMI) patients in Pakistan. The primary objective was to measure the change in left ventricular ejection fraction (LVEF) over six months. Secondary objectives included evaluating mortality, rehospitalization rates, and incidences of major adverse cardiovascular events (MACE). Multivariate regression analysis was employed to adjust for potential confounders. Methods The study was conducted from January to December 2023 at the National Institute of Cardiovascular Diseases (NICVD) satellite centers in Sukkur, Nawab Shah, and Khairpur. A total of 300 AMI patients presenting within 24 hours of symptom onset were included. Participants were divided into two groups: the EIS group (n = 150) received percutaneous coronary intervention (PCI) within 24 hours of admission, while the delayed treatment group (n = 150) received standard therapy, with invasive procedures performed after 24 hours if clinically indicated. Data were collected at baseline, during hospitalization, and at three- and six-months post-AMI. Results The EIS group demonstrated a significantly greater improvement in LVEF compared to the delayed treatment group (13.1% [95% CI, 10.8%-15.4%] vs. 7.5% [95% CI, 5.8%-9.2%], p < 0.001). Mortality was lower in the EIS group (3% [n = 4] vs. 9% [n = 13], p = 0.01), as were rehospitalizations for heart failure (7% [n = 10] vs. 14% [n = 21], p = 0.02) and incidences of MACE (8% [n = 12] vs. 16% [n = 24], p = 0.01). Multivariate regression analysis confirmed that EIS was independently associated with better LVEF improvement (coefficient = 5.78 [95% CI, 4.21-7.35], p < 0.001). Conclusion Early invasive treatments significantly enhance left ventricular function recovery and reduce mortality and rehospitalization rates in AMI patients in Pakistan. These findings advocate for the implementation of timely PCI interventions in resource-limited settings to improve clinical outcomes, particularly emphasizing cost-effectiveness and the availability of PCI., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Review Board (IRB) of Sindh Institute of Cardiovascular Diseases issued approval SICVD/79. The study titled "Impact of Early Invasive Strategy on Left Ventricular Function Recovery in Acute Myocardial Infarction Patients in Pakistan," authored by Dr. Shahbaz et al., has received ethical approval number SICVD/79. Ethical recommendations include obtaining informed consent, ensuring confidentiality, minimizing risks, and maintaining the right to withdraw. Participants should be selected fairly, and adverse events must be promptly reported and addressed. The integrity of data should be preserved, and the potential benefits must justify any risks. Participants should have access to study results and beneficial treatments post-study. These measures ensure ethical conduct and participant well-being throughout the study. The study was conducted at the National Institute of Cardiovascular Diseases (NICVD) in Karachi, Pakistan. However, it's important to clarify that the research was specifically carried out in the satellite centers of NICVD located in Sukkur, Nawab Shah, and Khairpur. Ethical approval was obtained from the Sindh Institute of Cardiovascular Diseases (SICVD), which oversees the ethical conduct of research across all NICVD centers, including these satellite locations. The IRB approval number SICVD/79 pertains to this approval, ensuring that the study adhered to the necessary ethical standards across all involved sites. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Shaikh et al.)

Objective: The present umbrella review aims to collate and summarize the findings from previous meta-analyses on the Triglyceride and Glucose (TyG) Index, providing insights to clinicians, researchers, and policymakers regarding the usefulness of this biomarker in various clinical settings., Methods: A comprehensive search was conducted in PubMed, Scopus, and Web of Science up to April 14, 2024, without language restrictions. The AMSTAR2 checklist assessed the methodological quality of the included meta-analyses. Statistical analyses were performed using Comprehensive Meta-Analysis (CMA) software., Results: A total of 32 studies were finally included. The results revealed significant associations between the TyG index and various health outcomes. For kidney outcomes, a high TyG index was significantly associated with an increased risk of contrast-induced nephropathy (CIN) (OR = 2.24, 95% CI: 1.82-2.77) and chronic kidney disease (CKD) (RR = 1.46, 95% CI: 1.32-1.63). High TyG index was significantly associated with an increased risk of type 2 diabetes mellitus (T2DM) (RR = 3.53, 95% CI: 2.74-4.54), gestational diabetes mellitus (GDM) (OR = 2.41, 95% CI: 1.48-3.91), and diabetic retinopathy (DR) (OR = 2.34, 95% CI: 1.31-4.19). Regarding metabolic diseases, the TyG index was significantly higher in patients with obstructive sleep apnea (OSA) (SMD = 0.86, 95% CI: 0.57-1.15), metabolic syndrome (MD = 0.83, 95% CI: 0.74-0.93), and non-alcoholic fatty liver disease (NAFLD) (OR = 2.36, 95% CI: 1.88-2.97) compared to those without these conditions. In cerebrovascular diseases, a higher TyG index was significantly associated with an increased risk of dementia (OR = 1.14, 95% CI: 1.12-1.16), cognitive impairment (OR = 2.31, 95% CI: 1.38-3.86), and ischemic stroke (OR = 1.37, 95% CI: 1.22-1.54). For cardiovascular outcomes, the TyG index showed significant associations with an increased risk of heart failure (HF) (HR = 1.21, 95% CI: 1.12-1.30), atrial fibrillation (AF) (SMD = 1.22, 95% CI: 0.57-1.87), and hypertension (HTN) (RR = 1.52, 95% CI: 1.25-1.85)., Conclusion: The TyG index is a promising biomarker for screening and predicting various medical conditions, particularly those related to insulin resistance and metabolic disorders. However, the heterogeneity and methodological quality of the included studies suggest the need for further high-quality research to confirm these findings and refine the clinical utility of the TyG index., (© 2024. The Author(s).)

A panel of primary care and diabetes specialists conducted focused literature searches on the current role of glycaemic control in the management of type 2 diabetes and revisited the evolution of evidence supporting the importance of early and intensive blood glucose control as a central strategy to reduce the risk of adverse long-term outcomes. The optimal approach to type 2 diabetes management has evolved over time as the evidence base has expanded from data from trials that established the role of optimising glycaemic control to recent data from cardiovascular outcomes trials (CVOTs) demonstrating organ-protective effects of newer glucose-lowering drugs (GLDs). The results from these CVOTs were derived mainly from people with type 2 diabetes and prior cardiovascular and kidney disease or multiple risk factors. In more recent years, earlier diagnosis in high-risk individuals has contributed to the large proportion of people with type 2 diabetes who do not have complications. In these individuals, a legacy effect of early and optimal control of blood glucose and cardiometabolic risk factors has been proven to reduce cardiovascular and kidney disease events and all-cause mortality. As there is a lack of RCTs investigating the potential synergistic effects of intensive glucose control and organ-protective effects of newer GLDs, this article re-evaluates the evolution of the scientific evidence and highlights the importance of integrating glycaemic control as a pivotal early therapeutic goal in most people with type 2 diabetes, while targeting existing cardiovascular and kidney disease. We also emphasise the importance of implementing multifactorial management using a multidisciplinary approach to facilitate regular review, patient empowerment and the possibility of tailoring interventions to account for the heterogeneity of type 2 diabetes., (© 2024. The Author(s).)

Background: Tirzepatide, a novel dual agonist of glucagon-like-peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), has demonstrated greater magnitude of weight loss compared to semaglutide in a phase 3 clinical trial. However, the effect of tirzepatide on incidence of type 2 diabetes (T2D) in individuals with overweight and obesity, and the effect on major adverse cardiovascular outcomes in individuals with pre-existing T2D, remains unknown., Methods: We performed a retrospective cohort study of anonymised electronic medical records using the TriNetX network (TriNetX LLC, Cambridge, MA, USA) a global federated database. The data used in this study was collected on 5th June 2024. Two cohorts of individuals were generated: 1) without pre-existing T2D and, 2) with T2D. We adopted an active comparator new user design on new initiations of either tirzepatide or semaglutide therapy. Analysis began from the index event which was defined as individuals on respective therapy for 6 months only. Analysis of outcomes was conducted off-drug, in individuals without a pre-existing history of the disease of interest. Individuals were followed up for 12 months post the index event. Primary outcome for cohort 1 was incidence of T2D, and for cohort 2 was composite: all-cause mortality, cerebral infarction, acute coronary syndrome, and heart failure. Secondary outcomes for cohort 1 were change in HbA1c and body weight and for cohort 2 : incidence of micro- and macrovascular complications, suicidal ideation and/or attempt, and all-cause mortality. We propensity score matched (1:1) for potential confounders: baseline demographics, socioeconomic circumstances, HbA1c, weight, relevant co-morbidities, and anti-obesity, hypoglycaemic and cardioprotective agents., Findings: The study population without T2D consisted of 13,846 individuals, equally split between tirzepatide and semaglutide users. Tirzepatide was associated with both lower risk for incident T2D (HR 0.73, 95% CI 0.58-0.92, p < 0.001) and greater weight loss (-7.7 kg, [95% CI -6.8, -8.5 kg], p < 0.001), compared to semaglutide (-4.8 kg, [95% CI -3.9, -5.6 kg], p < 0.001). In individuals with pre-existing T2D (n = 8446), tirzepatide was associated with lower risk of the composite outcome (HR 0.54, 95% CI 0.38-0.76, p < 0.001), cerebral infarction (HR 0.45, 95% CI 0.24-0.84, p = 0.010) and all-cause mortality (HR 0.33, 95% CI 0.15-0.73, p = 0.004) compared to semaglutide., Interpretation: Tirzepatide is associated with significantly reduced risk of developing T2D and major adverse cardiovascular events in individuals living with obesity and T2D respectively. Randomised controlled trials investigating the utility of dual incretin agonists in the primary prevention of T2D and cardiovascular disease in higher risk populations are now required., Funding: Nil., Competing Interests: MA receives a fellowship from the Novo Nordisk UK research foundation and JDRF. DJC has received investigator-initiated grants from Astra Zeneca and Novo Nordisk, support for education from Perspectum with any financial remuneration from pharmaceutical company consultation made to the University of Liverpool. GHI is an employee of TriNetX LLC. UA has received honoraria from Eli Lilly, Procter & Gamble, Viatris, Grunenthal and Sanofi for educational meetings and funding for attendance to an educational meeting from Diiachi Sankyo. UA has also received investigator-led funding by Procter & Gamble and is a council member of the Royal Society of Medicine's Vascular, Lipid & Metabolic Medicine Section. JPHW consults widely for pharmaceutical companies in relation to obesity and diabetes (fees paid to the University of Liverpool via his institution) and has received research grants from industry. He has received lecture fees from commercial organisations including the pharmaceutical industry while providing unpaid support to various charities in relation to his interest in obesity and diabetes. All other authors declare that there are no financial relationships or activities that might bias, or be perceived to bias, their contribution to this manuscript., (© 2024 The Author(s).)

Background: While current guidelines recommend amiodarone and dronedarone for rhythm control in patients with atrial fibrillation (AF) and coronary artery disease (CAD), there was no comparative study of antiarrhythmic drugs (AADs) on the cardiovascular outcomes in general practice., Methods: This study included patients with AF and CAD who received their first prescription of amiodarone, class Ic AADs (flecainide, propafenone), dronedarone or sotalol between January 2016 and December 2020. The primary outcome was a composite of hospitalization for heart failure (HHF), stroke, acute myocardial infarction (AMI), and cardiovascular death. We used Cox proportional regression models, including with inverse probability of treatment weighting (IPTW), to estimate the relationship between AADs and cardiovascular outcomes., Results: Among the AF cohort consisting of 8752 patients, 1996 individuals had CAD, including 477 who took dronedarone and 1519 who took other AADs. After a median follow-up of 38 months, 46.3% of patients who took dronedarone and 54.4% of patients who took other AADs experienced cardiovascular events. Compared to dronedarone, the use of other AADs was associated with increased cardiovascular events after adjusting for covariates (hazard ratio [HR] 1.531, 95% confidence interval [CI] 1.112-2.141, p = 0.023) and IPTW (HR 1.491, 95% CI 1.174-1.992, p = 0.012). The secondary analysis showed that amiodarone and class Ic drugs were associated with an increased risk of HHF. The low number of subjects in the sotalol group limits data interpretation., Conclusion: For patients with AF and CAD, dronedarone was associated with better cardiovascular outcomes than other AADs. Amiodarone and class Ic AADs were associated with a higher risk of cardiovascular events, particularly HHF., Competing Interests: Declaration of competing interest The corresponding author has full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Conflict of interests is none., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Hypertension is an important contributor to cardiovascular disease (CVD) in breast cancer (BC) survivors; however, research on blood pressure (BP) and CVD outcomes in BC survivors is limited., Objectives: The purpose of this study was to better characterize the association between BP and CVD in a large, longitudinal cohort of BC patients., Methods: Women with invasive BC diagnosed from 2005 to 2013 at Kaiser Permanente Northern California were matched 1:5 to women without BC. Patient data were obtained from electronic health records. Multivariable Cox regression and penalized spline models were used to explore the linear and nonlinear relationship of systolic blood pressure (SBP) and diastolic blood pressure (DBP) on CVD outcomes., Results: BC cases (n = 12,713) and controls (n = 55,886) had median follow-up of 9.6 years (IQR: 5.0-11.9 years). Women with BC had a mean age of 60.6 years; 64.8% were non-Hispanic White. For ischemic heart disease (IHD), every 10 mmHg increase in SBP and DBP was associated with 1.23 (95% CI: 1.14-1.33) and 1.10 (95% CI: 0.98-1.24) risk, respectively, in women with BC. For stroke, every 10 mmHg increase in SBP and DBP was associated with a 1.45 (95% CI: 1.34-1.58) and 1.91 (95% CI: 1.68-2.18) risk, respectively. A U-shaped relationship was observed between heart failure/cardiomyopathy and BP. The associations between BP and risk of IHD, stroke, and any primary CVD were not statistically different comparing women with BC to controls, but risks varied by BC status for heart failure/cardiomyopathy ( P for interaction = 0.01)., Conclusions: Women with and without BC showed similar risks for IHD, stroke, and any primary CVD suggesting similar BP targets should be pursued regardless of BC survivorship status., Competing Interests: The Pathways Heart Study is supported by the National Cancer Institute (R01 CA214057, U01CA195565). This publication was partially supported by a grant from Alpha Phi. The contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding agency. The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: There are many sex-specific factors affecting myocardial infarction (MI) outcomes in males and females. This study aimed to evaluate the relationship between reproductive factors and cardiovascular outcomes in women after ST-elevation MI., Method: This retrospective cohort study was initiated in 2016-2017 at Chamran Hospital, Isfahan, Iran. One hundred eighty women with a diagnosis of ST-elevation MI were followed up for 3 years, and any occurrence of cardiovascular events (CVs) was recorded. All information regarding reproductive factors was recorded via questionnaire. This information was compared between women with cardiovascular events and women without adverse events using a sample t test, chi-square test, and multiple backward logistic regression analysis. SPSS version 24 was used to conduct all analyses., Result: Sixty-four women with a mean age of 65.81 ± 13.14 years experienced CV events, and 116 women with a mean age of 65.51 ± 10.88 years did not experience CV events. A history of ischemic heart disease and diabetes mellitus were more prevalent in women with CV events (P = 0.024 and P = 0.019). After adjusting for ischemic heart disease and diabetes mellitus, oral contraceptive pill (OCP) usage was more prevalent in women with CV events than in women without CV events (60.9% vs. 40.4%, P = 0.008). There was a greater chance of CV events in women with OCP usage (OR = 3.546, P = 0.038) and a lower chance of CV events in women with greater age at menarche (OR = 0.630, P = 0.009) and longer breastfeeding duration (OR = 0.798, P = 0.041) according to multiple backward logistic regression models., Conclusion: Based on this study, OCP consumption is a risk factor, while older age at menarche and longer duration of breastfeeding are protective factors for cardiovascular outcomes in women after STEMI., (© 2024. The Author(s).)

Cardiovascular risks and complications remain elevated in patients with type 2 diabetes even after appropriate control of contributing factors like glycemic control, hypertension, and lipid profile. More efficient methods are needed to address this issue in type 2 diabetics. Newer drugs like glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have shown a cardioprotective effect in addition to glycemic control. This systematic review aims to study the latest literature findings on the cardiovascular effects of GLP-1 RAs in patients with type 2 diabetes. We used PubMed, Google Scholar, Science Direct, and Biomed Central databases for our data collection. Our review adheres to the 2020 Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines. The outcomes evaluated in the review include major adverse cardiovascular events (MACE), heart failure, stroke, all-cause mortality, and effects on cardiovascular risk factors. After careful inspection and quality check, we included 14 articles in the systematic review. GLP-1 RAs were associated with a significant reduction in cardiovascular mortality, all-cause mortality, nonfatal myocardial infarction (MI), and nonfatal stroke, especially in patients with existing cardiovascular risk factors. However, more evidence is required to determine if these benefits extend to those without such risk factors. Limited data suggest that GLP-1 RAs might have a protective effect on arrhythmias, but this area needs further investigation. Despite their potential, several barriers hinder the widespread use of GLP-1 RAs. In conclusion, GLP-1 RAs significantly reduce cardiovascular mortality, all-cause mortality, nonfatal MI, and stroke, with minor effects on hospitalization due to heart failure. Benefits are greater in patients with cardiovascular risk factors. A comprehensive, multilevel approach to policy development and implementation is necessary to optimize the use of these medications in eligible populations., Competing Interests: Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, Sreenivasan et al.)