Incidence of new onset type 2 diabetes in adults living with obesity treated with tirzepatide or semaglutide: real world evidence from an international retrospective cohort study.

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.

Dapagliflozin in Heart Failure and Acute Myocardial Infarction: A Systematic Review of the Association in Diabetic Patients.

This systematic review explores the impact of dapagliflozin on heart failure (HF) and acute myocardial infarction (MI) in patients with type 2 diabetes mellitus. By analyzing recent studies, including both randomized controlled trials (RCTs) and retrospective analyses, this review provides insights into the cardiovascular effects of this sodium-glucose cotransporter 2 (SGLT2) inhibitor. The findings consistently demonstrate the benefits of dapagliflozin in reducing HF-related hospitalizations and improving outcomes for patients with established HF. These positive effects appear to extend beyond glycemic control, suggesting multiple mechanisms of action. The impact of dapagliflozin on acute MI outcomes is less clear, with mixed results across studies. Importantly, dapagliflozin shows promise in improving the quality of life of patients and is generally well-tolerated. The review suggests that dapagliflozin may play a significant role in managing cardiovascular risk in diabetic patients, particularly those with or at risk of HF. While the evidence is encouraging, the review also highlights areas requiring further investigation. These include determining the patient subgroups most likely to benefit from dapagliflozin, elucidating the precise mechanisms underlying its cardioprotective effects, and carrying out long-term outcome studies.

The association of fatty liver index and metabolic syndrome with cardiovascular outcomes, liver-related mortality, and all-cause mortality: a nationwide cohort study.

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.

Blood Pressure and Cardiovascular Risk in Women With Breast Cancer: The Pathways Heart Study.

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.

The Imperative to Enhance Cost-Effectiveness for Cardiovascular Therapeutic Development.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide. Therapeutic agents, such as those that lower low-density lipoprotein cholesterol, have been a critical factor in mitigating CVD event risk and demonstrate the important role that drug discovery plays in reducing morbidity and mortality. However, rapidly rising development costs, diminishing returns, and an increasingly challenging regulatory environment have all contributed to a declining number of cardiovascular (CV) therapeutic agents entering the health care marketplace. For pharmaceutical companies, a traditional cardiovascular outcomes trial (CVOT) can be a major financial burden and impediment to CV agent development. They can take as long as a decade to conduct, delaying potential investment return while carrying risk of failure. For patients, lengthy CVOTs delay drug accessibility. Without cost-effective CVOTs, drug innovation may be compromised, with CV patients bearing the consequences. This paper reviews potential approaches for making CV drug development more cost-effective.

Effects of dipeptidyl peptidase 4 inhibitors on the risk of acute respiratory failure in patients with type 2 diabetes mellitus: a meta-analysis of cardiovascular outcomes trials.

Dipeptidyl peptidase 4 (DPP-4) inhibitors are new antidiabetic drugs. Their effects on the respiratory system remain unclear. This study aimed to determine the association between DDP-4 inhibitors and acute respiratory failure (ARF) among patients with type 2 diabetes mellitus (T2DM). A meta-analysis was performed by searching the PubMed, Embase, and CENTRAL databases up to July 3rd, 2024, to identify randomized controlled, double-blind, and placebo controlled-cardiovascular outcomes trials (CVOTs) that enrolled participants with T2DM. A total of 6,532 studies were initially retrieved; ultimately, 5 large CVOTs enrolling 47,714 adult T2DM patients were included in the meta-analysis. Overall, there were a nonsignificant increase in the risk of ARF in the DDP-4 inhibitor group compared with the placebo group (RR, 1.72; 95% CI, 0.59 to 4.97; p = 0.319). This is the first meta-analysis to evaluate the association between DDP-4 inhibitors and ARF among T2DM patients. In general, these findings suggest that DPP-4 inhibitors may slightly, but non-significantly, increase the risk of ARF in T2DM patients. As few studies are available and few ARF events occurred, further well-designed large-scale studies need to be performed.

Evaluating Cardiovascular Benefits of Glucagon-Like Peptide-1 Receptor Agonists (GLP-1 RAs) in Type 2 Diabetes Mellitus: A Systematic Review.

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.

Assessing the therapeutic and toxicological profile of novel GLP-1 receptor agonists for type 2 diabetes.

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.

Synergistically improved cardiovascular outcomes in type 2 diabetes mellitus patients with combined treatment of SGLT-2 inhibitors and pioglitazone.

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.

Impact of Early Invasive Strategy on Left Ventricular Function Recovery in Acute Myocardial Infarction Patients in Pakistan.

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.

Estimation of Serum Malondialdehyde (a Marker of Oxidative Stress) as a Predictive Biomarker for the Severity of Coronary Artery Disease (CAD) and Cardiovascular Outcomes.

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.

Assessing Cardiovascular Risk with Coronary Artery Calcium and Carotid Intima-Media Thickness in Patients with Negative Stress Echocardiography.

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.

Cardiovascular outcomes with semaglutide by severity of chronic kidney disease in type 2 diabetes: the FLOW trial.

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.

Risk of cardiovascular outcomes with bempedoic acid in high-risk statin intolerant patients: a systematic review and meta analysis.

Aim: Statin intolerance and myopathy is a major issue with prolonged use of statins myopathy. Bempedoic acid can be a good alternative for those intolerant to statins. This systematic review aims to observe incidence of major adverse cardiovascular events (MACE) and other adverse events, in high-risk statin intolerant patients receiving bempedoic acid. Methods: Literature search was conducted via Google Scholar, Science Direct and PubMed, after which screening, selection and data extraction of articles was done. Meta-analysis was performed on RevMan 5.4. Subgroup analysis was also conducted and heterogeneity was evaluated. Risk of bias was performed using ROB2 assessment scale. (CRD42024536827). Results: Only six randomized controlled trials were used in final analysis consisting of 17,844 patients. Treatment with bempedoic acid was associated with a reduced risk of MACE compared with placebo (RR 0.86; 95% CI [0.79, 0.94] p = 0.0005), with myocardial infarction significantly reduced. Incidence of adverse effects was increased with bempedoic acid (RR: 1.02; 95% [1.00, 1.03] p = 0.01) but no significant difference was observed. Incidence of myalgia was reduced in bempedoic group as well. Conclusion: Bempedoic acid is a safe and effective alternative to statins in high-risk patients intolerant to statins, decreasing the risk of MACE.

What is this summary about? Low density lipoprotein (LDL-C) also known as 'bad cholesterol', is the culprit behind many heart diseases. Statins are first-line treatment to reduce LDL-C. Despite being extremely effective, some people are intolerant and experience side effects such as sleep disorders, intestinal diseases and most commonly, effects on muscles ranging from muscle pain to breakdown of muscles leading to kidney damage. Bempedoic acid is a once-a-day medication, increasing LDL-C clearance from blood, reducing the risk of heart attack and diabetes and is effective for patients intolerant to statins. This article provides insights into incidences of major heart-related, and other adverse events in patients receiving bempedoic acid.What were the results? Muscle pain and major heart-related events were reduced (especially heart attack) in patients receiving bempedoic acid as compared with those receiving placebos. Muscle weakness and other adverse events were seen in patients receiving bempedoic acid, but serious adverse events were not significantly different from those receiving placebos.What do the results mean? Bempedoic acid is a safe and effective treatment that can be given to patients who cannot tolerate statins or develop side effects to it, as it reduces the risk of heart-related adverse events.

Ashwagandha's Multifaceted Effects on Human Health: Impact on Vascular Endothelium, Inflammation, Lipid Metabolism, and Cardiovascular Outcomes-A Review.

Withania somnifera, commonly known as Ashwagandha, has been popular for many years. Numerous studies have shown that the extract of this plant, due to its wealth of active substances, can induce anti-inflammatory, neuroprotective, immunomodulatory, hepatoprotective, cardioprotective, anti-diabetic, adaptogenic, anti-arthritic, anti-stress, and antimicrobial effects. This review examines the impact of Ashwagandha extract on the vascular endothelium, inflammation, lipid metabolism, and cardiovascular outcomes. Studies have shown that Ashwagandha extracts exhibit an anti-angiogenic effect by inhibiting vascular endothelial growth factor (VEGF)-induced capillary sprouting and formation by lowering the mean density of microvessels. Furthermore, the results of numerous studies highlight the anti-inflammatory role of Ashwagandha extract, as the action of this plant causes a decrease in the expression of pro-inflammatory cytokines. Interestingly, withanolides, present in Ashwagandha root, have shown the ability to inhibit the differentiation of preadipocytes into adipocytes. Research results have also proved that W. somnifera demonstrates cardioprotective effects due to its antioxidant properties and reduces ischemia/reperfusion-induced apoptosis. It seems that this plant can be successfully used as a potential treatment for several conditions, mainly those with increased inflammation. More research is needed to elucidate the exact mechanisms by which the substances contained in W. somnifera extracts can act in the human body.

Reproductive factors and risk of cardiovascular outcomes in women with ST-elevation myocardial infarction.

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.

Levothyroxine Treatment of Subclinical Hypothyroidism and the Risk of Adverse Cardiovascular Events.

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.

Associations of SGLT-2i with Cardiorenal Outcomes Among Diabetics with Prostate Cancer on Hormone Therapy.

Background: 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 two years from HT initiation. Results: After propensity score matching, 2,155 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 (HR 0.689, 95% CI 0.582-0.816; 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.

Diagnostic and prognostic value of triglyceride glucose index: a comprehensive evaluation of meta-analysis.

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.

Monoclonal Gammopathy of Undetermined Significance and Associated Cardiovascular Outcomes in a Hospital Setting-A Fresh Perspective.

There is a paucity of data on the cardiovascular implications of monoclonal gammopathy of undetermined significance, especially among hospitalized patients. Our study aimed to investigate the association between MGUS and cardiovascular outcomes in a hospital setting using the National Inpatient Sample database. MGUS patients were sampled using ICD-10 codes. The patients were stratified into two cohorts based on the presence or absence of MGUS. Comorbidities and cardiovascular outcomes were collected using ICD 10 DM codes. CV outcomes were evaluated before and after 1:1 matching for age, gender, and race. Furthermore, a sensitivity analysis was performed on the matched population, which excluded patients with diabetes mellitus, prior myocardial infarction, chronic kidney disease (stages 3-5), dialysis, hypertension, obesity, metabolic syndrome, cancer, antiplatelets, and oral anticoagulant use and was adjusted for smoking, dyslipidemia, and aspirin use to evaluate the cardiovascular outcomes. MGUS patients had more heart failure, atrial fibrillation, venous thromboembolism, aortic aneurysm, aortic stenosis, aortic regurgitation, mitral stenosis, mitral regurgitation, conduction disorder, cor pulmonale, peripheral vascular disease, and acute myocardial infarction. After matching, MGUS was associated with heart failure, atrial fibrillation, venous thromboembolism, aortic stenosis, mitral regurgitation, conduction disorder, cor pulmonale, and peripheral vascular disease. MGUS was linked to a wide spectrum of cardiovascular diseases in an inpatient setting. Further studies are needed to formulate appropriate recommendations for the screening and management of cardiovascular complications in individuals with MGUS.