Reduction In Cardiovascular Events Research Articles

Long-term kidney outcomes of semaglutide in obesity and cardiovascular disease in the SELECT trial.

The SELECT trial previously reported a 20% reduction in major adverse cardiovascular events with semaglutide (n = 8,803) versus placebo (n = 8,801) in patients with overweight/obesity and established cardiovascular disease, without diabetes. In the present study, we examined the effect of once-weekly semaglutide 2.4 mg on kidney outcomes in the SELECT trial. The incidence of the pre-specified main composite kidney endpoint (death from kidney disease, initiation of chronic kidney replacement therapy, onset of persistent estimated glomerular filtration rate (eGFR) < 15 ml min-1 1.73 m-2, persistent ≥50% reduction in eGFR or onset of persistent macroalbuminuria) was lower with semaglutide (1.8%) versus placebo (2.2%): hazard ratio (HR) = 0.78; 95% confidence interval (CI) 0.63, 0.96; P = 0.02. The treatment benefit at 104 weeks for eGFR was 0.75 ml min-1 1.73 m-2 (95% CI 0.43, 1.06; P < 0.001) overall and 2.19 ml min-1 1.73 m-2 (95% CI 1.00, 3.38; P < 0.001) in patients with baseline eGFR <60 ml min-1 1.73 m-2. These results suggest a benefit of semaglutide on kidney outcomes in individuals with overweight/obesity, without diabetes.ClinicalTrials.gov identifier: NCT03574597 .

#1447 Calcimimetics improve impaired cardiac function and contractility in chronic phosphate loading by activating the CaSR/cAMP signaling cascade

Abstract Background and Aims High phosphate loading stimulate the synthesis of PTH and FGF23 and is associated with increased cardiovascular (CV) mortality. In hemodialysis patients, the administration of calcimimetics led to reductions in PTH and FGF23 and the latter was associated with a lower rate of CV events. We have previously shown that mice with a high dietary phosphate load show elevated PTH and FGF23 levels and develop impaired systolic cardiac function, which could be improved by calcimimetics. Calcimimetics are allosteric activators of the calcium-sensing receptor (CaSR). Phosphate (Pi) was shown to inactivate the parathyroid CaSR at concentrations &amp;gt;1.4 mM Pi. Whether calcimimetics contribute to CV event reduction indirectly via lowering PTH and FGF23 or directly via activation of the cardiac CaSR is unknown. Method Wild-type mice were fed a high phosphate diet (HPD) ± etelcalcetide (Etl) or a normal phosphate diet (NPD), cardiac function was assessed by echocardiography and Millar catheterization, and cardiac tissue was harvested for histology and RNAseq analyses. In addition, isolated adult mouse cardiomyocytes (AMCM) were stimulated ex vivo with PTH, FGF23 or Pi, contractility and calcium handling were measured with the addition of Etl and activity analyses were performed. Results In addition to the positive effect on HPD-induced systolic cardiac dysfunction, Etl improved impaired LV contractility and reduced fibrosis. RNAseq analyses revealed reduced Ca, PKA and cAMP signaling by HPD. Ex vivo stimulation of AMCM with PTH and FGF23 had no functional effects. In contrast, Pi significantly worsened contractility and Ca handling, which was blunted by Etl co-stimulation. Downstream of cardiac CaSR, Pi reduced the formation of cAMP, which led to PKA-dependent dephosphorylation of PLN and subsequently to lower Serca2a activity, which was ultimately responsible for the reduced contractility. Etl led to improved cardiomyocyte contractility via increased cAMP synthesis and increased PLN phosphorylation and Serca2a activity. Conclusion Our data suggest that Etl ameliorates the Pi-induced pathologic cardiac phenotype associated with high phosphate load via direct activation of CaSR/cAMP signaling cascade, resulting in improvement of cardiomyocyte contractility.

Impact of metabolic bariatric surgery on outcomes and the 10-year risk of major adverse cardiovascular events during a 7-year period: a retrospective cohort study.

Metabolic bariatric surgery offers enduring weight reduction and alleviation of obesity-related comorbidities, including dyslipidemia, diabetes, hypertension, and major adverse cardiovascular events (MACE). Long-term data on one-anastomosis gastric bypass (OAGB) and single-anastomosis duodenal-jejunal bypass with sleeve gastrectomy (SADJB-SG) is lacking, necessitating this investigation. In this multicenter prospectively-collected retrospective observational study, 830 adult Taiwanese patients (682 OAGB, 148 SADJB-SG) who underwent surgery from January 1, 2011, to December 31, 2017, were initially identified. Following protocol, 224 patients (177 OAGB, 47 SADJB-SG) with complete follow-up data at various intervals up to three years after surgery were included in the final analysis. The study's primary focus is to evaluate the long-term safety, efficacy, and durability of OAGB and SADJB-SG in promoting weight loss and diabetes remission. Additionally, changes in 10-year and lifetime risks of MACE before and 3-year after surgery are assessed using Taiwan MACE risk prediction model and the China-PAR project model. SADJB-SG patients exhibit higher diabetes prevalence, lower body mass index, and more severe diabetes compared to OAGB. Both groups demonstrate significant improvements in body mass index, diabetes, hypertension, and dyslipidemia three years after surgery, with the most substantial improvements occurring in the second year. The Taiwan MACE risk model reveals a significant reduction in 10-year MACE and stroke risks for both groups. The China-PAR project model indicates a synchronized reduction in atherosclerotic cardiovascular disease 10-year and lifetime risk in both OAGB and SADJB-SG groups. OAGB and SADJB-SG exhibit sustained improvements in weight reduction and obesity-related comorbidities over three years after surgery. Notably, both procedures contribute to a substantial reduction in 10-year MACE, stroke, and atherosclerotic cardiovascular disease risks. These findings underscore the efficacy of OAGB and SADJB-SG in the context of metabolic bariatric surgery.

Dapagliflozin Improves Angiogenesis after Hindlimb Ischemia through the PI3K-Akt-eNOS Pathway.

Recently, the vascular protective effect of anti-diabetic agents has been receiving much attention. Sodium glucose cotransporter 2 (SGLT2) inhibitors had demonstrated reductions in cardiovascular (CV) events. However, the therapeutic effect of dapagliflozin on angiogenesis in peripheral arterial disease was unclear. This study aimed to explore the effect and mechanism of dapagliflozin on angiogenesis after hindlimb ischemia. We first evaluated the effect of dapagliflozin on post-ischemic angiogenesis in the hindlimbs of rats. Laser doppler imaging was used to detect the hindlimb blood perfusion. In addition, we used immunohistochemistry to detect the density of new capillaries after ischemia. The relevant signaling pathways of dapagliflozin affecting post-ischemic angiogenesis were screened through phosphoproteomic detection, and then the mechanism of dapagliflozin affecting post-ischemic angiogenesis was verified at the level of human umbilical vein endothelial cells (HUVECs). After subjection to excision of the left femoral artery, all rats were randomly distributed into two groups: the dapagliflozin group (left femoral artery resection, receiving intragastric feeding with dapagliflozin (1 mg/kg/d), for 21 consecutive days) and the model group, that is, the positive control group (left femoral artery resection, receiving intragastric feeding with citric acid-sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days). In addition, the control group, that is the negative control group (without left femoral artery resection, receiving intragastric feeding with citric acid-sodium citrate buffer solution (1 mg/kg/d), for 21 consecutive days) was added. At day 21 post-surgery, the dapagliflozin-treatment group had the greatest blood perfusion, accompanied by elevated capillary density. The results showed that dapagliflozin could promote angiogenesis after hindlimb ischemia. Then, the ischemic hindlimb adductor-muscle tissue samples from three rats of model group and dapagliflozin group were taken for phosphoproteomic testing. The results showed that the PI3K-Akt-eNOS signaling pathway was closely related to the effect of dapagliflozin on post-ischemic angiogenesis. Our study intended to verify this mechanism from the perspective of endothelial cells. In vitro, dapagliflozin enhanced the tube formation, migration, and proliferation of HUVECs under ischemic and hypoxic conditions. Additionally, the dapagliflozin administration upregulated the expression of angiogenic factors phosphorylated Akt (p-Akt) and phosphorylated endothelial nitric oxide synthase (p-eNOS), as well as vascular endothelial growth factor A (VEGFA), both in vivo and in vitro. These benefits could be blocked by either phosphoinositide 3-kinase (PI3K) or eNOS inhibitor. dapagliflozin could promote angiogenesis after ischemia. This effect might be achieved by promoting the activation of the PI3K-Akt-eNOS signaling pathway. This study provided a new perspective, new ideas, and a theoretical basis for the treatment of peripheral arterial disease.

Long-term weight loss effects of semaglutide in obesity without diabetes in the SELECT trial.

In the SELECT cardiovascular outcomes trial, semaglutide showed a 20% reduction in major adverse cardiovascular events in 17,604 adults with preexisting cardiovascular disease, overweight or obesity, without diabetes. Here in this prespecified analysis, we examined effects of semaglutide on weight and anthropometric outcomes, safety and tolerability by baseline body mass index (BMI). In patients treated with semaglutide, weight loss continued over 65 weeks and was sustained for up to 4 years. At 208 weeks, semaglutide was associated with mean reduction in weight (-10.2%), waist circumference (-7.7 cm) and waist-to-height ratio (-6.9%) versus placebo (-1.5%, -1.3 cm and -1.0%, respectively; P < 0.0001 for all comparisons versus placebo). Clinically meaningful weight loss occurred in both sexes and all races, body sizes and regions. Semaglutide was associated with fewer serious adverse events. For each BMI category (<30, 30 to <35, 35 to <40 and ≥40 kg m-2) there were lower rates (events per 100 years of observation) of serious adverse events with semaglutide (43.23, 43.54, 51.07 and 47.06 for semaglutide and 50.48, 49.66, 52.73 and 60.85 for placebo). Semaglutide was associated with increased rates of trial product discontinuation. Discontinuations increased as BMI class decreased. In SELECT, at 208 weeks, semaglutide produced clinically significant weight loss and improvements in anthropometric measurements versus placebo. Weight loss was sustained over 4 years. ClinicalTrials.gov identifier: NCT03574597 .

Routine Functional Testing or Standard Care in High-Risk Patients after Percutaneous Coronary Intervention.

This review aimed to collate the available evidence on outcomes following routine functional stress testing vs standard of care (i.e. symptom-guided stress testing) in high-risk patients following percutaneous coronary intervention (PCI). The most recent pragmatic POST-PCI trial provided randomized evidence showing that routine functional stress testing post-PCI did not lead to a reduction in 2-year ischemic cardiovascular events or all-cause mortality, as compared to a symptom-guided standard-of-care approach. This was also true for sub-analyses including multivessel or left main disease, diabetics, as well as following imaging or physiology guided PCI. In the absence of a change in their clinical or functional status suggestive of stent failure, post-PCI routine periodic stress testing in stable patients on guideline-directed medical therapy is currently not recommended by American clinical practice guidelines. While evidence on the cost-effectiveness of routine stress testing strategy is scarce, physician, payer, and policy-level interventions to reduce inappropriate use of routine functional testing need to be addressed.

Balancing Innovation and Affordability in Anti-Obesity Medications: The Role of Alternative Weight Maintenance Program

Abstract Despite remarkable clinical advances in highly effective anti-obesity medications, their high price and potential budget impact pose a major challenge in balancing equitable access and affordability. While most attention has been focused on the amount of weight loss achieved, less consideration has been paid to interventions to sustain weight loss after an individual stops losing weight. Using a policy simulation model, we quantified the impact of a weight maintenance program following the weight loss plateau from the initial full-dose GLP-1s or incretin mimetic use on long-term health care savings and the loss of some health benefits (e.g., maintenance of weight loss, improvements in cardiometabolic risk factors, and reductions in diabetes and cardiovascular events). Our model suggested that compared to continuous long-term full-dose GLP-1s or incretin mimetic drugs, the alternative weight maintenance program would generate slightly fewer clinical benefits while generating substantial savings in lifetime health care spending. Using less expensive and potentially less effective alternative weight maintenance programs may provide additional headroom to expand access to anti-obesity medications during the active weight-loss phase without increasing total health care spending.

Classical and Novel Lipid-Lowering Therapies for Diabetic Patients with Established Coronary Artery Disease or High Risk of Coronary Artery Disease-A Narrative Clinical Review.

Diabetic atherosclerosis is a complex process that is characterized by diffuse and unstable lesions increasing 2-4-fold the risk of adverse cardiovascular (CV) events. Diabetic dyslipidemia has a predominant role in coronary artery disease (CAD) and has been the target of classical and emerging pharmaceutical agents with established or promising CV benefits. The aim of the present narrative review was to summarize the effects of classical and novel lipid-lowering pharmaceutical agents on lipid profile and CV outcomes in diabetic patients with established CAD or high risk of CAD. Statins remain the first-line treatment for all diabetic patients since they considerably ameliorate lipid parameters and non-lipid CV risk factors, leading to reduced CV morbidity and mortality. Complementary to statins, ezetimibe exerts lipid-lowering properties with modest but significant reductions in major adverse cardiovascular events (MACEs) and CV mortality. PCSK9 inhibitors considerably reduce LDL-C levels and lower MACEs in diabetic patients. On the other hand, fibrates may confer a very modest decline in MACE incidence, while the CV impact of omega-3 fatty acids is promising but remains questionable. Bempedoic acid and inclisiran have a potential therapeutic role in the management of diabetic dyslipidemia, but this is still not adequately documented. Given the heightened CV risk among individuals with diabetes, more decisive results would be of great importance in the utility of all these drugs.

Factors Associated With Coronary Angiography Performed Within 6 Months of Randomization to the Conservative Strategy in the ISCHEMIA Trial.

ISCHEMIA (International Study of Comparative Health Effectiveness With Medical and Invasive Approaches) did not find an overall reduction in cardiovascular events with an initial invasive versus conservative management strategy in chronic coronary disease; however, there were conservative strategy participants who underwent invasive coronary angiography early postrandomization (within 6 months). Identifying factors associated with angiography in conservative strategy participants will inform clinical decision-making in patients with chronic coronary disease. Factors independently associated with angiography performed within 6 months of randomization were identified using Fine and Gray proportional subdistribution hazard models, including demographics, region of randomization, medical history, risk factor control, symptoms, ischemia severity, coronary anatomy based on protocol-mandated coronary computed tomography angiography, and medication use. Among 2591 conservative strategy participants, angiography within 6 months of randomization occurred in 8.7% (4.7% for a suspected primary end point event, 1.6% for persistent symptoms, and 2.6% due to protocol nonadherence) and was associated with the following baseline characteristics: enrollment in Europe versus Asia (hazard ratio [HR], 1.81 [95% CI, 1.14-2.86]), daily and weekly versus no angina (HR, 5.97 [95% CI, 2.78-12.86] and 2.63 [95% CI, 1.51-4.58], respectively), poor to fair versus good to excellent health status (HR, 2.02 [95% CI, 1.23-3.32]) assessed with Seattle Angina Questionnaire, and new/more frequent angina prerandomization (HR, 1.80 [95% CI, 1.34-2.40]). Baseline low-density lipoprotein cholesterol <70 mg/dL was associated with a lower risk of angiography (HR, 0.65 [95% CI, 0.46-0.91) but not baseline ischemia severity nor the presence of multivessel or proximal left anterior descending artery stenosis >70% on coronary computed tomography angiography. Among ISCHEMIA participants randomized to the conservative strategy, angiography within 6 months of randomization was performed in <10% of patients. It was associated with frequent or increasing baseline angina and poor quality of life but not with objective markers of disease severity. Well-controlled baseline low-density lipoprotein cholesterol was associated with a reduced likelihood of angiography. These findings point to the importance of a comprehensive assessment of symptoms and a review of guideline-directed medical therapy goals when deciding the initial treatment strategy for chronic coronary disease. URL: https://www.clinicaltrials.gov; Unique identifier: NCT01471522.

Vericiguat suppresses ventricular tachyarrhythmias inducibility in a rabbit myocardial infarction model.

The VICTORIA trial demonstrated a significant decrease in cardiovascular events through vericiguat therapy. This study aimed to assess the potential mechanisms responsible for the reduction of cardiovascular events with vericiguat therapy in a rabbit model of myocardial infarction (MI). A chronic MI rabbit model was created through coronary artery ligation. Following 4 weeks, the hearts were harvested and Langendorff perfused. Subsequently, electrophysiological examinations and dual voltage-calcium optical mapping studies were conducted at baseline and after administration of vericiguat at a dose of 5 μmol/L. Acute vericiguat therapy demonstrated a significant reduction in premature ventricular beat burden and effectively suppressed ventricular arrhythmic inducibility. The electrophysiological influences of vericiguat therapy included an increased ventricular effective refractory period, prolonged action potential duration, and accelerated intracellular calcium (Cai) homeostasis, leading to the suppression of action potential and Cai alternans. The pacing-induced ventricular arrhythmias exhibited a reentrant pattern, attributed to fixed or functional conduction block in the peri-infarct zone. Vericiguat therapy effectively mitigated the formation of cardiac alternans as well as the development of reentrant impulses, providing additional anti-arrhythmic benefits. In the MI rabbit model, vericiguat therapy demonstrates anti-ventricular arrhythmia effects. The vericiguat therapy reduces ventricular ectopic beats, inhibiting the initiation of ventricular arrhythmias. Furthermore, the therapy successfully suppresses cardiac alternans, preventing conduction block and, consequently, the formation of reentry circuits.

Statins As Anti-Hypertensive Therapy: A Systematic Review and Meta-Analysis.

Hypertension is the most prevalent condition in clinical practice. Hypertension, diabetes, and hypercholesterolaemia are major contributing factors to cardiovascular diseases. They commonly coexist in a single patient. Statins have been used as prominent medicines for the reduction of cardiovascular events. Statins have been shown to reduce blood pressure in patients with hypertension and have lipid-lowering properties in recent articles. Statins reduce blood pressure because of their impact on endothelial function, their interactions with the renin-angiotensin system, and their influence on major artery compliance. This meta-analysis aimed to ascertain the effectiveness and efficacy of statins for managing hypertension in patients with hypertension. Systematic searches were conducted on PubMed, Science Direct, Embase, Cochrane Library, and Google Scholar. Randomized controlled trials, systematic trials, and cohort studies were retrieved using keywords on statins and their use in patients with hypertension. Exclusion criteria included studies that were not in the English language, studies that did not include patients on statins with hypertension, studies that did not provide enough information, technical reports, opinions, or editorials, and studies involving patients < 18 years old. The inclusion criteria were randomized controlled trials, meta-analyses, adult patients aged > 18 years old, and studies that were freely available or through institutional login. This meta-analysis scrutinized 9361 randomized controlled trials, clinical trials, meta-analyses, and systematic reviews, of which 32 articles including 25 randomized controlled trials and seven meta-analyses were included in the final analysis. This meta-analysis of the role of statins in hypertensive patients aimed to determine the outcome of hypertension control along with antihypertensive medication. Our study showed that statins are useful in reducing both systolic and diastolic blood pressure. We used a heterogeneous model for analysis due to variations in the study characteristics. The I2 value was 0.33 (0.76, 0.10) for systolic blood pressure and 0/88 (0.86, 0.90) for diastolic blood pressure. The I2 value for the seven meta-analyses included in the study was 1.79 (2.88, 0.69).

Colchicine for the Prevention of Cardiovascular Disease: Potential Global Implementation.

Targeting traditional cardiovascular risk factors is effective in reducing recurrent cardiovascular events, yet the presence of residual cardiovascular risk due to underlying systemic inflammation is a largely unaddressed opportunity. This review aims to comprehensively assess the evolving role of colchicine as a therapeutic approach targeting residual inflammatory risk in the context of those with coronary artery disease (CAD). Inflammation plays a significant role in promoting atherosclerosis, and targeting anti-inflammatory pathways has the potential to decrease cardiovascular events. Low-dose colchicine (0.5mg/day orally), when added to guideline-directed medical care for CAD, safely decreases major adverse cardiovascular events (MACE) by 31% in stable atherosclerosis patients and 23% in those after recent myocardial infarctions. Meta-analyses of recent randomized control trials further support both the efficacy and safety of colchicine, particularly when added to other standard cardiovascular therapies, including statin therapy. The European Society of Cardiology and other national guidelines endorse the use of low-dose colchicine in patients across the spectrum of CAD. Recently, colchicine was FDA-approved in the United States as the first anti-inflammatory therapy for the reduction of cardiovascular events. In a period of a rising incidence of CAD across the globe, colchicine represents a unique opportunity to decrease MACE due to its large magnitude of benefits and general affordability. However, challenges with drug interactions must be addressed, especially in those regions where HIV, hepatitis, and tuberculosis are prevalent. Colchicine is safe and effective at reducing cardiovascular events across a broad spectrum of coronary syndromes. The ability to simultaneously target traditional risk factors and mitigate residual inflammatory risk marks a substantial advancement in cardiovascular prevention strategies, heralding a new era in the global battle against CAD.

Alirocumab and cardiovascular outcomes according to sex and lipoprotein(a) after acute coronary syndrome: ODYSSEY OUTCOMES

BackgroundThe ODYSSEY OUTCOMES trial (NCT01663402) compared the effects of the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo on major adverse cardiovascular events (MACE) in patients with recent acute coronary syndrome (ACS). ObjectiveWe assessed efficacy and safety of alirocumab versus placebo according to sex and lipoprotein(a) level. MethodsThis prespecified analysis compared the effects of alirocumab versus placebo on lipoproteins, MACE (coronary heart disease death, non-fatal myocardial infarction, fatal/non-fatal ischemic stroke, unstable angina requiring hospitalization), death, total cardiovascular events, and adverse events in 4762 women and 14,162 men followed for a median of 2.8 years. In post-hoc analysis, we evaluated total cardiovascular events according to sex, baseline lipoprotein(a), and treatment. ResultsWomen were older, had higher baseline LDL-C levels (89.6 vs 85.3 mg/dL) and lipoprotein(a) (28.0 vs 19.3 mg/dL) and had more co-morbidities than men. At 4 months, alirocumab lowered LDL-C by 49.4 mg/dL in women and 54.0 mg/dL in men and lipoprotein(a) by 9.7 and 8.1 mg/dL, respectively (both p < 0.0001). Alirocumab reduced MACE, death, and total cardiovascular events similarly in both sexes. In the placebo group, lipoprotein(a) was a risk factor for total cardiovascular events in women and men. In both sexes, reduction of total cardiovascular events was greater at higher baseline lipoprotein(a), but this effect was more evident in women than men (pinteraction=0.08). Medication adherence and adverse event rates were similar in both sexes. ConclusionsAlirocumab improves cardiovascular outcomes after ACS irrespective of sex. SummaryAfter recent ACS, addition of alirocumab to GDMT improves outcomes consistently in women and men. Reduction of total cardiovascular events was greater at higher baseline Lp(a).

Antithrombotic therapy in acute coronary syndrome

Dual antiplatelet therapy (DAPT) is the cornerstone of maintenance medication following acute coronary syndromes (ST elevation myocardial infarction, non-ST elevation myocardial infarction, unstable angina). Over the last decade, P2Y12 inhibition in addition to low-dose acetylsalicylic acid has been intensively debated. In patients with acute coronary syndromes, balancing the reduction in cardiovascular events and increase in major bleeding during treatment with more potent P2Y12 inhibitors such as prasugrel and ticagrelor is still an issue. A special focus is on patients already treated with oral anticoagulants for stroke prevention in atrial fibrillation who require additional platelet inhibition following coronary stenting. This article summarizes the major recommendations given in the most recent Guideline for "Acute Coronary Syndromes" published by the European Society of Cardiology (ESC). The recommendations finally address strategies to reduce an increased bleeding risk based on clinical predictors.

Cardiovasculoprotective Effects of Estrogen and its Use as Hormonal Replacement Therapy

Epidemiologic studies have shown that the incidence of cardiovascular disease is closely related to gender. This is because endogenous estrogens have broad effects on the circulatory system, leading to the hypothesis that estrogens are cardiovascular protective, underlying their use as hormone replacement therapy (HRT) to reduce the incidence of cardiovascular disease. However, large prospective clinical trials (HERS and WHI) do not support this. This review aims to better understand the cardiovascularoprotective effects of estrogen and answer the question of whether estrogen can be used as hormonal replacement therapy in post-menopausal women to prevent cardiovascular events by incorporating data from the most recent prospective clinical trial, the KEEPS study. HERS and WHI reported no reduction in cardiovascular events in postmenopausal women using HRT, even showing an increased risk of thromboembolism. This study was criticized because participants had been menopausal for 12 years, so the KEEPS study was conducted with participants within three years of menopause, with the result that there was no significant reduction in the progression of atherosclerosis between the HRT group and the placebo group. The KEEPS study states that HRT is safe, and no thromboembolic events were found. Although endogenous estrogen has cardiovascular protective effects, estrogen hormone therapy cannot reduce cardiovascular events in postmenopausal women despite metabolic improvements and beneficial effects such as improvement of postmenopausal-related symptoms, maintaining bone density, and improving sexual function.

Understanding The Role of SGLT2 Inhibitors in Cardiovascular Risk Reduction for Type 2 Diabetes Patients-A Literature Review

Introduction: Type 2 diabetes mellitus (T2DM) is associated with an increased risk of cardiovascular events and heart failure. Sodium-glucose cotransporter 2 (SGLT2) inhibitors have emerged as a novel class of antidiabetic agents with potential cardiovascular benefits. This systematic review aims to evaluate the impact of SGLT2 inhibitors on reducing cardiovascular events and heart failure hospitalizations in patients with T2DM. Aims: The review aims to comprehensively evaluate the impact of SGLT2 inhibitors on reducing cardiovascular events, including MACE, and HF hospitalizations in patients with T2DM. Methods: A comprehensive literature search was conducted in major electronic databases like PubMed, Google Scholar and Science Direct to identify relevant studies. Studies investigating the cardiovascular outcomes of SGLT2 inhibitors in T2DM patients were included. Data extraction and quality assessment were performed independently by three reviewers using predefined criteria. Results: A total of 17 studies met the inclusion criteria and were included in the review. The analysis of clinical trials, including EMPA-REG OUTCOME, CANVAS Program, and DECLARE-TIMI 58, demonstrated significant reductions in MACE and HF hospitalizations with SGLT2 inhibitors compared to placebo or standard care. Real-world evidence from studies such as the CVD-REAL and EASEL studies further supported these findings, showing consistent cardiovascular benefits of SGLT2 inhibitors in routine clinical practice. The findings suggest that SGLT2 inhibitors are associated with a reduction in cardiovascular events, including myocardial infarction, stroke, and cardiovascular mortality, as well as a decreased risk of heart failure hospitalizations in patients with T2DM. Conclusion: This systematic review provides evidence supporting the cardiovascular benefits of SGLT2 inhibitors in T2DM management. The findings underscore the importance of considering these agents as part of comprehensive cardiovascular risk reduction strategies in T2DM patients. Further research is necessary to explicate the mechanisms underlying these benefits and optimize their clinical use.

The Net Clinical Outcome of Dual-Pathway Inhibition in Clinical Practice: The "Xarelto plus Acetylsalicylic Acid: Treatment Patterns and Outcomes in Patients with Atherosclerosis" Registry.

Background: In the COMPASS trial, the combination of acetylsalicylic acid (ASA) plus 2.5 mg rivaroxaban twice daily (dual-pathway inhibition, DPI) has been shown to be superior to ASA monotherapy for the reduction in ischemic major adverse cardiovascular events (MACEs, i.e., cardiovascular death, stroke, or myocardial infarction). Methods: The international XATOA registry (Xarelto plus Acetylsalicylic acid: Treatment patterns and Outcomes in patients with Atherosclerosis) is a prospective post-approval registry that investigates the cardiovascular outcomes of patients taking ASA plus 2.5 mg rivaroxaban. The aim of this pre-specified analysis was to determine the net clinical outcome (NCO), i.e., a combination of MACEs and bleeding events, of DPI in patients from daily clinical practice. Results: Among the 5615 patients, the presence of multiple risk factors resulted in an increase in the total risk of experiencing an NCO event, e.g., from 1.27% (one risk factor) to 2.18% (two risk factors) and 4.07% (three or more risk factors), respectively, with ischemic MACE representing the primary driver of bleeding complications. Conclusions: In the real-world XATOA registry, the annual rate of NCO events was low and numerically similar to those seen in the treatment group in the randomized COMPASS trial.

Bridging Metabolic-Associated Steatotic Liver Disease and Cardiovascular Risk: A Potential Role for Ketogenesis.

The prevalence of cardiovascular diseases (CVDs) is a growing global health concern. Recent advances have demonstrated significant reductions in acute cardiovascular events through the management of modifiable cardiovascular risk factors. However, these factors are responsible for about 50% of the global cardiovascular disease burden. Considering that CVDs are one of the top mortality causes worldwide, the concept of residual cardiovascular risk is an important emerging area of study. Different factors have been proposed as sources of residual risk markers, including non-HDL particles characterization, as well as inflammation measured by serum and imaging technics. Among these, metabolic-associated steatotic liver disease (MASLD) remains controversial. Two opposing viewpoints contend: one positing that fatty liver disease merely reflects classical risk factors and thus adds no additional risk and another asserting that fatty liver disease independently impacts cardiovascular disease incidence. To address this dilemma, one hypothetical approach is to identify specific hepatic energy-yielding mechanisms and assess their impact on the cardiovascular system. Ketogenesis, a metabolic intermediate process particularly linked to energy homeostasis during fasting, might help to link these concepts. Ketogenic metabolism has been shown to vary through MASLD progression. Additionally, newer evidence supports the significance of circulating ketone bodies in cardiovascular risk prediction. Furthermore, ketogenic metabolism modification seems to have a therapeutic impact on cardiovascular and endothelial damage. Describing the relationship, if any, between steatotic liver disease and cardiovascular disease development through ketogenesis impairment might help to clarify MASLD's role in cardiovascular risk. Furthermore, this evidence might help to solve the controversy surrounding liver steatosis impact in CVD and might lead to a more accurate risk assessment and therapeutic targets in the pursuit of precision medicine.

Alcohol, health loss, and mortality: can wine really save the good name of moderate alcohol consumption?

It is estimated that one‑third of the world's population consumes alcohol. At the same time, it is well‑known that excessive alcohol consumption in one of the leading causes of premature mortality. The history of production of alcoholic beverages, especially wine, dates back as long as 8000 years. However, people soon realized adverse effects of alcohol abuse and tried to limit its consumption. Higher alcohol consumption is associated with health loss and increased risk of all‑cause mortality. It is linearly associated with a greater risk of many types of cancers, liver disease, incidence of atrial fibrillation, hemorrhagic stroke, or heart failure. Although many scientific societies recommend reduction of alcohol intake and specify the recommended limits of consumption, there is no proven safe amount of alcohol for the general population. There are conflicting data on the effect of low‑to‑moderate alcohol consumption on mortality, with most of the studies indicating a J‑shaped curve related mostly to a reduction of coronary artery disease complications, including cardiovascular death. Among different types of alcohol, red wine consumption may have different health effects, due to its high content of antioxidative polyphenols. Wine, together with abundance of plant‑based foods, olive oil, and fish, is an important part of the Mediterranean diet. There are both observational and randomized studies documenting a wide spectrum of health‑promoting effects of such a diet, especially a reduction in major adverse cardiovascular events. People who want to drink alcohol should be advised to limit their consumption to a minimum, and should consider choosing red wine.

Cardiac Rehabilitation Increases Plasma Klotho Levels.

Background: Mineral metabolism (MM), mainly fibroblast growth factor-23 (FGF-23) and klotho, has been linked to cardiovascular (CV) diseases. Cardiac rehabilitation (CR) has been demonstrated to reduce CV events, although its potential relationship with changes in MM is unknown. Methods: We performed a prospective, observational, case-control study, with acute coronary syndrome (ACS) patients who underwent CR and control patients (matched by age, gender, left ventricular ejection fraction, diabetes, and coronary artery bypass grafting), who did not. The inclusion dates were from August 2013 to November 2017 in CR group and from July 2006 to June 2014 in control group. Clinical, biochemical, and MM biomarkers were collected at discharge and six months later. Our objective was to evaluate differences in the modification pattern of MM in both groups. Results: We included 58 CR patients and 116 controls. The control group showed a higher prevalence of hypertension (50.9% vs. 34.5%), ST-elevated myocardial infarction (59.5% vs. 29.3%), and treatment with angiotensin-converting enzyme inhibitors (100% vs. 69%). P2Y12 inhibitors and beta-blockers were more frequently prescribed in the CR group (83.6% vs. 96.6% and 82.8% vs. 94.8%, respectively). After six months, klotho levels increased in CR patients whereas they were reduced in controls (+63 vs. -49 pg/mL; p < 0.001). FGF-23 was unchanged in the CR group and reduced in controls (+0.2 vs. -17.3 RU/dL; p < 0.003). After multivariate analysis, only the change in klotho levels was significantly different between groups (+124 pg/mL favoring CR group; IC 95% [+44 to +205]; p = 0.003). Conclusions: In our study, CR after ACS increases plasma klotho levels without significant changes in other components of MM. Further studies are needed to clarify whether this effect has a causal role in the clinical benefit of CR.