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Background: Aortic valve repair is currently the only effective treatment for calcific aortic valve stenosis (CAVS), as no pharmacological therapies exist to prevent or slow its progression. Recent promising results showed that glucagon-like peptide-1 (GLP-1) attenuates the calcification of aortic valve interstitial cells. Therefore, we conducted a two-sample Mendelian randomization analysis to investigate the effect of GLP-1 receptor agonism (GLP-1Ra) on the risk of CAVS. Methods: The inverse variance weighted (IVW) method was used to obtain the primary causal inference, and several sensitivity analyses, including MR-Egger, were performed to assess the robustness of the results. Results: Based on the IVW estimates, the GLP-1Ra showed a neutral effect on the risk of CAVS (odds ratio [OR] per 1 mmol/mol decrease in glycated hemoglobin = 0.87, 95% CI = [0.69, 1.11], p = 0.259; I2 = 4.5%, Cohran's Q = 2.09, heterogeneity p = 0.35; F statistic = 16.8). A non-significant effect was also derived by the sensitivity analyses. No evidence of horizontal pleiotropy was identified. Conclusions: GLP-1Ra was not significantly associated with the risk of CAVS. Furthermore, pragmatically designed studies are required to evaluate the effect of GLP-1Ra on the clinical course of CAVS in different patient subgroups. [ABSTRACT FROM AUTHOR]

All recent guidelines on cardiovascular prevention have highlighted the role of a healthy diet and lifestyle advocating an holistic approach to reduce the cardiovascular burden among the population. Despite these efforts, registries have reported that only a minority of healthcare professionals provide advice on diet and lifestyle, and, in most cases, counseling is suboptimal for several reasons. Cardiovascular benefits linked to lifestyle and nutrition seem to be underestimated by many patients and doctors. This overview aims to summarize well-established benefits related to lifestyle and nutrition, discuss the current debates in this field in order to improve awareness among the medical community and promote better implementation of non-pharmaceutical measures to prevent the occurrence of atherothrombotic events, by reducing cardiovascular risk factors such as hypertension, diabetes, dyslipidemia, and obesity. [ABSTRACT FROM AUTHOR]

Chronic coronary syndromes (CCS) comprehend a wide spectrum of conditions related to coronary artery disease (CAD). CCS definition includes either those patients who experienced an acute coronary syndrome such as myocardial infarction (MI) or unstable angina (UA), and the ones in which CAD has been detected through screening. This aspect creates a potential issue in differentiating medical treatments and modalities and timing for follow up. Another critical aspect is represented by the gap between American and European guidelines, which have been most recently updated respectively in 2023 and 2019. Furthermore, it is not clear what kind of patient must be screened for the detection for CAD and how to manage the eventual follow-up. Lastly, the latest guidelines are not clear for the choice of medical therapy and which are the patients who benefit the most from the eventual revascularization. The aim of this review is to analyze the issues related to the incongruities about CCS and propose potential options for adequate treatment and follow up. [ABSTRACT FROM AUTHOR]

Psychiatric conditions, such as depression, anxiety, bipolar disorder, and schizophrenia, are increasingly recognized as significant risk factors for cardiovascular disease (CVD). This review systematically analyzes evidence from various databases to provide a comprehensive understanding of the impact of psychiatric illnesses on the incidence, management, and prognosis of CVD. Key findings suggest a bidirectional relationship between psychiatric disorders and CVD, indicating that mental health conditions can predispose individuals to CVD, while CVD can exacerbate or trigger psychiatric symptoms. The review explores the underlying mechanisms of these associations, including behavioral factors, stress responses, and medication side effects. It also examines the challenges in managing CVD patients with comorbid psychiatric conditions, emphasizing the importance for integrated care approaches. This review underscores the necessity of considering mental health as an integral component of cardiovascular care and calls for further research to develop tailored management strategies for these complex conditions, ultimately aiming to improve patient outcomes and quality of life. This comprehensive analysis provides valuable insights for future investigations and guides clinicians in optimizing care for patients with both psychiatric and cardiovascular conditions. [ABSTRACT FROM AUTHOR]

Acute hyperglycemia is a transient increase in plasma glucose level (PGL) frequently observed in patients with ST-elevation myocardial infarction (STEMI). The aim of this review is to clarify the molecular mechanisms whereby acute hyperglycemia impacts coronary flow and myocardial perfusion in patients with acute myocardial infarction (AMI) and to discuss the consequent clinical and prognostic implications. We conducted a comprehensive literature review on the molecular causes of myocardial damage driven by acute hyperglycemia in the context of AMI. The negative impact of high PGL on admission recognizes a multifactorial etiology involving endothelial function, oxidative stress, production of leukocyte adhesion molecules, platelet aggregation, and activation of the coagulation cascade. The current evidence suggests that all these pathophysiological mechanisms compromise myocardial perfusion as a whole and not only in the culprit coronary artery. Acute hyperglycemia on admission, regardless of whether or not in the context of a diabetes mellitus history, could be, thus, identified as a predictor of worse myocardial reperfusion and poorer prognosis in patients with AMI. In order to reduce hyperglycemia-related complications, it seems rational to pursue in these patients an adequate and quick control of PGL, despite the best pharmacological treatment for acute hyperglycemia still remaining a matter of debate. [ABSTRACT FROM AUTHOR]

Antiphospholipid syndrome (APS), also known as Hughes syndrome, is an acquired autoimmune and procoagulant condition that predisposes individuals to recurrent thrombotic events and obstetric complications. Central is the role of three types of antiphospholipid antibodies that target phospholipid-binding proteins: lupus anticoagulant (LAC), anti-β2-glycoprotein I (β2-GPI-Ab), and anti-cardiolipin (aCL). Together with clinical data, these antibodies are the diagnostic standard. However, the diagnosis of APS in older adults may be challenging and, in the diagnostic workup of thromboembolic complications, it is an underestimated etiology. The therapeutic management of APS requires distinguishing two groups with differential risks of thromboembolic complications. The standard therapy is based on low-dose aspirin in the low-risk group and vitamin K antagonists in the high-risk group. The value of direct oral anticoagulants is currently controversial. The potential role of monoclonal antibodies is investigated. For example, rituximab is currently recommended in catastrophic antiphospholipid antibody syndrome. Research is ongoing on other monoclonal antibodies, such as daratumumab and obinutuzumab. This narrative review illustrates the pathophysiological mechanisms of APS, with a particular emphasis on cardiovascular complications and their impact in older adults. This article also highlights advancements in the diagnosis, risk stratification, and management of APS. [ABSTRACT FROM AUTHOR]

A study published in the European Heart Journal examines the lifelong impact of adiposity (excess body fat) on cardiac structure and function. The study analyzed data from 1690 individuals who underwent repeated body mass index (BMI) measurements and echocardiography at various ages. The findings suggest that increased BMI from a young age is associated with adverse changes in cardiac anatomy and function, including structural injury, diastolic dysfunction, and systolic dysfunction. The study highlights the importance of proactive preventive interventions against obesity and the need for further research on interventions such as diet, exercise, and drug therapy. [Extracted from the article]

Individual patient data (IPD) meta-analyses build upon traditional (aggregate data) meta-analyses by collecting IPD from the individual studies rather than using aggregated summary data. Although both traditional and IPD meta-analyses produce a summary effect estimate, IPD meta-analyses allow for the analysis of data to be performed as a single dataset. This allows for standardization of exposure, outcomes, and analytic methods across individual studies. IPD meta-analyses also allow the utilization of statistical methods typically used in cohort studies, such as multivariable regression, survival analysis, propensity score matching, uniform subgroup and sensitivity analyses, better management of missing data, and incorporation of unpublished data. However, they are more time-intensive, costly, and subject to participation bias. A separate issue relates to the meta-analytic challenges when the proportional hazards assumption is violated. In these instances, alternative methods of reporting time-to-event estimates, such as restricted mean survival time should be used. This statistical primer summarizes key concepts in both scenarios and provides pertinent examples. [ABSTRACT FROM AUTHOR]

Background: Traditional combustion cigarette (TCC) smoking is an established risk factor for several types of cancer and cardiovascular diseases. Circulating microRNAs (miRNAs) represent key molecules mediating pathogenetic mechanisms, and potential biomarkers for personalized risk assessment. TCC smoking globally changes the profile of circulating miRNAs. The use of heat‐not‐burn cigarettes (HNBCs) as alternative smoking devices is rising exponentially worldwide, and the circulating miRNA profile of chronic HNBC smokers is unknown. We aimed at defining the circulating miRNA profile of chronic exclusive HNBC smokers, and identifying potentially pathogenetic signatures. Methods: Serum samples were obtained from 60 healthy young subjects, stratified in chronic HNBC smokers, TCC smokers and nonsmokers (20 subjects each). Three pooled samples per group were used for small RNA sequencing, and the fourth subgroup constituted the validation set. Results: Differential expression analysis revealed 108 differentially expressed miRNAs; 72 exclusively in TCC, 10 exclusively in HNBC and 26 in both smoker groups. KEGG pathway analysis on target genes of the commonly modulated miRNAs returned cancer and cardiovascular disease associated pathways. Stringent abundance and fold‐change criteria nailed down our functional bioinformatic analyses to a network where miR‐25‐3p and miR‐221‐3p are main hubs. Conclusion: Our results define for the first time the miRNA profile in the serum of exclusive chronic HNBC smokers and suggest a significant impact of HNBCs on circulating miRNAs. [ABSTRACT FROM AUTHOR]

In the recently published clinical practice guidelines by the American Heart Association/American College of Cardiology, a central part has been dedicated to the revascularization, as new evidence came up increasing our knowledge on this relevant topic. Providing symptom relief, preventing major adverse cardiovascular events and improving long-term survival is ultimately the aim of coronary revascularization. Such ambitious goals should be actively pursued, as suggested thoroughly in the text, sharing the clinical decision making with the patient. Aim of this commentary is to highlight critical messages from the recent guideline, especially in complex clinical scenarios such as angiographically intermediate coronary artery stenoses, significant left main disease and multivessel disease with severe left ventricular dysfunction. [ABSTRACT FROM AUTHOR]

Aims Despite growing evidence supporting the clinical utility of optical coherence tomography (OCT) guidance during percutaneous coronary interventions (PCIs), there is no common agreement as to the optimal stent implantation parameters that enhance clinical outcome. Methods and results We retrospectively examined the predictive accuracy of suboptimal stent implantation definitions proposed from the CLI-OPCI II, ILUMIEN-IV OPTIMAL PCI, and FORZA studies for the long-term risk of device-oriented cardiovascular events (DoCE) in the population of large all-comers CLI-OPCI project. A total of 1020 patients undergoing OCT-guided drug-eluting stent implantation in the CLI-OPCI registry with a median follow-up of 809 (quartiles 414–1376) days constituted the study population. According to CLI-OPCI II, ILUMIEN-IV OPTIMAL PCI, and FORZA criteria, the incidence of suboptimal stent implantation was 31.8%, 58.1%, and 57.8%, respectively. By multivariable Cox analysis, suboptimal stent implantation criteria from the CLI-OPCI II [hazard ratio 2.75 (95% confidence interval 1.88–4.02), P < 0.001] and ILUMIEN-IV OPTIMAL PCI [1.79 (1.18–2.71), P = 0.006] studies, but not FORZA trial [1.11 (0.75–1.63), P = 0.597], were predictive of DoCE. At long-term follow-up, stent edge disease with minimum lumen area <4.5 mm2 [8.17 (5.32–12.53), P < 0.001], stent edge dissection [2.38 (1.33–4.27), P = 0.004], and minimum stent area <4.5 mm2 [1.68 (1.13–2.51), P = 0.011] were the main OCT predictors of DoCE. Conclusion The clinical utility of OCT-guided PCI might depend on the metrics adopted to define suboptimal stent implantation. Uncovered disease at the stent border, stent edge dissection, and minimum stent area <4.5 mm2 were the strongest OCT associates of stent failure. [ABSTRACT FROM AUTHOR]

Bivalirudin, a bivalent direct thrombin inhibitor, has been developed to reduce bleeding without any trade-off in thrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). Despite showing a superior safety profile compared with unfractionated heparin (UFH), bivalirudin is not considered the anticoagulant of choice in ACS patients undergoing PCI, mainly because of an increased rate of acute stent thrombosis (ST) shown by several randomized controlled trials (RCTs), in addition to limited availability in certain countries and increased costs. However, RCTs on bivalirudin have been characterized by several confounding factors hindering the interpretation of its safety and efficacy compared with UFH among the spectrum of ACS patients. Furthermore, a significant body of evidence has demonstrated that the risk of acute ST can be mitigated by a full-dose infusion regimen following PCI, without compromising the favorable safety profile compared to UFH. In light of the increased understanding of the prognostic relevance of bleeding events and the excellent safety profile of bivalirudin, recent trial evidence may allow for this anticoagulant agent to reemerge and have a more prominent role in the management of ACS patients undergoing PCI. [ABSTRACT FROM AUTHOR]

Aortic stenosis (AS) is the most frequent form of valvular heart disease in developed countries, and severe AS is a major cause of morbidity and mortality in the elderly. Since many of these patients often have a high or prohibitive risk for surgical aortic valve replacement (SAVR), transcatheter aortic valve implantation (TAVI) has emerged as an established therapy and is now becoming a common practice, even in low-risk patients. As severe AS and coronary artery disease (CAD) are often concomitant, a matter of debate is whether, how, and when to treat coexisting CAD. The aim of this commentary is to analyze the rationale for the diagnostic evaluation and management of CAD in TAVI candidates, as proposed by the recent EAPCI/ESC consensus statement. [ABSTRACT FROM AUTHOR]

Background and aims: Bempedoic Acid (BA) is a novel Lipid-Lowering Therapy (LLT). We performed a systematic review and meta-analysis to assess the efficacy and safety of BA in patients with hypercholesterolemia. Methods: PubMed, Scopus, and Cochrane library databases were searched for randomised controlled trials evaluating the efficacy and/or safety of BA compared with placebo. Trials investigating dosages other than 180 mg/die were excluded. Major adverse cardiovascular events (MACE) were the primary efficacy endpoint. LDL-cholesterol reduction was the primary laboratory endpoint. Pre-specified safety endpoints included muscle-related adverse events, new-onset diabetes, and gout. The protocol was registered on PROSPERO (temporary ID:399,867). Results: Study search identified 275 deduplicated results. 11 studies, encompassing 18,315 patients (9854 on BA vs 8461 on placebo/no treatment) were included. BA was associated with a reduced risk of MACE (OR 0.86, 95% CI 0.79–0.95), myocardial infarction (OR 0.76, 95% CI 0.64–0.88) and unstable angina (OR 0.69, 95% CI 0.54–0.88) compared to control, over a median follow up of 87 (15–162) weeks. BA was associated with a reduction of LDL-Cholesterol (mean difference [MD]–22.42,95% CI − 24.02% to − 20.82%), total cholesterol (− 16.50%,95% − 19.21% to − 13.79%), Apo-B lipoprotein (− 19.55%, − 22.68% to − 16.42%) and high-sensitivity CRP (− 27.83%, − 31.71% to − 23.96%) at 12 weeks. BA was associated with a higher risk of gout (OR 1.55, 95% CI 1.27–1.90) as compared with placebo. Efficacy on laboratory endpoints was confirmed, with a variable extent, across patients on statin or ezetimibe background therapy. Conclusions: The improved cholesterol control achieved with BA translates into a reduced risk of MACE, including myocardial infarction and coronary revascularisation. The drug has a satisfactory safety profile except for an increased risk of gout. [ABSTRACT FROM AUTHOR]

Aims: Interleukin‐1 (IL‐1) blockade may improve exercise capacity in patients with heart failure (HF) patients. The extent of the improvement and its persistence beyond discontinuation of IL‐1 blockade is unknown. Methods and results: The primary objective was to determine changes in cardiorespiratory fitness and cardiac function on‐treatment with IL‐1 blocker, anakinra, and off‐treatment, after treatment cessation. We performed cardiopulmonary exercise testing, Doppler echocardiography, and biomarkers in 73 patients with HF, 37 (51%) females, 52 (71%) Black–African–American, before and after treatment with anakinra 100 mg daily. In a subset of 46 patients, testing was also repeated after treatment cessation. Quality of life was assessed in each patient using standardized questionnaires. Data are presented as median and interquartile range. Treatment with anakinra for 4 [2–12] weeks was associated with a significant improvement in high‐sensitivity C‐reactive protein (from 6.2 [3.3–15.4] to 1.4 [0.8–3.4] mg/L, P < 0.001), peak oxygen consumption (VO2peak, from 13.9 [11.6–16.6] to 15.2 [12.9–17.4] mL/kg/min, P < 0.001). Ventilatory efficiency, exercise time, Doppler‐derived signs and biomarkers of elevated intracardiac pressures, and quality‐of‐life measures also improved with anakinra. In the 46 patients in whom off‐treatment data were available 12 [4–12] weeks later, many of the favourable changes seen with anakinra were largely reversed (from 1.5 [1.0–3.4] to 5.9 [1.8–13.1], P = 0.001 for C‐reactive protein, and from 16.2 [14.0–18.4] to 14.9 [11.5–17.8] mL/kg/min, P = 0.017, for VO2peak). Conclusions: These data validate IL‐1 as an active and dynamic modulator of cardiac function and cardiorespiratory fitness in HF. [ABSTRACT FROM AUTHOR]

Optimal risk assessment for primary prevention remains highly challenging. Recent registries have highlighted major discrepancies between guidelines and daily practice. Although guidelines have improved over time and provide updated risk scores, they still fail to identify a significant proportion of at-risk individuals, who then miss out on effective prevention measures until their initial ischemic events. Cardiovascular imaging is progressively assuming an increasingly pivotal role, playing a crucial part in enhancing the meticulous categorization of individuals according to their risk profiles, thus enabling the customization of precise therapeutic strategies for patients with increased cardiovascular risks. For the most part, the current approach to patients with atherosclerotic cardiovascular disease (ASCVD) is homogeneous. However, data from registries (e.g., REACH, CORONOR) and randomized clinical trials (e.g., COMPASS, FOURIER, and ODYSSEY outcomes) highlight heterogeneity in the risks of recurrent ischemic events, which are especially higher in patients with poly-vascular disease and/or multivessel coronary disease. This indicates the need for a more individualized strategy and further research to improve definitions of individual residual risk, with a view of intensifying treatments in the subgroups with very high residual risk. In this narrative review, we discuss advances in cardiovascular imaging, its current place in the guidelines, the gaps in evidence, and perspectives for primary and secondary prevention to improve risk assessment and therapeutic strategies using cardiovascular imaging. [ABSTRACT FROM AUTHOR]