Management of dyslipidemia in coronary artery disease: the present and the future.

Coronary artery disease (CAD) remains a leading cause of global morbidity and mortality, necessitating continuous refinement in the management of dyslipidemia, one of its major risk factors, to mitigate cardiovascular risks. Previous studies have proven the critical role of immediate and robust low-density lipoprotein cholesterol (LDL-C) reduction in the aftermath of acute coronary syndrome (ACS). Emphasizing the evidence supporting this approach, we delve into the impact of early intervention on cardiovascular outcomes and propose optimal strategies for achieving rapid LDL-C lowering, while also providing the rationale for early proprotein convertase subtilisin/kexin 9 inhibitor use after an ACS. Given the importance of the residual lipidemic risk, we present an overview of emerging therapeutic avenues poised to reshape dyslipidemia management, such as bempedoic acid, lipoprotein(a) inhibition, ApoC3 modulation, and angiopoietin-like protein 3 targeting. This comprehensive review amalgamates current evidence with future prospects, offering a holistic perspective on the management of dyslipidemia in CAD. By exploring both the urgency for immediate post-ACS LDL-C reduction and the exciting advancements on the horizon, this article provides a roadmap for clinicians navigating the intricate landscape of lipid-lowering therapies in CAD.

Ischemia testing and revascularization in patients with monomorphic ventricular tachycardia: A relic of the past?

Testing for myocardial ischemia in patients presenting with sustained monomorphic Ventricular Tachycardia(VT) even without evidence of acute myocardial infarction is a tempting strategy that is frequently utilized in clinical practice. Monomorphic VT is mainly caused by re-entry around chronic myocardial scar and active ischemia has no role in its pathogenesis, thus making testing for ischemia futile, at least in theory. This systematic literature review sought to address the usefulness of ischemia testing (mainly coronary angiography) in patients presenting with monomorphic VT through 8 selected studies after evaluating a total of 130 published manuscripts. Particularly, we sought to unveil whether coronary angiography and possibly concomitant revascularization leads to lesser tachycardia recurrence. Our conclusion can be summarized as follows: this approach whether combined with revascularization or not, does not seem to reduce VT recurrence nor does it affect mortality in such patients. Even though most of the published literature points at this direction, validation from randomized controlled trials is imperative.

One-year outcomes following a hypertensive urgency or emergency.

There are scarce data on the comparative prognosis between patients with hypertensive emergencies (HE), urgencies (HU), and those without HU or HE (HP). Our study aimed to compare cardiovascular (CV) outcomes of HE, HU, and HP during a 12-month follow-up period. The population consisted of 353 consecutive patients presenting with HE or HU in a third-care emergency department and subsequently referred to our hypertension center for follow-up. After both groups completed scheduled follow-up visits, patients with HU were matched one-to-one by age, sex, and hypertension history with HP who attended our hypertension center during the same period. Primary outcomes were 1) a recurrent hypertensive HU or HE event and 2) non-fatal CV events (coronary heart disease, stroke, heart failure, or CV interventions), while secondary outcomes were 1) all-cause death, 2) CV death, 3) non-CV death, and 4) any-cause hospitalization. Events were prospectively registered for all three groups. During the study period, 81 patients were excluded for not completing follow-up. Among eligible patients(HE = 94; HU = 178), a total of 90 hospitalizations and 14 deaths were recorded; HE registered greater CV morbidity when compared with HU (29 vs. 9, HR 3.43, 95 % CI 1.7-6.9, p = 0.001), and increased CV mortality (8 vs. 1, HR 13.2, 95 % CI 1.57-110.8, p = 0.017). When opposing HU to HP, events did not differ substantially. Cox regression models were adjusted for age, sex, CV and chronic kidney disease, diabetes mellitus, and smoking. During 1-year follow-up, the prognosis of HU was better than HE but not different compared to HP. These results highlight the need for improved care of HU and HE.

LOX-1 Receptor: A Diagnostic Tool and Therapeutic Target in Atherogenesis.

Low-density lipoprotein (LDL) and oxidized LDL (oxLDL) are major contributors to atherogenesis, as endogenous antigens, via several receptors such as LOX 1. A PubMed search was conducted in order to identify relevant articles regarding LOX-1's role in the atherosclerosis, diagnosis, prognostic use and molecules that could be used for therapy. The references of the manuscripts obtained were also reviewed, in order to find additional relevant bibliography. LOX-1 is a lectin-like pattern recognition receptor, mostly expressed in endothelial cells (ECs) which can bind a variety of molecules, including oxLDL and C-reactive protein (CRP). LOX-1 plays a key role in oxLDL's role as a causative agent of atherosclerosis through several pathologic mechanisms, such as oxLDL deposition in the subintima, foam cell formation and endothelial dysfunction. Additionally, LOX-1 acts a scavenger receptor for oxLDL in macrophages and can be responsible for oxLDL uptake, when stimulated. Serum LOX-1 (sLOX-1) has emerged as a new, potential biomarker for diagnosis of acute coronary syndromes, and it seems promising for use along with other common biomarkers in everyday clinical practice. In a therapeutic perspective, natural as well as synthetic molecules exert anti-LOX-1 properties and attain the receptor's pathophysiological effects, thus extensive research is ongoing to further evaluate molecules with therapeutic potential. However, most of these molecules need further trials in order to properly assess their safety and efficacy for clinical use. The aim of this review is to investigate LOX-1 role in atherogenesis and explore its potential as diagnostic tool and therapeutic target.

Acute Coronary Syndromes in Women: A Narrative Review of Sex-Specific Characteristics.

Acute coronary syndromes (ACSs) encompass a spectrum of life-threatening cardiovascular conditions, including unstable angina (UA) and myocardial infarction. While significant progress has been made in the understanding and management of ACS over the years, it has become increasingly evident that sex-based differences play a pivotal role in the pathophysiology, presentation, and outcomes of these conditions. Despite this recognition, the majority of clinical research in the field has historically focused on male populations, leading to a significant knowledge gap in understanding the unique aspects of ACS in women. This review article aims to comprehensively explore and synthesize the current body of literature concerning the sex-specific characteristics of ACS, shedding light on the epidemiology, risk factors, clinical presentation, diagnostic challenges, treatment strategies, and prognosis in women. By elucidating the distinct aspects of ACS in women, this review intends to foster greater awareness and improved clinical management, ultimately contributing to enhanced cardiovascular care for female patients.

The effect of SGLT2 inhibitors on the endothelium and the microcirculation: from bench to bedside and beyond.

AIMS: The beneficial cardiovascular effects of sodium-glucose cotransporter 2 (SGLT2) inhibitors irrespective of the presence of diabetes mellitus are nowadays well established and they already constitute a significant pillar for the management of heart failure, irrespective of the ejection fraction. The exact underlying mechanisms accountable for these effects, however, remain largely unknown. The direct effect on endothelial function and microcirculation is one of the most well studied. The broad range of studies presented in this review aims to link all available data from the bench to bedside and highlight the existing gaps as well as the future directions in the investigations concerning the effects of SGLT2 inhibitors on the endothelium and the microcirculation. METHODS AND RESULTS: An extensive search has been conducted using the MEDLINE/PubMed database in order to identify the relevant studies. Preclinical data suggest that SGLT2 inhibitors directly affect endothelial function independently of glucose and specifically via several interplaying molecular pathways, resulting in improved vasodilation, increased NO production, enhanced mitochondrial homeostasis, endothelial cell viability, and angiogenesis as well as attenuation of oxidative stress and inflammation. Clinical data systematically confirm this beneficial effect on the endothelium, whereas the evidence concerning the effect on the microcirculation is conflicting. CONCLUSION: Preclinical and clinical studies indicate that SGLT2 inhibitors attenuate endothelial and microvascular dysfunction via a combination of mechanisms, which play a role in their beneficial cardiovascular effect.

A network meta-analysis of the antithrombotic strategies in patients with atrial fibrillation and percutaneous coronary interventions: Focus on bleeding.

BACKGROUND: We performed a network meta-analysis of randomized controlled trials comparing non-vitamin K antagonist oral anticoagulant (NOAC)-based versus vitamin K antagonists (VKA)-based regimens in patients with atrial fibrillation (AF) and acute coronary syndromes or PCI, aiming to examine the precise impact of recently established antithrombotic strategies on major bleeding as primary end-point and other safety and efficacy as secondary end-points. METHODS: A literature search was conducted for randomized controlled trials. Our search took place in three major databases. The primary endpoint of our study was bleeding. To combine direct and indirect evidence across trials, a frequentist network meta-analysis with a random-effects model was used. RESULTS: Five studies were found eligible for the meta-analysis enrolling a total of 11,542 patients. Five studies (N = 4903 patients) contributed to the network. Compared to the triple antithrombotic therapy (TAT)-based VKA, only the dual antithrombotic therapy (DAT) based NOAC reduced the bleeding (RR 0.57, 95%CI 0.40-0.82). There was no statistically significant difference between DAT-based VKA (RR = 0.66, 95%CI = 0.40-1.09) or TAT-based NOAC (RR = 0.80, 95%CI = 0.43-1.49). DAT-based NOAC ranked best (P-score = 0.91), followed by DAT-based VKA (P-score = 0.67), TAT-based NOAC (P-score = 0.40), and TAT-based VKA (P-score = 0.03). CONCLUSION: The network meta-analysis of four antithrombotic strategies, demonstrated that in patients with AF undergoing PCI the combination of DAT-based NOAC is associated with a significantly lower risk of major bleeding events. This strategy does not seem to be less effective in terms of prevention of ischemic events compared to the other regimens.

Broad Electrocardiogram Syndromes Spectrum: From Common Emergencies to Particular Electrical Heart Disorders.

Electrocardiogram (ECG) still remains a very useful diagnostic method in modern cardiology. Its broad availability, noninvasiveness and good sensitivity explain why it plays a capital role in the very beginning of the process of diagnosis for every patient, with or without cardiac-related complaints. For the practitioner, good training in ECG interpretation is mandatory. Sometimes, the ECG trace reveals particular aspects that may cause confusion and complicate decision-making. In this article, we present several less common situations underlying the general context and ECG features. The syndromes studied have a high pathological significance and may range from acute emergencies that call for a rapid therapeutical response to chronic syndromes that require prolonged observation, monitoring and risk stratification.

Lipoprotein-associated Phospholipase A2 in Coronary Artery Disease.

Coronary artery disease (CAD) is the leading cause of morbidity and mortality in western societies. Therefore the identification of novel biomarkers to be used as diagnostic or therapeutic targets is of significant scientific interest. Lipoprotein-associated phospholipase A2 (Lp-PLA2) is one such protein shown to be involved in endothelial dysfunction, vascular inflammation and atherogenesis. Several epidemiological studies have associated high Lp-PLA2 activity with an increased risk for CAD even when other CAD risk factors or inflammation markers were included in the multivariate analysis. These findings were strengthened by the results of relevant meta-analyses. However, randomized trials failed to establish Lp-PLA2 as a therapeutic target. Specifically, pharmaceutical inhibition of Lp-PLA2 when compared to the placebo failed to demonstrate a significant association with improved prognosis of patients with stable CAD or after an acute coronary syndrome (ACS). This review focuses on the available data that have investigated the potential role of Lp- PLA2 as a biomarker for CAD.