Diagnostic utility of sortilin & other biomarkers in the diagnosis of carotid & coronary atherosclerosis in individuals with arterial hypertension.

Background & objectives Cardiovascular diseases (CVDs) are a leading cause of mortality worldwide. The aim of this investigation was to study the role of biological markers in predicting the risk of carotid and coronary artery atherosclerosis. Methods A total of 161 males in the age group of 30-65 yr were included in this study. All participants underwent biochemical analyses [cholesterol, low density lipoprotein cholesterol (LDL-C), triglycerides, glucose, (interleukin) IL-8, IL-10, (proprotein convertase inhibitors subtilisin/kexin type 9) PCSK9, sortilin, creatinine]; ECG; echocardiography; coronary angiography; ultrasound doppler of brachiocephalic arteries. Based on PCSK9 levels, participants were divided into four groups: group 1, n=41 individuals with PCSK9 level of 100-250 ng/ml; group 2, n=37 individuals with PCSK9 level of 251-400 ng/ml; group 3, n=51 individuals with PCSK9 level of 401-600 ng/ml and group 4, n=32 individuals with PCSK9 level of 601-900 ng/ml. Results Sortilin level was the highest in group 2. Group 3 individuals had the highest level of IL-8. Correlation analysis of the entire data set revealed the relationship of relative left ventricular thickness index with age, cardiovascular risk, body mass index, intima-media thickness and left ventricular mass index; sortilin had a negative relationship of weak strength with age and smoking, a direct relationship between the risk of cardiovascular complications and with IL-10. Interpretation & conclusions Sortilin is the innovative marker of CVDs. In the present investigation, we demonstrated the clear increase in the inflammatory markers (IL-8) in individuals with subclinical atherosclerosis. This fact can be explained by the oxygen stress activation. In individuals with coronary artery stenosis (50% and more), the increase in IL-10 levels demonstrates, to our opinion, the activation of antioxidant protection activation.

Frequent Extrasystolic Arrhythmia: Perceived Psychological Well-Being Evaluation.

BACKGROUND: To estimate quality of life (QOL) in patients with frequent extrasystolic arrhythmia (ES) using the SF-36 Health Status Survey. MATERIALS AND METHODS: The patient group consisted of 634 individuals (42-79 y.o) with ES >700 per 24 hours, as diagnosed by Holter ECG, and the control group included 106 patients (38-79 y.o.) with ES <700 per 24 hours. None of the patients had atrial fibrillation. The "early" ES subgroup A (n=192) experienced ES preceding the transmitral blood flow peak in the cardiac cycle (peak E) according to pulsed wave Doppler in transthoracic echocardiography (EchoCG). The "late" subgroup B (n=442) had ES after the transmitral blood flow peak, irrespective of the electric topic localization. Laboratory and instrumental methods included standard lipidograms, Holter ECG, EchoCG, Doppler ultrasound of brachiocephalic arteries, and coronary angiography. For QOL evaluation, we used the SF-36 Health Status Survey. RESULTS: The patient groups did not differ with respect to main laboratory findings, instrumental parameters, and comorbidities, with the exception of type and quantity of ES. Physical and mental health to the SF-36 Health Status Survey indicated lower summary point scores in patient subgroup A ("early" ES) in comparison with the control group. The parameters were non-significantly lower in subgroup B. CONCLUSIONS: The SF-36 Health Status Survey serves to assess the QOL in patients with ES. Frequent ES, especially its "early" variant in which ventricular systole precedes the transmitral blood flow peak in the biomechanic cardiac cycle is a predictor for lower QOL scores in patients with cardiovascular pathology.

Quality of Life Evaluation in Patients with Paroxysmal Atrial Fibrillation.

BACKGROUND: To estimate quality of life (QoL) in patients with paroxysmal atrial fibrillation (AF) using the SF-36 Health Status Survey. MATERIALS AND METHODS: In a single-center study involving 6,630 patients, we defined a group of 97 patients having an incidental finding of atrial fibrillation (AF). The control group included 99 patients from the same primary cohort, but without paroxysmal AF. The two study groups matched closely in anthropometric parameters and comorbidity. All patients underwent standard laboratory and instrumental research methods. In the primary visit, at the time of AF detection, we evaluated the patients QoL using the classical SF-36 Health Status Survey. At the second visit (6±0.5 months follow-up) and third visit (12±0.5 months follow-up), we re-evaluated the QoL using the SF-36 Health Status Survey. RESULTS: The absolute majority (95/97; 98%) of patients of the main group had a special variant of extrasystoles, namely the early atrial "P on T" type (versus 4.0% incidence in the control group) [OR 846 (382;187,000)]. The main group showed a significantly greater frequency of supraventricular extrasystoles. At the 1st visit, there was no group differences in QoL scores between the main and control groups (p>0.05). However, at 6 and 12 months follow-up, metrics of physical and mental health differed significantly between groups stratified by low and high QoL (p<0.05). The asymptomatic patients with paroxysmal AF and high compliance in oral anticoagulant therapy showed higher physical activity and social functioning. CONCLUSIONS: Paroxysmal AF in asymptomatic patients is a predictor for declining QoL during 12 months follow-up in patients with cardiovascular pathology. The paroxysmal AF patients who had high compliance of oral anticoagulant therapy proved to have improved physical activity and social functioning.

Perceived Psychological Well-Being in Patients with Hemodynamically Insignificant Carotid Arteries Stenosis.

BACKGROUND: Analysis of the perception of the disease in borderline stenosis of the orifice of the internal carotid artery (ICA) (up to 69% in diameter) in asymptomatic patients. SUBJECTS AND METHODS: 48 patients (28 men and 20 women). Group 1: stenosis up to 49% - 23 people (13 men, 10 women), mean age 50.4±16.1 y.o. Group 2: stenosis 50-59% - 18 people (10 men, 8 women), mean age 57.3±16 y.o. Group 3: stenosis 60-69% - 7 people (5 men, 2 women), mean age 61±12.3 y.o. All patients underwent ultrasound Doppler of brachiocephalic arteries, examination with Brief Illness Perception Questionnaire E. Broadbent (Russian version). RESULTS: According to the results of examination of patients with ICA stenosis, patients with more pronounced lesions (60-69%) more often have a type of reaction "negative attitude to the consequences of the disease". CONCLUSIONS: The majority of patients (54.2%) have a "negative type of attitude towards the consequences of the disease". This type of attitude to the disease is most pronounced in women and patients with stenosis of the ICA 60-69%. It is necessary to perform the psychological work with patients with carotid stenosis in order to form in them more adaptive types of perception of the disease, understanding of the disease and a positive attitude towards treatment.

Application of SF-36 Health Status Survey in Patients with Arterial Hypertension.

BACKGROUND: To estimate quality of life (QOL) in patients with arterial hypertension (AH) using SF-36 Health Status Survey. SUBJECTS AND METHODS: We included 268 patients (144 men, 124 women) with grade 1-3 AH (subgroup 1 - with coronary stenosis less than 50% (n=158), subgroup 2 - with coronary artery stenosis of 50% or more (n=110)). In the control group - 80 people (47 men, 33 women) without AH. Laboratory and instrumental methods included total cholesterol, low-density lipoprotein cholesterol, triglycerides, glucose, creatinine, electrocardiography, echocardiography, Doppler ultrasound of brachiocephalic arteries, stress echocardiography with physical exercises and coronary angiography. For QOL evaluation we used SF-36 Health Status Survey. RESULTS: According to the results of the SF-36 Health Status Survey, when assessing physical (PH) and mental (MH) among the groups, there was a significant decrease in summary points in patients of subgroup 2, in whom, according to coronary angiography, it was revealed stenosis of the carotid arteries 50% and more. Anxiety and depression predominated in men. Patients with corrected cholesterol and LDL-cholesterol levels, as well as after coronary angioplasty, were assessed for QOL with limited physical activity, but with high social functioning. CONCLUSIONS: AH, especially with hemodynamically significant atherosclerosis of the coronary arteries are the predictors for QOL worsening in cardiological patients, mostly in men. Using of the international questionnaire "SF-36 Health Status Survey" is advisable to assess the QOL in patients with cardiovascular diseases. In this sense, the interaction of a cardiologist and a psychotherapist is appropriate and justified for the most optimal management of a patient with this pathology.

Cryptogenic Stroke In The Context of Pandemic-Related Stress: The Role of Arterial Hemodynamics.

BACKGROUND: Up to 45% of ischemic strokes are cryptogenic, which is an impediment to proposing preventative measures. In this investigation we aimed to study underlying heart arrhythmias in patients with cryptogenic stroke, taking into consideration the context of the COVID-19 pandemic and stressful lockdown conditions. SUBJECTS AND METHODS: In this cross-sectional study we observed 52 patients with cryptogenic stroke >1 month after acute presentation, and a control group consisting of 88 patients without stroke. All patients undewent the laboratory and instrumental investigation consisting of the following: lipid spectrum; hemostasiograms; hemoglobin A1c; transthoracic or/and transesophageal echocardiography; 24-hours monitoring of ECG; computer tomography or magnetic resonance imaging of the brain. We studied the hemodynamics of the common carotid arteries using Doppler ultrasound imaging and digital sphygmography (SG). RESULTS: The groups were indentical with respect to the preponderance of study parameters (sex, age, comorbidities, instrumental and laboratory data). The ischemic stroke group had a statistically significant difference in the prevalence of the first type of extrasystolic arrhythmia according to our gradation of extrasystoles, which are ventricular systoles of extrasystolic contraction appearing before the transmitral blood flow peak (peak E in echocardiography). We observed that earlier ventricular systoles of extrasystole in the cardiac cycle predicted for greater growth of hemodynamic and kinetic parameters. Calculating the indices of a four-field table established the significant relationship between the moment of appearance of extrasystolic ventricular contraction in the cardiac cycle and the risk for cryptogenic stroke (normalized value of the Pearson coefficient (C`) of the two paramaters was 0.318). CONCLUSIONS: Extrasystolic arrhythmia appeared as an additional risk factor of earlier stroke. The most dangerous type of arrhythmia was when the ventricular contraction of the extrasystole appeared before the transmitral blood flow peak in the cardiac cycle. This observation could present a risk-marker for brain-related cardiovascular complications such as stroke, which might be patients suffering from different internal diseases, especially in the context of environmental stress conditions of the current pandemic and its related lockdown measures.

Renal protection: a leading mechanism for cardiovascular benefit in patients treated with SGLT2 inhibitors.

Initially developed as glucose-lowering drugs, sodium-glucose co-transporter type 2 inhibitors (SGLT2i) have demonstrated to be effective agents for the risk reduction of cardiovascular (CV) events in patients with type 2 diabetes mellitus (T2DM). Subsequently, data has emerged showing a significant CV benefit in patients treated with SGLT2i regardless of diabetes status. Renal protection has been initially evaluated in CV randomized trials only as secondary endpoints; nonetheless, the positive results gained have rapidly led to the evaluation of nephroprotection as primary outcome in the CREDENCE trial. Different renal and vascular mechanisms can account for the CV and renal benefits enlightened in recent literature. As clinical guidelines rapidly evolve and the role of SGLT2i appears to become pivotal for CV, T2DM, and kidney disease management, in this review, we analyze the renal effects of SGLT2, the benefits derived from its inhibition, and how this may result in the multiple CV and renal benefits evidenced in recent clinical trials.

Functional differentiation of cytotoxic cancer drugs and targeted cancer therapeutics.

There is no nationally or internationally binding definition of the term "cytotoxic drug" although this term is used in a variety of regulations for pharmaceutical development and manufacturing of drugs as well as in regulations for protecting medical personnel from occupational exposure in pharmacy, hospital, and other healthcare settings. The term "cytotoxic drug" is frequently used as a synonym for any and all oncology or antineoplastic drugs. Pharmaceutical companies generate and receive requests for assessments of the potential hazards of drugs regularly - including cytotoxicity. This publication is intended to provide functional definitions that help to differentiate between generically-cytotoxic cancer drugs of significant risk to normal human tissues, and targeted cancer therapeutics that pose much lesser risks. Together with specific assessments, it provides comprehensible guidance on how to assess the relevant properties of cancer drugs, and how targeted therapeutics discriminate between cancer and normal cells. The position of several regulatory agencies in the long-term is clearly to regulate all drugs regardless of classification, according to scientific risk based data. Despite ongoing discussions on how to replace the term "cytotoxic drugs" in current regulations, it is expected that its use will continue for the near future.

Arterial vascular complications predictive score in extrasystolic arrhythmia "EX-prognosis".

BACKGROUND: The aim of this study was the creation of an optimal model for predicting arterial vascular complications in patients with extrasystolic arrhythmia. METHODS: A single-center prospective study was performed with involving 634 patients with supraventricular or ventricular extrasystoles (ES) of 700 or more per 24 hours. The control group consisted of 106 people with ES less than 700 per 24 hours. The main and control groups were initially equivalent in anthropometric criteria and concomitant pathology. The list of examinations included laboratory methods (including lipid profile, coagulograms), as well as instrumental studies (transthoracic and/or transesophageal echocardiography (EchoCG), Doppler ultrasound of the brachiocephalic arteries and arteries of the lower extremities, 24-hours ECG monitoring, according to the indications - computed tomography or magnetic resonance imaging of the brain, coronary angiography, stress echocardiography. Prospective observation of patients performed for 1 year after the initial examination. Combined end points: development of arterial vascular complications - stroke, myocardial infarction, distal arterial embolism of other locations. We studied the data on identified complications. Next, we built models for predicting complications in various ways: Decision Tree; Bootstrap Forest; Boosted Tree; Neural Boosted; Support Vector Machines; Fit Stepwise; Nominal Logistic; Generalized Regression Lasso; Generalized Regression Forward Selection; Generalized Regression Pruned Forward Selection; Generalized Regression Elastic Net; Generalized Regression Ridge. To assess the quality of the models and compare them we used cross-validation with 30 replications. RESULTS: The highest profit values with minimal values of false positive results were obtained for the Bootstrap Forest model. Basing on this model, we created arterial vascular complications predictive score in extrasystolic arrhythmia "EX-prognosis" that included the following parameters: atheroma type III in carotid arteries - 3 points; age 69+ years old - 2 points; ES appearing before transmitral blood flow peak in cardiac cycle 700 and more per 24 hours - 1 point; carotid arteries stenosis, non-significant - 1 point. If total number is 3 and more points, the risk of arterial vascular complications within 1 year is high. CONCLUSIONS: We recommend to use the scale "EX-prognosis" in the clinical practice. For a quick assessment of the total risk, it is optimal to implement the risk14.exe program - calculator - developed by us for a personal computer, based on this scale.

Atrial fibrillation as a new independent risk factor for thromboembolic events: hemodynamics and vascular consequence of long ventricular pauses.

BACKGROUND: Atrial fibrillation (AF) is a leading risk factor of arterial thromboembolic events. Aim is to study the main arteries hemodynamics and kinetics in AF and to propose the functional classification of AF. METHODS: We included 188 patients (80 as the control). We performed 24-hours ECG monitoring, blood lipids analysis, echocardiography, stress echocardiography, coronary angiography, renal arteries angiography, ultrasound Doppler of brachiocephalic arteries, abdominal aorta branches, renal arteries, lower extremities arteries, sphygmography. Patients were divided into 3 groups up to the duration of maximum pauses between ventricular complexes in AF: 1) with a pause <1 second (64); 2) with a pause of ≥1, but <2 seconds (62); 3) ≥2 seconds (62). We analyzed the thromboembolic events within 1 year. RESULTS: We observed the increase of linear blood flow velocity and volume flow in patients with AF during the spreading of the wave after a long pause between ventricles' contractions. The longer the pause between the ventricles' contractions, the more increase of arteries kinetics parameters is observed. The most frequent incidence of thromboembolic events within 1 year was in group 3. CONCLUSIONS: We propose a functional classification of AF: 1) AF with the pauses of less than 1 second; 2) more 1, but less than 2 seconds; and 3) 2 or more seconds. The most unfavorable is AF with pauses of 2 seconds or more. We supplemented the CHA2DS2-VASc Score with the new independent risk factor - type of AF - in accordance with the maximum duration of pauses between cardiac cycles.

Proprotein convertase subtilisin kexin type 9 and main artery atherosclerosis in patients with arterial hypertension.

BACKGROUND: Aim of our investigation is to study the relationship between the level of proprotein convertase subtilisin kexin type 9 (PCSK9) and atherosclerotic process of coronary and brachiocephalic arteries in patients with arterial hypertension (AH). METHODS: Our investigation was performed in regional railway hospital. In our investigation we included 161 male train drivers who had AH with achieved target grades 1-2. All patients were performed laboratory tests including cholesterol, LDL-C, triglycerides, glucose, hemostasiograms, PCSK9. Patients were divided into groups up to the PCSK9 level: in group 1 (N.=41) we included patients with PCSK9 level 108-250 ng/mL; group 2 (N.=37) 251-400 ng/mL; group 3 (N.=45) 420-560 ng/mL and group 4 (N.=38) 580-860 ng/mL. All patients were performed coronary angiography, ultrasound Doppler of brachiocephalic arteries, electrocardiography, transthoracic echocardiography. RESULTS: The groups of the patients were identical in age, Body Mass Index, triglycerides, LDL-C, glucose, cholesterol levels. Also, there was no significant difference in the dependence of PCSK9 level on smoking status (χ2=3.1; P=0.3) and the presence of family history of AH (χ2=0.9; P=0.8). It was found that in the 1st group, patients with normal Body Mass Index had normal carotid intima-media thickness ≤1 mm in most of the cases (34.1%). The severity of brachiocephalic and coronary arteries atherosclerosis was more advanced in the 4th group. The atherosclerotic plaques determine the cardiovascular risk in patients with AH. CONCLUSIONS: The level of PCSK9 in male patients is an additional cardiovascular risk factor independent from the traditional risk factors. The PCSK9 level is correlated with atherosclerotic severity process of brachiocephalic arteries (P=0.08; r=0.2). The concentration of PCSK9 in the blood serum more than 580 ng/mL in patients with AH determines more severe coronary arteries atherosclerosis. If more the level of PCSK9 than more cardiovascular risk (P=0.002).

The operation of carotid endarterectomy: is it an effective method of treatment of arterial hypertension?

BACKGROUND: The aim of this study was to establish the relationship between arterial hypertension (AH) and hemodynamically significant atherosclerotic stenosis of carotid bifurcation and study the effect of carotid endarterectomy (CEA) on the course of AH. METHODS: In our investigation we included 320 patients: 243 (75.9%) men and 77 (24.1%), the mean age - 59.6±8.2. All patients underwent CEA operation. Patients were divided into groups: I (320) - before CEA surgery and AH; II (320) - the same patients after CEA operation. All patients underwent laboratory tests, ECG, chest X-ray, ultrasound of the kidneys, thyroid gland, computer tomography (CT) of adrenal glands, of the brain, echocardiography, ultrasound or angiography of the renal arteries. Before and after the CEA, there were made Doppler ultrasound of brachiocephalic arteries, 24 hours blood pressure (BP) monitoring. Additional visits were made by 73 patients in 3, 6 and 12 months after the CEA. RESULTS: Most of the patients had significant decrease of BP in the postoperative period, which was observed in 257 (80.3%) patients on days 2-7, in 58 (18.1%) - did not change significantly, and only 5 (1.6%) had the increasing of BP. In 29 (39.7%) patients 1 year after CEA, there was no need to use antihypertensive therapy due for the normalization of BP after the surgery. CONCLUSIONS: It is necessary to highlight the cerebrovascular AH into a separate form of the secondary AH. The CEA has prominent, stable antihypertensive effect on these patients.

Comparing benefits from sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in randomized clinical trials: a network meta-analysis.

INTRODUCTION: Glucagon-like peptide 1 receptor agonists (GLP1-RA) and sodium-glucose cotransporter-2 inhibitors (SGLT2i) were individually proven to reduce major adverse cardiovascular events (MACE) in type 2 diabetes mellitus (T2DM) patients, but the relative magnitude of benefits from these two drug classes is debated. We aimed to review current available data on GLP1-RA and SGLT2i in T2DM patients and compare their efficacy and safety in this population. EVIDENCE ACQUISITION: We systematically searched MEDLINE/PubMed, the Cochrane Library, Google Scholar, Embase, www.tctmd.com, www.clinicaltrials.gov, www.clinicaltrialresults.org, from inception to September 17, 2020 for randomized controlled trials (RCTs) comparing the effects of GLP1-RA vs. SGLT2i vs. optimal medical therapy (OMT) in adult T2DM patients. Three authors independently screened references and extracted data using a predefined data collection form. Outcomes were analyzed using an indirect comparison meta-analysis of aggregate study-level data. The primary combined efficacy outcome comprised cardiovascular death, nonfatal myocardial infarction (MI), or nonfatal stroke. Secondary efficacy outcomes included all-cause mortality, cardiovascular mortality, non-fatal MI, non-fatal stroke, heart failure hospitalizations (HFH), and worsening renal function (WRF). EVIDENCE SYNTHESIS: Eleven RCTs enrolling a total of 98572 patients were included; 56004 (57%) patients were derived from GLP1-RA RCTs and 42568 (43%) from SGLT2i RCTs. At a median follow-up of 3.0±1.3 years, compared with OMT, both GLP1-RA and SGLT2i similarly reduced the rate of the composite primary outcome (risk ratio [RR] 0.88; 95% confidence interval [95% CI] 0.83-0.93 and RR 0.88, 95% CI: 0.82-0.95, respectively) with no difference between the drug classes (RR 1.00, 95% CI: 0.92-1.10). Both classes similarly reduced MI rate, cardiovascular and all-cause mortality compared with OMT; stroke reduction was only observed with GLP1-RA with no difference in the indirect comparison with SGLT2i; conversely, only SGLT2i were effective in preventing HFH. Both GLP1-RA and SGLT2i were protective against WRF, with a major efficacy of SGLT2i in the indirect comparison. CONCLUSIONS: This meta-analysis report that GLP1-RA and SGLT2i reduced with a similar efficacy not only MACE as MI, but also cardiovascular mortality and all-cause mortality at a median 3-year follow-up. SGLT2i were more protective in HFH and WRF than GLP1RA. These new data highlight the efficacy of SGLT2i not only in HF and chronic kidney disease (CKD) but also in ischemic heart diseases (IHD), with a homogeneity among the class, whereas the results observed with GLP1-RA are heterogenous. These findings will help clinical's decisions to optimize therapeutic strategies for diabetic patients.

Extrasystolic arrhythmia: is it an additional risk factor of atherosclerosis?

BACKGROUND: Extrasystolic arrhythmia is not included in the list of risk factors of atherosclerosis. The aim of this investigation was to determine the relationship between atherosclerosis of main arteries and extrasystolic arrhythmia. METHODS: We included 286 patients in our investigation. We performed 24-hours ECG monitoring, blood lipids analysis, transthoracic echocardiography, ultrasound Doppler of brachiocephalic arteries, abdominal aorta branches, lower extremities arteries, renal arteries. If prescribed we performed stress echocardiography, transesophageal echocardiography, coronary angiography, renal arteries angiography, pancerebral angiography. So, the investigation was made for the active revealing of atherosclerotic signs. The main parameters of heart biomechanics and main arteries kinetics we calculated using apexcardiography and sphygmography and included: speed, acceleration, power, work in each phase of the cardiocycle by apexcardiography, as well as in period of prevalence of inflow over outflow and in period of prevalence of outflow over inflow in sphygmography. All the patients were divided into two main groups according to the quantity of extrasystoles per 24 hours: 1 group - less than 3000, 2 group -3000 extrasystoles and more per 24 hours. RESULTS: We determined that the atherosclerotic process was more advanced and more often the group 2. The atherosclerosis was more severe in patients with extrasystoles before the mitral valve opening and in fast ventricles' filling phase in cardiocycle. The main parameters of heart biomechanics and main arteries kinetics (speed, acceleration, power, work) calculated by apexcardiography and sphygmography increased with the further tendency: if earlier extrasystole appears in cardiocycle, than more changes were observed. Analyzing the methods of physics for fluid movement - Newton equation for liquids and Reynold number - we demonstrated that in extrasystolic arrhythmia in first post-extrasystolic wave there are the conditions for the turbulent blood flow that can cause the onset and progressing of atherosclerotic process. CONCLUSIONS: Extrasystolic arrhythmia is an additional risk factor of main arteries atherosclerosis. Especially this thesis is fair for the extrasystoles that appear in cardiocycle before the mitral valve opening and in fast ventricles' filling phase.

Hemodynamic arterial changes in heart failure: a proposed new paradigm of "heart and vessels failure".

BACKGROUND: Although heart failure (HF) is one of the most common conditions affecting the heart, little attention has been placed on the role of arteries in contributing to the progression of this disease. We sought to determine the hemodynamic change of arteries in HF patients subdivided according to left ventricular ejection fraction. The major goal was to establish the active compensatory role of arteries in HF. METHODS: Using sphygmography, we systematically studied a cohort of 228 HF patients and 52 healthy controls. We focused on the common carotid as the main elastic artery and the posterior tibial as the main muscular artery. Moreover, we categorized the three HF groups, HFrEF, HFmrEF, HFpEF, into two subgroups (A and B) according to the presence or absence of HF signs at baseline. RESULTS: We discovered that all the parameters of measured arterial kinetics, i.e., work, power, acceleration, and speed, were significantly increased (P<0.001 by one-way ANOVA) in the groups without HF signs. In contrast, all the arterial kinetics parameters were significantly reduced (P<0.001) in the groups exhibiting HF signs. Similar results were obtained in both types of arteries and were consistently observed across all the three different types of HF, although with some differences in magnitude. Finally, we discovered that HFpEF patients exhibited more compromised arterial function vis-à-vis HFrEF patients. CONCLUSIONS: We provide the first documentation of an active compensatory role of arteries during HF. Mechanistically, we explain these findings by a dual activity of large arteries accomplished via an active propulsive work and a concurrent hemodynamic suction. These underestimated arterial functions partially compensate for the heart dysfunction in HF, underlining a key interplay between the heart and the vessels. We propose a new paradigm that we define as "heart and vessels failure" that explicitly focuses on both heart and vessels' interaction during the progression of HF.

Women and Diabetes: Preventing Heart Disease in a New Era of Therapies.

Despite major advances in cardiovascular research over the past decade, women with type 2 diabetes have a high risk of cardiovascular events. Several factors contribute to the poor prognosis for women, including higher levels of frailty and comorbidities, but their cardiovascular risk is underestimated and there is suboptimal implementation and uptitration of new evidence-based therapies, leading to high morbidity and mortality. Recent studies highlight the need for better management of diabetes in women that can be pursued and achieved in light of recent results from randomised controlled trials demonstrating evidence of the benefits of new therapeutic strategies in improving cardiovascular outcomes and quality of life of women covering the entire cardiovascular continuum. This review critically discusses the multiple benefits for women of new pharmacological treatments, such as glucagon-like peptide-1 receptor agonists, sodium-glucose cotransporter type 2 inhibitors (SGLT2i), proprotein convertase subtilisin/kexin type 9 inhibitors, inclisiran, icosapent ethyl and bempedoic acid in preventing cardiovascular events, and treatments, such as angiotensin receptor neprilysin inhibitors, SGLT2i, vericiguat and omecamtiv mecarbil, for preventing heart failure.

Pathophysiology and management of recreational drug-related acute coronary syndrome: ANMCO position statement.

Recreational drug use may cause coronary artery disease through several mechanisms. An increasing number of young patients with drug-related acute coronary syndrome have been reported over recent years. The present position statement reports the most recent epidemiological data on acute coronary syndrome in the setting of drug abuse, describes the main pathophysiological mechanisms underlying coronary artery disease and acute events in these patients, and provides practical recommendations on management and an overview of prognosis.

The interplay between cardiology and diabetology: a renewed collaboration to optimize cardiovascular prevention and heart failure management.

Type 2 diabetes mellitus (T2DM) portends high risk of atherosclerotic cardiovascular (CV) events and of CV mortality; moreover, this group of patients has a very high probability of developing heart failure (HF). In this review, we discuss new advances in pharmacological treatment both in CV prevention and in HF management with a special focus on T2DM patients. A large number of randomized clinical trials and meta-analyses provided strong evidence about therapeutic strategies acting on glucose metabolism, such as GLP-1 RA and SGLT2i and about lipid-lowering treatment, such as PCSK9i and icosapent ethyl. Moreover, SGLT2i demonstrated strong evidence of benefit particularly in HF management both in diabetic and non-diabetic patients. The pathophysiological bases of multiple mechanisms of benefit of this class of drug explain the unexpected and remarkable results demonstrated both by prevention trials and by trials dedicated only to HF (like DAPA-HF). These, new drugs in the CV therapeutic armamentarium are establishing a new comprehensive approach from prevention to therapy of HF, giving more emphasis on HF classification in four stages (A→D). New therapies, which are on the horizon, promise to further reduce CV mortality and morbidity in HF patients irrespective of diabetic status.