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Abstract Background The aim of this study was to evaluate the association between simple, combined lipid biomarkers, and 20-year cumulative incidence of new type 2 diabetes mellitus (T2DM) among adults participating in the ATTICA cohort study (2002–2022). Methods The present analysis included data from 2000 individuals free of T2DM at baseline (age 43 ± 13 years; 51% women). Sociodemographic, anthropometric, lifestyle, clinical, and biochemical parameters were collected at baseline and follow-up examinations; combined lipid markers were evaluated. Results The 20-year cumulative incidence of T2DM was 26.3% (95%CI 24.4, 28.3%). All, simple and combined lipid markers were independently associated with new T2DM onset. The accuracy of simple and combined markers was approximately 75%, without any significant differences between simple and combined indices. The additive correct classification gain of lipid markers to glucose metabolism indices on 20-year new T2DM cumulative incidence varied between 0.9% for cardiometabolic index to 10.6% for LDL-cholesterol. Conclusions Lipid profile is associated with the long-term onset of T2DM. Evaluated through simple or combined markers, lipid profiles can be utilized for identifying and improving risk stratification in individuals at high risk for T2DM, while also enhancing the effectiveness of primary prevention measures and public health strategies.

Background and aimThis study aims to investigate the role of the built environment in terms of urban-rural disparities in cardiovascular disease (CVD) epidemiology, focusing on middle- and long-term CVD risk assessment. Moreover, this study seeks to explore sex-specific differences in urban and rural settings.MethodsThe ATTICA Study is a prospective study conducted from 2002 onwards. At baseline, a random sample of 3,042 CVD-free adults (49.8% men) were randomly drawn from the population of the Attica region, in Greece, with 78% dwelling in urban and 22% in rural municipalities. Follow-up examinations were performed in 2006, 2012, and 2022. Of the total participants, 1,988 had complete data for CVD assessment in the 20-year follow-up.ResultsThe 10-year and 20-year CVD incidence was 11.8%, 28.0% in rural municipalities and 16.8%, 38.7% in urban municipalities, respectively (ps

The objective of this study was to investigate spatiotemporal variability of cardiovascular disease (CVD) occurrence and identify spatial clusters on Attica region (Greece), over a 20-year period (2002-2022). The 10- and 20-year occurrence of fatal and non-fatal cardiovascular disease was obtained from the ATTICA study, which was conducted between 2002 and 2022. The sample used in this analysis included 1,935 (49,8% males) and 1,902 participants (49.5% males), respectively. CVD occurrence rate at the municipality level were mapped, and spatial autocorrelation analysis was performed to identify statistically significant clusters and outliers in the Attica region. The mapping of CVD occurrence rates revealed an observable increase in most municipalities during the observation period. In addition, a statistically significant clustering of high CVD occurrence rates was found in the most urbanized municipalities of the study area over the period under study. These findings underscore the need for targeted interventions, focusing on urban populations, to effectively address this trend. Highlights: • This study addresses the research gap on CVD trends in Attica, Greece, over 20 years. • CVD rates rose notably in the most urbanized municipalities of central Athens, while suburban areas maintained lower levels. • Positive spatial autocorrelation analysis was revealed for both the 10-year and 20-year CVD occurrence rates.

Objective: The purpose of this study was to examine sex-related differences in the long-term (20-year) incidence of cardiovascular disease (CVD) and its determinants. Methods: In 2002, 3,042 apparently healthy Greek adults were recruited, and in 2022, the 20-year follow-up was conducted with 2,169 participants, 1,988 of whom had completed CVD assessments. Sex-specific analyses using nested Cox proportional hazards were performed, as well as classification and regression tree (CRT) analysis modeling. Results: Overall, men exhibited higher CVD incidence rates during the 20-year period compared to women; age-adjusted analyses revealed, however, that women displayed higher CVD rates between 55 and 75 years old. CVD mortality and premature mortality were more pronounced in men. Although, CVD presentation in women lagged men, over survival was comparable. Moreover, the CVD risk factors burden was greater in women beyond the age of 35. Clinical risk factors and adherence to the Mediterranean dietary pattern emerged as the most significant predictors of sex-specific 20-year CVD incidence. Conclusion: This study highlights various sex disparities in CVD, challenging prevailing perceptions that CVD is a men's phenomenon. Tailoring prevention strategies to address sex-specific differences, particularly through lifestyle interventions, could effectively reduce CVD burden.

This comprehensive review explores the incidence, pathophysiology, and management of atrial fibrillation (AF) following percutaneous closure of patent foramen ovale (PFO). Although AF is considered a common adverse event post PFO closure, its incidence, estimated at

Refractory recurrent pericarditis is a troublesome condition that severely impairs the quality of life of affected patients and significantly increases healthcare spending. Until recently, therapeutic options included only a few medications and most of the patients resorted to chronic glucocorticoid treatment with steroid dependence. In the most recent decade, the introduction of interleukin-1 blockers in clinical practice has revolutionized the treatment of glucocorticoid-dependent and colchicine-resistant recurrent pericarditis due to their excellent efficacy and good safety profile. The rationale for the introduction of this class of medications in clinical practice is the autoinflammatory nature of recurrent pericarditis in a substantial rate of cases, with interleukin-1 being the main pro-inflammatory cytokine involved in this context. This review aims to discuss the contemporary available evidence from original research and real-world data on interleukin-1 blocker use in refractory recurrent pericarditis, in terms of indications, mechanism of action, efficacy, side effects, and recommended treatment protocols. Moreover, novel treatment proposals, such as hydroxychloroquine, beta blockers, and cannabidiol, which showed encouraging preliminary results, are addressed. Finally, gaps in knowledge, unmet needs, and future perspectives related to recurrent pericarditis are thoroughly discussed.

Patent foramen ovale (PFO) is a remnant of the foetal circulation resulting from incomplete occlusion of the septum primum and septum secundum. Although prevalent in about 25% of the population, it mainly remains asymptomatic. However, its clinical significance in situations such as cryptogenic stroke, migraine, and decompression illness (DCI) has been well described. Recent randomised clinical trials (RCTs) have demonstrated the efficacy of percutaneous PFO closure over pharmacological therapy alone for secondary stroke prevention in carefully selected patients. Notably, these trials have excluded older patients or those with concurrent thrombophilia. Furthermore, the role of closure in other clinical conditions associated with PFO, like decompression sickness (DCS) and migraines, remains under investigation. Our review aims to summarise the existing literature regarding epidemiology, pathophysiological mechanisms, optimal management, and closure indications for these special patient groups.

This study aimed to evaluate the association between adherence to the Mediterranean diet and the 20-year incidence of type II diabetes mellitus (T2DM) among adults from the ATTICA study. This study involved a prospective cohort of 3042 men and women recruited at baseline from the Attica region in Greece. Sociodemographic, anthropometric, lifestyle, and clinical characteristics were evaluated at baseline and follow-up examinations; adherence to the Mediterranean diet was assessed through the MedDietScore (range 0–55); four Mediterranean diet trajectories were identified (i.e., increasing, decreasing, and sustained high and sustained low adherence levels). For the present analysis, data from 2000 individuals with complete information were used (age 43 ± 13 years; 49% men). Over the 20-year period, 26.3% (95%CI 24.4%, 28.3%) of participants developed T2DM; men exhibited a 1.5-times higher incidence compared to women (p < 0.001). Individuals consistently close to the Mediterranean diet throughout the studied period had an improved glycemic and lipidemic profile (at baseline and at 10-y follow-up) (all p-values < 0.001) and showed a 21% reduction in their 20-year risk of developing T2DM compared to those who were consistently away (RR = 0.79, 95%CI 0.47, 0.86). A long-term adherence to the Mediterranean diet is protective against the onset of T2DM and, therefore, could be incorporated in public health actions for the prevention of the disease.

Recurrent pericarditis is a problematic clinical condition that impairs the quality of life of the affected patients due to the need for repeated hospital admissions, emergency department visits, and complications from medications, especially glucocorticoids. Unfortunately, available treatments for recurrent pericarditis are very limited, including only a handful of medications such as aspirin/NSAIDs, glucocorticoids, colchicine, and immunosuppressants (such as interleukin-1 (IL-1) blockers, azathioprine, and intravenous human immunoglobulins). Until recently, the clinical experience with the latter class of medications was very limited. Nevertheless, in the last decade, experience with IL-1 blockers has consistently grown, and valid clinical data have emerged from randomized clinical trials. Accordingly, IL-1 blockers are a typical paradigm shift in the treatment of refractory recurrent pericarditis with a clearly positive cost/benefit ratio for those unfortunate patients with multiple recurrences. A drawback related to the above-mentioned medications is the absence of universally accepted and established treatment protocols regarding the full dose administration period and the need for a tapering protocol for individual medications. Another concern is the need for long-standing treatments, which should be discussed with the patients. The above-mentioned unmet needs are expected to be addressed in the near future, such as further insights into pathophysiology and an individualized approach to affected patients.

Background: The long-term effects of high fish intake rich in n-3 fatty acids for deterring cardiovascular disease (CVD) and related adverse outcomes in healthy individuals have not been yet elucidated.Purpose: To evaluate the association between total seafood, as well as small fish, intake on 10- and 20-year CVD incidence and mortality in healthy adults.Methods: A prospective cohort study (n = 2,020) was conducted in healthy community dwelling adults in Athens, Greece, selected following age- and sex-based random multistage sampling (mean ± SD age at baseline: 45.2 ± 14.0 years). Seafood (high (>2 servings/week) vs. low (≤2 servings/week) intake), including small fish rich in n-3 fatty acids (high (>1 serving/week) vs. low (≤1 serving/week) intake), consumption was evaluated by semi-quantitative food frequency questionnaire at baseline. The occurrence of non-fatal and/or fatal CVD events (ICD-10) was assessed during 10- and 20-year follow-up periods.Results: Only 32.7% and 9.6% of participants had high seafood and small fish intakes, respectively. Participants with high seafood intake had 27% decreased 10-year CVD risk (adj. HR:0.73; 95% CI:0.55-0.98) and 74% lower attributable mortality (adj. HR:0.26; 95% CI:0.11-0.58). Participants with high seafood intake also sustained a 24% lower 20-year risk of CVD mortality (adj. HR: 0.76; 95% CI: 0.55-0.98). Moreover, participants with high small fish intake had a lower 10-year CVD risk and 76% decreased risk of 10-year CVD mortality (adj. HR:0.24; 95% CI:0.06-0.99), even among normotensive individuals (adj. HR:0.31; 95% CI:0.13-0.73). When analogous analyses focused on 20-year CVD incidence and mortality, similar but not significant associations were observed (all p-values >0.10).Conclusion: High intake of seafood, and particularly small fish rich in n-3 fatty acids, was associated with a lower risk of 10-year fatal and non-fatal CVD. Thus, public health interventions aimed at enhancing small fish consumption may most effectively deter long-term CVD outcomes, particularly among low risk normotensive individuals.

Objectives: The aim of this study was to assess the capacity of optimized multipoint pacing (MPP) over optimized cardiac resynchronization therapy (CRT), in terms of clinical, functional, and echocardiographic parameters among patients with dyssynchronous heart failure (HF). Methods: Eighty patients (Caucasian, 77.5% male, 68.4 ± 10.1 years, and 53.8% ischemic cardiomyopathy) sequentially received optimized CRT and optimized MPP over 6- and 12-month periods in a single-arm clinical trial. Clinical, laboratory, and echocardiographic assessment was conducted at baseline and after the completion of each step. Results: Significant additive effects of optimized MPP over optimized CRT were noted with regard to 6-min walking distance (baseline/optCRT/optMPP: 293 ± 120 m vs 367 ± 94 m vs 405 ± 129 m and p

Objective: The efficacy of renal sympathetic denervation (RDN) has been affirmed by a number of recent clinical studies, despite controversies in this field over the last five years. Therefore, it is of paramount importance that hypertension experts debate the merits of RDN by revealing and expressing their personal beliefs and perspectives regarding this procedure. Methods: A cross-sectional survey was conducted among Greek leaders of the Hypertension Excellence Centers with the use of a closed-type questionnaire specifically designed to elicit information and evaluate the respondent's views and perspectives about RDN efficacy, safety and ideal target patient population. Results: A total of 36 participants completed the survey. Based on the results, RDN was considered efficient (91.7%) and safe (94.5%), while the overwhelming majority of the participants felt confident in the long-term efficacy (88.9%) of the intervention and that it lacks reliable predictors of blood pressure response (94.5%). Patients with resistant (91.7%), ultra-resistant (94.4%), and uncontrolled hypertension (80.6%) were suggested as ideal candidates for RDN. Establishing a close co-operation between interventionalists and hypertension experts was considered essential to ensure the efficacy (97.2%) as well as the safety (97.3%) of the procedure. Conclusion: The vast majority of Greek hypertension experts surveyed were convinced of the efficacy and safety of RDN based on the preponderance of available scientific and clinical data. Identification of the ideal patient group remains controversial. Respondents generally agreed on the necessity of building close collaborative relationships between interventionalists and hypertension experts in order to improve RDN clinical outcome.

Objective Postoperative atrial fibrillation (POAF) is a common complication affecting approximately one-third of patients after cardiac surgery and valvular interventions. This umbrella review systematically appraises the epidemiological credibility of published meta-analyses of both observational and randomised controlled trials (RCT) to assess the risk and protective factors of POAF.Methods Three databases were searched up to June 2021. According to established criteria, evidence of association was rated as convincing, highly suggestive, suggestive, weak or not significant concerning observational studies and as high, moderate, low or very low regarding RCTs.Results We identified 47 studies (reporting 61 associations), 13 referring to observational studies and 34 to RCTs. Only the transfemoral transcatheter aortic valve replacement (TAVR) approach was associated with the prevention of POAF and was supported by convincing evidence from meta-analyses of observational data. Two other associations provided highly suggestive evidence, including preoperative hypertension and neutrophil/lymphocyte ratio. Three associations between protective factors and POAF presented a high level of evidence in meta-analyses, including RCTs. These associations included atrial and biatrial pacing and performing a posterior pericardiotomy. Nineteen associations were supported by moderate evidence, including use of drugs such as amiodarone, b-blockers, glucocorticoids and statins and the performance of TAVR compared with surgical aortic valve replacement.Conclusions Our study provides evidence confirming the protective role of amiodarone, b-blockers, atrial pacing and posterior pericardiotomy against POAF as well as highlights the risk of untreated hypertension. Further research is needed to assess the potential role of statins, glucocorticoids and colchicine in the prevention of POAF.PROSPERO registration number CRD42021268268.

Endothelial dysfunction (ED) is characterized by imbalanced vasodilation and vasoconstriction, elevated reactive oxygen species (ROS), and inflammatory factors, as well as deficiency of nitric oxide (NO) bioavailability. It has been reported that the maintenance of endothelial cell integrity serves a significant role in human health and disease due to the involvement of the endothelium in several processes, such as regulation of vascular tone, regulation of hemostasis and thrombosis, cell adhesion, smooth muscle cell proliferation, and vascular inflammation. Inflammatory modulators/biomarkers, such as IL-1α, IL-1β, IL-6, IL-12, IL-15, IL-18, and tumor necrosis factor α, or alternative anti-inflammatory cytokine IL-10, and adhesion molecules (ICAM-1, VCAM-1), involved in atherosclerosis progression have been shown to predict cardiovascular diseases. Furthermore, several signaling pathways, such as NLRP3 inflammasome, that are associated with the inflammatory response and the disrupted H2S bioavailability are postulated to be new indicators for endothelial cell inflammation and its associated endothelial dysfunction. In this review, we summarize the knowledge of a plethora of reviews, research articles, and clinical trials concerning the key inflammatory modulators and signaling pathways in atherosclerosis due to endothelial dysfunction.

The study aimed to assess the trajectories of lifestyle characteristics and their association with 20-year cardiovascular disease (CVD) incidence. In 2002, 3042 Greek adults (aged: 45 (12) years) free of CVD were enrolled. In 2022, the 20-year follow-up was performed on 2169 participants; of those, 1988 had complete data for CVD. The 20-year CVD incidence was 3600 cases/10,000 individuals; the man-to-woman ratio was 1.25, with the peak difference in the 35–45 age group (i.e., 2.1); however, a reversal of the trend was observed in the age-groups 55–65 and 65–75, with a resumption of an almost equal incidence in those >75 years. In multi-adjusted analysis, age, sex, abnormal waist circumference, hypercholesterolemia, hypertension, and diabetes were positively associated with 20-year CVD risk, explaining 56% of the excess CVD risk, whereas an additional 30% was attributed to lifestyle trajectories; being physically active throughout life-course and being close to the Mediterranean diet were protective, while continuous smoking was detrimental against CVD risk. Mediterranean diet adherence protected against CVD development even if not sustained, while quitting smoking or engaging in physical activities during the 20-year observation did not offer any significant protection. A life-course personalized approach that is cost-effective and long-term sustained is needed to prevent CVD burden.

Background: The presence of an electrocardiographic (ECG) strain pattern—among other ECG features—has been shown to be predictive of adverse cardiovascular outcomes in asymptomatic patients with aortic stenosis. However, data evaluating its impact on symptomatic patients undergoing TAVI are scarce. Therefore, we tried to investigate the prognostic impact of baseline ECG strain pattern on clinical outcomes after TAVI. Methods: A sub-group of patients of the randomized DIRECT (Pre-dilatation in Transcatheter Aortic Valve Implantation Trial) trial with severe aortic stenosis who underwent TAVI with a self-expanding valve in one single center were consecutively enrolled. Patients were categorized into two groups according to the presence of ECG strain. Left ventricular strain was defined as the presence of ≥1 mm convex ST-segment depression with asymmetrical T-wave inversion in leads V5 to V6 on the baseline 12-lead ECG. Patients were excluded if they had paced rhythm or left bundle branch block at baseline. Multivariate Cox proportional hazard regression models were generated to assess the impact on outcomes. The primary clinical endpoint was all-cause mortality at 1 year after TAVI. Results: Of the 119 patients screened, 5 patients were excluded due to left bundle branch block. Among the 114 included patients (mean age: 80.8 ± 7), 37 patients (32.5%) had strain pattern on pre-TAVI ECG, while 77 patients (67.5%) did not exhibit an ECG strain pattern. No differences in baseline characteristics were found between the two groups. At 1 year, seven patients reached the primary clinical endpoint, with patients in the strain group demonstrating significantly higher mortality in Kaplan–Meier plots compared to patients without left ventricular strain (five vs. two, log-rank p = 0.022). There was no difference between the strain and no strain group regarding the performance of pre-dilatation (21 vs. 33, chi-square p = 0.164). In the multivariate analysis, left ventricular strain was found to be an independent predictor of all-cause mortality after TAVI [Exp(B): 12.2, 95% Confidence Intervals (CI): 1.4–101.9]. Conclusion: Left ventricular ECG strain is an independent predictor of all-cause mortality after TAVI. Thus, baseline ECG characteristics may aid in risk-stratifying patients scheduled for TAVI.

Diving is a fascinating activity, but it does not come without any cost; decompression illness (DCI) is one of the most frequent diseases occurring in divers. Rapid surfacing after diving causes alveolar rupture and bubbles release, which enter in the systemic circulation and could embolize numerous organs and tissues. The presence of patent foramen ovale (PFO) contributes to the passage of venous gas bubbles into the arterial circulation, increasing the risk of complications related to DCI. The diagnosis is established with a detailed medical history, a comprehensive clinical evaluation, and a multimodal imaging approach. Although the percutaneous closure of PFO is ambiguous for divers, as a primary prevention strategy, transcatheter management is considered as beneficial for DCI recurrence prevention. The aim of this study is to introduce the basic principles of DCI, to review the pathophysiological connection between DCI and PFO, to highlight the risk factors and the optimal treatment, and, last but not least, to shed light on the role of closure as primary and secondary prevention.

BackgroundSudden cardiac death (SCD) is a global public health issue, accounting for 10–20% of deaths in industrialized countries. Identification of modifiable risk factors may reduce SCD incidence.MethodsThis umbrella review systematically evaluates published meta-analyses of observational and randomized controlled trials (RCT) for the association of modifiable risk and protective factors of SCD.ResultsFifty-five meta-analyses were included in the final analysis, of which 31 analyzed observational studies and 24 analyzed RCTs. Five associations of meta-analyses of observational studies presented convincing evidence, including three risk factors [diabetes mellitus (DM), smoking, and early repolarization pattern (ERP)] and two protective factors [implanted cardiac defibrillator (ICD) and physical activity]. Meta-analyses of RCTs identified five protective factors with a high level of evidence: ICDs, mineralocorticoid receptor antagonist (MRA), beta-blockers, and sodium-glucose cotransporter-2 (SGLT-2) inhibitors in patients with HF. On the contrary, other established, significant protective agents [i.e., amiodarone and statins along with angiotensin-converting enzyme (ACE) inhibitors in heart failure (HF)], did not show credibility. Likewise, risk factors as left ventricular ejection fraction in HF, and left ventricular hypertrophy, non-sustain ventricular tachycardia, history of syncope or aborted SCD in pediatric patients with hypertrophic cardiomyopathy, presented weak or no evidence.ConclusionsLifestyle risk factors (physical activity, smoking), comorbidities like DM, and electrocardiographic features like ERP constitute modifiable risk factors of SCD. Alternatively, the use of MRA, beta-blockers, SGLT-2 inhibitors, and ICD in patients with HF are credible protective factors. Further investigation targeted in specific populations will be important for reducing the burden of SCD.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020216363, PROSPERO CRD42020216363.

Background: Renal functional reserve (RFR), defined as the difference between stress and resting glomerular filtration rate (GFR), may constitute a diagnostic tool to identify patients at higher risk of developing acute kidney injury or chronic kidney disease. Blunted RFR has been demonstrated in early stages of hypertension and has been attributed to impaired vascular reactivity due to an overactive sympathetic nervous system (SNS). Objective: The purpose of this study was to investigate whether RFR correlates with other phenotypes expressing overactivity of the SNS in patients with essential hypertension and preserved renal function. Methods: Thirty-six patients with untreated essential hypertension and a GFR >60 mL/min/1.73 m2 were enrolled. The following parameters were measured: RFR, 24-h ambulatory blood pressure (BP) profile, a treadmill stress test, and an echocardiographic examination. Urine and venous samples were obtained at specific time points for the determination of clinical parameters, and both resting and stress GFR were calculated by using endogenous creatinine clearance for the measurement of RFR after an acute oral protein load (1 g/kg). Results: Twenty-one patients had a RFR

BackgroundLeft atrial (LA) function is linked to atrial fibrillation (AF) pathogenesis. AF catheter ablation decreases disease burden with potentially favorable effects on cardiac function. Atrial volume-pressure loops can optimally assess the LA function.ObjectiveTo investigate changes in LA function by volume-pressure loops after paroxysmal AF ablation and explored potential differences between the radiofrequency and cryoballoon ablation.MethodsWe analyzed 44 patients undergoing paroxysmal AF ablation from 2 centers, 22 treated with radiofrequency and 22 with cryoablation. Pre- and post-procedure, all patients underwent a real-time three-dimensional transthoracic ECG to evaluate LA volume, while simultaneously recording LA pressure following transseptal puncture. Volume-pressure loops pre- and post-procedure were created by paired data. Areas of A-loop (LA booster pump function) and V-loop (LA reservoir function), and the stiffness constant determining the slope of the exponential curve during LA filling were calculated.ResultsAverage LA pressure, A-wave amplitude, and V-wave amplitude were increased post-procedurally (p < 0.001). Overall, A-loop area decreased (p = 0.001) and V-loop area tended to increase (p = 0.07). The change in both A-loop and V-loop areas was similar between radiofrequency- and cryoballoon-treated patients (p = 0.18 and p = 0.52, respectively). However, compared with cryoballoon-treated patients, radiofrequency-treated patients had higher increase in the stiffness constant (b = 0.059; 95% CI: 0.022–0.096; p = 0.006).ConclusionAF catheter ablation by the radiofrequency or cryoballoon is associated with the decrease of the booster pump function and increase of the reservoir function. Moreover, there is a post-procedural increase of LA pressure which is associated with an acute increase in LA stiffness in radiofrequency ablation, but not in cryoablation.

Background: MicroRNAs have been linked to angiogenesis and could prove to be valuable future therapeutic targets in ischemic cardiovascular diseases.Methods: Ten-week-old male C57Bl/6 mice were subjected to left femoral artery ligation and were treated with microRNA-126 mimic at a dose of 5 mg/kg (Group A, n = 10) or 5 mg/kg microRNA mimic negative control (Group B, n = 10) on days 1, 3, and 7. Laser Doppler imaging was performed to verify successful ligation on day 0 and to evaluate differences in the ischemic-to-normal (I/N) hind limb perfusion ratio on day 28. Muscle tissue expression of microRNA-126 and vascular endothelial growth factor (VEGF) was determined via PCR.Results: Following microRNA-126 mimic administration in Group A subjects, we noted a stepwise increase in I/N hind limb perfusion ratio (Day 0: 0.364 ± 0.032 vs. Day 8: 0.788 ± 0.049 vs. Day 28: 0.750 ± 0.039, p = 0.001). In Group B a stepwise increase in I/N hind limb perfusion ratio was observed (Day 0: 0.272 ± 0.057 vs. Day 8: 0.382 ± 0.020 vs. Day 28: 0.542 ± 0.028, p = 0.074). Muscle tissue expression of microRNA-126 in the ischemic hind limb of Group A was 350-fold lower compared to the ischemic hind limb of Group B (p < 0.001). A higher expression (14.2-fold) of VEGF in the ischemic hind limb of microRNA-126-treated mice compared to that of control group was detected (p < 0.001). A statistically significant negative correlation was noted between microRNA-126 and VEGF tissue expression levels in the ischemic limbs of the entire study population.Conclusion: MicroRNA-126 delivery in the ischemic hind limb of mice improved vascular perfusion with VEGF upregulation.

Major cardiovascular (CV) outcome trials with glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are currently available. These agonists have proven their CV safety, in harmony with the US Food and Drug Administration (FDA) recommendation for antidiabetic drugs. The potential cardioprotective effect of incretin-based therapies is attributed to their multiple non-glycaemic actions in the CV system, including changes in insulin resistance, weight loss, reduction in blood pressure, improved lipid profile and direct effects on the heart and vascular endothelium. Liraglutide, semaglutide and albiglutide have been demonstrated to reduce the risk of major adverse cardiac events (MACE), whereas lixisenatide and extended-release exenatide had a neutral effect. Thus, it is conceivable that there are different drug-specific properties across the class of GLP-1 RAs. In this review, we discuss the results of the five recently published randomised CV outcome trials with GLP-1 RAs, along with the potential differences and the pleiotropic actions of these agents on the CV system. Keywords: Cardiovascular disease, Diabetes mellitus, Randomised controlled trials, Treatment

Background: Arterial stiffness is linked to the progression of atherosclerosis, while activation of vitamin D receptor exerts favorable cardiovascular effects in patients with renal insufficiency. In this study, we investigated the effects of oral treatment with paricalcitol, a potent vitamin D receptor activator, on arterial stiffness and osteopontin, a marker of atherosclerosis, in hypertensive patients with chronic kidney disease (CKD) and secondary hyperparathyroidism. Methods: We followed up 29 treated hypertensive patients (mean age: 74.1 years, 19 men, office blood pressure = 132/85 mmHg) with CKD stages 3–5 (mean glomerular filtration rate [GFR] = 19.4 ml/min/1.73 m2) who were on therapy with oral paricalcitol for 1 year. The control group consisted of 10 age-, sex-, and GFR-matched hypertensive patients with secondary hyperparathyroidism. Results: After 1 year of treatment with paricalcitol compared to baseline, there was no statistical difference in levels of GFR, office blood pressure, and osteopontin (p = NS for all), while carotid-femoral PWV was reduced from 11.8 ± 2.6 m/s to 11.2 ± 2.4 m/s (p

Arrhythmias in pericardial syndromes have been poorly investigated and available data are mainly obtained from relevant studies however having different endpoints from arrhythmias. Thus, the incidence and prevalence of any type of arrhythmias may be actually higher than generally considered. Atrial arrhythmias, mainly atrial fibrillation and flutter have been reported as the most common rhythm disturbances in the setting of acute pericarditis. Concerning pathophysiology of atrial arrhythmias, in contrast to earlier hypothesis that they occur exclusively in the presence of an underlying structural heart disease, recent data support an arrhythmogenic potential of acute pericardial inflammation regardless of the presence of heart disease. In cases of myopericarditis, namely primarily pericarditis with evidence of myocardial involvement (i.e., troponin elevation without however overt left ventricular dysfunction and/or segmental wall motion abnormalities), ventricular arrhythmias appear to prevail. With reference to the rest of pericardial syndromes data on arrhythmias development are even more sparce. In particular, in constrictive pericarditis atrial tachyarrhythmias are the most commonly detected and seem to be related to disease severity and possibly to the underlying etiology. In this review we have summarized the available information on the incidence and prevalence of arrhythmias in pericardial syndromes. We wish to emphasize that the clinical significance of arrhythmias in this setting in terms of prognosis and optimal medical treatment (including need and safety of anticoagulation in atrial fibrillation/flutter complicating acute pericarditis), should be further investigated.

Antithrombotic treatment including anticoagulants and antiplatelets has evolved during the last decades, and several recommendations have been included in the latest guidelines regarding the proper management of patients undergoing vascular surgery. However, there are significant differences compared to older recommendations, and indications vary among patients with peripheral artery disease, carotid disease, and abdominal aortic aneurysm. In this mini review, we critically evaluate all these data to produce useful conclusions for everyday clinical practice. Keywords: Antithrombotic treatment, Antiplatelet treatment, Anticoagulant, Vascular surgery

Natural disasters such as tsunami, hurricanes, and earthquakes may have a negative impact on cardiac health. The aim of our systematic review is to evaluate the impact of earthquakes on the incidence of acute coronary syndromes and cardiac mortality and to examine the impact of the time of earthquakes on the incidence of acute coronary syndromes. MEDLINE and Cochrane databases were searched for studies assessing the impact of earthquakes on acute coronary syndromes from inception until December 20, 2017. Reference lists of all included studies and relevant review studies were also searched. A total of 26 studies on 12 earthquake disasters were included in the systematic review. The existing data show a significant negative impact of the Great East Japan, Christchurch, Niigata-Chuetsu, Northridge, Great Hanshin-Awaji, Sichuan, Athens, Armenia, and Noto Peninsula earthquakes on the incidence of acute coronary syndromes. By contrast, studies on the Newcastle, Loma Prieta, and Thessaloniki earthquakes did not show a significant correlation with myocardial infarction and cardiac mortality. In conclusion, earthquakes may be associated with increased incidence of acute coronary syndromes and cardiovascular mortality. There are conflicting data about the impact of the timing of earthquakes on the occurrence of acute coronary syndromes. Preventive measures to promote the adjustment of healthcare systems to treat cardiovascular diseases after natural disasters should be immediately implemented particularly in high-risk regions. Keywords: Earthquakes, Acute coronary syndrome, Myocardial infarction, Natural disaster

Abstract Ranolazine is a new medication for the treatment of refractory angina. However, except its anti‐anginal properties, it has been found to act as an anti‐arrhythmic. The aim of our systematic review is to present the existing data about the impact of ranolazine in ventricular arrhythmias. We searched MEDLINE and Cochrane databases as well clinicaltrials.gov until September 1, 2017 to find all studies (clinical trials, observational studies, case reports/series) reported data about the impact of ranolazine in ventricular arrhythmias. Our search revealed 14 studies (3 clinical trials, 2 observational studies, 8 case reports, 1 case series). These data reported a beneficial impact of ranolazine in ventricular tachycardia/fibrillation, premature ventricular beats, and ICD interventions in different clinical settings. The existing data highlight the anti‐arrhythmic properties of ranolazine in ventricular arrhythmias.

Currently, renal denervation (RDN) has proven its overall procedural and renal safety in registries and trials. Available data, suggest that vascular complications are rather scarce in modern studies using established neuromodulation catheters of different technologies and kidney parameters are mainly maintained stable overtime in RDN patients. Identification of the impact of energy delivery at vascular level by means of advanced methodologies such as optical coherence tomography (OCT) is a meaningful research tool. This accumulation of evidence on the acute and late effects of the procedure in the renal artery tissue especially when a new catheter is tested, as in the present work can further enhance our knowledge on the pathophysiology and clinical outcome of RDN.

Individuals with hypertension that engage in regular exercise comprise a special patient group that needs a careful approach to differentiate hypertensive cardiac damage from physiologic cardiac adaptations. Echocardiography is the diagnostic modality of choice in such cases. Hypertensive left ventricular hypertrophy is expected to resemble isometric exercise-associated hypertrophy in some but not all cases. On the other side, the hearts of regularly exercising individuals are expected to be normal or present with a variable mix of increased end-diastolic volume and increased wall thickness. It is therefore important to clearly document the type, frequency and duration of exercise performed. Diastolic dysfunction even without hypertrophy is often the first and only presentation in hypertension. On the contrary, diastolic function in athletes may be enhanced in order to maintain a stroke volume in high heart rates. Novel imaging techniques such as global longitudinal strain are helpful to identify subclinical systolic dysfunction that is inconsistent with athletic cardiac changes. Keywords: Left ventricular hypertrophy, Athlete's heart

Background: following the publication of SYMPLICITY HTN-3 the field of renal of denervation was put on hold. Although SYMPLICITY HTN-3 was well-designed and sham-controlled trial it failed to show any meaningful reduction in office or 24 h ambulatory blood pressure. The procedure was however safe and allowed research to continue. Although several pitfalls of the study have been pointed out, incomplete renal denervation was also implicated. Since then, a great deal of basic and clinical research took place and will be briefly commented on in this article. Methods and results: Before and after SYMPLICITY-HTN-3, numerous uncontrolled, single or unblinded studies have shown substantial office BP reduction ranging from −7.7 to −32 mmHg and ambulatory BP ranging from −2.2 to 10.2 mmHg. Average weighted office systolic BP reduction was −20.8 mmHg and weighted average 24 h ambulatory BPM reduction was −7.8 mmHg. National and international registries have shown similar BP reductions, but results remained unconvincing due to lack of reliable sham controls. In recent years, 5 well-designed sham – controlled studies (beyond, SYMPLICITY-HTN-3) have been published. Of those studies two were single center and three were multicenter international studies. Four studies used single tip or multi-electrode, radiofrequency catheters and one used focused ultrasound. The three multicenter studies reported positive-placebo subtracted results and established BP reductions measured both in the office and by ambulatory monitoring. No serious adverse events were reported. Conclusions: It can therefore be concluded that the latest sham controlled studies established efficacy and safety of renal denervation.

Maintenance of endothelial cell integrity is an important component of human health and disease since the endothelium can perform various functions including regulation of vascular tone, control of hemostasis and thrombosis, cellular adhesion, smooth muscle cell proliferation, and vascular inflammation. Endothelial dysfunction is encompassed by complex pathophysiology that is based on endothelial nitric oxide synthase uncoupling and endothelial activation following stimulation from various inflammatory mediators (molecular patterns, oxidized lipoproteins, cytokines). The downstream signaling via nuclear factor-κB leads to overexpression of adhesion molecules, selectins, and chemokines that facilitate leukocyte adhesion, rolling, and transmigration to the subendothelial space. Moreover, oscillatory shear stress leads to pro-inflammatory endothelial activation with increased monocyte adhesion and endothelial cell apoptosis, an effect that is dependent on multiple pathways and flow-sensitive microRNA regulation. Moreover, the role of neutrophil extracellular traps and NLRP3 inflammasome as inflammatory mechanisms contributing to endothelial dysfunction has recently been unveiled and is under further investigation. Consequently, and following their activation, injured endothelial cells release inflammatory mediators and enter a pro-thrombotic state through activation of coagulation pathways, downregulation of thrombomodulin, and an increase in platelet adhesion and aggregation owing to the action of von-Willebrand factor, ultimately promoting atherosclerosis progression.