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Abstract: Proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i) represent a novel class of hypolipidemic drugs, providing an additional therapeutic option over conventional hypolipidemic treatments. Given the constantly lowering recommended LDL-C goals, low goal achievement rate and low compliance with treatment, new hypolipidemic drug classes may substantially contribute to residual risk reduction for atherosclerotic cardiovascular disease (ASCVD). This review aims to summarize contemporary evidence on the clinical role of PCSK9i in ASCVD prevention. PubMed and MEDLINE databases were searched for keywords in studies on PCSK9i and ASCVD. Approved PCSK9i are the monoclonal antibodies (Mabs), evolocumab and alirocumab, targeting PCSK9, and inclisiran, a small interfering RNA inhibiting PSCK9 synthesis. Overall, PCSK9i effectively reduced LDL-C and other atherogenic lipoproteins, including apolipoprotein B and lipoprotein(a) primarily. PSCK9i Mabs improved imaging markers reflecting coronary atherosclerotic plaque vulnerability and reduced ASCVD events in high-risk patients after short-term treatment ( < 3 years follow-up). They are currently indicated as a third-line treatment for secondary prevention and primary prevention in patients with familial hypercholesterolemia at high risk of not achieving their LDL-C goals. Patients with higher baseline ASCVD risk receive greater benefits from PCSK9i. Recent evidence suggests that evolocumab was effective and safe after long-term treatment. Ongoing trials investigate new therapeutic indications for PCSK9i while their cost-effectiveness is still being considered. PCSK9i is a novel hypolipidemic drug class currently indicated for reducing residual risk in secondary ASCVD prevention and high-risk patients.

Background The noncoding antisense transcript for β-secretase-1 (BACE1-AS) is a long noncoding RNA with a pivotal role in the regulation of amyloid-β (Aβ). We aimed to explore the clinical value of BACE1-AS expression in atherosclerotic cardiovascular disease (ASCVD). Methods Expression of BACE1-AS and its target, β-secretase 1 (BACE1) mRNA, was measured in peripheral blood mononuclear cells derived from 434 individuals (259 without established ASCVD [non-CVD], 90 with stable coronary artery disease [CAD], and 85 with acute coronary syndrome). Intima-media thickness and atheromatous plaques evaluated by ultrasonography, as well as arterial wave reflections and pulse wave velocity, were measured as markers of subclinical ASCVD. Patients were followed for a median of 52 months for major adverse cardiovascular events (MACE). Results In the cross-sectional arm, BACE1-AS expression correlated with BACE1 expression (r = 0.396, p Conclusion BACE1-AS is associated with the incidence and severity of ASCVD.

Accumulating evidence suggests that endothelial dysfunction is implicated in the pathogenesis and severity of coronavirus disease 2019 (COVID-19). In this context, vascular impairment in COVID-19 might be associated with clinical manifestations and could refine risk stratification in these patients.This systematic review aims to synthesize current evidence on the frequency and the prognostic value of vascular dysfunction during acute and post-recovery COVID-19. After systematically searching the MEDLINE, clinicaltrials.gov and the Cochrane Library from 1 December 2019 until 05 March 2022, we identified 24 eligible studies with laboratory confirmed COVID-19 and a thorough examination of vascular function. Flow-mediated dilation (FMD) was assessed in 5 and 12 studies in acute and post-recovery phase respectively; pulse wave velocity (PWV) was the marker of interest in three studies in the acute and four studies in the post-recovery phase.All studies except for one in the acute and in the post-recovery phase showed positive association between vascular dysfunction and COVID-19 infection. Endothelial dysfunction in two studies and increased arterial stiffness in three studies were related to inferior survival in COVID-19.Overall, a detrimental effect of COVID-19 on markers of endothelial function and arterial stiffness that could persist even for months after the resolution of the infection and provide prognostic value was congruent across published studies. Further research is warranted to elucidate clinical implications of this association.

The increase in cardiovascular risk after the menopausal transition remains partly explained until today. Further research is needed to identify risk factors potentially modifiable by primary prevention practices. This cross-sectional study, part of a larger prospective project, aims to investigate possible associations between dietary patterns and indices of vascular structure and function among healthy postmenopausal women.Postmenopausal women (n = 310) without clinically overt cardiovascular disease were recruited consecutively from a University Menopause Clinic over three years. Dietary intake was assessed by a validated food frequency questionnaire and the MedDietScore. In addition, we assessed anthropometric/biochemical parameters, including the Triglyceride-glucose index (TyG-Index), body fat distribution [triceps skinfold (TSF), mid-upper arm circumference (MUAC)] and physical activity. The vascular assessment included carotid-femoral pulse wave velocity (PWV), carotid and femoral-artery intima-media thickness (IMT) and atheromatous plaques presence.Consumption of non-refined cereals was associated with carotid-bulb IMT (RDietary patterns are associated with metabolic indices and subclinical atherosclerosis in postmenopausal women independently of traditional cardiovascular risk factors, total energy intake or physical activity.

Aims The clinical value of carotid atherosclerosis markers for residual risk stratification in high atherosclerotic cardiovascular disease (ASCVD) risk patients is not established. We aimed to derive and validate optimal values of markers of carotid subclinical atherosclerosis improving risk stratification in guidelines-defined high ASCVD risk patients. Methods and results We consecutively analysed high or very high ASCVD risk patients from a cardiovascular (CV) prevention registry (n = 751, derivation cohort) and from the Atherosclerosis Risk in Communities (ARIC) study (n = 2,897, validation cohort). Baseline ASCVD risk was defined using the 2021 European Society of Cardiology guidelines (clinical ESCrisk). Intima-media thickness excluding plaque, average maximal (avg.maxWT), maximal wall thickness (maxWT) and number of sites with carotid plaque were assessed. As primary endpoint of the study was defined the composite of cardiac death, acute myocardial infarction and revascularization after a median of 3.4 years in both cohorts and additionally for 16.7 years in the ARIC cohort. Results MaxWT > 2.00 mm and avg.maxWT > 1.39 mm provided incremental prognostic value, improved discrimination and correctly reclassified risk over the clinical ESCrisk both in the derivation and the validation cohort (P < 0.05 for net reclassification index, integrated discrimination index and Delta Harrell’s C index). MaxWT < 0.9 mm predicted very low probability of CV events (negative predictive value = 97% and 92% in the derivation and validation cohort, respectively). These findings were additionally confirmed for very long-term events in the validation cohort. Conclusion Integration of carotid ultrasonography in guidelines-defined risk stratification may identify patients at very high-risk in need for further residual risk reduction or at very low probability for events.

Depression and atherosclerotic cardiovascular disease (ASCVD) are commonly clustered in affected patients. Endothelial dysfunction is an early marker of ASCVD while also reported in patients with depression. Emerging evidence suggests that selective serotonin receptor inhibitors (SSRIs) may improve endothelial function. However, clinical studies assessing flow-mediated dilation (FMD), the gold-standard method to evaluate conduit artery endothelial function, in response to SSRIs treatment included limited number of patients and did not provide consistent results. In the present study we aim to evaluate the effect of SSRIs treatment on endothelial function assessed by longitudinal changes in FMD.We performed a systematic review to retrieve and subsequently meta-analyze eligible studies in patients with depression who received SSRIs and had available measurements of FMD change before and after treatment. In 5 studies and 323 individuals in total, SSRIs were associated with increased FMD at the end of follow-up compared to baseline measurement (pooled mean change 1.97 %, 95 % CI 0.17, 3.77, P = 0.032, ISubstantial heterogeneity regarding with respect to follow-up duration, demographics, and SSRIs agents.SSRIs significantly improve FMD, the gold-standard marker of endothelial function. Further investigation is warranted for the role of FMD as a possible therapeutic biomarker in patients with depression and established or subclinical ASCVD.CRD42021252241.

The aim of this study was to calculate the average operational cost per sub-type of stroke patient and to investigate cost drivers (e.g. ALoS, NIHSS score, age) correlated to cost.Direct medical costs (diagnostic imaging and clinical laboratory exams, overheads/bed cost, pharmaceuticals, ringers and other non-durables and inpatient rehabilitation) per patient were calculated from the providers' (hospitals') perspective. Resource use data derived from the "SUN4P" web-based registry and unit costs were retrieved from publically available sources and were assigned to resource use.The sample comprised 6,282 inpatient days of 750 patients (mean age: 75.5±13.3 years) admitted from July 2019 to July 2021, in nine public hospitals. Mean length of stay was 8.4±7.6 days and mean total operational cost was calculated to €1,239.4 (from which 45% and 35% related to diagnostic exams and overheads/bed cost respectively). Mean cost related to hemorrhagic stroke patients that were discharged alive was calculated significantly higher compared to mean cost related to ischemic stroke patients who didn't undertake thrombolysis and were also discharged alive from the hospital (€2,155.2 vs. €945.2, p0.001). Linear regression analysis revealed that length of stay was significantly correlated with cost (coefficient beta=232, 95% CI confidence interval = 220-243, p0.001).These findings are in accordance with current evidence and should be thoroughly assessed to rationalize inpatient reimbursement rates in order to achieve improved value of care.

The aim of this study was to present the descriptive characteristics of the Stroke Units Necessity for Patients (SUN4P) registry.The study population derived from the web-based SUN4P registry included 823 patients with first-ever acute stroke. Descriptive statistics were used to present patients' characteristics.The vast majority of patients (80.4%) had an ischemic stroke, whereas 15.4% had a hemorrhagic stroke. Hypertension was the leading risk factor in both patients. The patients with ischemic stroke had higher prevalence of traditional cardiovascular risk factors such as diabetes mellitus, dyslipidemia and smoking and most commonly cryptogenic stroke (39%). National Institutes of Health Stroke Scale (NIHSS) was higher among patients with hemorrhagic in comparison to those with ischemic stroke (10.5 vs 6 respectively). Moreover, all patients had similar rate of disability prior to stroke, as shown by Modified Rankin Scale (mRS=0).These data are in accordance with current evidence and should be thoroughly assessed in order to ensure optimal therapeutic management of stroke patients.

To assess stroke patient-reported experiences and hospital staff experiences, during hospital stay.Stroke patient-reported experiences (n=387) were recorded using the translated and culturally adapted NHS-Stroke Questionnaire into Greek and staff experiences (n=236) were investigated using the Compassion Satisfaction and Burnout subscales of the ProQOL questionnaire.Staff's mean compassion satisfaction score was 39.2 (SD=6.3) and mean burnout score was 24.3 (SD=5.6). Only 38.5% of the staff stated that there is smooth cooperation with healthcare professionals of other specialties/disciplines. Personnel working in an NHS Hospital was more satisfied and less burned-out when compared to personnel working at a University Hospital (p=0.02 and p0.001, respectively). Mean total patient-reported experiences score was 81.9 (SD=9.5). Bivariate analysis revealed statistically significant differences for total patient-reported experiences among the eight study hospitals (p0.001).Health policy planners and decision-makers must take into consideration the results of such self-reported measures to establish innovative techniques to accomplish goals such as staff-specialization, continuous training and applying formal frameworks for efficient cooperation amongst different disciplines.

To assess stroke patient-reported experiences and hospital staff experiences, during hospital stay. Methods: Stroke patient-reported experiences (n=387) were recorded using the translated and culturally adapted NHS-Stroke Questionnaire into Greek and staff experiences (n=236) were investigated using the Compassion Satisfaction and Burnout subscales of the ProQOL questionnaire. Results: Staff’s mean compassion satisfaction score was 39.2 (SD=6.3) and mean burnout score was 24.3 (SD=5.6). Only 38.5% of the staff stated that there is smooth cooperation with healthcare professionals of other specialties/disciplines. Personnel working in an NHS Hospital was more satisfied and less burned-out when compared to personnel working at a University Hospital (p=0.02 and p0.001). Conclusions: Health policy planners and decision-makers must take into consideration the results of such self-reported measures to establish innovative techniques to accomplish goals such as staff-specialization, continuous training and applying formal frameworks for efficient cooperation amongst different disciplines.

The aim of this study was to present the descriptive characteristics of the Stroke Units Necessity for Patients (SUN4P) registry. Methods: The study population derived from the web-based SUN4P registry included 823 patients with first-ever acute stroke. Descriptive statistics were used to present patients’ characteristics. Results: The vast majority of patients (80.4%) had an ischemic stroke, whereas 15.4% had a hemorrhagic stroke. Hypertension was the leading risk factor in both patients. The patients with ischemic stroke had higher prevalence of traditional cardiovascular risk factors such as diabetes mellitus, dyslipidemia and smoking and most commonly cryptogenic stroke (39%). National Institutes of Health Stroke Scale (NIHSS) was higher among patients with hemorrhagic in comparison to those with ischemic stroke (10.5 vs 6 respectively). Moreover, all patients had similar rate of disability prior to stroke, as shown by Modified Rankin Scale (mRS=0). Conclusions: These data are in accordance with current evidence and should be thoroughly assessed in order to ensure optimal therapeutic management of stroke patients.

The aim of this study was to calculate the average operational cost per sub-type of stroke patient and to investigate cost drivers (e.g. ALoS, NIHSS score, age) correlated to cost. Methods: Direct medical costs (diagnostic imaging and clinical laboratory exams, overheads/bed cost, pharmaceuticals, ringers and other non-durables and inpatient rehabilitation) per patient were calculated from the providers’ (hospitals’) perspective. Resource use data derived from the “SUN4P” web-based registry and unit costs were retrieved from publically available sources and were assigned to resource use. Results: The sample comprised 6,282 inpatient days of 750 patients (mean age: 75.5±13.3 years) admitted from July 2019 to July 2021, in nine public hospitals. Mean length of stay was 8.4±7.6 days and mean total operational cost was calculated to €1,239.4 (from which 45% and 35% related to diagnostic exams and overheads/bed cost respectively). Mean cost related to hemorrhagic stroke patients that were discharged alive was calculated significantly higher compared to mean cost related to ischemic stroke patients who didn’t undertake thrombolysis and were also discharged alive from the hospital (€2,155.2 vs. €945.2, p

Background Despite continuous improvements of diagnostic and therapeutic algorithms for cardiovascular disease (CVD), mortality from CVD remains high suggesting unaddressed residual risk. Remnant cholesterol (RC) consists the cholesterol content of triglyceride-rich lipoproteins, which along with LDL cholesterol infiltrate the arterial wall, accumulate and cause atherosclerosis. Increased remnant cholesterol (RC) levels have been previously associated with future adverse cardiac events despite hypolipidemic therapy. However, a mechanistic association of RC levels with human atherosclerosis in vivo has not been proven in a clinical setting. Purpose To evaluate the association of RC levels with the presence and extend of subclinical carotid atherosclerosis. Methods In this retrospective cohort study, 438 subjects from the Athens Vascular Registry without clinically overt CVD or treatment with statin were recruited. Atherosclerotic burden was assessed by B-mode carotid ultrasonography using: 1. Maximal carotid wall thickness [maxWT, the highest intima-media thickness (IMT) or highest atherosclerotic plaque thickness (PLQ) if present derived from all carotid sites], 2. Total thickness (sumWT, sum of maximal wall thickness), 3) high plaque burden (PLQ ≥2) and 4) average carotid IMT (avgIMT). RC was calculated using the formula RC=total cholesterol-LDL-C-HDL-C. Results Mean (SD) age was 54.8±12.4 years old with 41% being males. Subjects with RC>median (=18mg/dl) had higher sumWT (6.12±0.7 vs 5.57±1.7, p=0.002), maxWT (1.61±0.7 vs 1.43±0.7, p=0.008) and avgIMT (0.88±0.16 vs 0.83±0.16, p=0.003) vs RCmedian was associated with higher odds for increased sumWT (highest tertile, OR: 2.15 95% CI 1.26–3.66, p=0.006) and maxWT (OR: 2.15 95% CI: 1.38–3.33, p=0.001), and a higher plaque burden (≥2 plaques, OR: 2.1 95% CI 1.93–3.1, p Conclusion In a statin-naive population without clinically overt CVD, increased RC levels were associated with the presence and extend of subclinical carotid atherosclerosis. These findings provide novel mechanistic insight into mechanisms associated with increased CVD risk in individuals with high RC levels. Funding Acknowledgement Type of funding sources: None.

Background Among high cardiovascular (CV) risk patients, there is emerging need to recognize those who will benefit from new treatments targeting residual risk. Readily available modalities providing reclassification value would be clinically useful in this setting. Preliminary data suggest that carotid ultrasonography using plaque burden but not intima-media thickness (IMT) is associated with very high risk. Objectives We aimed to assess the reclassification ability of two markers of carotid atherosclerosis in high-risk patients, reflecting total atherosclerotic burden and the most severe lesion and to compare them with the routinely used carotid indices IMT and number of carotid plaques. Methods In an ongoing registry of patients who visited a cardiovascular protection clinic for cardiovascular risk assessment, we enrolled 735 consecutively recruited patients (mean age 63.1 years, 68.8% male) classified as high or very-high CV risk according to 2019 European Society of Cardiology /European Atherosclerosis Society Guidelines. Sum of carotid wall thickness (sumWT) and maximal wall thickness (maxWT) using high-resolution ultrasonography at baseline were used to assess the total burden and the most severe carotid lesion, respectively. These markers integrate maximum plaque height or maximum IMT if no plaque is present. All patients were followed for a median of 41 months and the primary end-point consisted of CV mortality, acute myocardial infarction or coronary revascularization. Results After adjustment for traditional CV risk factors, maxWT and sumWT were associated with the primary end-point (hazard ratio [HR]=1.73 (95% confidence interval [CI]:1.39 to 2.17) and 1.19 (95% CI 1.10 to 1.30) respectively). Both markers were superior in terms of reclassification and discrimination to identify very high risk over validated CV risk scores including the Heartscore and the SMART score (net reclassification index [NRI]=0.624, p Conclusions The use of two novel cumulative markers of atherosclerotic burden improves risk stratification and discriminates high from very high CV risk. Given that carotid ultrasonography is a readily available modality, its clinical application for risk refinement of high-risk patients to facilitate treatment decisions merits further investigation. Funding Acknowledgement Type of funding sources: None.

SARS-CoV-2 (Covid-19) infection has recently become a worldwide challenge with dramatic global economic and health consequences. As the pandemic is still spreading, new data concerning Covid-19 complications and related mechanisms become increasingly available. Accumulating data suggest that the incidence of cardiac arrest and its outcome are adversely affected during the Covid-19 period. This may be further exacerbated by drug-related cardiac toxicity of Covid-19 treatment regimens. Elucidating the underlying mechanisms that lead to Covid-19 associated cardiac arrest is imperative, not only in order to improve its effective management but also to maximize preventive measures. Herein we discuss available epidemiological data on cardiac arrest during the Covid-19 pandemic as well as possible associated causes and pathophysiological mechanisms and highlight gaps in evidence warranting further investigation. The risk of transmission during cardiopulmonary resuscitation (CPR) is also discussed in this review. Finally, we summarize currently recommended guidelines on CPR for Covid-19 patients including CPR in patients with cardiac arrest due to suspected drug-related cardiac toxicity in an effort to underscore the most important common points and discuss discrepancies proposed by established international societies., Highlights • Covid-19 pandemic is associated with increased incidence of cardiac arrest. • Cardiac, non-cardiac causes and drug-related toxicity may jointly contribute to cardiac arrest associated with Covid-19. • Recommendations for cardiac arrest management are modified during the pandemic. • Recommendations for prevention and management of drug-related toxicity related to Covid-19 are summarized.

The aim of this study was to assess stroke patients' experiences in regards to hospital stay and during discharge. A cross-sectional study with retrospective data collection was conducted including patients (n=135) with first-ever acute stroke, who were admitted in seven Public Hospitals in Greece ("Stroke Units Necessity for Patients, SUN4P" registry). The translated version of the NHS-Stroke Questionnaire in the Greek was used. 48.2% of patients rated their overall experience from the care they received as very good/excellent. 66% of patients reported that they participated in decision making about their care and 21.5% reported not having received help from the hospital's social services regarding any benefits/aids, thus lowering their overall patient experience score (p=0.017). Decision and policymakers must consider factors affecting stroke patients 'experiences during their hospitalization. The development of a national stroke patients' experiences database can help prioritize relevant actions and draw up a commonly accepted management and services redesign framework for patients.

The aim of this study was to evaluate accessibility of stroke patients to optimal healthcare technology in Greece. Methods: The study population consisted of 313 first ever stroke patients derived from the "Stroke Units Necessity for Patients, SUN4P" registry. Descriptive statistics were used, to present patients' characteristics and resources utilization Results: The vast majority of patients (91.7%) conducted a CT scan during the acute phase (within the first 24hours). Almost, (65%) were admitted to wards of Internal Medicine Departments, whereas only 21% of patients were admitted to a Stroke Unit. Of note, a total of 6.9% of ischemic stroke patients received intravenous thrombolytic therapy with recombinant tissue plasminogen activator (rtPA). Conclusions: Preliminary results from SUN4P underline the urgent necessity for the re-organization of acute stroke care in Greece, as rates of admissions to stroke units and rtPA treatment during the acute phase are currently below optimal.