Major clinical outcomes in symptomatic vs. asymptomatic atrial fibrillation: a meta-analysis.

BACKGROUND AND AIMS: Current guidelines suggest that asymptomatic atrial fibrillation (AF) is independently associated with increased risks of stroke and mortality compared with symptomatic AF. Considering that recent investigations have provided conflicting results, the present study aimed to evaluate the association between symptom status and clinical outcomes in patients with AF. METHODS: Medline, Cochrane Library, and Scopus were searched until 25 March 2024. Triple-independent study selection, data extraction and quality assessment were performed. Evidence was pooled using random-effects meta-analyses. RESULTS: Thirty-six studies (217 850 participants) were included. Based on the frequentist analysis, symptomatic individuals had no significant difference in the risk of all-cause mortality [hazard ratio (HR) .97, 95% confidence interval (CI) .80-1.17], cardiovascular mortality (HR 1.04, 95% CI .72-1.49), thromboembolism (HR 1.06, 95% CI .87-1.28), stroke (HR 1.06, 95% CI .84-1.34), hospitalization (HR 1.34, 95% CI .89-2.02), and myocardial infarction (HR .98, 95% CI .70-1.36), compared to the asymptomatic group. Symptomatic patients had a 33% increased risk of new-onset heart failure (HR 1.33, 95% CI 1.19-1.49) and a 30% lower risk of progression to permanent AF (HR .70, 95% CI .54-.89). The Bayesian analysis yielded comparable results, yet the association between symptom status and new-onset heart failure was not significant (HR 1.27, 95% credible interval .76-1.93; Bayes factor = 1.2). Symptomatic patients had higher odds of receiving antiarrhythmic drugs (odds ratio [OR] 1.64, 95% CI 1.33-2.03) and ablation therapy (OR 1.47, 95% CI 1.06-2.05) compared to asymptomatic cases. CONCLUSIONS: The risk of major clinical outcomes did not differ between individuals with and without AF-related symptoms. Asymptomatic patients had a greater hazard of progression to permanent AF.

Effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus: A systematic review and multilevel meta-analysis.

AIM: The present systematic review aimed to summarize the available evidence from published randomized controlled trials (RCTs) regarding the effect of tirzepatide on albuminuria levels and renal function in patients with type 2 diabetes mellitus. MATERIALS AND METHODS: Medline (via PubMed), Cochrane Library and Scopus were searched until 20 October 2023. Double-independent study selection, data extraction and quality assessment were performed. Evidence was pooled with a three-level mixed-effects meta-analysis. RESULTS: In total, 9533 participants from eight RCTs were analysed. All RCTs had a low risk of bias, according to the Cochrane Collaboration tool (RoB2). Tirzepatide was associated with a significantly greater reduction in urine albumin-to-creatinine ratio compared with controls [mean difference (MD) -26.9%; 95% confidence interval (CI) (-34.76, -19.04); p < .001; level of evidence (LoE) moderate]. This effect remained significant in participants with baseline urine albumin-to-creatinine ratio ≥30 mg/g [MD -41.42%; 95% CI (-54.38, -28.45); p < .001; LoE moderate]. Based on subgroup analysis, the comparative effect of tirzepatide was significant against placebo and the insulin regimen, whereas no difference was observed compared with semaglutide. The beneficial effect of tirzepatide on albuminuria levels remained significant across all investigated doses (5, 10 and 15 mg), showing a dose-response relationship. A neutral effect was observed on the estimated glomerular filtration rate [MD 0.39 ml/min/1.73m2 ; 95% CI (-0.64, 1.42); p = .46; LoE moderate]. CONCLUSION: Our findings suggest that tirzepatide probably leads to a significant reduction in albuminuria across all administered doses, while its use is associated with a neutral effect on creatinine clearance as a measure of renal function.

Effects of glucagon-like peptide-1 receptor agonists on glycated haemoglobin and continuous glucose monitoring metrics as adjunctive therapy to insulin in adults with type 1 diabetes: A meta-analysis of randomized controlled trials.

AIMS: To conduct a meta-analysis of randomized controlled trials (RCTs) to evaluate the effect of glucagon-like peptide-1 receptor agonists (GLP-1RAs) on glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics as an adjunct to insulin therapy in adults with type 1 diabetes mellitus (T1D). METHODS: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library, and Google Scholar up to 27 May 2024. Dual-independent study selection, data extraction, and quality assessment were performed. Results were summarized using random-effects meta-analysis. RESULTS: Six RCTs were identified, involving a total of 378 individuals with T1D. The use of GLP-1RAs in addition to standard insulin therapy was associated with a significant reduction in HbA1c (mean difference [MD] -0.21%, 95% confidence interval [CI] -0.36 to -0.06; p = 0.007) and a similar time in range (TIR) compared to placebo (MD -0.22%, 95% CI -2.39 to 1.95; p = 0.84). GLP-1RA therapy resulted in a significantly higher time below range (MD 1.13%, 95% CI 0.50 to 1.76; p < 0.001) and a lower time above range compared with placebo (MD -1.83%, 95% CI -2.51 to -1.15; p < 0.001). Nonsignificant differences were noted for the secondary outcomes, including the mean amplitude of glucose excursion, continuous overall net glycaemic action for 60 min, mean daily glucose, coefficient of variation, and mean standard deviation of weekly glucose levels. CONCLUSION: Our findings suggest that, in individuals with T1D, add-on therapy with GLP-1RAs does not confer significant benefits in terms of CGM metrics and is associated with a longer time below the target glycaemic range.

Endothelial Protection by Sodium-Glucose Cotransporter 2 Inhibitors: A Literature Review of In Vitro and In Vivo Studies.

Endothelial dysfunction often precedes the development of cardiovascular diseases, including heart failure. The cardioprotective benefits of sodium-glucose cotransporter 2 inhibitors (SGLT2is) could be explained by their favorable impact on the endothelium. In this review, we summarize the current knowledge on the direct in vitro effects of SGLT2is on endothelial cells, as well as the systematic observations in preclinical models. Four putative mechanisms are explored: oxidative stress, nitric oxide (NO)-mediated pathways, inflammation, and endothelial cell survival and proliferation. Both in vitro and in vivo studies suggest that SGLT2is share a class effect on attenuating reactive oxygen species (ROS) and on enhancing the NO bioavailability by increasing endothelial nitric oxide synthase activity and by reducing NO scavenging by ROS. Moreover, SGLT2is significantly suppress inflammation by preventing endothelial expression of adhesion receptors and pro-inflammatory chemokines in vivo, indicating another class effect for endothelial protection. However, in vitro studies have not consistently shown regulation of adhesion molecule expression by SGLT2is. While SGLT2is improve endothelial cell survival under cell death-inducing stimuli, their impact on angiogenesis remains uncertain. Further experimental studies are required to accurately determine the interplay among these mechanisms in various cardiovascular complications, including heart failure and acute myocardial infarction.

Coronary Plaque Erosion: Epidemiology, Diagnosis, and Treatment.

Plaque erosion (PE), a distinct etiology of acute coronary syndromes (ACSs), is often overshadowed by plaque ruptures (PRs). Concerning its epidemiology, PE has garnered increasing recognition, with recent studies revealing its prevalence to be approximately 40% among ACS patients, challenging earlier assumptions based on autopsy data. Notably, PE exhibits distinct epidemiological features, preferentially affecting younger demographics, particularly women, and often manifesting as a non-ST-segment elevation myocardial infarction. There are seasonal variations, with PE events being less common in winter, potentially linked to physiological changes and cholesterol solidification, while peaking in summer, warranting further investigation. Moving to molecular mechanisms, PE presents a unique profile characterized by a lesser degree of inflammation compared to PR, with endothelial shear stress emerging as a plausible molecular mechanism. Neutrophil activation, toll-like receptor-2 pathways, and hyaluronidase 2 expression are among the factors implicated in PE pathophysiology, underscoring its multifactorial nature. Advancements in intravascular imaging diagnostics, particularly optical coherence tomography and near-infrared spectroscopy coupled with intravascular ultrasound, offer unprecedented insights into plaque composition and morphology. Artificial intelligence algorithms show promise in enhancing diagnostic accuracy and streamlining image interpretation, augmenting clinician decision-making. Therapeutically, the management of PE evolves, with studies exploring less invasive approaches such as antithrombotic therapy without stenting, particularly in cases identified early through intravascular imaging. Additionally, the potential role of drug-coated balloons in reducing thrombus burden and minimizing future major adverse cardiovascular events warrants further investigation. Looking ahead, the integration of advanced imaging modalities, biomarkers, and artificial intelligence promises to revolutionize the diagnosis and treatment of coronary PE, ushering in a new era of personalized and precise cardiovascular care.

The Role of Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in Heart Failure.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF and is associated with poor outcomes, only limited alternative pharmaceutical options are available in clinical practice. The objective of this narrative review is to provide a comprehensive analysis of the current evidence on the effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on diuretic resistance in HF patients. The primary emphasis is placed on clinical data that assess the impact of SGLT-2 inhibitors on fluid balance, symptom improvement, and clinical outcomes and secondarily on safety profile and potential adverse effects associated with SGLT-2 inhibitor use in acute decompensated HF. The current evidence on the efficacy of SGLT-2 on diuretic resistance remains controversial. Findings from observational and randomized studies are quite heterogenous; however, they converge on the notion that although SGLT-2 inhibitors show promise for mitigating diuretic resistance in HF, their diuretic effect may not be potent enough to be widely used to relieve objective signs of congestion in patients with HF. Importantly, the introduction of SGLT-2 inhibitors in HF treatment appears to be generally well tolerated, with manageable adverse effects. Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT-2 inhibitors on diuretic resistance in HF.

Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an overview of 36 systematic reviews.

The recently published randomized trials (RCTs) evaluating the effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) in heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) led researchers to perform a plethora of systematic reviews (SRs), often providing contradictory conclusions. This overview of reviews was aimed at summarizing the evidence of these SRs, quantifying the overlap, re-analyzing the evidence in case new studies that were identified, and mapping knowledge gaps. Literature search was conducted through Medline, Scopus, and Cochrane until March 22, 2023. Overall, 36 SRs synthesizing results from 18 RCTs were identified. A substantial overlap was identified among the SRs synthesizing large heart failure or cardiovascular outcome trials (CVOTs). Regarding the composite outcome of cardiovascular (CV) mortality or hospitalization for heart failure (HHF), all authors reported a significant favorable effect. A beneficial effect was also noted for CV and all-cause mortality, albeit not significant. Our meta-analysis demonstrated a significant improvement in health-related quality-of-life (HRQoL) as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS, MD = 1.97, p < 0.001), Total Symptom Score (KCCQ-TSS, MD = 2.29, p < 0.001), Clinical Summary Score (KCCQ-CSS, MD = 1.59, p < 0.001), and the 6-min walking distance (MD = 10.78 m, p = 0.032). Regarding safety, SGLT2i were associated with a significantly lower risk of serious adverse events compared to placebo (RR = 0.94, p = 0.002). The use of SGLT2i in HFpEF is both efficient and safe. Further research is required to clarify the impact of SGTL2i on different subphenotypes of HFpEF and the cardiorespiratory capacity of these patients.

Efficacy and safety of once-weekly versus once-daily basal insulin analogues in the treatment of type 2 diabetes mellitus: A systematic review and meta-analysis.

AIM: To summarize the evidence of recently published randomized controlled trials (RCTs) studying efficacy, in terms of glycaemic control, and safety of the newly developed once-weekly basal insulin analogues. METHODS: A systematic literature search was conducted through Medline (via PubMed), Cochrane Library and Google Scholar until June 30, 2023. Double-independent study selection, data extraction and quality assessment were performed. Results were summarized with random-effects meta-analysis. RESULTS: A total of 3962 patients with type 2 diabetes mellitus (T2DM) among nine RCTs were analysed. All RCTs had low risk of bias according to the Cochrane Collaboration risk-of-bias tool (RoB2). Once-weekly insulins demonstrated better efficacy in glycated haemoglobin (HbA1c) reduction (mean difference [MD] -0.13%, 95% confidence interval [CI] -0.23, -0.03; P = 0.08) and a significantly greater time in range compared with once-daily insulin analogues (MD 3.54%, 95% CI 1.56, 5.53; P = 0.005). Based on subgroup analyses, the reduction in HbA1c and the odds of achieving an end-of-treatment HbA1c <6.5% were significantly greater for icodec compared to the once-daily insulin (MD -0.18%, 95% CI -0.27, -0.09 [P < 0.001] and odds ratio [OR] 1.75, 95% CI 1.34, 2.29 [P < 0.001], respectively). Once-weekly insulins were associated with higher odds of level 1 hypoglycaemia during the 24-hour period (OR 1.3, 95% CI 1.04, 1.64; P = 0.02) but were safer in terms of level 2 or 3 nocturnal hypoglycaemic events (OR 0.74, 95% CI 0.56, 0.97; P = 0.03). No difference was observed regarding serious adverse events between the two groups. CONCLUSION: The once-weekly basal insulin analogues seem to be at least equally efficient in glycaemic management and safe compared to once-daily injections in people with T2DM. Phase 4 RCTs are expected to shed further light on the effectiveness and safety of once-weekly insulin therapy over the long term.

Appraisal methods and outcomes of AMSTAR 2 assessments in overviews of systematic reviews of interventions in the cardiovascular field: A methodological study.

This study aimed to assess the methods and outcomes of The Measurement Tool to Assess systematic Reviews (AMSTAR) 2 appraisals in overviews of reviews (overviews) of interventions in the cardiovascular field and identify factors that are associated with these outcomes. MEDLINE, Scopus, and the Cochrane Database of Systematic Reviews were searched until November 2022. Eligible were overviews of cardiovascular interventions, analyzing systematic reviews (SRs) of randomized controlled trials (RCTs). Extracted data included characteristics of overviews and SRs and AMSTAR 2 appraisal methods and outcomes. Data were synthesized using descriptive statistics and logistic regression to explore potential associations between the characteristics of SRs and extracted AMSTAR 2 overall ratings ("High-Moderate" vs. "Low-Critically low"). The original results on individual AMSTAR 2 items were entered into the official AMSTAR 2 online tool and the recalculated overall confidence ratings were compared to those provided in overviews. All 34 overviews identified were published between 2019 and 2022. Rating of overall confidence following the algorithm suggested by AMSTAR 2 developers was noted in 74% of overviews. The 679 unique included SRs were mainly of "Critically low" (53%) or "Low" (18.7%) confidence and underperformed in items 2 (Protocol, no = 65.2%) and 7 (List of excluded studies, no = 84%). The following characteristics of SRs were significantly associated with higher overall ratings: Cochrane origin, pharmacological interventions, including exclusively RCTs, citation of methodological and reporting guidelines, protocol, absence of funding and publication after AMSTAR 2 release. Generally, overviews' authors tended to deviate from the original rating scheme and ascribe higher ratings to SRs compared to the official AMSTAR 2 online tool. Most SRs included in overviews of cardiovascular interventions have critically low or low confidence in their results. Overviews' authors should be more transparent about the methods used to derive the overall confidence in SRs.

Sodium-Glucose Co-transporter-2 Inhibitors in Type 1 Diabetes Mellitus: The Framework for Recommendations for Their Potential Use.

The growing prevalence of overweight/obesity, the persistence of inadequate glycemic control among the majority of affected individuals, and the still unacceptably high risk of cardiovascular morbidity and mortality among population with type 1 diabetes mellitus (T1D), impose an urgent need for the introduction of non-insulin glucose-lowering agents in the therapeutic armamentarium. Given that their antihyperglycemic mechanism of action is independent of endogenous insulin secretion and that the observed cardio-renal benefits are unrelated to their glucose-lowering properties, one can speculate that the use of sodium-glucose co-transporter-2 inhibitors (SGLT2is) could provide benefits in T1D, similar to the ones observed among individuals with type 2 diabetes mellitus, chronic kidney disease (CKD), and heart failure. Available evidence from randomized controlled trials suggests that treatment with SGLT2is as adjunct to insulin in T1D results in modest reductions in glycated hemoglobin and body weight. Additionally, SGLT2is ameliorate albuminuria, and thus delay or prevent the development of CKD in T1D. However, use of SGLT2is is associated with an increased risk of diabetic ketoacidosis (DKA) in T1D. This commentary aims at providing a framework for practical recommendations regarding the potential use of SGLT2is in adults with T1D, based on the individual's risk level for DKA development, the presence of inadequate glycemic control and related cardio-renal complications.

Are Oxidative Stress Biomarkers Reliable Part of Multimarker Panel in Female Patients with Type 2 Diabetes Mellitus?

Background: Oxidative stress and inflammation are the key features of metabolic diseases, including type 2 diabetes mellitus (T2D). However, studies that explored redox homeostasis parameters in relation to T2D show discrepant results. Accordingly, we aimed to examine the potential reliability of oxidative stress biomarkers [i.e., determined by malondialdehyde (MDA), advanced oxidation protein products (AOPP) and catalase (CAT)] in addition to traditional cardiometabolic parameters in relation to T2D in female cohort. Methods: A total of 214 women (of them 40.6% T2D) were consecutively recruited in the study. Principal component analysis with varimax rotation was performed to determine the adequate number of factors consisting of anthropometric, traditional cardiometabolic and redox status markers. Results: MDA and AOPP concentrations were lower, but CAT activity was higher in T2D group as compared with controls (P < 0.001, P = 0.002, P < 0.001). Traditional markers related factor (i.e., with positive loading of waist circumference, triglycerides, uric acid, high sensitivity C-reactive protein and negative loadings of high-density lipoprotein cholesterol) was found to be independently related with T2D in multivariate binary regression analysis, whereas oxidative stress related factor (i.e., with positive loading of MDA and AOPP) lost its independent prediction after adjustment for confounding factors (i.e., age, menopausal status, antihypertensive, and hypolipemic therapies). Increased Traditional markers related factor was associated with more than three times higher probability for T2D onset (OR = 3.319, p < 0.001). Conclusion: Oxidative stress biomarkers, i.e., MDA, AOPP, and CAT are not superior over traditional cardiometabolic markers in relation to T2D in female population. Future studies with both gender included are needed to confirm such results.

Sodium-Glucose Cotransporter-2 Inhibitors in Patients With Acute Coronary Syndrome: A Modern Cinderella?

PURPOSE: Atherosclerotic cardiovascular disease remains a prominent global cause of mortality, with coronary artery disease representing its most prevalent manifestation. Recently, a novel class of antidiabetic medication, namely sodium-glucose cotransporter-2 (SGLT2) inhibitors, has been reported to have remarkable cardiorenal advantages for individuals with type 2 diabetes mellitus (DM), and they may reduce cardiorenal risk even in individuals without pre-existing DM. Currently, there is no evidence regarding the safety and efficacy of these drugs in acute coronary syndrome (ACS), regardless of diabetes status. This review aims to comprehensively present the available preclinical and clinical evidence regarding the potential role of SGLT2 inhibitors in the context of ACS, as adjuncts to standard-of-care treatment for this patient population, while also discussing potential short- and long-term cardiovascular benefits. METHODS: A literature search was performed through MEDLINE (via PubMed), Cochrane Central Register of Controlled Trials, and Scopus until February 26, 2024. Eligible were preclinical and clinical studies, comprising randomized controlled trials (RCTs), real-world studies, and meta-analyses. FINDINGS: Evidence from preclinical models indicates that the use of SGLT2 inhibitors is associated with a blunted ischemia-reperfusion injury and decreased myocardial infarct size, particularly after prior treatment. Although RCTs and real-world data hint at a potential benefit in acute ischemic settings, showing improvements in left ventricular systolic and diastolic function, decongestion, and various cardiometabolic parameters such as glycemia,body weight, and blood pressure, the recently published DAPA-MI (Dapagliflozin in Myocardial Infarction without Diabetes or Heart Failure) trial did not establish a clear advantage regarding surrogate cardiovascular end points of interest. SGLT2 inhibitors appear to provide a benefit in reducing contrast-induced acute kidney injury events in patients with ACS undergoing percutaneous coronary intervention. However, data on other safety concerns, such as treatment discontinuation because of hypotension, hypovolemia, or ketoacidosis, are currently limited. IMPLICATIONS: Despite the well-established cardiovascular benefits observed in the general population with type 2 DM and, more recently, in other patient groups irrespective of diabetes status, existing evidence does not support the use of SGLT2 inhibitors in the context of ACS. Definitive answers to this intriguing research question, which could potentially expand the therapeutic indications of this novel drug class, require large-scale, well-designed RCTs.

The Effect of Cardiac Resynchronization Therapy on Right Ventricular Function: A Systematic Review and Meta-Analysis.

Background: Right ventricular (RV) failure is an important predicting factor regarding overall and event-free survival regardless of baseline left ventricular (LV) function in patients with severe heart failure (HF). Previous studies have indicated that cardiac resynchronization therapy (CRT) improves LV and RV reverse remodeling in patients with systolic dyssynchrony within the left ventricle. However, there is conflicting evidence regarding the role of CRT in RV function. The aim of this systematic review and meta-analysis was to examine the implications of CRT on RV function indices. Methods: A systematic literature search was conducted using the MedLine and EMBASE databases and the Cochrane Library from their inception until 18 March 2024. Eligible were studies providing information on RV function indices, both at baseline and after CRT. Evidence was summarized using random-effects meta-analytic models. Results: In total, 30 studies were deemed eligible. CRT resulted in a significant improvement in right ventricular fractional area change (mean difference (MD) 5.11%, 95% confidence interval (CI) 2.83 to 7.39), tricuspid annular plane systolic excursion (TAPSE, MD 1.63 mm, 95% CI 1.10 to 2.16), and myocardial systolic excursion velocity (MD 1.85 cm/s, 95% CI 1.24 to 2.47) as well as a significant decrease in pulmonary artery systolic pressure (MD -6.24 mmHg, 95% CI -8.32 to -4.16). A non-significant effect was observed on TAPSE to PASP ratio and right ventricular global longitudinal strain. Conclusions: Our meta-analysis demonstrates that CRT is associated with a significant improvement in echocardiographic parameters of RV function. Further investigation is necessary to elucidate how these changes, both independently and in conjunction with LV improvement, impact patients' long-term prognosis, and to identify the specific patient populations expected to derive the greatest benefit.

amstar2Vis: An R package for presenting the critical appraisal of systematic reviews based on the items of AMSTAR 2.

Systematic reviews (SRs) have an important role in the healthcare decision-making practice. Assessing the overall confidence in the results of SRs using quality assessment tools, such as "A MeaSurement Tool to Assess Systematic Reviews 2" (AMSTAR 2), is crucial since not all SRs are conducted using the most rigorous methods. In this article, we introduce a free, open-source R package called "amstar2Vis" (https://github.com/bougioukas/amstar2Vis) that provides easy-to-use functions for presenting the critical appraisal of SRs, based on the items of AMSTAR 2 checklist. An illustrative example is outlined, describing the steps involved in creating a detailed table with the item ratings and the overall confidence ratings, generating a stacked bar plot that shows the distribution of ratings as percentages of SRs for each AMSTAR 2 item, and creating a "ggplot2" graph that shows the distribution of overall confidence ratings ("Critically Low," "Low," "Moderate," or "High"). We expect "amstar2Vis" to be useful for overview authors and methodologists who assess the quality of SRs with AMSTAR 2 checklist and facilitate the production of pertinent publication-ready tables and figures. Future research and applications could further investigate the functionality or potential improvements of our package.

Vascular Alterations Following COVID-19 Infection: A Comprehensive Literature Review.

SARS-CoV-2, the causative agent of the ongoing COVID-19 pandemic, has revealed a broader impact beyond the respiratory system, predominantly affecting the vascular system with various adverse manifestations. The infection induces endothelial dysfunction and immune system dysregulation, creating an inflammatory and hypercoagulable state. It affects both microvasculature and macrovasculature, leading to thromboembolic events, cardiovascular manifestations, impaired arterial stiffness, cerebrovascular complications, and nephropathy, as well as retinopathy-frequently observed in cases of severe illness. Evidence suggests that SARS-CoV-2 infection may result in persistent effects on the vascular system, identified as long-term COVID-19. This is characterized by prolonged inflammation, endotheliopathy, and an increased risk of vascular complications. Various imaging modalities, histopathological studies, and diagnostic tools such as video capillaroscopy and magnetic resonance imaging have been employed to visualize vascular alterations. This review aims to comprehensively summarize the evidence concerning short and long-term vascular alterations following COVID-19 infection, investigating their impact on patients' prognosis, and providing an overview of preventive strategies to mitigate associated vascular complications.

Risk of subclinical atherosclerosis in primary Sjogren's syndrome: A systematic review and meta-analysis.

BACKGROUND: Currently, the guidelines for prevention and management of atherosclerosis in patients with Sjogren's syndrome (SS) do not differentiate from those concerning the general population. OBJECTIVES: The present systematic review aimed to summarize evidence from primary studies assessing the risk of subclinical atherosclerosis in patients with primary SS (pSS). METHODS AND RESULTS: Literature was searched until June 2023. Eligible records were randomized controlled trials and observational studies comparing subclinical atherosclerosis markers between pSS patients and healthy controls. DerSimonian-Laird random effects models were used to calculate overall effect estimates. Totally, 19 observational studies comprising 1625 participants were included. Compared to healthy controls, pSS patients had significantly higher values of carotid-femoral intima-media thickness (cfIMT) (MD= 0.07 mm; 95 % CI= [0.04, 0.11]; p <0.001) and were more frequently diagnosed with atherosclerotic plaques (OR= 1.9; 95 % CI= [1.32, 2.74]; p <0.001). Moreover, pSS patients showed a decreased flow and nitrate-mediated dilation (MD = -2.48 %; 95 % CI= [-4.57, -0.39]; p = 0.02, MD= -2.11 %; 95 % CI= [-3.22, -1.01]; p <0.001, respectively). Similar results were observed for the pulse-wave velocity (MD= 0.7 m/s; 95 % CI= [0.36, 1.05]; p <0.001) and the ankle-brachial index (OR= 5.78; 95 % CI= [2.23, 14.99]; p = 0.003). Based on meta-regression analyses, only the disease duration and erythrocyte sedimentation rate were positively and significantly associated with higher cfIMT values. CONCLUSION: Patients with pSS have an increased risk of subclinical atherosclerosis compared to healthy population and thus possibly require early and disease-specific intervention. Further research is warranted for more accurate cardiovascular risk management in SS.

Effectiveness and safety of injectable PCSK9 inhibitors in dyslipidaemias' treatment and cardiovascular disease prevention: An overview of 86 systematic reviews and a network metaanalysis.

OBJECTIVE: Multiple systematic reviews (SR) have been performed on the effects of proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), often providing conflicting findings. This overview and network meta-analysis (NMA) aimed to summarize SR findings on the efficacy and safety of PCSK9i and provide an updated NMA. MATERIALS AND METHODS: MEDLINE (Pubmed), Scopus, Cochrane, Epistemonikos and Google Scholar were searched from inception to September 21, 2023 for SRs of randomized controlled trials (RCTs) and from January 1, 2020 to September 21, 2023 for additional RCTs. Double-independent study selection, data extraction and quality assessment were performed. Qualitative analysis was performed for SRs and a frequentist random-effects model NMA was performed for RCTs. RESULTS: Totally, 86 SRs and 76 RCTs were included. Alirocumab (77/86 [90%]) and evolocumab (73/86 [85%]) were mostly analyzed. Associations from SRs (35/42 [83%]) and the updated NMA indicated PCSK9i benefit on major adverse cardiovascular events (MACEs). Reductions were also noted for cerebrovascular events (47/66 [71%]), coronary revascularization (29/33 [88%]) and myocardial infarction (41/63 [65%]). Alirocumab was associated with reductions on all-cause mortality (RR=0.82, 95%CI [0.72,0.94]). Data on any CV event reduction were conflicting (7/16 [44%]). Inclisiran appeared effective only on MACEs (RR=0.76, 95%CI [0.61,0.94]). No reductions in heart failure were observed (0/16). No increases were identified between PCSK9i and any (0/35) or serious adverse events (0/52). However, PCSK9i were associated with injection-site reactions (20/28 [71%]). CONCLUSION: PCSK9i appeared to be effective in CV outcomes and their clinical application was generally safe.

From a Cup of Tea to Cardiovascular Care: Vascular Mechanisms of Action.

Tea consumption is increasingly recognized for its potential benefits to cardiovascular health. This study reviews the available research, concentrating on the major components of tea and their mechanisms of action in the cardiovascular system. Tea is abundant in bioactive compounds, such as flavonoids and polysaccharides, which possess significant antioxidant and anti-inflammatory properties. These compounds play a crucial role in mitigating oxidative stress and inflammation, thereby supporting cardiovascular health. They enhance endothelial function, leading to improved vascular relaxation and reduced arterial stiffness, and exhibit antithrombotic effects. Additionally, regular tea consumption is potentially associated with better regulation of blood pressure, improved cholesterol profiles, and effective blood sugar control. It has been suggested that incorporating tea into daily dietary habits could be a practical strategy for cardiovascular disease prevention and management. Despite the promising evidence, more rigorous clinical trials are needed to establish standardized consumption recommendations and fully understand long-term effects. This review offers a more comprehensive analysis of the current evidence based on endothelium function and identifies the gaps that future research should address.