Search Results (111)

Background: Atrial fibrillation (AF) is one of the most common heart rhythm disorders encountered in clinical practice. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF, but certain questions still remain unanswered, in particular whether AF-related inflammation is a cause or a consequence of the arrhythmia, and whether inflammation reflects underlying disease or AF itself. At the current state of the art, scientific evidence on the role of oral anticoagulants (OAC) in modulating pro-inflammatory cytokines implicated in the pathogenesis of AF remains scarce. The aim of our study was to evaluate, in a population of AF patients undergoing OAC, the different roles of anticoagulant therapy [Vitamin K antagonists (VKAs) and direct oral anti-coagulants (DOACs)] in modulating the levels of inflammatory biomarkers in AF. Methods: The Strat-AF study is an observational, prospective, single center, hospital-based study enrolling elderly patients with AF. Results refer to 170 subjects with complete clinical and biohumoral assessment. Results: At multivariate logistic regression analysis, adjusted for several covariates, VKA treatment was an independent protective predictor for having a high grade of inflammation not balanced by anti-inflammatory cytokine levels [OR = 0.26 (0.10–0.69), p = 0.007]. Conclusions: These results from the Strat-AF study are “generators of hypotheses” and provide preliminary evidence for the differential effects of VKAs and DOACs on inflammatory biomarkers (e.g., IL-6, TNF-α) in AF patients. These findings suggest that inflammatory biomarkers could enhance stroke risk prediction models, potentially improving a tailored AF management. Full article

Background/Objectives: The composition of the thrombus is not taken into account in the etiology determination of patients with acute ischemic stroke (AIS); however, it varies depending on the origin of the thrombus, as atherothrombotic thrombi contain more red blood cells and cardioembolic thrombi contain more fibrin and platelets. Radiomics has the potential to provide quantitative imaging data that may vary depending on the composition of thrombi. The aim of this study is to predict cardioembolic and atherothrombotic thrombi using radiomic features (RFs) from non-contrast computed tomography (NCCT) brain scans. Methods: A total of 845 RFs were extracted from each of the 41 patients included in the study. A predictive model was used to classify patients as either cardioembolic or atherothrombotic, and the results were compared with the TOAST criteria-based classification. Results: Ten RFs (one shape feature and nine texture features) were found to demonstrate a statistically significant correlation with cardioembolic or atherothrombotic origins. The predictive radiomics model achieved an area under the curve (AUC) of 0.842 and an accuracy of 0.902 (p < 0.001) in classifying stroke etiology. Conclusions: Radiomics based on NCCT can help to determine the etiology of AIS. Full article

Coronary no-reflow (CNR) is the failure of blood to reperfuse ischemic myocardial tissue after restoration of the vasculature. CNR poses a significant clinical challenge in the treatment of patients with ST-segment elevation myocardial infarction (STEMI), as it increases mortality and the risk of major adverse cardiac events (MACEs). Myocardial ischemia with subsequent reperfusion results in severe damage to the cardiac microcirculation. The pathophysiological causes of CNR include cardiomyocyte vulnerability, capillary and endothelial damage, leukocyte activation, reactive oxygen species (ROS) production, and changes in microRNA profiles and related gene expression. The impact of percutaneous coronary intervention (PCI) on the occurrence of CNR cannot be overlooked, as it can provoke distal atherothrombotic embolization. Current standards of pharmacological therapy for CNR are confined to intracoronary vasodilators and antiplatelet agents. As our understanding of the pathogenesis of the CNR phenomenon improves, opportunities emerge for developing novel therapeutic strategies. The following literature review provides an overview of the pathophysiology of the no-reflow phenomenon (based on animal and preclinical studies), contemporary treatment trends, and current therapeutic approaches. Full article

Background: Atherosclerotic cardiovascular disease (ASCVD) is often perceived as a male-dominant condition, yet recent European data show that more women live with and die from it. Gender disparities have been reported in the management of dyslipidemia, with women less likely to receive high-intensity lipid-lowering therapy and to reach low-density lipoprotein cholesterol (LDL-C) goals. This study aimed to assess sex-specific differences in response to and tolerance of PCSK9-targeted therapies—monoclonal antibodies (evolocumab, alirocumab) and small interfering RNA (inclisiran)—as well as LDL-C goal attainment according to current ESC guidelines. Methods: We conducted a prospective registry of patients initiating PCSK9-targeted therapy at a specialized lipid center between April 2018 and June 2024. Baseline lipid profiles were recorded and monitored over follow-up. Results: Of the 341 patients, 122 (35.8%) were women and 219 (64.2%) were men, with a mean age of 66.4 ± 12.6 years for the women and 63.9 ± 11.8 years for the men. The women more frequently had heterozygous familial hypercholesterolemia (HeFH) (61.5% vs. 38.4%, p < 0.001) and a lower prevalence of previous cardiovascular events compared to the men (62.3% vs. 84.5%, p < 0.001). A higher proportion of the women were classified as high cardiovascular risk compared to the men (37.7% vs. 15.5%, p < 0.001). Risk categories were assigned according to ESC guidelines, with LDL-C targets of <70 mg/dL for high-risk patients and <55 mg/dL for very high risk patients, along with a ≥50% LDL-C reduction for both categories. In the very high risk group, fewer women achieved LDL-C targets at the first two follow-up visits (first follow-up: 50.0% vs. 76.6%, p = 0.008; second follow-up: 55.3% vs. 68.1%, p = 0.049). Although treatment prescription and tolerance were similar between sexes, women showed smaller LDL-C reductions at the first follow-up (51.7 ± 23.9% vs. 57.3 ± 24.9%, p = 0.044). Conclusions: PCSK9-targeted therapies were effective in both sexes at third follow-up, although women showed a tendency toward a delayed response and lower target attainment, indicating the potential need for more personalized management strategies. Full article

Background: Atrial fibrillation (AF) is the most common supraventricular arrythmia and one of the most commonly encountered heart conditions in clinical practice. Emerging evidence suggests a significant role of inflammation in the pathogenesis of AF. Population studies have also suggested an association between AF and cognitive impairment and dementia. The aim of this study is therefore to assess, in a population of AF patients on oral anticoagulant therapy, the association between circulating biomarkers involved in the pathogenesis of AF and the cognitive and motor performances of the enrolled patients. Methods: The Strat-AF study is an observational, prospective, single-center, hospital-based study enrolling elderly patients with AF. Results refer to 180 subjects who underwent a complete clinical, biohumoral, cognitive, and functional evaluation. Results: At multivariate logistic regression, Clot Lysis Time (CLT) and circulating levels of von Willebrand Factor (vWF) remained significantly associated with pathological performances at the Stroop test (expressed as execution time) [OR 95% CI 1.54 (1.02–2.35), p = 0.042 and 1.75 (1.08–2.82), p = 0.023, respectively]. With regard to the Short Physical Performance Battery (SPPB), the circulating levels of IL-8 remained significantly associated with the clinical endpoint [OR 95% CI 2.19 (1.13–4.25), p = 0.020]. Conclusions: Our results suggest a potential innovative tool able to identify AF patients at risk of worse prognosis in terms of cognitive and motor performances. The clinical relevance of these results is due to the fact that we have no efficient methods to predict a deterioration in the cognitive performance and, consequently, the possible onset of dementia in AF patients undergoing oral anticoagulant therapy. Full article

Background: Aspirin is part of the therapeutic antithrombotic armamentarium for the management of patients with established clinically relevant atherosclerosis or thrombotic cardiovascular disease. Personalized medicine identifies those who benefit most or face fewer risks from aspirin. The role of aspirin in primary prevention is still debatable. We aimed to assess the risks and benefits of aspirin in this setting, using the data of the prospective VITAL (VITamins and Lifestyle) study. Methods: We conducted a retrospective evaluation of the VITAL cohort. In this analysis, participants were split according to aspirin usage. Aspirin use was evaluated regarding all-cause mortality, CV mortality, major cardiovascular event (MACE), myocardial infarction, coronary heart disease, total stroke, and hemorrhagic stroke. The hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated to explore the association between cardiovascular events and aspirin usage. The estimates were adjusted for demographic and clinical variables. Results: The aspirin users (n = 11,570) were older, more frequently men, the body mass index was higher, and the proportion of smokers was smaller compared with non-users (n = 13,927). After adjusting for demographic and clinical variables, aspirin was not identified as a predictor of cardiovascular death (HR 1.17, 95%CI 0.89 to 1.55), major cardiovascular events (HR 1.04, 95%CI 0.89 to 1.22), coronary heart disease (HR 1.16, 95%CI 0.98 to 1.37), nor stroke (HR 1.01, 95%CI 0.77 to 1.31). Conclusion: In this retrospective analysis of the VITAL cohort, aspirin was not associated with a reduced risk of cardiovascular mortality or events. Full article

Objective: This study aimed to investigate potential specific molecular and neuroimaging biomarkers for stroke subtype recurrence to improve secondary stroke prevention. Methods: A retrospective analysis was conducted on a prospective stroke biobank. The main endpoint was to evaluate the association between different biomarkers and the recurrence of stroke subtypes. Serum levels of interleukin 6 (IL-6) and tumor necrosis factor-alpha (TNF-a) were analyzed as inflammation biomarkers; N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) and microalbuminuria were used as atrial/endothelial dysfunction biomarkers, while leukoaraiosis (LA) and soluble TNF-like inducers of apoptosis (sTWEAK) were used as biomarkers for blood–brain barrier dysfunction. Demographic and clinical variables were also included. Results: A total of 5038 stroke patients were included, with a mean follow-up of 4.9 years (±3.3). Stroke recurrences were observed in 18.4% of patients (927 individuals). The main results found were as follows: LA was independently associated with lacunar stroke recurrence (adjusted OR 9.50; 95% CI: 3.12–28.93). NT-pro-BNP levels higher than >1000 pg/mL were independently associated with cardioembolic stroke recurrence (adjusted OR 1.80; 95% CI: 1.23–2.61). Persistently elevated TNF-a levels (>24 pg/mL) after stroke recurrence showed an adjusted OR of 21.26 (95% CI: 12.42–37.59) for atherothrombotic subtype, whereas persistently high sTWEAK levels (>7000 pg/mL) after a second hemorrhagic stroke showed an adjusted OR of 4.81 (95% CI: 2.86–8.07) for hemorrhagic subtype. Conclusions: The presence of LA and high levels of NT-pro-BNP, TNF-a, and sTWEAK were associated with an increased risk for lacunar, cardioembolic, atherothrombotic, and hemorrhagic stroke recurrences, respectively. Full article

Ticagrelor, a reversible platelet P2Y₁₂ receptor antagonist, exerts various pleiotropic actions, some of which are at least partially mediated through adenosine. We studied the ticagrelor and adenosine effect on the angiogenic properties of progenitor CD34⁺-derived endothelial colony-forming cells (ECFCs). Angiogenesis studies were performed in vitro using capillary-like tube formation and spheroid-based angiogenesis assays. The effects of adenosine receptor antagonists, including DPCPX (A₁ antagonist), SCH58621 (A_2A antagonist), MRS1706 (A_2B inverse agonist and antagonist), MRS1220 (A₃ antagonist) and adenosine deaminase (ADA), were also investigated. Ticagrelor, adenosine, and their combination increased capillary-like tube formation and spheroid sprout formation by ECFCs in a dose-dependent manner. This effect was significantly reduced by SCH58621, MRS1706, and their combination, as well as by ADA. By contrast, DPCPX and MRS1220 did not exhibit any inhibitory effects. Similar results were obtained when mature human umbilical vein endothelial cells (HUVECs) were studied. These results show that ticagrelor stimulates angiogenesis by progenitor and mature endothelial cells in an adenosine-dependent pathway in which the adenosine receptors A_2A and A_2B play major roles. The significance of these results at the clinical level in patients with atherothrombotic events and treated with ticagrelor needs to be investigated. Full article

The anti-oxidative and anti-inflammatory properties of high-density lipoprotein (HDL) are thought to be mediated by paraoxonase 1 (PON1), a calcium-dependent hydrolytic enzyme carried on a subfraction of HDL that also carries other anti-oxidative and anti-inflammatory proteins. In humans and mice, low PON1 activity is associated with elevated oxidized lipids and homocysteine (Hcy)-thiolactone, as well as proteins that are modified by these metabolites, which can cause oxidative stress and inflammation. PON1-dependent metabolic changes can lead to atherothrombotic cardiovascular disease, Alzheimer’s disease, and cancer. The molecular bases underlying these associations are not fully understood. Biochemical, proteomic, and metabolic studies have significantly expanded our understanding of the mechanisms by which low PON1 leads to disease and high PON1 is protective. The studies discussed in this review highlight the changes in gene expression affecting proteostasis as a cause of the pro-oxidative and pro-inflammatory phenotypes associated with attenuated PON1 activity. Accumulating evidence supports the conclusion that PON1 regulates the expression of anti-oxidative and anti-inflammatory proteins, and that the disruption of these processes leads to disease. Full article

Background/Objectives. A Mediterranean diet (MD) has been associated with neuroprotective effects. We aimed to assess the MD’s association with stroke prognosis and the potential mediators involved. Methods. Seventy patients with acute anterior circulation ischemic stroke were included. Dietary patterns were evaluated using the MEDAS scale, a food-frequency questionnaire, and a 24 h recall. Circulating biomarkers including insulin resistance (HOMA index), adipokines (resistin, adiponectin, leptin), choline pathway metabolites (TMAO, betaine, choline), and endothelial progenitor cells (EPCs) were measured. Early neurological improvement (ENI) at 24 h, final infarct volume, and functional outcome at 3 months were assessed. Results. Adherence to MD and olive oil consumption were associated with a lower prevalence of diabetes and atherothrombotic stroke, and with lower levels of fasting glycemia, hemoglobinA1C, insulin resistance, and TMAO levels. Monounsaturated fatty acids and oleic acid consumption correlated with lower resistin levels, while olive oil consumption was significantly associated with EPC mobilization. Multivariate analysis showed that higher MD adherence was independently associated with ENI and good functional prognosis at 3 months. EPC mobilization, lower HOMA levels, and lower resistin levels were associated with ENI, a smaller infarct volume, and good functional outcome. Conclusions. MD was associated with better prognosis after ischemic stroke, potentially mediated by lower insulin resistance, increased EPC mobilization, and lower resistin levels, among other factors. Full article

Atherosclerosis is a chronic inflammatory disorder which remains the main cause of cardiovascular morbidity and mortality, with carotid atherosclerosis (CA) being a major cause of ischemic stroke. Epigenetic regulation plays a significant role in CA progression and stroke, yet the impact of circulating microRNA expression, associated with atherogenesis, has not been clearly defined. We included 81 patients with moderate–severe CA (mean age 67 ± 7 years, 53% male), 42% of whom had prior ipsilateral ischemic stroke (i.e., were symptomatic). A total of 24 miRs were identified and their plasma expression levels were measured. We observed that several microRNAs were up-regulated in stroke survivors, namely miR-200c-3p (30.6 vs. 29.7, p = 0.047), miR-106b-3p (31.01 vs. 30.25, p = 0.004), and miR-494-5p (39 vs. 33, p < 0.001), while others (miR183-3p [25.5 vs. 28.6, p < 0.001], miR-126-5p [35.6 vs. 37.1, p = 0.03], and miR-216-3p [12.34 vs. 16.2, p < 0.001]) had lower plasma levels in symptomatic patients. In a multivariable logistic regression model for symptomatic CA, the only miRs showing statistical significance were miR-106b-5p, miR-183-3p, miR-216-3p, and miR-494-5p. Cluster analysis demonstrated differential miR expression in CA patients depending on their stroke status. Epigenetic modulation, represented as complex interplay between circulating miRs of different atherogenic potential, may play a significant role in CA development and progression. In our study, we show possible candidates for future research regarding CA and stroke. Full article

Oxidative stress constitutes a main molecular mechanism underlying cardiovascular diseases (CVDs). This pathological mechanism can be triggered by NADPH oxidases (NOXs), which produce reactive oxygen species (ROS). In fact, the different NOXs have been associated with myocardial infarction, atherothrombosis, and stroke. More specifically, we will focus on the implications of NOXs in atherothrombotic stroke. Each NOX member participates in a different way in the several stages of this disease: endothelial dysfunction, immune cell infiltration, foam cell genesis, vascular smooth muscle cells (VSMC) proliferation, and atherosclerotic plaque formation. Additionally, some NOXs are involved in plaque instability, thrombosis, ischemic stroke, and ischemia-reperfusion injury (IRI). Interestingly, the effects of NOXs in this pathology depend on the specific homolog, the cell type in which they are activated, and the stage of the disease. In this review we summarize the most up-to-date information about the implications of vascular NOXs in each of these processes. Finally, we highlight some limitations and future perspectives on the study of NOXs in CVDs. Full article

Background: Real-world data on the use of lipid-lowering therapy (LLT) in clinical practice show that about 80% of (very) high-cardiovascular (CV)-risk patients disregard the 2019 European Society of Cardiology (ESC) Guidelines’ recommendations on dyslipidemias. The availability of proprotein convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9mAb) should reduce this gap. Our aim was to provide data on PCSK9mAb use in clinical practice, investigating the achievement of the ESC Guidelines’ recommendations in the real world. Methods: Between April 2018 and December 2022, patients who started on PCSK9mAb therapy (140 mg of evolocumab or 75 mg or 150 mg of alirocumab, subcutaneous injection every 2 weeks) were included in a prospective registry. Our cohort consisted of 256 patients: 95 (37.1%) were women (mean age: 65.43 ± 11.12 yrs), 53 (20.7%) were at high CV risk, and 203 (79.3%) were at very high CV risk. Results: After one year of PCSK9mAb treatment, nearly 60% of patients demonstrated full adherence to the ESC Guidelines’ recommendations, defined as achieving at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C) levels along with reaching LDL-C target levels (≤55 and ≤70 mg/dL for very high and high risk, respectively). Concomitant high-dose statin therapy emerged as the primary predictor of LDL-C target attainment. Heterozygous familial hypercholesterolemia (HeFH), statin intolerance, and female gender were associated with a significant lower probability of achieving LDL-C target levels. Conclusions: Our analysis confirms that PCSK9mAb treatment is safe and effective, enabling 60% of our cohort to fully achieve the LDL-C guideline recommendations. The use of high-intensity statins emerged as a significant predictor of efficacy. Conversely, familial hypercholesterolemia and female gender were identified as predictors of therapeutic failure. Hence, it is crucial to address disparities in cardiovascular disease prevention between genders and to enhance strategies for managing elevated LDL-C in HeFH patients. Full article

Platelets play a significant role in hemostasis, forming plugs at sites of vascular injury to limit blood loss. However, if platelet activation is not controlled, it can lead to thrombotic events, such as myocardial infarction and stroke. To prevent this, antiplatelet agents are used in clinical settings to limit platelet activation in patients at risk of arterial thrombotic events. However, their use can be associated with a significant risk of bleeding. An enhanced comprehension of platelet signaling mechanisms should facilitate the identification of safer targets for antiplatelet therapy. Over the past decade, our comprehension of the breadth and intricacy of signaling pathways that orchestrate platelet activation has expanded exponentially. Several recent studies have provided further insight into the regulation of platelet signaling events and identified novel targets against which to develop novel antiplatelet agents. Antiplatelet drugs are essential in managing atherothrombotic vascular disease. The current antiplatelet therapy in clinical practice is limited in terms of safety and efficacy. Novel compounds have been developed in response to patient variability and resistance to aspirin and/or clopidogrel. Recent studies based on randomized controlled trials and systematic reviews have definitively demonstrated the role of antiplatelet therapy in reducing the risk of cardiovascular events. Antiplatelet therapy is the recommended course of action for patients with established atherosclerosis. These studies compared monotherapy with a P2Y12 inhibitor versus aspirin for secondary prevention. However, in patients undergoing percutaneous coronary intervention, it is still unclear whether the efficacy of P2Y12 inhibitor monotherapy after a short course of dual antiplatelet therapy depends on the type of P2Y12 inhibitor. This paper focuses on the advanced-stage evaluation of several promising antiplatelet drugs. Full article

The JAK2 V617F somatic variant is a well-known driver of myeloproliferative neoplasms (MPN) associated with an increased risk for athero-thrombotic cardiovascular disease. Recent studies have demonstrated its role in the development of thoracic aortic aneurysm (TAA). However, limited clinical information and level of JAK2 V617F burden have been provided for a comprehensive evaluation of potential confounders. A retrospective genotype-first study was conducted to identify carriers of the JAK2 V617F variant from an internal exome sequencing database in Yale DNA Diagnostics Lab. Additionally, the overall incidence of somatic variants in the JAK2 gene across various tissue types in the healthy population was carried out based on reanalysis of SomaMutDB and data from the UK Biobank (UKBB) cohort to compare our dataset to the population prevalence of the variant. In our database of 12,439 exomes, 594 (4.8%) were found to have a thoracic aortic aneurysm (TAA), and 12 (0.049%) were found to have a JAK2 V617F variant. Among the 12 JAK2 V617F variant carriers, five had a TAA (42%), among whom four had an ascending TAA and one had a descending TAA, with a variant allele fraction ranging from 11.2% to 20%. Among these five patients, 60% were female, and average age at diagnosis was 70 (49–79). The mean ascending aneurysm size was 5.05 cm (range 4.6–5.5 cm), and four patients had undergone surgical aortic replacement or repair. UKBB data revealed a positive correlation between the JAK2 V617F somatic variant and aortic valve disease (effect size 0.0086, p = 0.85) and TAA (effect size = 0.004, p = 0.92), although not statistically significant. An unexpectedly high prevalence of TAA in our dataset (5/594, 0.84%) is greater than the prevalence reported before for the general population, supporting its association with TAA. JAK2 V617F may contribute a meaningful proportion of otherwise unexplained aneurysm patients. Additionally, it may imply a potential JAK2-specific disease mechanism in the developmental of TAA, which suggests a possible target of therapy that warrants further investigation. Full article