In anticoagulated atrial fibrillation (AF) patients, the validity of models recommended for the stratification of the risk ratio between benefits and hemorrhage risk is limited. We hypothesize that both circulating and neuroimaging-based markers might improve the prediction of bleeding and thrombotic risk in anticoagulated AF patients. The Strat-AF study is an observational, prospective, single-center study enrolling 170 patients with AF; recruited patients are evaluated by means of a comprehensive protocol, with clinical, cerebral magnetic resonance imaging and circulating biomarkers assessment. The main outcome is the evaluation of cerebral microangiopathy related to the levels of circulating biomarkers of inflammation and extracellular matrix (ECM) remodeling. At multivariate logistic regression analysis adjusted for age, sex, CHA2DS2-VASc, HAS-BLED and type of anticoagulant, matrix metalloproteinases (MMP)-2 levels were significantly and positively associated with the presence of cerebral microbleeds (CMBs). A significant association between MMP-2, tissue inhibitor of metalloproteinases (TIMP)-1,-2,-4 levels and white matter hyperintensity was also found. Concerning the small vessel disease (SVD) score, MMP-2 and TIMP-1,-2 levels were associated with the presence of two and three or more signs of SVD, whereas TIMP-4 levels were associated with the presence of three signs of SVD with respect to patients with no instrumental signs of SVD. As regarding the presence of enlarged perivascular spaces (EPVS), a significant association was found for high levels of interleukin (IL)-8 and TIMP 1-2-3. These results demonstrate that patients with AF have evidence of impaired ECM degradation, which is an independent risk factor for thrombotic complications of AF patients on oral anticoagulant therapy. The incorporation of these markers in the prognostic schemes might improve their clinical capability in predicting stroke risk and thrombotic complications.

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.

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.

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.

Background. Atrial fibrillation is the most common arrhythmia, associated with increased risk of ischemic stroke and mortality. Neuroimaging has shown a high prevalence of cerebral small vessel disease markers in AF patients, but the underlying mechanisms remain unclear.Objectives. To investigate the association between microangiopathic and non-microangiopathic neuroimaging markers of cerebrovascular damage and cardiac morphological features in elderly atrial fibrillation patients on oral anticoagulants.Methods. We performed a cross-sectional analysis within the Strat-AF 2 study. From March 2021 to June 2022, we consecutively enrolled patients >65 years with AF on oral anticoagulants for thromboembolic prevention. All underwent clinical assessment, neuroimaging (magnetic resonance imaging, or computed tomography scan), and echocardiography.Results. A total of 179 patients were included (mean age 78.6 ± 6.7 years, 58% male): 100 underwent magnetic resonance imaging and 79 computed tomography. Non-lacunar infarcts were present in 26%, while 79.3% showed at least one cerebral small vessel disease marker. Mean indexed left atrial volume was 48.5 ± 19.8 mL/m². In multivariate analysis, non-paroxysmal atrial fibrillation was independently associated with non-lacunar infarcts (OR 2.95; 95% CI 1.07–8.12; p=0.036). Larger left atrial volume was independently associated with both moderate-to-severe medial temporal lobe atrophy (OR 1.025 per mL/m²; 95% CI 1.003–1.047; p=0.024) and lacunes (OR 1.008; 95% CI 1.010–1.017; p=0.05).Conclusions. In elderly AF patients on OAC, cardiac structural parameters were associated with both microangiopathic and non-microangiopathic brain lesions, even in the absence of prior ischemic stroke. Larger longitudinal studies are needed to confirm and clarify these associations.