Relationship between ω3 and ω6 polyunsaturated fatty acids and atrial fibrillation in acute ischemic stroke.

BACKGROUND & AIMS: Some ω3 polyunsaturated fatty acids (PUFAs) are said to demonstrate a dose-related risk of atrial fibrillation (AF), conversely, some ω6 PUFAs might have AF protective potential. However, few investigated the relation among ischemic strokes. Primarily, we aimed to examine a relation between ω3 and ω6 PUFAs and the presence of AF in ischemic strokes. Further, since, some PUFAs are said to affect the cardiac load, we secondarily aimed to investigate the association between ω3 and ω6 PUFAs and brain natriuretic peptide (BNP) and the occurrence of cerebral large vessel occlusion (LVO) in ischemic strokes with AF. METHODS: Consecutive patients with ischemic stroke admitted between 2012 and 2022 were retrospectively screened. Plasma levels of PUFAs, including eicosapentaenoic acid (EPA), docosahexaenoic acid, dihomo-γ-linolenic acid (DGLA) and arachidonic acid (AA), were assayed. Data were analyzed using a Poisson regression analysis with a robust variance estimator and a multiple linear regression analysis. RESULTS: We screened 2112 consecutive ischemic strokes, including 1574 (1119 [71%] males, median age 69 years). Lower DGLA (prevalence ratio (PR) 0.885, 95% CI 0.811-0.966, p = 0.006), lower AA (PR 0.797, 95% CI 0.649-0.978, p = 0.030), and higher EPA/AA ratio (PR 1.353, 95% CI 1.036-1.767, p = 0.026) were associated with AF. Checking the linearity between AF and PUFAs, negative linear trends were observed between DGLA quartiles (Q1: PR 1.901, Q2: PR 1.550, Q3: PR 1.423, Q4: 1.000, p < 0.001 for trend) and AA quartiles (Q1: PR 1.499, Q2: PR 1.204, Q3: PR 1.125, Q4: 1.000, p = 0.004 for trend), with positive linear trends between EPA/AA ratio quartiles (Q1: 1.000, Q2: PR 1.555, Q3: PR 1.612, Q4: PR 1.797, p = 0.001 for trend). Among patients with AF, a negative association between AA and BNP (unstandardized coefficient -1.316, 95% CI -2.290∼-0.342, p = 0.008) was observed, and lower AA was associated with LVO (PR 0.707, 95% CI 0.527-0.950, p = 0.021). CONCLUSION: Lower DGLA and AA and a higher EPA/AA ratio might be related to the development of AF in ischemic strokes. Further, AA might have a cardio-cerebrovascular protective role in ischemic strokes with AF.

Association Between Remnant Cholesterol and Risk of Incident Atrial Fibrillation: Population-Based Evidence From a Large-Scale Prospective Cohort Study.

BACKGROUND: Evidence for the relationship between remnant cholesterol (RC) and incident atrial fibrillation (AF) risk remains sparse and limited. METHODS AND RESULTS: Participants were enrolled between 2006 and 2010 and followed up to 2021. The multivariable Cox proportional hazards model was used to examine the relationship between RC quartiles and risk of incident AF. Subgroup analyses and sensitivity analyses were performed to explore the potential modification of the association and the robustness of the main findings. A total of 422 316 participants (mean age, 56 years; 54% women) were included for analyses. During a median follow-up of 11.9 years (first quartile-third quartile, 11.6-13.2 years), there were 24 774 AF events documented with an incidence of 4.92 events per 1000 person-years (95% CI, 4.86-4.98). Participants in higher RC quartiles had a lower risk of incident AF than those in the lowest quartile (first quartile): hazard ratio (HR)=0.96 (95% CI, 0.91-1.00) for second quartile; HR=0.92 (95% CI, 0.88-0.96) for third quartile; and HR=0.85 (95% CI, 0.81-0.89) for fourth quartile (P for trend <0.001). The association between RC quartiles and risk of incident AF was stronger in participants aged ≥65 years, in men, and in participants without history of diabetes when compared with control groups (P<0.001 for interaction). CONCLUSIONS: On the basis of data from this large-scale prospective cohort study, elevated RC was associated with a lower risk of incident AF.

Can Pre-Ablation Biomarkers Be Used to Predict Arrhythmia Recurrence after Ablation Index-Guided Atrial Fibrillation Ablation? / Os Biomarcadores podem ser Utilizados para Prever Recorrência de Arritmia após a Ablação de Fibrilação Atrial Guiada pelo Ablation-Index?

BACKGROUND: Ablation Index (AI) software has allowed better atrial fibrillation (AF) ablation results, but recurrence rates remain significant. Specific serum biomarkers have been associated with this recurrence. OBJECTIVES: To evaluate whether certain biomarkers could be used (either individually or combined) to predict arrhythmia recurrence after AI-guided AF ablation. METHODS: Prospective multicenter observational study of consecutive patients referred for AF ablation from January 2018 to March 2021. Hemoglobin, brain natriuretic peptide (BNP), C-reactive protein, high sensitivity cardiac troponin I, creatinine clearance, thyroid-stimulating hormone (TSH) and free thyroxine (FT4) were assessed for their ability to predict arrhythmia recurrence during follow-up. Statistical significance was accepted for p values of<0.05. RESULTS: A total of 593 patients were included - 412 patients with paroxysmal AF and 181 with persistent AF. After a mean follow-up of 24±6 months, overall single-procedure freedom from atrial arrhythmia was 76.4%. Individually, all biomarkers had no or only modest predictive power for recurrence. However, a TSH value >1.8 µUI/mL (HR=1.82 [95% CI, 1.89-2.80], p=0.006) was an independent predictor of arrhythmia recurrence. When assessing TSH, FT4 and BNP values in combination, each additional "abnormal" biomarker value was associated with a lower freedom from arrhythmia recurrence (87.1 % for no biomarker vs. 83.5% for one vs. 75.1% for two vs. 43.3% for three biomarkers, p<0.001). Patients with three "abnormal" biomarkers had a threefold higher risk of AF recurrence compared with no "abnormal" biomarker (HR=2.88 [95% CI, 1.39-5.17], p=0.003). CONCLUSIONS: When used in combination, abnormal TSH, FT4 and BNP values can be a useful tool for predicting arrhythmia recurrence after AI-guided AF ablation.

FUNDAMENTO: O software ablation index (AI) permitiu melhorar os resultados da ablação de fibrilação atrial (FA), mas as taxas de recorrência permanecem significativas. Biomarcadores séricos específicos têm sido associados a essa recorrência. OBJETIVOS: Avaliar se certos biomarcadores podem ser utilizados (individualmente ou combinados) para predizer a recorrência de FA pós ablação guiada pelo AI. MÉTODOS: Estudo multicêntrico, observacional, prospectivo de pacientes consecutivos, encaminhados para ablação de FA de janeiro de 2018 a março de 2021. Hemoglobina, peptídeo natriurético cerebral (BNP), proteína C reativa, troponina I ultrassensível, clearance de creatinina, Hormônio Tireoestimulante (TSH), e Tiroxina livre (T4) foram avaliados quanto à capacidade de prever a recorrência de arritmias durante o acompanhamento. Valores de p <0,05 foram aceitos como estatisticamente significativos. RESULTADOS: Um total de 593 pacientes foram incluídos ­ 412 com FA paroxística e 181 com FA persistente. Durante o seguimento médio de 24±6 meses, 76,4% não apresentaram recidiva após ablação. Individualmente, os biomarcadores demonstraram um valor preditivo baixo ou nulo para recorrência. No entanto, TSH >1,8 µUI/mL [HR=1,82 (IC95%, 1,89-2,80), p=0,006] foi um preditor independente de recorrência. Avaliando-se a combinação de TSH, FT4 e BNP, a adição de cada valor "anormal" foi associada a uma menor sobrevida livre de recorrência (87,1% se nenhum vs. 83,5% se um vs. 75,1% se dois vs. 43,3% se três biomarcadores, p<0,001). Doentes com três biomarcadores "anormais" apresentaram três vezes maior probabilidade de recorrência de FA, comparativamente aos que não apresentaram nenhum biomarcador "anormal" (HR=2,88 [IC95%, 1,39-5,17], p=0,003). CONCLUSÕES: Quando combinados, valores anormais de TSH, FT4 e BNP podem ser uma ferramenta útil para prever a recorrência de FA pós ablação guiada pelo AI.

Triglyceride-Glucose Index Predicts Major Adverse Cardiovascular and Cerebrovascular Events in Patients with Atrial Fibrillation.

This study aimed to explore the relationship between the trajectory of the triglyceride-glucose (TyG) index and the occurrence of major adverse cardiovascular and cerebrovascular events (MACCE) in patients with atrial fibrillation (AF).This prospective study included 1979 patients with AF, who were initially selected from the Kailuan study. Patients of AF were split into four groups according to the value of TyG index. The clinical endpoint was MACCE, including myocardial infarction and ischemic stroke. Cox proportional hazard models were employed to examine the hazard ratio (HR) and 95% confidence interval (CI) for MACCE in various trajectory groups.The mean age of all patients with AF was 67.65 ± 11.15 years, and 1752 (88.53%) were male. Over a median follow-up duration of 5.31 years, in total 227 MACCE were recorded. MACCE cumulative incidence in Quartile 4 (26.96%) was significantly higher than those in other quartiles (P = 0.023). Multivariate Cox proportional hazards regression analysis showed that a higher TyG index (Quartile 4) was significantly and positively linked to MACCE in patients with AF (P = 0.023, HR: 2.103; 95% CI: 1.107-3.994).The evaluated TyG index is significantly associated with an increased risk of MACCE in patients with AF.

Plasma triglyceride is associated with the recurrence of atrial fibrillation after radiofrequency catheter ablation: A retrospective study.

BACKGROUND: The purpose of this study was to explore the association between triglycerides (TGs) and the risk of atrial fibrillation (AF) recurrence. METHODS AND RESULTS: Included were adult patients with AF who underwent radiofrequency catheter ablation in the Affiliated Changzhou Second People's Hospital of Nanjing Medical University. The enrolled patients were divided into the AF recurrence group and the sinus rhythm (SR) maintenance group. The univariate Cox regression analysis and Kaplan-Meier survival curve were performed estimate the association between TG and the risk of AF recurrence. Of the 402 patients, 79 (19.7%) experienced recurrence of AF after ablation. The TG level was significantly higher in the AF recurrence group than in the SR-maintaining group. Patients were grouped by quartile of TG levels, with Quartile 1 and Quartile 2 defined as the low concentration group, Quartile 3 as the moderate concentration group, and Quartile 4 as the high concentration group. Multivariate Cox regression analysis showed that the moderate concentration group (p = .02, hazard ratio [HR]: 2.331, 95% confidence interval [CI]: 1.141-4.762) and high concentration group (p = .007, HR: 2.873, 95% CI: 1.332-6.199) were associated with an increased risk of AF recurrence compared with the low concentration group. The median follow-up was 1.17 years, it is indicated that a higher risk of recurrent AF was observed in the moderate concentration and high concentration group (log-rank: χ2 = 7.540, p = .023). CONCLUSION: Our data suggest that an elevated TG level measured before catheter ablation is associated with an increased risk of AF recurrence.

Predictive Value of Serum microRNA-29b-3p in Recurrence of Atrial Fibrillation After Radiofrequency Catheter Ablation.

Objective: Atrial fibrillation (AF) is a common arrhythmia. This study explored serum miR-29b-3p expression in AF patients and its value in predicting AF recurrence after radiofrequency catheter ablation (RFCA). Methods: Totally 100 AF patients who underwent RFCA were enrolled, with 100 individuals without AF as controls. Serum miR-29b-3p expression in participants was determined using RT-qPCR. The correlation between miR-29b-3p and atrial fibrosis markers (FGF-21/FGF-23) was assessed by Pearson analysis. The diagnostic efficacy of serum miR-29b-3p and FGF-21/FGF-23 in predicting AF recurrence after RFCA was analyzed by the receiver operating characteristic (ROC) curves. The Kaplan-Meier method was adopted to evaluate the effect of miR-29b-3p expression on the incidence of AF recurrence after RFCA. The independent risk factors for AF recurrence after RFCA were analyzed by logistic regression analysis. Results: Serum miR-29b-3p was poorly expressed in AF patients. After RFCA, AF patients showed elevated serum miR-29b-3p expression. Serum miR-29b-3p expression in AF patients negatively correlated with serum FGF-21 and FGF-23 concentrations. The cut-off values of serum miR-29b-3p, FGF-21, and FGF-23 in identifying AF recurrence were 0.860 (sensitivity: 100.00%, specificity: 39.71%), 222.2 pg/mL (sensitivity: 96.88%, specificity: 32.35%) and 216.3 ng/mL (sensitivity: 53.13%, specificity: 70.59%), respectively. Patients with low miR-29b-3p expression had a significantly higher incidence of AF recurrence than patients with high miR-29b-3p expression. Serum miR-29b-3p expression was one of the independent risk factors for AF recurrence after RFCA. Conclusion: Low miR-29b-3p expression in AF patients has certain predictive values and is one of the independent risk factors for AF recurrence after RFCA.

Transcriptomic Analysis of Extracellular Vesicles in the Search for Novel Plasma and Thrombus Biomarkers of Ischemic Stroke Etiologies.

Accurate etiologic diagnosis provides an appropriate secondary prevention and better prognosis in ischemic stroke (IS) patients; still, 45% of IS are cryptogenic, urging us to enhance diagnostic precision. We have studied the transcriptomic content of plasma extracellular vesicles (EVs) (n = 21) to identify potential biomarkers of IS etiologies. The proteins encoded by the selected genes were measured in the sera of IS patients (n = 114) and in hypertensive patients with (n = 78) and without atrial fibrillation (AF) (n = 20). IGFBP-2, the most promising candidate, was studied using immunohistochemistry in the IS thrombi (n = 23) and atrium of AF patients (n = 13). In vitro, the IGFBP-2 blockade was analyzed using thromboelastometry and endothelial cell cultures. We identified 745 differentially expressed genes among EVs of cardioembolic, atherothrombotic, and ESUS groups. From these, IGFBP-2 (cutoff > 247.6 ng/mL) emerged as a potential circulating biomarker of embolic IS [OR = 8.70 (1.84-41.13) p = 0.003], which was increased in patients with AF vs. controls (p < 0.001) and was augmented in cardioembolic vs. atherothrombotic thrombi (p < 0.01). Ex vivo, the blockage of IGFBP-2 reduced clot firmness (p < 0.01) and lysis time (p < 0.001) and in vitro, diminished endothelial permeability (p < 0.05) and transmigration (p = 0.06). IGFBP-2 could be a biomarker of embolic IS and a new therapeutic target involved in clot formation and endothelial dysfunction.

Left atrial size modify the association between uric acid and atrial fibrillation in patients with coronary artery disease.

BACKGROUND AND AIMS: The potential influence of left atrial size on the relationship between uric acid and atrial fibrillation has not been fully investigated. This study aims to evaluate the interaction effect of left atrial size on the association between uric acid and atrial fibrillation in patients with coronary artery disease. METHODS AND RESULTS: This retrospective cohort study, conducted from January 2018 to October 2022, included 2004 patients undergoing Drug-Eluting Stent implantation for coronary artery disease. Utilizing logistic regression models with the product of left atrial enlargement (LAE) and uric acid, interaction effects were assessed. Among the participants, 383 had LAE, and 159 experienced atrial fibrillation. After adjusting for covariates, continuous uric acid levels were associated with an increased risk of atrial fibrillation in patients without LAE (OR:1.631, 95% CI: 1.284-2.072), but not in those with LAE (OR:1.069, 95% CI: 0.848-1.348). A significant interaction of uric acid levels was observed between groups with and without LAE (p = 0.046). Restricted cubic spline curves indicated a J-shaped relationship between uric acid and atrial fibrillation in the absence of LAE. However, the association between uric acid levels and atrial fibrillation in the LAE group remained unchanged with increasing uric acid levels. CONCLUSION: The study suggested that left atrial size modified the association between uric acid and atrial fibrillation in patients with coronary artery disease. Uric acid serves as a potential biomarker for atrial fibrillation risk, especially in individuals without LAE.

Is pre-diabetes a predictor of events in patients with atrial fibrillation?

BACKGROUND: Diabetes mellitus (DM) increases the probability of presenting atrial fibrillation (AF) and it is a predictor of its ischemic stroke. There is limited information of the association between glycated hemoglobin (HbA1c) levels and ischemic, embolic or bleeding events in patients with pre-DM and AF. METHODS: To investigate whether the presence of pre-DM in patients with AF predicts ischemic or bleeding events, myocardial infarction or mortality, we performed a retrospective study with a final cohort of 2993 non-diabetic patients with AF and data of glycated hemoglobin (HbA1c). We divided the cohort in two groups: those with normal glucose (n = 1351) and those with pre-diabetes (n = 1642). Incidence rates were calculated as the number of events per 100 person-years and were then compared between groups. Competitive hazard regression analysis for non-fatal events(death as the competing event) and conventional Cox regression for mortality were performed. RESULTS: There was not difference between groups for incidence rates of the different events per 100 person-years. Even considering HbA1c as continuous variable, the unadjusted analysis showed no relation between levels of HbA1c and more risk of events. This association remained not significant after adjustment for CHA2DS2-VASc score, HAS-BLED score and anticoagulation therapy. CONCLUSION: In this study of 2993 non-diabetic patients with new-onset AF, we have not found an association between HbA1c and worse prognosis when it is in the range of pre-diabetes.

Correlation of epicardial adipose tissue and inflammatory indices in patients with STEMI and implications for atrial arrhythmias.

BACKGROUND: Epicardial adipose tissue(EAT) is associated with inflammation in previous studies but is unknown in patients with ST-segment elevation myocardial infarction(STEMI).This study investigated the correlation between epicardial fat and inflammatory cells obtained by cardiac magnetic resonance (CMR) and the effect on atrial arrhythmias in patients with STEMI. METHODS: This was a single-center, retrospective study. We consecutively selected patients who all completed CMR after Percutaneous Coronary Intervention (PCI) from January 2019 to December 2022 and then had regular follow-ups at 1, 3, 6, 9, and 12 months. The enrolled patients were grouped according to the presence or absence of atrial arrhythmia and divided into atrial and non-atrial arrhythmia groups. RESULTS: White blood cell, neutrophil, lymphocyte, C-reactive protein, EATV, LVES, LVED were higher in the atrial arrhythmia group than in the non-atrial arrhythmia group, and LVEF was lower than that in the non-atrial arrhythmia group (p < 0.05); EATV was significantly positively correlated with each inflammatory indices (white blood cell: r = 0.415 p < 0.001, neutrophil:r = 0.386 p < 0.001, lymphocyte:r = 0.354 p < 0.001, C-reactive protein:r = 0.414 p < 0.001); one-way logistic regression analysis showed that risk factors for atrial arrhythmias were age, heart rate, white blood cell, neutrophil, lymphocyte, C-reactive protein, EATV, LVES, LVED; multifactorial logistic regression analysis showed that neutrophil, lymphocyte, C-reactive protein, EATV, and LVES were independent risk factors for atrial arrhythmias; ROC analysis showed that the area under the curve (AUC) for neutrophil was 0.862; the AUC for lymphocyte was 1.95; and the AUC for C-reactive protein was 0.862. reactive protein was 0.852; AUC for LVES was 0.683; and AUC for EATV was 0.869. CONCLUSION: In patients with STEMI, EAT was significantly and positively correlated with inflammatory indices; neutrophil, lymphocyte, C-reactive protein, EATV, and LVES were independent risk factors for atrial arrhythmias and had good predictive value.

Anti-Xa Monitoring of Apixaban (ZyQuis) in Venous Thrombo-Embolism and Atrial Fibrillation.

Apixaban is a direct oral Xa inhibitor and is indicated for the treatment of venous thrombo-embolism (VTE) and prevention of stroke in atrial fibrillation (AF). Recently, a generic (ZyQuis, Zydus Lifesciences Limited, India) has received Food and Drug Administration approval. While bioequivalence has been demonstrated with Eliquis (Bristol-Myers Squibb/Pfizer, UK), it is necessary to monitor its effectiveness prior to acceptance in medical practice. This prospective study independently evaluated Apixaban (ZyQuis) at two accredited laboratories. Participants were converted from Warfarin or Rivaroxaban to Apixaban 5 mg bd for a duration of one month. Peak anti-Xa levels were measured 3-4 h post the morning dose. The samples were processed on the Atellica COAG 360 (Siemens Healthineers, Marburg, Germany) analyzers with a chromogenic anti-Xa assay (Innovance, reference interval 69-321 ng/mL). There were 26 participants; 5 men, 21 women; mean ± standard deviation age of 46 ± 12 years. Indications for anticoagulation included: VTE (88.5%) and AF (11.5%). 69.2% of the participants had at least one comorbidity. 96.2% of the anti-Xa levels were within the laboratory's 95% reference interval. Mean anti-Xa activity was 191 ± 69 ng/mL and 186 ± 68 ng/mL measured at respective laboratories. Mean differences in anti-Xa measurements represented by Bland-Altman statistics were small (bias of -2.6%, 95% confidence interval -1.11 to -4.09) and a strong correlation was observed on Deming regression analysis (0.995). Apixaban (ZyQuis) was effective for the management of VTE and AF as evidenced by anti-Xa activity.

Identification of Plasmatic MicroRNA-206 as New Predictor of Early Recurrence of Atrial Fibrillation After Catheter Ablation Using Next-generation Sequencing.

BACKGROUND: Catheter ablation (CA) of atrial fibrillation (AF) is indicated in patients with recurrent and symptomatic AF episodes. Despite the strict inclusion/exclusion criteria, AF recurrence after CA remains high. Identification of a novel biomarker that would predict AF recurrence would help to stratify the patients. The aim of the study was to seek novel biomarkers among the plasmatic microRNAs (miRNAs, miRs). METHODS: A prospective monocentric study was conducted. A total of 49 consecutive AF patients indicated for CA were included. Blood sampling was performed prior to CA. RNA was isolated from plasma using commercial kits. In the exploration phase, small RNA sequencing was performed in ten AF patients (five with and five without AF recurrence) using Illumina instrument. In the validation phase, levels of selected miRNAs were determined using quantitative reverse transcription polymerase chain reaction (qRT-PCR) in all participants. RESULTS: Altogether, 22 miRNAs were identified as altered between the groups by next-generation sequencing (using the DESeq2 algorithm). Using qRT-PCR, levels of the five most altered miRNAs (miR-190b/206/326/505-5p/1296-5p) were verified in the whole cohort. Plasma levels of hsa-miR-206 were significantly higher in patients with early (within 6 months) AF recurrence and showed an increase of risk recurrence,2.65 times by every increase in its level by 1 unit in the binary logistic regression. CONCLUSION: We have identified a set of 22 plasmatic miRNAs that differ between the patients with and without AF recurrence after CA and confirmed hsa-miR-206 as a novel miRNA associated with early AF recurrence. Results shall be verified in a larger independent cohort.

Difference Between Estimated GFR Based on Cystatin C Versus Creatinine and Incident Atrial Fibrillation: A Cohort Study of the UK Biobank.

RATIONALE & OBJECTIVE: The difference between cystatin C-based and creatinine-based estimated glomerular filtration rate (eGFRdiff) has been suggested to reflect factors distinct from kidney function that are associated with cardiovascular risk. However, the association between eGFRdiff and atrial fibrillation (AF) risk has not been extensively evaluated. STUDY DESIGN: Prospective cohort study. SETTING & PARTICIPANTS: Using data from the UK Biobank, this study included 363,494 participants with measured serum creatinine and cystatin C levels and without a prior diagnosis of AF or a history of related procedures. EXPOSURE: Estimated GFRdiff, calculated as cystatin C-based eGFR minus creatinine-based eGFR. Estimated GFRdiff was also categorized as negative (<-15mL/min/1.73m2), midrange (-15 to 15mL/min/1.73m2), or positive (≥15mL/min/1.73m2). OUTCOME: Incident AF. ANALYTICAL APPROACH: Subdistribution hazard models were fit, treating death that occurred before development of AF as a competing event. RESULTS: During the median follow-up period of 11.7 years, incident AF occurred in 18,994 (5.2%) participants. In the multivariable-adjusted model, participants with a negative eGFRdiff had a higher risk of incident AF (subdistribution HR [SHR], 1.25 [95% CI, 1.20-1.30]), whereas participants with a positive eGFRdiff had a lower risk of AF (SHR, 0.81 [95% CI, 0.77-0.87]) compared with those with a midrange eGFRdiff. When eGFRdiff was treated as a continuous variable in the adjusted model, every 10mL/min/1.73m2 higher eGFRdiff was associated with a 0.90-fold decrease in the risk of incident AF. LIMITATIONS: A single measurement of baseline serum creatinine and cystatin C levels. CONCLUSIONS: The difference between cystatin C- and creatinine-based eGFRs was associated with the risk of AF development. A higher eGFRdiff was associated with a lower risk of AF. These findings may have implications for the management of patients at risk of incident AF. PLAIN-LANGUAGE SUMMARY: The difference between cystatin C-based estimated glomerular filtration rate (eGFR) and creatinine-based eGFR has recently gained attention as a potential indicator of cardiovascular outcomes influenced by factors other than kidney function. This study investigated the association between the differences in 2 eGFRs (cystatin C-based eGFR minus creatinine-based eGFR) and incident atrial fibrillation (AF) among>340,000 participants from the UK Biobank Study. Compared with those with a near zero eGFR difference, participants with a negative eGFR difference had a higher risk of AF, while those with a positive eGFR difference had a lower risk. These findings suggest that measuring eGFR differences may help identify individuals at a higher risk of developing AF.

Association of C-reactive protein level with adverse outcomes in patients with atrial fibrillation: A meta-analysis.

BACKGROUND: Studies on the association between C-reactive protein (CRP) level and poor outcomes have been yielded controversial results in patients with atrial fibrillation (AF). This meta-analysis sought to investigate the utility of elevated CRP level in predicting adverse outcomes in AF patients. METHODS: Two authors systematically searched PubMed and Embase databases (until December 10, 2022) for studies evaluating the value of elevated CRP level in predicting all-cause mortality, cardiovascular death, stroke, or major adverse cardiovascular events (MACEs) in AF patients. The predictive value of CRP was expressed by pooling adjusted hazard ratio (HR) with 95% confidence intervals (CI) for the highest versus the lowest level or per unit of log-transformed increase. RESULTS: Ten studies including 30,345 AF patients satisfied our inclusion criteria. For the highest versus the lowest CRP level, the pooled adjusted HR was 1.57 (95% CI 1.34-1.85) for all-cause mortality, 1.18 (95% CI 0.92-1.50) for cardiovascular death, and 1.57 (95% CI 1.10-2.24) for stroke, respectively. When analyzed the CRP level as continuous data, per unit of log-transformed increase was associated with a 27% higher risk of all-cause mortality (HR 1.27; 95% CI 1.23-1.32) and 16% higher risk of MACEs (HR 1.16; 95% CI 1.05-1.28). CONCLUSIONS: Elevated CRP level may be an independent predictor of all-cause mortality, stroke, and MACEs in patients with AF. CRP level at baseline can provide important prognostic information in risk classification of AF patients.

Association of proprotein convertase subtilisin/kexin type 9 (PCSK9) levels with abnormally high ankle-brachial index in atrial fibrillation.

BACKGROUND: High ankle-brachial index (ABI) has been associated with increased risk of worse outcomes in the general population. Few data on atrial fibrillation (AF) exist. Experimental data suggest that proprotein convertase subtilisin/kexin type 9 (PCSK9) contributes to vascular calcification but clinical data on this association are lacking. AIMS: We wanted to investigate the relationship between circulating PCSK9 levels and an abnormally high ABI in patients suffering from AF. METHODS: We analyzed data from 579 patients included in the prospective ATHERO-AF study. An ABI≥1.4 was considered high. PCSK9 levels were measured coincidentally with ABI measurement. We used optimized cut-offs of PCSK9 for both ABI and mortality obtained from Receiver Operator Characteristic (ROC) curve analysis. All-cause mortality according to the ABI value was also analyzed. RESULTS: One hundred and fifteen patients (19.9%) had an ABI ≥1.4. The mean (standard deviation [SD]) age was 72.1 (7.6) years, and 42.1% of patients were women. Patients with ABI ≥1.4 were older, more frequently male, and diabetic. Multivariable logistic regression analysis showed an association between ABI ≥1.4 and serum levels of PCSK9 > 1150 pg/ml (odds ratio [OR], 1.649; 95% confidence interval [CI], 1.047-2.598; P = 0.031). During a median follow-up of 41 months, 113 deaths occurred. In multivariable Cox regression analysis, an ABI ≥1.4 (hazard ratio [HR], 1.626; 95% CI, 1.024-2.582; P = 0.039), CHA2DS2-VASc score (HR, 1.249; 95% CI, 1.088-1.434; P = 0.002), antiplatelet drug use (HR, 1.775; 95% CI, 1.153-2.733; P = 0.009), and PCSK9 > 2060 pg/ml (HR, 2.200; 95% CI, 1.437-3.369; P < 0.001) were associated with all-cause death. CONCLUSIONS: In AF patients, PCSK9 levels relate to an abnormally high ABI ≥1.4. Our data suggest PCSK9 role in contributing to vascular calcification in AF patients.

Relaxin-2 plasma levels in atrial fibrillation are linked to inflammation and oxidative stress markers.

Relaxin-2 exerts many favourable cardiovascular effects in pathological circumstances such as atrial fibrillation (AF) and heart failure, but the mechanisms underlying its actions are not completely understood. Since inflammation and fibrosis are pivotal processes in the pathogenesis of AF, our aim was to study the relationship between relaxin-2 plasma levels in left atrium (LA) and peripheral vein with molecules implicated in fibrosis, inflammation and oxidative stress in AF patients, and to evaluate the anti-fibrotic ability of relaxin-2 in normal human atrial cardiac fibroblasts (NHCF-A). Peripheral vein relaxin-2 plasma levels were higher than LA relaxin-2 plasma levels in men while, in women, peripheral vein relaxin-2 levels were increased compared to men. AF patients with higher levels of relaxin-2 exhibited a reduction in H2O2 plasma levels and in mRNA levels of alpha-defensin 3 (DEFA3) and IL-6 in leucocytes from LA plasma. Relaxin-2-in-vitro treatment inhibited NHCF-A migration and decreased mRNA and protein levels of the pro-fibrotic molecule transforming growth factor-ß1 (TGF-ß1). Our results support an association between relaxin-2 and molecules involved in fibrosis, inflammation and oxidative stress in AF patients, and reinforce an anti-fibrotic protective role of this hormone in NHCF-A; strengthening the relevance of relaxin-2 in AF physiopathology, diagnosis and treatment.

Galectin-3 is an independent predictor of postoperative atrial fibrillation and survival after elective cardiac surgery.

BACKGROUND: Postoperative atrial fibrillation (POAF) is a frequent complication after heart surgery and is associated with thromboembolic events, prolonged hospital stay, and adverse outcomes. Inflammation and fibrosis are involved in the pathogenesis of atrial fibrillation. OBJECTIVE: The purpose of this study was to assess whether galectin-3, which reflects preexisting atrial fibrosis, has the potential to predict POAF and mortality after cardiac surgery. METHODS: Four hundred seventy-five consecutive patients (mean age 67.4 ± 11.8 years; 336 (70.7%) male) undergoing elective heart surgery at the Medical University of Vienna were included in this prospective single-center cohort study. Galectin-3 plasma levels were assessed on the day before surgery. RESULTS: The 200 patients (42.1%) who developed POAF had significantly higher galectin-3 levels (9.60 ± 6.83 ng/mL vs 7.10 ± 3.54 ng/mL; P < .001). Galectin-3 significantly predicted POAF in multivariable logistic regression analysis (adjusted odds ratio per 1-SD increase 1.44; 95% confidence interval 1.15-1.81; P = .002). During a median follow-up of 4.3 years (interquartile range 3.4-5.4 years), 72 patients (15.2%) died. Galectin-3 predicted all-cause mortality in multivariable Cox regression analysis (adjusted hazard ratio per 1-SD increase 1.56; 95% confidence interval 1.16-2.09; P = .003). Patients with the highest-risk galectin-3 levels according to classification and regression tree analysis (>11.70 ng/mL) had a 3.3-fold higher risk of developing POAF and a 4.4-fold higher risk of dying than did patients with the lowest-risk levels (≤5.82 ng/mL). CONCLUSION: The profibrotic biomarker galectin-3 is an independent predictor of POAF and mortality after cardiac surgery. This finding highlights the role of the underlying arrhythmogenic substrate in the genesis of POAF. Galectin-3 may help to identify patients at risk of POAF and adverse outcome after cardiac surgery.

Plasma lipoprotein-associated phospholipase A2 is associated with acute ischemic stroke in patients with atrial fibrillation.

OBJECTIVE: To investigate the association between lipoprotein-associated phospholipase A2 (Lp-PLA2) concentration and the incidence of acute ischemic stroke (AIS) in patients with atrial fibrillation (AF). METHODS: A total of 257 patients admitted to the Kaifeng Central Hospital were enrolled in this study. Receiver operating characteristic (ROC) curve analysis and multivariate logistic regression analysis were used to determine the association between Lp-PLA2 and AIS in patients with AF. RESULTS: In AF group, plasma Lp-PLA2 concentrations were significantly higher in patients with AIS than in those without it (277.4 vs 155.1, p < 0.001). And in the group of AIS patients, patients with AF also had a significantly higher level of Lp-PLA2 concentration than those without (277.4 vs 204.2, p < 0.001). The analysis of the ROC curve showed a significant diagnostic value of Lp-PLA2 for the incidence of AIS in patients with AF (AUC = 0.840, 95% CI: 0.737-0.871, p < 0.001), and the optimal cut-off point was 220.5 ng/ml, with a sensitivity and specificity of 82.14% and 75.5%, respectively. All AF patients were divided into two subgroups: the high Lp-PLA2 group (≥220.5 ng/ml) and the low Lp-PLA2 group (<220.5 ng/ml). And multivariate logistic regression analysis showed that after adjustment of confounders, Lp-PLA2 (OR 12.48, 95%CI 5.73-27.16, p < 0.001) was independently associated with the incidence of AIS in patients with AF. CONCLUSIONS: Plasma Lp-PLA2 concentration was independently associated with the development of AIS in patients with AF. Lp-PLA2 is a potential biomarker for stratification of risk for AIS in patients with AF.

Plasma growth differentiation factor-15 in patients with "lone" atrial fibrillation.

BACKGROUND: Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor ß superfamily, correlated with various stimuli, including cardiovascular disease. The association between plasma GDF-15 level and "lone" AF, that is, AF of unknown etiology (UeAF), is uncertain. METHODS: All patients aged 60 years or younger. AF patients were hospitalized for primary catheter ablation. Patients with sinus rhythm admitted for other diseases during the same period were included in the control group. ELISA was used to measure plasma GDF-15 concentrations. RESULTS: 60 UeAF patients, 60 paroxysmal AF (PAF) patients, and 70 control patients were enrolled. The mean age was 44.6 years. In the UeAF group, no patients had traditional clinical risk factors. The plasma GDF-15 level in the UeAF group was (1028.5 ± 180.5) pg/ml, higher than in the control group, and moderately lower than in the PAF group. In all patients, positive correlations were found between plasma GDF-15 level and age (R = 0.210, p < 0.05), and between plasma GDF-15 level and left atrial diameter (LAD; R = 0.338, p < 0.05; in the UeAF group: R = 0.475, p < 0.05; in the PAF group: R = 0.504, p < 0.05). CONCLUSIONS: Our study first investigated the role of GDF-15 in UeAF. The plasma GDF-15 level in UeAF patients was higher than in sinus rhythm patients and lower than in PAF patients. Moreover, GDF-15 was positively correlated with age and LAD. The role of GDF-15 in UeAF needs further study.