Common and specific proteins and pathways in heart and cerebral ischemia.

OBJECTIVE: To understand the similarities and differences between acute ischemic stroke and acute myocardial infarction (AMI) to help in the development of specific or common treatment strategies. METHODS: Using an aptamer-based proteomic array, we measured and compared 1310 circulating proteins in the blood of 40 patients with AIS, 9 patients with AMI, and 31 healthy controls. Pathway enrichment analysis was performed using GSEA and g:profiler. RESULTS: Ninety-four proteins were differentially expressed in AIS, and 284 were differentially expressed in AMI. Of these, 8 were specific to cerebral ischemia, and 197 were specific to myocardial infarction. Forty-two proteins were altered in both ischemia processes. Most altered pathways in AIS could be classified as immune response, cell cycle processing, molecular transport, or signaling. Pathways altered in AMI were mostly related to lipid metabolism and transport, highlighting cholesterol metabolic processes and estrogen signaling. In both types of ischemia, we found pathways related to metabolism, specifically purine metabolism, and signaling processes, such as TNF signaling or MAPK1/3. CONCLUSIONS: The present study revealed proteins and pathways that were specifically altered in cerebral ischemia, in cardiac ischemia, or in both diseases, providing information on the similarities and differences of ischemic conditions. The role of common and specific proteins and pathways should be explored in detail to find possible therapeutic targets.

Blood biomarker changes following therapeutic hypothermia in ischemic stroke.

INTRODUCTION: Therapeutic hypothermia is a promising candidate for stroke treatment although its efficacy has not yet been demonstrated in patients. Changes in blood molecules could act as surrogate markers to evaluate the efficacy and safety of therapeutic cooling. METHODS: Blood samples from 54 patients included in the EuroHYP-1 study (27 treated with hypothermia, and 27 controls) were obtained at baseline, 24 ± 2 h, and 72 ± 4 h. The levels of a panel of 27 biomarkers, including matrix metalloproteinases and cardiac and inflammatory markers, were measured. RESULTS: Metalloproteinase-3 (MMP-3), fatty-acid-binding protein (FABP), and interleukin-8 (IL-8) increased over time in relation to the hypothermia treatment. Statistically significant correlations between the minimum temperature achieved by each patient in the hypothermia group and the MMP-3 level measured at 72 h, FABP level measured at 24 h, and IL-8 levels measured at 24 and 72 h were found. No differential biomarker levels were observed in patients with poor or favorable outcomes according to modified Rankin Scale scores. CONCLUSION: Although the exact roles of MMP3, FABP, and IL-8 in hypothermia-treated stroke patients are not known, further exploration is needed to confirm their roles in brain ischemia.

Serum S-100B adds incremental value for the prediction of symptomatic intracranial hemorrhage and brain edema after acute ischemic stroke.

Background: Early identification of patients developing symptomatic intracranial hemorrhage and symptomatic brain edema after acute ischemic stroke is essential for clinical decision-making. Astroglial protein S-100B is a marker of blood-brain barrier disruption, which plays an important role in the formation of intracranial hemorrhage and brain edema. In this study, we assessed the prognostic value of serum S-100B for the development of these complications. Methods: Serum S-100B levels were measured within 24 h from symptom onset in 1749 consecutive acute ischemic stroke patients from the prospective, observational, multicenter BIOSIGNAL cohort study (mean age 72.0 years, 58.3% male). To determine symptomatic intracranial hemorrhage or symptomatic brain edema, follow-up neuroimaging was performed in all patients receiving reperfusion therapy or experiencing clinical worsening with an NIHSS increase of ⩾4. Results: Forty six patients (2.6%) developed symptomatic intracranial hemorrhage and 90 patients (5.2%) developed symptomatic brain edema. After adjustment for established risk factors, log10S-100B levels remained independently associated with both symptomatic intracranial hemorrhage (OR 3.41, 95% CI 1.7-6.9, p = 0.001) and symptomatic brain edema (OR 4.08, 95% CI 2.3-7.1, p < 0.001) in multivariable logistic regression models. Adding S-100B to the clinical prediction model increased the AUC from 0.72 to 0.75 (p = 0.001) for symptomatic intracranial hemorrhage and from 0.78 to 0.81 (p < 0.0001) for symptomatic brain edema. Conclusions: Serum S-100B levels measured within 24 h after symptom onset are independently associated with the development of symptomatic intracranial hemorrhage and symptomatic brain edema in acute ischemic stroke patients. Thus, S-100B may be useful for early risk-stratification regarding stroke complications.

General practitioners' perceptions on opportunistic single-time point screening for atrial fibrillation: A European quantitative survey.

Background: There is no clear guidance on how to implement opportunistic atrial fibrillation (AF) screening in daily clinical practice. Objectives: This study evaluated the perception of general practitioners (GPs) about value and practicalities of implementing screening for AF, focusing on opportunistic single-time point screening with a single-lead electrocardiogram (ECG) device. Methods: A descriptive cross-sectional study was conducted with a survey developed to assess overall perception concerning AF screening, feasibility of opportunistic single-lead ECG screening and implementation requirements and barriers. Results: A total of 659 responses were collected (36.1% Eastern, 33.4% Western, 12.1% Southern, 10.0% Northern Europe, 8.3% United Kingdom & Ireland). The perceived need for standardized AF screening was rated as 82.7 on a scale from 0 to 100. The vast majority (88.0%) indicated no AF screening program is established in their region. Three out of four GPs (72.1%, lowest in Eastern and Southern Europe) were equipped with a 12-lead ECG, while a single-lead ECG was less common (10.8%, highest in United Kingdom & Ireland). Three in five GPs (59.3%) feel confident ruling out AF on a single-lead ECG strip. Assistance through more education (28.7%) and a tele-healthcare service offering advice on ambiguous tracings (25.2%) would be helpful. Preferred strategies to overcome barriers like insufficient (qualified) staff, included integrating AF screening with other healthcare programs (24.9%) and algorithms to identify patients most suitable for AF screening (24.3%). Conclusion: GPs perceive a strong need for a standardized AF screening approach. Additional resources may be required to have it widely adopted into clinical practice.

Association of blood-based biomarkers with radiologic markers and cognitive decline in atrial fibrillation patients.

BACKGROUND: Atrial fibrillation (AF) has been associated with an increased risk of silent brain infarcts (SBI) and cognitive impairment, even in patients with low embolic risk. We aimed to test the association between 11 blood-biomarkers representing different AF-related pathways, and SBI, white matter hyperintensities (WMH), and cognitive decline in patients with AF and low embolic risk. METHODS: The present study followed a cross-sectional design. 70 patients with a history of AF and CHADS2 score ≤1, and 10 controls with neither AF nor SBI were included. All patients underwent a 3T brain MRI. Cortical and large subcortical ischemic lesions were considered presumed embolic origin lesions. White matter hyperintensities (WMH) were measured according to the Fazekas scale. A subset of patients underwent cognitive evaluation with the MoCA test. Circulating proteins were measured under blind conditions in a laboratory at Roche Diagnostics, Germany. RESULTS: 45 patients presented SBI in the MRI, and 25 did not. Ang-2, FGF-23, and BMP-10 were increased in patients with SBI. Ang-2 was elevated only in patients with embolic infarcts, whereas FGF-23 and BMP-10 tended to be elevated in patients with both types of infarcts. Ang-2 (OR = 1.56 [0.94-2.59], p = 0.087), and BMP-10 (OR = 4.83 [0.99-23.60], p = 0.052) were the biomarkers that showed the highest association with SBI when entered in a multivariable logistic regression model corrected by age. No biomarker was found associated with WMH or mild cognitive impairment. CONCLUSIONS: BMP-10, and Ang-2 were increased in patients with SBI. Its usefulness to detect SBI in AF patients should be further explored.

Blood-biomarkers and devices for atrial fibrillation screening: Lessons learned from the AFRICAT (Atrial Fibrillation Research In CATalonia) study.

BACKGROUND AND OBJECTIVE: AFRICAT is a prospective cohort study intending to develop an atrial fibrillation (AF) screening program through the combination of blood markers, rhythm detection devices, and long-term monitoring in our community. In particular, we aimed to validate the use of NT-proBNP, and identify new blood biomarkers associated with AF. Also, we aimed to compare AF detection using various wearables and long-term Holter monitoring. METHODS: 359 subjects aged 65-75 years with hypertension and diabetes were included in two phases: Phase I (n = 100) and Phase II (n = 259). AF diagnosis was performed by baseline 12-lead ECG, 4 weeks of Holter monitoring (NuuboTM), and/or medical history. An aptamer array including 1310 proteins was measured in the blood of 26 patients. Candidates were selected according to p-value, logFC and biological function to be tested in verification and validation phases. Several screening devices were tested and compared: AliveCor, Watch BP, MyDiagnostick and Fibricheck. RESULTS: AF was present in 34 subjects (9.47%). The aptamer array revealed 41 proteins with differential expression in AF individuals. TIMP-2 and ST-2 were the most promising candidates in the verification analysis, but none of them was further validated. NT-proBNP (log-transformed) (OR = 1.934; p<0.001) was the only independent biomarker to detect AF in the whole cohort. Compared to an ECG, WatchBP had the highest sensitivity (84.6%) and AUC (0.895 [0.780-1]), while MyDiagnostick showed the highest specificity (97.10%). CONCLUSION: The inclusion and monitoring of a cohort of primary care patients for AF detection, together with the testing of biomarkers and screening devices provided useful lessons about AF screening in our community. An AF screening strategy using rhythm detection devices and short monitoring periods among high-risk patients with high NT-proBNP levels could be feasible.

Blood-Based Biomarkers to Search for Atrial Fibrillation in High-Risk Asymptomatic Individuals and Cryptogenic Stroke Patients.

Background: Atrial fibrillation (AF) increases the risk of ischemic stroke in asymptomatic individuals and may be the underlying cause of many cryptogenic strokes. We aimed to test the usefulness of candidate blood-biomarkers related to AF pathophysiology in two prospective cohorts representative of those populations. Methods: Two hundred seventy-four subjects aged 65-75 years with hypertension and diabetes from the AFRICAT cohort, and 218 cryptogenic stroke patients aged >55 years from the CRYPTO-AF cohort were analyzed. AF was assessed by 4 weeks of monitoring with a wearable Holter device (NuuboTM™). Blood was collected immediately before monitoring started. 10 candidate biomarkers were measured by automated immunoassays (Roche, Penzberg) in the plasma of all patients. Univariate and logistic regression analyses were performed in each cohort separately. Results: Atrial fibrillation detection rate was 12.4% (AFRICAT cohort) and 22.9% (CRYPTO-AF cohort). 4 biomarkers were significantly increased in asymptomatic individuals with AF [Troponin-T, Angiopoietin-2 (Ang-2), Endocan, and total N-terminal pro-B type natriuretic peptide (NT-proBNP)] and 7 biomarkers showed significantly higher concentrations in cryptogenic stroke patients with AF detection [growth differentiation factor 15, interleukin 6, Troponin-T, Ang-2, Bone morphogenic protein 10, Dickkopf-related protein 3 (DKK-3), and total NT-proBNP]. The models including Ang-2 and total NT-proBNP [AUC 0.764 (0.665-0.863)], and Ang-2 and DKK-3 [AUC = 0.733 (0.654-0.813)], together with age and sex, showed the best performance to detect AF in high-risk asymptomatic individuals, and in cryptogenic stroke patients, respectively. Conclusion: Blood-biomarkers, in particular, total NT-proBNP, DKK-3, and Ang-2, were associated with AF reflecting two mechanistically different pathways involved in AF pathophysiology (AF stretch and vascular changes). The combination of these biomarkers could be useful in AF screening strategies in the primary care setting and also for searching AF after cryptogenic stroke.

Feasible approaches and implementation challenges to atrial fibrillation screening: a qualitative study of stakeholder views in 11 European countries.

OBJECTIVES: Atrial fibrillation (AF) screening may increase early detection and reduce complications of AF. European, Australian and World Heart Federation guidelines recommend opportunistic screening, despite a current lack of clear evidence supporting a net benefit for systematic screening. Where screening is implemented, the most appropriate approaches are unknown. We explored the views of European stakeholders about opportunities and challenges of implementing four AF screening scenarios. DESIGN: Telephone-based semi-structured interviews with results reported using Consolidated criteria for Reporting Qualitative research guidelines. Data were thematically analysed using the framework approach. SETTING: AF screening stakeholders in 11 European countries. PARTICIPANTS: Healthcare professionals and regulators (n=24) potentially involved in AF screening implementation. INTERVENTION: Four AF screening scenarios: single time point opportunistic, opportunistic prolonged, systematic single time point/prolonged and patient-led screening. PRIMARY OUTCOME MEASURES: Stakeholder views about the challenges and feasibility of implementing the screening scenarios in the respective national/regional healthcare system. RESULTS: Three themes developed. (1) Current screening approaches: there are no national AF screening programmes, with most AF detected in symptomatic patients. Patient-led screening exists via personal devices, creating screening inequity. (2) Feasibility of screening: single time point opportunistic screening in primary care using single-lead ECG devices was considered the most feasible. Software algorithms may aid identification of suitable patients and telehealth services have potential to support diagnosis. (3) Implementation requirements: sufficient evidence of benefit is required. National screening processes are required due to different payment mechanisms and health service regulations. Concerns about data security, and inclusivity for those without primary care access or personal devices must be addressed. CONCLUSIONS: There is an overall awareness of AF screening. Opportunistic screening appears the most feasible across Europe. Challenges are health inequalities, identification of best target groups for screening, streamlined processes, the need for evidence of benefit and a tailored approach adapted to national realities.

Proteins and pathways in atrial fibrillation and atrial cardiomyopathy underlying cryptogenic stroke.

Background: Atrial fibrillation (AF) is one of the most prevalent causes of cryptogenic stroke. Also, apart from AF itself, structural and remodelling changes in the atria might be an underlying cause of cryptogenic stroke. We aimed to discover circulating proteins and reveal pathways altered in AF and atrial cardiomyopathy, measured by left atrial volume index (LAVI) and peak atrial longitudinal strain (PALS), in patients with cryptogenic stroke. Methods: An aptamer array (including 1310 proteins) was measured in the blood of 20 cryptogenic stroke patients monitored during 28 days with a Holter device as a case-control study of the Crypto-AF cohort. Protein levels were compared between patients with (n = 10) and without AF (n = 10) after stroke, and the best candidates were tested in 111 patients from the same cohort (44 patients with AF and 67 without AF). In addition, in the first 20 patients, proteins were explored according to PALS and LAVI values. Results: Forty-six proteins were differentially expressed in AF cases. Of those, four proteins were tested in a larger sample size. Only DPP7, presenting lower levels in AF patients, was further validated. Fifty-seven proteins correlated with LAVI, and 270 correlated with PALS. NT-proBNP was common in all the discovery analyses performed. Interestingly, many proteins and pathways were altered in patients with low PALS. Conclusions: Multiple proteins and pathways related to AF and atrial cardiomyopathy have been revealed. The role of DPP7 as a biomarker for stroke aetiology should be further explored. Moreover, the present study may be considered hypothesis-generating.

New candidate blood biomarkers potentially associated with white matter hyperintensities progression.

We aimed to discover blood biomarkers associated with longitudinal changes in white matter hyperintensities (WMH). This study was divided into a discovery phase and a replication phase. Subjects in both studies were patients with hypertension, aged 50-70, who underwent two magnetic resonance imaging (MRI) sessions and blood extractions over a 4-year follow-up period. In the discovery phase, we screened 1305 proteins in 12 subjects with WMH progression and in 12 matched control subjects. We found that 41 proteins were differentially expressed: 13 were upregulated and 28 were downregulated. We subsequently selected three biomarkers for replication in baseline and follow-up samples in 80 subjects with WMH progression and in 80 control subjects. The selected protein candidates for the replication were MMP9 (matrix metalloproteinase-9), which was higher in cases, MET (hepatocyte growth factor receptor) and ASAH2 (neutral ceramidase), which were both lower in cases of WMH progression. Baseline biomarker concentrations did not predict WMH progression. In contrast, patients with WMH progression presented a steeper decline in MET over time. Furthermore, cases showed higher MMP9 and lower ASAH2 levels than controls at the follow-up. These results indicate that MMP9, MET, and ASAH2 are potentially associated with the progression of WMH, and could therefore be interesting candidates to validate in future studies.

Predictive model for atrial fibrillation in hypertensive diabetic patients.

BACKGROUND: Several scores to identify patients at high risk of suffering atrial fibrillation have been developed. Their applicability in hypertensive diabetic patients, however, remains uncertain. Our aim is to develop and validate a diagnostic predictive model to calculate the risk of developing atrial fibrillation at five years in a hypertensive diabetic population. METHODS: The derivation cohort consisted of patients with both hypertension and diabetes attended in any of the 52 primary healthcare centres of Barcelona; the validation cohort came from the 11 primary healthcare centres of Terres de l'Ebre (Catalonia South) from January 2013 to December 2017. Multivariable Cox regression identified clinical risk factors associated with the development of atrial fibrillation. The overall performance, discrimination and calibration of the model were carried out. RESULTS: The derivation data set comprised 54 575 patients. The atrial fibrillation rate incidence was 15.3 per 1000 person/year. A 5-year predictive model included age, male gender, overweight, heart failure, valvular heart disease, peripheral vascular disease, chronic kidney disease, number of antihypertensive drugs, systolic and diastolic blood pressure, heart rate, thromboembolism, stroke and previous history of myocardial infarction. The discrimination of the model was good (c-index = 0.692; 95% confidence interval, 0.684-0.700), and calibration was adequate. In the validation cohort, the discrimination was lower (c-index = 0.670). CONCLUSIONS: The model accurately predicts future atrial fibrillation in a population with both diabetes and hypertension. Early detection allows the prevention of possible complications arising from this disease.

Predicting Atrial Fibrillation with High Risk of Embolization with Atrial Strain and NT-proBNP.

The aim of the study was to determine markers of atrial dysfunction in patients with cryptogenic stroke to predict episodes of paroxysmal atrial fibrillation with high risk of embolization (HpAF). We classified patients included in the Crypto-AF study, Cryptogenic Stroke registry, to detect paroxysmal atrial fibrillation (pAF) with wearable Holter, according to the longest episode of pAF in three groups: without pAF detection, episodes of pAF shorter than 5 h, and episodes of pAF longer than 5 h (HpAF). Atrial dysfunction surrogates were evaluated: EKG pattern, Holter record and echocardiography parameters (left atria volume (LAVI), and peak atrial longitudinal and contraction strain (PALS and PACS). The level of N-terminal pro b-type natriuretic peptide (NT-proBNP) was determined. All patients were followed for 2 years to detect pAF and stroke recurrence. From 308 patients, 253 patients with high quality Holter analysis were selected. The distribution was No pAF 78.6% (n = 199), pAF < 5 h 7.9% (n = 20), and HpAF > 5 h 13.4% (n = 34). Age of the patients and combination of PALS and NT-proBNP independently predicted HpAF OR 1.07 (1.00; 1.15) and OR 3.05 (1.08; 8.60) respectively. The validity of PALS and NT-proBNP to detect patients at risk of HpAF was higher than the validity of age (AUC 0.82, sensitivity 78.95%, specificity 63%). Patients with PALS < 25% and NT-proBNP > 283 pg/ml had more detection of pAF during follow-up 35% vs. 5.1% OR 2.33 (1.05-5.13) (p < 0.001). Multimodal assessment of atrial dysfunction with PALS and NT-proBNP improved the prediction of pAF episodes with high embolic risk in patients with cryptogenic stroke.

Risk of Atrial Fibrillation, Ischemic Stroke and Cognitive Impairment: Study of a Population Cohort ≥65 Years of Age.

PURPOSE: To evaluate a model for calculating the risk of AF and its relationship with the incidence of ischemic stroke and prevalence of cognitive decline. MATERIALS AND METHODS: It was a multicenter, observational, retrospective, community-based study of a cohort of general population ≥6ct 35 years, between 01/01/2016 and 31/12/2018. Setting: Primary Care. Participants: 46,706 people ≥65 years with an active medical history in any of the primary care teams of the territory, information accessible through shared history and without previous known AF. Interventions: The model to stratify the risk of AF (PI) has been previously published and included the variables sex, age, mean heart rate, mean weight and CHA2DS2VASc score. Main measurements: For each risk group, the incidence density/1000 person/years of AF and stroke, number of cases required to detect a new AF, the prevalence of cognitive decline, Kendall correlation, and ROC curve were calculated. RESULTS: The prognostic index was obtained in 37,731 cases (80.8%) from lowest (Q1) to highest risk (Q4). A total of 1244 new AFs and 234 stroke episodes were diagnosed. Q3-4 included 53.8% of all AF and 69.5% of strokes in men; 84.2% of all AF and 85.4% of strokes in women; and 77.4% of cases of cognitive impairment. There was a significant linear correlation between the risk-AF score and the Rankin score (p < 0.001), the Pfeiffer score (p < 0.001), but not NIHSS score (p 0.150). The overall NNS was 1/19. CONCLUSION: Risk stratification allows identifying high-risk individuals in whom to intervene on modifiable risk factors, prioritizing the diagnosis of AF and investigating cognitive status.

Blood-based biomarkers and stem cell therapy in human stroke: a systematic review.

Stroke is one of the main causes of death and disability worldwide. Cell therapy represents a promising therapeutic approach to improve stroke outcome. Measurement of blood-based biomarkers might serve as a proof-of-concept to monitor the mechanisms undergirding these treatments, and such compounds could be used as surrogate biomarkers to monitor the safety and efficacy of cell therapies in the future. Additionally, the measurement of biomarkers that correlate with circulating stem cells in observational studies might be of interest to improve the understanding of how these cells are spontaneously mobilized and carry out their action after stroke. Thus, a systematic review has been herein performed on blood-based biomarkers assessed in stroke patients treated with cell therapy or in observational studies in which circulating stem cells have been measured after stroke.

Cardioembolic Ischemic Stroke Gene Expression Fingerprint in Blood: a Systematic Review and Verification Analysis.

An accurate etiological classification is key to optimize secondary prevention after ischemic stroke, but the cause remains undetermined in one third of patients. Several studies pointed out the usefulness of circulating gene expression markers to discriminate cardioembolic (CE) strokes, mainly due to atrial fibrillation (AF), while only exploring them in small cohorts. A systematic review of studies analyzing high-throughput gene expression in blood samples to discriminate CE strokes was performed. Significantly dysregulated genes were considered as candidates, and a selection of them was validated by RT-qPCR in 100 patients with defined CE or atherothrombotic (LAA) stroke etiology. Longitudinal performance was evaluated in 12 patients at three time points. Their usefulness as biomarkers for AF was tested in 120 cryptogenic strokes and 100 individuals at high-risk for stroke. Three published studies plus three unpublished datasets were considered for candidate selection. Sixty-seven genes were found dysregulated in CE strokes. CREM, PELI1, and ZAK were verified to be up-regulated in CE vs LAA (p = 0.010, p = 0.003, p < 0.001, respectively), without changes in their expression within the first 24 h after stroke onset. The combined up-regulation of these three biomarkers increased the probability of suffering from CE stroke by 23-fold. In cryptogenic strokes with subsequent AF detection, PELI1 and CREM showed overexpression (p = 0.017, p = 0.059, respectively), whereas in high-risk asymptomatic populations, all three genes showed potential to detect AF (p = 0.007, p = 0.007, p = 0.015). The proved discriminatory capacity of these gene expression markers to detect cardioembolism even in cryptogenic strokes and asymptomatic high-risk populations might bring up their use as biomarkers.

N-Terminal Pro B-Type Natriuretic Peptide's Usefulness for Paroxysmal Atrial Fibrillation Detection Among Populations Carrying Cardiovascular Risk Factors.

Background: Atrial fibrillation (AF) systematic screening studies have not shown a clear usefulness in stroke prevention, as AF might present as paroxysmal and asymptomatic. This study aims to determine the usefulness of some blood-biomarkers to identify paroxysmal atrial fibrillation in the context of a screening programme. Methods: A total of 100 subjects aged 65-75 years with hypertension and diabetes were randomly selected. AF was assessed by conventional electrocardiogram (ECG) and 4 weeks monitoring with a wearable Holter device (Nuubo™). N-terminal pro B-type natriuretic peptide (NT-proBNP), apolipoprotein CIII (ApoC-III), von Willebrand factor (vWF), ADAMTS13, urokinase plasminogen activator surface receptor (uPAR), and urokinase plasminogen activator (uPA) were determined in serum/plasma samples and the levels were compared depending on AF presence and mode of detection. Results: The AF prevalence in the studied population was found to be 20%. In seven subjects, AF was only detected after 1 month of Holter monitoring (hAF group). NT-proBNP levels were higher in subjects with AF compared with subjects with no AF (p < 0.0001), even when only taking into account the hAF group (p = 0.031). No significant differences were found in the other biomarkers. The NT-proBNP >95 pg/ml cut-off showed high sensitivity and specificity to detect AF (95%, 66.2%) or hAF (85.72%, 66.2%) and was found to be an independent predictor of AF and hAF in a logistic regression analysis. NT-proBNP correlated with AF burden (r = 0.597, p = 0.024). Conclusion: NT-proBNP was elevated in AF cases not identified by ECG; thus, it may be used as a screening biomarker in asymptomatic high-risk populations, with a promising cut-off point of 95 pg/ml that requires further validation.