Prediction of underlying atrial fibrillation in patients with a cryptogenic stroke: results from the NOR-FIB Study

Background - Atrial fibrillation (AF) detection and treatment are key elements to reduce recurrence risk in cryptogenic stroke (CS) with underlying arrhythmia. The purpose of the present study was to assess the predictors of AF in CS and the utility of existing AF-predicting scores in The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study. Method - The NOR-FIB study was an international prospective observational multicenter study designed to detect and quantify AF in CS and cryptogenic transient ischaemic attack (TIA) patients monitored by the insertable cardiac monitor (ICM), and to identify AF-predicting biomarkers. The utility of the following AF-predicting scores was tested: AS5F, Brown ESUS-AF, CHA2DS2-VASc, CHASE-LESS, HATCH, HAVOC, STAF and SURF. Results - In univariate analyses increasing age, hypertension, left ventricle hypertrophy, dyslipidaemia, antiarrhythmic drugs usage, valvular heart disease, and neuroimaging findings of stroke due to intracranial vessel occlusions and previous ischemic lesions were associated with a higher likelihood of detected AF. In multivariate analysis, age was the only independent predictor of AF. All the AF-predicting scores showed significantly higher score levels for AF than non-AF patients. The STAF and the SURF scores provided the highest sensitivity and negative predictive values, while the AS5F and SURF reached an area under the receiver operating curve (AUC) > 0.7. Conclusion - Clinical risk scores may guide a personalized evaluation approach in CS patients. Increasing awareness of the usage of available AF-predicting scores may optimize the arrhythmia detection pathway in stroke units

Age, modifiable risk factors, and mortality. : A 42 years prospective follow-up study in a general population.

Risikoforebygging er en viktig del av alt helsearbeid, men det meste av evidens med hensyn på forebyggende helsearbeid er fremkommet ved studier utført på middelaldrende befolkningsgrupper med ulik ekstern validitet, med variabel oppfølgingstid, og med overvekt av menn. Modifiserbare risikofaktorer har potensielt ulik innvirkning i ulike aldersgrupper, i ulike faser av en lengre oppfølgingstid og med hensyn på forskjellige endepunkter (dødelighet: total og årsaksspesifikk). Målsetning: å studere forskjeller og likheter i effekten av livsstilsrelaterte risikofaktorer (særlig kroppsmasseindeks, fysisk aktivitet og lungefunksjon) på total dødelighet og årsaksspesifikk dødelighet som følge av hjerneslag og koronar hjertesykdom i ulike aldersgrupper av menn og kvinner i en generell norsk befolkning med 42 års oppfølgingstid. Materiale og metode: 6811 tilfeldig utvalgte menn og kvinner i alderen 20-79 og bosatt i Bergen i 1964 ble invitert til en utvidet helseundersøkelse etter Blodtrykksundersøkelsene. 5653 personer møtte frem til undersøkelsen der 208 kliniske og selvrapporterte variabler ble registrert. Datamaterialet ble koblet mot Levekårsundersøkelsene i 1970-80-90 og 2000, Dødsårsaksregisteret (2005) og Folkeregisteret (2007). Cox-regresjon ble brukt for å studere sammenhengen mellom utvalgte variabler og dødelighet. Resultater: Kroppsmasseindeks er assosiert til overdødelighet i yngre aldersgrupper, men er tilsynelatende inverst assosiert til dødelighet i eldre aldersgrupper, selv etter justering for multiple variabler og i subgruppeanalyser av de friskeste i utvalget. Fysisk aktivitet er minst like sterkt assosiert til overlevelse blant de eldre som i de yngre aldersgruppene, i motsetning til de fleste andre kjente risikofaktorer som har avtakende styrke i sin assosiasjon til død med økende alder. Lungefunksjon er inverst assosiert til risiko for dødelig hjerneslag. Validiteten av hjerneslag og koronar hjertesykdom registret som tilgrunnliggende dødsårsak i Dødsårsaksregisteret i perioden 1965-2005 er tilfredsstillende for bruk i epidemiologisk forskningsarbeid. Konklusjon: Livsstil har implikasjoner for overlevelse i alle aldersgrupper. Fysisk aktivitet, kroppsmasseindeks og lungefunksjon er viktige livsstilsrelaterte prediktorer for god helse og økt overlevelse også blant gamle

Lower bone mineral density in older female endurance skiers – a cross-sectional, observational study

Background: Physical activity (PA) is generally beneficial for bone health, but the effect of high levels of PA over many years, in older women, is unknown. Methods: T-score from Dual-energy X-ray absorptiometry (DXA), and self-reported baseline characteristics were recorded for 24 female, cross-country-skiing-competitors, aged 68–76 years, from the Birkebeiner Ageing Study. Data from 647 women in the same age range from the Tromso-6 population study, with recorded DXA findings, were used for comparison. Results: The athletes reported a median(range) of 9(1–34) participations in the 54 km, yearly ski-race, indicating long-term PA. They also reported more moderate and high levels of PA than women in the general population (52% vs. 12 and 30% vs. 0%, respectively). The athletes had lower body mass index (BMI) than the controls (mean BMI 21.7 vs 26.9 kg/m2, p  Conclusions: This pilot study suggests that long-term, high levels of PA are associated with low bone mineral density in older women, and the finding might be due to differences in BMI. Despite the lower bone mineral density the athletes did not report more fractures

Increased risk of atrial fibrillation among elderly Norwegian men with a history of long-term endurance sport practice

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence increases with increasing age. In middle-aged men, endurance sport practice is associated with increased risk of AF but there are few studies among elderly people. The aim of this study was to investigate the role of long-term endurance sport practice as a risk factor for AF in elderly men. A cross-sectional study compared 509 men aged 65–90 years who participated in a long-distance cross-country ski race with 1768 men aged 65–87 years from the general population. Long-term endurance sport practice was the main exposure. Self-reported AF and covariates were assessed by questionnaires. Risk differences (RDs) for AF were estimated by using a linear regression model. After multivariable adjustment, a history of endurance sport practice gave an added risk for AF of 6.0 percent points (pp) (95% confidence interval 0.8–11.1). Light and moderate leisure-time physical activity during the last 12 months reduced the risk with 3.7 and 4.3 pp, respectively, but the RDs were not statistically significant. This study suggests that elderly men with a history of long-term endurance sport practice have an increased risk of AF compared with elderly men in the general population

Increased risk of atrial fibrillation among elderly Norwegian men with a history of long-term endurance sport practice

Atrial fibrillation (AF) is the most common cardiac arrhythmia. The prevalence increases with increasing age. In middle-aged men, endurance sport practice is associated with increased risk of AF but there are few studies among elderly people. The aim of this study was to investigate the role of long-term endurance sport practice as a risk factor for AF in elderly men. A cross-sectional study compared 509 men aged 65–90 years who participated in a long-distance cross-country ski race with 1768 men aged 65–87 years from the general population. Long-term endurance sport practice was the main exposure. Self-reported AF and covariates were assessed by questionnaires. Risk differences (RDs) for AF were estimated by using a linear regression model. After multivariable adjustment, a history of endurance sport practice gave an added risk for AF of 6.0 percent points (pp) (95% confidence interval 0.8–11.1). Light and moderate leisure-time physical activity during the last 12 months reduced the risk with 3.7 and 4.3 pp, respectively, but the RDs were not statistically significant. This study suggests that elderly men with a history of long-term endurance sport practice have an increased risk of AF compared with elderly men in the general population

Atrial fibrillation in cryptogenic stroke and TIA patients in the nordic atrial fibrillation and stroke The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Main results

Introduction: Secondary stroke prevention depends on proper identification of the underlying etiology and initiation of optimal treatment after the index event. The aim of the NOR-FIB study was to detect and quantify underlying atrial fibrillation (AF) in patients with cryptogenic stroke (CS) or transient ischaemic attack (TIA) using insertable cardiac monitor (ICM), to optimise secondary prevention, and to test the feasibility of ICM usage for stroke physicians. Patients and methods: Prospective observational international multicenter real-life study of CS and TIA patients monitored for 12 months with ICM (Reveal LINQ) for AF detection. Results: ICM insertion was performed in 91.5% by stroke physicians, within median 9 days after index event. Paroxysmal AF was diagnosed in 74 out of 259 patients (28.6%), detected early after ICM insertion (mean 48 ± 52 days) in 86.5% of patients. AF patients were older (72.6 vs 62.2; p < 0.001), had higher pre-stroke CHA₂DS₂-VASc score (median 3 vs 2; p < 0.001) and admission NIHSS (median 2 vs 1; p = 0.001); and more often hypertension (p = 0.045) and dyslipidaemia (p = 0.005) than non-AF patients. The arrhythmia was recurrent in 91.9% and asymptomatic in 93.2%. At 12-month follow-up anticoagulants usage was 97.3%. Discussion and conclusions: ICM was an effective tool for diagnosing underlying AF, capturing AF in 29% of the CS and TIA patients. AF was asymptomatic in most cases and would mainly have gone undiagnosed without ICM. The insertion and use of ICM was feasible for stroke physicians in stroke units

Atrial fibrillation in cryptogenic stroke and transient ischaemic attack – The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Rationale and design

Abstract Purpose: Paroxysmal atrial fibrillation is often suspected as a probable cause of cryptogenic stroke. Continuous longterm ECG monitoring using insertable cardiac monitors is a clinically effective technique to screen for atrial fibrillation and superior to conventional follow-up in cryptogenic stroke. However, more studies are needed to identify factors which can help selecting patients with the highest possibility of detecting atrial fibrillation with prolonged rhythm monitoring. The clinical relevance of short-term atrial fibrillation, the need for medical intervention and the evaluation as to whether intervention results in improved clinical outcomes should be assessed. Method: The Nordic Atrial Fibrillation and Stroke Study is an international, multicentre, prospective, observational trial evaluating the occurrence of occult atrial fibrillation in cryptogenic stroke and transient ischaemic attack. Patients with cryptogenic stroke or transient ischaemic attack from the Nordic countries are included and will have the Reveal LINQVR Insertable cardiac monitor system implanted for 12 months for atrial fibrillation detection. Biomarkers which can be used as predictors for atrial fibrillation and may identify patients, who could derive the most clinical benefit from the detection of atrial fibrillation by prolonged monitoring, are being studied. Conclusion: The primary endpoint is atrial fibrillation burden within 12 months of continuous rhythm monitoring. Secondary endpoints are atrial fibrillation burden within six months, levels of biomarkers predicting atrial fibrillation, CHA2DS2-VASc score, incidence of recurrent stroke or transient ischaemic attack, use of anticoagulation and antiarrhythmic drugs, and quality of life measurements. The clinical follow-up period is 12 months. The study started in 2017 and the completion is expected at the end of 2020

Atrial fibrillation in cryptogenic stroke and transient ischaemic attack – The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study: Rationale and design

Purpose: Paroxysmal atrial fibrillation is often suspected as a probable cause of cryptogenic stroke. Continuous long-term ECG monitoring using insertable cardiac monitors is a clinically effective technique to screen for atrial fibrillation and superior to conventional follow-up in cryptogenic stroke. However, more studies are needed to identify factors which can help selecting patients with the highest possibility of detecting atrial fibrillation with prolonged rhythm monitoring. The clinical relevance of short-term atrial fibrillation, the need for medical intervention and the evaluation as to whether intervention results in improved clinical outcomes should be assessed. Method: The Nordic Atrial Fibrillation and Stroke Study is an international, multicentre, prospective, observational trial evaluating the occurrence of occult atrial fibrillation in cryptogenic stroke and transient ischaemic attack. Patients with cryptogenic stroke or transient ischaemic attack from the Nordic countries are included and will have the Reveal LINQ® Insertable cardiac monitor system implanted for 12 months for atrial fibrillation detection. Biomarkers which can be used as predictors for atrial fibrillation and may identify patients, who could derive the most clinical benefit from the detection of atrial fibrillation by prolonged monitoring, are being studied. Conclusion: The primary endpoint is atrial fibrillation burden within 12 months of continuous rhythm monitoring. Secondary endpoints are atrial fibrillation burden within six months, levels of biomarkers predicting atrial fibrillation, CHA2DS2-VASc score, incidence of recurrent stroke or transient ischaemic attack, use of anticoagulation and antiarrhythmic drugs, and quality of life measurements. The clinical follow-up period is 12 months. The study started in 2017 and the completion is expected at the end of 2020

Biomarkers Predictive of Atrial Fibrillation in Patients with Cryptogenic Stroke. Insights from The Nordic Atrial Fibrillation and Stroke (NOR-FIB) Study

BACKGROUND: There are currently no biomarkers used to select cryptogenic stroke (CS) patients for monitoring with insertable cardiac monitors (ICMs), the most effective tool for diagnosing atrial fibrillation (AF) in CS. The purpose of this study was to assess clinically available biomarkers as predictors of AF.METHODS: Eligible CS and cryptogenic transient ischemic attack (TIA) patients underwent 12-month monitoring with ICMs, clinical follow-up, and biomarker sampling. Levels of cardiac and thromboembolic biomarkers, taken within 14 days from symptom onset, were compared between patients diagnosed with AF (n=74) during monitoring and those without AF (n=185). Receiver operating characteristic (ROC) curves were created. Biomarkers reaching area under ROC curve (AUC) ≥ 0.7 were dichotomized by finding optimal cut-off values and used in logistic regression establishing their predictive value for increased risk of AF in unadjusted and adjusted models.RESULTS: B-type natriuretic peptide (BNP), N-terminal pro-brain natriuretic peptide (NT-proBNP), creatine kinase, D-dimer, high-sensitivity cardiac Troponin I and T were significantly higher in the AF than non-AF group. BNP and NT-proBNP reached predefined AUC level, 0.755 and 0.725 respectively. Optimal cut-off values were 33.5 ng/L for BNP, and 87 ng/L for NT-proBNP. Regression analysis showed that NT-proBNP was a predictor of AF in both unadjusted, odds ratio (OR) 7.72 (95% confidence interval [CI] 3.16-18.87), and age and sex adjusted models, OR 4.82 (95% CI 1.79-12.96).CONCLUSION: Several clinically established biomarkers were associated with AF. NT-proBNP performed best as AF predictor and could be used for selecting patients for long-term monitoring with ICMs