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.

Atrial fibrillation in cryptogenic stroke and TIA patients in 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.

Underlying causes of cryptogenic stroke and TIA in the nordic atrial fibrillation and stroke (NOR-FIB) study - the importance of comprehensive clinical evaluation.

BACKGROUND: Cryptogenic stroke is a heterogeneous condition, with a wide spectrum of possible underlying causes for which the optimal secondary prevention may differ substantially. Attempting a correct etiological diagnosis to reduce the stroke recurrence should be the fundamental goal of modern stroke management. METHODS: Prospective observational international multicenter study of cryptogenic stroke and cryptogenic transient ischemic attack (TIA) patients clinically monitored for 12 months to assign the underlying etiology. For atrial fibrillation (AF) detection continuous cardiac rhythm monitoring with insertable cardiac monitor (Reveal LINQ, Medtronic) was performed. The 12-month follow-up data for 250 of 259 initially included NOR-FIB patients were available for analysis. RESULTS: After 12 months follow-up probable stroke causes were revealed in 43% patients, while 57% still remained cryptogenic. AF and atrial flutter was most prevalent (29%). In 14% patients other possible causes were revealed (small vessel disease, large-artery atherosclerosis, hypercoagulable states, other cardioembolism). Patients remaining cryptogenic were younger (p < 0.001), had lower CHA2DS2-VASc score (p < 0.001) on admission, and lower NIHSS score (p = 0.031) and mRS (p = 0.016) at discharge. Smoking was more prevalent in patients that were still cryptogenic (p = 0.014), while dyslipidaemia was less prevalent (p = 0.044). Stroke recurrence rate was higher in the cryptogenic group compared to the group where the etiology was revealed, 7.7% vs. 2.8%, (p = 0.091). CONCLUSION: Cryptogenic stroke often indicates the inability to identify the cause in the acute phase and should be considered as a working diagnosis until efforts of diagnostic work up succeed in identifying a specific underlying etiology. Timeframe of 6-12-month follow-up may be considered as optimal. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02937077, EudraCT 2018-002298-23.

Increased headache prevalence in female adolescents and adult women with early menarche. The Head-HUNT Studies.

BACKGROUND: Age at menarche is associated with cardiovascular events and lifestyle factors such as body mass index (BMI), certain women's diseases like breast cancer and endometriosis and with occurrence of certain physical symptoms during puberty. It is unclear whether age at menarche is an independent determinant of headache. OBJECTIVES: The aim of the study was to explore age of menarche in relation to headache prevalence in a large population-based study of both adolescents and adult women (HUNT). METHODS: In the Nord-Trøndelag Health Study in Norway 1995-97 (HUNT 2), a total of 26,636 (57%) of 46,506 invited women responded to questions regarding menarche and headache (Head-HUNT). In the youth part of HUNT 2, 3196 female students were interviewed about their headache complaints and 2766 (87%) responded to questions regarding menarche. All the final analyses were adjusted for age, use of oral contraceptives and BMI, and for adults also for educational level. RESULTS: Headache was more prevalent amongst females with menarche ≤ 12 years, both amongst adolescents (OR=1.3, 95% CI=1.1-1.5) and adults (OR=1.1, 95% CI=1.1-1.2), evident for migraine and non-migrainous headache. CONCLUSION: Headache, both migraine and non-migrainous headache, was more prevalent amongst both adolescents and adult females with early menarche. Early menarche may increase headache susceptibility, or be a consequence of a common pathogenetic factor, e.g., sensitivity to estrogens.

Hormone replacement therapy and headache prevalence in postmenopausal women. The Head-HUNT study.

Conflicting evidence exists whether hormone replacement therapy (HRT) is a risk factor for headache. The aim of the study was to examine the prevalence of headache and migraine amongst postmenopausal women using HRT. In the Nord-Trøndelag Health Study 1995-97 (HUNT 2), 18,323 (62%) out of 29,679 women aged 40 years or more responded to headache questions (Head-HUNT). Amongst the 6007 postmenopausal women, 5507 (92%) responded to questions regarding use of HRT (2375 used or had used it) and questions related to headache (2407 had complaints). There was a significant association between headache and present use of HRT, both with local [odds ratio (OR) = 1.4, 95% confidence intervals (CI) 1.1-1.7] and systemic (OR = 1.6, 95% CI 1.4-1.9) application. This was found for non-migrainous headache (OR = 1.3, 95% CI 1.1-1.5) and migraine (OR = 1.6, 95% CI 1.4-1.9). Both migraine and non-migrainous headache were more probably amongst users of postmenopausal HRT than amongst those who had never used HRT. Whether HRT caused headache or was used partly because of headache cannot be determined in this cross-sectional study.