Biomarkers predictive of atrial fibrillation in patients with cryptogenic stroke. Insights from the Nordic Atrial Fibrillation and Stroke (NOR‐FIB) study

Abstract

Background and purpose There are currently no biomarkers 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 ischaemic attack 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 curves were created. Biomarkers reaching area under the receiver operating characteristic curve ≥ 0.7 were dichotomized by finding optimal cut‐off values and were 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 and high‐sensitivity cardiac troponin I and T were significantly higher in the AF than non‐AF group. BNP and NT‐proBNP reached the predefined area under the curve 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 7.72, 95% confidence interval 3.16–18.87) and age‐ and sex‐adjusted models (odds ratio 4.82, 95% confidence interval 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.

Investigation of Stroke Risk Factors and Prognostic Indicators in NVAF Patients with Low CHA₂DS₂-VASc Scores

“…21) NT-proBNP was found to be a predictor of stroke in patients with AF. 13) In a subanalysis of ENGAGE AF-TIMI 48, the prognostic value of NT-proBNP for stroke in patients with NVAF was further verified. 22) The mechanism of NT-proBNP as a predictor of stroke risk in patients with NVAF may be that the increase in NT-proBNP may reflect atrial structural and functional impairments.…”

“…There are few research on clinically independent risk factors for low-risk NVAF (other than the CHA2DS2-VASc score). [12][13][14] Additionally, little study has been done on the prognosis of low-risk NVAF patients who experience stroke, including in-hospital mortality. Investigating the traits of patients with ischemic stroke and poor prognosis among individuals at low risk according to the CHA2DS2-VASc score is therefore important.…”

Diagnostic Utility of N-Terminal Pro-B-Type Natriuretic Peptide in Identifying Atrial Fibrillation Post-Cryptogenic Stroke: A Systematic Review and Meta-Analysis

“…Advanced machine learning algorithms may also aid in the prognostication of patients with suspected AF [ 40 ]. In addition to NT-proBNP, other biomarkers have been traditionally used; however, their efficacy in detecting AF has been variable and comparatively suboptimal for clinical use [ 41 ]. A detailed overview of these biomarkers is provided in Table 5 .…”

“…Furthermore, standard cardiovascular laboratory parameters such as triglycerides and total cholesterol have also been shown to enhance the ability of NT-proBNP to distinguish between stroke of cardioembolic or large-artery atherosclerotic origin [ 54 ]. A recent prospective study also identified several biomarkers associated with AF in cryptogenic stroke patients [ 41 ]. Notably, NT-proBNP emerged as the robust predictor of AF at baseline and after 12-month follow-up [ 41 ].…”

“…A recent prospective study also identified several biomarkers associated with AF in cryptogenic stroke patients [ 41 ]. Notably, NT-proBNP emerged as the robust predictor of AF at baseline and after 12-month follow-up [ 41 ]. Despite numerous proposals for tools or scores to assess the likelihood of AF post-stroke [ 17 , 20 , 55 , 56 ], a standardized system remains elusive.…”