A Review of Biomarkers for Ischemic Stroke Evaluation in Patients With Non-valvular Atrial Fibrillation

Abstract

Atrial fibrillation (AF) is the most prevalent cardiac arrhythmia worldwide and results in a significantly increased ischemic stroke (IS) risk. IS risk stratification tools are widely being applied to guide anticoagulation treatment decisions and duration in patients with non-valvular AF (NVAF). The CHA2DS2-VASc score is largely validated and currently recommended by renowned guidelines. However, this score is heavily dependent on age, sex, and comorbidities, and exhibits only moderate predictive power. Finding effective and validated clinical biomarkers to assist in personalized IS risk evaluation has become one of the promising directions in the prevention and treatment of NVAF. A number of studies in recent years have explored differentially expressed biomarkers in NVAF patients with and without IS, and the potential role of various biomarkers for prediction or early diagnosis of IS in patients with NVAF. In this review, we describe the clinical application and utility of AF characteristics, cardiac imaging and electrocardiogram markers, arterial stiffness and atherosclerosis-related markers, circulating biomarkers, and novel genetic markers in IS diagnosis and management of patients with NVAF. We conclude that at present, there is no consensus understanding of a desirable biomarker for IS risk stratification in NVAF, and enrolling these biomarkers into extant models also remains challenging. Further prospective cohorts and trials are needed to integrate various clinical risk factors and biomarkers to optimize IS prediction in patients with NVAF. However, we believe that the growing insight into molecular mechanisms and in-depth understanding of existing and emerging biomarkers may further improve the IS risk identification and guide anticoagulation therapy in patients with NVAF.

Atrial Fibrillation Detected by Implantable Monitor in Embolic Stroke of Undetermined Source: A New Clinical Entity

“…In the ATTICUS trial [ 9 ], the detection rate of CPAF by ICM in ESUS patients (23%) was similar to our results. In our study, it is not surprising to find that AF risk factors such as age, coronaropathy history, left atrial dilatation, and atrial hyperexcitability were independently associated with CPAF diagnosis [ 21 , 22 , 23 , 24 ]. Interestingly, clinical severity assessed by the NIHSS scale was not a predictor of CPAF diagnosis in ESUS patients.…”

“…In the first hypothesis, the absence of a causality link between CPAF and ESUS might be considered based on both stroke clinico-radiological patterns and AF diagnostic temporality. Thus, CPAF incidence in the ESUS population might only be supported by a higher prevalence of the cardiovascular risk factors and cardio-morphological abnormalities underlying AF without presuming a causality link with ESUS [ 18 , 24 ]. The results of the STROKE-AF study [ 27 ] support this hypothesis.…”

Prognostic Impact of Atrial Fibrillation Pattern and other Clinical Biomarkers in Patients with Stroke Admitted in a Tertiary Hospital in Cebu City from 2015-2022

“…Certain biological markers of inflammation have also been evaluated to be predictors for the pattern of atrial fibrillation; however, few studies have assessed the association of these markers with mortality in patients with AF-related stroke. 4 It is believed that cerebral ischemia triggers an inflammatory response in both the brain and peripheral circulation, which leads to the up-regulation of inflammatory cytokines. 3 Increased circulating levels of inflammatory cytokines have been regularly associated with poor outcomes after stroke.…”

“…High MPV was found to be a predictive marker for long term recurrent stroke and mortality after. 4 Serum uric acid is another molecular indicator of inflammation and oxidative stress. It was suggested that serum uric acid impaired vascular tone and endothelial dysfunction contributing to ischemic changes.…”

microRNAs as biomarkers of risk of major adverse cardiovascular events in atrial fibrillation

“…Thus, markers for the onset and development of AF, as well as risk predictors for MACE, have been identified either from prospective and randomized clinical trials or from studies that, in any case, have recruited a large number of patients. Among them, parameters derived from cardiac and renal functions, and coagulation have helped in the understanding of the pathophysiological pathways leading to AF as well as in the forecast of risk for MACE ( 7 , 8 ). More recently, inflammation began to be considered as a new factor that plays an important role not only in the onset of AF, but also in the AF-related MACE.…”