Circulating Levels of Biomarkers of Cerebral Injury in Patients with Atrial Fibrillation.

Atrial fibrillation (AF) is a source of altered brain perfusion and ischemia, potentially leading to cerebral injury and blood brain barrier (BBB) disruption, which may result in the permeation of neurospecific molecules into the bloodstream. We retrospectively analyzed circulating levels of biomarkers of cerebral injury: Astrocyte-specific glial acidic fibrillary protein (GFAP), calcium-binding protein B (S100 b), stress response marker growth differential factor 15 (GDF15), and microtubule associated Tau protein, in patients with AF and non-AF controls. A total of 196 AF cases and 47 non-AF controls were enrolled in this study all without previous clinical stroke or cerebral injury. Plasma samples were obtained from the Intermountain INSPIRE biobank registry. AF status was determined at the time of the sample draw using clinical diagnosis. Assessment of circulating biomarkers was conducted with EIA. Multivariate linear modeling, using natural log, and square root transformation of the biomarkers, was done adjusting for (1) CHA2DS2-VASc and anticoagulation, and (2) age, gender, coronary artery disease and anticoagulation. Circulating Tau, GDF15, and GFAP were elevated in AF cases. After multivariate adjustment, GFAP and Tau remained significantly elevated in the AF, whereas the signal for GDF15 was confounded by age. In conclusion, circulating biomarkers of neuronal and glial injury Tau and GFAP are elevated in patients with AF that are consistent with subclinical cerebral injury and disruption of the BBB, which can predispose these patients to the development of cognitive dysfunction and/or dementia later in life.

The role of microRNAs in the development, regulation, and treatment of atrial fibrillation.

BACKGROUND: MicroRNAs (miRNA)s regulate expression of genes involved in various processes including cardiac automaticity, conduction, excitability, and fibrosis and therefore may provide a diagnostic utility to identify high-risk patients for atrial fibrillation (AF). In this study, we tested the hypothesis that specific profiles of circulating miRNAs can identify patients with AF and can also help to identify patients at high risk of AF recurrence after ablation. METHODS: Two patient populations were studied: 140 AF cases (93 paroxysmal and 47 persistent) and 50 healthy controls, and 141 AF ablation cases with (n = 86) and without (n = 55) 1-year recurrence. Assessment of several previously identified AF-associated plasma miRNAs (21, 29a, 133a, 133b, 150, 328) was performed with TaqMan assays, using synthetic miRNAs as standards. RESULTS: The AF cases compared to the healthy controls were older and were more often male and hypertensive. After multivariate adjustment, higher miRNA-21 levels significantly decreased the risk of AF (OR = 0.93 per fmol/µl (95% CI = 0.89-0.98, p = 0.007)). There were no significant differences in circulating miRNAs between the AF subtypes of persistent and paroxysmal. Among the AF ablation cases, miRNA-150 was lower for those with AF recurrences at 1 year (adjusted OR = 0.98 per 500,000 fmol/µl; 95% CI = 0.965, 0.998; p = 0.039). CONCLUSIONS: Decreased circulating miRNA-21 is associated with AF, but not with AF subtypes, suggestive that molecular mechanisms responsible for the onset and progression of the AF may be different. Circulating miRNA-150 was significantly associated with a reduction in 1-year AF recurrence post ablation suggestive of adverse structural and electrical remodeling as recurrence mechanisms.