Blood biomarkers useful for improving stroke risk prediction in AF

Higher concentrations of the blood biomarkers cystatin C, factor VIII, interleukin (IL)‐6, and N‐terminal B‐type natriuretic peptide (NT‐proBNP), are strongly associated with increased risk of stroke in atrial fibrillation (AF), according to data from the REGARDS* study. Moreover, these markers improve the prediction of stroke risk when added to the CHA₂DS₂VASc score.

REGARDS involved 30,239 Black and White adults aged ≥45 years. Of these, 175 participants (63 percent women, 37 percent Black adults) with baseline AF and available blood biomarker data were included in the analysis.

Over 5.2 years, 81 ischaemic stroke events occurred. Patients with AF and a subsequent stroke tended to be White, men, regular users of warfarin, and have a history of cardiovascular comorbidities, such as hypertension, left ventricular hypertrophy, and heart failure.

Multivariable Cox analysis showed that stroke risk was associated with upper tertiles of the following biomarkers: cystatin C (hazard ratio [HR], 3.16, 95 percent confidence interval [CI], 1.04–9.58), factor VIII antigen (HR, 2.77, 95 percent CI, 1.03–7.48), IL‐6 (HR, 9.35, 95 percent CI, 1.95–44.78), and NT‐proBNP (HR, 4.21, 95 percent CI, 1.24–14.29).

Based on the number of the said blood biomarkers in the highest tertile, a risk score was developed. The corresponding adjusted HRs of stroke for one, two, and three or more elevated blood biomarkers, as opposed to none, were 1.75 (95 percent CI, 0.57–5.40), 4.97 (95 percent CI, 1.20–20.5), and 9.51 (95 percent CI, 2.22–40.8). This multimarker risk score led to a net reclassification improvement of 0.34 (95 percent CI, 0.04–0.65) when incorporated to the CHA₂DS₂VASc score.

The present data provide proof of concept that measuring circulating blood biomarkers may be useful in improving stroke risk prediction in patients with AF, beyond the presently used risk prediction models.

*Reasons for Geographic and Racial Differences in Stroke