Stratifying Stroke Risk in Atrial Fibrillation: Beyond Clinical Risk Scores

Shadi Yaghi, MD; Hooman Kamel, MD

Disclosures

Stroke. 2017;48(10):2665-2670. 

In This Article

Prediction of Stroke Risk Based on Serum Biomarkers

High-Sensitivity Cardiac Troponin

Cardiac troponin (cTnT) is a serum biomarker of myocardial injury or dysfunction.[35] Highly sensitive cTnT assays can detect concentrations 10× lower than the levels detected by conventional assays.[35] Studies have shown an association between high-sensitivity cTnT with cardiovascular and cerebrovascular events.[36,37]

In the RE-LY study (randomized evaluation of long-term anticoagulation therapy), subjects in the highest quartile of high-sensitivity cTnT had a significantly elevated risk of stroke when compared with those in the lowest quartile (HR, 1.99; 95% CI, 1.17–3.39).[38] Similarly, a recent study found that high-sensitivity cTnT level ≥23 ng/L was independently associated with stroke or systemic embolism risk (HR, 1.98; 95% CI, 1.42–2.78).[39] In addition, adding high-sensitivity cTnT to the CHA2DS2-VASc score improved the C statistic from 0.63 to 0.65.

N-Terminal Pro-B-Type Natriuretic Peptide

NT-proBNP (N-terminal pro-B-type natriuretic peptide) is another biomarker released by the myocardium in the setting of stretch and may be increased with structural heart disease, heart failure, and ventricular strain.[40] NT-proBNP is an independent predictor of cardiovascular events[37] and stroke,[41] particularly of cardioembolic subtype.[42]

In the RE-LY trial, patients with AF with the highest quartile of NT-proBNP faced a higher stroke risk when compared with those in the lowest quartile (adjusted HR, 2.4; 95% CI, 1.41–4.07).[38] Similar findings were demonstrated in another study, and the addition of NT-proBNP level to the CHA2DS2-VASc score improved its C statistic from 0.62 to 0.65.[43]

Inflammatory Biomarkers

Biomarkers of inflammation have been shown to be associated with ischemic stroke risk[44] and cardiovascular events.[45] Inflammation is one of the proposed factors leading to thrombus formation in patients with AF. An analysis of patients in the SPAF-III trial (Stroke Prevention in Atrial Fibrillation) found an independent association between C-reactive protein levels and cardiovascular events and cardiovascular mortality, but not specifically stroke.[46] In RE-LY, subjects in the highest quartile of levels of an inflammatory cytokine (IL-6) faced a significantly higher stroke and systemic embolism risk when compared with those in the lowest quartile (HR, 2.03; 95% CI, 1.27–3.26).[47] The addition of IL-6 improved the C statistic of the CHA2DS2-VASc score from 0.62 to 0.64. However, when more standard cardiac biomarkers, such as high-sensitivity cTnT and NT-proBNP, were added to the model, IL-6 was no longer associated with stroke or systemic embolism risk. Another study showed increased rates of all-cause mortality in those with the highest quartile of IL-6 (HR, 1.93; 95% CI, 1.57–2.37) and C-reactive protein levels (HR, 1.49; 95% CI, 1.24–1.79), but these biomarkers were not associated with stroke or systemic embolism risk.[48]

Age, Biomarkers, and Clinical History Score

Based on the above data, investigators developed the age, biomarkers, and clinical history score to predict stroke and systemic embolism risk in patients with AF. This score was derived from a cohort of 14 701 patients and externally validated in a separate cohort of 1400. In this derivation/validation study, the age, biomarkers, and clinical history score was superior to the CHA2DS2-VASc score in predicting the risk of stroke and systemic embolism in both the derivation cohort (C statistic, 0.68 versus 0.62; P<0.001) and the validation cohort (C statistic, 0.66 versus 0.58; P<0.001).[49]

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