A combined clinical and genetic risk score improved risk stratification for incident intracerebral hemorrhage among anticoagulant users compared to a clinical risk score alone (C index 0.57 vs 0.53).
Cohort (n=5,530)
Yes
Does a combined clinical and genetic risk score improve risk stratification for incident intracerebral hemorrhage compared to a clinical risk score alone in anticoagulant users?
Integrating a genetic risk score with a standard clinical risk score improves the prediction and risk stratification of intracerebral hemorrhage in patients taking anticoagulants.
Effect estimate: HR 1.33 (95% CI 1.11-1.59)
BACKGROUND: Intracerebral hemorrhage (ICH) is the most devastating adverse outcome for patients on anticoagulants. Clinical risk scores that quantify bleeding risk can guide decision-making in situations when indication or duration for anticoagulation is uncertain. We investigated whether integration of a genetic risk score into an existing risk factor-based CRS could improve risk stratification for anticoagulation-related ICH. METHODS: We constructed 153 genetic risk scores from genome-wide association data of 1545 ICH cases and 1481 controls and validated them in 431 ICH cases and 431 matched controls from the population-based UK Biobank. The score that explained the largest variance in ICH risk was selected and tested for prediction of incident ICH in an independent cohort of 5530 anticoagulant users. A CRS for major anticoagulation-related hemorrhage, based on 8/9 components of the HAS-BLED score, was compared with a combined clinical and genetic risk score incorporating an additional point for high genetic risk for ICH. RESULTS: Among anticoagulated individuals, 94 ICH occurred over a mean follow-up of 11.9 years. Compared with the lowest genetic risk score tertile, being in the highest tertile was associated with a two-fold increased risk for incident ICH (hazard ratio, 2.08 95% CI, 1.22-3.56). Although the CRS predicted incident ICH with a hazard ratio of 1.24 per 1-point increase (95% CI 1.01-1.53), adding a point for high genetic ICH risk led to a stronger association (hazard ratio of 1.33 per 1-point increase 95% CI, 1.11-1.59) with improved risk stratification (C index 0.57 versus 0.53) and maintained calibration (integrated calibration index 0.001 for both). The new clinical and genetic risk score showed 19% improvement in high-risk classification among individuals with ICH and a net reclassification improvement of 0.10. CONCLUSIONS: Among anticoagulant users, a prediction score incorporating genomic information is superior to a clinical risk score alone for ICH risk stratification and could serve in clinical decision-making.
Mayerhofer et al. (Thu,) conducted a cohort in Anticoagulation-related Intracerebral Hemorrhage (n=5,530). Combined clinical and genetic risk score vs. Clinical risk score alone was evaluated on Incident intracerebral hemorrhage (HR 1.33, 95% CI 1.11-1.59). A combined clinical and genetic risk score improved risk stratification for incident intracerebral hemorrhage among anticoagulant users compared to a clinical risk score alone (C index 0.57 vs 0.53).