Stroke risk in older British men: Comparing performance of stroke-specific and composite-CVD risk prediction tools

Stroke risk is currently estimated as part of the composite risk of cardiovascular disease (CVD). We investigated if composite-CVD risk prediction tools QRISK3 and Pooled Cohort Equations-PCE, derived from middle-aged adults, are as good as stroke-specific Framingham Stroke Risk Profile-FSRP and QStroke for capturing the true risk of stroke in older adults. External validation for 10y stroke outcomes was performed in men (60-79y) of the British Regional Heart Study. Discrimination and calibration were assessed in separate validation samples (FSRP n = 3762, QStroke n = 3376, QRISK3 n = 2669 and PCE n = 3047) with/without adjustment for competing risks. Sensitivity/specificity were examined using observed and clinically recommended thresholds. Performance of FSRP, QStroke and QRISK3 was further compared head-to-head in 2441 men free of a range of CVD, including across age-groups. Observed 10y risk (/1000PY) ranged from 6.8 (hard strokes) to 11 (strokes/transient ischemic attacks). All tools discriminated weakly, C-indices 0.63-0.66. FSRP and QStroke overestimated risk at higher predicted probabilities. QRISK3 and PCE showed reasonable calibration overall with minor mis-estimations across the risk range. Performance worsened on adjusting for competing non-stroke deaths. However, in men without CVD, QRISK3 displayed relatively better calibration for stroke events, even after adjustment for competing deaths, including in oldest men. All tools displayed similar sensitivity (63-73 %) and specificity (52-54 %) using observed risks as cut-offs. When QRISK3 and PCE were evaluated using thresholds for CVD prevention, sensitivity for stroke events was 99 %, with false positive rate 97 % suggesting existing intervention thresholds may need to be re-examined to reflect age-related stroke burden.