Carotid Plaque Composition and Prediction of Incident Atherosclerotic Cardiovascular Disease

Background: Whether information on carotid plaque composition contributes to prediction of incident atherosclerotic cardiovascular disease (ASCVD) remains to be investigated. We determined the sex-specific added value of carotid plaque components for predicting incident ASCVD events, beyond traditional cardiovascular risk factors. Methods: Between 2007 and 2012, participants from the population-based Rotterdam Study with asymptomatic carotid wall thickening >2.5 mm on ultrasonography were invited for carotid magnetic resonance imaging. Among 1349 participants (mean age: 72 years [SD±9.3], 49.5% women) without cardiovascular disease, we assessed plaque thickness, luminal stenosis (>30%), presence of intraplaque hemorrhage, lipid-rich necrotic core, and calcification. Follow-up for ASCVD was complete until January 1, 2015. Using Cox proportional hazards models, we fitted sex-specific prediction models including traditional cardiovascular risk factors (base model). We extended the base model by single and simultaneous additions of plaque characteristics and calculated improvement of model performance by the C statistics. Results: During a median follow-up of 4.8 years, 60 men and 48 women developed ASCVD. In women, presence of intraplaque hemorrhage was associated with incident ASCVD (adjusted hazard ratio, 3.37 [95% CI, 1.81–6.25]). The C statistic (95% CI) improved from 0.73 (0.66–0.79) to 0.76 (0.70–0.83) after single addition of intraplaque hemorrhage to the base model. Simultaneous addition of plaque components, plaque thickness, and stenosis did not change the results. In men, only carotid stenosis was statistically significantly associated with incident ASCVD (adjusted hazard ratio, 1.75 [95% CI, 1.00–3.08]); yet, the association diminished after the addition of other plaque characteristics, and no improvements were observed in C statistics. Conclusions: Presence of intraplaque hemorrhage contributes to the prediction of incident ASCVD in women, beyond traditional cardiovascular risk factors, other plaque components, plaque size, and stenosis.