Aim: Cardiovascular disease (CV) risk-stratification could be improved by adding measures of (subclinical) atherosclerosis to current risk scores, especially in intermediate-risk individuals. Our aim was to prospectively evaluate the additive value of non-invasive measurements of atherosclerosis(NIMA) for CV risk-stratification on top of traditional CV risk factors(tCVRF) in a middle-aged population-based cohort.

Methods: Carotid plaques, Intima-Media-Thickness(IMT), Ankle-Brachial-Index at rest(ABI-r) and after exercise(ABI-ex), Pulse-Wave-Velocity(PWV), Augmentation-Index(AIx), Central-Augmented-Pressure(CAP), and Central-Systolic-Pressure(CSP) were measured in 1367 CVD-free participants aged 50–70 years. CV-disease(CVD) was evaluated and validated after a mean follow-up of 3.8 years. The additive value of NIMA on top of tCVRF was evaluated using R², area-under-the-curve(AUC), and net-reclassification-improvement(NRI)-analyses.

Results: CVD was reported in 39 men and 32 women. Individual NIMA did not increase R² and AUC of the baseline-model (including tCVRF) and additionally showed no substantial reclassification, except for plaque-thickness in women(total-NRI=30.2%,p=0.021). In intermediate-risk men, baseline-model was improved by CSP(NRI=20.0%), plaque-thickness (NRI=19.2%), plaque-presence(NRI=16.7%), and ABI-r(NRI=13.6%). In intermediate-risk women all individual NIMA improved baseline-model(IMT showed highest NRI(102%). Combined NIMA improved risk-stratification in all women, and even more in intermediate-risk women. In men, combined NIMA showed additive value in intermediate-risk only. The optimal combinations were PWV-AIx-CSP-CAP-IMT in men(total-NRI=14.5%(p=0.087),IDI=0.016(p=0.148),clinical-NRI=46.0%), and IMT-plaque-thickness in women(total-NRI=28.0%(p=0.009),IDI=0.047(p=0.061),clinical-NRI=169.2%).

Conclusions: In a middle-aged population-based cohort, individual NIMA had additive value on top of tCVRF in intermediate-risk women, and to a lesser extent in intermediate-risk men and could improve CV risk-stratification. Combined NIMA resulted in larger reclassification in both men and women at intermediate-risk, but the optimal combination of NIMA differs between men and women.