Improvements in risk stratification for the occurrence of cardiovascular disease by imaging subclinical atherosclerosis: a systematic review.

CONTEXT Imaging for subclinical atherosclerosis on top of conventional risk factor assessment may improve risk prediction for the occurrence of cardiovascular disease events in asymptomatic individuals. OBJECTIVE To systematically review the available evidence on this issue. DATA SOURCES PubMed MEDLINE was systematically searched on 7 September 2011. STUDY SELECTION Studies were included that evaluated the added value of flow mediated dilation (FMD), carotid intima-media thickness (CIMT), carotid plaques and/or coronary artery calcification (CAC) scoring in the prediction of risk for developing fatal or non-fatal cardiovascular events. DATA EXTRACTION Data on general study characteristics and the added predictive performance of imaging markers in terms of discrimination, calibration and (re)classification were extracted. RESULTS 25 studies were selected that provided information on added predictive value of FMD (n=2), CIMT (n=12), carotid plaques (n=6) and/or CAC (n=9). Heterogeneity existed across studies in the conventional risk models that were used and in the measurements of the imaging marker. The added predictive value, quantified by the difference in c-index, of FMD, CIMT, carotid plaques or CAC ranged from 0.00 to 0.01 for FMD, from 0.00 to 0.03 for CIMT, from 0.01 to 0.05 for carotid plaque and from 0.05 to 0.13 for CAC. The reported net reclassification improvement (NRI) by the imaging markers ranged from -1.4% to 12% for CIMT, 8% to 11% for carotid plaques, 14% to 25% for CAC and 29% for FMD). Although the definition of intermediate cardiovascular risk varied across studies, the NRI was the highest in those at intermediate cardiovascular risk. CONCLUSIONS Published evidence on the added value of atherosclerosis imaging varies across the different markers, with limited evidence for FMD and considerable evidence for CIMT, carotid plaque and CAC. The added predictive value of additional screening may be primarily found in asymptomatic individuals at intermediate cardiovascular risk. Additional research in asymptomatic individuals is needed to quantify the cost effectiveness and impact of imaging for subclinical atherosclerosis on cardiovascular risk factor management and patient outcomes.