Estimation of Recurrent Atherosclerotic Cardiovascular Event Risk

Quick Takes

  • The SMART2 risk score is useful for estimating 10-year ASCVD risk (fatal and nonfatal events) among adults with established ASCVD.
  • The clinical utility was demonstrated across a range of treatment thresholds and this is relevant to treatment intensification.
  • The risk score was adapted to CVD incident from several global regions.

Study Questions:

Does the SMART2 risk score identify risk of atherosclerotic cardiovascular disease (ASCVD) events across different geographic regions among adults with established ASCVD?


Data from the Utrecht Cardiovascular Cohort-Secondary Manifestations of ARTerial disease (SMART) cohort, including adults 40–80 years of age, were used to derive a 10-year risk prediction model for recurrent ASCVD events (nonfatal myocardial infarction, nonfatal stroke, or cardiovascular mortality) using a Fine and Gray competing risk-adjusted model. Established ASCVD included coronary artery disease, cerebrovascular disease, peripheral artery disease, or abdominal aortic aneurysm events. The model was then recalibrated to four regions across Europe, and to Asia (excluding Japan), Japan, Australia, North America, and Latin America using contemporary cohort data from each target region. External validation was performed using data from seven cohorts. These cohorts included the Clinical Practice Research Datalink, SWEDEHEART, the international REduction of Atherothrombosis for Continued Health (REACH) Registry, the Estonian Biobank, Spanish Biomarkers in Acute Coronary Syndrome and Biomarkers in Acute Myocardial Infarction (BACS/BAMI), the Norwegian COgnitive Impairment After STroke, and the Bialystok PLUS/Polaspire.


A total of 8,355 adults were included in the Utrecht Cardiovascular Cohort-SMART cohort. During a median follow-up time of 8.2 years (interquartile range 4.2–12.5 years), a total of 1,707 ASCVD events occurred. Data were collected between 1996–2019. Mean age at baseline was 61 ± 9 years and 74% were male. The validation cohort included 369,044 adults with established ASCVD, of whom 62,807 experienced an ASCVD event. Median follow-up times ranged from 1.9 years for REACH to 6.5 years for the Estonian Biobank.

C-statistics ranged from 0.605 (95% confidence interval [CI], 0.547–0.664) in BACS/BAMI to 0.772 (95% CI, 0.659–0.886) in REACH Europe high-risk region. The most heterogeneity in discrimination results was found in data from Western Europe. Sensitivity analyses of REACH data from Western Europe (n = 12,882) demonstrated that sex-specific and location-specific model derivations and recalibrations did not improve discriminative model performance. The clinical utility of the model was demonstrated across a range of clinically relevant treatment thresholds for intensified treatment options.


The investigators concluded that the SMART2 risk score provides an updated, validated tool for the prediction of recurrent ASCVD events in patients with established ASCVD across European and non-European populations. The use of this tool could allow for a more personalized approach to secondary prevention based on quantitative rather than qualitative estimates of residual risk.


The SMART2 risk score provides a clinically useful tool to estimate 10-year ASCVD risk among adults with established ASCVD, using easily measured clinical variables. The strength of this risk score is the validation in geographically diverse populations.

Keywords: Acute Coronary Syndrome, Aortic Aneurysm, Abdominal, Atherosclerosis, Cardiovascular Diseases, Cerebrovascular Disorders, Coronary Artery Disease, Myocardial Infarction, Peripheral Arterial Disease, Primary Prevention, Risk Assessment, Risk Factors, Secondary Prevention, Stroke, Vascular Diseases

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