Introduction. Primary prevention of cardiovascular disease is based on subjects’ stratification into risk categories according to their predicted risk of event over a given time period, generally 10 years. The risk category triggers the treatment [1]; however, risk stratification is based on arbitrarily-chosen thresholds, showing sometimes no clinical utility [2]. Current research is moving forward the concept of “long-term” risk prediction, to better discriminate risk in young subjects and women. Therefore, long–term risk could be specially beneficial in the Italian population, considered at low incidence of event. Aims. To develop a long-term prediction model of first major cardiovascular event and to assess its clinical utility in the Italian population. Methods. N=5247 35-69 years old men and women free of cardiovascular disease were enrolled in four independent population-based cohorts conducted between 1986 and 1993 in Brianza (Northern Italy). Absolute 20-year risk of first fatal or non-fatal coronary or ischemic stroke event during follow-up (MONICA validated) was estimated from gender-specific Cox models including age, total- and HDL-cholesterol, systolic blood pressure, anti-hypertensive treatment, diabetes and smoking. The Area Under the ROC-Curve (AUC), computed taking censoring into account and adjusted for over-optimisms, was a measure of model discrimination. “High-risk” subjects were identified based on several threshold values for the 20-year predicted risk. Clinical utility was defined in terms of fraction of missed events (events among those considered at low-risk) and unnecessary treatment (false:true positives ratio). A Net Benefit curve analysis, which plots a weighted difference between true and false positives along all the possible threshold values, was also provided. Results. Kaplan-Meier 20-year risk was 16.1% in men (315 events) and 6.1% in women (123 events). Model discrimination (AUC=0.737 in men, 0.801 in women) did not change significantly as compared to 10-year prediction time interval. In men, with respect to risk stratification based on the number of risk factors, a 20% predicted risk cut-off would miss less events (36% vs. 50%) and reduce unnecessary treatment (false:true positive ratio: 2.2 vs. 3.0). Similarly in women the 8% risk threshold would miss 23% of events with a false:true positive ratio of 4.5, compared to 42.3% and 5.8, respectively, of the strategy based on the number of risk factors. In both genders, the Net Benefit for predicted risk was higher than for the count of risk factors along all the possible risk thresholds. Conclusions. Long-term prediction has good discrimination ability and is clinically useful for risk stratification in primary prevention. Together with model development, a clinical utility analysis is crucial to identify the optimal stratification according to different public health goals.

Long-term prediction of first major cardiovascular event: model development and assessment of clinical utility

VERONESI, GIOVANNI;GIANFAGNA, FRANCESCO;FERRARIO, MARCO MARIO ANGELO
2013-01-01

Abstract

Introduction. Primary prevention of cardiovascular disease is based on subjects’ stratification into risk categories according to their predicted risk of event over a given time period, generally 10 years. The risk category triggers the treatment [1]; however, risk stratification is based on arbitrarily-chosen thresholds, showing sometimes no clinical utility [2]. Current research is moving forward the concept of “long-term” risk prediction, to better discriminate risk in young subjects and women. Therefore, long–term risk could be specially beneficial in the Italian population, considered at low incidence of event. Aims. To develop a long-term prediction model of first major cardiovascular event and to assess its clinical utility in the Italian population. Methods. N=5247 35-69 years old men and women free of cardiovascular disease were enrolled in four independent population-based cohorts conducted between 1986 and 1993 in Brianza (Northern Italy). Absolute 20-year risk of first fatal or non-fatal coronary or ischemic stroke event during follow-up (MONICA validated) was estimated from gender-specific Cox models including age, total- and HDL-cholesterol, systolic blood pressure, anti-hypertensive treatment, diabetes and smoking. The Area Under the ROC-Curve (AUC), computed taking censoring into account and adjusted for over-optimisms, was a measure of model discrimination. “High-risk” subjects were identified based on several threshold values for the 20-year predicted risk. Clinical utility was defined in terms of fraction of missed events (events among those considered at low-risk) and unnecessary treatment (false:true positives ratio). A Net Benefit curve analysis, which plots a weighted difference between true and false positives along all the possible threshold values, was also provided. Results. Kaplan-Meier 20-year risk was 16.1% in men (315 events) and 6.1% in women (123 events). Model discrimination (AUC=0.737 in men, 0.801 in women) did not change significantly as compared to 10-year prediction time interval. In men, with respect to risk stratification based on the number of risk factors, a 20% predicted risk cut-off would miss less events (36% vs. 50%) and reduce unnecessary treatment (false:true positive ratio: 2.2 vs. 3.0). Similarly in women the 8% risk threshold would miss 23% of events with a false:true positive ratio of 4.5, compared to 42.3% and 5.8, respectively, of the strategy based on the number of risk factors. In both genders, the Net Benefit for predicted risk was higher than for the count of risk factors along all the possible risk thresholds. Conclusions. Long-term prediction has good discrimination ability and is clinically useful for risk stratification in primary prevention. Together with model development, a clinical utility analysis is crucial to identify the optimal stratification according to different public health goals.
2013
Veronesi, Giovanni; Gianfagna, Francesco; Chambless, Le; Giampaoli, S; Mancia, G; Cesana, G; Ferrario, MARCO MARIO ANGELO
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11383/1907528
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus ND
  • ???jsp.display-item.citation.isi??? ND
social impact