Evaluation of the Framingham risk score in the European Prospective Investigation of Cancer-Norfolk cohort: does adding glycated hemoglobin improve the prediction of coronary heart disease events?
BACKGROUND
There is a continuous relationship between glycated hemoglobin (HbA(1c)) and coronary heart disease (CHD) risk, even below diagnostic thresholds for diabetes mellitus.


METHODS
To evaluate the Framingham risk score in a UK population-based prospective cohort (European Prospective Investigation of Cancer [EPIC]-Norfolk) and to assess whether adding HbA(1c) improves the prediction of CHD. Participants aged 40 to 79 years were recruited from UK general practices, attended a health check, and were followed up for CHD events and death. The Framingham risk score was computed for 10,295 individuals with data on age, total cholesterol, high-density lipoprotein cholesterol, systolic blood pressure, diabetes mellitus, and smoking status. We developed a Cox proportional hazards regression model with the original Framingham covariates and then added HbA(1c) to determine whether this improved the prediction of CHD. Model discrimination was compared by using area under the receiver operating characteristic curves (AUROCs), and the correctness of reclassification was determined by calculating the net reclassification improvement and the integrated discrimination improvement. The main outcome measures were CHD-related hospital admission and death.


RESULTS
A total of 430 men and 250 women developed CHD during 8.5 years of follow-up. The AUROC for the original Framingham risk score was 0.71. Using the Framingham variables with coefficients fitted from the EPIC-Norfolk data, the AUROC was 0.72 for men and 0.80 for women, compared with 0.73 and 0.80, respectively, in a score including HbA(1c). This difference was significant for men only (P = .005). The net reclassification improvement was 3.4% (P = .06) in men and -2.2% (P = .27) in women.


CONCLUSIONS
The Framingham risk score predicts CHD in this cohort. The addition of HbA(1c) made a small but statistically significant improvement to discrimination in men but not in women, without significant improvement in reclassification of risk category.
MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, England.
Rebecca K
RK
Simmons
Stephen
S
Sharp
S Matthijs
SM
Boekholdt
Lincoln A
LA
Sargeant
Kay-Tee
KT
Khaw
Nicholas J
NJ
Wareham
Simon J
SJ
Griffin
D003327:Coronary Disease / Q000097:blood* / Q000453:epidemiology; D005260:Female; D006442:Glycated Hemoglobin / Q000032:analysis*; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012372:ROC Curve; D015203:Reproducibility of Results; D018570:Risk Assessment; D012307:Risk Factors; D006113:United Kingdom / Q000453:epidemiology
D006442:Glycated Hemoglobin