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Evaluation of the Framingham Risk Score in the European Prospective Investigation of Cancer–Norfolk CohortDoes Adding Glycated Hemoglobin Improve the Prediction of Coronary Heart Disease Events?
Rebecca K. Simmons, PhD;
Stephen Sharp, MSc;
S. Matthijs Boekholdt, MD, PhD;
Lincoln A. Sargeant, PhD;
Kay-Tee Khaw, PhD;
Nicholas J. Wareham, PhD;
Simon J. Griffin, DM
Arch Intern Med. 2008;168(11):1209-1216.
Background There is a continuous relationship between glycated hemoglobin (HbA1c) 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 HbA1c 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 HbA1c 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 HbA1c. 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 HbA1c made a small but statistically significant improvement to discrimination in men but not in women, without significant improvement in reclassification of risk category.
Author Affiliations: MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Cambridge, England (Drs Simmons, Sargeant, Wareham, and Griffin and Mr Sharp); Department of Cardiology, Academic Medical Center, Amsterdam, the Netherlands (Dr Boekholdt); and Department of Clinical Gerontology, University of Cambridge School of Clinical Medicine, Addenbrooke's Hospital, Cambridge (Dr Khaw).
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