Glycated haemoglobin and the risk of cardiovascular disease, diabetes and all-cause mortality in the Copenhagen City Heart Study.

Abstract

OBJECTIVE: Individuals with diabetes mellitus (DM) have a considerably elevated risk of developing serious health problems including cardiovascular disease (CVD). Long-term elevated levels of blood glucose in nondiabetic individuals may also be associated with increased risk of CVD. The aim of this study was to investigate the relationships between glycated haemoglobin A(1c) (HbA(1c) ) and CVD, DM and all-cause mortality. SUBJECTS AND DESIGN: The Copenhagen City Heart Study is a prospective study of individuals from the Danish general population. The cohort was followed for 10 years via national registers with respect to incident CVD, DM and all-cause mortality. Follow-up was 100% complete. RESULTS: A total of 5127 subjects were included, of whom 597 had DM. In the nondiabetic population, HbA(1c) was significantly associated with incident CVD events in both univariate [hazard ratio (HR) 1.38, 95% CI 1.11-1.71] and multivariate analyses (HR 1.31, 95% CI 1.05-1.64). In the nondiabetic population, increased levels of HbA(1c) were correlated with developing DM. There was a threefold increase in risk of incident DM per unit increase in HbA(1c) with a univariate HR of 3.83 (95% CI 1.96-7.51). This relationship was essentially unchanged after multivariate adjustments (HR 4.19, 95% CI 2.01-8.71). Furthermore, we found that net reclassification improvement for diagnosed DM and CVD was significantly improved with the addition of HbA(1c) in the analyses. Although not statistically significant, we found a strong trend towards an association between HbA(1c) and all-cause mortality (HR 1.21, 95% CI 0.99-1.47). We did not find the same associations amongst the population with DM. CONCLUSION: In the Danish general population, HbA(1c) was strongly associated with CVD in individuals without DM.