Association of glycated hemoglobin A1c levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium

Abstract

Background: Biomarkers may contribute to improved cardiovascular risk estimation. Glycated hemoglobin A_1c (HbA_1c) is used to monitor the quality of diabetes treatment. Its strength of association with cardiovascular outcomes in the general population remains uncertain. This study aims to assess the association of HbA_1c with cardiovascular outcomes in the general population.<p> <p>Methods: Data from six prospective population-based cohort studies across Europe comprising 36,180 participants were analyzed. HbA_1c was evaluated in conjunction with classical cardiovascular risk factors (CVRFs) for association with cardiovascular mortality, cardiovascular disease (CVD) incidence, and overall mortality in subjects without diabetes (N=32,496) and with diabetes (N=3684).<p> <p>Results: Kaplan–Meier curves showed higher event rates with increasing HbA_1c levels (log-rank-test: p<0.001). Cox regression analysis revealed signifcant associations between HbA_1c (in mmol/mol) in the total study population and the examined outcomes. Thus, a hazard ratio (HR) of 1.16 (95% confdence interval (CI) 1.02–1.31, p=0.02) for cardiovascular mortality, 1.13 (95% CI 1.03–1.24, p=0.01) for CVD incidence, and 1.09 (95% CI 1.02–1.17, p=0.01) for overall mortality was observed per 10 mmol/mol increase in HbA_1c. The association with CVD incidence and overall mortality was also observed in study participants without diabetes with increased HbA_1c levels (HR 1.12; 95% CI 1.01–1.25, p=0.04) and HR 1.10; 95% CI 1.01–1.20, p=0.02) respectively. HbA_1c cut-of values of 39.9 mmol/mol (5.8%), 36.6 mmol/mol (5.5%), and 38.8 mmol/mol (5.7%) for cardiovascular mortality, CVD incidence, and overall mortality, showed also an increased risk.<p> <p>Conclusions: HbA_1c is independently associated with cardiovascular mortality, overall mortality and cardiovascular disease in the general European population. A mostly monotonically increasing relationship was observed between HbA_1c levels and outcomes. Elevated HbA_1c levels were associated with cardiovascular disease incidence and overall mortality in participants without diabetes underlining the importance of HbA_1c levels in the overall population.