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

• Published in: Cardiovascular diabetology Vol. 20; no. 1; pp. 1 - 13
• Main Authors: Sinning, Christoph, Makarova, Nataliya, Völzke, Henry, Schnabel, Renate B., Ojeda, Francisco, Dörr, Marcus, Felix, Stephan B., Koenig, Wolfgang, Peters, Annette, Rathmann, Wolfgang, Schöttker, Ben, Brenner, Hermann, Veronesi, Giovanni, Cesana, Giancarlo, Brambilla, Paolo, Palosaari, Tarja, Kuulasmaa, Kari, Njølstad, Inger, Mathiesen, Ellisiv Bøgeberg, Wilsgaard, Tom, Blankenberg, Stefan, Söderberg, Stefan, Ferrario, Marco M., Thorand, Barbara
• Format: Journal Article
• Language: English
• Published: London BioMed Central 15.11.2021; BMC
• Subjects: Age; Angina pectoris; Angiology; BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe); Biomarkers; Blood pressure; Cardiology; Cardiovascular disease; Cardiovascular diseases; Cardiovascular risk; Cholesterol; Community medicine, Social medicine: 801; Computer centers; Diabetes; Diabetes mellitus; Glucose; Glycated hemoglobin A1c (HbA1c); Health sciences: 800; Heart attacks; Heart failure; Helsefag: 800; Hemoglobin; High density lipoprotein; Medical disciplines: 700; Medicine; Medicine & Public Health; Medisinske Fag: 700; MORGAM (MONICA Risk Genetics Archiving and Monograph); Mortality; Original Investigation; Population; Population studies; Risk assessment; Risk factors; Samfunnsmedisin, sosialmedisin: 801; Stroke; VDP; Italy; Sweden; Norway; Europe; Germany; BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe); HbA; Mortality; Cardiovascular risk; Biomarkers; ); MORGAM (MONICA Risk Genetics Archiving and Monograph); Glycated hemoglobin A
• ISSN: 1475-2840; 1475-2840
• DOI: 10.1186/s12933-021-01413-4

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. 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). Results Kaplan–Meier curves showed higher event rates with increasing HbA 1c levels (log-rank-test: p < 0.001). Cox regression analysis revealed significant 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% confidence 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-off 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. 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.