Association of glycated hemoglobin A <sub>1c</sub> levels with cardiovascular outcomes in the general population: results from the BiomarCaRE (Biomarker for Cardiovascular Risk Assessment in Europe) consortium

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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.

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.

Supplementary Information

The online version contains supplementary material available at 10.1186/s12933-021-01413-4.

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Author and article information

Contributors

Christoph Sinning:

ORCID: http://orcid.org/0000-0002-7331-8840

c.sinning@uke.de

Journal

Journal ID (nlm-ta): Cardiovasc Diabetol

Journal ID (iso-abbrev): Cardiovasc Diabetol

Title: Cardiovascular Diabetology

Publisher: BioMed Central (London )

ISSN (Electronic): 1475-2840

Publication date (Electronic): 15 November 2021

Publication date PMC-release: 15 November 2021

Publication date Collection: 2021

Volume: 20

Electronic Location Identifier: 223

Affiliations

[1 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Department of Cardiology, , University Heart & Vascular Center Hamburg, ; Martinistr. 52, 20246 Hamburg, Germany

[2 ]GRID grid.452396.f, ISNI 0000 0004 5937 5237, German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, ; Hamburg, Germany

[3 ]GRID grid.5603.0, Department of Study of Health in Pomerania/Clinical-Epidemiological Research, Institute for Community Medicine, , University Medicine Greifswald, ; Greifswald, Germany

[4 ]GRID grid.452396.f, ISNI 0000 0004 5937 5237, German Center for Cardiovascular Research (DZHK), Partner Site Greifswald, ; Greifswald, Germany

[5 ]GRID grid.5603.0, Department of Internal Medicine B, , University of Medicine Greifswald, ; Greifswald, Germany

[6 ]GRID grid.6936.a, ISNI 0000000123222966, German Heart Center Munich, , Technical University, ; Munich, Germany

[7 ]GRID grid.452396.f, ISNI 0000 0004 5937 5237, German Center for Cardiovascular Research (DZHK), Partner Site Munich Heart Alliance, ; Munich, Germany

[8 ]GRID grid.6582.9, ISNI 0000 0004 1936 9748, Institute of Epidemiology and Medical Biometry, , University of Ulm, ; Ulm, Germany

[9 ]GRID grid.4567.0, ISNI 0000 0004 0483 2525, German Research Center for Environmental Health, Institute of Epidemiology, , Helmholtz Zentrum München, ; Neuherberg, Germany

[10 ]GRID grid.411327.2, ISNI 0000 0001 2176 9917, Institute for Biometrics and Epidemiology, German Diabetes Center, , Leibniz Institute for Diabetes Research at Heinrich Heine University, ; Düsseldorf, Germany

[11 ]GRID grid.7497.d, ISNI 0000 0004 0492 0584, Division of Clinical Epidemiology and Ageing Research, , German Cancer Research Center, ; Heidelberg, Germany

[12 ]GRID grid.7700.0, ISNI 0000 0001 2190 4373, Network Aging Research, , University of Heidelberg, ; Heidelberg, Germany

[13 ]GRID grid.18147.3b, ISNI 0000000121724807, Department of Medicine and Surgery, EPIMED Research Center, , University of Insubria at Varese, ; Varese, Italy

[14 ]GRID grid.7563.7, ISNI 0000 0001 2174 1754, Department of Medicine and Surgery, , University of Milano-Bicocca, ; Milan, Italy

[15 ]GRID grid.14758.3f, ISNI 0000 0001 1013 0499, Finnish Institute for Health and Welfare, Division Public Health and Welfare, ; Helsinki, Finland

[16 ]GRID grid.10919.30, ISNI 0000000122595234, Department of Community Medicine, , UiT The Arctic University of Norway, ; Tromsö, Norway

[17 ]GRID grid.10919.30, ISNI 0000000122595234, Brain and Circulation Research Group, , UiT The Arctic University of Norway, ; Tromsö, Norway

[18 ]GRID grid.412244.5, ISNI 0000 0004 4689 5540, Neurological Department, , University Hospital of North Norway, ; Tromsö, Norway

[19 ]GRID grid.12650.30, ISNI 0000 0001 1034 3451, Department of Public Health and Clinical Medicine, , Umeå University, ; Umeå, Sweden

[20 ]GRID grid.452622.5, German Center for Diabetes Research (DZD), ; Munich, Neuherberg, Germany

[21 ]GRID grid.13648.38, ISNI 0000 0001 2180 3484, Institute for Health Services Research in Dermatology and Nursing (IVDP), , University Medical Center Hamburg-Eppendorf, ; Hamburg, Germany

Author information

Christoph Sinning http://orcid.org/0000-0002-7331-8840

Barbara Thorand http://orcid.org/0000-0002-8416-6440

Article

Publisher ID: 1413

DOI: 10.1186/s12933-021-01413-4

PMC ID: 8594211

PubMed ID: 34781939

SO-VID: 75f4fa3c-89d1-4949-b92b-22ca71665bc4

License:

Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

History

Date received : 2 August 2021

Date accepted : 4 November 2021

Funding

Funded by: eu projects morgam

Award ID: BMH4-CT98-3183

Funded by: genomeutwin

Award ID: QLG2-CT-2002-01254

Funded by: engage

Award ID: HEALTH-F4-2007-201413

Funded by: chances

Award ID: HEALTH-F3-2010-242244

Funded by: biomarcare

Award ID: HEALTH-F2-2011-278913

Funded by: eucanshare

Award ID: No. 825903

Funded by: affect-eu

Award ID: No. 847770

Funded by: medical research council, london

Award ID: No. 80983

Custom metadata

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: biomarkers,glycated hemoglobin a1c (hba1c),cardiovascular risk,mortality,biomarcare (biomarker for cardiovascular risk assessment in europe),morgam (monica risk genetics archiving and monograph)

Data availability:

ScienceOpen disciplines: Endocrinology & Diabetes

Keywords: biomarkers, glycated hemoglobin a1c (hba1c), cardiovascular risk, mortality, biomarcare (biomarker for cardiovascular risk assessment in europe), morgam (monica risk genetics archiving and monograph)