HbA_1c levels in non-diabetic older adults – No J-shaped associations with primary cardiovascular events, cardiovascular and all-cause mortality after adjustment for confounders in a meta-analysis of individual participant data from six cohort studies

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Background:
To determine the shape of the associations of HbA_1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations.

Methods:
The associations of HbA_1c with all-cause mortality, cardiovascular mortality and primary cardiovascular events (myocardial infarction or stroke) were assessed in non-diabetic subjects ≥50 years from six population-based cohort studies from Europe and the USA and meta-analyzed. Very low, low, intermediate and increased HbA_1cwere defined as <5.0, 5.0 to <5.5, 5.5 to <6.0 and 6.0 to <6.5 % (equals <31, 31 to <37, 37 to <42 and 42 to <48 mmol/mol), respectively, and low HbA_1c was used as reference in Cox proportional hazards models.

Results:
Overall, 6,769 of 28,681 study participants died during a mean follow-up of 10.7 years, of whom 2,648 died of cardiovascular disease. Furthermore, 2,493 experienced a primary cardiovascular event. A linear association with primary cardiovascular events was observed. Adjustment for cardiovascular risk factors explained about 50 % of the excess risk and attenuated hazard ratios (95 % confidence interval) for increased HbA_1c to 1.14 (1.03–1.27), 1.17 (1.00–1.37) and 1.19 (1.04–1.37) for all-cause mortality, cardiovascular mortality and cardiovascular events, respectively. The six cohorts yielded inconsistent results for the association of very low HbA_1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA_1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA_1c levels with mortality outcomes were identified: race/ethnicity; alcohol consumption; BMI; as well as biomarkers of iron deficiency anemia and liver function. Associations for very low HbA_1c levels lost statistical significance in this cohort after adjusting for these confounders.

Conclusions:
A linear association of HbA_1c levels with primary cardiovascular events was observed. For cardiovascular and all-cause mortality, the observed small effect sizes at both the lower and upper end of HbA_1c distribution do not support the notion of a J-shaped association of HbA_1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results.

KeywordsGlycated hemoglobin, Cardiovascular disease, Myocardial infarction, Stroke, Mortality, Cohort study, Meta-analysis

Autoři: Ben Schöttker ^1,2*; W. Rathmann ³; C. Herder ^4,5; B. Thorand ⁶; T. Wilsgaard ⁷; I. Njølstad ⁷; G. Siganos ⁸; E. B. Mathiesen ⁸; K. U. Saum ¹; A. Peasey ⁹; E. Feskens ¹⁰; P. Boffetta ^11,12; A. Trichopoulou ¹²; K. Kuulasmaa ¹³; F. Kee ¹⁴; H. Brenner ¹; On Behalf Of The Chances Group
Působiště autorů: Division of Clinical Epidemiology and Aging Research, German Cancer Research Center, Im Neuenheimer Feld 1, 691 0 Heidelberg, Germany. ¹; Network Aging Research, University of Heidelberg, Bergheimer Straße 20, 6911 Heidelberg, Germany. ²; Institute for Biometrics and Epidemiology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf`m Hennekamp 6 , 022 Düsseldorf, Germany. ³; Institute for Clinical Diabetology, German Diabetes Center, Leibniz Center for Diabetes Research at Heinrich Heine University Düsseldorf, Auf`m Hennekamp 6 , 4022 Düsseldorf, Germany. ⁴; German Center for Diabetes Research (DZD), Ingolstädter Landstraße 1, 857 4 München-Neuherberg, Germany. ⁵; Institute of Epidemiology II, Helmholtz Zentrum München, German Research Center for Environmental Health, Postfach 112 , Neuherberg, Germany. ⁶; Epidemiology of Chronic Diseases Research Group, Department of Community Medicine, UiT The Arctic University of Norway, 037 Tromsø, Norway. ⁷; Brain and Circulation Research Group, Department of Clinical Medicine, UiT The Arctic University of Norway, 037 Tromsø, Norway. ⁸; Department of Epidemiology and Public Health, University College London, 1–19 Torrington Place, London WC1E 6BT, UK. ⁹; Division of Human Nutrition, Wageningen University, PO Box 8 9, 6700 EV Wageningen, The Netherlands. ¹⁰; Institute for Translational Epidemiology and The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ¹¹; Hellenic Health Foundation, Kaisareias and Alexandroupoleos, Athens 11527, Greece. ¹²; National Institute for Health and Welfare (THL), PO Box 30, FI-00271 Helsinki, Finland. ¹³; UKCRC Centre of Excellence for Public Health, Queen’s University Belfast, Belfast, Northern Ireland. ¹⁴
Vyšlo v časopise: BMC Medicine 2016, 14:26
Kategorie: Research article
prolekare.web.journal.doi_sk: https://doi.org/10.1186/s12916-016-0570-1

© 2016 Schöttker et al. Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. 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.
The electronic version of this article is the complete one and can be found online at: https://bmcmedicine.biomedcentral.com/articles/10.1186/s12916-016-0570-1

Souhrn

Background:
To determine the shape of the associations of HbA_1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations.

Zdroje

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