SynthesisBMC medicine2016
HbA1c 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.
Synthesis in BMC medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Development of type 2 diabetes mellitus in people with intermediate hyperglycaemia.The Cochrane database of systematic reviews · 2018Pooled it
- Trial
- Glycemic markers and relation with arterial stiffness in Caucasian subjects of the MARK study.PloS one · 2017Trial
- Glycemic control in the context of frailty: a mortality risk assessment in older diabetic patients.Aging clinical and experimental research · 2026Article
- Interplay of glycated hemoglobin and traditional risk factors for the risk of atherosclerotic cardiovascular disease and all-cause mortality in people without diabetes.Cardiovascular diabetology · 2025Observational
- Positive Impact of Health Check-Ups and Guidance in the General Population: A Database-Based Cohort Study in Japan.AJPM focus · 2025Article
- Cardiac structure and function across the continuum of glucose metabolism.Physiological reports · 2025Article
- Machine learning-based coronary heart disease diagnosis model for type 2 diabetes patients.Frontiers in endocrinology · 2025Article
- Association between the stress-hyperglycemia ratio and all-cause mortality in community-dwelling populations: An analysis of the National Health and Nutrition Examination Survey (NHANES) 1999-2014.Journal of diabetes · 2024Article
- Hemoglobin A1c Serum Level Predicts 5-year Mortality in Patients with Cognitive Impairment.Journal of diabetes and metabolic disorders · 2023Article
- Flattening the biological age curve by improving metabolic health: to taurine or not to taurine, that' s the question.Journal of geriatric cardiology : JGC · 2023Article
- Synergistic effects of overweight/obesity and high hemoglobin A1c status on elevated high-sensitivity C-reactive protein in Chinese adults: a cross-sectional study.Frontiers in nutrition · 2023Article
- Article
- Association of glycated hemoglobin ACardiovascular diabetology · 2021Article
- Assessing the linear and non-linear association of HbADiabetologia · 2021Article
- Low HbA1c levels and all-cause or cardiovascular mortality among people without diabetes: the US National Health and Nutrition Examination Survey 1999-2015.International journal of epidemiology · 2021Article
- Choice of HbA1c threshold for identifying individuals at high risk of type 2 diabetes and implications for diabetes prevention programmes: a cohort study.BMC medicine · 2021Article
- Glycaemic markers and all-cause mortality in older adults with and without diabetes: the Atherosclerosis Risk in Communities (ARIC) study.Diabetologia · 2021Article
- Mitochondrial 8-hydroxy-2'-deoxyguanosine and coronary artery disease in patients with type 2 diabetes mellitus.Cardiovascular diabetology · 2020Article
- Comparison of the Effects of Fasting Glucose, Hemoglobin ANutrients · 2019Observational
Corrections and comments
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Authors and funding
17 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundTo determine the shape of the associations of HbA1c with mortality and cardiovascular outcomes in non-diabetic individuals and explore potential explanations.
methodsThe associations of HbA1c 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 HbA1c were 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 HbA1c was used as reference in Cox proportional hazards models.
resultsOverall, 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 HbA1c 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 HbA1c levels with the mortality outcomes and the pooled effect estimates were not statistically significant. In one cohort with a pronounced J-shaped association of HbA1c levels with all-cause and cardiovascular mortality (NHANES), the following confounders of the association of very low HbA1c 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 HbA1c levels lost statistical significance in this cohort after adjusting for these confounders.
conclusionsA linear association of HbA1c 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 HbA1c distribution do not support the notion of a J-shaped association of HbA1c levels because a certain degree of residual confounding needs to be considered in the interpretation of the results.
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