Glycated hemoglobin, prediabetes and the links to cardiovascular disease: data from UK Biobank

Welsh, C. et al. (2020) Glycated hemoglobin, prediabetes and the links to cardiovascular disease: data from UK Biobank. Diabetes Care, 43(2), pp. 440-445. (doi: 10.2337/dc19-1683) (PMID:31852727)

Abstract

OBJECTIVE: HbA1c levels are increasingly measured in screening for diabetes; we investigated whether HbA1c may simultaneously improve cardiovascular disease (CVD) risk assessment, using QRISK3, American College of Cardiology/American Heart Association (ACC/AHA), and Systematic COronary Risk Evaluation (SCORE) scoring systems. RESEARCH DESIGN AND METHODS: UK Biobank participants without baseline CVD or known diabetes (n = 357,833) were included. Associations of HbA1c with CVD was assessed using Cox models adjusting for classical risk factors. Predictive utility was determined by the C-index and net reclassification index (NRI). A separate analysis was conducted in 16,596 participants with known baseline diabetes. RESULTS: Incident fatal or nonfatal CVD, as defined in the QRISK3 prediction model, occurred in 12,877 participants over 8.9 years. Of participants, 3.3% (n = 11,665) had prediabetes (42.0–47.9 mmol/mol [6.0–6.4%]) and 0.7% (n = 2,573) had undiagnosed diabetes (≥48.0 mmol/mol [≥6.5%]). In unadjusted models, compared with the reference group (<42.0 mmol/mol [<6.0%]), those with prediabetes and undiagnosed diabetes were at higher CVD risk: hazard ratio (HR) 1.83 (95% CI 1.69–1.97) and 2.26 (95% CI 1.96–2.60), respectively. After adjustment for classical risk factors, these attenuated to HR 1.11 (95% CI 1.03–1.20) and 1.20 (1.04–1.38), respectively. Adding HbA1c to the QRISK3 CVD risk prediction model (C-index 0.7392) yielded a small improvement in discrimination (C-index increase of 0.0004 [95% CI 0.0001–0.0007]). The NRI showed no improvement. Results were similar for models based on the ACC/AHA and SCORE risk models. CONCLUSIONS: The near twofold higher unadjusted risk for CVD in people with prediabetes is driven mainly by abnormal levels of conventional CVD risk factors. While HbA1c adds minimally to cardiovascular risk prediction, those with prediabetes should have their conventional cardiovascular risk factors appropriately measured and managed.

• Item Type: Articles
• Additional Information: The work in this study was supported by a grant from Chest, Heart, and Stroke Association Scotland [Res16/A165].
• Status: Published
• Refereed: Yes
• Glasgow Author(s) Enlighten ID: Gill, Professor Jason and Ho, Dr Frederick and Ghouri, Dr Nazim and Anderson, Dr Jana and Jhund, Professor Pardeep and Mackay, Professor Daniel and Welsh, Dr Claire and Brown, Miss Rosemary and Ferguson, Dr Lyn and Mark, Professor Patrick and Welsh, Professor Paul and Lewsey, Professor Jim and Celis, Dr Carlos and Gray, Professor Stuart and Pell, Professor Jill and Cleland, Professor John and Sattar, Professor Naveed and Lyall, Dr Donald
• Authors: Welsh, C., Welsh, P., Celis Morales, C. A., Mark, P., Mackay, D., Ghouri, N., Ho, F., Ferguson, L. D., Brown, R., Lewsey, J., Cleland, J. G., Gray, S. R., Lyall, D. M., Anderson, J., Jhund, P. S., Pell, J., McGuire, D. K., Gill, J. M.R., and Sattar, N.
• College/School: College of Medical Veterinary and Life Sciences > School of Cardiovascular & Metabolic Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Mental Health and Wellbeing; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Public Health; College of Medical Veterinary and Life Sciences > School of Health & Wellbeing > Robertson Centre; College of Medical Veterinary and Life Sciences > School of Medicine, Dentistry & Nursing
• Journal Name: Diabetes Care
• Publisher: American Diabetes Association
• ISSN: 0149-5992
• ISSN (Online): 1935-5548
• Published Online: 18 December 2019
• Copyright Holders: Copyright © 2019 by the American Diabetes Association
• First Published: First published in Diabetes Care 43(2):440-445
• Publisher Policy: Reproduced in accordance with the publisher copyright policy

Project Code	Award No	Project Name	Principal Investigator	Funder's Name	Funder Ref	Lead Dept
172776		Associations of blood biomarkers with cardiovascular disease and related cardiometabolic outcomes and risk prediction in the clinical setting: UK biobank	Naveed Sattar	Chest Heart and Stroke Scotland (CHSS)	Res16/A165	Institute of Cardiovascular & Medical Sciences
303944		BHF Centre of Excellence	Rhian Touyz	British Heart Foundation (BHF)	RE/18/6/34217	CAMS - Cardiovascular Science