@article{9c4b96e4fb8141a19cb16acc2fc4be9e,
title = "Glycated hemoglobin, prediabetes, and the links to cardiovascular disease: Data from UK Biobank",
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 un-diagnosed 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-index0.7392) 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.",
author = "Claire Welsh and Paul Welsh and Celis-Morales, {Carlos A.} and Mark, {Patrick B.} and Daniel Mackay and Nazim Ghouri and Ho, {Fredrick K.} and Ferguson, {Lyn D.} and Rosemary Brown and James Lewsey and Cleland, {John G.} and Gray, {Stuart R.} and Lyall, {Donald M.} and Anderson, {Jana J.} and Jhund, {Pardeep S.} and Pell, {Jill P.} and McGuire, {Darren K.} and Gill, {Jason M.R.} and Naveed Sattar",
note = "Funding Information: Acknowledgments. This research was con ducted using the UK Biobank resource. The authors thank the participants of the UK Biobank. The work was performed under UK Biobank project number 9310. The authors thank Liz Coyle (University of Glasgow) for her excellent assistance in the preparation of this article. Funding. The work in this study was supported by a grant from Chest, Heart and Stroke Association Scotland (Res16/A165) and by the British Heart Foundation Research Excellence Award (RE/18/6/34217). Funding Information: The funders played no role in developing the analysis plan, conducting the analysis, or writing of the manuscript. Duality of Interest. D.K.M. reports personal fees from Boehringer Ingelheim, Janssen Research and Development LLC, Sanofi US, Merck Sharp and Dohme Corp., Merck & Co, Eli Lilly and Company, Novo Nordisk, GlaxoSmithKline, AstraZeneca, Lexicon, Eisai Inc., Esperion, Metavant, Pfizer, Afimmune, and Applied Therapeutics. N.S. has consulted for Amgen, AstraZeneca, Boehringer Ingelheim, Eli Lilly, Janssen, Napp, Novo Nordisk, Pfizer, and Sanofi and received grant support from Boehringer Ingelheim outside the submitted work. No other potential conflicts of interest relevant to this article were reported. Author Contributions. C.W. and P.W. wrote the first draft of the manuscript, which was edited by N.S. All authors were involved in data analysis and interpretation and in drafting and critically revising the manuscript, had access to study results, and reviewed and approved the final version of the manuscript for submission. P.W. and N.S. were involved in the design of the study. N.S. had final responsibility for the decision to submit for publication. N.S. is the guarantor of this work and, as such, had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Publisher Copyright: {\textcopyright} 2019 by the American Diabetes Association.",
year = "2020",
month = feb,
day = "1",
doi = "10.2337/dc19-1683",
language = "English (US)",
volume = "43",
pages = "440--445",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "2",
}