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Glycated Hemoglobin, Prediabetes, and the Links to Cardiovascular Disease: Data From UK Biobank

Lookup NU author(s): Dr Claire WelshORCiD


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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.

Publication metadata

Author(s): Welsh CE, Welsh P, Celis-Morales CA, Mark PB, Mackay D, Ghouri N, Hi FK, Ferguson LD, Brown R, Lewsey J, Cleland JG, Gray SR, Lyall DM, Anderson JJ, Jhund PS, Pell JP, McGuire DK, Gill JMR, Sattar N

Publication type: Article

Publication status: Published

Journal: Diabetes Care

Year: 2020

Volume: 43

Issue: 2

Pages: 440-445

Print publication date: 20/01/2020

Online publication date: 18/12/2019

Acceptance date: 27/10/2019

ISSN (print): 0149-5992

ISSN (electronic): 1935-5548

Publisher: American Diabetes Association


DOI: 10.2337/dc19-1683


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