• Claire Welsh, Paul Welsh, Carlos A Celis-Morales, Patrick B Mark, Daniel Mackay, Nazim Ghouri, Fredrick K Ho, Lyn D Ferguson, Rosemary Brown, James Lewsey, John G Cleland, Stuart R Gray, Donald M Lyall, Jana J Anderson, Pardeep S Jhund, Jill P Pell, Darren K McGuire, Gill Jason M R JMR Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K., and Naveed Sattar.
• Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K.
• Diabetes Care. 2020 Feb 1; 43 (2): 440-445.

ObjectiveHbA1c 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 MethodsUK 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.ResultsIncident 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.ConclusionsThe 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.© 2019 by the American Diabetes Association.

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