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Glycated Hemoglobin, Prediabetes, and the Links to Cardiovascular Disease: Data From UK Biobank
Claire Welsh1, Paul Welsh1, Carlos A Celis-Morales1
1Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, U.K.
Insights
Glycated hemoglobin (HbA1c) levels minimally improve cardiovascular disease (CVD) risk prediction. Managing conventional CVD risk factors is crucial for individuals with prediabetes.
Area of Science:
- Cardiology
- Endocrinology
- Preventive Medicine
Background:
- Glycated hemoglobin (HbA1c) is increasingly used for diabetes screening.
- Its utility in simultaneously improving cardiovascular disease (CVD) risk assessment alongside established scoring systems is under investigation.
Purpose of the Study:
- To evaluate if HbA1c measurement can enhance CVD risk prediction using QRISK3, ACC/AHA, and SCORE models.
- To assess the association between HbA1c levels, prediabetes, undiagnosed diabetes, and incident CVD.
Main Methods:
- Utilized UK Biobank data from 357,833 participants without baseline CVD or known diabetes.
- Employed Cox models to assess HbA1c associations with CVD, adjusting for classical risk factors.
- Determined predictive utility using C-index and net reclassification index (NRI).
Main Results:
- Incident CVD occurred in 12,877 participants over 8.9 years.
- Prediabetes and undiagnosed diabetes showed higher unadjusted CVD risk (HR 1.83 and 2.26, respectively).
- After adjustment, HbA1c added minimally to CVD risk prediction models (e.g., QRISK3 C-index increase of 0.0004).
Conclusions:
- The elevated unadjusted CVD risk in prediabetes is primarily linked to conventional risk factors.
- HbA1c offers minimal improvement to cardiovascular risk prediction.
- Intensified management of conventional cardiovascular risk factors is recommended for individuals with prediabetes.
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.