Prediabetes Defined by First Measured HbA1c Predicts Higher Cardiovascular Risk Compared With HbA1c in the Diabetes Range: A Cohort Study of Nationwide Registries

Objective: To assess the risk of major adverse cardiovascular events (MACE), all-cause mortality, and initiation of medical treatment in subjects with prediabetes according to first-time measured HbA1c.

Research design and methods: Through registry databases, we identified 326,305 Danish patients with a first HbA1c between 40-51 mmol/mol (5.8-6.8%) from 2011 to 2017. After exclusion of patients with prior disease, 84,678 patients were followed 12 months after first HbA1c measurement. Cox regression models were used to estimate hazard ratios (HRs) of MACE and standardized absolute risks. Cumulative incidences were used to analyse initiation of glucose-lowering, anti-hypertensive, cholesterol-lowering and anti-thrombotic medication.

Results: The 12-months risk of MACE and all-cause mortality increased gradually with increasing HbA1c until 47 mmol/mol (6.5%). Compared to HbA1c of 40-41 mmol/mol (5.8-5.9%), subjects with HbA1c of 46-47 mmol/mol (6.4-6.5%) had a 0.79% (95% CI 0.33-1.24) higher standardized absolute risk and a HR of 2.21 (95% CI 1.67-2.92) of MACE. Patients with a HbA1c of 48-49 mmol/mol (6.5-6.6%) had a -0.09% (95% CI -0.35-0.52) lower absolute risk and a HR of 1.33 (95% CI 0.87-2.05) of MACE. Initiation of medication was significantly lower among patients with HbA1c of 46-47 mmol/mol (6.4-6.5%) compared to patients with HbA1c of 48-49 mmol/mol (6.5-6.6%).

Conclusion: In the Danish population screened for diabetes with HbA1c, the highest risk of MACE and all-cause mortality was found in subjects with HbA1c just below the diagnostic threshold for diabetes. Our results highlight the need for increased focus on the treatment of cardiovascular risk-factors in subjects with prediabetes.