Prediabetes Defined by First Measured HbA Predicts Higher Cardiovascular Risk Compared With HbA 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 HbA.

RESEARCH DESIGN AND METHODS

Through registry databases, we identified 326,305 Danish patients with a first HbA between 40 and 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 HbA measurement. Cox regression models were used to estimate hazard ratios (HRs) of MACE and standardized absolute risks. Cumulative incidences were used to analyze initiation of glucose-lowering, antihypertensive, cholesterol-lowering, and antithrombotic medication.

RESULTS

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

CONCLUSIONS

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