Dysglycaemia screening and its prognostic impact in patients with coronary artery disease: experiences from the EUROASPIRE IV and V cohort studies

Abstract

Background: Glucose perturbations can be detected by fasting plasma glucose (FPG), HbA_1c, and the oral glucose tolerance test (OGTT). The highest yield is provided by OGTT. HbA_1c is considered more practical. We compare the diagnostic and predictive performance of these glycaemic indicators based on combined data from the EUROASPIRE IV (EAIV) and V (EAV) studies.

Methods: This cohort study was conducted in 79 centres in 24 European countries (EAIV) and 131 centres in 27 European countries (EAV). Eligible patients were aged 18-80 years, did not have diabetes, and were diagnosed with coronary artery disease 6-36 months (EAIV) or 6-24 months (EAV) before the investigation. Patients were investigated with OGTT (FPG and 2 h post-load glucose [2-hPG]) and HbA_1c. Follow-up of subsequent cardiovascular events was done by means of a questionnaire at least 1 year after the baseline investigation. Analyses were done in patients with both OGTT and HbA_1c data available. Outcome analysis in these patients was restricted to those with valid follow-up data available.

Findings: 16 259 patients were interviewed in EAIV (2012-13) and EAV (2016-17). 8364 patients had both OGTT and HbA_1C data and were included in the analysis population (3932 in EAIV and 4432 in EAV). Information on cardiovascular events was available in 7892 patients. Follow-up was for a median 1·6 years (IQR 1·2-2·0). The average patient age was 63·3 years (SD 9·8), and 6346 (75·9%) of 8364 patients were men. At baseline, 1856 (22·5%) of 8263 patients were determined to have newly detected type 2 diabetes using OGTT alone, compared with 346 (4·2%) using HbA_1c alone. New dysglycaemia, defined as newly detected type 2 diabetes or impaired glucose tolerance (IGT), was present in 3896 (47·1%) of the patients according to 2hPG. 2hPG 9 mmol/L or greater (162 mg/dL, adjusted hazard ratio [aHR] 1·58; 95% CI 1·27-1·95, p<0·0001), and HbA_1c 5·9% or greater (41 mmol/mol, aHR 1·48, 1·19-1·84; p=0·0010) were the strongest predictors of cardiovascular events, while FPG did not predict. A multivariable model showed that the effect of HbA_1c on cardiovascular events was mainly explained by 2hPG (aHR for 1 unit increase in HbA_1c 1·13, 0·98-1·30; p=0·11; and aHR for 1 unit increase in Ln[2hPG] 1·37, 1·08-1·74; p=0·0042).

Interpretation: 2hPG appears better than HbA_1c in detecting dysglycaemia and predicting its impact on future cardiovascular events in patients with coronary artery disease and should be recommended as the primary screening tool.

Funding: Swedish Heart-Lung Foundation, Region Stockholm (ALF), the Erling Persson Foundation, the Baltic Child Foundation.