Markers of subclinical cardiac disease associate with thresholds for pre-diabetes and diabetes in the general population: data from the ACE 1950 Study

Abstract

Abstract Background Diabetes mellitus (DM) is associated with increased risk of left ventricular (LV) remodeling and incident heart failure. However, the associations between dysglycemia and subclinical cardiac disease in middle-aged subjects recruited from the general population are not established. Purpose To assess the associations of dysglycemia and diagnostic DM thresholds with indices of subclinical cardiac injury and dysfunction in the general population. Methods We included participants born in 1950 from the Akershus Cardiac Examination 1950 Study with available biomarker measurements (n=3,688). We used regression models and restricted cubic splines (knots selected from lowest Akaike Information Criterion) to assess the association between glycated hemoglobin A1c (HbA1c) and cardiac troponin T (cTnT), N-terminal pro-B-type natriuretic peptide (NT-proBNP), C-reactive protein (CRP), and echocardiographic parameters. We classified participants with self-reported diagnosis of DM or HbA1c ≥6.5% (48 mmol/L) as DM, participants with HbA1c 5.7–6.5% as pre-DM, and participants with HbA1c <5.7% (39 mmol/mol) as no-DM. Results Mean age was 63.9±0.7 years, mean body mass index (BMI) 27.2±4.4 kg/m2, and 1,795 participants (49%) were women. DM was classified in 380 participants (10%), pre-DM in 1,630 participants (44%) and no-DM in 1,678 participants (46%). Increasing HbA1c concentrations were associated with younger age, male sex, obesity, hypercholesterolemia, hypertension, and established coronary artery disease in adjusted analyses. In models adjusted for age, sex, BMI, smoking, hypertension, atrial fibrillation, coronary artery disease and renal function, greater HbA1c was associated with increasing logcTnT and logCRP concentrations, decreasing logNT-proBNP concentrations and worse global longitudinal strain and E/e' (p<0.001 for all). LV mass index was not associated with HbA1c in adjusted models (p=0.23). All five associations were non-linear in the total study population (p<0.001 for non-linearity for all) with robust, linear associations in the pre-DM range of HbA1c, also in adjusted models, and attenuated associations in the no-DM and DM range (Figure 1). Conclusion We found robust, linear associations between HbA1c and indices of subclinical cardiac injury and dysfunction among participants classified as pre-DM, while associations were more attenuated among participants with DM. Preventive measures for cardiovascular disease should be considered also in patients with dysglycemia and HbA1c below the established cutoff for DM. Figure 1. P-values for overall trend Funding Acknowledgement Type of funding source: Public hospital(s). Main funding source(s): Akserhus University Hospital