Copeptin and adrenomedullin in a large cohort of patients with coronary heart disease and newly diagnosed glucose intolerance (“Silent diabetes study”)

Aims: Copeptin is used as a diagnostic marker for acute myocardial infarction, adrenomedullin as a prognostic marker for congestive heart failure. Both hormones may be involved in pathophysiology of metabolic syndrome.

Methods: We have used sera of the “Silent diabetes study” (1). Sera of 920 patients were eligible for this analysis, 777 of patients with elective coronary angiography, 143 with a acute coronary syndrome. All patients underwent an orale glucose tolerance test, patients with previous known diabetes were excluded. In coronary angiography, 59 patients had no coronary disease (no CHD), 152 patients had only stenosis <50% (beginning CHD), 164 had 1-vessel disease (1-VD), 172 had 2-vessel (2-VD) and 230 had 3-vessel disease (3-VD). In oGTT 393 patients had normal glucose tolerance (NGT), 279 had impaired glucose tolerance (IGT) and 105 had diabetes mellitus (DM). Copeptin and midregional-pro-adrenomedullin (MR-proADM) were measured in the BRAHMS-Kryptor assay (Thermo Fisher Scientific). Statistical analysis was performed by ANOVA and Kruskal-Wallis methods.

Results: Patients with no CHD had significantly lower copeptin levels (4.4±2.02pmol/l) compared to patients with beginning CHD (6.94±6.29, p=0.023), 1-VD (6.91±6.84, p=0.03), 2-VD (6.64±5.57, p=0.012) or 3-VD (8.93±10.2, p<0.0001). Differences between patient groups were not significant. Patients with 3-VD (0.71±0.27 nmol/l, p=0.0002) and beginning CHD (0.68±0.24, p=0.009) had higher ADM levels compared to no CHD patients (0.57±0.13). Both patients with DM (9.8±10.15pmol/l, p<0.0001) and IGT (8.11±9.17, p=0.0003) had higher copeptin levels compared to patients with NGT (6.1±5.91). There was no significant difference between patients with DM and IGT. Patients with NGT had lower MR-proADM levels (0.63±0.17 nmol/l) compared to patients with IGT (0.71±0.29, p<0.0001) or patients with DM (0.71±0.22, p=0.005).

Discussion: Copeptin is elevated in patients with CHD compared to those with no CHD but there is no grading to the severity of CHD. MR-proADM is elevated in patients with advanced CHD (3-VD) and in beginning CHD compared to no CHD patients. Both marker are elevated in patients with IGT and previously unknown DM. The early elevation of both hormones may argue for an early involvement in the development of metabolic-vascular syndrome.

(1) Doerr et al. Diabetologia 2011, 54: 2923–2930