Copeptin in cardiovascular disease and dysglycemia

Background: The impaired prognosis in patients with cardiovascular disease (CVD) and dysglycemia is not fully explained by traditional risk markers, among them hyperglycemia and hyperlipidemia. Understanding the developmental mechanism of CVD and identifying potential biomarkers are important parts in attempts to reduce cardiovascular mortality and morbidity in people with and without dysglyemia. The overall aim was to study biomarkers, in particular copeptin, in hopes of shedding light on the reasons for this association. Copeptin, a marker of vasopressin release, has been suggested to be involved in both the development of CVD and dysglycaemia. Aims: The general aims were to evaluate copeptin levels in relation to CVD and dysglycemia by studying: 1. the association between copeptin and Insulin-like Growth Factor Binding Protein-1 (IGBFP-1) and the development of levels over time in patients with acute myocardial infarction (MI) and type 2 diabetes mellitus (T2DM) (Study I) 2. the copeptin levels and their prognostic importance in patients with acute MI and newly detected glucose abnormalities (Study II) 3. the copeptin levels beyond the acute phase of MI, whether they differ between known and unknown MI and to explore the prognostic implications of copeptin in relation to markers of stress and heart failure (Study III) 4. whether copeptin is associated with early manifestations of atherosclerosis and the prognostic impact of copeptin in individuals without previous MI (Study IV) Acute MI and T2DM. Copeptin and IGFBP-1 were analyzed in patients with acute MI and known T2DM (median age 70 years; men 68%), measured at hospital admission (n=393) and discharge (n=309) and three months later (n=288). The primary outcome was cardiovascular events (CVE) after 2.5 years of follow up. The copeptin-levels were 21.8 pmol/L (median) at admission, 8.5 pmol/L at discharge and 8.4 pmol/L three months later. IGFBP-1 increased over time. Copeptin and IGFBP-1 correlated with each other at all time points. Copeptin, not IGBFP-1, remained a predictor for CVE at all time points in adjusted Cox-regression analysis. Acute MI and newly discovered glucose abnormalities. Copeptin was analyzed in patients (n=166) with acute MI without previously known glucose abnormalities (median age 64 years; 70% men) and in age and gender matched controls (n=168). Based on an oral glucose tolerance test the participants were classified as having normal (NGT) or abnormal glucose tolerance (AGT). The primary outcome was total mortality. The copeptin levels were higher in patients (median 10.5 pmol/L) than for controls (5.9 pmol/L; p<0.01). Patients with AGT had higher copeptin levels than those with NGT (p