Interleukin-6 and activin A are independently associated with cardiovascular events and mortality in type 2 diabetes: the prospective Asker and Bærum Cardiovascular Diabetes (ABCD) cohort study
1 Department of Medical Research, Bærum Hospital, Vestre Viken Hospital Trust, N-1309 Rud, Bærum, Norway
2 Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
3 K.G.Jebsen Cardiac Research Centre and Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Oslo, Norway
4 Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
5 Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
6 Institute of Clinical Medicine, University of Oslo, Oslo, Norway
7 Unit of Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
8 Department of Endocrinology, Obesity and Preventive medicine, Oslo University Hospital Aker, Oslo, Norway
Cardiovascular Diabetology 2013, 12:126 doi:10.1186/1475-2840-12-126Published: 30 August 2013
Novel and robust cardiovascular (CV) markers are needed to improve CV morbidity and mortality risk prediction in type 2 diabetes (T2D). We assessed the long term predictive value of 4 novel CV risk markers for major CV events and mortality.
We included patients with T2D who had cytokines (interleukin [IL]-6 and activin A [actA]), a maximum stress ECG test (evaluated by the normalization pattern in early recovery phase) and echocardiography (evaluated by a measure of the left ventricular filling pressure - E/Em) assessed at baseline. The primary endpoint was time to first of any of the following events: myocardial infarction, stroke, hospitalization for unstable angina pectoris and death. All outcomes were adjudicated by independent experts. We used Cox proportional hazard modeling, Harrell C-statistic and the net reclassification improvement (NRI) to assess the additional value beyond conventional markers (age, gender, prior CV disease, HDL, creatinine, diastolic BP, microalbuminuria).
At baseline the study cohort (n = 135, mean age/diabetes duration/HbA1c: 59 yrs/7 yrs/7.6% [59 mmol/mol], 26% females) had moderate elevated CV risk (42% microalbuminuria, mean Framingham 10 year CV-risk 9.6%). During 8.6 yrs/1153.7 person years, 26 patients experienced 36 events. All 4 novel risk markers were significantly associated with increased risk of the primary endpoint, however, only IL-6 and actA improved C-statistic and NRI (+0.119/43.2%, +0.065/20.3% respectively) compared with the conventional CV risk factors.
IL-6 and actA may provide prognostic information on CV events and mortality in T2D beyond conventional CV risk factors.