Interleukin-6 and activin A are independently associated with cardiovascular events and mortality in type 2 diabetes: the prospective Asker and B?rum Cardiovascular Diabetes (ABCD) cohort study

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• 作者：Anne Pernille Ofstad (13)
  Lars Gullestad (14) (15)
  Elsa Orvik (13)
  Svend Aakhus (14)
  Knut Endresen (14)
  Thor Ueland (16)
  P?l Aukrust (16) (17) (18)
  Morten W Fagerland (19)
  K?re I Birkeland (20)
  Odd Erik Johansen (13)
  
• 关键词：Type 2 diabetes ; Cardiovascular event ; MACE ; Inflammatory marker ; Cardiovascular risk ; Risk prediction
• 刊名：Cardiovascular Diabetology
• 出版年：2013
• 出版时间：December 2013
• 年：2013
• 卷：12
• 期：1
• 全文大小：307KB
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• 作者单位：Anne Pernille Ofstad (13)
  Lars Gullestad (14) (15)
  Elsa Orvik (13)
  Svend Aakhus (14)
  Knut Endresen (14)
  Thor Ueland (16)
  P?l Aukrust (16) (17) (18)
  Morten W Fagerland (19)
  K?re I Birkeland (20)
  Odd Erik Johansen (13)
  
  13. Department of Medical Research, B?rum Hospital, Vestre Viken Hospital Trust, N-1309 Rud, B?rum, Norway
  14. Department of Cardiology, Oslo University Hospital Rikshospitalet, Oslo, Norway
  15. K.G.Jebsen Cardiac Research Centre and Center for Heart Failure Research, Faculty of Medicine, University of Oslo, Oslo, Norway
  16. Research Institute of Internal Medicine, Oslo University Hospital Rikshospitalet, Oslo, Norway
  17. Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital Rikshospitalet, Oslo, Norway
  18. Institute of Clinical Medicine, University of Oslo, Oslo, Norway
  19. Unit of Biostatistics and Epidemiology, Oslo University Hospital, Oslo, Norway
  20. Department of Endocrinology, Obesity and Preventive medicine, Oslo University Hospital Aker, Oslo, Norway
  

文摘

Background 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. Methods 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). Results At baseline the study cohort (n--35, 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. Conclusions IL-6 and actA may provide prognostic information on CV events and mortality in T2D beyond conventional CV risk factors. Trial registration ClinicalTrials.gov: NCT00133718