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

Cardiovasc Diabetol. 2013 Aug 30:12:126. doi: 10.1186/1475-2840-12-126.

Abstract

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 = 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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Activins / blood*
  • Aged
  • Angina, Unstable / blood
  • Angina, Unstable / mortality
  • Biomarkers / blood
  • C-Reactive Protein / analysis
  • Cardiovascular Diseases / blood*
  • Cardiovascular Diseases / diagnosis
  • Cardiovascular Diseases / mortality*
  • Cardiovascular Diseases / physiopathology
  • Chi-Square Distribution
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / diagnosis
  • Diabetes Mellitus, Type 2 / mortality*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Disease Progression
  • Echocardiography, Stress
  • Electrocardiography
  • Female
  • Hospitalization
  • Humans
  • Interleukin-6 / blood*
  • Logistic Models
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Myocardial Infarction / blood
  • Myocardial Infarction / mortality
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Prospective Studies
  • Risk Factors
  • Stroke / blood
  • Stroke / mortality
  • Time Factors
  • Ventricular Function, Left
  • Ventricular Pressure

Substances

  • Biomarkers
  • IL6 protein, human
  • Interleukin-6
  • activin A
  • Activins
  • C-Reactive Protein

Associated data

  • ClinicalTrials.gov/NCT00133718