Inflammatory Biomarkers Interleukin-6 and C-Reactive Protein and Outcomes in Stable Coronary Heart Disease: Experiences From the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) Trial.
Held C, White HD, Stewart RAH, Budaj A, Cannon CP, Hochman JS, Koenig W, Siegbahn A, Steg PG, Soffer J, Weaver WD, Ostlund O, Wallentin L. Inflammatory biomarkers interleukin-6 and c-reactive protein and outcomes in stable coronary heart disease: Experiences from the stability (stabilization of atherosclerotic plaque by initiation of darapladib therapy) trial. J Am Heart Assoc. Oct 24 2017;6(10)
J Am Heart Assoc
BACKGROUND: Evaluation of cardiovascular prognosis in patients with stable coronary heart disease is based on clinical characteristics and biomarkers indicating dysglycemia, dyslipidemia, renal dysfunction, and possibly cardiac dysfunction. Inflammation plays a key role in atherosclerosis, but the association between inflammatory biomarkers and clinical outcomes is less studied in this population.
METHODS AND RESULTS: Overall, 15 828 patients with coronary heart disease in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trial were randomized to treatment with darapladib or placebo and observed for a median of 3.7 years. In 14 611 patients, levels of interleukin-6 (IL-6) and high-sensitivity C-reactive protein were measured in plasma samples: median levels were 2.1 (interquartile range, 1.4-3.2) ng/L and 1.3 (interquartile range, 0.6-3.1) mg/L, respectively. Associations between continuous levels or quartile groups and adjudicated outcomes were evaluated by spline graphs and Cox regression adjusted for clinical factors and cardiovascular biomarkers. IL-6 was associated with increased risk of major adverse cardiovascular events (quartile 4 versus quartile 1 hazard ratio [HR], 1.60; 95% confidence interval [CI], 1.30-1.97;
CONCLUSIONS: IL-6, an upstream inflammatory marker, was independently associated with the risk of major adverse cardiovascular events, cardiovascular and all-cause mortality, myocardial infarction, heart failure, and cancer mortality in patients with stable coronary heart disease. IL-6 might reflect a pathophysiological process involved in the development of these events.
CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00799903.
Medical Subject Headings
Aged; Benzaldehydes; C-Reactive Protein; Cause of Death; Coronary Disease; Female; Humans; Inflammation Mediators; Interleukin-6; Kaplan-Meier Estimate; Male; Middle Aged; Multivariate Analysis; Neoplasms; Oximes; Phospholipase A2 Inhibitors; Plaque, Atherosclerotic; Proportional Hazards Models; Prospective Studies; Risk Factors; Time Factors; Treatment Outcome