Inflammatory biomarkers and long-term outcome in young stable patients 3 months after a first myocardial infarction

Abstract

Abstract Background Inflammation is an important driver of coronary artery disease (CAD). Several circulating inflammatory biomarkers have been associated with outcome, both before and after established CAD. However, studies in established CAD have often been limited by short follow-up period or blood sampling in the acute phase of a coronary event, which introduces a bias from the inflammatory response activated during a myocardial infarction (MI). Purpose This study aimed to compare the predictive value of several inflammatory biomarkers in a population of young stable patients 3 months after a first time MI. Methods 382 men and women ≤60 years of age with a first time MI were included from three Swedish hospitals between 1996 and 2000. 383 age- and sex-matched healthy controls were recruited from the general population. Individuals with previous MI, chronic inflammatory disease, kidney disease (creatinine >200 µmol/L), diabetes mellitus type 1, drug addiction or psychiatric disease were excluded. Three months after the acute index event, 15 biomarkers known to be involved in atherosclerosis were analysed; C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-18, interferon-gamma (IFN-γ), tumor necrosis factor-alfa (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9. The Swedish population register and national patient register were used to analyse cardiovascular outcome including all-cause mortality, recurrent MI and heart failure (HF) during 20 years of follow-up. A variable importance analysis and a Cox regression model were used. Biomarkers were divided in tertiles and compared with the lowest tertile as a reference. Results At inclusion, 82% of cases were men with a mean age of 52 years. 19% were smokers, 34% had a diagnosis of hypertension and 11% had diabetes mellitus. The level of each biomarker in cases and controls is shown in Table. When biomarkers were compared, IL-6 was identified as the most important biomarker to predict outcome. In cases, IL-6 was associated with a composite outcome of all-cause mortality, non-fatal MI and non-fatal HF in a model adjusted for age, sex and cardiovascular risk factors (HR 1.96, 95% CI 1.37-2.80) (Figure). IL-6 also was associated with all-cause mortality (HR 2.42, 95% CI 1.45-4.04) and HF (HR 2.58, 95% CI 1.54-4.33). Conclusions When 15 inflammatory markers involved in atherosclerosis were analysed, IL-6 was the most important biomarker to predict long-term cardiovascular outcome. This study is unique considering the extended follow-up period of 20 years in young individuals with blood sampled in a convalescent phase after a first myocardial infarction. IL-6 is a promising biomarker to predict long-term prognosis and a possible treatment target.Table.Medians for all 15 biomarkersOutcome in relation to IL-6 level