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

Studies on predictive value of circulating inflammatory biomarkers after myocardial infarction (MI) have often been limited by blood sampling only in an acute setting and short follow-up time. We aimed to compare the long-term predictive value of nine inflammatory biomarkers, known to be involved in atherosclerosis, in young patients investigated three months after a first-time MI. Nine biomarkers (high-sensitivity C-reactive protein, interleukin (IL)-6, IL-18, monocyte chemoattractant protein-1, matrix metalloproteinase (MMP)-1, MMP-3, MMP-9, serum amyloid A and tumor necrosis factor-alfa) were sampled in 382 young (<60 years) patients and in age and sex-matched controls, three months after a first-time MI between 1996 and 2000. Swedish national patient registers were used to determine cardiovascular (CV) outcomes during 20 years of follow-up. In cases, random forest models identified IL-6 as the most important predictor of the primary composite endpoint of death, heart failure (HF) or MI hospitalization, and the separate endpoints death and HF hospitalization. IL-18 was the most important predictor of MI hospitalization. In a Cox regression, the highest tertile of IL-6 was associated with the composite endpoint (HR (95% CI) 1.91 (1.31–2.79)), death (2.38 (1.42–3.98)) and HF hospitalization (2.70 (1.32–5.50)), when adjusting for age, sex and CV risk factors. The highest tertile of IL-18 was associated with MI hospitalization (2.31 (1.08–4.91)) when severity of coronary atherosclerosis was added to the same type of model. When nine inflammatory markers involved in atherosclerosis were analyzed three months after the acute event in young MI patients, IL-6 and IL-18 were the most important biomarkers to predict long-term CV outcomes during 20 years of follow-up.