Extracellular matrix markers and risk of myocardial infarction: The HUNT Study in Norway

Aims Extracellular matrix remodelling may influence atherosclerotic progression and plaque stability. We hypothesized that evaluation of extracellular matrix markers, with potentially different roles during atherogenesis, could provide information on underlying mechanisms and risk of myocardial infarction (MI) in apparently healthy individuals. Methods We conducted a case-control study nested within the population-based HUNT2 cohort in Norway. A total of 58,761 men and women, free of known cardiovascular disease, were followed for a first MI. During 11.3 years of follow-up, 1587 incident MIs were registered, and these cases were compared with 3959 age- and sex-matched controls. Circulating levels of the ECM proteins CD147 (ECM metalloproteinase inducer; EMMPRIN), cartilage oligomeric matrix protein (COMP: thrombospondin-5) and YKL-40 (chitinase-3-like-1) were measured by enzyme immunoassays. Results We found an inverse association between COMP (quartile (Q) 4 vs. Q1: hazard ratio 0.81 (95% confidence interval: 0.67-0.98)) and YKL-40 (Q4 vs. Q1: hazard ratio 0.77 (0.62-0.95)) with incidence of MI after full multivariable adjustment. Serum CD147 was not associated with MI risk in adjusted analysis. Conclusion High levels of COMP and YKL-40 were associated with lower risk of incident MI, suggesting a potential beneficial role in promoting plaque stability in individuals without incident cardiovascular disease.