Abstract

Background: Identification of individuals with high risk for first-ever myocardial infarction (MI) can be improved. The objectives of the study ere to survey multiple protein biomarkers for association with the 5-year risk of incident MI and identify a clinically significant risk model that adds information to current common risk models. Methods: We employed an immunoassay platform that utilizes a sensitive, sample efficient molecular counting technology to measure 51 proteins in samples from the fourth survey (1994) in the Tromsø Study, a longitudinal study of men and women in Tromsø, Norway. A nested case control design was used with 182 first-ever MI cases (60 females/122 males) and 467 controls (277 females/190 males). Results: Of the proteins measured, 21 were predictors of MI before and after adjustment for traditional risk factors either in men, women or both. In stepwise multivariable analysis with these biomarkers and traditional risk factors, kallikrein; OR 0.58 (95% CI 0.47 - 0.71), matrix metalloproteinase 8; OR 1.41 (1.13 - 1.75), the interaction term CCL5/RANTES*women; OR 0.57 (0.44 - 0.74), the interaction term apolipoprotein B/apolipoprotein A1 ratio*men; OR 1.53 (1.27 - 1.84) and lipoprotein a; OR 1.33 (1.10 - 1.61) added significantly to the model with a net reclassification improvement of 0.10 (p=0.01), while the ROC area increased from 0.77 to 0.83, p<0.001. Conclusion: Novel protein biomarker models improve identification of MI risk above and beyond traditional risk factors with more than 10% better allocation to either high or low risk group than traditional risk factors alone.

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