LETTER TO THE EDITOR doi:10.1093/eurheartj/ehn149

New cardiovascular risk determinants do exist and are clinically useful I read with interest the article by Smulders et al., in which the authors noted that the key to understanding a statistically significant relationship between independent risk predic-tions, but no improvement in risk classifi-cations, lies with the statistical methodology used for the assessment.1 But, it seems to me that the final criteria for defining biomarkers for clinical use must be from information obtained from well-designed pro-spective outcome studies that show clinical management can be altered on the basis o