In Reply We recently reported that cardiovascular biomarkers were strongly associated with fatal and nonfatal cardiovascular events and mortality, but their addition to established risk factors resulted in only a small improvement in risk prediction metrics.

We agree with Drs Mangalesh and Nanna about the limitations of the C statistic in evaluating new risk factors. Evaluation of NRI focuses on risk reclassification, which might be a more applicable measure. In eTable 8 in Supplement 1, we presented the categorical NRIs separately for cases and noncases, showing that the addition of high-sensitivity cardiac troponin I, N-terminal pro-B-type natriuretic peptide, and high-sensitivity C-reactive protein to the base model correctly reclassified more cases than noncases regarding atherosclerotic cardiovascular disease events (NRI, 0.032 for cases vs 0.013 for noncases).