To the Editor: Dr Melander and colleagues1 suggested that gains in risk prediction using new biomarkers for cardiovascular disease are minimal using risk reclassification, a technique that can help determine whether new markers can change clinical decisions.2 In contrast to similar analyses using data from the Women's Health Study, the Physicians' Health Study, and the Framingham Heart Study, there was no improvement in risk stratification with new markers, including C-reactive protein (CRP).
However, the study's methods and conclusions raise some questions. First, while the authors presented the net reclassification improvement (NRI) for each of the new markers, they did not present the NRI for the traditional markers, thus providing no basis for comparison. The NRI is similar for traditional measures and for CRP in predicting cardiovascular disease,2 and this comparison would indicate the power of their study to detect important differences. Second, the NRI and integrated discrimination improvement (IDI) values were apparently computed using events as of 10 years of follow-up, reducing the number of analyzed cardiovascular events from 418 to 238, leading to a loss of information and power. Third, use of 3 categories rather than 4 reduces the size of the NRI,2 limiting comparability across studies. The previously used cut point of 10% seems justified given the decreasing costs of statins. Fourth, the nonsignificant P values for the IDI are surprising given that it is similar to a difference in R2,3 a highly sensitive test that should be comparable with the test of the hazard ratio.
The number of deaths due to noncardiovascular causes was also sizeable in these data. The authors did not compute the NRI for total death, although they did so for a variety of end-point definitions using the same risk categories. Despite the absence of clinical risk categories for mortality, the movement of individuals across the same risk levels would be of interest. In addition to the NRI, the reclassification calibration test2 would determine whether the predicted risks were closer to those observed for all comparisons.
Financial Disclosures: None reported.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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