Cardiovascular Disease Risk Prediction Factors

To the Editor: The Emerging Risk Factors Collaboration¹ (ERFC) reported on the addition of lipid-related markers to total cholesterol and high-density lipoprotein cholesterol (HDL-C) in the prediction of cardiovascular disease. We attempted to replicate the findings of eTable 1, which summarized the 26 studies that compared apolipoprotein B with the cholesterol markers.

Many discrepancies with the primary publications were found. First, 4 eligible studies, including the Framingham Offspring Study,² were not included. Second, 5 studies did not meet the entry criteria, which included approved definitions and recording of both fatal and nonfatal cardiovascular events. The Whitehall I study³ recorded only fatal ischemic heart disease and so should not have been eligible. Yet strokes were listed in eTable 1 even though they were not a protocol outcome. Third, in 19 of the 26 studies, the number of participants differed substantially between eTable 1 and the primary publication. In 14 studies, there were fewer participants whereas in 5 studies, there were more participants. For example, the ERFC study listed 1293 patients for the Quebec Cardiovascular Study vs the actual tally of 2072.⁴ The ERFC study listed 23 175 for the Women's Health Study vs 15 632 in the primary report.⁵ Fourth, the values for apolipoprotein B in 4 study reports differed substantially from those given by the ERFC and neither the methods to measure apolipoprotein B nor the results were given in 4 other studies. Furthermore, in at least 2 studies, apolipoprotein B was measured many years after collection with no documentation of adequate sample preservation. Fifth, the methods and results of 11 studies have not been recorded in the public domain.