Invited commentary

Abstract

This study is a prospective evaluation of the relationship between C-reactive protein (CRP), and D-dimer (DD) and the progression of peripheral arterial disease (PAD). The authors are probing an important yet controversial clinical area. For the average reader, the presentation will be confusing and somewhat bewildering, as this article has been written for those who understand these types of trials and statistics. However, even the casual reader will be able to understand the fundamental questions and conclusions. The authors studied 332 of 384 enrolled patients over a 7-year period. The patients were originally part of the Homocysteine and Progression of Atherosclerosis Study (HPAS). This trial started in 1991, and the first phase examined the relationship between the homocysteine level and progression of PAD. The second phase of the trial is a prospective, randomized, double-blind study examining the effects of folate vs placebo to prevent the progression of PAD. The current study represents a secondary set of objectives derived from the second phase trial. The authors are presenting data that examined the relationship between time to the various end points and baseline CRP and DD levels. The data were examined by life-table analysis and Cox proportional hazards analysis. The data showed that in subjects with symptomatic PAD, death from a cardiovascular cause was slightly more likely in those with elevated baseline DD and that DD was significantly associated with the occurrence of myocardial infarction. However, the study did not find a relationship between progression of PAD and baseline DD or CRP. The findings of this study appear straightforward and are very important, as several other studies have suggested that DD and CRP as good markers to predict progression of PAD. In summary, the study is extremely well designed and very well described. The study is important for two reasons. First, the authors have examined an important scientific and clinical question and have provided the reader with data showing that DD and CRP are not good markers of progression of PAD. These findings are contrary to several previous studies and as such are somewhat controversial. Second, this study is also important because it serves as an excellent example of how to design a clinical trial that has far reaching importance, yet examines very straightforward and simple hypotheses.