Over the last decade, attempts to identify and validate circulating biomarkers predictive of cardiovascular disease have begun to influence clinical practice, as well as to globally reshape thinking on the pathophysiology of vascular events. Acute phase reactant proteins, which classically reflect a response to acute injury or infection, incorporate molecules with proinflammatory and procoagulant functions. Given the compelling evidence relating atherosclerosis to inflammation, the notion that circulating levels of such molecules might be linked to the burden or activity of vascular disease seems logical. For primary or secondary prevention purposes, markers such as C-reactive protein offer utility in identifying subgroups of patients at increased risk for long-term events, which may be used to guide preventive nutritional, behavioral, and pharmacologic therapies.1Ridker P.M. Cushman M. Stampfer M.J. Tracy R.P. Hennekens C.H. Plasma concentration of C-reactive protein and risk of developing peripheral vascular disease.Circulation. 1998; 97: 425-428Crossref PubMed Scopus (843) Google Scholar, 2Ridker P. Hennekens C. Buring J. Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women.N Engl J Med. 2000; 342: 836-843Crossref PubMed Scopus (5027) Google Scholar, 3Ridker P.M. Rifai N. Clearfield M. Downs J. Weis S. Miles J. et al.Measurement of C-reactive protein for the targeting of statin therapy in the primary prevention of acute coronary events.N Engl J Med. 2001; 344 (1959-651)Crossref Scopus (1481) Google Scholar Failure of vascular interventions, including angioplasty, stenting, and surgical bypass, is a frequent problem that clearly relates to the magnitude of the injury response. Identifying subgroups of patients at an elevated risk for aggressive restenosis would be of great utility for the selection of optimal interventions and quite possibly for guiding adjunctive medical or other therapies to reduce the incidence of failure. To date, however, clinically useful biomarkers predictive of outcomes after interventions have yet to be clearly identified. Data on the predictive value of inflammatory markers in coronary interventions have been conflicting, although one interesting study reported a beneficial effect of targeted steroid therapy for patients with elevated C-reactive protein levels after coronary stenting.4Versaci F. Gaspardone A. Tomai F. Ribichini F. Russo P. Proietti I. et al.Immunosuppressive Therapy for the Prevention of Restenosis after Coronary Artery Stent Implantation (IMPRESS study).J Am Coll Cardiol. 2002; 40: 1935-1942Abstract Full Text Full Text PDF PubMed Scopus (220) Google Scholar Dr. Heider and colleagues have examined the levels of circulating adhesion (E selectin, P selectin, soluble intercellular adhesion molecule-1 (ICAM-1), and soluble vascular cell adhesion molecule-1 (VCAM-1) and inflammatory monocyte chemoattractant protein-1 (MCP-1) molecules after peripheral interventions for claudication in 44 subjects. The study is limited in assessing predictive values by a small patient cohort, particularly since only 32 of these patients received interventions, among which were a mixture of angioplasty alone and stenting. Heterogeneity among this small group in lesion anatomy, comorbid risk factors, and medical therapies further limits the ability to discriminate associations with the biomarkers. However, the authors were able to provide important new data on the nature and time course of the inflammatory response to peripheral catheter-based procedures. Their results suggest that angiography per se engenders an inflammatory response and offer the possibility that certain markers (E selectin, P selectin, and VCAM-1) may be predictive of poor outcome. Much larger (and likely multicenter) studies will need to be conducted to accurately identify and validate biomarkers for adverse outcomes after peripheral endovascular interventions.