Diagnostic methods 187 Usefulness of combined high-sensitive C-reactive protein and N-terminal-probrain natriuretic peptide for predicting cardiovascular events in patients with suspected coronary artery disease Po-Hsun Huang a,b,c , Tse-Min Lu a,b,c , Tao-Cheng Wu a,b,c , Feng-Yen Lin b,d , Yung-Hsiang Chen b,e , Jaw-Wen Chen a,c and Shing-Jong Lin a,b,c Objective We examined whether the combined use of high-sensitive C-reactive protein (hsCRP) and N-terminal- probrain natriuretic peptide (NT-proBNP) could increase the predictive value for future cardiovascular events. Background hsCRP and NT-proBNP both have been shown to be strong predictors of cardiovascular events in patients with coronary artery disease. Few data are, however, available to assess whether combined use of these two distinct biomarkers improves the risk stratification in predicting cardiovascular events. Methods A total of 205 participants with suspected coronary artery disease referred for coronary angiography were enrolled in the study. Plasma levels of hsCRP and NT-proBNP were measured before coronary angiography. Cox regression analyses were conducted for the 205 participants, with cardiovascular events being defined as nonfatal myocardial infarction, percutaneous coronary intervention, coronary artery bypass grafting, and ischemic stroke. Results All patients were divided into four groups by using median values of hsCRP (1.1 mg/l) and NT-proBNP (472.6 fmol/ml): group 1, low hsCRP/low NT-proBNP (n = 60); group 2, high hsCRP/low NT-proBNP (n = 42); group 3, low hsCRP/high NT-proBNP (n = 42); and group 4, high hsCRP/high NT-proBNP (n = 61). During a median follow-up of 4 years, there were 84 cardiovascular events (41%): 11 events (18%) in group 1, 13 events (31%) in group 2, 20 events (48%) in group 3, and 40 events (66%) in group 4 (P < 0.001). Patients with cardiovascular event had significantly attenuated flow-mediated vasodilation (3.6 ± 3.4 vs. 5.3 ± 3.5%, P = 0.001) and increased plasma levels of NT-proBNP (627 ± 330 vs. 458 ± 196 fmol/ml, P < 0.001). Simple linear regression analysis on all studied participants demonstrated significant associations between levels of hsCRP and NT-proBNP (hsCRP vs. NT-proBNP: r = 0.354, P < 0.001). Cox regression hazards model showed that combined use of NT-proBNP and hsCRP significantly increased predictive value for future cardiovascular events [hazard ratio (HR) 4.922, 95% confidence interval (CI), 2.519–9.617; P < 0.0001 for high hsCRP/high NT-proBNP vs. low hsCRP/low NT-proBNP]. Conclusion These findings demonstrated that a simple combination of distinct biomarkers of hsCRP and NT-proBNP might provide additional information for predicting cardiovascular events. Coron Artery Dis 19:187–193  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins. Coronary Artery Disease 2008, 19:187–193 Keywords: coronary artery disease, high-sensitive C-reactive protein, N-terminal-probrain natriuretic peptide a Division of Cardiology, Department of Internal Medicine, Taipei Veterans General Hospital, b Institute of Clinical Medicine, c Cardiovascular Research Center, National Yang-Ming University, d Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei and e Graduate Institute of Integrated Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan Correspondence to Shing-Jong Lin, MD, PhD, Division of Cardiology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shih-Pai Road, Taipei, Taiwan Tel: +886 2 2875 7229; fax: +886 2 2876-3336; e-mail: sjlin@vghtpe.gov.tw Received 24 July 2007 Revised 12 October 2007 Accepted 22 October 2007 Introduction Despite the availability of effective preventive measures, coronary artery disease (CAD) remains a leading cause of morbidity and mortality in most industrialized countries. Application of biomarkers that can be used to identify high-risk population and reliably predict prognosis in such group of patients with ischemic heart disease is of paramount clinical importance. Increasing evidence suggests that atherosclerosis is an inflammatory disease. The pathophysiological basis for the association between C-reactive protein (CRP) and cardiovascular events remains a topic of intense study. Numerous studies have confirmed the independent prognostic relevance of high- sensitive C-reactive protein (hsCRP) for the risk of cardiovascular events in patients with CAD and also in apparently healthy men and women [1–5]. Addition of hsCRP to traditional risk factors or endothelial function has been shown to increase predictive power to identify individuals at ‘intermediate risk’ into clinically relevant higher-risk or lower-risk categories [6]. CRP is not only a 0954-6928  c 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins