Diagnostic value of bilirubin concentrations compared with novel and traditional biomarkers in atherosclerosis with coronary artery disease Necat Yilmaz, MD, Hulya K. Cicek, MD, PhD, Ahmet Celik, MD, PhD, Vedat Davutoglu, MD. R easons behind the development of coronary artery disease (CAD) and their elimination are vitally important for life. A large number of risk factors have been described to be involved in the process of atherogenesis. In this respect, bilirubin seems to represent an important endogenous agent with cytoprotective activity against oxidative stress due to its potent antioxidant properties, which were demonstrated by in vitro, animal and human studies. In addition to being a potent antioxidant, bilirubin is considered to play a role in tissue protection against inlammatory damage by its anticomplement action. Coronary artery disease often occurs in the absence of traditional risk factors. Natural antioxidant defenses have evolved to protect humans against deleterious effects of free radicals. The primary enzymatic defenses are intracellular, but other antioxidant defenses are largely extracellular, including antioxidative substrates such as uric acid and unconjugated bilirubin, the predominant bile pigment in the intravascular compartment. For many years, the bile pigment was considered as a toxic waste product formed during heme catabolism. However, more recent evidence suggests that bilirubin is a potent physiological antioxidant that may provide important protection against atherosclerosis, coronary artery disease and inlammation. In 1994, Schwertner et al 1 were the irst to observe a signiicant inverse correlation between total bilirubin plasma concentrations and the prevalence of CAD. Subsequently, Hunt et al 2 noted that patients with early familial CAD have an average total serum bilirubin of 8.9 ± 6.1 µmol/L, compared with 12.4 ± 8.1 µmol/L in healthy control subjects. Low serum bilirubin concentrations have been shown to be independently and inversely associated with an increased risk for CAD. The strength of the association between bilirubin and CAD appears to be similar to that of high-density lipoprotein-cholesterol (HDL-C). The antioxidant capacity of bilirubin and its ability to provide potent scavenging of peroxyl radicals have led to suggestions that mildly increased circulatory bilirubin may have a physiologic function to protect against disease processes that involve oxygen and peroxyl radicals. Antioxidant activity and cardioprotective potential may be attributable to any of the bilirubin forms, including 3 unconjugated bilirubin, protein-bound unconjugated bilirubin, delta bilirubin or mono-/diconjugated bilirubin. Under physiological conditions, the predominant circulatory form of bilirubin is the unconjugated, albumin-bound form. 2 In recent years, “nontraditional factors”(Novel) such as high sensitive C-reactive protein, total- homocysteine, as well as oxidative stress have been proposed as risk factors for the development and progression of atherosclerosis and atherothrombotic cardiovascular disease. The purpose of this study was to examine the relationship between traditional concentrations and nontraditional biomarkers of CAD in coronary angiography patients and in apparently healthy control subjects. All patients referred to the Department of Cardiology, University of Gaziantep, between March and August 2003 for which clinical data were available were included in our study. Included were 319 subjects who were admitted to the hospital with chest pain and who underwent coronary angiography. The CAD group consisted of 262 patients (63 females and 199 males) with stenosis of the coronary arteries. The apparently healthy control group consisted of 50 subjects (17 females and 23 males). Coronary artery disease was divided into groups according to the maximum coronary stenosis at angiography: 0-20% (no detectable CAD), 20-49% (mild disease), 50-70% (moderate disease), and 70-100% (severe disease). Other classiication of severity of the disease was assessed by counting both the number of diseased vessels (0 to 3). All subjects were questioned for established cardiovascular risk factors, including diabetes, smoking, medication and hypertension. The study was approved by the local Ethics Committee, and the individuals participating in the study gave their informed consent. Although the healthy subjects did not have coronary angiograms they underwent comprehensive physical examination by a physician, completed the World Health Organization standard Rose questionnaire on chest pain, and answered other questions regarding their past medical history. None of the individuals in the healthy group had angina or a prior history of CAD. All of them had normal electrocardiograms according to Minnesota Coding Criteria. All patients were monitored for somatic illness throughout the investigation period and were Bilirubin in atherosclerosis with coronary artery disease 1262 Saudi Med J 2006; Vol. 27 (8) www.smj.org.sa 03BriefCom1262-1266.indd 1262 7/18/06 12:08:03 PM