title: Characterization of the effect of serum bilirubin concentrations on coronary endothelial function via measurement of high-sensitivity C-reactive protein and high-density lipoprotein cholesterol.
abstract: Bilirubin can prevent oxidation of low-density lipoprotein (LDL) and may protect against atherosclerosis and coronary heart disease (CHD). The goal of this study was to characterize the relationship between bilirubin and CHD through measurements of bilirubin concentration, coronary endothelial function, and markers of oxidative stress, inflammation, and lipid/glucose metabolism. The study population consisted of 141 patients without CHD who underwent Doppler flow study. Vascular reactivity was examined by intracoronary administration of papaverine, acetylcholine (ACh) and nitroglycerin using a Doppler guide wire. Serum bilirubin, high-sensitivity C-reactive protein (hsCRP), malondialdehyde-modified LDL, LDL cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and immunoreactive insulin were also measured. Homeostasis model assessment insulin resistance index and estimated glomerular filtration rate (eGFR) were calculated. Univariate analysis revealed that both percent change in coronary blood flow (CBF) and coronary artery diameter induced by ACh correlated positively with log-transformed bilirubin (r = 0.22, P < 0.05; r = 0.20, P < 0.05, respectively). Percent change in CBF in response to ACh correlated positively with eGFR (r = 0.24, P < 0.05) and correlated inversely with age, LDL-C, and log-transformed FPG (r = -0.24, P < 0.05; r = -0.17, P < 0.05, r = -0.22, P < 0.05, respectively). Multivariate analysis revealed that log-transformed bilirubin was the only independent predictor of percent change in CBF in response to ACh. Multivariate analysis revealed that log-transformed hsCRP and HDL-C were independent predictors of log-transformed bilirubin. These results suggest that a high level of bilirubin is associated with favorable coronary endothelial function, which may be mediated via the effect of bilirubin on inflammation and HDL-C.
authors.affiliation: Department of Cardiovascular, Respiratory and Metabolic Medicine, Graduate School of Medicine, Kagoshima University, 8-35-1 Sakuragaoka, Kagoshima, 890-8520, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yoshino
authors.forename: Shuichi
authors.initials: S
authors.lastname: Hamasaki
authors.forename: Sanemasa
authors.initials: S
authors.lastname: Ishida
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kataoka
authors.forename: Akiko
authors.initials: A
authors.lastname: Yoshikawa
authors.forename: Naoya
authors.initials: N
authors.lastname: Oketani
authors.forename: Keishi
authors.initials: K
authors.lastname: Saihara
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ichiki
authors.forename: So
authors.initials: S
authors.lastname: Kuwahata
authors.forename: Shoji
authors.initials: S
authors.lastname: Fujita
authors.forename: Takuro
authors.initials: T
authors.lastname: Takumi
authors.forename: Issei
authors.initials: I
authors.lastname: Yoshimoto
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Nakazaki
authors.forename: Chuwa
authors.initials: C
authors.lastname: Tei
mesh_terms: D000368:Aged; D001663:Bilirubin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D001783:Blood Flow Velocity; D001786:Blood Glucose / Q000032:analysis; D002097:C-Reactive Protein / Q000032:analysis*; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood*; D017023:Coronary Angiography; D003326:Coronary Circulation; D003327:Coronary Disease / Q000097:blood* / Q000175:diagnosis / Q000503:physiopathology; D003331:Coronary Vessels / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D017078:Laser-Doppler Flowmetry; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D018384:Oxidative Stress; D011237:Predictive Value of Tests; D014463:Ultrasonography; D014665:Vasodilator Agents
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D018836:Inflammation Mediators; D014665:Vasodilator Agents; D002097:C-Reactive Protein; D001663:Bilirubin