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CLINICAL RESEARCH: BIOMARKERS

Urinary biopyrrins levels are elevated in relation to severity of heart failure

Jun Hokamaki, MD^*, Hiroaki Kawano, MD^*,*, Michihiro Yoshimura, MD^*, Hirofumi Soejima, MD^*, Shinzo Miyamoto, MD^*, Ichiro Kajiwara, MD^*, Sunao Kojima, MD^*, Tomohiro Sakamoto, MD^*, Seigo Sugiyama, MD^*, Nobutaka Hirai, MD^*, Hideki Shimomura, MD, Yasuhiro Nagayoshi, MD, Kenichi Tsujita, MD, Izuru Shioji, BS, Shinya Sasaki, BS and Hisao Ogawa, MD^*

^* Department of Cardiovascular Medicine, Kumamoto University School of Medicine, Kumamoto, Japan
Division of Cardiology, Fukuoka Tokushukai Hospital, Fukuoka, Japan
Shino-Test Corporation, Tokyo, Japan

Manuscript received August 25, 2003; revised manuscript received December 24, 2003, accepted January 8, 2004.

^* Reprint requests and correspondence: Dr. Hiroaki Kawano, Department of Cardiovascular Medicine, Kumamoto University School of Medicine, 1-1-1 Honjo, Kumamoto City 860-8556, Japan.
koumei{at}gpo.kumamoto-u.ac.jp

OBJECTIVES: We investigated the relationship between the urinary levels of biopyrrins and the severity of heart failure (HF).

BACKGROUND: Oxidative stress is evident in heart disease and contributes to the development of ventricular dysfunction in patients with HF. Biopyrrins, oxidative metabolites of bilirubin, have been discovered as potential markers of oxidative stress.

METHODS: We measured the levels of urinary biopyrrins and plasma B-type natriuretic peptide (BNP) in 94 patients with HF (59 men; mean age 65 years) and 47 control subjects (30 men; mean age 65 years). Urine and blood samples were taken after admission in all subjects. Further urine samples were obtained from 40 patients after treatment of HF.

RESULTS: The urinary biopyrrins/creatinine levels (µmol/g creatinine) were the highest in patients in New York Heart Association (NYHA) class III/IV (n = 26; 17.05 [range 7.85 to 42.91]). The urinary biopyrrins/creatinine levels in patients in NYHA class I (n = 35; 3.46 [range 2.60 to 5.42]) or II (n = 33; 5.39 [range 3.37 to 9.36]) were significantly higher than those in controls (2.38 [range 1.57 to 3.15]). There were significant differences in urinary biopyrrins/creatinine levels among each group. The treatment of HF significantly decreased both urinary biopyrrins/creatinine levels (from 7.43 [range 3.84 to 17.05] to 3.07 [range 2.21 to 5.71]) and NYHA class (from 2.5 ± 0.1 to 1.7 ± 0.1). Log biopyrrins/creatinine levels were positively correlated with log BNP levels (r = 0.650, p < 0.001).

CONCLUSIONS: These results indicate that urinary biopyrrins levels are increased in patients with HF and are elevated in proportion to its severity.

Abbreviations and Acronyms   BNP = B-type natriuretic peptide   HF = heart failure   LVEF = left ventricular ejection fraction   NYHA = New York Heart Association   ROS = reactive oxygen species

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