Plasma concentration of serotonin is a novel biomarker for coronary microvascular dysfunction in patients with suspected angina and unobstructive coronary arteries.
OBJECTIVE
Although the importance of coronary microvascular dysfunction (CMD) has been emerging, reliable biomarkers for CMD remain to be developed. We examined the potential usefulness of plasma concentration of serotonin to diagnose CMD in patients with suspected angina and unobstructive coronary arteries.


RESULTS
We enrolled 198 consecutive patients (M/F 116/82, 60.2 ± 13.3 years old) who underwent acetylcholine provocation test and measured plasma serotonin concentration. Coronary microvascular dysfunction was defined as myocardial lactate production without or prior to the occurrence of epicardial coronary spasm during acetylcholine provocation test. Although no statistical difference in plasma concentration of serotonin [median (inter-quartile range) nmol/L] was noted between the vasospastic angina (VSA) and non-VSA groups [6.8 (3.8, 10.9) vs. 5.1 (3.7, 8.4), P = 0.135], it was significantly higher in patients with CMD compared with those without it [7.7 (4.5, 14.2) vs. 5.6 (3.7, 9.3), P = 0.008]. Among the four groups classified according to the presence or absence of VSA and CMD, serotonin concentration was highest in the VSA with CMD group. Importantly, there was a positive correlation between plasma serotonin concentration and baseline thrombolysis in myocardial infarction frame count (P = 0.001), a marker of coronary vascular resistance. The classification and regression trees analysis showed that plasma serotonin concentration of 9.55 nmol/L was the first discriminator to stratify the risk for the presence of CMD. In multivariable analysis, serotonin concentration greater than the cut-off value had the largest odds ratio in the prediction of CMD [odds ratio (95% confidence interval) 2.63 (1.28-5.49), P = 0.009].


CONCLUSIONS
Plasma concentration of serotonin may be a novel biomarker for CMD in patients with angina and unobstructive coronary arteries.
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Yuji
Y
Odaka
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Jun
J
Takahashi
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Ryuji
R
Tsuburaya
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Kensuke
K
Nishimiya
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Kiyotaka
K
Hao
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Yasuharu
Y
Matsumoto
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Kenta
K
Ito
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Yasuhiko
Y
Sakata
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Satoshi
S
Miyata
Bioscience Division, Tosoh Corp., 2743-1 Hayakawa Ayase-shi, Kanagawa 252-1123, Japan.
Daisuke
D
Manita
Bioscience Division, Tosoh Corp., 2743-1 Hayakawa Ayase-shi, Kanagawa 252-1123, Japan.
Yuji
Y
Hirowatari
Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.
Hiroaki
H
Shimokawa
D000109:Acetylcholine / Q000494:pharmacology; D000787:Angina Pectoris / Q000175:diagnosis* / Q000503:physiopathology; D015415:Biomarkers / Q000378:metabolism; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000503:physiopathology; D003326:Coronary Circulation / Q000502:physiology; D003329:Coronary Vasospasm / Q000503:physiopathology; D003331:Coronary Vessels / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D017202:Myocardial Ischemia / Q000503:physiopathology; D012701:Serotonin / Q000378:metabolism*; D014665:Vasodilator Agents / Q000494:pharmacology
D015415:Biomarkers; D014665:Vasodilator Agents; D012701:Serotonin; D000109:Acetylcholine
Coronary artery spasm ; Coronary microvascular dysfunction; Serotonin 