Plasma concentration of serotonin is a novel biomarker for coronary microvascular dysfunction in patients with suspected angina and unobstructive coronary arteries

Odaka, Yuji; Takahashi, Jun; Tsuburaya, Ryuji; Nishimiya, Kensuke; Hao, Kun; Matsumoto, Yasuharu; Ito, Kei; Sakata, Yasuhiko; Miyata, Satoshi; Manita, Daisuke; Hirowatari, Yuji; Shimokawa, Hiroaki

doi:10.1093/eurheartj/ehw448

Cited by 44 publications

(34 citation statements)

References 37 publications

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“…27 Plasma 5-HT has been recently proposed as a marker of atherosclerotic vascular lesions, 27 and coronary microvascular dysfunction. 28 The latter appears of peculiar relevance for SSNHL patients since microvascular implication are considered in both cases.…”

Section: Discussionmentioning

confidence: 99%

Plasma Serotonin is Elevated in Adult Patients with Sudden Sensorineural Hearing Loss

et al. 2020

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Background The roles of thrombophilia and cardiovascular risk factors in sudden sensorineural hearing loss (SSNHL) remain controversial. Cochlear microthrombosis and vasospasm have been hypothesized as possible pathogenic mechanisms of SSNHL. This article investigates the circulating serotonin and homocysteine levels besides thrombophilia screening in patients with idiopathic SSNHL. Methods A total of 133 SSNHL patients and age- and sex-matched controls were investigated (discovery cohort). Measurement included common inherited natural coagulation inhibitors, factor VIII, von Willebrand factor (VWF), antiphospholipid antibodies, homocysteine, and serotonin (whole blood, platelet, and plasma) levels, along with frequent relevant genetic variants. A validation cohort (128 SSNHL patients) was studied for homocysteine and serotonin levels. Results and Conclusion In the discovery cohort, 58.6% of patients exhibited thrombophilia, of which most had a low to moderate titers of antiphospholipid antibodies and high levels of factor VIII/VWF. Twenty-seven patients (20%) had mild-to-moderate hyperhomocysteinemia or were homozygous for the methylenetetrahydrofolate reductase (MTHFR) C677T mutation. Regarding serotonin, SSNHL patients had elevated whole blood levels that remained within the normal range and normal platelet content. However, approximately 90% patients of both cohorts had elevated plasma serotonin. Elevated plasma serotoninemia was accompanied by serotonylation of platelet rhoA protein. This study shows that increased plasma serotonin appears as a biomarker of SSNHL (specificity: ∼96%, sensitivity: ∼90%) and could participate in the pathophysiology of SSNHL.

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Section: Discussionmentioning

confidence: 99%

Plasma Serotonin is Elevated in Adult Patients with Sudden Sensorineural Hearing Loss

et al. 2020

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“…It mediates vasoconstriction by 5‐HT 2A receptors on vascular smooth muscle cells, and also promotes platelet aggregation . However, the role of serotonin in VSA is controversial . Sarpogrelate hydrochloride, a selective 5‐HT 2A antagonist, suppresses platelet aggregation and inhibits thrombus formation and vascular smooth muscle cell proliferation, and is widely used to improve vascular function in peripheral arterial disease .…”

Section: Discussionmentioning

confidence: 99%

“…10 However, the role of serotonin in VSA is controversial. [29][30][31] Sarpogrelate hydrochloride, a selective 5-HT 2A antagonist, suppresses platelet aggregation and inhibits thrombus formation and vascular smooth muscle cell proliferation, and is widely used to improve vascular function in peripheral arterial disease. 10 It has been also reported to inhibit serotonin-induced coronary vasospasm in an animal study 32 and to improve exercise capacity by increasing collateral flow in effort angina.…”

Section: Independent Predictors Of Angiographically Complete Remissmentioning

confidence: 99%

Effect of sarpogrelate and high‐dose statin on the reduction of coronary spasm in vasospastic angina: A two by two factorial, pilot randomized study

Kim

Choi

Song

et al. 2019

Clinical Cardiology

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Background Vasospastic angina (VSA) is characterized by coronary spasm, which can be aggravated by vasoactive substances such as serotonin. Hypothesis Sarpogrelate, a selective serotonin receptor antagonist, and high‐dose statin have some effects on the reduction of coronary spasm in patients with VSA. Methods We recruited 100 patients with angiographically confirmed VSA, and randomly assigned them into four groups: sarpogrelate with high‐dose statin (Group A, n = 25), sarpogrelate with low‐dose or no statin (Group B, n = 25), placebo with high‐dose statin (Group C, n = 25), and placebo with low‐dose or no statin (Group D, n = 25). The primary endpoint was the remission of coronary spasm on 1‐year follow‐up provocation test. Results The most common site of coronary spasm was left anterior descending artery (42%). Most patients (96%) took calcium channel blockers, and 46% were treated with vasodilators. Overall, 40% of patients reported no chest pain at 1 year, and 23% showed complete remission of coronary spasm on 1‐year follow‐up provocation test. No difference was observed in symptomatic and angiographically complete remission rate between the sarpogrelate and the placebo group. Although the apolipoprotein B level at the 1‐year follow‐up was significantly lower in the high‐dose statin group, symptomatic and angiographic outcomes were not different according to statin intensity. Distal thrombolysis in myocardial infarction (TIMI) flow on initial provocation test was independently associated with angiographically complete remission. Conclusions Sarpogrelate or high‐dose statin did not significantly improve the angiographic remission rate in patients with VSA. Distal TIMI flow on initial provocation test could predict the complete remission of coronary spasm at follow‐up.

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“…As shown in Figure 3 , intracoronary administration of ACh (20, 50, and 100 μg) into the left coronary artery (LCA) and that of ACh (25 and 50 μg) into the right coronary artery induced epicardial coronary spasm accompanied by chest pain and ischaemic ECG changes. Chest pain, ischaemic ECG changes, and myocardial lactate production 7 were already noted at the timing of administration of 20 μg of ACh into the LCA before the occurrence of epicardial coronary spasm at 100 μg, indicating that microvascular spasm (MVS) preceded epicardial coronary spasm. Thus, we diagnosed that she had both epicardial coronary spasm and MVS, and initiated drug therapy with a calcium antagonist (benidipine 8 mg/day).…”

Section: Case Presentationmentioning

confidence: 94%

A case of recurrent takotsubo-like cardiomyopathy associated with pheochromocytoma exhibiting different patterns of left ventricular wall motion abnormality and coronary vasospasm: a case report

Sato

Takahashi

Amano³

et al. 2020

European Heart Journal - Case Reports

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Background Takotsubo-like cardiomyopathy associated with pheochromocytoma (Pheo-TTS) is a recognized but uncommon disorder. While Pheo-TTS might more often recur and the pattern of left ventricular (LV) wall motion abnormality is more diverse compared with primary TTS, it remains to be elucidated whether coronary functional abnormalities are also involved. Case summary A 50-year-old woman was referred with a chief complaint of transient chest pain, dyspnoea, and paroxysmal thyroid swelling that usually developed after meals. In the past, she had been admitted to emergency rooms three times due to pulmonary oedema following the above attacks. Serial cardiac catheterizations showed normal coronary arteries and morphologically different types of LV dysfunction each time; apical LV ballooning at the first, basal LV ballooning at the second, and diffuse LV hypokinesis at the last admission. Acetylcholine (ACh) provocation testing for coronary vasospasm was negative at the second admission. During hospitalization in our department, abdominal ultrasonography for screening detected a right adrenal mass and the urinary normetanephrine level was increased. The adrenal tumour was urgently removed surgically and finally she was diagnosed as having norepinephrine-secreting pheochromocytoma. Acetylcholine testing was again performed just after the operation, showing both epicardial and microvascular coronary spasms. Since the operation, she has been free of symptoms. Importantly, ACh testing at 1-year follow-up showed that epicardial spasm was no longer noted, whereas coronary microvascular spasm persisted. Discussion Adrenal pheochromocytoma could cause recurrent attacks of catecholamine surges with different patterns of LV dysfunction, where coronary vasospasm may also be involved along the coronary arteries.

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Plasma concentration of serotonin is a novel biomarker for coronary microvascular dysfunction in patients with suspected angina and unobstructive coronary arteries

Abstract: Plasma concentration of serotonin may be a novel biomarker for CMD in patients with angina and unobstructive coronary arteries.

Cited by 44 publications

References 37 publications

Plasma Serotonin is Elevated in Adult Patients with Sudden Sensorineural Hearing Loss

Plasma Serotonin is Elevated in Adult Patients with Sudden Sensorineural Hearing Loss

Effect of sarpogrelate and high‐dose statin on the reduction of coronary spasm in vasospastic angina: A two by two factorial, pilot randomized study

A case of recurrent takotsubo-like cardiomyopathy associated with pheochromocytoma exhibiting different patterns of left ventricular wall motion abnormality and coronary vasospasm: a case report

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