Coronary artery spasm, an important player in ischemic heart disease, is associated with inflammation of coronary adventitia and perivascular adipose tissue (PVAT) in patients with vasospastic angina, a new study suggests.[1]
Japanese researchers, led by Dr Kazuma Ohyama (Tohoku University Graduate School of Medicine, Sendai, Japan), made their finding by using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT), an imaging modality that they say may be useful in assessing disease activity.
“Although invasive methods, such as coronary angiography and provocation with acetylcholine, are currently indispensable for diagnosis of vasospastic angina, a multimodality approach, especially 18F-FDG PET/CT imaging, may become useful as a noninvasive tool for assessment of this disorder,” they write.
Activation of Rho-kinase is a molecular switch for vascular smooth muscle contraction and is a central mechanism of coronary spasm in animals and humans, the authors write.
They also note they have previously shown optical coherence tomography (OCT) permits precise measurement of the vasa vasorum (VV) and that adventitial inflammatory changes, including the formation of VV, play important roles in the pathogenesis of coronary spasm in pigs and humans.
To test their hypothesis that coronary artery spasm is associated with perivascular inflammation in patients with vasospastic angina (VSA), Ohyama et al prospectively examined 27 patients with acetylcholine-induced diffuse spasm in the left anterior descending (LAD) artery and 13 patients suspected of having angina but without organic coronary lesions or coronary spasm.
They used CT coronary angiography and 18F-FDG PET/CT to assess coronary PVAT volume and coronary perivascular FDG uptake in the LAD.
In addition, they used OCT to examine adventitial VV formation in the LAD, and they also measured Rho-kinase activity in circulating leukocytes.
Patient characteristics were similar in both groups.
CT coronary angiography and 18F-FDG PET/CT showed that coronary PVAT volume and coronary perivascular FDG uptake were significantly increased in the patients with VSA compared with patients without VSA.
Coronary perivascular target-to-background ratio (TBR) at the spastic LAD was significantly greater in the VSA group than in the non-VSA group (1.04 ± 0.03 vs 0.85 ± 0.04, both P<0.01).
There was a significant positive correlation between the extent of coronary perivascular TBR and coronary vasoconstriction responses to acetylcholine in the VSA group compared with the non-VSA group (P<0.01).
In addition, there was a significant positive correlation between the extent of coronary PVAT volume index and that of coronary perivascular TBR in the VSA group but not in the non-VSA group.
OCT showed that adventitial VV formation significantly increased in the VSA group compared with the non-VSA group (0.086 ± 0.006 mm2 vs 0.045 ± 0.006 mm2; P<0.01).
Rho-kinase activity in circulating leukocytes was also significantly higher in the VSA group than in the non-VSA group. However, after medical treatment, both coronary perivascular FDG uptake and Rho-kinase activity significantly decreased in the VSA group.
New Insights for Treatment
In an accompanying editorial,[2] Dr John F. Beltrame and Dr Peter J. Psaltis write that Ohyama et al have provided “compelling” evidence that PVAT-associated inflammation plays a role in epicardial coronary artery spasm.
“The pathogenetic mechanism of coronary artery spasm not only involves vascular smooth muscle cell hyper-reactivity but also a perivascular inflammatory process,” Beltrame told theheart.org | Medscape Cardiology in email correspondence.
“This paper by international leaders in the pathophysiology of coronary artery spasm has comprehensively demonstrated that perivascular adipose tissue–associated inflammation contributes to the pathogenesis of coronary artery spasm, and this provides new insights into its pathogenesis and thus a new potential target in its treatment,” he said.
It has long been established that vascular smooth muscle hyper-reactivity is a fundamental cause of the coronary artery spasm responsible for VSA, and current therapies target the inhibition of vascular smooth muscle contraction.
Inflammation has also been implicated, but previous studies have focused on a systematic inflammatory response, Beltrame said.
“This paper identifies that inflammation within the coronary artery wall, within the PVAT, is related to increased coronary vasoreactivity, thus therapies that target the PVAT inflammatory response may also modulate coronary vasoreactivity, thereby providing a new therapeutic target in the treatment of this disabling and potentially life-threatening condition,” he said.
Ohyama and Beltrame report no relevant financial relationships.
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