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Interventional Diagnostic Procedure: A Practical Guide for the Assessment of Coronary Vascular Function
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Unveiling Phenotypic Heterogeneity in Coronary Spastic Angina Through Multidimensional Risk Profiling: The FUJI-SPASM
Takamitsu Nakamura1, Tuan Hoang Nguyen1, Takeo Horikoshi1
1Department of Cardiovascular Medicine, University of Yamanashi Faculty of Medicine, Chuo, Japan.
JACC. Advances
|March 30, 2026
Summary
Coronary spastic angina (CSA) presents two distinct phenotypes: metabolic and inflammatory. Both share a vulnerability to low high-density lipoprotein cholesterol (HDL-C), with inflammation adding further risk for coronary spasm.
Area of Science:
- Cardiology
- Internal Medicine
- Biochemistry
Background:
- Coronary spastic angina (CSA) is a functional coronary disorder characterized by recurrent ischemia without significant atherosclerosis.
- The interplay between metabolic and inflammatory abnormalities in CSA pathogenesis is not well understood.
Purpose of the Study:
- To identify distinct CSA phenotypes based on metabolic and inflammatory profiles.
- To determine phenotype-specific factors influencing coronary spasm and endothelial dysfunction.
Main Methods:
- Analysis of 568 patients from the FUJI-SPASM registry with suspected CSA and no obstructive coronary artery disease.
- Unsupervised k-means clustering using 20 clinical and biochemical variables to define phenotypes.
- Regression analyses to identify phenotype-specific determinants of coronary spasm and endothelial dysfunction.
Main Results:
- Two CSA phenotypes were identified: Cluster 0 (metabolic-dominant) and Cluster 1 (inflammation-dominant).
- Low high-density lipoprotein cholesterol (HDL-C) was linked to coronary spasm in both phenotypes.
- Elevated high-sensitivity C-reactive protein (hs-CRP) was independently associated with spasm in the inflammation-dominant cluster.
Conclusions:
- CSA exhibits distinct metabolic and inflammatory phenotypes with varying spasm determinants.
- Reduced HDL-C is a shared risk factor, while inflammation exacerbates spasm risk.
- A stratification approach using HDL-C and hs-CRP offers a framework for personalized CSA risk assessment.
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