A Brief History of Cardiac Syndrome X: A Biochemical View

When coronary angiography became more widely used
in the 1960s, it was soon apparent that not all patients with
clinical suspicion of coronary artery diseases had obstruction
of the epicardial coronary arteries.1 In 1967, Likoff et al.2
reported on 15 women ranging in age from 30 to 53 years
with chest pain despite normal coronary angiograms, but
with electrocardiogram (ECG) abnormalities at rest (STsegment depression or T-wave inversion) accentuated by
exercise. It was the starting point of the story.
Six years later, in 1973, Kemp et al.3 published the 1st
defnitive study and termed this disease “syndrome X” to denote
the uncertainty of the chest pain etiology in these patients.
This term was subsequently used by other investigators but
often with different criteria as to its defnition.
Cardiac syndrome X (CSX) or microvascular angina is a
clinical defnition that refers to patients with 3 features: 1)
chest pain, 2) positive stress test and ST-segment depression,
and 3) normal coronary arteries on angiography.1, 4
The pathological mechanism responsible for CSX is not
clearly understood, in spite of extensive studies. Endothelial
dysfunction,5 myocardial ischemia,6 abnormal pain
perception, infection,7 and estrogen defciency are among
the most commonly suggested pathogenic mechanisms.8
Given the high frequency of Helicobacter pylori (H.
pylori) infection in CSX and the probable causative effect
of chronic infection in vascular disease, H. pylori has a
probable role in the pathogenesis of CSX.9 In 2009, we
hypothesized th