A prospective study of C-reactive protein as a state marker in Cardiac Syndrome X

Cardiac Syndrome X (CSX), the presence of angina pectoris despite normal epicardial coronary arteries seen on invasive angiography, is known to be associated with an elevation of several inflammatory biomarkers, suggesting a possible role for inflammation in its pathogenesis. We sought to establish if C-reactive protein (CRP) levels varied with disease severity and so whether it is a state or trait marker. We studied 16 CSX patients with typical angina pectoris, normal coronary arteries and an electrically positive exercise stress test (EST) and 13 age- and sex-matched healthy controls (HC). CSX patients were followed up at a subsequent visit with repeated exercise stress testing and CRP measurement. We found that CRP levels were significantly higher in the CSX group compared to the HC (1.5 [0.8-4.5] v 0.8 [0.4-1.4] mg/L, p = 0.02). This elevation in CRP persisted throughout the study length. CRP correlated with time to symptoms on EST at enrolment and at the second visit (r = -0.690, df = 10, p = 0.013 and r = -0.899, df = 4, p = 0.015, respectively). At the follow-up visit, 50% of CSX patients developed electrically and symptomatically negative ESTs. The mean CRP of this group was significantly lower than that of the CSX patients with ongoing symptoms and positive ESTs (1.2 ± 0.2 v 2.8 ± 0.6. mg/L, p = 0.018) and did not differ significantly from that of healthy controls. CRP levels also dropped in patients whose symptoms improved while they increased in patients who became more symptomatic (p = 0.027). We conclude that the results of this small study support the concept of CSX being an inflammatory-mediated condition with CRP levels prospectively varying with functional measures of disease severity. This indicates that CRP is a state marker in CSX.