Central Sensitization Drives Symptom Burden in Microvascular Angina: A Cross-Sectional Case-Control Study

Objective: Microvascular angina (MVA), a phenotype of ischemia with non obstructive coronary arteries, produces chest pain despite normal epicardial vessels. Central sensitization (CS) may amplify symptoms, but its magnitude in confirmed MVA is unclear.

Method: We conducted a single center cross sectional study. Adults with MVA undergoing coronary angiography and age- and sex matched healthy volunteers completed the Central Sensitization Inventory (CSI), Hospital Anxiety and Depression Scale (HADS), and chest pain questionnaires. MVA required documented ischemia with ≤ 50% epicardial stenosis. The primary outcome was the difference in mean CSI score; secondary outcomes were the proportion with CSI ≥ 40 and correlations between CSI, angina measures, and HADS subscores.

Results: We enrolled 200 participants; 138 (69%) were male; and the mean age was 61 ± 11 years. Mean CSI-Part A was higher in MVA versus controls (43 ± 15 vs. 19 ± 11; P < 0.001), and clinically significant CS was more prevalent (62% vs. 10%). Within MVA, CSI correlated with chest pain intensity (r = 0.58), weekly episode frequency (r = 0.46), HADS-Anxiety (r = 0.51), and HADS-Depression (r = 0.44) (all P < 0.001). In adjusted models, each 10-point increase in CSI was associated with a 0.47 standard deviation rise in pain score (β = 0.47, 95% confidence interval 0.29–0.64; P < 0.001); the model explained 39% of pain-score variance (R² = 0.39).

Conclusion: Central sensitization is highly prevalent and strongly linked to angina burden in MVA, supporting a heart brain contribution to symptom generation. Interventions that reduce central pain amplification may provide meaningful benefit beyond standard anti ischemic therapy.

Keywords: Central sensitization, chest pain amplification, coronary microvascular dysfunction, ischemia with non-obstructive coronary arteries, microvascular angina