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 [CI]: 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.