Turk Kardiyol Dern Ars. Ahead of Print: TKDA-93273 | DOI: 10.5543/tkda.2025.93273

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

Hüseyin Tezcan¹, Kadri Murat Gürses¹, Muhammed Ulvi Yalçın¹, Yasin Özen¹, Bülent Behlül Altunkeser¹, Nazif Aygül¹, Kenan Demir¹, Abdullah Tunçez¹, Esra Şen Bülbül¹, Ezgi Akyıldız Tezcan^2
1Department of Cardiology, Konya Selcuk University Medical Faculty Hospital, Konya, Türkiye
²Department of Physical Medicine and Rehabilitation, Selcuk University Faculty of Medicine, Konya, Türkiye

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.

Keywords: Central sensitization, chest pain amplification, coronary microvascular dysfunction, ischemia with non‑, obstructive coronary arteries (INOCA), microvascular angina

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