Central Sensitization in Women With Ischemia and No Obstructive Coronary Artery Disease: A Pilot Study

Introduction: Myocardial ischemia with no obstructive coronary arteries (INOCA) is more common in women and associated with adverse cardiovascular outcomes. INOCA patients have recurrent chest pain and reduced quality of life, and therapeutic strategies are poorly defined. Central nervous system factors can promote and maintain spontaneous clinical pain. We explored central sensitization in INOCA. Methods: Twenty-nine women diagnosed with INOCA based on coronary angiography were enrolled. Baseline demographics, risk factors, and angina burden by the Seattle Angina Questionnaire (SAQ) was assessed. Generalized pain hypersensitivity was assessed using the validated Central Sensitization Inventory (CSI), with scores ≥40 indicating the presence of central sensitization. Functional capacity was determined by Duke Activity Status Index (DASI). A DASI score ≤34 is prognostic of major adverse cardiac events. Depressive symptoms were assessed using the Beck Depression Inventory. Descriptive statistics and Pearson correlations were performed; p-value ≤.05 was considered significant. Results: Mean age was 55.4±10 years and body mass index (BMI) was 30.1±7 kg/m 2 . Cardiac risk factors were prevalent with 59% hypertension, 55% hyperlipidemia, and 21% diabetes. SAQ scores indicated a high angina burden: 49.3±25.7 (angina frequency) and 39.3±27.6 (angina stability). Mean CSI score was 40.5±17, and 62% had CSI scores ≥40, indicating central sensitization. Mean DASI score was 33.3±18.6. A majority (52%) had a DASI score ≤34, indicative of guarded prognosis. CSI scores correlated positively with depression (r=0.78, p=0.00001) and BMI (r=0.39, p=0.04), and negatively with DASI (r=-0.36, p=0.05), indicating impaired physical functioning in those with higher levels of central pain sensitivity. Conclusions: Nearly two-thirds of women with INOCA have central sensitization. Central pain amplification is associated with angina, depression, obesity, and a limited functional capacity in mid-life INOCA women. The role of the central nervous system in persistent chest pain should be further investigated and may lead to novel therapeutic strategies.