Introduction: The Paradox of Clear Arteries
For decades, the clinical management of chest pain has been dominated by a binary focus: the presence or absence of obstructive coronary artery disease (CAD). However, a significant proportion of patients—predominantly women—present with classic anginal symptoms but show no evidence of macrovascular obstruction during angiography. This condition, often termed Ischemia with No Obstructive Coronary Arteries (INOCA), has historically been dismissed as benign. Recent evidence, however, suggests that these patients suffer from microvascular dysfunction or vasospasms and carry a higher risk of adverse cardiovascular events. The WOMANOCA nationwide cohort study provides a critical lens into the long-term healthcare utilization of this population, challenging the notion that a clean angiogram equates to clinical resolution.
Study Design and Methodology
The WOMANOCA (Women with symptoms of angina or non-specific chest pain but no obstructive CAD) study utilized the robust Danish national registries to track healthcare contacts over a three-year period. The cohort included all Danish women diagnosed with a first instance of either angina pectoris or non-specific chest pain between 2009 and 2019 who were subsequently found to have no obstructive CAD (defined as <50% stenosis).
The researchers matched 17,836 women with angina and 42,832 women with non-specific chest pain to a reference population of 303,247 asymptomatic women, matched 1:5 by age. The primary outcomes included cardiac-related hospital readmissions, general practitioner (GP) consultations, out-of-hours consultations, and diagnostic procedures such as electrocardiograms (ECGs). Cox regression models were employed to estimate hazard ratios (HR) with 95% confidence intervals (CI), adjusting for relevant comorbidities and socioeconomic factors.
Key Findings: A Sustained Clinical Footprint
The results of the WOMANOCA study underscore a significant and sustained healthcare burden among women without obstructive CAD. Compared to the reference population, women in both symptomatic groups experienced substantially higher rates of healthcare contact.
Cardiac Readmissions
Women diagnosed with angina exhibited a more than threefold increase in the risk of cardiac-related hospital readmissions (HR 3.24; 95% CI 3.10–3.38). Notably, those diagnosed with non-specific chest pain also faced a nearly threefold risk (HR 2.87; 95% CI 2.78–2.97). When comparing the two symptomatic groups directly, the angina cohort had a 16% higher risk of readmission than the non-specific chest pain cohort, suggesting that while both groups are at high risk, a formal diagnosis of angina may correlate with higher symptom severity or clinical concern.
Primary Care and Out-of-Hours Consultations
Interestingly, the study found that women with non-specific chest pain had a higher frequency of GP direct consultations and out-of-hours medical contacts compared to both the reference group and the angina group. This suggests a pattern of diagnostic uncertainty. Without a definitive cardiovascular diagnosis, these patients may cycle through the primary care system more frequently in search of answers for their persistent symptoms.
Diagnostic Testing
The utilization of ECGs was significantly higher in the non-specific chest pain group. This frequent re-testing likely reflects the clinical dilemma faced by providers: how to manage a patient with recurring symptoms and a ‘normal’ previous cardiac workup. The lack of a clear treatment pathway for non-obstructive pain leads to repetitive, and often redundant, diagnostic cycles.
Expert Commentary: The Cost of Diagnostic Gaps
The findings from WOMANOCA highlight a critical gap in the current cardiovascular care continuum. The ‘non-specific’ label is often a clinical ‘wastebasket’ that fails to account for functional disorders like coronary microvascular dysfunction (CMD) or coronary artery spasm.
From a mechanistic perspective, the higher readmission rates and primary care visits are biologically plausible. Microvascular dysfunction affects the small resistance vessels of the heart, which cannot be visualized on standard coronary angiograms. Patients with CMD often experience symptoms that are just as debilitating as those with obstructive CAD. Furthermore, the psychological impact of being told ‘nothing is wrong’ while symptoms persist can lead to increased anxiety, which may further exacerbate healthcare-seeking behavior.
Clinicians should consider that ‘no obstructive CAD’ does not mean ‘no cardiac disease.’ The integration of provocative testing or non-invasive functional imaging (such as cardiac MRI for stress perfusion) may provide the definitive diagnosis needed to stabilize these patients and reduce their reliance on emergency and primary care services.
Conclusion
The WOMANOCA study demonstrates that the healthcare burden following a diagnosis of chest pain in women with no obstructive CAD is heavy and persistent. These women are not ‘cured’ by a clear angiogram; rather, they continue to utilize healthcare resources at rates significantly higher than their asymptomatic peers. To alleviate this burden, healthcare systems must move beyond the obstructive model of CAD and implement structured pathways for the diagnosis and management of functional coronary disorders. Only by addressing the underlying cause of the symptoms can we reduce the cycle of readmissions and improve the quality of life for this large and underserved patient population.
Funding and Clinical Registry Information
This study was supported by various Danish health foundations. Data were retrieved from the Danish National Patient Registry and the Danish Civil Registration System. No specific clinical trial registration number is applicable as this was a retrospective registry-based cohort study.
References
1. Dalsgaard JL, et al. The use of healthcare contacts following a first diagnosis of chest pain among women with no obstructive coronary artery disease: results from the WOMANOCA nationwide cohort study. Eur Heart J Qual Care Clin Outcomes. 2025.
2. Kunadian V, et al. EAPCI Expert Consensus Document on Ischaemia with Non-obstructive Coronary Arteries in Women. Eur Heart J. 2020;41(37):3504-3520.
3. Ford TJ, et al. Stratified Medical Therapy Using Invasive Coronary Function Testing in Angina: The CorMicA Trial. J Am Coll Cardiol. 2018;72(23 Pt A):2841-2855.
