Sex differences in patients with ANOCA and confirmed coronary vasomotor dysfunction

Background

Patients with angina pectoris without epicardial coronary stenoses (ANOCA) frequently suffer from coronary vasomotor disorders. These include coronary spasm and microvascular dysfunction. The current ESC guidelines recommend invasive coronary function testing to confirm the diagnosis. However, sex differences in this patient population have so far been insufficiently investigated.

Purpose

The aim of this study was to examine sex differences in clinical presentation, cardiovascular risk factors and invasive measurement results of coronary function testing in ANOCA patients with confirmed coronary vasomotor dysfunction.

Methods

For this analysis, 156 consecutive ANOCA patients (mean age 63 years, 66% women) with normal left ventricular ejection fraction were recruited. All patients underwent coronary angiography with invasive coronary function testing (acetylcholine and adenosine testing (CFR/IMR)) between 2018 and 2025. All patients showed at least one pathological test result, leading to a vasomotor disorder endotype. Demographic factors, cardiovascular risk factors, presentation of clinical symptoms, laboratory parameters, echocardiographical and intraprocedural data were collected for all patients. The analysis focused on sex differences.

Results

48% of patients (n = 75) had isolated coronary spasm, 3% had impaired CFR or increased microvascular resistance (n = 5), and 49% had a mixed form (n = 76). Women more frequently exhibited microvascular spasm than men (71% vs. 45%), whereas men more often had epicardial spasm compared to women (53% vs. 25%, p = 0.002).

Univariate analysis showed that dyspnea (66% vs. 44%, p = 0.007), diabetes (22% vs. 5%, p = 0.011), and HFpEF (35% vs. 13%, p = 0.004) were significantly more common in women than in men. Multivariate analysis identified diabetes (OR 5.4, CI 1.4–20.4, p = 0.011) and HFpEF (OR 3.5, CI 1.4–9.0, p = 0.008) as predictors of female sex, while epicardial coronary spasm was a predictor of male sex (OR 3.6, CI 1.7–7.6, p = 0.001).

Conclusions

ANOCA patients with coronary vasomotor disorders exhibit significant sex differences. In women, a predominantly microvascular disease pattern associated with HFpEF and diabetes is observed, whereas in men, epicardial coronary spasm predominates. In particular, with regard to existing differences in the pharmacological treatment of epicardial and microvascular vasomotor disorders, the findings may have important implications for sex-specific selection of therapy.

These findings underscore the importance of sex-specific precision medicine, particularly in patients with ANOCA.