Long-Term Cardiovascular Risk in Patients With ANOCA: A Clinical Reality to Consider?

Chronic stable angina (CSA) remains one of the most frequent reasons for referral to diagnostic coronary angiography (CAG). In a substantial proportion of these patients, no obstructive coronary lesions or stenoses are identified, a condition referred to as angina with no obstructive coronary arteries (ANOCA). This group has been considered to be at higher cardiovascular risk (CVR), mainly due to persistent symptoms, a high burden of cardiovascular risk factors, and the potential presence of microvascular dysfunction or vasospasm. However, long-term evidence comparing their prognosis with that of the general population remains limited.

In this context, the study by Olesen et al. provides long-term follow-up data aimed at evaluating 15-year CVR in patients with ANOCA referred for CAG due to stable angina, compared with a cohort from the general population. Data were obtained from Danish national registries and included patients ≥18 years of age who underwent elective CAG for suspected CSA between 2003 and 2021, in whom the absence of obstructive coronary artery disease (stenosis <50%) and no prior history of myocardial infarction (MI) were documented, thus defining the ANOCA cohort.

Each ANOCA case was matched in a 1:5 ratio by age and sex with individuals from the general population without a history of cardiovascular disease. The maximum follow-up was 15 years, with a mean follow-up of 10.7 years. Evaluated outcomes included MI, ischemic stroke, and all-cause mortality.

During long-term follow-up, the 15-year cumulative incidence of MI was identical in both cohorts (3.5% in ANOCA vs. 3.5% in the general population). The age- and sex-adjusted incidence rate ratio showed a trend toward a lower relative risk in the ANOCA group (IRR 0.89; 95% CI: 0.81–1.00). In contrast, the risk of ischemic stroke was slightly higher in patients with ANOCA (3.7% vs. 2.9%), with an absolute risk difference of 0.8% (95% CI: 0.5–1.2).

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All-cause mortality was slightly lower in the ANOCA cohort compared with the general population (25.4% vs. 26.3%), with an absolute difference of −0.9% (95% CI: −1.8 to −0.1) and an IRR of 0.86 (95% CI: 0.83–0.90).

Stratified analyses showed that men and older patients (≥75 years) had more favorable risk profiles compared with the general population. In contrast, a specific subgroup—patients with diffuse non-obstructive coronary artery disease—exhibited a significantly increased risk of MI, ischemic stroke, and mortality, clearly differentiating them from patients with minimal or no coronary disease.

Conclusions

In this population-based observational study, patients with ANOCA exhibited a 15-year risk of MI similar to that of the general population, a slightly lower overall mortality, and a modestly increased risk of ischemic stroke. Importantly, subgroups with higher vulnerability were identified—particularly younger patients, women, and those with diffuse non-obstructive coronary artery disease—highlighting the need for more precise risk stratification in this population.

Original Title: 15-Year Cardiovascular Risk in Patients With Angina Without Obstructive Coronary Arteries.

Reference: Olesen KKW, Madsen M, Würtz M, Thim T, Mortensen MB, Sørensen HT, Maeng M. 15-Year Cardiovascular Risk in Patients With Angina Without Obstructive Coronary Arteries. JACC Cardiovasc Interv. 2025 Dec 22;18(24):3009-3020. doi: 10.1016/j.jcin.2025.09.014. Epub 2025 Nov 14. PMID: 41240023.