Environmental determinants of coronary flow reserve and microvascular resistance in ANOCA patients

Background Coronary microvascular dysfunction is increasingly recognized as a contributor to angina in patients without obstructive coronary artery disease (ANOCA). Coronary flow reserve (CFR) and index of microvascular resistance (IMR) are key invasive measures of microvascular function. Effects of environmental factors, including air pollution, noise, temperature, and green space, on chronic and acute coronary syndrome have been recently recognized, but their impact on coronary microvasculature in ANOCA patients remains unclear. Purpose We aimed to investigate associations between high-resolution, residential environmental exposures and coronary microvascular function, as measured by CFR and IMR, in a ANOCA cohort in Belgium, part of the ENACT project. We also explored potential sex-specific differences in these associations. Methods We analyzed 380 patients (mean 64.8 ± 10.8 years, 182 males) undergoing an ANOCA protocol across two centers between October 2019 and November 2024. Environmental exposures at participants’ residential addresses were modeled using high-resolution interpolation, including particulate matter (PM₂.₅, PM₁₀), nitrogen dioxide (NO₂), ozone (O₃), temperature, raodway and aircraft noise, distance to major roads and airports, and neighborhood greenness (NDVI). Linear regression analyses adjusted for age, sex, active smoking, diabetes, hypertension, BMI, personal and family cardiovascular history, chronic kidney disease, obstructive sleep apnea, study centre, and area-level deprivation (BIMD). Analyses were performed in the total population and stratified by sex. Results For CFR, 30-day mean PM₂.₅ was inversely associated with CFR in males (β = −0.342; 95% CI: −0.667 to −0.017; p = 0.039) but not in females. Ozone exposure showed consistent positive associations, particularly the 30-day mean (total population: β = 0.355; 95% CI: 0.041–0.669; p = 0.027; males: β = 0.568; 95% CI: 0.112–1.025; p = 0.015). Mean temperature on the day before the ANOCA protocol was positively associated with CFR in the total population (β = 0.389; 95% CI: 0.103–0.676; p = 0.008) and in males (β = 0.683; 95% CI: 0.267–1.099; p = 0.001). Noise, road proximity, airport distance, and NDVI were not significantly associated. For IMR, associations were generally weaker. Short-term PM₂.₅ exposure was positively associated with IMR in females (β = 2.310; 95% CI: 0.171–4.448; p = 0.034), whereas most other exposures showed no consistent associations. Conclusion In this Belgian multicenter ANOCA cohort, coronary microvascular function showed sex-specific sensitivity to environmental exposures. PM₂.₅ was linked to lower CFR in males and higher IMR in females, while ozone and temperature were positively associated with CFR, especially in males. These findings underscore the relevance of sex differences and high-resolution environmental modeling in understanding microvascular health.