Highlight
- Chronic exposure to PM2.5 particulate matter is significantly associated with epicardial coronary endothelial dysfunction (EED), an early stage of coronary artery disease.
- Invasive coronary vasoreactivity testing confirms that higher PM2.5 levels correlate with impaired coronary artery dilation response.
- Each 1 µg/m3 increment in PM2.5 exposure increases the odds of endothelial dysfunction by approximately 7.8%, independent of traditional cardiovascular risk factors.
- Study underscores the importance of environmental air quality as a modifiable risk factor for early vascular injury and CAD development.
Study Background
Coronary endothelial dysfunction (ED) represents a critical early pathophysiological stage in atherosclerosis and coronary artery disease (CAD). It is characterized by impaired ability of coronary arteries to dilate in response to vasodilators, often preceding clinically overt CAD. Traditional risk factors such as hypertension, dyslipidemia, diabetes, and smoking have been well-established contributors to endothelial dysfunction. Recently, environmental factors like air pollution, especially fine particulate matter less than 2.5 micrometers in diameter (PM2.5), have emerged as nontraditional cardiovascular risk factors implicated in systemic inflammation and vascular injury.
PM2.5 particles penetrate deeply into the respiratory tract and enter systemic circulation, provoking oxidative stress, inflammation, and endothelial injury. However, while associations between PM2.5 and cardiovascular morbidity and mortality are well documented, direct evidence linking chronic PM2.5 exposure to coronary endothelial function—measured invasively—has been limited. This study aimed to fill this knowledge gap by assessing the relationship between long-term PM2.5 exposure and epicardial coronary endothelial function in a large cohort.
Study Design and Methods
This observational study prospectively enrolled 1,485 patients with angina and nonobstructive CAD who underwent coronary reactivity testing at Mayo Clinic from 2000 through 2023. The study population had a median age of 51.7 years, with a wide interquartile range (42.7–60.1 years). Key inclusion criteria were typical angina symptoms and the absence of significant coronary artery obstruction on angiography.
Coronary endothelial function was assessed invasively using intracoronary acetylcholine infusion with quantitative coronary angiography. Epicardial endothelial dysfunction (EED) was defined as a percent change in coronary artery diameter of less than -20% in response to acetylcholine, indicating vasoconstriction or lack of expected vasodilation.
Residential addresses at the time of testing were geocoded and linked to spatially resolved (0.01° × 0.01° resolution) monthly PM2.5 exposure data derived from environmental monitoring, averaged over two years prior to testing to estimate chronic exposure. The 2-year averaging was selected to capture sustained exposure.
Statistical analysis employed a generalized propensity score with a gamma-distributed model to generate stabilized inverse probability weights, helping to control for confounding by indication. Multivariable logistic regression models adjusted for demographic and clinical variables including age, sex, body mass index (BMI), and cardiovascular comorbidities examined associations between PM2.5 levels (modeled as a continuous variable) and odds of EED.
Key Findings
The analysis revealed that individuals exposed to PM2.5 concentrations above the Environmental Protection Agency (EPA) standards of 9 µg/m3 were younger yet had surprisingly worse lipid profiles despite fewer traditional cardiovascular comorbidities. This suggests that environmental exposure may independently influence coronary endothelial health beyond classic risk factors.
In weighted multivariable regression analyses, each incremental 1 µg/m3 increase in chronic PM2.5 exposure was associated with a 7.8% increase in the odds of epicardial endothelial dysfunction (Odds Ratio: 1.078; 95% Confidence Interval: 1.021–1.139; P = 0.007). This relationship persisted even after adjustment for age, sex, BMI, hypertension, diabetes, and dyslipidemia, underscoring the robustness of the association.
These findings provide compelling evidence for a dose-response association between PM2.5 and coronary endothelial injury, verified by the gold standard invasive testing rather than indirect or surrogate markers.
Expert Commentary and Biological Plausibility
This study offers a significant advance in establishing a causal pathway linking ambient air pollution to subclinical coronary artery disease mechanisms. The use of invasive coronary reactivity testing confers a high degree of experimental precision and clinical relevance. Prior epidemiological studies have demonstrated higher cardiovascular risk with PM2.5 exposure, but this study uniquely characterizes the endothelial functional impairment that likely initiates the atherogenic cascade.
Mechanistically, inhalation of PM2.5 triggers systemic oxidative stress, inflammatory mediator release, and endothelial nitric oxide synthase (eNOS) inhibition, all contributing to endothelial dysfunction. The coronary circulation, with its high metabolic demands and sensitivity to vasomotor regulation, may be particularly vulnerable.
Limitations include the observational design, which cannot definitively prove causation, potential residual confounding, and reliance on residential address for exposure estimates without accounting for time spent indoors or workplace exposures. The cohort’s composition — patients with angina and no obstructive CAD — may limit generalizability to other populations, including healthy individuals or those with established CAD.
Conclusion and Clinical Implications
This large prospective observational study conclusively associates chronic exposure to fine particulate air pollution (PM2.5) with invasive measures of epicardial coronary endothelial dysfunction, a critical early event in atherosclerosis and CAD pathology. These results reinforce environmental air pollution as a modifiable and significant nontraditional cardiovascular risk factor.
From a clinical perspective, these findings support the importance of environmental health policies aimed at reducing PM2.5 pollution levels to prevent early vascular injury and downstream cardiovascular events. For cardiology practitioners, awareness of air pollution’s vascular impact should be integrated into comprehensive cardiovascular risk assessment and patient counseling.
Future research directions include longitudinal studies tracking progression from endothelial dysfunction to clinical CAD events, intervention trials testing whether reductions in PM2.5 exposure improve endothelial function, and explorations of molecular pathways linking pollution to vascular injury.
Funding and ClinicalTrials.gov
The cited original research does not specify funding sources within the abstract. The study was conducted using Mayo Clinic patient data from 2000 to 2023. No ClinicalTrials.gov identifier is provided, consistent with the observational cohort design.
References
- Manzato M, Kalhor P, Nogami K, et al. Chronic PM2.5 Exposure Is Associated With Invasively Assessed Coronary Endothelial Dysfunction. J Am Coll Cardiol. 2026;88(9):937-947. PMID: 42159534.
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- Libby P. Inflammation in atherosclerosis. Arterioscler Thromb Vasc Biol. 2012;32(9):2045-2051.
- Mills NL, Robertson S, Gardner F, et al. Inhalation of diesel exhaust causes vascular dysfunction and impairs endogenous fibrinolysis. Circulation. 2005;112(25):3930-3936.
