Sept. 30, 2026
Air pollution, a contributor to cardiovascular disease, is gaining attention for its significant impact on cardiovascular outcomes. It's ranked second as a global risk factor for premature death and poor health.
Fine particulate matter with a diameter < 2.5 µm (PM2.5) is one of the major components of air pollution. Mayo Clinic Cardiovascular Medicine researchers found that this nontraditional cardiovascular risk factor is associated with epicardial coronary endothelial dysfunction determined by invasive coronary vasoreactivity testing in patients with angina and non-obstructive coronary artery disease (CAD). Their research suggests a potential biological link between PM2.5 and CAD. The study was published in JACC.
Early artery exposure
Coronary endothelial dysfunction represents an early stage of CAD. The endothelium is the inner lining of blood vessels and one of the earliest sites of vascular injury that can contribute to atherosclerosis if damaged.
The researchers knew about air pollution and vascular health. PM2.5 has been linked to myocardial infarction, heart failure, stroke and death. It has also been linked to faster progression of coronary calcium on computerized tomography, meaning plaque builds up more quickly in people who breathe more polluted air.
"What we didn't have was evidence of the air pollution effect directly on the endothelium of coronary arteries, the vessels of the heart that are eventually responsible for chest pain and myocardial infarction," says Matteo Manzato, M.D., a cardiovascular diseases research fellow at Mayo Clinic in Rochester, Minnesota, and first author of the study. "This study moves the effect of pollution on the cardiovascular system to an earlier stage than we thought. By the time a patient arrives with an event, the vascular injury has been accumulating silently for years. This means that we need to act earlier than we think when addressing environmental exposures. Although our cohort was selected for patients with angina, the coronary arteries were normal or near normal on angiography."
Inspiring future generations
The authors dedicate the research to the memory of Dr. Amir Lerman, who was senior author of the study. Dr. Lerman was a cardiovascular physician-scientist who became a world authority on microvascular function and cardiovascular disease during his nearly 40 years at Mayo Clinic. The authors share that Dr. Lerman's mentorship and dedication to cardiovascular science continue to inspire people across the globe.
The idea for this research came from a personal and a scientific place for Dr. Manzato. "I grew up in one of the most polluted regions of Europe, so air pollution has never been an abstract topic for me," Dr. Manzato says. "Then, during medical school, I worked with a team studying coronary plaque composition, instability and impaired healing in relation to air pollution exposure. The work left me with a question I could not answer: Is air pollution only a destabilizer of plaque that already exists, or is it a primordial insult, something acting at the very beginning of coronary atherosclerosis before we even see a plaque?"
At Mayo Clinic, Dr. Manzato had the opportunity to answer the question. "Thanks to the visionary work of Dr. Amir Lerman, who spent decades building a cohort of patients with angina and no obstructive coronary disease undergoing invasive coronary reactivity testing, we could study the effect of air pollution on the coronary endothelium."
Exceeding limits
The World Health Organization and the Environmental Protection Agency (EPA) established regulatory standards and long-term objectives to reduce PM2.5 pollution levels. Still, more than 90% of individuals worldwide are exposed to levels above recommended limits, according to the research.
Study findings:
- The researchers studied 1,485 individuals with angina and nonobstructive coronary arteries.
- The median age was 51.7 years, and 71% of patients were women.
- For each patient, researchers took the residential address at the time of the procedure and calculated the average PM2.5 concentration over the preceding two years.
- During coronary reactivity testing, incremental doses of acetylcholine were infused into the left anterior descending artery and the vessel response was measured.
- In the cohort, 403 individuals (27%) had endothelial dysfunction. They were exposed to higher levels of PM2.5 than those without.
- For each unit increase in PM2.5 exposure, the risk of having coronary endothelial dysfunction significantly increased by 7%.
A particularly interesting finding: The association between air pollution and endothelial dysfunction was present even at relatively low exposures. "The median PM2.5 exposure in our cohort was 8.22 µg/m3, below the current EPA annual standard of 9 µg/m3, and its effect was still detectable. Meeting the current regulatory standards does not appear to mean that the air we breathe is completely safe from a cardiovascular standpoint," Dr. Manzato says.
The researchers expected that if PM2.5 injured the vasculature, the damage would not be confined to the endothelium. "We anticipated at least some degree of endothelium-independent impairment, meaning abnormal vasomotor function at the level of the smooth muscle and the microcirculation," Dr. Manzato says. "However, coronary flow reserve, which is a marker of endothelium-independent microvascular function, was nearly identical between exposure groups. This tells us that the effects of pollution are probably confined to the endothelium itself."
Next steps
Future studies are needed to test targeted interventions focused on reducing exposure to air pollutants and their damaging effect on cardiovascular health.
"It's also important to educate the cardiology world about assessing social and environmental exposures, which go well beyond pollution itself," Dr. Manzato says. "It means knowing the air quality in the communities where patients live and work and recognizing how to address non-traditional cardiovascular risk factors for a more comprehensive cardiovascular prevention."
For more information
Manzato M, et al. Chronic PM2.5 exposure is associated with invasively assessed coronary endothelial dysfunction. JACC. 2026;88:948.
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