Air Pollution Causes Cardiovascular Damage Via Lung-Mediated Mechanisms           

Key Point

New evidence sheds light on the biological mechanisms linking exposure to air pollutants with cardiovascular disease.

The American Heart Association (AHA) recently published a statement regarding potential biological mechanisms that link air pollution to cardiovascular diseases through direct effects of air pollutants on the lung. Two studies in the August 15 American Journal of Respiratory and Critical Care Medicine provide evidence that explain how these mechanisms function, which in turn will guide efforts to reduce exposure to the most toxic pollutants.

In the first study, Kai-Jen Chuang, of National Taiwan University in Taipei, and colleagues concluded that urban air pollution may be associated with systemic inflammation, oxidative stress, activation of blood coagulation, impairment of the fibrinolytic system, and alterations in the autonomic nervous system among young healthy people. The researchers also identified sulfate and ozone (O3) as two major traffic-related pollutants contributing to these damaging effects, which occurred after one day of exposure to urban air pollution in Taipei.

“Our study results support the viewpoint of the AHA’s expert panel on biological mechanisms of air pollution effects on cardiovascular events,” the investigators stated. “Gaseous and particulate air pollutants together with their soluble components may enter the lung and activate pulmonary neural reflexes and local inflammation to alter the autonomic nervous system, induce systemic inflammation/oxidative stress, and increase blood coagulability.”

The researchers investigated whether biological mechanisms correlating pollution with cardiovascular events occur simultaneously with urban air pollutant exposure. The investigators recruited 76 young healthy students (ages 18 to 25) from Taipei and collected one blood sample per month for three months. Samples were tested for levels of high-sensitivity C-reactive protein (hsCRP), 8-hydroxy-2’-deoxyguanosine (8-OHdG), plasminogen activator fibrinogen inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) in plasma, and heart rate variability.

The investigators found that increases in hsCRP, 8-OHdG, fibrinogen, and PAI-1, as well as decreases in heart rate variability indices, were associated with increased levels of particles with aerodynamic diameters less than 10 and 2.5 µm, as well as with sulfate, nitrate, and O3 in single-pollutant models. In two-pollutant models, the increase in 8-OHdG, fibrinogen, and PAI-1, as well as the reduction in heart rate variability, remained significantly associated with three-day-averaged sulfate and O3 levels. The researchers also found moderate associations between blood markers of hsCRP, fibrinogen, PAI-1, and heart rate variability indices.

The research team pointed out that recent epidemiologic evidence has linked impaired endothelium-dependent vascular reactivity with cardiovascular diseases; it has also associated high levels of hsCRP and fibrinogen with dysfunctional endothelium in cardiac patients. Furthermore, previous reports indicated that hsCRP concentration induces PAI-1 expression and activity in human aortic endothelial cells, while increased expression of PAI-1 “was demonstrated in the media layer of the arterial segment with atherosclerotic changes and considered as an acute reaction of the vascular endothelium, especially in atheromatous arteries,” the researchers stated. “On the basis of these findings, we conclude that close relations exist between cardiovascular risk increase and impairment in endothelial function and vascular activity related to air pollution.”

These studies contribute to growing evidence that points to a link between increases in fibrinogen, hsCRP, and PAI-1 concentrations and increased cardiovascular disease risk, the investigators noted. They also believe that cardiovascular disease risk might also increase with a decline in autonomic nervous system control related to air pollution or the withdrawal of vagal activity, as the cardiac autonomic alteration of time-domain and frequency-domain heart rate variability indices in their study occurred without major modifications by blood markers.

“Because sulfate and O3 are two typical secondary pollutants and represent similar groups or sources of pollutants in most urban air pollution, our findings imply that risk-based air pollution control policies should focus not only on emissions of primary pollutants but also on secondary aerosol precursors to maximize the benefits of health risk reduction,” the researchers stated.

EFFECT OF DIESEL EXHAUST

In a related study, Håkan Törnqvist, MD, of Umeå University in Sweden, and colleagues investigated the vascular and systemic effects of combustion-derived air pollution in healthy volunteers. In a double-blind, randomized, crossover study, 15 men were exposed to diesel exhaust (particulate concentration, 300 µg/m3) generated from an idling engine, or filtered ambient air for one hour. Twenty-four hours after the initial exposure, the investigators observed a selective and persistent impairment of endothelium-dependent vasodilation that occurs in the presence of mild systemic inflammation among participants who had inhaled diesel exhaust.

Resting forearm blood flow, blood pressure, and basal fibrinolytic markers after 24 hours were similar in both groups, while diesel exhaust increased plasma cytokine concentrations but appeared to reduce endothelium-dependent forearm vasodilation induced by bradykinin (which releases tPA), and acetylcholine (which does not release tPA). However, there were no differences in either endothelium-independent vasodilation (induced by sodium nitroprusside and verapamil, neither of which release tPA) or bradykinin-induced acute plasma tPA release.

“These findings suggest that combustion-derived air pollution may have important systemic and adverse vascular effects for at least 24 hours after exposure,” the investigators stated. “Exposure to air pollution causes airway inflammation and has an important negative effect on respiratory health.” Dr. Törnqvist and colleagues acknowledged that while the biological mechanisms that underlie the cardiovascular effects of particulate matter air pollution are unknown, pulmonary inflammation could result in systemic consequences that damage the cardiovascular system.

“It is useful to integrate epidemiological and toxicological approaches to elucidate the mechanism of the effects of air pollution on health,” Joel D. Kaufman, MD, MPH, of the University of Washington in Seattle, stated in an accompanying editorial. “Many questions remain to be answered. While these questions should by no means slow the important efforts to reduce exposures and benefit global public health, we must continue with careful investigations into the details of the biological mechanisms of air pollution’s effects.”           

—John Merriman

Reference
Chuang KJ, Chan CC, Su TC, et al. The effect of urban air pollution on inflammation, oxidative stress, coagulation, and autonomic dysfunction in young adults. Am J Respir Crit Care Med. 2007;176(4):370-376.
Kaufman JD. Air pollution and mortality: are we closer to understanding the how? Am J Respir Crit Care Med. 2007;176(4):325-326.
Törnqvist H, Mills NL, Gonzalez M, et al. Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am J Respir Crit Care Med. 176(4):395-400.

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