Douglas L. Rodermund and Dr. Clive Arden Pope, Economics

Exposure to elevated concentrations of ambient particulate matter (PM) has been implicated as a risk factor for cardiovascular disease and mortality. Repeated long-term exposure to PM contributes to pulmonary and systemic oxidative stress, inflammation, atherosclerosis and increased risk of ischemic heart disease and death.1 Short-term elevated PM exposures and related inflammation may also contribute to acute complications of atherosclerosis by increasing the risk of atherosclerotic plaque rupture, acceleration of acute ischemic events and endothelial dysfunction. The endothelium is a layer of thin flat cells lining the interior surface of blood vessels and is directly involved with regulation of vascular processes. Our understanding of endothelial cell responses has led to the development of tests that are believed to reflect endothelial function. Given the central role of the endothelium in maintaining vascular homeostasis and the development of atherosclerosis, endothelial function testing may serve as a “barometer” 2 for cardiovascular health and risk. This study, in conjunction with a pilot study conducted by Dr. C. Arden Pope III which seeks to examine the potential effects of short-term fine particulate air pollution on endothelial function, reviews the growing literature to further evaluate endothelial function.

The endothelium is a single-cell lining covering the inner surface of blood vessels, cardiac valves, and numerous body cavities.3 The location of the endothelium inside the blood vessels allows it to “sense” changes in hemodynamic forces and blood-borne signals and “respond” by releasing vasoactive substances. There are many vasoactive substances, the most common is nitric oxide (NO). NO is the endothelium-derived relaxing factor that plays the most pivotal role in the maintenance of vascular tone and reactivity. NO along with other endothelium-derived vasoactive factors work in concert to maintain vasomotion, smooth muscle proliferation, thrombosis, inflammation, coagulation, fibrinolysis and oxidation.

Endothelium dysfunction occurs when the endothelium fails to produce endothelium-derived vasoactive factors, and is defined as the loss of one or more of the above mentioned functions. Endothelial dysfunction may arise from a number of classical risk factors such as diabetes, smoking, hypertension and aging. Other novel/emerging risk factors may include infection, inflammation, physical inactivity and obesity. The resulting conditions promote impaired vasomotion, a pro-thrombotic state, a pro-inflammatory state and proliferation in the arterial wall, which leads to atherosclerotic plaque formation, plaque rupture and decreased blood flow.4 At that time patients become predisposed to cardiovascular events such as myocardial infarction and ischemic stroke. Given this causal relationship between endothelial dysfunction and acute coronary syndromes numerous methods have been devised to assess endothelial dysfunction.

Various methods to quantify endothelial function have been developed, each with its advantages and disadvantages. The most common methods are quantitative coronary angiography, brachial artery catheterization, vascular tonometry and brachial artery ultrasound. Quantitative coronary angiography is an expensive, invasive procedure that carries many risks; however, it allows clinicians to look directly at the point of interest in the heart and to directly quantify endothelial function. Brachial artery catheterization is still invasive, which increases the risk of injury or infection; however the brachial artery is more accessible than coronary arteries and provides the most similar results to direct coronary quantification. Vascular tonometry is noninvasive, safe and faster than all other methods. One serious disadvantage to the vascular tonometry method, however, is that its results may be biased due to structural aspects of the vasculature other than the endothelium. The brachial artery ultrasound method is the most common of the four, it is safer and faster than the invasive methods and closely correlates to endothelial dysfunction in coronary circulation. The ultrasound method, however, is highly operator-dependent, provides poor resolution relative to arterial size and thus may result in inaccurate measurements.

A growing body of evidence suggests that fine particulate air pollution is linked to increased risk of cardiovascular morbidity and mortality through systemic inflammation.1 Owing to this evidence and the knowledge that systemic inflammation may be a risk factor for endothelial dysfunction and subsequently cardiovascular disease and mortality, the endothelium may be the pathophysiological pathway through which particulate air pollution affects the body. Recent studies demonstrate that systemic inflammation caused by elevated levels of ambient particulate air pollution as well as environmental tobacco smoke may induce endothelial dysfunction leading to cardiovascular disease and death.5,6,7 These studies suggest a link between endothelial dysfunction and air pollution. These studies however are not fully conclusive and future research is required into the link between air pollution, systemic inflammation and the endothelium.

The pathophysiological pathways through which air pollution affects the body are not yet fully understood. However, as methods of measuring endothelial function and study designs improve epidemiologists and others may have the tools necessary to fully understand the connection between air pollution and acute ischemic events. Studies similar to those of Brook et al (2002) and most recently Dr. C Arden Pope III will continue to help clarify the relationship between the particles we inhale and accompanying health risks.

References

1. Pope CA, Dockery DW. Critical review: health effects of fine particulate air pollution: lines that connect. J Air & Waste Manag Assoc. 2006;56:709-742.
2. Vita FA, Keaney JF. Endothelial function- a barometer for cardiovascular risk? Circulation. 2002;106:640-642.
3. Verma S, Anderson TJ. Fundamental of endothelial function for the clinical cardiologist. Circulation. 2002;105:546-549.
4. Widlansky ME, Gokce N, Keaney JF, Vita JA. The clinical implications of endothelial dysfunction. J AM Coll Cardiol. 2003;42:1149-1160.
5. Brook RD, Brook JR, Urch B, Vincent R, Rajagopalan S, Silverman F. Inhalation of fine particulate air pollution and ozone causes acute arterial vasoconstriction in healthy adults. Circulation. 2002;105:1534-1536.
6. Celermajer DS, Adams MR, Clarkson P, Robinson J, McCredie R, Donald A, Deanfield JE. Passive smoking and impaired endothelium-dependent arterial dilatation in healthy young adults. N Eng J Med. 1996;334:150-154.
7. Woo KS, Chook P, Leong HC, Huang XS, Celermajer DS. The impact of heavy passive smoking on arterial endothelial function in modernized Chinese. J Am Coll Cardiol. 2000;36:1228-1232.
8. Rodermund DL. The effects of air pollution on endothelial function: an annotated bibliography. Department of Economics Brigham Young University, Working Paper. 2007.