Air Pollution Increases DVT Risk

Long-term exposure to particulate air pollution is associated with altered coagulation function and increased risk of deep vein thrombosis (DVT), a new study suggests [1].

The study, published in the May 12, 2008, issue of the Archives of Internal Medicine, was conducted by a group led by Dr Andrea Baccarelli (Harvard School of Public Health, Boston, MA).

They note that exposure to particulate air pollution has been associated with increased short- and long-term morbidity and mortality from heart disease and stroke and that hypercoagulability and enhanced thrombosis have been indicated as one mechanistic pathway that mediates such effects, but there is no evidence currently available relating air pollution exposure to DVT. They therefore examined whether long-term exposure to air pollution was associated with increased thrombotic susceptibility and higher DVT risk in a large case-control study conducted in the Lombardy region in northern Italy.

The cases included 871 patients who were Lombardy region residents and had been diagnosed from January 1995 through September 2005 as having lower-limb DVT with or without symptomatic pulmonary embolism (PE). The controls included 1210 healthy Lombardy region residents who were recruited by asking each of the cases for a list of friends and then selecting individuals using an algorithm that balanced the age distribution of the controls to that of the cases. The exposure to particulate matter of less than 10 µm in aerodynamic diameter (PM10) was estimated in the year before DVT diagnosis (cases) or examination (controls) through monitors located at 53 sites throughout the Lombardy region and was assessed for each subject on the basis of their residential address.

Results showed that higher mean PM10 levels in the year before the examination were associated with shortened prothrombin time in both DVT cases and controls. In addition, exposure to increased concentrations of particulate air pollution in the year before diagnosis was associated with increased DVT risk after researchers controlled for clinical and environmental covariates. Each increase of 10 µg/m3 in PM10 was associated with a 70% increase in DVT risk. The DVT risk increase associated with air-pollution levels was smaller in women and limited to those who were not using oral contraceptives or hormone therapy at the time of diagnosis.

Population	OR (95% CI)	p
All subjects	1.70 (1.30 - 2.23)	0.001
Males	2.07 (1.50 - 2.84)	<0.001
Females	1.40 (1.02 - 1.92)	0.04
Females using oral contraceptives or hormones	0.97 (0.58 - 1.61)	0.89
Females not using oral contraceptives or hormones	1.64 (1.05 - 2.57)	0.03

The authors note that hormone therapies are independent risk factors for DVT, which is also confirmed in this study by the higher prevalence of oral contraceptive and hormone use in the cases compared with the controls. They add that use of oral contraceptives and hormone therapy induces changes in coagulation factors that are similar in characteristics and degree to the coagulation changes observed after exposure to air particles, and they surmise that "prothrombotic mechanisms are already activated in those receiving hormone therapy, so that they undergo less or no further induction after air-particle exposure."

They conclude: "Given the magnitude of the observed effects and the widespread diffusion of particulate pollutants, our findings introduce a novel and common risk factor into the pathogenesis of DVT and, at the same time, give further substance to the call for tighter standards and continued efforts aimed at reducing the impact of urban air pollutants on human health."

Editorial questions magnitude of effect

In an accompanying editorial, Dr Robert D Brook (University of Michigan, Ann Arbor) says that what is most surprising from the current results is not that air pollutants are associated with venous thrombosis, but rather the large magnitude of the reported risk. Noting that the adjusted odds ratio for DVT or PE was 1.70 for every 10-µg/m3 elevation in PM10, he points out that the risk of DVT could increase by as much as 10-fold or more, for a not-too-uncommon annual mean PM10 level of 50 µg/m3. "Put into context, this is the acceptable annual concentration limit for PM10 in the United States as designated by the 1997 National Ambient Air Quality Standards (NAAQS) set by the Environmental Protection Agency. Importantly, these levels of particle pollution occur within North American cities and are actually exceeded on a regular basis throughout much of the emerging urban world," Brook notes. He adds that on the basis of this data, even levels of PM10 that are well within compliance of the annual NAAQS might increase the risk for DVT, and at more extreme levels, air pollutants might increase the risk for DVT by an even greater magnitude than several of the major established risk factors, which he says appears somewhat questionable.

He gives another example of smoking cigarettes, which causes repetitive daily exposure to particles at levels much higher than even the dirtiest air-pollution days in this study, but it is associated with a much more modest increase in DVT risk. Therefore, he says that either air pollution is particularly toxic or this case-control study erroneously overestimated the true risk.

But he also comments: "Even in light of these considerations, given the study findings, some degree of clinically meaningful association between ambient particulate air pollution and venous thrombosis appears to be likely existent and worthy of future attention.

"If future studies corroborate their findings and address some of the limitations, it may be proven that the actual totality of the health burden posed by air pollution, already known to be tremendous, may be even greater than ever anticipated," Brook says. "To loosely paraphrase an aphorism, you do not need to know every last detail about the archer who shot you with a poison arrow before you know that you need to pull the arrow out," he concludes.

The authors have disclosed no relevant financial relationships.

Sources

1.   Baccarelli A, Martinelli A, Zanobetti A, et al. Exposure to particulate air pollution and risk of deep vein thrombosis. Arch Intern Med 2008; 168:920-927.

2.  Brook R D. Air pollution. What is bad for the arteries might be bad for the veins. Arch Intern Med 2008; 168:909-911.