Last year the results of a multinational, prospective cohort study, the Prospective Urban and Rural Epidemiology (PURE) study, were published, detailing the impact of air pollution on cardiovascular disease. Conducted over nearly 20 years and enrolling communities in 21 countries of varying socioeconomic levels, over 150,000 participants were followed for a median of 9.3 years (corresponding to 1.4 million person-years). Ambient PM2.5 levels were used as a proxy for air quality.
Each 10 μg/m3 increase in PM2.5 was associated with a 5% increase in risk for cardiovascular disease (CVD) events, including a 3% increase for myocardial infarction, a 7% increase for stroke, and an overall 3% increase for CVD mortality. Although the hazard ratios appear at first glance to be fairly low, this increase was found per each 10 ug/m3 increment; also, given the ubiquitous nature of air pollution, the cumulative effects are quite significant. This study found that the population attributable fraction (PAF) for PM2.5 was 13.9% for CVD events, 8.4% for myocardial infarction, 19.6% for stroke, and 8.3% for CVD mortality. Thus nearly 10% of CVD deaths and heart attacks, as well as 20% of strokes wouldn’t occur if the air were cleaner.
Traffic related air pollution (TRAP) specifically is thought to be an important contributor to the cardiovascular morbidity and mortality observed in multiple trials. For example, exposure to TRAP has been linked to over a 3-fold increase in risk for myocardial infarction within the hour following exposure, regardless of whether this exposure occurs from driving, riding a bike, public transport, etc., and is even greater among people with CVD risk factors such as diabetes.
Some of this risk is mediated via vascular dysfunction; changes in aortic hemodynamics as well as transient increases in blood pressure following TRAP exposure have both been well-documented. Both systolic and diastolic pressure increase after exposure to TRAP, and while physical activity generally helps to mitigate the effects of TRAP, at high levels of coarse and larger particulate matter, it may actually exacerbate it.
Data from the Women’s Health Initiative (WHI) found that among postmenopausal women, proximity to a major roadway was associated with an increased risk for hypertension; for example, moving from 1000m to 100m distance was linked to a nearly 10% higher prevalence of hypertension. The WHI also found that road proximity as well as exposure to NO2 were associated with atrial fibrillation in postmenopausal women, suggesting multiple mechanisms mediated by different airborne toxins.
In a recent randomized and double-blind clinical trial, L-arginine supplementation was given to 118 adults with elevated blood pressure, to determine if it could prevent the increase in blood pressure following exposure to TRAP, and potentially mitigate the associated cardiovascular harm. At a dose of 3g L-arginine given three times per day (a total daily dose of 9g) for 2 weeks or placebo, participants took a 2 hour walk along a busy road on day 14. L-arginine significantly reduced both ambulatory and resting blood pressure during and after the walk compared with the placebo group, with no adverse effects reported, and mitigated the blood pressure increase observed in the placebo group. Systolic, diastolic, and mean arterial pressure were 5.3 mmHg, 4.3 mmHg, and 4.6 mmHg lower, respectively, compared to placebo shortly following the walk. There were no differences between groups in the changes to ST-segment levels or other plasma biomarkers, and no associations with any specific air pollutant concentrations.
This effect on blood pressure is consistent with a previous meta-analysis of 11 randomized and double-blinded placebo controlled trials which demonstrated a significant reduction in pressure following L-arginine supplementation; 5.39 mmHg systolic and 2.66 mmHg diastolic at doses ranging from 4 to 24 g/day.
This study appears to be the first to demonstrate a potential benefit for nutritional supplementation to directly mitigate the effects of TRAP on cardiovascular risk. There are certainly other concerns related to air pollution, however, which suggest other interventions may also be appropriate. For example, in an analysis of over 1300 women aged 65-80, a higher omega-3 index was associated with a higher volume of healthy white matter in the brain. But perhaps just as importantly, the omega-3 index appeared to mitigate the harmful effects of PM2.5 on brain atrophy, an important finding given that particulate matter has been linked to neurotoxicity and smaller white matter volumes, possibly mediated via myelin loss or chronic microglial activation. Additionally, fish oil supplementation has been shown to mitigate some of the air pollution induced cardiac and lipid adverse effects in a small clinical trial.
Lastly, in a prospective cohort of nearly 550,000 participants in the US, although particulate matter was associated with increases in cardiovascular and cerebrovascular disease risk, adherence to the Mediterranean diet mitigated this increase in risk, suggesting that a fruit and vegetable rich diet and higher antioxidant intake is likely to be an important component in mitigating air pollution toxicity. Thus, targeted nutritional supplements such as L-arginine and omega-3 fatty acids, combined with an antioxidant and polyphenol rich diet, appear to be leading strategies to mitigate the adverse effects of air pollution on cardiovascular disease risk.
Related Biotics Research Products: