The longer you live in a polluted city, the more quickly you develop risk factors for heart attack and stroke, researchers found. We have known that air pollution can be fatal since some 12,000 people died during the smog that choked London in 1952. Today, air pollution is suspected of killing 1.3 million people a year, the World Health Organization (WHO) has estimated. Previously, researchers assumed that air pollution primarily caused lung disease and cancer, but in the past decade they began to realize that its larger impact is increased heart attack and strokes.

The evidence linking outdoor air pollution to cardiovascular disease in humans is still circumstantial and not smoking-gun proof - it shows correlation, not causation. But new studies are strengthening the case against air pollution by looking at the development of atherosclerosis, or hardening of the arteries. In atherosclerosis, inflammation and fatty plaques building up on the artery wall make the vessels thicker and stiffer, raising the risk of heart attack and stroke.

In a new PLoS Medicine study, a multi-institutional team of researchers reports early results from the ongoing 10-year Multi-Ethnic Study of Atherosclerosis and Air Pollution (MESA Air). The researchers followed 5,660 people aged 45-84 living in six US cities and who had no pre-existing heart disease.

"Many previous studies have demonstrated links between exposure to air pollution and heart disease," said first author Dr Sara Adar, an assistant professor of epidemiology at the University of Michigan School of Public Health in Ann Arbor, USA. "This study is important because we followed people over time. This allowed us not only to ask if people in higher polluted areas have thicker arteries but if they also experience a faster rate of thickening of their vessels over time."

The bad news is that people living in areas with high levels of air pollution did develop thicker blood vessels more quickly. The good news is that in places where air pollution decreased, so did the rate of atherosclerosis buildup.

The researchers measured the thickness of the carotid artery by ultrasound at the beginning of the study in 2000 and several years later. This artery supplies blood to the neck, head and brain, and atherosclerosis there can cause stroke. The average thickness of the carotid artery increased by 14 micrometers a year, but participants living the more polluted locations in a city had more rapid thickening than those in less polluted parts - giving them an estimated 2% higher risk of stroke.

But how does air pollution cause atherosclerosis? That is where animals come in, because with air pollution it is infeasible to do the long-term controlled studies needed to establish causality in people, explains Dr Jesus Araujo, the director of environmental cardiology at University of California, Los Angeles, USA, and author of a study in the May issue of Arteriosclerosis, Thrombosis, and Vascular Biology. The WHO estimated that reducing particules of 10 micrometers in pollution from 70 to 20 micrograms per cubic meter could cut air quality related deaths by 15%. But working with mice, Dr Araujo previously found that much smaller particles (less than 2.5 micrometers), such as in vehicle exhausts, are the most toxic ingredients in outdoor air pollution. The MESA Air study measures these ultrafine particles to gauge local air pollution.

Now Dr Araujo has shown that ultrafine particles in diesel exhaust damage blood vessels by changing cholesterol molecules. The "good" HDL cholesterol switches from being protective to being harmful. Normally, HDL inhibits oxidative stress and inflammation in the arteries and removes fatty buildup from plaques in the arteries. But in the mice breathing diesel exhaust, "the HDL molecules lost these good qualities and promoted more oxidation and inflammation instead."

Dr Araujo's work bolsters the MESA Air study by explaining the molecular changes that occur in the cholesterol when living with air pollution. It is only part of the causation picture. Other researchers are investigating other changes to proteins, DNA, and inflammatory and metabolic processes. They are finding links to diabetes, too.

Having diesel trucks rumble past your bedroom window at four in the morning exposes you to other risk factors for cardiovascular disease besides exhaust fumes - namely stress, which can also raise blood pressure and alter metabolism and blood chemistry. There is also more to air pollution than the air outside. The MESA Air study is also looking at indoor pollution over time.

There is clearly more to learn about air pollution and human health. But, say Dr Araujo and some other researchers, the policy implications are very clear: lowering levels of air pollution below the current recommended levels would greatly benefit public health.