Systems Biology
Proteasome Recognized
as Nuclear Player on Gene-transcription Team
Pharmacology
Sense of Security May Be False
with Tried and True Anti-inflammatories
Immunology
Discovery of Calcium Channel
Protein Illuminates T Cell Signaling
Medical Education Reform
• New Curriculum Revs Up for Summer
• Introduction to the Profession: Entering Students Take the Plunge
Cutting Air Pollution Shown to Save Lives
Enoxaparin Beats Heparin in Clot-busting Trial
Kass Lecture Promotes Advance of Women in Surgery
HMS Faculty Inaugurate Medical Foundation in Dubai
Rabkin Fellows Chosen for ’06–’07
• The Enabling Side of a Disabled Child
• Ethics in Research: Are We Teaching by Example?
Cutting Air Pollution Shown to Save Lives
The highly influential Harvard Six Cities cohort study lasting from 1970 to 1990 linked fine particulate air pollution with increased mortality in 1993. Now a follow-up study examining the same cities and individuals from 1990 to 1998 reinforces the original findings and associates a long-term drop in air pollution with decreased risk of death. The findings appear in the March 15 American Journal of Respiratory and Critical Care Medicine.
Illustration by Rachel Eastwood, based on original courtesy of the EPA
Tiny toxins. Smokestacks and tailpipes produce bits of pollution so small that about 28 2.5 micrometer particles fit across the diameter of a single human hair. These particles, composed of acids, metals, and organic chemicals, flow through the nose and throat into the lungs and bloodstream, where they cause serious cardiovascular and respiratory disease.
The original study determined causes of death among 8,096 white adult participants
in six U.S. cities using death certificates. In the same cities, researchers
measured the concentrations of fine particulate matter (PM2.5), particles
smaller than 2.5 micrometers in diameter that form from the emissions
of power plants and automobiles. When inhaled, these minuscule particles
make their
way deep into the lungs and bloodstream, where they have toxic effects.
The study found that as concentrations of fine particles increased,
mortality from lung cancer and cardiopulmonary disease also increased.
Francine Laden, HSPH assistant professor of environmental epidemiology and HMS assistant professor of medicine at Brigham and Women’s Hospital, and colleagues continued these observations from 1990 to 1998. The annual mean PM2.5 concentrations, based on estimates because the original study’s air-monitoring stations had been removed, decreased in each city, as did death rates. Using overall averages across the cities and controlling for an increase in life expectancy, Laden found that for every µg/m3 decrease in PM2.5 concentrations, death rates dropped by 3 percent, primarily for cardiovascular and respiratory diseases, two leading causes of death in the United States. These findings suggest that the adverse effects of long-term PM2.5 on health may be partly reversible. “Our study shows that if you reduce pollution, you save lives,” said Laden.
These results came at a crucial time in air quality policymaking since the Environmental Protection Agency has proposed new National Ambient Air Quality Standards, which were open to public comment until April 17. The proposal keeps annual mean PM2.5 concentration limits at 15 µg/m3 despite recommendations from the EPA’s board of external scientific advisers to lower limits to 13 or 14 µg/m3. This study supports the science advisers’ recommendations that “lower is better,” said Laden.
Enoxaparin Beats Heparin in Clot-busting Trial
A study in the April 6 New England Journal of Medicine has found that a new blood-thinning strategy using enoxaparin (Lovenox) is superior to the standard blood-thinning strategy using unfractionated heparin when treating heart attack patients.
When a complete artery blockage causes a heart attack, clearing that artery quickly is paramount. “Time is muscle. As each minute ticks by, some amount of heart tissue becomes irretrievably lost,” said first author Elliott Antman, HMS professor of medicine at Brigham and Women’s Hospital. Although many physicians feel the best means of opening the artery is angioplasty, not every hospital can perform the procedure. Worldwide, the most common treatment is a three-pronged pharmacological clot-busting approach that involves a drug to break up the fibrin mesh forming the clot, an antiplatelet drug (usually aspirin), and an anticoagulant.
This study, enlisting more than 20,000 myocardial infarction patients from 674 hospitals in 48 countries, examined the performance of two different anticoagulant strategies in this pharmacological regimen. The patients all received fibrinolysis and aspirin, but were randomized to also receive either standard 48-hour therapy with unfractionated heparin or enoxaparin as the blood-thinning component for the duration of hospitalization.
Unfractionated heparin has a variable effect on coagulation because its long sugar chains indiscriminately bind to proteins. To ensure proper dosing, it requires multiple blood-clotting tests each day. The drug must be administered in an intravenous infusion and, once treatment stops, the coagulation cascade sometimes springs back into action and forms new clots.
Enoxaparin, a low–molecular weight heparin enriched with short sugar chains, has a reliable anticoagulation effect that requires no monitoring of the clotting system. It can be administered twice a day by injection, and no rebound effect has been reported. Enoxaparin has been associated with more bleeding than unfractionated heparin, however.
The enoxaparin group showed a 17 percent reduction in the risk of death or nonfatal heart attack and a 26 percent reduction in the need for urgent revascularization. These findings indicate that for every 1,000 ST-elevated myocardial infarction patients treated with enoxaparin instead of unfractionated heparin, there would be 15 fewer nonfatal second heart attacks, seven fewer bypass surgeries, and six fewer deaths, all at the cost of four additional episodes of bleeding. Antman and colleagues believe these findings suggest that doctors should now use enoxaparin instead of unfractionated heparin when giving clot-busting drugs to heart attack patients.
This double-blind study required that neither patients nor their doctors knew which treatment they were receiving, so every patient received either an IV infusion of unfractionated heparin and placebo injections or an IV infusion of placebo and enoxaparin injections. These efforts, according to Antman, along with independent statistical analysis by HMS researchers, helped avoid conflicts of interest in the study, which was funded by a grant from Sanofi-Aventis, the makers of Lovenox.