In a study in the March 7 issue of The Journal of Experimental Medicine, Arita and colleagues identify an anti-inflammatory lipid in humans that is derived from an essential fatty acid in fish oil.

Fatty fish contain large amounts of omega-3 fatty acids--diet-derived essential fatty acids known to benefit patients with cardiovascular disease and arthritis. This research group recently identified a new class of aspirin-triggered bioactive lipids, called resolvins, the activity of which may in part explain the beneficial effects of omega-3 fatty acids. Resolvins are made from the omega-3 fatty acids by cellular enzymes and can reduce inflammation in mice. The main bioactive component of this class of lipids was identified in mice and named resolvin E1.

The researchers have now identified this lipid in plasma taken from volunteers given omega-3 fatty acids and aspirin. Human resolvin E1, the authors show, inhibits both the migration of inflammatory cells to sites of inflammation and the turning on of other inflammatory cells.

This study also reveals a potential pitfall of COX-2 inhibitors, drugs designed to block inflammation, which have been shown to have negative cardiovascular side effects. COX-2 is involved in making resolvin E1 and the authors suggest that inhibition of vascular COX-2 by these inhibitors might block the synthesis of resolvin E1, which would eliminate an important anti-inflammatory pathway. The experiment to prove this idea, however, has yet to be done.

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Patients entered the study with LDL-cholesterol levels between 130 mg/dL and 250 mg/dL. More than half of the patients taking Lipitor at 10 mg doses achieved LDL-cholesterol levels of 100 mg/dL or lower.

TNT is an investigator-led trial coordinated by an independent steering committee and was funded by Pfizer. The study enrolled men and women between 35 and 75 years of age in 14 countries.

"In addition to providing outstanding benefits at the lowest and highest doses of Lipitor in the TNT study, it's important to note that patients achieved these benefits safely," Dr. Feczko said. "This is critical new information that potentially could have a significant impact on how physicians approach the treatment of heart disease."

Coronary heart disease is the leading cause of death in the United States, and the majority of Americans with elevated cholesterol, a leading risk factor for heart attacks, are not at their recommended goal levels. Updated guidelines issued by the National Cholesterol Education Program confirm the added benefit of prescribing cholesterol-lowering medication like Lipitor, along with diet modification and exercise, to patients at risk for cardiovascular disease. In addition, the NCEP panel has recommended an LDL- cholesterol level of less than 100 mg/dL as the goal of therapy for patients at high risk of coronary heart disease.

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