Infections might also act from a distance, in what I call an echo effect. When the body fights infections, inflammatory mediators can escape into the blood and travel to distant sites. These substances can, in theory, stimulate the white cells in atherosclerotic plaques, thereby prompting plaque growth or rupture. Clinical trials to see whether limited courses of antibiotics will prevent recurrent heart attacks are under way. A recently completed trial suggests, however, that antibiotics do not forestall recurrences in heart attack survivors.
INFLAMMATION’S essential role in atherosclerosis implies that anti-inflammatory medicines might slow this disease, and some (including aspirin) are already in use or under study. But logic and the investigations conducted so far suggest a need to look elsewhere as well.
Aspirin belongs to the class of drugs called NSAIDs (nonsteroidal anti-inflammatory drugs), a group that also claims such popular painkillers as ibuprofen and naproxen. Like other NSAIDs, aspirin can block the formation of certain lipid mediators of inflammation, including the prostaglandins, which generate pain and fever. Strong data from well-performed clinical trials indicate that aspirin shields against heart attacks and, in some patients, against mini strokes (technically, transient ischemic attacks, or TIAs). But the low doses that afford this protection probably reduce the clotting propensity of blood instead of quieting inflammation.
Scientists have little clinical data relating to the effects of other NSAIDs on atherosclerosis, and some evidence suggests that selective inhibitors of the prostaglandin- producing enzyme COX-2 might actually enhance thrombus development in some patients. Cortisone and related steroids could prove too toxic for longterm use, and no data support their utility in reducing atherosclerotic complications.
Even if anti-inflammatory drugs proved effective, they might have to be given for years on end to keep atherosclerosis at bay. That prospect worries me, because ongoing interference with inflammation could come at too high a price: increased risk of infection. One day someone could devise a way to halt the chronic, destructive inflammation of atherosclerosis without undermining overall immunity. But I suspect that a more practical strategy would concentrate on defusing the triggers at the root of arterial inflammation.
Fortunately, some means are at hand already. A heart-healthy diet, regular exercise and, for obese individuals, weight loss can reduce the risk of a heart attack and combat diabetes. In addition, since 1994 several impeccably designed and executed clinical trials have established beyond a doubt that lipid-lowering drugs can reduce the likelihood of atherosclerotic complications and can prolong life seemingly across the board—that is, in individuals with a broad range of risk levels. Researchers have not yet nailed down the mechanism behind the success of the lipid-lowering drugs, which do not seem to reduce arterial stenosis substantially. But studies of cells, whole animals and humans suggest that lipid lowering (as might be expected from the foregoing discussion) might help by limiting inflammation, thereby minimizing plaque buildup and make existing plaques less likely to rupture.
Recent analyses of the statins (widely prescribed lipid-controlling drugs) support this notion. They confirm that the drugs can decrease inflammation in patients. Experiments on isolated cells and laboratory animals indicate as well that the drugs’ anti-inflammatory effects may not depend entirely on changing the concentrations of lipids in the blood. Statins— which decrease the levels of LDL and related bad lipids by increasing their disposal in the body—also limit the availability of chemicals that enable cells to respond to inflammatory mediators.