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Can treating inflammation reduce risk of cardiovascular disease?

Robin Wulffson MD's picture
heart attack, stroke, prevention, methotrexate, canakinumab, Ilaris

Can treating inflammation reduce the risk of cardiovascular disease? That question is the focus of two new clinical trials; one is being conducted by the National Institutes of Health (NIH) and pharmaceutical manufacturer Novartis.

The researchers are evaluating whether treating inflammation can reduce the risk of a heart attack or stroke; if they obtain favorable results, the findings could lead to new therapies to treat cardiovascular disease. Previous studies have primarily focused on well-known risk factors such as hypertension and elevated cholesterol levels. The new studies will test the theory that inflammation plays a significant role in the underlying biology that makes heart disease the number one cause of death and stroke the number four cause of death in the United States.

Inflammation is a component of the body’s normal healing response to injury. When the walls of the coronary arteries, which provide blood to the heart, or the carotid arteries, which carry blood to the brain, are damaged from the effects of negative health factors such as smoking, obesity, and elevated cholesterol, the immune system as part of the inflammatory response releases cells that travel to the damaged area to repair the injury. However, the repeated attack of irritants, particularly in individuals with genetic factors for cardiovascular disease, the immune system can overreact. Instead of protecting the blood vessels, the inflammation becomes chronic; thus, leading to the accumulation and potential rupture of plaques (arterial deposits), which can result in heart attacks and strokes.

During the past two decades, research has revealed that individuals with chronic inflammation are at significantly higher risk of heart attack and stroke compared with those with evidence of little or no such inflammation. This inflammation can be detectable at low levels with a high-sensitivity test for a marker called C-reactive protein. Whether the risk can be reduced by inhibiting or shutting down the process with anti-inflammatory agents drugs, however, is currently not known.

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In recent years, significant progress in stroke and heart attack prevention has been made; researchers note that this is due to the cumulative impact of prevention strategies that include more aggressive use of cholesterol and-lowering drugs, blood pressure-lowering drugs, anti-smoking programs, exercise programs, and healthy diet advice. From 2002 through 2007, heart attack admissions among seniors dropped almost 25%. Furthermore, a recent study reported that stroke deaths declined by nearly 20% in the decade ended in 2008. Despite those promising statistics, however, both conditions are major health concerns. According to the American Heart Association, more than 1.25 million Americans suffer a heart attack each year and nearly 800,000 suffer a stroke.

The NIH study will test whether the widely used generic anti-inflammatory drug methotrexate can reduce major cardiovascular events in 7,000 patients with a history of heart attack; these individuals also have either diabetes or a cluster of prediabetic risk factors known as the metabolic syndrome. Enrollment is expected to begin at more than 350 sites in the US and Canada next March. Gary Gibbons, director of the NIH’s National Heart, Lung and Blood Institute, noted that these individuals are at high risk for cardiovascular disease and do not respond well to currently-available therapies. The Novartis trial is testing the company’s anti-inflammatory antibody known as canakinumab (Ilaris).

Both methotrexate and canakinumab directly target certain inflammatory pathways with little or no effect on other cardiovascular risk factors. Current preventive medications, including anticoagulants such as aspirin, and cholesterol-lowering statins, which reduce LDL (“bad cholesterol”), also lower inflammation. Therefore, studies that report a benefit from statins and anticoagulants do not separate which medication is of the most benefit in heart attack and stroke prevention.

The researchers note that it will be difficult to determine benefits from methotrexate and canakinumab because all study participants will be treated with optimal therapy; those receiving either of the anti-inflammatory agents will also be given statins and be compared against patients who are on aggressive statin and other therapies that may also reduce inflammation.


See also:
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This is an excellent and informative article. Keep up the great work and keep me updated on all related developments.
Thank you