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  F E A T U R E S  
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  UC Davis Shines in Nutrition Research  
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  FEATURES
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GETTING TO THE HEART OF THE MATTER

 "" PHOTO — UC Davis cardiologist Tissa Kappagoda says low-fat, high-fiber diet is the key to good health.
 
UC Davis cardiologist Tissa Kappagoda says low-fat, high-fiber diet is the key to good health.
   

Cardiovascular disease claims as many lives as the next five leading causes of death combined. Perhaps for no major killer is diet so closely linked.

C. Tissa Kappagoda, UC Davis Health System cardiologist and director of the UC Davis Cardiac Rehabilitation and Coronary Artery Disease Reversal Program, has devoted much of his career searching for ways to prevent heart attacks. He believes lifestyle plays a critical role, with diet being an important component.

Dismissing the recent high-fat fads, he maintains that a diet high in fiber and low in fat, especially saturated fat, is key. And Kappagoda has clinical evidence to back him up: He recently completed a 10-year follow-up on heart patients who participated for two years in his lifestyle program, which included dietary modifications, blood pressure control and stress reduction. Those who stayed with the program recommendations throughout the 10 years, Kappagoda reports, had an accumulated event rate of only 1 to 2 percent, compared to 18 percent who did not complete the program. The event rate in patients who do not have access to a cardiac rehabilitation program after recovering from a heart attack is more than 50 percent over five years.

"This is not high-tech medicine, but the results are very good," Kappagoda says modestly. He is now in the midst of a similar study of individuals with type 2 diabetes, who statistically are at similar risk for having an acute coronary event as those who have already had a heart attack.

Also on the forefront of cardiovascular disease and nutrition research are Iswarlal Jialal, UC Davis professor of pathology and director of the Laboratory for Atherosclerosis and Metabolic Research, and Sridevi Devaraj, associate professor of pathology and an investigator in Jialal's laboratory.

Both are pioneers in the hottest new line of research in heart disease: inflammation. At one time, cardiovascular dogma compared arteries to kitchen pipes: they both clog, according to the old model, when sticky, waxy substances gradually accumulate on the walls, narrowing the opening and finally sealing off flow. Now most believe that many heart attacks occur as a sudden event, when plaque ruptures and a clot forms. Inflammation seems to play a critical role in this scenario.

PHOTO — UC Davis researchers Iswarlal Jialal and Sridevi Devaraj are studying C-reactive protein's role in heart disease. Levels of the protein are associated with an individual's body weight.  ""

UC Davis researchers Iswarlal Jialal and Sridevi Devaraj are studying C-reactive protein's role in heart disease. Levels of the protein are associated with an individual's body weight.
 
   

Evidence is mounting that a key player in the inflammatory process is C-reactive protein (CRP), a substance long linked to inflammatory conditions, but only more recently implicated in heart disease. Through a series of complex experiments, Jialal and Devaraj have elucidated several independent effects of CRP that can lead to heart disease, including promoting plaque build-up (by increasing white blood cell binding to blood vessel walls and stimulating the release of other adhesion molecules) and thrombus formation (by stimulating an enzyme that inhibits the breakdown of clots). Jialal's research recently provided a novel twist — while CRP was thought to be produced mainly in the liver, Jialal found that the cells in the artery wall also produce CRP, potentially contributing to plaque.

Until their landmark studies, CRP was recognized mainly as a risk marker of heart disease rather than a direct participant in its pathogenesis.

"CRP is not just an innocent bystander," says Jialal, who is also the Robert E. Stowell Endowed Chair in Experimental Pathology. "It is a key culprit."

And the dietary connection? Studies show that body weight is associated with CRP levels, and one way to reduce CRP levels is to lose weight.

Jialal and Devaraj have tried to pinpoint single factors, such as antioxidants and flavonoids in specific foods, that might reduce the risk of heart disease, but with only mixed results.

Jialal agrees with Kappagoda that a diet high in fiber and low in saturated fats is everyone's best bet against heart disease. "Maybe there isn't one factor in healthy foods that make the difference," he muses. "Perhaps it is like an orchestra — maybe it is the network of effects in fruits, vegetables and whole grains that makes a difference."

In a study led by Devaraj, the research team showed that orange juice fortified with plant sterols was effective in lowering LDL cholesterol (bad cholesterol) levels by approximately 10 percent. This provides an effective heart-healthy treatment choice for individuals with mildly elevated cholesterol who do not want to take a drug to lower their cholesterol. In addition, the orange juice may be an alternative to higher doses of statins in individuals already taking statins to lower LDL cholesterol. While plant sterols have been available in margarines for a few years, Devaraj says lowering cholesterol with plant sterol-fortified orange juice includes an ideal heart-healthy option that also provides other healthy nutrients, such as vitamin C, folate and potassium.

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  "CRP is not just an innocent bystander, it is a key culprit." — Iswarlal Jialal, Professor of Pathology  
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