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One More Piece of the Puzzle
New Connection Established between Plasma Lipoprotein(a) Concentrations and Triglyceride Metabolism

CHORI Senior Scientist Ronald Krauss, MD, and his colleagues in the Center for the Prevention of Obesity, Cardiovascular Disease and Diabetes have identified a new factor that may contribute to negative effects that very low-fat, high carbohydrate diets can have on cholesterol and heart disease risk. The new study builds on previously known information about low-density lipoproteins, or LDL, known most commonly as "bad" cholesterol.

"It's been known for at least 40 years that there is a form of LDL in the blood that has a genetically determined modification, or change, that makes the LDL even more damaging to the arteries, and that is plasma lipoprotein(a), or Lp(a)," Dr. Krauss explains.

As Dr. Krauss and others have found, traditional low-fat, high-carbohydrate diets recommended for reducing LDL and heart disease risk actually have the unexpected effect of increasing the levels of this Lp(a) particle. Because these low-fat diets also increase the levels of blood fats, or triglycerides, Dr. Krauss wondered if they could find a relationship between triglycerides and Lp(a).

"There hasn't been a very strong triglyceride connection known before," says Dr. Krauss, but in fact Dr. Krauss did find such a relationship by studying a particular protein that is associated with triglyceride in the blood called apo C-III.

"There was a significant correlation between the diet-induced increases in Lp(a) and higher levels of triglyceride-associated apo C-III. Although the publication doesn't identify the specific dietary cause of this effect, we believe it's the result of the high carbohydrate intake that is generally part of low-fat diets."

There is huge variation in Lp(a)levels across the population - the largest variation, in fact, in any blood measurement - and for the most part, that variation is controlled most strongly by genetics. These dietary changes are relatively small on top of that," says Dr. Krauss.

"What our study does suggest, however, is that if you are going to try and improve Lp(a) levels, what you don't want to do is to go on a very low-fat, high- carbohydrate diet. In fact, we have not yet identified effective dietary approaches for treating high Lp(a), although very large doses of niacin, which must be given under medical supervision, can have some benefit."

While the impact of diet on Lp(a) is only a piece of the puzzle, researchers like Dr. Krauss and his colleagues at CHORI are continuing to explore other avenues as well, such as searching for the genetic basis for variation in heart disease risk and response to treatments.

With the connection between triglyceride metabolism and Lp(a) levels now established, however, Dr. Krauss has identified one more route by which bad cholesterol develops, and one more data set suggesting that low-fat, high-carbohydrate diets may have damaging effects.

"The larger issue is understanding more clearly how we can improve the overall spectrum of risk factors for heart disease by optimizing diet," says Dr. Krauss, "and this effect of diet on Lp(a) is one of the considerations."

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Monday, May 16, 2011 11:33 PM

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