You know all about cholesterol, right? You know what your HDL and your LDL should be right? Well, did you know there is another lipoprotein that may have as much, maybe more, of an effect on your risk of coronary heart disease as either of the other two?
It's known as lipoprotein (a) or Lp (a). ( Call it "Lp- little a"). But don't rush out to your doctor's office just yet to have a blood sample taken. Even if it's high, researchers don't know how to lower it. But they're working on it. In fact UT Southwestern researchers have made the most significant advances so far unraveling the genetics of Lp (a), said Dr. Jonathan Cohen, an assistant professor and nutrition scholar in the Center for Human Nutrition. He has been working in the lab of Dr. Helen Hobbs associate professor of internal medicine and molecular genetics and one of the leading researchers in the quest to understand and the mysterious Lp (a).
"Several studies have shown that high levels of Lp (a) are associated with coronary artery disease, " Dr. Cohen said. Lp (a) is a low-density lipoprotein (LDL) that has on its surface apoplipoprotein (a). Apo (a) is a large protein that is structurally similar to plasminogen, a protein involved in dissolving clots." Because of the similarity between apo (a) and plasminogen, we think apo (a) may provide a link between clotting and atherosclerosis," Dr. Cohen said.
"One problem is that Lp(a) levels do not respond to traditional pharmacological or dietary interventions," he explained. In a large definitive study of many families, Dr. Hobbs and her colleagues showed that about 90 percent of the variation in Lp (a) levels between individuals is genetically determined. If both your parents have high Lp (a) levels, then you most likely do too. "This is very interesting," Dr. Cohen said. "It's a quantitative trait, like height or weight or cholesterol level, and it's almost purely genetically determined, which very few quantitative traits are."
Dr. Hobbs' group also found that an individual's Lp(a) level is determined almost entirely by DNA sequences in the gene that encodes apo (a). "The significance of this is that this physiological trait can be understood in terms of a single gene, whereas any other trait, like height or weight, is influenced by multiple genes," he said. Lp (a) appears to be unique among all these traits. Hopefully we can find drugs or agents that act directly on the gene."
The apo (a) gene varies greatly in size and sequence between individuals, Dr. Cohen said. In fact, there are up to 100 different forms of the gene, each associated with a different Lp (a) level. Researchers have shown that there is an inverse correlation between the size of the apo (a) gene and the blood levels of Lp (a). In other words, people with large forms of the gene would have low Lp (a) levels, and people with small forms of the gene would have high Lp (a) levels. Dr. Cohen expects to publish findings related to this research this year.
He said researchers know there are other factors which determine Lp (a) levels. "We know that African Americans have Lp (a) levels two or three times higher than Caucasians, but it does not appear to predict coronary artery disease in that population," he said." About 20 percent of Caucasians have Lp (a) levels greater than 30 milligrams per deciliter, and that level carries with it a risk of having a heart attack that is twofold greater than those with levels below 30 mg/dL. If you have a high Lp (a) level and high cholesterol, then your relative risk of having a heart attack goes up about fivefold over normal."
So, should people have their Lp(a) level measured along with their high-density lipoproteins (HDL) and LDL? "If it would stimulate them to make changes, then, yes," Dr. Cohen said. "But he cautioned, "it's not a routine test, nor is it widely available."
