Low density lipoprotein cholesterol (LDL-C) is the famous bad cholesterol. Lowering it lowers the risk of heart attacks and strokes – cardiovascular (CV) diseases. That much is well established. Statins lower the risk of CV disease to a degree that seems to be directly proportional to the degree that they lower LDL-C. Other things, diet, intestinal bypass surgery and some other drugs also seem to do good in direct connection with their ability to lower LDL-C. Can we equate lower LDL-C with improvement in CV risk? Not so fast.
Now we’ve come to understand that some drugs that lower LDL-C do not prevent bad CV events at least not when added on top of statins. Just lowering LDL-C may not work. Niacin and a group of medications called fibrates fall into this group of medications that lower LDL-C but don’t help prevent CV events in concordance with that lowering. This could be because they do other things that we don’t understand that counteract the good of changing cholesterol or the mechanism of lowering LDL-C is important.
What all the things that work like statins have in common according to a recent review of this issue, is they all, including statins increase, either directly or indirectly LDL receptors on cells that take LDL-C out of the blood and into cells. (1) These receptors are on cells all over the body but 70% of them are in the liver. LDL receptors were discovered in 1972 by Joseph Goldstein and Micheal Brown for which they were awarded the Nobel Prize in 1985.
So using the lowering of LDL-C as a surrogate for improving life expectancy is no longer considered adequate for giving approval to a new drug. You have to show directly, that it also does the good things that we expect lower bad cholesterol to do. The new cholesterol lowering drug class, PCXK9 inhibitors also work by increasing LDL receptors. They do an even better job of lowering LDL-C than statins do. But that is still not a free pass. The data to show that they improved outcomes of cardiovascular disease is still being studied and takes years.
We’ve learned the hard way, famously and recently with estrogens for post menopausal women, and also some diabetes and weight loss drugs, and now with some cholesterol altering drugs, that everything is not what it seems. Youthfulness, lower blood sugar, weight loss and lower LDL cholesterol isn’t always good.
John DiTraglia M.D. is a Pediatrician in Portsmouth. He can be reached by e-mail- firstname.lastname@example.org or phone-354-6605.