Updated May, 2006
Researchers have now shown that reducing LDL cholesterol to 70 mg/dl or lower saves lives- and have provided the means to achieve these low levels. And while it will take years (or longer) for most practicing doctors to "notice" this information and to put it into practice (and for the professional bodies to turn the bureaucratic wheels sufficiently to update treatment guidelines,) the researchers themselves, having tapped out the LDL possibilities, are moving on to greener pastures. Namely, they are working on HDL cholesterol.
HDL cholesterol "should" be 45 or higher for men, and 55 or higher for women. But ideally it should be above 60 for everybody - evidence suggests that for every 1 mg/DL increase in HDL, the risk of heart disease drops by 2 - 3%. HDL cholesterol apparently picks up cholesterol from the arterial walls (where it causes atherosclerosis - narrowing of the arteries) and takes it to the liver where it can be metabolized. It also has anti-inflammatory effects and other effects that benefit the arteries and keep them healthy.
Most intriguingly, a recent study has suggested that one form of synthetic HDL cholesterol can actually halt or even reverse coronary artery disease. ( Read about this "plaque dissolver" here.) Unfortunately, currently available drug therapy for increasing HDL levels are only modestly useful, at best. ( Read how to increase your HDL levels here.)
What HDL "solutions" are coming?
The good news is that big pharma (and their very smart researchers) have recognized that the company that figures out how to increase HDL with minimal side effects wins. And major efforts are being made to develop such drugs.
Among these are the cholesteryl ester transfer protein (CETP) inhibiting drugs. CETP is a "bad" molecule that, among other things, moves cholesterol from the HDL form to the LDL form. Inhibiting this molecule is, therefore, a promising approach to increasing HDL cholesterol levels. Pfizer's CETP inhibitor (a drug called torcetrapib) has looked very promising in early trials, and a major phase 3 trial (the kind of trial the FDA considers when deciding whether a new drug can be marketed) should be yielding results in 2006. Several other companies have CETP inhibitors in the pipeline. One company (Avant Pharmaceuticals) is even developing an anti-CETP vaccine.
The PPAR drugs (peroxisome proliferation activated receptor agonists) are another class of drugs being studied to raise HDL levels, that work by stimulating a pro-HDL gene. Several companies are working on PPAR compounds, but research is not as far along as for the CETP drugs.
A very interesting line of research is with peptides that mimic HDL. The Apo-A1 used in the Milano studieswas such a substance, and its effect on clearing cholesterol from arterial walls was impressive. Unfortunately, the Apo-A1 has to be given intravenously, so could never be used for chronic therapy. A company called Esperion (recently purchased by Pfizer) is working to make similar peptides that can be taken orally.
Several approaches are being made to increase the efficiency of available HDL (rather than increasing the actual HDL levels.) Recent evidence suggests, for instance, that the diabetic drug pioglitazone (made by Takeda) can increase the size of HDL particles - and larger HDL particles may be "better" at clearing cholesterol than smaller HDL particles.
It will take a few years for the researchers to work out which (if any) of these approaches will pan out - but raising HDL cholesterol levels (or improving the function of available HDL levels) has clearly been moved off the back burner. This is now clearly a major goal of the pharmaceutical companies, and if the profit motive is not legislated into illegality in the meantime, a significant breakthrough in the prevention (and probably reversal) of coronary artery disease seems inevitable.
