Wednesday, June 4, 2008

What Next, Down is Up? An HDL Conundrum

Man, and I thought quantum physics was wacky stuff! Study after study has shown that higher HDL is strongly associated with cardiovascular health. HDL Cholesterol efflux mechanisms and the entire mechanics of reverse cholestrol transport have been proposed, studied, and experimentally observed. Now this!

In what could be a landmark study recently published in the Journal of the American Medical Association, researchers conducted a meta-analysis of the data from the Copenhagen City Heart Study (over 9000 persons with two decades of followup), the Copenhagen General Population Study (an ongoing study of over 30,000 persons), and the Copenhagen Ischemic Heart Disease Study (2500 persons referred for angiography). The conclusion, "Lower plasma levels of HDL cholesterol due to heterozygosity for loss-of-function mutations in ABCA1 were not associated with an increased risk of IHD." The lead investigator added, "The principal finding of this study is that heterozygosity for loss-of-function mutations in ABCA1 associated with substantial, lifelong lowering of plasma levels of HDL cholesterol, but not with corresponding higher levels of plasma triglycerides or atherogenic remnant lipoproteins, did not predict an increased risk of ischemic heart disease."

Now, let's review their findings - this time in English! The researchers looked for mutations in a key gene (ABCA1) that lowers HDL Cholesterol (HDL) and reduces cholesterol efflux from the artery wall but does not affect triglycerides. As expected, the group with the mutations had an HDL that averaged 17mg/dl lower than the general population and that 17mg/dl reduction should have translated to a 70% risk increase based on the results of the Copenhagen City Heart Study. However, this low HDL group did not appear to have any more risk than average. It was only in the presence of low HDL and high triglycerides that they found higher heart disease risk.

The findings suggest that, although low HDL is consistently associated with higher heart disease risk, it is not, by itself, a cause. The practical implication is not to dismiss low HDL as a marker for heart disease but to question its true role. It further suggests that simply raising HDL (as is the target of many new drugs such as CETP antagonists) is not enough and it must be considered in relation to other factors that often appear in conjunction with low HDL such as high triglycerides. Of course, this provides additional validation for the 60/60/60 Track Your Plaque principle. Keep that HDL high and those TGs low!

Wacky stuff!



Anonymous said...

So is this study telling us that we only have to worry about our ( my ) low HDL ( 39 ) if our ( my ) Triglycerides our high also ( 49 for me ) ?

HeartHawk said...


Another study I read just today in the Journal of the American College of Cardiology suggested that it is Apo-A1 (the surface protein of HDL) that appears to correlate the closest with reduction for risk and that very high HDL (without an increase in Apo-A1) actually increases risk.

Study after study shows rising HDL is associated with decreased risk. The novel theory here is that HDL is merely a marker for "good stuff" and it is not HDL per se that decreases risk but other things that typically occur along with higher HDL such as an increase in Apo-A1 and/or lower TGs. These studies show that in cases where TGs do not decrease or Apo-A1 does not increase in conjunction with higher HDL there appears to be no benefit.

At the end of the day, you still want higher HDL assuming the rest of your lipoproteins behave in a normal fashion.



Anonymous said...

After 6 months of statin therapy, supplemented recently by fish oil and niacin, and continuous but modest weight loss, I've got my HDL up above 50 (from below 40) and my LDL to below 80 (from above 90), suggesting that more of the same is called for. At the same time, my triglycerides have gone from above 100 to 40. Do you think it's possible to bring them too low?

More generally, I would imagine that the changes that people realize with drugs and diet would vary quite a lot. It seems to me that there isn't much good advice available on how to manage and handle these changes, and what's enough of a good thing. And presumably people exist who from the outset have low HDL and high LDL, and also low triglycerides, too (just guessing, but it seems plausible). I imagine they would find it very hard to get advice on drug and dietary therapy. Do you have any insight on these areas?

HeartHawk said...

Dear Anon:

You have pretty much hit the nail on the head - we are all different and all respond differently to different treatment. That is why it is so vital to track your treatments and response over time to determine your patterns (it is also why I continue to unabashedly flack for Track Your Plaque as it seems to be the only program that fully buys into this notion where as others only pay it lip-service and push whatever one-size-fits-all book or product they sell).

As far as optimum lipids are concerned Track Your Plaque uses 60-60-60 LDL-HDL-Triglycerides as it guideline but only a guideline (many members also also throw in a 4th "60" of 60ng/dL Vitamin D blood-level because of its dramatic effects). It looks like your basic lipids are about where mine are, I shoot for LDLs and HDLs in the 50-70 range and keep my triglycerides rock bottom usually below 40 and yes I do keep my Vitamin D level at or above 60 as well. There is some suggestion that dropping LDL below 40 or 50 may be harmful but I know of no limit to raising HDL or lowering Triglycerides. I also have a similar drug/supplement regimen as you but always look to decrease my statin dose (I take 5mg of Crestor) by adding other supplement and lifestyle changes

AS much as it is self-serving I still have to recommend you check out the Track Your Plaque website at Although it is a membership site (a mere $6.65 a month after the first 3-months) there is still a ton of free stuff and info including free books, newletters, special reports, and a primer on the basics.



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