The Curious Case of HDL Cholesterol

by | Mar 9, 2009

cholesterol chemical structureDrug treatments that raise the “good” high density lipoprotein (HDL) cholesterol do not improve health outcomes, according to a new analysis. But some researchers suspect raising HDL through lifestyle changes may still be effective in treating heart disease.

HDL is the form of cholesterol that actively removes dangerous lipids from the blood, and has long been thought to be protective against heart disease. This form of cholesterol is believed to work in opposition to low density lipoprotein (LDL) cholesterol, which is strongly correlated with heart disease and cardiovascular mortality. Thus the ratio of HDL to LDL cholesterols is often considered the most important indicator of heart disease risk.

Strong clinical evidence shows that LDL lowering drugs like statins can protect against heart disease and cardiovascular mortality. However there is still no effective way of improving cardiovascular outcomes by directly targeting HDL cholesterol.

Pharmacological treatments that raise HDL cholesterol levels include fibrates, niacin and a Pfizer drug called Torcetrapib. However, trials that tested these drugs for improved cardiovascular outcome have yielded mixed results. Rather than lowering mortality risk, evidence suggests that fibrates and Torcetrapib actually increase mortality in patients. Some trials have shown niacin to be effective at reducing cardiovascular events, but the data are inconsistent.

A new meta-analysis published in the British Medical Journal asked whether pharmacological treatments that are known to raise HDL can improve cardiovascular outcomes. After adjusting for several known confounders (including the effect of LDL cholesterol) pharmacological treatments that raise HDL were not effective at protecting against heart disease.

Does this mean that HDL is not important for heart disease? Not necessarily.

The original studies that implicated HDL in heart protection were observational. For example, it was shown in the Framington Heart Study that people with HDL levels greater than 60 mg/dL have a reduced risk of heart disease compared to individuals with lower HDL. Likewise, individuals with less than 40 mg/dL of blood HDL are considered at risk for coronary heart disease, even when LDL cholesterol is relatively low.

Additionally, lifestyle choices that contribute to raising HDL are associated with a lower risk of heart disease. Examples of these are physical activity, weight loss, not smoking, increased omega-3 fatty acid consumption, decreased trans fat consumption, alcohol consumption and dietary soluble fiber. Also, diets low in saturated fat but relatively high in unsaturated fats have been shown to raise HDL and decrease heart disease risk.

All these HDL raising activities can improve cardiovascular outcome. However, this does not mean that HDL itself prevents heart disease. Rather, it seems to be a good biomarker (observational correlate) of heart disease.

Why are pharmacological methods of raising HDL not helpful (and possibly even harmful) at treating heart disease?

One possible explanation for this discrepancy is the observation that HDL has different forms, some that are protective and others that are harmful. For instance, some interventions may raise HDL cholesterol by limiting its breakdown (harmful), while others raise it by increasing HDL production (more beneficial). Also, some methods that increase HDL do so in a way that creates new problems, such as increased blood pressure.

The complex interaction between pharmacological interventions, HDL metabolism and cardiovascular outcome may have made it difficult to detect any benefit of raising HDL cholesterol in this meta-analysis. Since pharmacological intervention for raising HDL does not consistently help (and sometimes harms) cardiovascular outcome, lifestyle changes remain the most promising target for raising HDL to protect against heart disease.

Anyone want to guess how high my HDL cholesterol is??

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15 Responses to “The Curious Case of HDL Cholesterol”

  1. Make Money Online says:

    Nice title there. I was reminded one Benjamin Button. Anyways i was not aware about all this, thanks for the detailed and insightful post.

  2. Matt Shook says:

    I wouldn’t wish statins upon my worst enemy…they have the potential to destroy your liver and can cause psychosis.My guess is your HDL is 84 mg/dL…seems like a good even number.

  3. Mike says:

    Huh, I thought this article was gonna be about how HDL cholesterol reverses aging, and will make me as handsome as Brad……

  4. Mike says:

    Oops :)But good article though, I love your science ones. I think it is so weird how so few of our medications work, and this reminds me of so many vitamins/minerals/phytochemicals that had promise, but was shown to do nothing. How did Mother Nature get so much smarter than the thousands of scientists on this planet?!Why did you have your cholesterol measured in the first place?

  5. Zachary says:

    What’s normal/good for the two kinds of cholesterols? Is there any way to find out other than getting a blood test?

  6. Anonymous says:

    Eeeew! Took one look at your pic and it reminded me of organic chemistry….

  7. Darya Pino says:

    @MattStatins aren’t perfect, but they are still one of the most effective drugs with relatively minor side effects. Some people are not able to control cholesterol with diet (though the vast majority of people can).Great guess!! Last time I had it checked (~1 yr ago) I was at 81 mg/dL. My doctor told me to never come back ;)—–@MikeHDL does reverse aging. I got mine tested because I was curious. It is weird how resistant doctors are to doing the test. But once my dad had a stroke at a young age (~55) they allowed it.—–@ZacharyGreat question. For HDL cholesterol, as I mention in the post, greater than 60 mg/dL may reduce your risk of heart disease. Lower than 40 mg/dL increases risk.For LDL cholesterol, there is more debate. The accepted "cutoff" is 130 mg/dL, but there are some scientists who believe your total cholesterol should be under 150 mg/dL. You certainly want to keep total cholesterol under 200 mg/dL.Yes, you need blood work to get it tested. Diet has a tremendous impact on both kinds of cholesterol. Cutting out saturated fat, reducing calories and lowering your weight will improve LDL. But if this happens on a "low fat" diet (<20% calories from fat–fat replaced with carbohydrates), HDL will also decrease. This is bad. Maintain high HDL while improving LDL by eating good mono and polyunsaturated fats. Replace both saturated fat and refined carbohydrates in your diet with healthy fats, vegetable protein and whole grains.—–@AnonI love organic chemistry 🙂

  8. Matt Shook says:

    @DaryaI’ve heard statins are effective for short-term treatments with few side effects. However, if you are planning on using the drug long-term then you can expect some serious side effects after six months. I’m not a medical professional, but what I’ve read and heard about statins from NDs is not promising…I was going to say 81 (my favorite number actually), guess I should have gone with my gut feeling. ;)Speaking of feelings, I think I have will harbor some pretty hard feelings for you and my bro after this crap…you should be ashamed of yourselves…;)

  9. Darya Pino says:

    @MattI haven’t heard much bad news about statins. My understanding is that they are among the most successful drugs ever created. I would be interested in more data if you have it.81 is my favorite number too. Also probably Kobe’s ;)But kidding aside, I was really confused and saddened by that incident. I’m still not really sure how that all happened, but I hope to never see anything like it again.

  10. Matt Shook says:

    @DaryaStatins are somewhat effective at helping people with high cholesterol avoid heart attacks, but that does not mean they improve their quality of life.I have gathered most of my understanding from talking with friends and relatives who are fairly well versed on the subject. Here’s a few articles…UC San Diego has a fairly large statin study underway. A New York Times report as well…I’ll post more about the more links relating to the serious side effects once I locate them again…———————————-Is 81 really your favorite number too? Why?It was a nasty spill…really sucks since it was a blow out and there was only a few seconds left in the quarter.

  11. Anonymous says:

    Funny how all I knew growing up was that cholesterol is bad, and thats why I can’t have more than 2 eggs at a time; I love eggs now, and eat the yolks with no worries!

  12. Darya Pino says:

    @MattI read a study today that statins may protect against Alzheimer’s disease. There are positive and negative sides (disagreeing studies) in pretty much everything health-related, largely because of human variability and differences in experimental design. How we interpret these discrepancies is largely determined by where we are coming from. I try my best to base my opinions on evidence and rely on my training to do this fairly (there are certain warning signs of bad science I have learned to view with skepticism). But I am aware it is silly to pretend I am 100% impartial. I interpret new findings in the light of things I already know (or think I know), but I am happy to admit my bias that stems from the research I have done. And I appreciate when readers like you challenge it.In general I have seen more positive studies about statins (especially lately) than negative ones. I am not 100% sold, but in my opinion there are worse alternatives.I am with you in being wary of relying on pills to treat a medical ailment that can so easily be treated with food. But not 100% of heart disease cases can be treated with food. For those people, statins could save their lives.And if that is true, it is a wonderful thing.-81 is the number of points Kobe dropped on Toronto a few years back. In case you can’t tell, I have a bit of a crush on him and his awesomeness.

  13. Matt Shook says:

    @DaryaI agree that if you’re a 65 year-old with high cholesterol and an unhealthy diet, statins can prolong your life. The thing that irks me is that some doctors are prescribing statins as “preventative” medicine to young folks. This is really bad news to me…I understand your POV and why you are skeptical of most opinions regarding prescription meds that do not have well-researched (and well-funded) studies to back them up. However, I also believe most research critical of pharmaceuticals will never transpire due to financial obstacles.I think we could go back and forth forever about this…we’ll have to battle it out if we’re ever in OC at the same time.———————————I was aware of the eighty-one bomb he dropped on Toronto…that was nifty and all, but it told me he needs to learn how to share the ball. ;)I’ve fancied “81” ever since I developed a man-crush for this guy’s hockey skills back in the ’90s.

  14. Darya Pino says:

    @MattInteresting perspective. I guess I am not as cynical about science funding. In my experience good research gets paid for eventually.Would love to sit and chat one day. You’re a character :)Watching the game vs Toronto it is obvious that if he hadn’t scored like that, the Lakers would have lost the game. There was no other Lakers back then. Things are different now.

  15. Diane says:

    My HDL is 127. Big particles too. I have low inflammation. I’m a 59 year old female. Big deal. I just found out I have aorta plaque with a bit of leakage, but a very strong heart. I was told I don’t have a cardiac problem. At least 85% of people over 50 have plaque somewhere in their bodies! I don’t think we were meant to live longer then 50 generally. Just the act of eating and breathing will give you inflammation, and we need both, so we’re doomed.

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