Monday, February 08, 2010

Lipoprotein(a) and oxidised lipids: What's your mimium requirement?

Just briefly, from this paper:




The paper was written before the Lp(a) is oxLDL paper, so the authors are showing the two seperate plots, one is the amount of oxidised phospholipid per unit LDL and the other is Lp(a).

I like the similarities in the curves! Life should be logical.

From the practical point of view, at what level of Lp(a) do you need to hurry in making out your will? Look at graph B.

Obviously there is a "least risk" value for Lp(a), but if you had null genes for apo(a), and so come out with zero Lp(a), you would still be in exactly the same risk category as the sextiles 3 and 4 but wouldn't be worrying about it! So, in this study, using this Lp(a) assay, for people eating modern food, anything below 24mg/dl has the same risk as zero Lp(a). Perhaps lower if you are lucky.

Note also from graph A that having undetectable oxidised lipids per unit LDL in your blood DOUBLES your risk of incident CVD. That's it. No oxLDL [ie no Lp(a), whichever you please] DOUBLES your risk of heart disease.

EDIT: I guess "is observationally associated with" would be a better phrase. Don't want to sound like the AHA about cholesterol here!

And you thought your genes evolved apo(a) to kill you!

Wrong.

Peter
at

11 comments:

  1. donny8 Feb 2010, 15:20:00

    They were really so tight for space that the bottom of the graph needed to be truncated? I guess graph-makers can't help themselves.

    Chainey, are you sure you're not just making butter when you shake your cream to make sure it's well mixed? Shake real good and eat the butter.

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  2. Ned Kock8 Feb 2010, 15:30:00

    A J-curve pattern, as with many health-related variable relationships. Very interesting!

    This is one of the reasons why I like using WarpPLS to do statistical analyses of almost any kind (warppls.com; and sorry for the shameless plug in).

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  3. Unknown8 Feb 2010, 17:33:00

    Wow, this is really getting interesting!

    Are you aware of any research regarding the mechanism(s) by which niacin lowers lp(a)?

    Does it affect how the liver "senses" the need for it (e.g. does niacin fool the liver into thinking that there are less oxidized lipids requiring clearance)? Does it merely block/impair the synthesis of lp(a) in the liver? Does niacin somehow reduce the amount of oxidized lipids (e.g. reduce/prevent tissue damage)? Other ideas?

    By analogy, if niacin acts to reduce the need for police officers by reducing crime, I would think it a good treatment. Alternatively, if niacin acts to reduce the *availability* of police officers, but not the crime rate itself, then I would be more inclined to question such a solution.

    I am not well-versed in the relevant research, however, my overall impression is that lp(a) reduction via niacin treatment does indeed improve outcomes?

    I've lowered lp(a) from 88 to 44, and this was while adhering to an unfortunate low-fat diet. Looking forward to my latest results in a week...

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  4. Peter8 Feb 2010, 20:42:00

    Hi Chainey, I guess a certain amount floats up like cream on milk but to get it all out you need some sort of industrial centrifuge... I guess this is how we get cream and skimmed milk from cow's milk!

    Yes Donny, bit of a garnish to their plot there. I guess they're not the first or the last to do that. Fitdays weight charts use the same dodge!

    Hi Ned, yes those curves are everywhere. Those stats are way beyond me!

    Hi Onschedule,

    As far as I am aware niacin is pretty much a Good Drug. As I see it it activates the HM74 receptors, who's normal ligand is beta hydroxybutyrate. If you get the metabolic effects of LC eating without the LC eating itself, it suggest to me that the carbs themselves are not a problem so much as the effects of the switches they throw.... Obviously a few ketones should activate the receptors without all of those pills and flushes but the niacin does seem to do positive things compared to most pharmaceuticals! I don't really chase the relevant research as I'm more interested in what might be the normal processes using ketones without the meds.

    Peter

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  5. woly9 Feb 2010, 04:40:00

    Very interesting! Could the reason why saturated fat lowers lp(a) be due to its low oxidation potential?

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  6. woly9 Feb 2010, 06:59:00

    Also, I just thought I would post an interesting article I found that discusses the possible evolutionary advantages of lp(a) and its possible mechanisms in both its negative and *positive* effects.

    http://qjmed.oxfordjournals.org/cgi/content/full/93/2/75

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  7. Anonymous9 Feb 2010, 17:20:00

    Notice Figure 3B

    See how if you are in the higher two tertiles of Lp(a) with a low framingham score your risk is HALF that of those in the lowest tertile? This must be contributing to the "J".

    Pretty interesting and fits with the centenarians, etc.

    As my framingham risk is low ( CAC 0 trumps framingham anyway) that may be reassuring to those of us with Lp(a) and otherwise low risk.

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  8. JohnN9 Feb 2010, 19:57:00

    @Woly:
    The link you cited is working, please clarify. And if it's the 2000 review by Lippi and Guidi the full link is:
    http://qjmed.oxfordjournals.org/cgi/content/full/93/2/75

    One other comment: there is evidence that Lp(a) is necessary for tissue repair (being a growth factor of smooth cells; Lp(a) presence in wound or damage to the intima in CD - a la "Unified Theory" of Rath and Pauling) and perhaps against cancer malignancy.

    Taken together, the presence of Lp(a) seems to indicate injuries sustained by the body and not a pathogen which is unfortunately the conclusion of most papers or this paper or the study cited below (just the title alone reveals the researchers bias):

    "High lipoprotein(a) level promotes both coronary atherosclerosis and myocardial infarction: a path analysis using a large number of autopsy cases."

    http://heart.bmj.com/content/95/24/1997.abstract

    Regards,
    John

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  9. Unknown10 Feb 2010, 05:26:00

    Hi Kurt.

    Do you also have high Lp(a) ?

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  10. Peter10 Feb 2010, 10:09:00

    Hi Woly,

    I've had the QJM article for some time and there are a lot of ideas but they were working without the data that oxLDL is Lp(a) and the benefits of targeted delivery of oxidised phospholipids. It makes a lot more sense when you have this information... The whole saturated fat thing is hard to fathom. Preemptive secretion or response to injury???? I tend towards the later and assume that there is less damage going on if sat fat intake is high...

    Kurt, I tend to glaze over whenever someone mentions Framingham scores. Probably comes from not living in Framingham. But yes, CAC scores make me prick my ears up!

    John, yep.

    Hi Karol, from a comment elsewhere in this series Kurt does have elevated Lp(a). High enough it's probably all the short kringle IV repeat stuff. I really like CAC scoring!

    Peter

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  11. Dr. B G11 Feb 2010, 00:00:00

    woly,

    The reason why saturated fatty acids lowers Lp(a) (and makes them less dense which is MORE important for our purposes) is because fatty acids bind PPAR. All things that improve PPAR will lower Lp(a) (and raise particle buoyance and raise HDLs):
    ---low carb (because high carbs degrade PPAR receptors and anti-inflammator activity)
    ---niacin/ketones
    ---keeping the immune system untriggered (no dairy (exc ghee), no gluten/grains, no legumes, etc)
    ---omega-3 fatty acids
    ---saturated fats

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