Friday, May 15, 2009

Cholesterol and heart attack survival

OK, I have to share this one.

Take 517 sequential NSTEMI*(see edit) heart attack victims and measure their LDL cholesterol on admission to hospital. You know, that artery clogging lipoprotein of which you cannot have too little, the lower the better, take this statin blah blah. Divide those patients up in to cardiological Nirvana (those with a value below 105mg/dl, mean value 79mg/dl) or those with astronomically high LDL, ie > 105mg/dl, mean 144mg/dl. Gasp at the hypercholesterolaemia and be afraid.

BTW the MEAN LDL in the low group was 79mg/dl, some must have been well below this because the upper end of the range was 105mg/dl. What is someone with an LDL of below 60mg/dl doing having a heart attack, if the lipid hypothesis is correct? Oh, that means that....

Anyway. Wait three years and then do a body count. The heap is twice the size in the low cholesterol group than the high cholesterol group. This is statistically significant, p= 0.005, I checked the number of zeros. There may be some biological significance too, especially for those who died. I have mentioned previously the possibility of falling LDL being accompanied by a black cloak and scythe.

The paper doesn't mention CV mortality at 3 years, so I'll assume it is as bad in the low LDL group as the higher LDL group. Virtually all listed CV outcomes were non (statistically) significantly worse in the low LDL group.

So the lower the better, if you want to be dead that is!

My take home message is that having a low LDL cholesterol, as guesstimated by your cardiologist using the Friedwald equation, is very bad news if you have just had a heart attack.

So what does matter for survival?

In the low LDL group there were 38% with diabetes, in the higher LDL group 27% were diabetic, p=0.013. Mmmmmmm sugar.....

Does hyperglycaemia matter if you want to survive? Or perhaps HbA1c?

Certainly having a low LDL on admission is associated with an increased risk of being dead three years later.


Oh! Perhaps a continuous infusion of LDL might improve all cause mortality!!!!!! Now, where can I get a grant to test this hypothesis?

EDIT: NSTEMI added to increase accuracy, NSTEMI "only" represents more than half of all heart attack victims, see comments.


Unknown said...

Hi there,
You seem to be taking these results out of context and ignoring the hypothesis that was tested and trying to apply the results in a general way. The study was clearly about patients with NSTEMI and the results are applicable to the general population and the hypothesis to be tested was that patients suffering from NSTEMI have a worse outcome DESPITE
lower LDL i.e. lower LDL is not protective against the specific condition of NSTEMI.
Your opening sentence was wrong ("Take 517 sequential heart attack victims and measure their LDL cholesterol on admission" ). No,No,No they didn't study 517 "heart attack" victims they studied 517 patients with the specific type of heart attack called NSTEMI. Their hypotheseis tells us they expected lower LDL not to be effective for those types of patients anyweay. Please try to be more accurate in future.
"careless talk costs lives"
British WW2 slogan.

L said...

hi peter,

good post. unless the other peter is right.

i was reading your older posts trying to figure out your position on fish oil supplementation. do you recommend it for cardiovascular health or just to get the EFA (DHA). Dr. Davis of the heart scan blog recommends upward of 3000 ml EPH+DHA. is this misguided? i mean the guy even recommends oat bran (WTF?!). i can't find anything that explains how omega 3 by itself helps prevent heart disease. mum has prescription fish oil (Lovaza) but for some reason won't touch it. she gives no explanation. should i be opportunistic or follow her lead?

hope you enjoy glasgow. if you get a chance, drive a little west to port glasgow and pay homage at Louie's for me. culinary heaven!!! although other than that it's the arm pit of the north.

Dr. B G said...

Welcome back!!

I'm going to have to pull that and compare the TGs and HDLs too. Why do these trials FOCUS only on LDL (which are wrong anyway by Friedewald 'calc' since the TGs are typically high/low HDLs due to excessive carb intake). I was being rhetorical. You don't need to respond :) D*mn that Ancel Keys devil.

You're an angel Peter for posting.

L -- Davis advises 3-6 grams of EPA DHA (add the two up when you read a omega-3 supplement fats -- for high quality products this is about 5 to 10 capsules daily, or 1 to 2 tablespoons)

Actually he advises less oat bran now on the TYP forum (yeah -- he hasn't discussed as much on the public blog unfortunately, no time for him) and only oat bran if one is somewhat insulin sensitive. Oat bran drives my glucoses up unless I'm working out HARD CORE.

Fish oil is fantastic stuff.


Daniel said...

Peter C,

I don't see why the fact that the study investigated NSTEMI heart attacks is relevant.

NSTEMI heart attacks are one of the three main types of heart attacks. All NSTEMI means is that you can't tell it's a heart attack from an electrocardiogram, usually because the blockage is only partial or temporary.

L said...

dr b,

thanks for the input. sorry for the typo. i hope no one ran off to chug my number.

. said...

I believe Petro is correct in his analysis: NSTEMI is also a heart attack, but with partial or temporary blockage, and so with less and smaller damage; STEMI is caused by a prolonged period of blocked blood supply, affects a large area of the heart muscle, and so causes changes on the ECG. Despite of these differences, both are heart attacks and, on what concerns the 1-year acute myocardial infarction outcomes, STEMI and NSTEMI are probably not so different after all -

Mark said...

Peter C wrote:
"The study was clearly about patients with NSTEMI and the results are applicable to the general population and the hypothesis to be tested was that patients suffering from NSTEMI have a worse outcome DESPITE lower LDL i.e. lower LDL is not protective against the specific condition of NSTEMI."

Considering they compared one NSTEMI group with another, the conclusion that high LDL is statistically significantly and rather biologically significantly correlated with DECREASED deaths is true. So Peter (the blog owner) is right on the money with that.

You are comparing crazy off the charts LDL that would have most people cringing with orthodox and kosher LDL that would make anyone happy and the correlation is strongly against what anyone would suspect if they believe in the lipid hypothesis. I'm not sure how Peter the hyperlipider took things out of context in a significant way, as you claim.

You yourself say: "The study was clearly about patients with NSTEMI and the results are applicable to the general population" indicating that it WAS applicable to the general population, yet your tone suggests otherwise. Why is this? Typo?


Lynn M. said...

36% of the lower LDL group were on lipid-lowering therapy (presumably statins) at time of admission versus 24% of the higher LDL group. No mention is made of what percentages were on lip-lowering therapy after the NSTEMI. Perhaps the conclusion of this study should be that use of lipid-lowering therapy at admission was associated with decreased 3-year survival in patients with NSTEMI.

karl said...

Copuldn't this just mean that the low LDL group is self selected for people with high Lp(a)?

Peter said...

Well that's what happens when you put up a post and head to work.

NSTEMI represents "more than half of all people experiencing a heart attack", according to the American College of Cardiology. These are people who don't get a PCI unless the cardiologist is over enthusiastic or is behind with his mortgage payments. It is THE typical heart attack, assuming "more than half of all people experiencing a heart attack" defines "typical".

Lynn, you're right on the money there! I should have seen that but the plumber had postponed from Wednesday to Saturday and the builder is scheduled to put the floor in to the lobby on Sunday (pipes in before floor) and I had to move the washing machine and.... The effect is exactly what was seen in the J-LIT study, which demonstrated the increased cardiac mortality at the lowest TC and LDL levels.

There is no sub analysis as to statin treated vs non stain treated in this current paper, any more than there is sub analysis by HbA1c, but it's a plausible hypothesis.

There's a whole load of mealy mouthed explanations in the discussion and apparently there's an editorial in the same journal which (I've got it but not read it yet because the plumber will be back next Thursday and I have to.....) will probably turn out to be as amusing as the editorial covering the paper that showed a low fat diet elevates both oxLDL and lip(a): They're being pulled out of the arterial wall by the healing powers of a low fat diet!!!!!!!! I'm not kidding.

Anyway, I've added NSTEMI as an edit to the post on the basis of Peter C's comment.

BTW there's an interesting comment about the dangers of questioning the CV benefits of statins back on the JUPITER post. Play safe, as always. Being honest is, unfortunately, not always in your personal best interest. Many THINCS members do not display their membership and many skeptics are not part of THINCS on the basis of this sort of event. You can understand why. Tough sh*t Larry, good luck.


ItsTheWooo said...

Hi Peter,
Forgive me if my short attention span missed this bit of information, but were the groups self selecting? That is to say, did the groups with the low LDL do things to get their LDL low, such as more vigorous statin use and low fat dieting? Or were both groups the same med/lifestyle wise?
My thinking is that:
1) Low LDL group has a lot more fear/anxiety about heart attack death (family history?)
2) Low LDL group is doing things more vigorously to lower LDL
3) Either family history or LDL lowering interventions (high carb/low fat/drugs) are the real reason low LDL is associated with mortality

Whereas the suckers with the high LDL are eating their burgers and not taking their drugs... and this may be saving their life... or it may just be happenstance that they aren't as afraid of death because they don't have the same genetic risk as the self-selecting low LDL group does.

But I"m always glad to hear low LDL doesn't mean jack. My latest cholesterol results:
TOtal 229
57 triglycerides
84 HDL
134 LDL

This seems to have worsened (last time my trigs were 30s and my ldl was 119) but then again I eat a lot more now haha.

mtflight said...


genial. I loved the humor, and as always enjoyed the post!

Take care and keep surprising us from time to time :-)


Peter said...

Hi ItsTheWoo,

It's a "snapshot plus follow on" study so there's no way of teasing those factors out, and all of them are potentially valid. Perhaps the best argument for it being LDL per se is the J-LIT study where everyone got the same dose of simvastatin for 5 years, increasing to 10 years, and the spike in both all cause and cardiac mortality was amazing at what is now regarded as not even optimally low LDL levels.

It seems inconceivable that current optimal therapeutic targets are killing people, but I think they might well be. Careless talk may be dangerous, but it's nothing compared to statinating down to 60mg/dl LDL. Certainly that's the impression from J-LIT.

Alex, glad you enjoyed it... Creased me up. I suspect the same applies to STEMIs too but I've not seen any data on this. Those guys in Detroit are playing with their future careers, publishing a study like this. More kudos to them for not failing to publish.


. said...

Dear All/Peter, I just want to add this interesting reference to this debate:

"Lipid Levels in Patients Hospitalized with CAD: An Analysis of 136,905 Hospitalizations in GWTG-CAD"

Brad Reid said...


Not a bad tape explaining some of the economic politics of the defamation of saturated fats. Worth the 9 minutes it takes to view it.


HHMB said...

I've been following this blog for about a year and half, but haven't posted before. I went off Lipitor, experimentally, about 8 months ago, and my lipids have changed as follows:

HDL 30 > 50

LDL 116 > 200

Trig 59 > 77

I'd better hope that high LDL is meaningless! Or should I, experimentally, go back on to statins?

Any thoughts?

Chris (Hugo's my 12-year-old son)

JohnN said...

Re. "Lipid Levels in Patients Hospitalized with CAD: An Analysis of 136,905 Hospitalizations in GWTG-CAD."

Interesting conclusion indeed where after recognizing that:

"In a large cohort of hospitalized CAD patients, almost half have admission LDL levels < 100 mg/dL, whereas less than a quarter of patients have LDL >130 mg/dL."

The author goes on to make this statement:

"These findings provide further support for recent guideline revisions with even lower LDL goals."

Ken said...

Off Topic - if and when you (or anyone) have the time.
You mentioned HbA1c. In the following are they half suggesting that low D3 levels could be the result of developing an 'abnormal carbohydrate metabolism'?
Are the results more consistent with that idea than with low D3 levels as a cause of abnormal carbohydrate metabolism ?

Relationships of low serum vitamin D3 with anthropometry and markers of the metabolic syndrome and diabetes in overweight and obesity"The inverse relationship of vitamin D3 with high to extreme HbA1c [24,25] and/or FPG [7,8] may indicate that it is the long-term, severely abnormal (carbohydrate) metabolism of TIIDM [7,26,27] and muscle insulin resistance [28], that is associated with hypovitaminosis D3. HbA1c, a glycated protein, is a predictor of 2-hour glucose in oral glucose tolerance testing, [29] an indicator of chronic hyperglycaemia, protein glycation damage [30] and oxidative stress [31]. Many new, profound and interacting mechanisms link hypovitaminosis D with other correlates of the metabolic syndrome, including renin regulation [1]. Vitamin D-upregulated protein-1 reportedly modulates endothelial oxidative stress, macrophage and smooth muscle function, depending on the stage of atherosclerosis [32,33]."

Peter said...


You could argue that there is a parallel to ascorbate (glucose/ascorbate antagonism), perhaps the pro inflammatory effects of hyperglycaemia through NFkappaB require activation of the VDR to regulate the inflammation. This would produce a differential in the D3/25(OH)D3 requirement of a LC vs SAD eater to maintain adequate 1,25(OH)2D3 levels. Your ideas hold water to me as there is so little emphasis on D3 in the original LC literature...

JohnN, are you suggesting low LDL causes heart attacks? You've been reading the J-LIT study rather more than the average cardiologist (not hard!). Now what conclusion might I draw from the very small proportion of heart attack victims who have an LDL > 130mg/dl? Hmmmmmm

Chris (Hugo), My LDL is calculated to be >260mg/dl, if I remember correctly. I, like you, require de novo cholesterol synthesis in my brain to keep my synapses working, so no statin for me. Anyone who wants to play with these drugs should do some serious basic grass roots reading before playing.

BTW am I reading that correctly, you stopped Lipitor and your HDL went from 30 to over 50? You must have started eating some fat too, or Lipitor actually suppresses HDL... And as JohnN points out over half of the people with heart attacks, "real" stentable heart attacks, have an LDL below 100mg/dl on admission, but less than a quarter have an LDL >130mg/dl. That's if you believe these number mean anything per se, rather than reflecting sugar or fat intake.

JB, not had chance to watch the video Chris (CR) put up, might get to see it if it's quiet after consults tonight.

Peter said...

With all this uncertainty, I feel a little bit better about my pesky habit of ignoring all my doctors, refusing all medications, and being a very "non-compliant" patient.

Peter said...

Hi Jim,

You might enjoy this post, and Dr BG's recent post here!


Kim Murphy said...

I'm wondering how one would raise LDL while not raising LDL-P. Asking for someone I know. Statin patient. LDL of 37, LDL-P of nearly 1,600. History of familial hypercholesterolemia. Already on a low carb / low fat) I suspect low calorie. This is an elderly person. Thank you.