Hit or miss: the new cholesterol targets

(Todd Allen) #1

https://ebm.bmj.com/content/early/2020/07/20/bmjebm-2020-111413.full

Abstract
Drug treatment to reduce cholesterol to new target levels is now recommended in four moderate- to high-risk patient populations: patients who have already sustained a cardiovascular event, adult diabetic patients, individuals with low density lipoprotein cholesterol levels ≥190 mg/dL and individuals with an estimated 10-year cardiovascular risk ≥7.5%. Achieving these cholesterol target levels did not confer any additional benefit in a systematic review of 35 randomised controlled trials. Recommending cholesterol lowering treatment based on estimated cardiovascular risk fails to identify many high-risk patients and may lead to unnecessary treatment of low-risk individuals. The negative results of numerous cholesterol lowering randomised controlled trials call into question the validity of using low density lipoprotein cholesterol as a surrogate target for the prevention of cardiovascular disease.

Discussion
This analysis highlights the discordance between a well-researched clinical guideline written by experts and empirical evidence gleaned from dozens of clinical trials of cholesterol reduction. It further underscores the ongoing debate about lowering cholesterol in general and the use of statins in particular. In this analysis over three-quarters of the cholesterol lowering trials reported no mortality benefit and nearly half reported no cardiovascular benefit at all.

The widely held theory that there is a linear relationship between the degree of LDL-C reduction and the degree of cardiovascular risk reduction is undermined by the fact that some RCTs with very modest reductions of LDL-C reported cardiovascular benefits while others with much greater degrees of LDL-C reduction did not (MEGA, ALLIANCE, SEAS, ODYSSEY FH 1 and 2, SPIRE 1 and 2).5–9 23 This lack of exposure–response relationship is illustrated in figure 3, where the scatter plot and the calculated correlation coefficient ® suggest there is no correlation between the percent reduction in LDL-C and the absolute risk reduction in cardiovascular events. Moreover, consider that the Minnesota Coronary Experiment, a 4-year long RCT of a low-fat diet involving 9423 subjects, actually reported an increase in mortality and cardiovascular events despite a 13% reduction in total cholesterol.24 What is clear is the lack of clarity of these issues. In most fields of science the existence of contradictory evidence usually leads to a paradigm shift or modification of the theory in question, but in this case the contradictory evidence has been largely ignored simply because it doesn’t fit the prevailing paradigm.25 26

Cholesterol out of range, am I going to die?
Getting mad at these detractors
(Gregory - You can teach an old dog new tricks.) #2

Golden!

(Bunny) #3

In other words when you leave home to go see your cardiologist don’t forget your wallet?

Was looking at this Spanish study which is interesting concerning Vitamin C:

“…The cumulative risk of a cardiovascular event was 0.07% in the highest tertile versus 0.12% in the lowest tertile of vitamin C intake. We found that higher vitamin C intake was associated with a lower risk of CVD in the age-adjusted analysis (Table 2). …” …More

(Gregory - You can teach an old dog new tricks.) #4

From the study:

Conclusions Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes. Findings from the Minnesota Coronary Experiment add to growing evidence that incomplete publication has contributed to overestimation of the benefits of replacing saturated fat with vegetable oils rich in linoleic acid.

This was almost 50 years ago… I’m sure it slipped through the cracks somewhere while the subsidized seed oil companies ramped up production…

(You've tried everything else; why not try bacon?) #5

The Minnesota Coronary study, conducted by Ancel Keys and Ivan Franz as principal investigators, was withheld from publication for over 17 years, because the results failed to meet expectations. This is documented by Gary Taubes, who actually interviewed Dr. Franz, in Good Calories, Bad Calories. Ancel Keys insisted that his name be taken off the study, and when Franz finally published the results, it was in an obscure journal that very few people in the field looked at.

There is an episode of “This American Life,” in which Dr. Franz’s son describes finding the data tapes from the study in his father’s basement after his death, and how the reanalysis of the data showed the negative correlation between cholesterol levels and cardiovascular risk. It is worth noting that, while a positive correlation is not necessarily proof of causality, a negative correlation is in fact proof of a lack of causality.

(Gregory - You can teach an old dog new tricks.) #6

Dr. David Diamond has talked about Statin trials that were stopped early, because early results that showed some small benefit that started disappearing the longer the trials continued…

It didn’t stop them from publishing the early results and touting the misleading relative benefit.

I think that there were also some increased mortality figures for the statin group as the trials continued…

(Gregory - You can teach an old dog new tricks.) #7

Here’s a link to a 2016 re-evaluation of the Minnesota Coronary study.

Re-evaluation of the traditional diet-heart hypothesis: analysis of recovered data from Minnesota Coronary Experiment (1968-73)

Conclusions Available evidence from randomized controlled trials shows that replacement of saturated fat in the diet with linoleic acid effectively lowers serum cholesterol but does not support the hypothesis that this translates to a lower risk of death from coronary heart disease or all causes.

What’s more:

There was a 22% higher risk of death for each 30 mg/dL (0.78 mmol/L) reduction in serum cholesterol

Lowering your cholesterol, just might kill you…

(Gregory - You can teach an old dog new tricks.) #8

This stuff is easy to find if you go looking for it…

# Low cholesterol is associated with mortality from stroke, heart disease, and cancer: the Jichi Medical School Cohort Study

Conclusions: Low cholesterol was related to high mortality even after excluding deaths due to liver disease from the analysis. High cholesterol was not a risk factor for mortality.

(Bob M) #9

My only issue with a lot of this is that those of us (like me) with “low” cholesterol appear to be doomed to an early death from a variety of diseases apparently cured by high TC/LDL.

(Gregory - You can teach an old dog new tricks.) #10

I suspect that low TC associated with higher mortality, is accompanied by other health issues…

The take away for me, is that it can’t be shown that higher levels of TC, can be shown to cause higher incidence of CVD…

(Bob M) #11

Cannot might be a bit too strong. While I think it’s unlikely there are LDL BBs that are just waiting to create heart disease, it’s plausible that perhaps if something occurs to cause heart disease (Dr. Kendrick’s damage to the endothelium hypothesis), maybe a higher LDL is associated with a higher response than a lower LDL? I don’t think that’s the case, but that’s one argument I see.

I have ridiculously high Lp(a). The knock against this is similar: does having a high Lp(a) mean that if there is damage leading to CHD, would having a higher Lp(a) mean higher levels of CHD?

These seem to explain the correlation between higher LDL or Lp(a) and higher CHD: the underlying disease is not CAUSED by higher LDL or Lp(a), but might be exacerbated by these, once the disease starts.

(Bunny) #12

Higher saturated fat and linoleic acid in the diet, does this matter in ratios?

I doubt you could control the intake of either very accurately.

Not enough linoleic acid your looking at blood clots from what the research indicates.

You not only have CVD but you also have CHD Risk.

When you put it all together from hundreds of pieces of research it spells out Vitamin C deficiencies as the root cause and too much dietary sugars or endogenously high glucose.

(Bob M) #13

I’m a disbeliever in anything Vitamin C. Sorry.

(Gregory - You can teach an old dog new tricks.) #14

While you make some excellent points, the question remains is there really any benefit to lowering LDL or TC?

At what point is LDL > 0 less likely to be involved in the process?

Chemical ( biochemical? ) reactions do not cease until the necessary ingredients, and necessary environment no longer exist…

It seems particularly absurd to me to think that LDLc above 100 is more likely to be involved in artery deposition than, say, 50.

Of course, the amount of small particles available, does seem to matter.

(Bunny) #15

It would be nice to know why?

Any science behind that train of thought?

(Gregory - You can teach an old dog new tricks.) #16

See above:

(Bunny) #17

When they are measuring serum Cholesterol; LDL, HDL and Lp(a) and particle size, it is because that is all you have left repairing the damage to the endothelium because your missing this:

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(Gregory - You can teach an old dog new tricks.) #18

That doesn’t answer the question of at what point > 0 does cholesterol stop being used to repair damage ?

If it doesn’t stop being used, what is the benefit of lowering it?

( I realize I’m mostly preaching to the choir here… )

(Bunny) #19

To be honest it does not matter if it (cholesterol) is low or high the glycocalyx shield is what matters.

My blood work always comes out “normal” after being ketogenic, it use to be “abnormal“ even as a child.

(Todd Allen) #20

Noticed that the link I originally posted no longer gives the full paper which is now behind a paywall. Fortunately there is scihub:
https://sci-hub.tw/http://dx.doi.org/10.1136/bmjebm-2020-111413