A news report of a blog report of an article?

Here's the blog:
http://drmalcolmkendrick.org/2015/05/18/hats-off-to-the-japanese/

And here's the article:
https://www.karger.com/Article/Abstract/381654

The lowest mortality rate for men was associated with LDL between 120-139 mg/dl. Mortality went up on both the low end and high end.

For total cholesterol, mortality for men was lowest between 200-230 mmol/l.

I've read some of Malcolm Kendrick's stuff. I even have his latest book checked out from the library (but haven't read it yet). The gist of his message seems to be that looking at relative risk makes the absolute risk seem overblown.

High LDL does seem to be a significant risk at the highest levels, but not at the levels normally recommended for treatment.

Total cholesterol just has too many confounders mixed in, so almost nobody pays attention to it anymore, but even your graph shows risk increases at higher levels.

The Japanese study sited in the article in the OP shows modest increase in all-cause mortality, but the increased risk for CHD mortality was more significant.

So what can we take from all of this?

Cholesterol does seem to help the immune system, so that may be why all-cause mortality doesn't increase much with higher levels.

It is a factor in CHD, and the mechanism is sort of known, but it's complex, and inflammation is a big factor as well.

If your LDL is off-the-charts high, that's a valid reason to worry.

If your LDL is mildly high, get your inflammation markers checked, like CRP.

In terms of mechanisms of plaque formation, this article is pretty good:
http://www.scientificamerican.com/article/atherosclerosis-the-new-view/

Yeah, I think the risk is overblown and statins are prescribed too aggressively.

But it's a hot-button for me since the only reason I went low-carb was to reduce CHD risk. Most of my risk markers improved except for LDL concentration.

I'm at the age where I have to worry about this stuff. You have a few more years before it's a concern.

Interestingly, my risk of death by cancer seems to go down starting about now. CHD is my main concern from here on out.

I just read Kendrick's book, The Great Cholesterol Con. It said the same thing. High cholesterol has almost no realtioship with CAD. The exception he mentions is men under age 50 who have very high cholesterol levels. He even points out that women over 50 tend to develop a higher risk of CAD if you lower their cholesterol. They do better with higher cholesterol.

About the only "cholesterol" I worry about is triglycerides as higher levels can match higher levels of CAD risk (not a cause though). I also spare a thoug for Lp (a) because that can also correlate to CAD risk and mine was a bit high a couple of years back.

As far as I'm concerned, who cares if cholesterol is high for me because it has absolutely no dangers for me. It's like saying I have a greater risk of CAD if I grow I mustache just because peri/post menopausal women tend to grow mustaches around the same time that CAD could start showing up. I'm not really fussed about it.

The only reason I like seeing "improved" cholesterol numbers in low carbers is because that is often a worry for people against trying it. It is easier to say "See? LCHF improves cholesterol" than "Cholesterol improved but it doesn't matter anyways". Most people that I know won't believe it.

Kendrick's theory is that stress causes CAD. Seems over simplified to me. I do think cholesterol is just a marker of poor health that means you could develop CAD, I don't beleieve it is the cause.

wabmester wrote: »

I'm looking forward to reading his book, but most of the stuff I've read from him focuses on epidemiological studies. Those are great for forming hypotheses, but that's about it.

Once you move beyond epidemiology, there's good evidence that LDL plays a role in heart disease.

For one thing, when they look at the mechanism of plaque formation, LDL in the arterial wall starts the process.

They also look at people with genetic mutations. Those with mutations that cause high LDL have high rates of heart disease, and those with mutations that cause low LDL have lower rates of heart disease.

The most recent drug target is PCSK9 because people with PCSK9 mutations (and low LDL) have about 1/2 the risk of heart disease as those without the mutation.

So LDL is definitely a factor. It's not the only factor, and there's no clearly optimal level yet.

I still haven't seen any long-term studies of low-carb diets and heart disease -- just short-term studies and risk factors.

Bleh, I think you are mixing up info on the PCSK9 mutations...those with mutations have homozygous familial hypercholesterolemia, over expressing PCSK9 & degrading LDL-Receptors too easily. Less LDL-Receptors = more serum LDL-C. The OTHER drug target with mutations involved Cholesterol Ester Transferase (CETP)-inhibitors; persons with these mutations lacked Cholesterol Ester Transferase, thus had abnormally high HDL & longer longevity. Ultimately, CETP-inhibition as a drug target has been abandoned due to increased risk in cardiovascular mortality...hypothesized to be due to an increase in the wrong subtype of HDL, not associated with increased cardiovascular protection.

V_Keto_V wrote: »

wabmester wrote: »

I'm looking forward to reading his book, but most of the stuff I've read from him focuses on epidemiological studies. Those are great for forming hypotheses, but that's about it.

Once you move beyond epidemiology, there's good evidence that LDL plays a role in heart disease.

For one thing, when they look at the mechanism of plaque formation, LDL in the arterial wall starts the process.

They also look at people with genetic mutations. Those with mutations that cause high LDL have high rates of heart disease, and those with mutations that cause low LDL have lower rates of heart disease.

The most recent drug target is PCSK9 because people with PCSK9 mutations (and low LDL) have about 1/2 the risk of heart disease as those without the mutation.

So LDL is definitely a factor. It's not the only factor, and there's no clearly optimal level yet.

I still haven't seen any long-term studies of low-carb diets and heart disease -- just short-term studies and risk factors.

Bleh, I think you are mixing up info on the PCSK9 mutations...those with mutations have homozygous familial hypercholesterolemia, over expressing PCSK9 & degrading LDL-Receptors too easily.

There appear to be multiple mutations. A couple are associated with FH. But I was referring to this one:

http://sitn.hms.harvard.edu/flash/2015/a-potential-new-weapon-against-heart-disease-pcsk9-inhibitors/

Inactivated PCSK9 decreases LDL so much that one rare individual with two inactive copies of PCSK9 has LDL levels of 14! [3,8-9]. Researchers then examined a long-term study of heart disease risk to compare risk in participants with and without these inactivating mutations. Not only was an inactivating PCSK9 mutation associated with a 15-28% reduction in LDL, but these patients also had a whopping 47-88% reduction in heart disease risk [3,10]. In addition, their very low cholesterol levels do not appear to cause any negative effects elsewhere in the body. This study, published in 2006 in the New England Journal of Medicine, cemented the status of PCSK9 as a very attractive and potentially lucrative drug target.

Right. I view drugs that lower LDL as using a sledgehammer to fix a watch. Few docs look at treating the cause -- just relieving the symptoms (and creating new ones).

But high LDL is a risk factor. And LDL goes up on a low-carb diet. I'm sticking with low-carb, though. Other risk factors go down, and I'm guessing that inflammation goes down as well. Perhaps less LDL is oxidized and fewer plaques are formed.

It would be nice to know that for sure. I'd love to see a study that shows low-carb reduces plaque formation, or better yet, that plaques regress on low-carb.

Anybody want to do that study?

My impression is that calcified plaques are stable plaques, and it's the unstable plaques that pose the biggest risk.

But I guess I shy away from supplements on a philosophical basis. The high rate of heart disease seems to be a relatively recent phenomenon. So that suggests to me that some relatively recent change in our diet or other environmental factor is probably the cause.

It may be as simple as the increase in refined carbs. But maybe the types of fats we're eating now is also a factor. I'd love to know the answer.