20 December 2018

Wikipedia's Standards are Off the Rails

Recently, some advocates of low carb and healthy lifestyles have been deleted from Wikipedia. This seems to be driven by an editor called Skeptic from Britain.

The reason given is that their views represent fringe views outside of the mainstream. In my opinion, this is arbitrary and an improper reason. If the people in question were nobodys, (like me), that would be fine. But they're not. They are respected authors, scientists, doctors and filmmakers with an alternative point of view.

Deleted pages include Malcolm Kendrick, Tom Naughton, Jimmy Moore, and Uffe Ravnskov. I suppose it's only a matter of time before Taubes, Atkins, and Lustig get deleted too.

Point of view should not be a consideration for deletion, but rather their accomplishments. After all, even the Unabomber has a page. He has an unconventional point of view. Should he be removed? of course not.

If you are interested in writing to the donations department this is the email. donate@wikimedia.org

Update from Tom Naughton of Fathead, ehich was also proposed for deletion.
"I've been tweeting about this whole issue for a couple of days, which drew the attention of Jimmy Wales, the founder of Wikipedia. His first several replies were long explanations of Wikipedia policies, the apparent message being that nothing was wrong, no violations of policy, no biases in tagging for deletion, move along, folks, nothing here to see. That ticked me off, because the editor’s bias could hardly be more obvious.  That’s why in my previous post, I said Wales was making a fool of himself on Twitter defending this nonsense.
I need to take back the insult now, apologize to Wales, and give credit where credit is due. "In a couple of Twitter exchanges, I pointed that Fat Head was targeted for deletion right after I wrote about Kendrick. I asked if he truly believed this editor was making objective decisions, which seemed highly unlikely.
"He replied that he didn’t know what Fat Head is and was unaware of it being targeted for deletion. He then sent me a private message asking for more information. I sent links demonstrating who the editor had targeted, how he’d changed his handle twice in a matter of days while continuing the targeting, etc.
"Wales responded that such behavior was against policy and could lead to an editor being banned.  He said he’d look into the matter."
Here's hsi response:
"Strong keep – As others have noted, WP:IDONTLIKEIT is not a valid reason for deletion. It is worth noting that the proposer is a serial name changer and POV pusher who has now apparently left the project. A quick research of the film reveals that in addition to the sources that User:Strikerforce rightly says are enough to ‘barely’ pass notability, I found an article at Motley Fool and this one at Vulture. It is not a major film to be sure, but there seems to be no reason for deletion other than the POV pushing of the proposer."

Here is the full conversation in Wikipedia Kendrick Deletion page.

I wrote the following letter to Wikimedia.org.

In the last few weeks, many advocates of low carb diets and healthy lifestyles have been removed from Wikipedia including Dr. Malcolm Kendrick, Uffe Ravsnkov, and now Tom Naughton. They are published and notable authors, scientists, doctors, and filmmakers with a non-mainstream PoV. The editor cites their non-mainstream views as the reason for removal. This is unethical and contrary to Wiki’s mission.

The editor who proposed their deletion Skeptic from Britain cited their non-mainstream points of view as the reason for their deletion. Based on that standard, you should also delete Ted Kaczynski. You have a responsibility to have reasonable, consistent standards.

The standard for inclusion should be related to their notoriety and impact, not their specific points of view. I am very disappointed in this recent turn, and in my opinion, it is contrary to the public's and Wikipedia's best interests.

I recently donated $6 to Wikimedia and I would like a refund of that money. I will not financially support any organization that suppresses points of view that are contrary to the mainstream.

Should I simply protest this donation through my credit card, or is there a better way for me to receive a refund? Please advise.


I'm pretty hacked off about this.

Edit: The following is the response I received from an unpaid volunteer of Wikipedia. I am still going to withdraw my contribution until Wikipedia cleans up their standards about biog. If you want to do the same, this is the email. donate@wikimedia.org 

"Regardless of his medical credentials, Dr Kendrick - along with the readers of his blog - exhibits a fundamental inability or unwillingness to understand how Wikipedia works. Articles on Wikipedia are deleted according to our Deletion Policy: <https://en.wikipedia.org/wiki/Wikipedia:Deletion_policy>. "Big Pharma" do not have any say in the matter, despite Dr Kendrick's consipiracy theories.

"The article in question was deleted after a debate at <https://en.wikipedia.org/wiki/Wikipedia:Articles_for_deletion/Malcolm_Kendrick
>, because members of the community established that it was unsuitable for inclusion due to a lack of verifiable information from independent sources. If such sources are not provided during the deletion discussion - which they were not - then this indicates that the topic is not currently notable enough for a Wikipedia article. Dr Kendrick's theories and their validity had literally no bearing on the matter.

"If you believe after reading the deletion policy that the article was unfairly deleted, you can ask the administrator who deleted the article for a fuller explanation. If after an explanation you still believe the deletion was unfair, you can bring up the article at Deletion Review (https://en.wikipedia.org/wiki/Wikipedia:Deletion_review) where the community can take another look to see if the article was deleted in error.

"With regard to your donation, this channel is entirely staffed and managed by volunteers, and we have no involvement in the donation program. You will need to contact the Wikimedia Foundation directly to request a refund; the donations dapartment can be contacted at donate@wikimedia.org .

"Yours sincerely,

"Wikipedia - https://en.wikipedia.org/
"Disclaimer: all mail to this address is answered by volunteers, and responses are not to be considered an official statement of the Wikimedia Foundation. For official correspondence, please contact the Wikimedia Foundation by certified mail at the address listed on https://www.wikimediafoundation.org/

E4E take:
In my opinion, he is worth every cent they pay him. I found his response snarky and insulting. The discussion page regarding Kendrick's deletion is full of ad hominem statements and attacks on the people who were defending Dr. Kendrick. They attacked his science, but then said that the science isn't the issue, it's the lack of notoriety of Kendrick. There is some discussion of the lack of "verifiable information from independent sources" as mentioned by the volunteer. 

I simply do not have the time or energy to dig in and understand all of the wikipedia rules and regulations about biographical entries. Apparently, for inclusion, there must be significant external reporting on the person in question. This seems like an odd standard for someone carrying the standard of a non-mainstream view, but those are the rules.

Here are some references to the jihad against the low carb community.
The Skeptical Cardiologist (disagrees with Kendrick scientifically, but thinks deletion is wrong)
Reddit thread
Reddit page on Kendrick

A Couple of Posts that I think are pretty well-stated:
"Secondary sources, as you describe, should be unnecessary unless the subject (of the biographical page entry)'s existence has been seriously challenged by a reader. My interest is in keeping Wikipedia as a usable reference source for most web users. A subject of a biographical page is notable, by such a definition, each time a visitor to Wikipedia types in the subject's name, which the visitor almost certainly got from somewhere else i.e. from a secondary source. The great benefit of a comprehensive compendium of knowledge of all kinds, from the very trivial to the most profound, is its inclusiveness. A serendipitous wander wherever my interest takes me is another of the great pleasures of the site. These things are what I pay for when I contribute to Wikipedia's various appeals and they will be lost if too many gatekeepers try to keep material off it. Editors should concentrate on keeping pages as accurate as possible, on distinguishing clearly between orthodox and heterodox viewpoints, and on keeping the tone of the page polite, not on deleting serious entries about real people.Shirley49 (talk) 22:45, 5 December 2018 (UTC) — Shirley49 (talk • contribs) has made few or no other edits outside this topic."

"We are now talking at cross-purposes. My point is that the way some Wikipedia editors now work is destroying the web-site for the general reader. The rules for posts have become so legalistic that they are almost impenetrable. The basic rule should be simple. If someone posts something which can be factually disputed, the person who wishes to do this should do so and the matter can then be debated online. If an agreed consensus can be reached, that should stand. If not, the view, which is judged to be the mainstream or majority view, should stand, but at the base of the page should be a link to a separate page where the minority view or views can find expression. This is a common procedure elsewhere, like in the civil courts, where dissenting judgements are routine. If this were to occur, Wikipedia could then be freed of the charge of censorship of unpopular views or of ideas which challenge the rich and influential. Secondary sources can look impressive, but how much is: "You scratch my back and I'll scratch yours"? I feel the main problem with science today is, that with a few notable exceptions, the mainstream scientist lacks the ability to interest and educate the lay-person. If Wikipedia has no wish for the small amounts of money I sometimes send it, I can spend it on something else.Shirley49(talk) 02:33, 6 December 2018 (UTC)"

Bottom Line of Wikipedia
Yes, WP sides with the mainstream, it's by intent and by design, see for example here and here. It's part of our structure, what we are for. But the internet is vast, so there are plenty of other places to write. What can make an article accepted here, is sources (WP:RS) as described at for example WP:NACADEMIC or WP:AUTHORGråbergs Gråa Sång (talk) 19:22, 6 December 2018 (UTC)

23 January 2018

Dr. Malcolm Kendrick's Series on What Causes Heart Disease

Malcolm Kendrick is a very smart guy.

Dr. Kendrick graduated from medical school in Aberdeen and trained as a General Practitioner in Scotland. After ten years he split his time between General Practice and education. On the doctor side, Malcolm currently lives and works in Cheshire in General Practice, Intermediate Care, and Out of Hours. On the education side, Malcolm set up the online educational system for the European Society of Cardiology, working with the European Commission, and also set up the first website for the National Institute for Clinical Excellence (NICE) in the UK.

Malcolm is an original member of the Centre for Evidence-Based Medicine in Oxford and of The International Network of Cholesterol Sceptics (THINCS). The latter comprises a group of scientists, doctors, and researchers who share the belief that cholesterol does not cause cardiovascular disease. This is the field of medicine for which Malcolm is best known.

"His long-term interest in the epidemiology of cardiovascular disease has resulted in many publications in journals such as the BMJ, Medical Hypotheses, Pulse, and PharmacoEconomics. His breadth and depth of expertise in this area led to his election to Who’s Who in 2009.

"The Great Cholesterol Con was the book that firmly placed Malcolm on the world stage of the ‘diet-cholesterol-heart’ hypothesis and his army of followers are eagerly awaiting his next bout of wit and wisdom. Malcolm blogs at drmalcolmkendrick.org and lectures by invitation. Married with two children and two cats, Malcolm would like more people to challenge the status quo, and never just accept the party line. He likes to ski, golf, sail."

He is a practicing doctor in Scotland and an author.
His website home
His about page
Wikipedia article
His books on Amazon
A paper written in 2022
From the book titles, you can see that he is not a mainstream go-with-the-flow kind of guy.

Please look at his writings, you will see a no-nonsense follow-the-data approach. It's good reading.

He started a series called What Causes Heat Disease in January 2016. As of January 21, 2018, he is on installment number 44. It is not simple to find all of the links to each of the posts in sequence, so I have made it a project to do that. [Now up to 61 on Jan 16, 2019]

It is provocative, super-interesting, and need I say it is also quite different from what your cardiologist will tell you. I got up to 10, then decided to catalog this. I'm going to reread from the start and put a little about the content of each as I progress.
  1. What Causes Heart Disease I, 01/18/2016, Introduction. Everything causes heart disease; nothing causes heart disease. What is heart disease (Cardiovascular disease or CVD)? CVD is caused by a process, not a thing. "My simple credo is that, if your hypothesis cannot explain everything about CVD you cannot explain anything."
  2. What Causes Heart Disease II, 01/21/2016, Framing the problem. Start with "What kills people?" There are many complications and variations. The "reverse hypothesis," i.e. the primary cause of a heart attack is simply a blood clot blocking a coronary artery, has two contradictions. An infarction does not mean that a clot develops, and collateral circulation develops. Ischemic stroke and MI have the same underlying disease process. It is very complex.
  3. What Causes Heart Disease III, 01/25/2016, Data from different countries used different standards so is unreliable. Starting at the end--the formation of the final, often fatal, blood clot. Surprisingly, he adds statins to the list of things that reduce the risk of blood clots (although not by much). But not because of their impact on cholesterol, but rather because of anti-coagulant effects--like aspirin. He hints at another effect statins have. Now the controversy--the two steps to CVD are considered to be 1. formation of an atherosclerotic plaque, and 2. clot formation on top of the plaque. But it's strange that the two processes share many risk factors. Perhaps they "are simply two different manifestations of exactly the same underlying disease process." Occam's razor.
  4. What Causes Heart Disease IV, 02/08/2016, Lots of causes of CVD, but only 1 underlying process. He covers the first of four stages that culminate in the development of an atherosclerotic plaque that culminates in the final fatal blood clot--endothelial damage. He looks at three aspects: Nitric Oxide synthesis, consequences of endothelial damage, and tissue factor (a clotting agent). NO is created in the endothelium. It relaxes blood vessels and is an anti-coagulant. Perhaps the single most powerful factor to increase NO synthesis is sunlight. Wow! The implications of this alone are tremendous. Biomechanical stress (turbulent blood flow, stretching and bending of the blood vessel, high shear stress, high blood pressure, rapid blood flow, points where the blood has to change direction violently) is thought to be the highest damaging factor. The tissue factor is inside all blood vessel walls and immediately forms a clot if there is damage. Once the damage is covered, the clot stops. Then what happens to it? To be continued in the next part.
  5. What Causes Heart Disease V, 02/13/2016, Start with some background about how the hypotheses of CVD developed and changed. How does the clot get inside the arterial wall? Endothelial cells grow over the clot. But now you just have a clot in the wall of the blood vessel. This doesn't seem too smart. What happens to the clot? If your body is working right, some of the new endothelial cells convert into macrophages and clear up the clot itself as the new endothelium is forming. But if the damage/clot process happens too rapidly or repeatedly in the same place, the body simply can't keep up with the cleanup. Then the clot turns into "a pulpy mass containing cholesterol crystals and fatty globules."
  6. What Causes Heart Disease VI, 02/21/2016, Recapping, there is a four-step process that happens with CVD. Endothelial damage, clot formation/dysfunctional clot formation, clot repair/dysfunctional clot repair, and the final fatal blood clot. Plasminogen in clots causes the destruction of the clot by slicing apart the fibrinogen (good). Plasminogen activation inhibitor (PAI) prevents that. Triglycerides enhance PAI and therefore impair breakdown of the clots! Therefore hypertriglyceridemia is bad. Fibrinogen. According to the Scottish Heart study, High cholesterol has no effect, but "‘Fibrinogen is a strong predictor of coronary heart disease, fatal or non-fatal, new or recurrent, and of death from an unspecified cause, for both men and women."  The study found that "Unexpectedly, individuals with low plasma fibrinogen had a low incidence of coronary events even when serum LDL cholesterol was high."  Smoking, stress, sleep apnea, diabetes, and depression all raise fibrinogens. Lp(a) is a type of LDL but with a "backward-threaded" plasminogen molecule. So Lp(a) folded into a blood clot blocks plasminogen, preventing a clot from breaking itself down. Aside, LP(a) is found in mammals that do not produce their own Vitamin C. It provides a permanent plug for holes in tissue because scurvy prevents collagen production. Lp(a) level in the blood is thought to be largely genetic, but there is evidence that ensuring more than minimum vitamin C and fish oil (2)/flaxseed can reduce Lp(a).
  7. What Causes Heart Disease VII, 03/01/2016, Yes heart disease is multifactorial, i.e. many things can cause it, but they all trigger the same process. If you can't do this, your hypothesis is off. It's not the cholesterol. He focused on blood clotting factors and found that factors that increased clotting were bad and vice versa. HDL inhibits platelet activation in the endothelium and increases NO production. ‘Plaques are clots, and clots are plaques. It is all due to blood clotting.’  It is staring you in the face. It has been staring humanity in the face for over a hundred and sixty years. Ever since Rokitansky and Virchow started to look closely. There is no cholesterol in the story. It's something that just happens to be there.
  8. What Causes Heart Disease VIII, 03/10/2016,  The body can heal plaques. (Probably not once calcified, but that is another issue). This chapter relates to the third step--Clot repair / dysfunctional clot repair. Endothelial progenitor cells (EPCs, repair stem cells) are an important part of the picture. Exercise, l-arginine/citrulline, ACE inhibitors, and statins all increase NO levels and EPCs. "...statins do have some benefits in CVD. Not enough, in my opinion, to overcome the damage that they can do. However, the benefit is there, it is real. I knew it could be nothing to do with the impact of statins on lowering LDL, as LDL has nothing to do with CVD (well, almost nothing). So there had to be another effect. And that effect is, in my opinion, almost entirely to do with the ability of statins to increase nitric oxide (NO) production..." Many people saw that statins reduced cholesterol and improved CVD outcomes. Therefore, they assumed that correlation = causation and low cholesterol is the key.
  9. What Causes Heart Disease IX, 03/16/2016, Modern medicine's disease paradigm has forced the shoe onto the wrong foot. Confirmation bias and cognitive dissonance take over and researchers make excuses for contradictory data. "Me; ‘The French have higher cholesterol levels than the Russians and one-tenth the rate of CVD.' A.N. Expert: ‘The French are protected by drinking red wine and eating lightly cooked vegetables and garlic.’ is an example of an ad hoc hypothesis. A new type of study called a teleoanalysis was brought in to try to legitimize ad hoc hypotheses. In a nutshell, they create a hypothesis, assume a study has been done, and declare victory. In other words, they make shit up. "...teleoanalysis provides the answer to questions that would be obtained from studies that have not been done and often, for ethical and financial reasons, could never be done.’ Lol.
  10. What Causes Heart Disease X, 03/22/2016, Calcification in arteries. Coronary Artery Calcium (CAC). The best way to look at calcification is as an end stage of plaque development. It may actually be a protective mechanism that puts a hard cap on top of the plaque to prevent it from escaping into the bloodstream and clogging other blood vessels. Not all plaques calcify. Vitamins K and D seem to be protective, and Warfarin seems to increase calcification. Calcification seems to have the effect of making plaques more stable. Conclusions: 1. After the age of 40-50, if your CAC score is zero, your risk of CVD is low. 2. If your CAC score is high, it means you have been developing plaques for quite a while, and your risk is higher. "[However, bear in mind that CAC represents your history, not necessarily your future]." 3. Calcification can reverse. Vitamin K2 seems to help this. 4. Calcification is not a cause of CVD. Rather it seems to be an end state of the process. 5. There is no evidence that reversing calcification improves CVD risk. "But it seems likely there would be benefit."
  11. Sunbathing is Good for You, 3/23/2016, ‘Results: Sunburn, high intermittent sun exposure, skin awareness histories, and solar elastosis were statistically significantly inversely associated with death from melanoma.’‘Conclusion: Sun exposure is associated with increased survival from melanoma.’
  12. What Causes Heart Disease XI, 03/26/2016, A new study has come out about people with coronary artery disease (CAD). The headline says "Depressed CAD Patients May be at Higher Risk For MI, Death"  CAD patients with depression are much more likely to die. Depression creates dysfunction in the hormonal response to stress (HPA-axis). Abnormal cortisol levels--low in the morning, high the rest of the time. Cortisol is a direct antagonist to insulin, and severe depression can actually cause T2 diabetes! It can also cause clotting abnormalities: higher fibrinogen, higher Plasminogen Activator Inhibitor, which prevents clot repair. "Diabetes/raised blood sugar levels are directly damaging to the endothelium. Raised fibrinogen and PAI-1 are very powerful risk factors for CVD, primarily because they make the blood more likely to clot, and the clot more difficult to clear up." 
  13. Lower Cholesterol Has No Effect On Heart Disease, 4/24/2016, Hope3 trial for rosuvastatin. Showed no difference between the treatment and placebo groups. Accelerate trial tested evacetrapib. "Despite reducing levels of low-density lipoprotein (LDL, or “bad” cholesterol) by 37 percent and raising levels of high-density lipoprotein (HDL, or “good” cholesterol) by 130 percent, the drug failed to reduce rates of major cardiovascular events, including heart attack, stroke, angina or cardiovascular death." "Researchers, looking at those living in Framingham, in the US, found that younger men with high cholesterol levels were more likely to die from CVD. From this, they concluded. Raised cholesterol causes CVD.  ACCELERATE clearly falsifies their simplistic hypothesis. It is a black swan." The evidence is very clear: increased cholesterol is not a cause of nor associated with CVD. Greater cholesterol lowering using polyunsaturated fat increases the risk of death. Yet here's what the British Heart Foundation, as well as other heart disease associations, say. "Here is what the BHF currently say about saturated fats (SFA): ‘Swap these for unsaturated fats. Eating too much saturated-fat increases the amount of cholesterol in your blood.’"
  14. What Causes Heart Disease XII, 04/25/2016, The four-step process is really overlapping processes. Now, the role of lipoproteins. Bottom Line: High levels of LDL increase the risk of blood clots forming (oxidized LDL is really bad), High levels of HDL reduce the risk of blood clots forming, VLDL/triglycerides increase the risk of blood clots forming. All this is not because cholesterol clogs the arteries, but rather because of their impact on clotting. So lipoproteins do have a role in this. Kendrick apparently  believes the role is small (supported by research as well, see links below.)
  15. What Causes Heart Disease XIII, 05/07/2016, Heart Disease and Inflammation - Take nothing at face value. Many leading researchers have enormous financial stakes in drug trials--often undisclosed. Inflammation as a cause of CVD is not an unreasonable hypothesis, but... There seems to be an association, but is it causal. Inflammation is actually a healing process. If you sprain your ankle, the damage causes an injury and healing process that results in swelling and pain. The swelling and pain did not cause the swollen ankle. "Whenever I see anyone stating that inflammation is a cause of anything I simply change the word inflammation to the word ‘healing,’ to see how sensible it then sounds." Autoimmune diseases, e.g. rheumatoid arthritis and asthma are the result of runaway inflammation, and anti-inflammatory can help. RICE for injuries is now thought to be misguided because "‘Anything That Reduces Inflammation Also Delays Healing [I cannot resist stating that, this is because inflammation is healing]"   People who take corticosteroids may get "iatrogenic Cushing's syndrome." This anti-inflammatory regime increases CVD risk. "In short, if CVD is primarily a disease of inflammation, then potent anti-inflammatory agents ought to reduce the risk. Instead, they increase it massively. There is no doubt that inflammation is associated with CVD. Equally, if you measure C-reactive protein (a marker of inflammation), a high level is associated with a higher risk of CVD. However, it is not a cause, and if you try to reduce inflammation you will almost certainly increase the risk of CVD, not decrease it. Ergo. Inflammation is a sign of active CVD."
  16. What Causes Heart Disease XIV, 05/18/2016, Age and sex are two of the most prominent risk factors associated with CVD. There is no doubt that there is an association and a strong one. The calculators used by doctors generally overstate CVD risk. "...if the two most powerful risk factors you have for CVD, cannot be explained, are not explained, then you really have a major problem. Even if you cannot even comprehend that you do."If you cannot explain why age, and gender, cause CVD… you cannot explain CVD."
  17. What Causes Heart Disease XV, 05/31/2016, Everyone "knows" pizza is bad for you. However there was a study assessing the impact of pizza on heart disease. It showed that pizza helps. Upon discovery that the study was done by Italians, the expert said, "Oh yes, but Italian pizzas are much healthier than those in the UK." Pulled straight out of thin air, ad hoc hypotheses like these are extremely common. "There was no point in saying what things may, or may not, cause CVD – and compiling an ever-lengthening list of ‘risk’ factors. I had to work out the process through which any factor may operate, both causal and protected." HE questioned, "Can you link any and all factors, known to cause CVD by their impact on one of two things: Endothelial damage (which triggers blood clot formation) or Increasing blood coagulability (making clots more like to form, become bigger and/or less easy to break down). For all the lists of the usual suspects, he had a "reasonable" view of the mechanism associated with clotting. Warfarin was one of his potential black swans because despite functioning as an anticoagulant, it appeared to have little or no impact on CVD risk. His belief is through its connection with Vitamin K, Warfarin inhibits normal "intrinsic" clotting, whereas the clots that occur in CVD start with the damage to the endothelium and subsequent exposure of blood to the tissue factor, so no effect. This is an extrinsically driven clotting mechanism. But Warfarin also inhibits the cleanup of clots through the Vitamin K channel. E4E query: It is possible that this explanation of Warfarin is just another ad hoc hypothesis? A "just-so" story? Who knows. Kendrick goes on to say "In the spirit of true scientific endeavour, I welcome as many attacks/contradictions as people can think of. What does not kill a scientific hypothesis can only make it stronger."
  18. What Causes Heart Disease XVI, 06/08/2017, He discusses how sickle cell anemia and migraine headaches both cause CVD through their link with the clotting system. From an article in BMJ, "Cardiovascular disease was 50% more likely among the women with migraine. Heart attack was 39% more likely, stroke 62% more likely, and these women were 73% more likely to have a revascularization procedure." There's not much research in the area, but he found that migraine is associated with, or causes, blood clotting abnormalities – and also damage to the endothelium in one study. He also cites a case in which Warfarin was successfully used to treat migraines. He challenges the reader to suggest another mechanism besides clotting that is consistent with this set of information. Sickle cell disease (SCD) is the other topic of this post. There is a strong association between SCD and CVD. The abnormal shape of the red blood cells causes both clotting problems and increased endothelial damage. "...sickling process leads to vascular occlusion, tissue hypoxia, and subsequent reperfusion injury, thus inducing inflammation and endothelial injury. This causes a blunted response to nitric oxide (NO) synthase inhibition." "In one short section on SCD, we have virtually everything I have been writing about in this series so far. There is: Reduced NO synthesis, damage to the endothelium, increased risk of blood clotting in general, increased platelet activation and adhesion, inhibition of endothelial cell repair and proliferation, increased risk of CVD, and accelerated atherosclerotic plaque development." Sickling also causes hypertension in the pulmonary arteries which is extremely rare. Therefore SCD must be a very powerful contributor to CVD.
  19. What Causes Heart Disease XVII, 06/19/2016, Epidemiology of CVD. In 1948, the World Health Organization (WHO) came up with standard codes for the International Classification of Disease (ICD). Although the codes were standardized, it is not clear if the standards used were the same everywhere. In fact, it's certain they weren't. At least it was a step in the right direction and it is [probably improving over time. The MONICA project attempted to standardize this. CVD deaths have been declining in the UK since 1980, the introduction and increasing use of statins had little or no impact on the decrease. OTOH, Latvia and Russia had CVD death charts that map well onto social and political upheaval.
  20. What Causes Heart Disease XVIII, 07/12/2016, Talking about cholesterol. Here's the bottom line: a. LDL is pro-coagulant and – at very high levels e.g. in FH – increases the risk of CVD [though it is difficult to disentangle this from intertwined genetic pro-coagulant factors]. b. VLDL (triglycerides) are pro-coagulant and increase the risk of CVD. c. HDL is anticoagulant and protects against CVD. This then brings us to statins, and how they work. First to re-iterate that statins do reduce the risk of CVD [Something, I have never disputed]. However, they do it not by lowering LDL, but because they have anticoagulant effects. Not that potent, about the same as aspirin, but the effect does exist.
  21. What Causes Heart Disease XIX, 07/31/2016, Ancel Keys and the diet-heart hypothesis. Sixty years ago Keys proposed that consuming cholesterol raised blood cholesterol, which then caused heart disease. He later changed his story to saturated fat raising cholesterol, thereby... Many did not agree with him, but he was very influential and his view became accepted as dogma and set the agenda for discussion of CVD. Kendrick does not see any eating behavior that powerfully links diet to CVD. "The only link that I can see is that people who eat a higher carbohydrate diet are more likely to become obese and develop diabetes. Or, perhaps I should say, develop diabetes and become obese." "...[Keys] certainly succeeded in anchoring almost all discussions within the wider hypothesis that CVD is primarily due to diet. It is not." A lot of people in the comments to this post insist that CVD does have to do with diet. e4e take: I believe that Kendrick deliberately overstated the case against diet being a cause of CVD. I think there is a subtle distinction at play: unless you are eating poison, the specifics of what you eat have little to do with the process of CVD. At the same time, deficiencies of certain nutrients can and do enhance the CVD process. Changing your dietary patterns may change your overall health and shift your nutrient intake patterns. He did state in an earlier post that a lack of vitamin C causes scurvy and can impact Lp(a) expression. If I were to attempt a slightly more pedantic statement, perhaps something like, "Assuming you have adequate intakes of important nutrients and are meeting your body's needs at a reasonable calorie balance, the specifics of your food intake have little impact on CVD health at a population level."
  22. What Causes Heart Disease XX, 08/21/2016, Stress/strain. Stress is what creates a response, strain is the biological and chemical processes that result in the body from stress. Strain can be measured by dysfunction in the HPA axis (hypothalamic, pituitary, adrenal). A normal cortisol secretion rises in the morning, goes down, rises at lunch, and goes down and up quite a lot for the rest of the day. It is, basically, flexible. An unhealthy cortisol secretion is more of a flat line. It does not peak in the morning, then it does not fall so much. "...hypothesis being that if someone is exposed to repeated activation of the HPA-axis it eventually becomes unable to cope. The system becomes damaged/inflexible." If you are exposed to constant negative stressors, you are likely to burn out your HPA-axis, and you will end up with abnormal cortisol secretion, and suchlike. You will then develop central obesity, high blood pressure, high VLDL levels, low HDL levels, high levels of fibrinogen, and many other clotting factors. All of these things will increase endothelial damage, stimulate blood clotting, and impair the repair systems. Country-level data on Latvia and Lithuania during times of crisis may be good evidence for the impact of strain on CVD.
  23. What Causes Heart Disease XXI, 09/21/2016, Use of proton pump inhibitors (PPIs) increases the risk of CVD. There are two known effects. 1. PPIs tend to cause platelets to aggregate or clump more. But this does not seem to be the important mechanism. More damning is #2: PPIs tend to inhibit the excretion of NO. Here's what Kendrick says. "...PPIs inhibit NO production, through a biochemical system that is well known and has been clearly established. NO is probably the vital molecule in heart health. It protects the endothelium, it prevents blood clots, it stimulates the production of endothelial progenitor cells. Therefore, anything that damages NO synthesis will – inevitably – increase the risk of CVD."
  24. What Causes Heart Disease XXII, No XXII exists
  25. What Causes Heart Disease XXIII, 12/24/2016, The dietary guidelines are under attack. The Minnesota Coronary Experiment proved that the hypothesis that "saturated fat causes heart disease" is invalid. In fact, the replacement of saturated fat with polyunsaturated vegetable oils actually increased death from all causes. This study is important because it was the largest trial to test this. It was run by Ancel Keys and was finished before the nutritional guidelines were developed. The results were not published until MANY years later. Kendrick says "A bunch of liars hid the results." Which may be true. I tend to take the more generous view that well-meaning people were blinded by confirmation bias and cognitive dissonance. This is not an excuse. Shame on the people who hid the results and contributed directly or indirectly to an enormous amount of human suffering and chronic diseases. "The McGovern hearings which set the entire direction of nutritional thinking, and guidelines, took place in 1977. The MCE trial ran from 1968 to 1973. Had the data from this study been made available, the dietary guidelines in the US, the UK, and the rest of the world (In their current form, demonising saturated fat) simply could not have been written." It comes back to three things: Protect the endothelium (lining of blood vessels) from harm, reduce the risk of blood clots forming – especially over areas of endothelial damage, and reduce the size and tenacity (difficulty of being broken down) of the blood clots that develop. How to protect the endothelium? The number one agent that protects the endothelium is nitric oxide (NO). Thus, anything that stimulates NO synthesis will be protective against CVD. This brings us to sunshine and vitamin D. Sunlight on the skin directly stimulates NO synthesis, which has been shown to reduce blood pressure, improve arterial elasticity, and a whole host of other beneficial things for your cardiovascular system, not least a reduction in blood clot formation. Sunlight on the skin also creates vitamin D, which has a significant impact on NO synthesis in endothelial cells, alongside many other actions. It also prevents cancer, so you get a double benefit. "avoiding the sun is as bad for you as smoking. In my (E4E) opinion, ordering people to avoid the sun may be the single most dangerous and damaging piece of health prevention advice there has ever been." See the post for more details about why sun exposure is not dangerous.
  26. What Causes Heart Disease XXIV, 01/16/2017, A refresher on Vitamin C and Lp(a). Humans lost the ability to generate Vitamin C 60 million years ago. High levels of glucose prevent Vitamin C from entering cells in the body, especially immune cells. Scurvy from lack of Vitamin C has many symptoms, but focus on bleeding in this post. Vitamin C is an important piece of collagen synthesis. Collagen repairs damaged blood vessels. As blood vessels "crack," Lp(a) fixes the damage. Lp(a) is resistant to removal and eventual repair. Thrombolysis is the word for the ordered breakdown of clots. (‘lyse’ means to break down). But, Lp(a) is inert to the chemicals that break down clots. So if you have high levels of Lp(a), your clots will be resistant to breaking down. G. C. Willis did scurvy studies on guinea pigs (which also do not produce vitamin C). Withholding Vitamin C, formed plaques, feeding them Vitamin C reversed plaques. But the longer you wait, the more resistant the plaques become. Here's what we know: A high level of Lp(a) is associated with a higher risk of CVD, There is a probable causal mechanism linking Lp(a) to CVD death; Lp(a) is synthesized in animals that cannot make their own Vitamin C. A lack of vitamin C causes blood vessels to crack open – and potentially leads to atherosclerotic plaques development. Animal models have shown that a lack of vitamin C does lead to rapid atherosclerotic plaque development, and that replacement of vitamin C causes rapid regression of atherosclerosis, Some evidence from humans suggests that vitamin C supplementation causes regression of atherosclerotic plaques, Vitamin C supplementation does seem to lead to a reduction in Lp(a) levels, L-carnitine supplementation does lead to a reduction in Lp(a) levels, L-carnitine supplementation may reduce overall mortality. L-carnitine is a protein found in beef. There is little good research on therapeutic or maintenance levels of most vitamins, and there is no profit motive to do so at this point. An interesting note from the comments: "Relative Ascorbate deficiency is almost universal, and scurvy is very much a drastic, almost complete deficiency. The joke of RDA will certainly prevent this drastic end-stage disease, but not more insidious chronic consequences of weak collagen. Pauling recommended 6-18 G of vit c per day. Nothing heals without vitamin C. Including I would guess, microscopic vascular defects. Many long-term conditions are quite possibly a result of the weak collagen caused by non-catastrophic ascorbate deficiency."
  27. What Causes Heart Disease XXV, 02/13/2017, The cholesterol hypothesis of heart disease is blown away by one graph--heart disease vs. cholesterol level in Russia and Switzerland. Switzerland has a cholesterol level of 248 and a death rate of 35; Russia has lower cholesterol at 197 and a death rate of about 270--834% higher. The establishment calls it a paradox and makes something up, but the reality is cholesterol is simply not the problem. CVD has been falling in most advanced Western countries for decades--well before statins, hypertension medications, stents, etc. This is probably largely due to reductions in smoking. Emergency medical interventions have also improved significantly. Other factors include the clean air laws passed in past decades and the removal of lead from motor fuel, pipes, and paints. "Lead causes endothelial dysfunction by binding and inhibiting endothelial nitric oxide synthase and decreasing nitric oxide production." The TACT study (Trial to Assess Chelation Therapy) was hoped to disprove the idea that chelation took lead out of the system and improved health. But oops,"...we found that we had about a 40% reduction in total mortality, a 40% reduction in recurrent MI, and about a 50% reduction in mortality [in patients with diabetes],"
  28. What Causes Heart Disease XXVI, 02/15/2017, A mainstream cardiology professor, Salim Yusuf has a youtube presentation where he says, "1. Saturated fat does raise LDL, a bit, but has no effect on CVD – maybe slightly beneficial. Monounsaturated fats are slightly beneficial. Polyunsaturated fats are neutral, 2. Carbohydrate intake is most closely associated with CVD. 3. Fruit and vegetable intake has little or no impact on CVD – nor does fish intake [He wonders where the five portions of fruit and vegetable intake recommendations actually came from]. Vegetables, in particular, have no benefit. 4. Legumes – beans and suchlike – are beneficial. 5. The recommendations on salt intake are completely wrong and set far too low. For those who do not have high blood pressure, low salt intake increases mortality. On the other hand, high salt intake does no harm. 6. He recommends higher potassium intake. 7. He criticizes Ancel Keys and lauds Nina Teicholz [Author of The Big Fat Surprise]. Yay.
  29. What Causes Heart Disease XXVII, 03/06/2017, In which Malcolm makes the imaginary elevator pitch to Bill Gates. ‘Blood clots can form and stick to the inside of artery walls. They then get absorbed into the artery wall itself, where, normally, they are cleared away by specialised white blood cells. But if blood clots keep forming rapidly, at the same point, or the blood clots are bigger and more difficult to shift when they form, they cannot be cleared away quickly enough, and so end up stuck inside the artery wall. This leads to a build-up of blood clot residue, and remnants in the artery wall itself. This means that repeated episodes of clotting, over time, build into thickenings, and narrow the larger arteries, mainly in the heart and the neck, growing somewhat like tree rings. These areas of damage are usually called atherosclerotic plaques.      In time, the process of blood clotting, over a vulnerable area, leads to heart attacks and strokes as the final, fatal blood clot forms over an area of the artery that is already thickened and narrowed. In short, atherosclerotic plaques are the remnants of blood clots. Heart attacks and strokes are the end result of the same processes that caused plaques to form in the first place. Heart disease is a disease of abnormal blood clotting. It is as simple as that. The end." The blood clotting hypothesis has been proposed and worked many times and for decades by different people. Kendrick believes it is the only hypothesis that reasonably fits all known facts about CVD. "Sometimes the truth stares us in the face, but we just choose not to look." Gil Lewis. It appears that the money and, therefore, research have all been funneled into the cholesterol hypothesis--which is clearly and demonstrably flawed. Pfizer was pursuing the clotting branch in their research and had a promising drug in development called doxazosin. Then they bought Warner-Lambert which made Lipitor (a statin). "The focus became Lipitor and lipids, lipids, lipids. Lo it came to pass that Pfizer never mentioned blood clotting ever again, lest it interfere with the LDL story. Pity really, because mighty Pfizer got it right in 1992." "At some point, this, the blood clotting hypothesis, the correct hypothesis will win. Maybe that time will be now."
  30. What Causes Heart Disease XXVIII, 03/17/2017, Holy crap! This one blindsided me. He tells the story of a drug trial to treat angina by Pfizer. After the trials, the subjects refused to give back their extra medications. It was a PDE5i inhibitor. It turns out the drug had a surprising side-effect—it helped men maintain erections. Yes, this is about Viagra. It turns out that even besides the erectile dysfunction angle, it has other positive effects. For one, it helps prevent pulmonary edema at high altitudes. It also treats Reynaud's syndrome as well as reducing high blood pressure in the lungs. "How does it do all these things? The answer is that it increases Nitric Oxide (NO) synthesis in endothelial cells. When it does this in the penis, it stimulates erections. In the heart, it opens up coronary arteries. In the lungs, it dilates the blood vessels; in fingers and toes, it opens up arteries. So, all of the many different effects, are all due to exactly the same process – increased NO synthesis. Viagra also lowers blood pressure – as you would expect." Here are the statistics from one study: 4.7% reduction in overall mortality, 38% reduction in MI (relative risk reduction), 14.6% reduction in death after an MI. Compared to stents, Viagra is even more impressive—stents give a 2% absolute reduction in mortality, and Viagra gives about 15%. Men with heart failure were 36% less likely to die (relative risk) if they took a PCE5i inhibitor. It reduces congestive heart failure probably by increasing angiogenesis. l-arginine/l-citrulline, direct sunlight on the skin, potassium, meditation, and Vitamins D and C all have a positive impact on NO in endothelial cells.  Viagra could probably save or improve millions of lives, but... Once ED became the prescription focus, research stopped on the CVD side. Now that Viagra is off-patent, there seems little hope that that avenue will ever be pursued. e4e note: there is a daily Cialis available. I believe it is for the treatment of ED. Off-label use of prescriptions is frowned upon by the medical establishment.
  31. Cholesterol-lowering – proven or not?, 03/20/2017, PCSK9 trials Repatha. evolcumab trials. This drug was highly successful in lowering cholesterol, yet if anything, mortality was worse. The trial was stopped in the middle to protect patients. Another nail in the cholesterol-causes-CVD-coffin. Tom Naughton of FatHead fame did a post about PCSK9 trials too. "Overall, no significant change was observed in all‐cause mortality or cardiovascular mortality.
  32. What Causes Heart Disease XXIX, 04/01/2017, Alcohol and lifestyle: 1: Do not smoke cigarettes (to which I would now add  – or anything else). 2: Take exercise – that you enjoy. Don’t try to drive yourself into the ground. Walking outside is particularly good, especially on a sunny day. 3: If you don’t drink alcohol, start. If you do drink, drink regularly – don’t binge drink – and make sure that you enjoy what you drink. Drink with friends, drink sociably, and don’t drink to get drunk. 4: If you hate your job, get another one – don’t feel trapped. 5: Make a new friend, join a club, find an area of life that you enjoy. Praise other people and try to compliment other people more often. 6: Look forward to something enjoyable every day, every month, and longer term. His take on alcohol "... alcohol – as a chemical – is not protective against CVD. It is protective because, in the various forms that humans drink it, it is relaxing, reduces stress/strain, and when it is drunk with friends, it is part of a lifestyle that is protective. ...In short, I do not believe drinking alcohol is a true ‘drug’ effect. The lifestyle around drinking has a major part to play. However, I may be wrong. Researchers have studied the effects of different types of drinks on factors that I consider key for CVD. Endothelial function, and blood clotting factors. It seems that red wine and beer are the most beneficial." There are also studies that show that high levels of alcohol consumption can have a negative impact on clotting stickiness. There seems to be a therapeutic window beyond which alcohol can be harmful. Non-drinkers and very heavy drinkers have similar outcomes. Where does heavy drinking start? Hm. The research did not test for this. They called heavy drinking anything more than two glasses a day. So they would have lumped those who drink 2.1 glasses of wine each day with those who drink 2.1 bottles of gin. Safe to say though, that having two drinks or so per day is likely to be beneficial.  By the way, red wine and beer are the alcohols in the studies discussed.
  33. What Causes Heart Disease XXIXb, 04/16/2017, Alcohol--Kendrick defends his claims about alcohol. One important objection is that the studies are observational/epidemiological, not randomized and placebo-controlled. That's true. It's also true that many things we know and believe have never had RCTs. The observational studies are the best that we have. But it's not definitive. Some readers also expressed concern that if Kendrick encourages people to drink in moderation, some will get carried away and become alcoholics, thereby causing them more harm than not drinking. While yes, this is a possibility, he believes that more people would benefit than would be harmed by the recommendation, so the total benefit favors moderate drinking even though, there will be some people who get worse. Cheers!
  34. What Causes Heart Disease XXX, 06/06/2017, On the hypothesis that inflammation causes CVD. A follow-on to XIII. According to Kendrick, inflammation is generally a healing result of damage, not a cause of damage. Reducing inflammation inhibits damage repair, so the I in RICE may actually slow down healing. In some cases, e.g. autoimmune diseases, inflammation is the body malfunctioning with inflammation actually causing damage, so in those cases, powerful anti-inflammatories are justified. But corticosteroids, a very potent anti-inflammatory, do not reduce CVD risk. Hm. In fact, many agents that reduce inflammation and suppress the immune system increase CVD risk. Even non-aspirin NSAIDs are beefing up their warnings.
  35. What causes heart disease – part thirty one (XXXI), 06/21/2017, What is the final action in CVD? "The final event in most heart attacks, and strokes, is the development of a large, and often fatal, blood clot. If this happens in an artery in the heart, a coronary artery, it cuts off blood supply to an area of the heart muscle and can lead to myocardial infarction (MI) [myocardium = heart muscle, infarction = death of tissue due to lack of oxygen]. There is a related, but different mechanism of action, in most, strokes. In this case, a blood clot that has formed in an artery in the neck (carotid artery), breaks off and travels to the brain where it gets stuck, blocking an artery. This leads to a cerebral infarction." This is a simplified view. There are studies and evidence from people who develop plaque extremely rapidly that the clotting function is the underlying cause.  "There is only one process. Atherosclerotic plaque are simply blood clots, in various stages of growth and/or repair. Plaque growth represents the formation of a new blood clot, at the same point, which is not cleared away properly. The final ‘thrombotic’ event is just a big enough clot forming to do real damage." There is ample evidence that plaques are formed by multiple episodes of clot and repair. "Was it possible, I asked myself, that blood clotting was not just responsible for the final clot, but also for the entire process of atherosclerosis? I believe that the evidence is out there, and clearly supportive, if you choose to look at it this way round. I suppose you could say that I do not believe in atherothrombosis. I believe in thromboatherosis (you’re right, I just made that word up). In thromboatherosis, plaques start and grow, through repeated thrombus formation at the same spot in an artery. In the end, a clot gets big enough to cause a stroke or heart attack. Sometimes the clot can be big enough to kill, without any underlying plaque, but normally it will form over an already existing plaque – where plaque rupture can be the trigger. In short, there is only one process in CVD. It is the development of atherosclerotic plaques through repeated thrombus formation, followed by the final thrombus formation. As you can see, this is actually very close to mainstream thinking. The only difference is that you have to flip your thinking through one hundred and eighty degrees, to see it upside down." e4e comment: IMHO, this hypothesis is really clean. It is predicated on only one (albeit complicated) process. There is lots of evidence for it, and alternate hypotheses, e.g. cholesterol theory, have lots of contradictory evidence and are clouded by commercial interests and the usual suspects of confirmation bias and cognitive dissonance. I am confident that it is not perfect in every way; there are too many variables. When looked at from a human evolutionary perspective, it just. makes. sense.
  36. What Causes Heart Disease XXXII, 07/12/2017,  for years Kendrick believed that stress was a main driver of CVD, but he had not identified the mechanism by which it occurs. In his words, "Negative psychological and/or physical stress → HPA-axis dysfunction → abnormal cortisol secretion → metabolic syndrome/type II diabetes → atherosclerosis → increased risk of CVD. Now, I think that this model is still perfectly usable, and it explains a lot. However, although I drew a simple arrow from metabolic syndrome/type II diabetes → atherosclerosis, this is the bit that Paul Rosch was talking about. What is actually happening here? It is all very well to state that something causes something else, but you still need to explain how."
  37. What Causes Heart Disease XXXIII, 07/29/2017, Viagra again. The idea that CVD begins with damage to the endothelium completely negates the cholesterol hypothesis of CVD. He follows with a letter from the mainstream that claims that "cholesterol deniers" are killing people. Kendrick shows evidence that debunks the cholesterol hypothesis and reiterates some of his arguments supporting the atherothrombosis hypothesis. But he goes on to say that statins do have some positive effects—just not because of the cholesterol-lowering. There is a study of atorvastatin that showed positive effects on nitric oxide and endothelial protection. He concludes with, "If you decide to look more closely at the process of CVD, and more closely at the actions of statins, a different picture emerges. One which fully supports endothelial damage as the first step in plaque formation. Because statins do many more things than LDL lowering. It could be said that statins are simply the poor man’s Viagra (other PDE5i inhibitors are available)."
  38. What causes heart disease part XXXIV (part thirty-four), 08/09/2017, Looking for contradictions. Refuting hypotheses in the health field is very difficult. There are always ad hoc hypotheses and variables of variables. Just in cholesterol, if you factor in all the types of cholesterol, there could be 25 factorial (25!) combinations to test. Even setting "Safe" levels of any single variable is difficult and mostly illogical. Effectively with the paradigm of the lower the better, everyone has high cholesterol. "When confronted with logic like this, the cholesterol hypothesis is perfectly protected from attack. It is a non-refutable hypothesis. As Karl Popper said, 'if you cannot construct your hypothesis in such a way that it can be refuted, it is not science,' a.k.a. nonsense." Which is why Kendrick looked for an entirely different pathway.
  39. What causes heart disease part XXXV (part thirty-five), 08/19/2017, The beginning of the end—bringing it all together.  Point 1. Lots of things seem to cause CVD, but there are so many that it is clear that there must be some underlying factor that ties them all together. Point 2. The evidence base is flawed and extremely complicated. It's impossible to control for all the possible and known factors, but you can't just throw out research that contradicts your prejudices or dismiss data as a paradox. Nor can you ignore the effects of conflict of and vested interest on studies. And by the way, peer review doesn't fix it. Studies are flawed, and judging them is very difficult. One result is that many of us let our preconceived notions and biases color our interpretations. The first step to fixing those biases is to know and acknowledge them. Here's what Kendrick says about his biases, "I am almost entirely anti-statin. I am not a great believer in blood pressure lowering – at least not at current levels. I do not believe in the cholesterol hypothesis, and I think that the anti-saturated fat dogma is completely bonkers and has no evidence to support it – at all. I believe that salt is good for and, in most people, protects against CVD. I believe that a high carbohydrate, low-fat diet is utterly bonkers—especially in those with diabetes. And suchlike. In short, I believe that almost everything we are told is good for you, is bad for you, and vice-versa. With the exception of smoking (bad) and exercise (good)."
  40. What causes heart disease part XXXVI (part thirty-six), 09/05/2017, Continuing to sum up. This is a really important post. Remember that atherosclerotic plaques develop only in large arteries, and never develop in veins. Why is that though? There are many possibilities, but most can be rejected easily. As "...plaques develop, you find that they most often occur at [points of] maximum biomechanical stress." A research paper observed this, but then attributed it to a leaky endothelium permitting LDL to pass through into the arterial wall. But wait, why in the world would an intact endothelium do this? Bottom line is that it doesn't unless the endothelium is damaged, which brings us back to square 1; CVD does not start with cholesterol, but rather with a damaged endothelium. There are people who believe that cholesterol can force its way through undamaged endothelium by various mechanisms. Kendrick proposes "a thought experiment if you like. Why would endothelial cells allow LDL to pass through them, to then allow LDL to be oxidised in the arterial wall behind? This process serves no physiological purpose, other than to kill you from cardiovascular disease! The idea that endothelial cells simply cannot prevent this from happening is, frankly, bonkers. ...the idea that an endothelial cell cannot prevent a relatively massive LDL molecule from entering the side facing the bloodstream, then passing straight through, then ejecting itself out the other side, is complete nonsense." Quick summary: "1: It is impossible for LDL to pass straight through a living endothelial cell. 2: Endothelial cells are tightly bound together, and will not allow anything to pass between them." He talks about fenestrations in capillaries which do allow nutrients to pass through the blood vessels, and how the brain manufactures its own cholesterol for brain cells, (it doesn't get it from the blood) as further evidence of difficulty in penetrating the endothelium. Finally, he discusses the vasa vasorum, which are vessels that feed blood and other nutrients into the large veins and arteries. There is no need for the endothelium to leak; the vessels get everything they need from the vasa vasorum. At this point, you "...realise that the cholesterol hypothesis, whilst it sounds superficially reasonable, requires mechanisms of action that just do not exist." 
  41. What causes heart disease part XXXVII (Part thirty-seven), 09/16/2017, Begin with the end in mind. What is the end-member of CVD? "The final event in cardiovascular disease is, in most cases, pretty much accepted... The formation of a blood clot." There's a ton of documentation that anything that reduces blood clotting also reduces CVD risk, while anything that increases clotting increases CVD risk. But the official party line was that the development of the blockage in the first case was not related to the final clotting event. This just doesn't seem right. Why in the world do you need two separate processes for this when one will suffice? The clotting system is extremely important and incredibly complex. Because of its importance, it is always ready to go from zero to 100 at a moment's notice. But it also has to be able to stop before it gets carried away. His analogy is like having one foot mashing the accelerator to the floor while the other is standing on the brake. The most powerful clotting mechanism is the "tissue factor," which sits under the endothelium. Exposure of blood to TF sets up a clot instantaneously. This makes sense--bleeding kills if unchecked. The only way a clot forms in arteries is damage to the endothelium. Once it forms, enzymes in the blood moderate the growth, and begin to break the clot down. But it's not like a scab on your skin. Obviously, if a scab broke off in an artery it would cause damage downstream. Rather, once the clot forms, moderates, and begins to clear, your body grows a new layer of endothelium over the old clot.  The new cells are created by endothelial progenitor cells, which actually have a function in addition to the endothelium. They can also convert themselves into macrophages, which clean away tiny pieces of the old "scab" and carry them to the lymph system for elimination. He calls this process healing, but others call it inflammation. Believing that inflammation causes CVD is like believing that firemen cause fires. Another note of importance is that one of the most stubborn constituents of the clot is a factor called apolipoprotein(a) or Lp(a). It is almost identical to LDL particles but with a single molecule difference that makes all the difference and makes it resistant to breaking down. He contemplates that the Lp(a) content may be a part of the belief that cholesterol is a problem, when in fact, it is a very similar molecule. 
  42. What causes heart disease part XXXVIII (part thirty-eight), 09/24/2017, What is this biomechanical stress? However you define it, it is clear that the plaques develop at spots of transition or change within the arteries, and at those spots, the initial damage happens to the endothelium. Here are some factors that are known to damage the endothelium: Smoking, air pollution, diabetes, cocaine use, dehydration, infections/sepsis, systemic lupus erythematosus (SLE), lead, stress hormones, avastin, omeprazole, Cushing’s disease, Kawasaki’s disease. They also are all identified causes of CVD. A young woman with lupus has an increased CVD risk of 5000%. Sickle cell anemia is even worse. Not only does it increase clotting, but by itself damages the endothelium. One of the challenges with this series is that in order to demonstrate how these completely disparate causes are related, you have to understand and identify their role within the underlying process. "There is no point in saying that, yes, they all cause heart disease, and that’s that; just add them to the list. There is a requirement to fit them within a single process, and it must make sense. It also has to be supported by the facts—as far as that is possible. Equally, there is no point in saying CVD is ‘multifactorial’, which is the normal defence of the mainstream when pressed on why many people, with no risk factors for CVD, still get CVD. The word “multifactorial” explains nothing; it is just an escape route for those pressed to explain the many ‘paradoxes’ or refutations that keep on appearing." Where are we now then, "...demonstrate[d] that the trigger factor for CVD is damage to the endothelium. If you don’t damage the endothelium nothing else happens. The damage happens at well-recognised places where the biomechanical stress is at its greatest. Which means that, with no biomechanical stress, there can be no atherosclerotic plaques. However, it takes more than just biomechanical stress. You also have to have at least one extra factor present to trigger endothelial dysfunction. " See you in the next post. Same bat-time, same bat-channel.
  43. What causes heart disease part XXXIX (thirty nine), 10/09/2017, There are four types of myocardial infarction: A myocardial infarction with no obstructive arterial disease, A myocardial infarction caused by stress, with no obstructive arterial disease, myocardial infarction that happens weeks after the thrombus forms, the ‘classic’ myocardial infarction with thrombus formation followed rapidly by infarction.  This "...leads to the inevitable conclusion that something else must be going on. Perhaps it is true that the infarction, due to extreme stress and build-up of lactic acid, does come first. Then, as a consequence, the clot forms in the artery." But now we have to ..."dig even deeper, to find the man that isn’t there. Banksy, a man who paints on walls, is never seen, but we know he was there because, otherwise, you can’t explain the painting."
  44. What causes heart disease part XL (part forty), 10/27/2017, On the importance of reducing stress in your life and having close family and community ties. France and Scotland have similar diets (Scotland is slightly lower in saturated fat and vegetables) and similar BMI and blood pressure The French smoke more and exercise less. Rates of diabetes and total cholesterol levels are identical. If you enter all the data into a CVD Risk calculator they come out very similar in terms of risk. Yet the reality is that Scots have five times the rate of CVD as the French. This is typically called the French paradox. However, there is no such thing as a paradox, just bad hypotheses. Ad hoc theories say the French drink more wine or eat more garlic. This is pure horse pucky. Kendrick says the French paradox should actually be called the "French refutation of the diet-heart hypothesis and the LDL hypothesis, and all other hypotheses about cardiovascular disease you can think of." One difference is not in what they eat, but rather how they eat. Scots tend to treat mealtimes as refueling stops on the way to the next thing, whereas the French "Time is taken, food is appreciated, families tend to eat together..." So Kendrick studied the effect of stress on metabolism. Cushing's disease is a disorder where stress hormones are pushed high by the adrenal glands. People with Cushing's are in perpetual fight or flight state. It also increases CVD risk by 600%. Time after time, we see high-stress events, like social and political upheaval followed by increases in CVD. It seems that reduction of stress, and close family and community links may be the silver bullet.
  45. What causes CVD part XL1 (Part forty-one), 11/12/2017, Discussion of the ORBITA study. Stents don't work. BMJ article with a double-blind, randomized, controlled trial comparing an operation to emplace stents with an operation that does nothing. Wow! Here are the results. "‘Percutaneous coronary intervention (PCI) is not significantly better than a placebo procedure in improving exercise capacity or symptoms even in patients with severe coronary stenosis, research has found." To be clear, this was about stents in a non-acute situation. Years ago, the standard of care was to graft a vein where there was a blockage in the coronary artery. As with stents, before the procedure was common and became the standard of care, there was virtually no research on efficacy. "Common sense " dictates that open artery = good, closing artery = bad. However, there was no actual research demonstrating that their preferred solution did much beyond lining the pockets of the medical establishment. Doctors used phrases like " “You have a time bomb in your chest” and its variant, “You are a walking time bomb.” Or, “...This narrowed coronary is a widow maker.” [E4E comment: I questioned the use of a specific blood pressure medication, and the cardiologist said, "High blood pressure is the silent killer." What a wanker.] And if patients wish to delay an intervention, a series of fear-mongering expressions hasten their resolve to proceed: “We must not lose any time by playing Hamlet.” Or, “You are living on borrowed time.” Or, “You are in luck—a slot is available on the operating schedule.” Maiming words can infantilize patients, so they regard doctors as parental figures to guide them to some safe harbour." Dr. Kendrick ends the post with this, "Those who have read my endless blog on the causes of on CVD will know I have long been highly sceptical of stenting as the answer to anything very much. Other than the removal of large sums of money from person A, to hospital B, and interventional cardiologist C. Why does it not work? How can it possibly not work? Because the heart is not simply a pump, arteries are not simply pipes, and humans are not inanimate objects whereby our function, or lack thereof, is purely dependant on some form of medical or surgical intervention. Thus endeth the lesson on stenting."
  46. What Causes Heart Disease XLII, 12/09/2017, More on stress/strain. Stress and other mental health issues drive numbers like a 1300% increase in risk of CVD, whereas factors like diet and cholesterol change risk by 10%. "Chronic stress → dysfunction of the hypothalamic pituitary adrenal axis (HPA-axis) → sympathetic overdrive + raised stress hormones → metabolic syndrome (raised BP, raised blood sugar, raised clotting factors, raised cortisol, raised all sorts of things) → endothelial damage + increased blood clotting → plaque formation and death from acute clot formation." Where should we be focusing?"And if you want to close this loop further, stress also increases LDL levels, in some studies by over 60%. So, when you see raised LDL, in association with increased CVD, it is not the LDL causing the CVD. It is stress, causing both."
  47. What causes heart disease part 43, 12/29/2017, What is stress? You have to separate stress from a person's body response to stress (strain). Some people have little response to stressful events, while others can have a massive response to seemingly minor events. "The hypothesis here is reasonably straightforward. It is as follows. Long-term negative stressors (or one overwhelming acute event) can create damage to the neurohormonal system that coordinates the physiological reaction to strain. This, in turn, has negative physiological effects that can lead to serious disease e.g. CVD, or diabetes, or both." When you go into fight or flight mode, "The blood pressure goes up, sweat glands are activated, blood clotting factors are released..." Measurement of stress hormones is tricky, with clear diurnal patterns putting noise into the data. Per Bjorntorp, a Swedish researcher demonstrated a strong linkage between stress hormones and metabolic syndrome (which in turn links to CVD). It turns out Cushing's disease in people pumps lots of stress hormones into people, and those people have much higher rates of Metabolic syndrome and CVD. We do not give people cortisol, but corticosteroids have many of the same effects on hormones. Guess what. If you take corticosteroids long-term, "The risk of CVD is increased by, up to, 600%."
  48. What Causes Heart Disease part 44, 01/12/2018, How to remain healthier and live longer, Actions that reduce CVD risk. Taking a statin for 30 years gives you a statistical extra 24 days of life—best case. Regular exercise gives you an extra four and a half years. Which makes exercise at least fifty-four times more effective than statins. The only CV medicines that make a major difference are anti-coagulants (blood thinners) such as warfarin, rivaroxaban, and apixaban. So here is the prescription: Exercise, Stop smoking, get sunshine and enjoy it. "These three things alone can add around sixteen years to your healthy lifespan."
  49. What Causes Heart Disease part forty-five, 1/27/2018, There are periodic studies that show that taking vitamins is bad. There is little economic benefit in studying the effects of vitamins. They're all off-patent. Optimal doses are also unclear; typically, we know the minimum dose to prevent disease. Nobody died in 2010 from taking vitamins; OTOH, 328,000 people died from prescribed medicines. Supplements to consider include Vitamin K2 5µg, Thiamine 7mg, Folic acid 7µg, Potassium 50mg, Magnesium 50mg, L-arginine 600mg, L-carnitine  50mg, L-citrulline 7mg, Co-enzyme Q10 3mg, then add Vitamin D and Vitamin C and multiply everything by 4x per day.
  50. What Causes Heart Disease part forty-five B - an addendum, 1/29/2018, Oops. A new paper just came out about Magnesium. It is much more important than he believed. Magnesium deficiency is quite common and difficult to test for. -zole drugs are a culprit in reducing magnesium.
  51. What causes heart disease part 46, 2/14/20018, The mind and poor social interactions. Negative stressors drive CVD significantly. One paper found that people with significant money worries are 13 times more likely to suffer a heart attack. Various mental illnesses reduce life expectancy by 10-20 years."When your mind goes wrong, your body follows." Strong social connections add 10-15 years to life expectancy.
  52. What causes heart disease part forty-seven, 3/13/2018, Raised cholesterol is not a factor for stroke. Statins reduce the risk of both heart attacks and stroke. Therefore, the cholesterol hypothesis is not correct. "...the beneficial effect of statins on the risk of stroke, flatly contradicts the cholesterol hypothesis." 
  53. What causes heart disease part forty-eight (48), 3/22/2018, Lead causes endothelial damage! Chelation therapy, which he had written off as "woo-woo medicine," actually works. Thalidomide and Avastin both hamper the generation of endothelial cells/angiogenesis, both are used to treat cancer, and Avastin leads to a higher incidence of CVD. There is no evidence that Thalidomide does. There is a paper that studies this, but he hasn't figured it out yet.
  54. Statins and Amyotrophic Lateral Sclerosis, 4/9/2018, Amyotrophic Lateral Sclerosis, aka Lou Gehrig's disease, affects 2-3 people per 100,000 in the US and Europe. It is a disease of the nervous system, in which, although you remain alert and able to think clearly, the ability to control your muscles deteriorates until you die of suffocation. A recent paper in the journal Drug Safety indicates that statins can greatly increase the risk of developing ALS. The researchers established an association, but the association was so large that it is believed to represent a causal relationship. The "safest" statin reported was linked to an 800% increase in ALS (so that 2-3 number would increase to about 20). The worst statin reported was Lovastatin, with an increase of over 10,000% (the 2-3 number goes to 200-300/100,000). In terms of risk to an individual, the odds are still very greatly in your favor that you will not develop ALS, even with statin use. For Lovastatin, the ratio fell from about 1 person per 50,000 to 1 in 500. However, given what Kendrick believes to be the relatively low efficacy of statins in reducing total mortality, is this a risk you want to take? This new information emphasizes the absolute criticality of cholesterol to the human body. There are signals in data that ALS is increasing in a number of countries, but the data is not reliable, as few countries accurately track ALS in mortality statistics.
  55. Very high LDL and no cardiovascular disease – at all, 5/12/2018, We seem to be past the main series on what causes heart disease, but Dr. Kendrick continues to put out interesting analysis of studies. This one is about a case study of a guy who has familial hypercholesterolemia--a genetic condition that drives very high blood cholesterol. He starts with a discussion of black swans. Essentially, if you believe that high cholesterol is the key driver of heart disease, the presence of someone with very high cholesterol and no heart disease should make you think about your hypothesis. Here's what he says: "Unfortunately, but predictably, the authors of the paper have not questioned the LDL approach. Instead, they fully accept that LDL does cause CVD. So, this man must represent ‘a paradox’. They have phrased it thus:"‘Further efforts are underway to interrogate why our patient has escaped the damaging consequences of familial hypercholesterolemia and could inform future efforts in drug discovery and therapy development.’ "To rephrase their statement. We know that high LDL causes CVD. This man has extremely high LDL, with no CVD, so something must be protecting him. I have an alternative, and much simpler explanation: LDL does not cause CVD. My explanation has the advantage that it fits the facts of this case perfectly, with no need to start looking for any alternative explanation."
  56. Eggs are Good for You - who knew!?, 5/28/2018, A little off the CHD track, but relevant to cholesterol. A large study of 500,000 people with this conclusion. ‘Among Chinese adults, a moderate level of egg consumption (egg consumption (up to less than 1 egg/day) was significantly associated with a lower risk of CVD, largely independent of other risk factors.
  57. What causes heart disease? – part 49 (nearly there), 6/15/2018, Flashback to university when a lecturer said that ‘cholesterol cannot get past the endothelium.’ She also said (heretically) ‘In this talk, I have concentrated mainly on the factors that may be involved in the progression of the early, low-lipid gelatinous lesion into the typical fibrous plaque with lipid-rich centre that is generally accepted as the significant lesion in occlusive vascular disease and have tried to emphasize the key role that may be played by fibrin.’ He talks about how heart attacks can happen whether or not there is a clot and how sometimes, even with a clot, the attack doesn't happen. Finally, he recaps his main hypothesis—that plaques occur when the endothelial damage process occurs faster than the healing process, lists 14 causes of CHD that have nothing to do with cholesterol, then tells about a case of sickle cell anemia in a child.
  58. Why saturated fat cannot raise cholesterol levels (LDL levels), 7/3/2018, The dietary goals of the United States (remember the food pyramid were premature and demonized dietary saturated fat (SFA) and cholesterol (eggs). George McGovern famously stated, "“Senators don’t have the luxury that the research scientist does of waiting until every last shred of evidence is in." This is despite the fact, that even Ancel Keys had stated unequivocally that dietary cholesterol had no effect on cholesterol in your body. The cholesterol guidance was finally corrected in 2015, almost 50 years later. And let's be crystal clear. The original guidelines were not based on the best science of the day about cholesterol. So they pivoted to saturated fat as the cause of increased cholesterol. Malcolm has something to say about that. It turns out that dietary fat goes from your gut, into the bloodstream, and then directly into your cells. It is not converted into cholesterol. Cholesterol is manufactured in your liver and sent out into the body where it is needed via LDLs (technically VLDLs). As the LDLs lose the cholesterol molecules, they get recycled by the liver. So what increases VLDL production (and therefore LDLs)? Carbohydrates!!! "If you eat more carbohydrates than your body needs, or can store, the liver converts the excess (primarily fructose and glucose) into fat in the liver. This process is called de novo lipogenesis (DNL). The fats that are synthesized are saturated fats, and only saturated fats. Once synthesized, they are then packed into VLDLs and sent out of the liver." There is no mechanism to convert saturated fat into cholesterol. There is a confounder. In studies, they have shown that replacing saturated fat with polyunsaturated fat (PUFA) from plants lowers LDLs. He believes it's due to the presence of stanols in the PUFAs. Stanols are essentially plant cholesterol. The researchers committed a cardinal sin. They changed two variables (dropped (SFA and increased PUFA). They then attributed the result to the SFA. It all gets somewhat complicated, but there is little or no reason to believe that SFA increases cardiovascular risk. There is a lot packed into this post. Read it.
  59. What causes heart disease - Part fifty, 7/23/2018, Malcolm goes through the criteria that help us understand causation from analytical and epidemiological studies. The postulates for lab work are (Robert Koch, 1882): The microorganism must be found in abundance in all organisms suffering from the disease but should not be found in healthy organisms, The microorganism must be isolated from a diseased organism and grown in pure culture, The cultured microorganism should cause disease when introduced into a healthy organism, The microorganism must be re-isolated from the inoculated, diseased experimental host and identified as being identical to the original specific causative agent. As well as Bradford Hill's Cannons [sic] of Causation (1965). from Wikipedia. Strength (effect size): A small association does not mean that there is not a causal effect, though the larger the association, the more likely that it is causal. Consistency (reproducibility): Consistent findings observed by different persons in different places with different samples strengthens the likelihood of an effect. Specificity: Causation is likely if there is a very specific population at a specific site and disease with no other likely explanation. The more specific an association between a factor and an effect is, the bigger the probability of a causal relationship. Temporality: The effect has to occur after the cause (and if there is an expected delay between the cause and expected effect, then the effect must occur after that delay). Biological gradient: Greater exposure should generally lead to greater incidence of the effect. However, in some cases, the mere presence of the factor can trigger the effect. In other cases, an inverse proportion is observed: greater exposure leads to lower incidence. Plausibility: A plausible mechanism between cause and effect is helpful (but Hill noted that knowledge of the mechanism is limited by current knowledge). Coherence: Coherence between epidemiological and laboratory findings increases the likelihood of an effect. However, Hill noted that "... lack of such [laboratory] evidence cannot nullify the epidemiological effect on associations". Experiment: "Occasionally, it is possible to appeal to experimental evidence". Analogy: The effect of similar factors may be considered. Nothing is black or white, but very few of the criteria above apply to the standard factors normally cited for CHD. The "flat paradigm" says that disease can be multi-factorial, but this is probably too granular. Rather, look at the underlying process involved. CHD is not from smoking in one person, lupus in another, and sickle cell in a third. All of those factors trigger a specific underlying process.
  60. What causes heart disease part 51 – ‘Athero-thrombosis’, 8/6/2018 - Recap: The mainstream view is that cardiovascular disease is caused by two completely different and unrelated processes. The first process is the development of plaque, where cholesterol pokes its nose under your endothelium; the second is development of a blood clot on top of that plaque, perhaps from something inside the plaque, or like a boil bursting or something like that. Malcolm HATES this view. It creates a lot of issues and complications in looking for causes and cures of heart disease. "For one thing, I do not like having to invoke two completely essentially unrelated processes to explain a single disease. Mainly though, even if it wasn’t deliberately designed to protect the ‘LDL-hypothesis,’ that is exactly what it does." Most atherosclerotic plaques contain cholesterol crystals. But those crystals can only come from red blood cells, not from LDL. So "Repeated blood clotting occurs first, followed by intra-plaque rupture." This is the opposite of the mainstream view, where the blood clot is just some end member state. Thus heart disease should really be described as thrombo-atherosis, not athero-thrombosis. "Blood clotting is not simply the final event in the CVD. It is the only event, and it is how atherosclerosis starts, grows and eventually kills you. Or, to put it another way, there are not two processes in cardiovascular disease, there is only one."
  61. What causes heart disease part 52, 8/16/2018 - The beginning of atherosclerotic plaque development. The idea that cholesterol simply "leaks" past the endothelium has never made any sense. A partial list of issues: 1. If it is leaking due to a pressure gradient, why is it not seen in all arteries, but rather only in some places? 2. Why does LDL never leak into vein walls? 3. Larger arteries have their own blood supply; why don't those vessels have the same problems as the arteries themselves? 4. Endothelium is seen everywhere to be impermeable to cholesterol as exemplified by the blood-brain barrier. The tight junctions in the endothelium prevents molecules and ions from penetrating. Cholesterol doesn't stand a chance. 5. It is possible to get past the endothelial layer if the endothelium allows it through transcytosis. "The idea that an endothelial cell would be programmed to absorb LDL from the bloodstream, then actively transport it through itself, then deposit it in the artery wall behind – for no reason whatsoever – defies all laws of biology and physiology..." He could go on but stops here. It's sufficient. The counter-argument has always been, "well the plaques contain cholesterol, so they must have leaked through the endothelium." To which Malcolm says, "...yes, after the endothelium was damaged by other factors." One argument against the clotting hypothesis is that the early stage of atherosclerosis, i.e. the fatty streaks are not related to clotting. He presents evidence that the fatty streaks are a completely different phenomenon not related to CVD. Fatty streaks do not turn into plaques. "...fatty streaks exist, but these ‘lesions’ are not the things that become atherosclerotic plaques. Plaques form in a completely different way." But, until the mid-90s, nobody knew about the existence of the epithelial progenitor cells, which "scab" over damaged endothelium, encrusting whatever is in there. This gave the LDL hypothesis time to take root and become the leading paradigm. "They couldn’t explain how massive molecules that are normally found in the bloodstream, could get inside the artery wall. So, they were defeated by the facile, impossible, ridiculous, LDL hypothesis. A great pity, because the encrustation theory explains what the LDL hypothesis cannot." Even statins, when they work, "...they increase nitric oxide synthesis in endothelial cells, and nitric oxide protects the endothelium, stimulates the growth of endothelial progenitor cells, and [NO] is also the most powerful anticoagulant agent known to nature."
  62. What causes heart disease part 53 – diabetes, 8/21/2018 - Diabetes increases CVD risk 3-500%. This does not make any real sense at all in the cholesterol theory. So how does high blood sugar cause endothelial damage? We go to another level of complexity now. Lining the endothelium is a layer of molecules called the glycocalyx. The glycocalyx is composed of hairlike strands of protein and sugars bound together (it's about 1 micrometer thick, so very thin). You know that slimy feel that fish have? That's their glycocalyx. Of course, there's a paper, ‘Loss of Endothelial Glycocalyx during acute hyperglycemia coincides with endothelial dysfunction and coagulation activation in vivo.’ The function of the glycocalyx: It protects the underlying endothelium from damage, Maintains the endothelial barrier function, Acts as a mechanical sensor for stress/shear stress, Mediates nitric oxide (NO) release, Anticoagulant (stops blood clotting) – many anticoagulant factors live here, including NO, Prevents adhesion of white blood cells and platelets. So this is what diabetes does. Still holding together.
  63. What causes heart disease part 54, 8/31/2018 - Health research is hard because of the "First do no harm" dictum. So the focus has always been to test interventions that will help make people better, not prove that something causes harm. This is a really good thing, although inconvenient in terms of demonstrating causality. That's part of the reason we rely on epidemiological studies to help us. Bradford Hill laid out the nine criteria to help determine the information that can be extracted from those studies and their validity. (See item 59 above for more detail). Sometimes we have a natural experiment that can be used to extract meaning. The most familiar example is the impact of smoking on people. There are also examples of drugs thought to be beneficial actually causing unintended harm. Thalidomide is a common example. There's another one quite relevant to this topic though—proton pump inhibitors (PPIs). These are drugs like omeprazole and other "-zole" medications created to help prevent heartburn. It turns out that PPIs inhibit NO synthesis. If you believe Kendrick's hypothesis of heart disease, you would expect therefore to see heart disease go up with the usage of PPIs. And it turns out that PPIs double heart disease risk. (See number 23 above). There are other drugs that have far worse impacts. Avastin, the generic name is Bevacizumab is a case in point.  It is a vascular endothelial growth factor inhibitor (VEGF-inhibitors). Its impact is in preventing or inhibiting repair of blood vessels as they try to build a new endothelial layer, as well as slowing the healing by inhibiting the macrophages that heal the damage site. Endothelial progenitor cells (EPCs) were once thought to be useful only in the development of the fetus, but more recently have been found to have a role in healing arteries as well. Arterial adverse events 2.40, Cardiac ischemia (heart attack) 5.16, Cerebral ischemia (stroke) 12.39, Venous adverse events 1.37, Bleeding 2.96, Arterial hypertension 4.81. So the 5.16 on heart attacks means you have a 5.16 times increased probability of a heart attack. A 3% probability goes to 15%+. Avastin easily satisfies all of the Bradford Hill criteria. But here's the thing—Avastin can increase CVD, only if Kenrick's hypothesis of heart disease is correct. It has no impact on LDL or any other cholesterol. So Avastin becomes the black swan in this. "The blackest of black swans. An agent, that is perfectly designed to create endothelial mayhem, causes CVD, with no explanation available within the LDL/cholesterol hypothesis."
  64. What causes heart disease, part 55 - albumin, 9/17/2018 - Maybe you have seen albumin listed on your blood tests and wondered what that was about. You know those pictures of starving children with their bellies distended? That is one of the impacts of having low serum albumin. It also happens to alcoholics because as liver damage increases, they are unable to produce sufficient albumin. There's also a link between albumin and CVD. Albumin is a protein that circulates in the blood and, among other things, helps maintain the glycocalyx. Deficiencies in albumin are a causal factor in CVD. ’This study unequivocally confirms the important association between SA (serum albumin) and individuals with chronic stable CAD’. There may not be too much you can do to raise your serum albumin, but eating sufficient protein is a start." At this point, however, the main point that I want to make here – again – is that, once you start to understand CVD as a process that is triggered by endothelial damage, you can start to look at the research on CVD in a completely different light. You can make associations where, using the LDL hypothesis, none exist. It also makes sense."
  65. What causes heart disease part 56 – a new paper, 9/23/2018 - The paper is called ‘Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia.’ You can see it here. It will be free access for a very limited time, so go fast. I can see only the abstract, not sure if I'm doing something wrong. Anyway, the summary is that people with Familial hypercholesterolemia live as long as others on average, LDL-C in FH people with and without heart disease is the same, and there is questionable benefit from cholesterol-lowering drugs (statins). Dr. Kendrick and Uffe Ravsnikov are both authors, as well as Michel de Logeril and David M. Diamond.
  66. What causes heart disease – part 57, 10/11/2018 - Blood pressure as a cause of CVD is complicated. The average is not the same as "normal." Mortality calculators let you take the systolic down to 90, with CVD risk decreasing at every step. However, below 90 you have hypotension, so exactly 90 is the best level. Lol. CVD risk from blood pressure rises, but only very slowly until a systolic of 160--then it increases faster. It is clear that blood pressure is a cause of arterial damage. Blood vessels in normally low-pressure areas like the lungs can develop atherosclerosis if blood pressure is elevated. Only blood vessels in high-pressure areas develop atherosclerosis. A 2000 paper called 'There is a non-linear relationship between mortality and blood pressure' concludes that the reported linearity between blood pressure and mortality is not in the data, but rather in the analysis of the data. EmotionsForEngineers wrote on blood pressure in 2014. We'll see what the next installment holds.
  67. What causes heart disease part 58 – blood pressure, 11/1/2018 - The cause of high blood pressure is mostly not known by doctors (e4e comment: Apparently you have to be an engineer to understand pressure in a tube). But Malcolm seems to be on it. He focuses on the narrowing of the pipes, I suspect there's also a stiffening component as well—pulses into a balloon will just expand the balloon, whereas in lead, it would cause hammering. One issue that high blood pressure does cause is the enlarging of the two ventricles, which can lead to congestive heart failure (a completely different animal than what Malcolm has been discussing in this series). He discusses causality. He says that cardiovascular disease probably causes hypertension rather than the reverse and talks about the biochemical basis for that view. The issue is that lowering blood pressure may lower blood flow to places where it is needed. "...dealing with the elderly can turn into a battle between the heart and the kidneys. Get one under control, and the other one goes off." He has liked ACE inhibitors for hypertension control in the past because they also increase NO synthesis. However, there is evidence that they can increase the risk of lung disease.
  68. What causes heart disease – part 59, 11/27/2018 - Summary of everything published to date from Dr. Kendrick. Thrombogenic theory vs. LDL/cholesterol hypothesis: "I will confine myself to one simple point. For the LDL hypothesis to be correct, it requires that LDL can travel past the lining of the artery, the endothelial cells, and into the artery wall behind. This is considered the starting point for atherosclerotic plaques to form." and that is impossible. Damage to the arterial wall must be the starting point. Most mainstream doctors are okay here. The next step is where divergence starts. It's not the LDL, it's the clotting. "If you damage the endothelium, the first thing that happens is that a blood clot forms at that point." Then, "most of the blood clot is shaved down in size by plasmin, an enzyme designed to break up (lyse) blood clots. Then a new layer of endothelium grows over the top of the remaining blood clot, and in this way, the clot becomes incorporated into the artery wall." "Every step of CVD is due to various aspects of blood clotting. You damage the artery wall, a blood clot forms, which is then incorporated into the artery wall. A plaque starts then grows. This description of how CVD starts and develops is the process that I believe to be correct." A few provisos: 1. Endothelial damage is always happening. This is normal. When the rate of damage exceeds the body's ability to repair, problems start. 2. There is a very long list of processes that can cause damage to be greater than repair, affecting either or both sides of the equation. This leads to another long list of blood factors that impact the two sides of the equation, including high fibrinogen, lipoprotein a (lp(a)), dehydration, blood sugar triglycerides, etc. Next, there is a list of substances that prevent new endothelial cells from being created. And factors that prevent the clearing of the clot that develops behind the new layer of endothelium. Interestingly, some anti-inflammatory drugs can cause CVD. Evidence is that inflammation is not a cause of CVD, but rather a response to CVD. In summary, "The LDL hypothesis is nonsense, it is wrong, and it does not remotely fit with any other factors known to cause CVD. The thrombogenic theory, on the other hand, fits with almost everything known about CVD." "CVD has no single, specific, cause. It should, instead, be seen as a process whereby damage exceeds repair, causing plaques to start developing, and grow – with a final, fatal, blood clot causing the terminal event. The next blog will be a review of the things that you can do to reduce your risk of CVD."
  69. What causes heart disease part 60 – prediction, 1/2/2019 - I recently went to my internist who told me that according to their online calculators, I should be on a statin. My total cholesterol was 181, HDL was 45, and triglycerides were about 75. He admitted that those numbers looked fine, but the computer says... I said I wasn't interested.  That was all very timely, as Dr. Kendrick has written a post specifically about online calculators. The American College of Cardiology has a calculator, and so does the UK health system. The American calculator overstates the risk of a cardiovascular event by 5-6 times, so if it tells you 10%, you're closer to 2%. And by the way, if you are over 60, it WILL say you are at high risk and recommend a statin. Although the UK calculator contains more factors, it is similarly inaccurate. UK researchers ran a regression study of factors that correlate with CVD. These are the top ten in order: 1. Chronic Obstructive Pulmonary Disease (usually a result of smoking), 2. Oral corticosteroid prescribed, 3. Age, 4. Severe mental illness, 5. Ethnicity South Asian, 6. Immunosuppressant prescribed, 7. Socio-economic-status quintile 3, 8. Socio-economic status quintile 4, 9. Chronic Kidney Disease, 10. Socio-economic status quintile 2. Notice that cholesterol is not in the top 10. Total cholesterol is at 25, systolic blood pressure is at 29, and LDL ("bad") cholesterol is at 46 out of 48 factors considered. Bottom line: Those calculators are useless. He discusses arterial calcification as a measure of what has happened in the past, but it has limited predictive accuracy. "What can the average person do to shift those odds in your favour? If you have read this blog from start to finish, I would imagine that you already know. If not, I am going to tell you next time. I am going to tell you how to change the odds, but I am unable to tell you how to get them to zero."
  70. What causes heart disease part 61 – strokes, 1/15/2019 - There are three main causes of strokes: Atrial fibrillation, blood clot, and a burst blood vessel in the brain (hemorrhagic). Atrial fibrillation is related to electrical malfunctioning of the heart, causing blood to sit a little too long, which allows a clot to form, which then blocks blood to the brain. Hemorrhagic stroke is when a blood vessel in the brain bursts. Neither of these is related to cardiovascular disease of this ongoing discussion. A blood clot is. This is the most common type of stroke and has exactly the same cause as a heart attack. Atherosclerotic plaques form, break off, then block a blood vessel. In the case of a stroke, it's a blood vessel to the brain--not the heart. 87% of all strokes are of this type. Papers repeatedly find that LDL cholesterol is not associated with stroke. The paper, "Inborn coagulation factors are more important cardiovascular risk factors than high LDL-cholesterol in familial hypercholesterolemia," co-written by Kendrick. Familial hypercholesterolemia has never been found as a risk factor in stroke. A 2010 paper in the Lancet cites various associations with stroke from the general population (not causes, but risk associations). LDL is not on the list. However, the ratio of ApoB to ApoA is.  This is primarily the ratio of triglycerides to HDL. "...which is an accurate reflection of ‘insulin resistance’ and bears no relationship to LDL." How can raised LDL be a factor for heart disease but not stroke (if the mechanisms are the same)? It can't. If raised LDL is not a risk factor, how can lowering LDL lower risk? It can't. (Statins do confer a small benefit, although not from cholesterol reduction). " A raised LDL is not, and has never been, a risk factor for stroke. Yet it is claimed that lowering the LDL level reduces the risk of stroke? In reality, the evidence from the statin trials proves, beyond any doubt, that any benefit achieved by statins cannot be through lowering the LDL level."
  71. What causes heart disease part 62, 1/19/2019 - The "I told you so" edition. A study recently came out that shows that a low cholesterol level increases mortality in patients who have already had a stroke. The paper is called ‘Lower Cholesterol Tied to Increased Mortality in Ischaemic Stroke Patients with Carotid Artery Stenosis.’ "...these findings suggest a careful consideration of aggressive treatment of hyperlipidaemia in patients with acute, first-ever ischaemic stroke with high-grade ICA stenosis and post-stroke functional dependence." "Of course, this study will be dismissed out of hand. “We should still be prescribing statins to people who have had ischaemic strokes,” we will be told. “Studies like this are purely observational,” we will be told. “A high cholesterol level still needs to be lowered” we will be told. Nothing to see here; please move along! I do become increasingly weary of finding evidence that directly and absolutely contradicts the cholesterol hypothesis. It never makes the slightest difference – to anything. Hopefully, a few people are out there listening, whose minds are not made of reinforced concrete."
  72. Response to the Lancet paper, 2/3/2019 - Not strictly speaking a part of the What causes heart disease thread, but certainly peripheral to it. This is a review of a recent paper in the Lancet that states, "Everyone over the age of 75 should be considered for cholesterol-lowering statins, experts have urged, after an analysis found up to 8,000 lives a year could be saved." A number of issues with the paper. 1. the authors are from a university group funded by the pharmaceutical industry and are literally the only people in the world allowed to have the data. They have conflicts galore out of the gate. This doesn't make them bad, but be wary. 2. Many of the papers reviewed for this study did not even contain people over 75 years old. 3. The study states a 21% reduction in "major vascular events." Sounds good, but... No mention of mortality, no mention of impacts on other types of events, not a mention of fatal CV events. If there had been good news, they would have trumpeted it. Also, even Major CV events have a wide range of severity and consequences, so the conclusions are vague. 4. Other events are important. If you reduce CV events but increase cancer, you haven't gained anything. You can prevent heart attacks by pushing people off cliffs. Lol. There are data from 2003, the last time it was made available to outsiders, that demonstrate that while statins do help reduce CV deaths, they increase other fatal events leading to a wash. I'll let Dr. K finish this. "What does this mean in reality? Well, gathering it all together. Statins (in the over 75s) do not reduce mortality. They do not prevent fatal MIs and strokes. Whilst they reduce serious cardiac events, previously published results demonstrate they do not reduce total serious adverse events. Which means that they are, wait for it, absolutely and completely useless." Update: Zoe Harcombe also did a takedown on this study.
  73. Adherence to statins saves lives, 2/17/2019 - Not! Adherence to anything saves lives. Whether it's the placebo effect or the healthy subject effect doesn't really matter. The paper "Association of Statin Adherence with Mortality in Patients with Atherosclerotic Cardiovascular Disease.’ is a nothing-burger. Read the post for more details.
  74. Cholesterol Games, 3/3/2019 - In which Dr. Kendrick rips the Daily Mail a new one. There has been a recent push to demonize "statin deniers." No new info, but fun to read.
  75. What causes heart disease - part 63, 3/18/2019 - Stress is the most important cause of heart disease. Unfortunately, it has been sidelined by cholesterol, blood pressure, and other symptoms. The word stress itself really should have been "strain," which is more descriptive of it. "... stress is the external force placed on an object--or a human being. Strain is the resulting deformation or damage that can occur. Therefore, it is the resultant strain that is the driver of ill health." There is plenty of population-level data that demonstrate that high levels of psychosocial stress and increased CVDS are associated. The next post will discuss the mechanism.
  76. Writer's Block, 6/4/2019, Malcolm confesses to writer's block. This was his attempt to get unstuck. There is a section of interest, though, in which he explains the issue of reproducibility in health research. 70% of a group of scientists see reproducibility of research as an issue, but... Suppose a study is positive, e.g. drug X reduces heart attacks. Now if somebody wishes to reproduce that study, the research ethics committee will tell you that you may not have a placebo arm because now it is unethical to withhold a drug with "proven" benefits from patients. "Thus, if a trial was flawed/biased/corrupt or simply done badly. That’s it. You are going to have to believe the results, and you can never, ever, have another go. Ergo, medicine cannot self-correct through non-reproducibility. Stupidity can now last forever. In fact, it is built in."
  77. What causes heart disease part 64 – Not changing your mind. 8/22/2019 - Not about heart disease per se, but rather about the difficulty of getting people to change their paradigms and think that maybe they have been wrong about something. He uses an unfortunate example of a geologist named Thomas Gold, who has some great contributions to geology, but the example is one where, in fact, Gold's hypothesis was tested and did not hold up. Not completely, definitively proven wrong, but a well in the Siljan Ring, which was supposed to prove his hypothesis, failed to prove his hypothesis about abiogenic oil. There may be some abiogenic oil and gas in the world, but it's likely not ubiquitous. Nonetheless, the principles laid out in this post are true. It is extremely difficult to get people to agree to change something, especially when there is a committee and groupthink involved. (e4e comment: and especially when cognitive dissonance and confirmation bias are involved.) "When people ask me why do you think people cling onto the cholesterol hypothesis with such tenacity, is this vast conspiracy driven by the pharmaceutical industry? I expect most of them think I will say yes. I mean, obviously, there is a vast conspiracy going on to protect profits from cholesterol-lowering. However, the main reason why people cling to ideas is the natural human response – which is to reject new ideas out of hand."   
  78. Review of statins needed, 9/7/2019 - High-intensity statins have been approved for OTC sale in the UK. "The European Society of Cardiology has decreed that there is no normal level for cholesterol, the lower, the better." Malcolm and Aseem Malhotra recently wrote a letter to"Sir Norman Lamb MP. Chairman of the Science and Technology Select Committee – at his request – asking for a review of statins, and safety issues."  There's a video here. Essentially they say that benefits are overstated, dangers and adverse effects are understated, and the data is not made available for independent analysis. We are left to trust the assessment of financially interested parties. Nothing new here, but the fight continues.
  79. What causes heart disease part 65 – Lead again, 9/23/2019 - Lead, the heavy metal, is associated with a higher risk of heart disease. Yes, it is an association, but the association is super strong. According to a recent study, 1 in 6 deaths is attributable to lead in the body. The broader question is, at what level of correlation effect do we begin to believe that the association may be causal. A typical benchmark might be something like if the odds ratio is affected by a factor of two, you might see something cutting through all the noise and inaccuracy of epidemiology. Red and processed meat typically show an odds ratio of about 1.2, so it is weak evidence. Lead, on the other hand, in one study, had an odds ratio of 8.37. It's bad stuff. You can get your blood tested for lead, and there are effective chelation therapies that can reduce lead in your body. As an aside, I really liked this quote, "...almost all diets are perfectly healthy. Vegetarian, paleo, keto, vegan (with a few essential nutrients thrown in, so you don’t die), HFLC, etc. In fact, the only non-healthy diet would be the one recommended by all the experts around the world. Namely, High carb, low fat (HCLF). The ‘eat well plate’, ‘the food pyramid’ – whatever it is now called. Stay away from that, and you will be fine."
  80. What causes heart disease part 66, 10/5/2019 - More on lead and the philosophy of his work. Lead is very nasty stuff. But... it does not fit into the cholesterol hypothesis of heart disease. So it is seen as a toxin, but the medical establishment picks on cholesterol, perhaps because they can. Lead fits in well with Malcolm's hypothesis, It provides "Fifteen ways of damaging the endothelium, four that inhibit repair, and two mechanisms for making blood clots more difficult to get rid of..." Sickle cell disease is another very nasty disorder that causes CVD but does not fit into the cholesterol hypothesis. It does fit into the three-step process. Finally vasculitis. It causes CVD but doesn't fit into the cholesterol hypothesis. "They all fit very neatly into the walls of the house that is called ‘endothelial damage’. How else can you explain how three such disparate things can possibly cause exactly the same disease." "...realised that the problem, the great problem in all research into CVD, is that very early on it was decreed that LDL/cholesterol causes CVD. Therefore, all thinking and any hypothesis on CVD required that LDL sat at the centre."
  81. What causes heart disease – a summary, 10/9/2019 - Malcolm is interviewed for a podcast by Ivor Cummins and explains his hypothesis. Another blog takes a stab at paraphrasing the hypothesis. Malcolm is happy with this, perhaps because he is so close to it and all the detail that it's hard for him to create something at a more digestible level for non-medical professionals.
  82. What causes heart disease - part 67 - The Blood Brain Barrier, 11/10/2019 - Another perspective on problems with the LDL/cholesterol version of heart disease. The brain contains a large amount of cholesterol. The endothelium of blood vessels in the brain is quite similar to that found in arteries. Endothelium does not allow for simple "leakage" of LDL, perhaps there is a cellular mechanism that allows passage through the cell? It seems odd that the brain manufactures its own cholesterol when it could otherwise possibly take it straight out of the blood. He found a paper, though, which states, "... the blood-brain barrier (BBB) prevents the uptake of lipoprotein-bound cholesterol from the circulation." This means then that LDL cannot get past intact arterial endothelium, therefore the LDL hypothesis is dead. QED.
  83. The Lancet Study, 12/11/2019 - Another study with conflicts of interest and questionable endpoints. It's called "Application of non-HDL cholesterol for population-based cardiovascular risk stratification:..." This one has a few instructive issues. First, it measures non-HDL cholesterol. Essentially, it is total cholesterol minus HDL modified by triglyceride count. LDL ("bad" cholesterol) is not directly measured. So in their formula, LDL is calculated as proportional to triglycerides, which are a known causal factor of CVD. Triglycerides are included in non-HDL as is LP(a), which is similar to LDL, but it has an extra protein stuck on the side which causes clots and prevents their breakdown. Finally, the endpoint measurements are important. The one we REALLY care about is total mortality. This study apparently used a combined end-point to measure efficacy and did not include total mortality. Malcolm says that if they don't include total mortality it was not relevant or significant. Toss this study; it tells us nothing.
  84. Another new study, 12/23/2019 - Here's the study: "Association between hyperlipidaemia and mortality after incident acute myocardial infarction or acute decompensated heart failure: a propensity score-matched cohort study and a meta-analysis." I fell asleep just reading the title. The words in the study are even worse if you're not used to jargon and acronyms in this field. This one didn't get nearly as much press as the LancetStudy above. Hmm. Could it be because it showed that higher LDL cholesterol may actually be protective against heart disease mortality? In fact, the cohort tested is the one thought to receive the highest benefit from lowering cholesterol by taking statins, This study shows that is not the case. The bottom line, "Clinical care should not focus on certain lipid targets." Things that make you shake your head.
  85. Coronary artery calcification (CAC), 1/17/2020 - Happy New Year. Dr. Kendrick starts out the year with a fascinating take on the CAC score. This is a test that speaks to the presence of calcification in the coronary artery. A low score is always considered good, a high score is not good, but may not be bad. How is this possible? When damage occurs to the endothelium and underlying blood vessels, it clots and attempts to heal. When the healing is not 100%, over time, the remaining tissue absorbs calcium and forms a cap, which is detectable by the CAC test. Calcium on a CAC test tells you that damage occurred some time ago and did not fully heal. Once a clot calcified, it is no longer dangerous generally. Statins actually increase calcification as does warfarin, as does intense exercise. It turns out that if the calcification and clotting are from intense exercise, it is much less dangerous than if it is from another cause like smoking or diabetes. The latter causes tend to create damage in the blood vessels with a goopy semi-liquid core, whereas exercise damage tends to be more fibrous and not dangerous. CAC does not tell you why the clot formed and whether it is dangerous. The issue with many diagnostic tests is that they are not useful guides to what you should now do. CAC is one such test. If your CAC is zero, don't worry. If it's positive, now what? Taking statins increases it, and exercise increases it. Is that good or bad? The jury is still out. Kendrick says "...CAC scans meet most of my criteria for ‘a bloody awful test that should not be done.’ It may or may not mean anything, there is no clear guidance as to what you can do about it if it is positive, and it spreads fear and anxiety in many, many, people." He believes that until we have some idea what to do about a high score, backed by good research, it probably should not be done. e4e take: CAC tests, as with mammograms, are in that world of tests where it is unclear if there is an actual population-wide benefit of doing them. The tests are not reliable enough to rule out false positives, and often more harm is done attempting to fix something that does not need to be fixed. Although people want to know their status, if it does not have a high chance of driving you in a beneficial direction, one should be wary. The stress alone from getting a positive test can drive worse outcomes. It's money that can be better spent. If you will stress out, just don't. Some people NEED to know and stress more from the uncertainty of knowing there is a test out there that they haven't had. There is very little upside to this test and more downside. It's best to spend your test money elsewhere. 
  86. COVID19 – the spike protein and blood clotting, 6/3/2021 - Kendrick is working on his book on heart disease, and in the process, COVID came through the world. COVID causes a lot of blood clotting issues as one of its effects. The "cytokine storm" caused as your immune system ramps up causes damage to the glycocalyx and the underlying endothelium, which causes many clots to form. One of the instigators of the immune response that causes the cytokine storm is the spike protein on COVID, which is essentially what makes up the vaccine. Given this, the vaccines probably cause increased clotting. It will be difficult to coax some deaths caused by the vaccine out of the data because there are already so many clotting-related issues.
  87. COVID19 and CVD – Bridging the Gap, 9/16/2021 - He starts out with the assertion that the immune system and blood clotting mechanism actually work together, and in fact, started deep in our evolution as the same thing. There's a lot of technical connecting the dots, and then the kicker--"...with COVID-19, we are looking at almost the same pathological process as seen in Systemic Lupus Erythematosus (SLE), with an added dash of antiphospholipid syndrome." So, of course, COVID is not Lupus, but it looks a lot like it, creating similar damage.
  88. Let’s talk about C – just you and me, 10/22/2021 - The good doctor does a deep dive on vitamins in general, and specifically, vitamin C. Much of this is an update of his past work on Vitamin C, where he talks about the importance of C in healing vascular damage without forming clots. He did have an interesting and surprising observation. Lp(a), that nasty lipoprotein is a form of LDL. It is what created the blockage in arteries. There is a proportion of Lp(a) to LDL, but in each person it is different. But the more LDL, the more LP(a) you will have in general. Vitamin C is required to create collagen in your body, which in turn prevents your body from using and cementing the Lp(a) to your blood vessels in the first place.
  89. The enduring mystery of heart disease – The Clot Thickens, 11/4/2021 - Dr. Kendrick has released his new book. The title is not just a silly pun, but also a description of what happens in heart disease. He has taken all that he has discovered during his long career of practicing medicine and geeking out on all the literature and converted it into a book.  I don't have much to say beyond everything that is written above. He says he gets deeper into many of the topics than he did on the blog.  I just bought it.
  90. Vitamins once more – mainly B vitamins and homocysteine – with a special mention for magnesium,12/6/2021 - Vitamins and minerals are essential to life. In modern times, due to many variables, there are some that end up in deficiency. An interesting and sad example is from Israel, where heavy reliance on mineral-free desalinated water leaves many with a magnesium deficiency. About 4,000 people die per year from that deficiency in Israel. He also cites a paper that proposes magnesium as a driver of cardiovascular disease and death. He recommends that you supplement, especially if you live in an area with soft water or experience atrial fibrillation. There is little or no downside. A dearth of B vitamins can also be dangerous. In this article, he focuses on B3 (niacin), B6 (pyroxidine), B9 (folate/folic acid), and B12 (cobalamin), which, if you are low in them (especially 6, 9, and 12), can increase a protein in your blood called homocysteine. High homocysteine in your blood damages endothelial cells. The man who discovered this relationship, Kilmer McCully) was blackballed from academia for a time. He then pivots to the role of B vitamins in the prevention of Alzheimer's and dementia where B1, B6, and B12 seem to have a particularly important role in preserving the nervous system, and cites some studies where this was observed in intervention. His final pivot in the article is to the corruption of what I will call the pharmaceutical-research complex, which has blessed poor studies that do not further the interests of drug companies.


Peter Attia's view. Dr. Attia is another very smart guy. His view is somewhat different than Dr. Kendrick's view. Attia focuses on the end-stage as being the infarction, rather than the clot breaking. There are also other differences.

Kendrick's view is that the clot occurs mainly (although not exclusively) because of physical damage to the endothelium. In "normal" circumstances, most of the clot will get cleaned up by the body, perhaps leaving behind some scar tissue. But if the clot has some malformation, or the person has an imbalance in some of the important blood factors, the cleanup either does not occur or is poorly done. At that point, the vessel will become blocked, or the clot may break loose because of defects in the clot.

Attia, on the other hand, seems to regard CVD as simply an inevitable outcome of age. Oxidation and damage happen inside the intima (the artery wall itself, behind the endothelium), then essentially spills over through the endothelium, where it clots, etc.

For me, Kendrick's view seems to hold together better. It contains both a pathology as well as a mechanism for reversing it if everything is working properly. Attia presents the damage as something that happens that cannot repair itself. That's the way the body usually works. Kendrick's view is that overall the body is doing its best to protect itself, but when it gets overloaded it simply can't keep up. This can be compared to the view that CVD is a horrible pathology.

In all likelihood, I am misinterpreting much (and perhaps they are saying something quite similar but explaining it differently), but Kendrick's view seems more biologically consistent with the way the body usually works.

Other posts during the series on What Causes Heart Disease.

Duane Graveline, 09/06/2016, Duane was a doctor who trained to be an astronaut. He was prescribed statins and had severe side-effects. He researched and studied these effects and developed the SpaceDoc website. He passed away.
Medical censorship in the twenty first century, 9/11/2016, Medical censorship. Tells stories about how researchers try to quash research and studies contrary to their beliefs and/or interests. This is an interesting read about limitations of studies, especially when researchers have a dog in the hunt. [e4e note: This post is mostly about how confirmation bias and cognitive dissonance destroy even intelligent people's ability to reason.] Read it, but there is little to learn about heart disease. There is interesting information about statin adverse effects.
Buy this new book, 09/26/2016, "There is a group of doctors, scientists and researchers called the International Network of Cholesterol Skeptics (THINCS) www.thincs.org. I am a member, and recently a number of us have contributed chapters to a new book called Fat and Cholesterol Don’t Cause Heart Attacks And Statins are Not the Solution."
Saturated fat and heart disease, 10/20/2016, "Total saturated fat intake was associated with a lower IHD (Ischaemic Heart Disease) risk..." It goes on to say that substituting anything for saturated fat increases heart disease risk. The main point of this post though is that questioning dogma can be professionally and legally risky for doctors and researchers. It is especially bad when the dogma is built on "common sense" and not research. "Made up scientific hypothesis are, I find, very difficult to dislodge with evidence." He talks about a few examples and crazy quotes from people entrenched in the dogma.
Those who promote a high fat low carbohydrate diet are silenced around the world, 11/13/2016, The curious case of Dr. Gary Fettke. Horrible process they have in Australia.
High cholesterol low heart disease – The Sami, 11/29/2016, Another paradox--people whose good health persists despite their efforts to kill themselves with unhealthy habits. The Sami are what we used to call the Lapps in Finland. "...the Sami, despite having very high cholesterol levels, a high level of smoking, a high-fat diet, and almost zero carbohydrate intake – and suchlike – had a very low rate of cardiovascular disease. This was particularly interesting for a couple of reasons. Firstly, most of the Sami live in Finland, and the Finns – at one time – had the highest rate of heart disease in the world. Not only that, but the Sami live in an area of Finland, North Karelia, which had the highest rate of heart disease in Finland. The worst of the worst.In addition, the Sami had considerably worse ‘traditional’ risk factors for heart disease than the surrounding population. Higher cholesterol and LDL, high-fat diet, far more smoking etc."
The diet-heart hypothesis suffers another attack – hoorah!, 12/16/2016, A Group of concerned Canadian Physicians and Allied Health Care providers put together recommendations about Canada's dietary guidelines. Their recommendations are as follows: 1. Clearly communicate to the public and healthcare professionals that the low-fat diet is no longer supported, and can worsen heart disease risk factors. 2. Be created without influence from the food industry. 3. Eliminate caps on saturated fats. 4. Be nutritionally sufficient, and those nutrients should come from real foods, not from artificially fortified refined grains. 5. Promote low-carb diets as at least one safe and effective intervention for people struggling with obesity, diabetes, and heart disease. 6. Offer a true range of diets that respond to the diverse nutritional needs of our population. 7. De-emphasize the role of aerobic exercise in controlling weight. 8. Recognize the controversy on salt and cease the blanket “lower is better” recommendation. 9. Stop using any language suggesting that sustainable weight control can simply be managed by creating a caloric deficit. 10. Cease its advice to replace saturated fats with polyunsaturated vegetable oils to prevent cardiovascular disease. 11. Stop steering people away from nutritious whole foods, such as whole-fat dairy and regular red meat. 12. Include a cap on added sugar, in accordance with the updated WHO guidelines, ideally no greater than 5% of total calories. 13. Be based on a complete, comprehensive review of the most rigorous (randomized, controlled clinical trial) data available; on subjects for which this more rigorous data is not available, the Guidelines should remain silent." Yay!

https://drmalcolmkendrick.org/2017/01/28/vitamin-c-an-update/, 01/28/2017, ‘Our results suggest that the early use of intravenous vitamin C, together with corticosteroids and thiamine may prove to be effective in preventing progressive organ dysfunction including acute kidney injury and reducing the mortality of patients with severe sepsis and septic shock. This one has nothing to do with heart disease, but VItamin C continues its march.
https://drmalcolmkendrick.org/2017/05/08/its-official-statins-do-not-have-any-side-effects/. 05/08/2017, discussion of a study that claims statin side effects are extremely rare. The study was conducted by companies that sell statins. He doesn't believe it and has comments about the studies. In any case, except in a minority of people, statins help very little.
https://drmalcolmkendrick.org/2017/05/22/cholesterol-lowering-the-end-of-the-beginning/, 05/22/2017, more on the statin side-effect studies and conflicts of interest in the researchers.
https://drmalcolmkendrick.org/2017/05/28/mike-cawdrey-a-tribute/, 05/28/2017, Mike Cawdery was a regular commenter on Kendrick's blog.
https://drmalcolmkendrick.org/2017/06/24/british-society-of-lifestyle-medicine-conference/, 06/24/2017, "This is a great grassroots movement of people, and many doctors, who are trying to achieve a more holistic approach to health. "
https://drmalcolmkendrick.org/2017/07/16/diabetes-unpacked-a-new-book/, He talks about a book that he contributed to that discusses the causal link between diet and diabetes. It should come as no surprise that he favors a low-carb, high-fat (LCHF) diet. This is consistent with e4e recommendations, so beware confirmation bias.


Evacetrapib trials fail
Great quote, "“We had an agent that seemed to do all the right things,” said Dr. Stephen J. Nicholls, the study’s principal investigator and the deputy director of the South Australian Health and Medical Research Institute in Adelaide. “It’s the most mind-boggling question. How can a drug that lowers something that is associated with benefit not show any benefit?” he said, referring to the 37 percent drop in LDL levels with the drug." Here's the e4e answer to his question. The hypothesis that high LDL and low HDL cause heart disease is a failed hypothesis. Your company should now declare bankruptcy and stop selling statins before you kill more people.

Another article supports the link between erectile function and cardiovascular health mediated by nitric oxide.

Zoe Harcombe's blog on Cholesterol Replacement by Plant Sterols
plant sterols have been shown to lower/reduce blood cholesterol“. They also stated “However, there are no human intervention studies demonstrating that plant sterols reduce the risk of coronary heart disease.

Also this link demonstrating that  The higher the cholesterol, the lower the deaths from CVD (cardiovascular disease) for men; The higher the cholesterol, the lower the deaths from CVD (cardiovascular disease) for women; The higher the cholesterol, the lower the deaths from any cause for men;  The higher the cholesterol, the lower the deaths from any cause for women.