[By heart disease I mean, the development of atherosclerotic plaques in large arteries. Mainly the coronary arteries (supplying blood to the heart) and carotid arteries (supplying blood to the brain). This, I will refer to as Cardiovascular Disease CVD. Not entirely accurate, but language never is.]
At this point, I am going to start at the end. What kills people? (Or what causes myocardial and cerebral infarctions). You might think that this was clear cut, but of course it is not, far from it. For example, there is a major cause of death from ischaemic strokes that has nothing whatsoever to do with CVD. This is Atrial Fibrillation.
Atrial fibrillation (AF), is a condition where the upper chambers in the heart (atria) do not contract in a regular and co-ordinated fashion. Instead, they fibrillate – AF definition : ‘(of a muscle, especially in the heart) make a quivering movement due to uncoordinated contraction of the individual fibrils.’ AF is pretty common.
People who have AF tend to develop blood clots in the atria. These can break loose, and are then ejected from the heart into other parts of the body. Quite commonly these clots travel into the brain. As the artery the clot is traveling down narrows, the clot gets stuck, and blood supply is cut off, leading to an area of ‘ischaemia’ (no oxygen) and a stroke. A cerebral infarction.
Which means that it is perfectly possible to have strokes (cerebral infarctions) that are unrelated to CVD. If, that is, you define CVD as the development of atherosclerotic plaques. You can also have strokes where an artery in the brain bursts, causing bleeding into brain tissue, which is called a haemorrhagic stroke. This is clinically indistinguishable from an ischaemic stroke. You need a brain scan to see what type of stroke has happened.
Ergo, whist death from a stroke is clearly a form of cardiovascular disease, many strokes have nothing whatsoever to do with atherosclerotic plaques – which is what I am calling CVD.
Equally you can die from something commonly defined as a ‘heart attack’ which has nothing to do with atherosclerotic plaque development either. You can, for example, develop a fatal arrhythmia. This is where the conduction system in the heart goes wonky, the heart stops contracting regularly, and you die. [Of course, quite often this happens as part of a myocardial infarction].
If we put aside these forms of dying of strokes and heart attacks, we can then focus more clearly on the event that kills you with CVD? Which is, in general, a clot forming on a vulnerable plaque, and blocking an artery, leading to a myocardial infarction (heart attack).
Looking at strokes. If a clot forms in a carotid artery, it does not tend to block the artery completely. Instead, a part of the clot breaks off, and travels up into the brain where is gets stuck – causing a stroke (as per AF).
But… there are those who disagree with this simple model. Mainly with regard to heart attacks. I am fully aware of a growing movement which states that the myocardial infarction (heart attack) happens first, then the clot forms afterwards. (Incidentally, this concept is not new; it was first proposed over eighty years ago. You may think that is seems completely mad. However, there is strong evidence that would appear to support this ‘reverse’ hypothesis’ (infarction first, then the blood clot forming in the artery).
For example, in many cases after a confirmed and accurately diagnosed myocardial infarction, you cannot find any blood clot in the artery leading to the infarcted area. In other cases, you can find a blood clot that is several days, or weeks old. This age of the clot can be established because of the ‘evolved’ state of the thrombus. In short, there is no ‘temporal’ connection between the blood clot forming and the heart attack occurring.
On the other hand, you can find an acute blockage of a coronary artery that has not caused any symptoms, let alone a myocardial infarction.
Anyway, if you try to bring these facts together you find that:
- Myocardial infarctions can occur without any clot being found in an artery
- A clot can form in coronary artery days, or weeks, before any symptoms of an MI
- A clot can fully obstruct the coronary artery, without causing a myocardial infarction
Given these facts (facts which, incidentally, are not in dispute), you can make a pretty strong case that there is no causal association between a blood clot blocking a coronary artery, and an MI taking place. Instead people can, and indeed do, argue that the process is the other way around. Infarction first, then clot.
Perhaps, now, you can begin to understand why it has taken me thirty years to try and work out the underlying process of CVD. At times I have thought that there isn’t any… but that is another story, for another place
The reverse hypothesis – why it is not correct
I have studied the ‘reverse hypothesis’ – if that is a reasonable term for it – for many years, and I believe that it is wrong. The primary cause of a heart attack is simply a blood clot blocking a coronary artery. However, there are two major complications that lead to the apparent contradictions listed above. In no particular order they are the following:
- An infarction does not mean that heart muscle dies
- Collateral circulation develops
What is an infarction?
Cardiology is, unfortunately, dominated by highly simplistic thinking. Namely, plaque develops, clot forms, infarction occurs. The infarction occurring within minutes of the clot formation.
But this is nothing like the reality of what actually happens. Heart muscle, like all tissues in the body, is enormously complicated. If you suddenly reduce the blood supply, it can do several different things. It can infarct, it can hibernate, or it can do nothing much.
Just to look at infarction. The dictionary definition is… ‘obstruction of the blood supply to an organ or region of tissue, typically by a thrombus or embolus, causing local death of the tissue.’ Well, I’ve got news for you, heart muscle does not die (not unless the organism surrounding it dies).
Infarction, in the case of myocardial infarction, does not mean death of the tissue. Instead, the heart muscle undergoes a complex transformation into a different cell type. One that needs far less oxygen to survive and one that cannot do the contracting thing. But it is not dead. Because dead cells become necrotic and necrotic cells disintegrate. After a heart attack do you see disintegrated areas of the heart? No, you most certainly do not. You see a form of scar tissue developing.
There is also a halfway house that lies between infarction, and nothing happening. This is ‘hibernation’, a state whereby heart muscle simply decides to stop contracting/beating (to save oxygen use). If you do MRI scans on the heart, in those with known heart disease, such ‘silent’ regions are a relatively common finding. Sometimes these regions wake up and start beating again, sometimes they do not. Sometimes they go on to infarct.
Adding further to the complication, if a coronary artery starts to narrow, the heart will create small ‘collateral’ blood vessels to get round the narrowing, and keep the blood supply up. When, and if, the artery fully blocks, the collateral circulation will maintain the blood flow, and so nothing very much will happen, even if the coronary artery is fully blocked. Many people survive on collateral circulation alone.
All of which means that, after an artery blocks, one of three things can happen:
- There is a sudden infarction (could be large enough to be fatal)
- The heart muscle decides to hibernate, if there is sufficient collateral circulation to keep things ticking along
- Nothing much happens. If there is high level of collateral circulation, the heart just carries on much as before.
Only in the first case will the obstructive blood clot closely precede the heart attack. In case two the hibernating heart muscle may later decide to infarct, if the circulation does not improve. This can happen under periods of high physical or psychological stress. Thus the formation of the blood clot can precede the infarction by days, weeks or months. Indeed, the clot may have been fully cleared away by the time infarction occurs.
In short, the apparent contradictions to the: clot → blockage → infarct hypothesis can be explained, reasonably easily. So long as you realise that what happens inside the heart is not a case of simple pipe-work, where there a fixed number of tubes (arteries) supply oxygen to a pump (the heart). If you block one tube, the pump is immediately damaged.
Heart attacks and strokes
However, my main reason for disbelieving the ‘reverse hypothesis’ is that the standard model works for both heart attacks and (most) ischaemic strokes.
In ischaemic strokes, as mentioned before, a blood clot forms over a plaque in a carotid artery. This rarely blocks the artery; as carotid arteries are much wider bore than coronary arteries. However, what happens next – after a variable time period – is that the clot breaks off and travels into the brain.
This is, essentially, exactly the same process as a heart attack – except the clot lodges further down the vascular tree. Not only are the processes of stroke and heart attack virtually identical, the risk factors for both are virtually identical. Perhaps most telling is the fact that people with plaques in their coronary arteries almost always have plaque in their carotid arteries, and vice-versa. For example, here is the title of a paper on this topc: ‘Tight relations between coronary calcification and atherosclerotic lesions in the carotid artery in chronic dialysis patients.’1
This is further supported by a study that has just come out, and published in BMJ open. Key points were:
- We studied the risk of heart disease following a stroke in those patients with no cardiac history. This study is the largest of its kind and, by bringing together multiple data sets, robustly quantifies the risk of heart disease following stroke. As with all meta-analyses, the main limitation of this work relates to publication bias.
- Most patients with stroke die of heart disease.
- One in three patients with ischaemic stroke with no cardiac history have more than 50% coronary stenosis.
- 3% are at risk of developing myocardial infarction within a year of their stroke.
- Patients with stroke need to be screened for silent heart disease and appropriate and aggressive management of total cardiovascular risk factors is required2.
In short, the two conditions are the same. It is beyond any reasonable doubt that with ischaemic stroke, and myocardial infarctions, we are looking at the same underlying disease. To be frank I don’t think may people would disagree with this. But it does lead to a critical point. Namely has anyone, ever, argued that cerebral infarctions (strokes) happen before the blood clot blocks an artery in the brain?
No they have not. Because to do so would, quite frankly, be bonkers. We can be absolutely certain that blood clots cause infarctions in the brain. Yet many people quite strongly argue that with myocardial infarction it is the other way around. For the reasons outlined above I do not, and cannot, believe this. There is only one process, and no need to start searching for another.
You may wonder why I have gone off in such a wide detour here? There are two reasons. First to make it clear that this area is gigantically complex. Secondly, to reinforce the point that wherever and however you look at CVD, alternative hypotheses have been proposed. Until you have tracked them down, and examined them fully, you cannot really move on.
Next: Some answers.
References:
1: http://www.ncbi.nlm.nih.gov/pubmed/20470277
Dr. Malcolm Kendrick 
re: In short, the tow conditions are the same.
two conditions?
More!
Sent from Samsung tablet
Ultimately what causes heart disease is bellyache from Erindoors, which is probably why ladies the world over are practically immune – the odd barking mad woman notwithstanding..
On Thursday, 21 January 2016, Dr. Malcolm Kendrick wrote:
> Dr. Malcolm Kendrick posted: “[By heart disease I mean, the development of > atherosclerotic plaques in large arteries. Mainly the coronary arteries > (supplying blood to the heart) and carotid arteries (supplying blood to the > brain). This, I will refer to as Cardiovascular Disease CVD. N” >
Though, I am only a lowly ophthalmologist practicing 20+ yrs, I have gone through this line of thinking before and agree with you that clotting plays a major role in the acute event. Many acute MI’s may, however, be caused by Vfib or asystole. Are these a direct result of ischemia from an acute clot or does the arrhythmia cause the acute clot in areas of stenosis or atheroma? And, what is the cause of the arrythmia? Is arrhythmia the primary cause of MI?
Good blogg
Great read ….I’m number 3 .. Nothing happened and
have a really strong heart! so I’m assuming I have a great network of collaterals…. Can’t wait for the answers…
This is so interesting. I love the way you think about things It’s like a medical mystery, just wish I had more time to research! Are we possibly having ”heart attacks’ all the time, i.e. blood vessels are becoming blocked, but this is not actually the problem? The problem is that some people just aren’t as efficient as developing a collateral circulation as others e.g. those who don’t exercise, those with impaired EPC regeneration and mobilization, those with impaired immune systems and those who don’t get enough flavenoids in their diet etc to create strong healthy new blood vessels ?
Many thanks for all the information.
On the basis of your hints, is this any good?:
1. Stress – emotional/physical, including smoking, pollution, radiation, herbicides, leads to oxidative stress and therefore to free radicals. Antioxidants, e.g. vitamins C & E act as scavengers and protect against free radicals by neutralising them by donating one of their electrons and ending the electron-stealing reaction.
2. Nitric oxide acts as a messenger for many intra and extra cellular processes. Stress reduces NO concentration. Augmented quantities of active forms of oxygen in the blood (increased lipid peroxidation products) will damage endothelial cells and cause a decrease in NO secretion. This is followed by more endothelial dysfunction, giving vasoconstriction, hypo-coagulation and proliferation of smooth muscle cells.
3. Free radicals can damage cardiomyocytes and affect contractile function.
4. Stresses can inhibit vascular endothelial growth factor (VEGF) and so will affect mobilisation and circulation of endothelial progenitor cells (EPCs) which restore the endothelium and help to maintain vascular health.
5. Stress results in quantitative changes in some hormones e.g. glucocorticoid, catecholamine and melatonin.
6. NO diminishes the production and secretion of stress hormones.
TS, on your point 1.
I’d look at the free radicals starting closer to their source near the start of the ETC in endothelial cell mitochondria (for example). That brings in all the cellular processes that control free radical production (insulin signalling, to name but one of many – see Hyperlipid for very much more). SODismutase, catalase, glutathione, B- vitamins and suppose eventually vitamin C. (Not trying to write the whole antioxidant chain, just some of the links along the way.)
There are fairly direct and relevant links between mitochonrial state and NO production (I don’t have the references to hand, but I recall that they were quite easy to find).
I can’t help but think that the root metabolic cause(s) are right at the ETC/energetics level (that’s not very precise, but I’ve not had 30 years to think about it).
Ken
Thank you Ken
Phew! Your final three paragraphs spoke very clearly to me; so with interest I await your answers.
During my nurse training in the 1970’s we were taught that after an MI some heart muscle dies. If bloods showed raised cardiac enzymes an MI was confirmed, CVA patients I don’t recall any relation to cardio thoracic. But it does make sense, the strong connection, the fragility or changes in the circulatory system. So what now, still so many deaths and disabilities,including my fabulous brother in law who ate well, played golf, travelled, happy in his family life. Developed angina, stented, died few days later aged 70 , same as his father.
So interesting Dr Kendrick to read your blog. Thank you.
Was thinking about my rel last night. In his twenties he had TB, isolation 6 months, in his thirties quite poorly with pancreatitis, inflamed oesophagus problems in his fifties. Not smoked for fifteen years. Very stressful job. In between he was fine, so was he laying down the problems. ? Barking up the wrong tree.
But what about the sympathetic/parasympathetic out of balance hypothesis?
Goran. I am looking at process, not cause. Of course, the sympathetic/parasympathetic balance is important. It plays a major part.
Thank you for this clarification.
I wonder if I am the only one who missed this point about “process” and “cause” although I now fully acknowledge that you are right.
But I guess it is natural to immaturely look for a cause when you are considering a process.
If you do not understand the process you cannot elucidate causes. I suspect many other are confusing the process/cause thing. As with most things, however, it is never as clear cut as you would like. After all the cause of TB is the tuberculus bacillus, the process of TB is closely entwined with the causal factor – as it must be. But the search for the causes, or causes of CVD has created a horrible mess.
Dr Sjoberg, to me your comments are far from immature. I think many of us feel badly let down by “experts” and as a result, are trying to take back control of our own destiny. From what I have read you have certainly done that.
We have to scour the Internet for little snippets of information here and there that seem to make some sense and wow, many of us seem to actually doing rather well as a result and that is very empowering.
I’m certainly no “expert” and much of what is being discussed now has moved way, way beyond my degree level clinical/biochemical knowledge. But I’m still scouring furiously for snippets of the process that may, just may, help me in the future.
Peggy,
I think you are right. You HAVE to do your best by your own search from the outside if you want to regain your health but of course with no guarantees.
The most important thing in my eyes is to get a reasonable overview map of the medical field that fits our reality. And this overview map tells me that it is Big Pharma that with great skill is running the medical business and exclusively in their own interest. The Gp’s are then “Only a Pawn in Their Game” where we are their innocent victims. This doesn’t say that there no other players on the market who want a piece of the cake we can offer as patients with serious diseases.
Can’t wait for the next one…
Thank you Malcolm. Can’t wait for your next installment. I share your brilliant insight with my patient classes on our low carb diet.
Let’s see, loss of ability to synthesize Vitamin C, decreased ability to make collagen…not important at the time due to high oral intake of Vitamin C with backup of lp(a) to “patch up” arterial defects in times of low Vitamin C intake…also complete turnaround in potassium to sodium ratio from high potassium/ low sodium to low potassium/ high sodium which results in a number of vascular insults/ effects…I’m thinking high potassium, higher vitamin C diet to counteract heart disease…
I was also wondering about pressure and angiogenesis. Does the body try and increase pressure within the blood vessels in order to bring more blood to endothelium at risk of hypoxia? Plaques increase the pressure of blood flow over them, increasing pressure on the endothelium and stimulating blood supply? So lowering blood pressure with only drugs would worsen the underlying hypoxia?http://www.sciencedaily.com/releases/2015/05/150529193554.htm ‘Blood pressure medications can lead to increased risk of stroke’
‘pressure and angiogenesis’
I think I’ve read that hypoxia can stimulate angiogenesis. This discussion has sent me searching for so much information that I need a little time to sit back and digest it all. This tid-bit is interesting:
“ECFCs can become dysfunctional in gestational diabetes (rescued by Vitamin D administration) Placenta 36 (4): 410–8. doi:10.1016/j.placenta.2015.01.195. PMID 25684656 ”
via
https://en.m.wikipedia.org/wiki/Endothelial_colony_forming_cell
Never seen this addressed so clearly, or indeed at all! Thank you Dr Kendrick
I’ll second that – Malcolm Kendrick is a Hero (yes with a capital H).He puts 95% of the medical establishment to shame. This is what using your brain means docs!
This part II is just what I was hoping for. Thank you for acknowledging the complexity involved and explaining why you do not believe the reverse hypothesis as I’ve asked others who only said it was ridiculous. I’m very keen to see those answers you promise above and have ordered your “Doctoring Data” book. Many thanks again.
Ridiculous has a tendency to become acknowledged truth over time. But in this case I just think it is wrong.
I did a lot of postmortems in my time. In sudden death, other than in rarer sudden adult death syndrome cases you would see either a 90% blockage or a thrombus with varying degrees of blockage with or without evidence of infarction at various stages, or so-called sub-endocardial infarction with generalised atherosclerosis. I wouldn’t buy the reverse hypothesis either. Clots can dissolve. I’ve felt that the endothelium is the big Cahoona in all of this. If your roof leaks you don’t blame the type of rain. I’m willing to be wrong of course, because if you’re not you’re no longer scientific
You are right. I hope.
Excuse my ignorance but what is:
“sudden adult death syndrome”
A piece of terminological inexactitude.
I’m quite interested in the circumstances under which the coronary artery collaterals develop. Seems it would be wise to encourage this. My father died of a heart attack at age 32, 64 years ago, and all my life I’ve been trying to figure out how to avoid such a fate. Your blog is very helpful in that process. Thanks a bunch.
Time to inaugurate the Kendrick school of cardiovascular medicine?
At least an MBE (my blood effort) or a knighthood? There are other far less worthy!
I think Baron Kendrick has a certain ring to it.
“Instead, the heart muscle undergoes a complex transformation into a different cell type. One that needs far less oxygen to survive and one that cannot do the contracting thing”
These cells that undergo this transformation sound suspiciously like cancer cells.
Perhaps. But they are not.
Do you have any reference to descriptions of the changes that these cells undergo?
“Do you have any reference to descriptions of the changes that these cells undergo?”
Perhaps Dr. Kendrick meant this:
Cell Biology of Ischemia/Reperfusion Injury (Kalogeris, 2014)
“Myocytes exposed to prolonged or repetitive intermittent ischemia may exhibit a second type of adaptive response that is characterized by a return to neonatal metabolic phenotype which favors the use of carbohydrates as an energy source. This phenomenon, wherein ischemic myocytes undergo a metabolic switch to a glycolytic phenotype with reduced contractile function and energy demands, is termed myocardial hibernation (Depre and Vatner, 2005, 2007; Slezak et al., 2009) (Fig. 6.3). As with myocardial stunning, hibernation allows myocardial cells to better withstand reductions in oxygen and nutrient delivery associated with subacute levels of ischemia in the absence of irreversible cardiomyocyte injury because contractile function is limited. The mechanisms involved in the assumption of this more ancestral phenotype appear to result from a reprogramming of cell metabolism that decreases energy utilization and via upregulation in the expression of stress and angiogenic proteins. Characteristic cell remodeling changes also occur in hibernating myocardium and include the appearance of polymorphic mitochondria, increased lysosome numbers, and decreased myofibril number. Increased vacuolar density and debris are consistent with autophagy, a mechanism of cell death that contributes to overall prolongation of survival of hibernating viable cells in ischemic organs by eliminating nonfunctional cells. Hibernating myocardium also contains apoptotic cells. Although these adaptive responses reduce myocyte number and contractile responses, hibernating cardiac myocytes can be rescued by restoring blood flow, which reprograms cell protein expression to normalize metabolism and contractile activity (Depre and Vatner, 2005, 2007; Slezak et al., 2009).”
Something like that, yes.
Hello Dr Kendrick. Your comment – “Perhaps most telling is the fact that people with plaques in their coronary arteries almost always have plaque in their carotid arteries, and vice-versa.” reminded me of a case study of a FH man in Brazil – Barros et al – http://tinyurl.com/h6teqqv
I realise FH presents its own set of special issues, and I’m not suggesting the man’s results were in any way common, but I remember being curious as to why the man’s carotid arteries were copping all the damage and his heart was apparently not too bad. The paper comments on similar clinical findings in a little girl (Palacio et al – Reference 20).
Sorry to throw in a FH tagent, but any thoughts?
In FH there are almost always coagulation issues going on as well, which would probably be relevant in these cases. I am aware that carotid and coronary atherosclerotic plaques have some subtle differences
I have been studying CVD for about 9 years. A very important opinion to me comes from Dr. Dwight Lundell. From one web site (http://www.whydontyoutrythis.com/2013/08/world-renown-heart-surgeon-speaks-out-on-what-really-causes-heart-disease.html) where he writes summarized as follows: Dr. Dwight Lundell is the past Chief of Staff and Chief of Surgery at Banner Heart Hospital , Mesa , AZ. As a heart surgeon with 25 years experience, performed over 5,000 open-heart surgeries. Inflammation in the artery wall is the real cause of heart disease. The injury and inflammation in our blood vessels is caused by the low fat diet recommended for years by mainstream medicine. Visualize rubbing a stiff brush repeatedly over soft skin until it becomes quite red and nearly bleeding. You kept this up several times a day, every day for five years. I have peered inside thousands upon thousands of arteries. A diseased artery looks as if someone took a brush and scrubbed repeatedly against its wall several times a day, every day. Simply stated, without inflammation being present in the body, there is no way that cholesterol would accumulate in the wall of the blood vessel and cause heart disease and strokes.
By the way I believe Coronary calcium scans of the heart tree are very important.
He saw inflammation. He didn’t ask what caused it.
Well, he seems to think it is the low fat diet. But even there, that is rather vague, because that’s not very specific.
Randell,
Thanks for that link!
All credit to this doctor for admitting that he got it wrong. For somebody in the public eye that takes courage. He too recognises the disaster that the SAD is although he doesn’t directly link any of the constituents to inflammatory conditions that he observed – perhaps he thinks it’s obvious. These days there is another factor which isn’t taken into consideration and that is GMO’s. These are alien to our biosystem and much has been written about the adverse effects they have. Are they also implicated in CVD? Would not surprise me but the American food industry or its branch office in Washington DC (FDA) isn’t going to check any time soon. Additionally he doesn’t mention insulin as a major factor, which given that the SAD results in excessive secretion is surprising. I’m not going to go over all the adverse effects that excessive insulin has – end up writing a book. It is very clear that excessive insulin is very damaging. For the sake of brevity I recommend that everyone who is not aware of just how damaging insulin can be and how it causes that damage reads Gary Taubes book Good Calories, Bad Calories (chapters 10 & 11 cover it). Excessive insulin with a lack of vitamin C and an imbalance in vitamins A, D & K2 and you have a recipe for disaster compounded by everything else that is inadequate in the typical diet. CVD is complex and has various triggering factors but, in my opinion, none more so than the SAD (or anywhere else where refined carbohydrates are consumed in excess) coupled with insufficient vitamin C.
Look up the PIMA Indians and their production of insulin and their risk of CVD
Anna and Barry – thank you for your comment.
About diet – read from here down “There is no escaping the fact that the more we consume prepared and processed foods, the more we trip the inflammation switch little by little each day. The human body cannot process, nor was it designed to consume, foods packed with sugars and soaked in omega-6 oils.” http://www.sott.net/article/242516-Heart-Surgeon-Speaks-Out-On-What-Really-Causes-Heart-Disease
To mention insulin from Dr. Lundell When your full cells reject the extra glucose, blood sugar rises producing more insulin and the glucose converts to stored fat.
What does all this have to do with inflammation? Blood sugar is controlled in a very narrow range. Extra sugar molecules attach to a variety of proteins that in turn injure the blood vessel wall. This repeated injury to the blood vessel wall sets off inflammation. When you spike your blood sugar level several times a day, every day, it is exactly like taking sandpaper to the inside of your delicate blood vessels.
While you may not be able to see it, rest assured it is there. I saw it in over 5,000 surgical patients spanning 25 years who all shared one common denominator — inflammation in their arteries.
Me thinks the likes of cardiology may not in the short term like where you’re heading with this. Angioplasty, CABG, and statins are so firmly entrenched and so profitable regardless of their abysmal outcomes and non existent scientific basis. However, like Popper said true revolutions usually come from the young or outsiders and you’ve proven through your works you should be listened to. Damn, we need more minds in the field like you!
Though, like the rest of your readers, I wait with baited breath your coming answers, I very much appreciate your method. The mental stimulation alone is worth following. But more importantly, the profound impact on society these answers could have is nothing short of astonishing and under appreciated, especially by physicians. Cheers!
Yes Mark, all well said, and I wish they’d fully adopt this method in schools.
Do you think the NHS really needs more money – or should just stop wasting it?
You are so right in my eyes!
Why are the outcomes for stents abysmal? It’s probably too daft a question to ask why the NHS continues to perform procedures that rarely work?
Because, if you stick a bit of ‘alien’ material into an artery, there is a tendency for the body to attempt to reject it. Also, if you have good collateral circulation, the stent achieves little by the way of improving blood flow. The reality is that stetns are moderately effective in an acute MI/blockage situation. However, in stable disease, they are utterly useless. But you can’t stop the boys when they really, really, want to play with their toys. And stents are the best toys ever.
Interesting comments. I always wondered. Have five of them in three sessions with stable angina. I seem to remember a paper that showed that standard?? medical therapy and stents had the same long term outcomes. Another paper (The Lancet13 August 1988, Vol.332(8607):349–360, doi:10.1016/S0140-6736(88)92833-4) showed that streptokinase plus aspirin were very effective (40% relative rate) over some 15 months. The paper is not Open Access.
Dr Kendrick, I find it encouraging that you have dealt wit the curious evidence that sometimes the clots develop after the heart attack rather than the other way round. I remember this subject arose a while back, and I wondered for a while if yet another pillar of medical science was about to fall!
You have clearly been very thorough in this study – it should get you a knighthood! Will you also try to write a peer reviewed paper about your findings?
Thank you for writing in this way, I, as a layman can begin to understand and explaining it all in several pieces makes you think about each part, rather than just rushing the conclusion.
What has struck me most is that we believe we, as “thinking” beings are in control, but this shows that our bodies are quietly (usually) working their way through our lives organising, planning and aiming to keep us going!
I have mentioned the role of microbes or fungi, respectively, in atherosclerosis, in the comment section of the previous post. (Fungi, because they are present in the plague, and the pleomorphic action of statins hits fungi too: statins block ergosterol (the fungal equivalent of cholesterol). But fungi would not be present and proliferate if nutrients were not plentiful in that niche. It must start with the very basic growth signals and ingredients and all points to iron, in that case.
Randomly on iron, seemingly off topic:
Iron mediates endothelial cell damage and blood-brain barrier opening in the hippocampus after transient forebrain ischemia in rats (Won, 2011)
“Blood cells are transported into the brain and are thought to participate in neurodegenerative processes following hypoxic ischemic injury. We examined the possibility that transient forebrain ischemia (TFI) causes the blood-brain barrier (BBB) to become permeable to blood cells, possibly via dysfunction and degeneration of endothelial cells in rats. Extravasation of Evans blue and immunoglobulin G (IgG) was observed in the hippocampal CA1-2 areas within 8 h after TFI, and peaked at 48 h. This extravasation was accompanied by loss of tight junction proteins, occludin, and zonula occludens-1, and degeneration of endothelial cells in the CA1-2 areas. Iron overload and mitochondrial free radical production were evident in the microvessel endothelium of the hippocampus before endothelial cell damage occurred. Administration of deferoxamine (DFO), an iron chelator, or Neu2000, an antioxidant, blocked free radical production and endothelial cell degeneration. Our findings suggest that iron overload and iron-mediated free radical production cause loss of tight junction proteins and degeneration of endothelial cells, opening of the BBB after TFI.”
And “iron deficiency” anemia diagnosed in Kawasaki disease means it is not being checked for iron in the place where it matters. Fungal connection to KD is emerging, too. Hepcidin – iron regulator and antifungal antimicrobial peptide is up in KD as well.
Bloodletting or leeches, anyone?
I have had a treatment where leeches were used. Uncomfortable but no horrible after effects!
Just in case the connection to iron, fungi and endothelial damage is not clear, here a study on exemplary fungal organism, Candida albicans:
Endothelial Cell Injury Caused by Candida albicans Is Dependent on Iron (Fratti, 1998)
Only trouble with your stuff Dr Malcolm is that you risk giving many GPs a good name which quite frankly, many do not deserve. However you also get good plumbers, just like any other trade! The complexity of human plumbing only makes the likelihood of poor understanding of human plumbing all the more likely. (I am non medical trained, 2 stents fitted 8 years ago, ditched the 5 pills 3 months later and going strong – I was informed by GP that the pills were for life (included statins of course) and he got very angry when I informed him of my choice. My research included yours. Best wishes
Thank you, I hope you continue to go strong for many years.
Thanks for sharing your inspiring story. Were yours bare-metal stents? or drug-eluting stents?
what kills people at the end of the day is lack of oxygen I guess, so lack of blood supply to the blood vessels could be the underlying process? Avastin prevents oxygen getting to artery wall. EPC’s localise to injured vessels (injured by hypoxia) and secrete angiogenic cytokines to increase blood supply, so the inflammatory immune response is the bodies attempt to help, but then over time everything gets compounded, as in the multistep development of cancerous tumours?
Dr Kendrick
Another excellent thought provoking essay; you have really stimulated by interest to the Next: Some answers.
A couple of points: I know you do not accept “inflammation” as a cause and I agree. It is simply a reaction to many “causes”. However, it does reflect the reasons why some drugs seem to show a trivial benefit; for example statins and their effect on reducing NF-κΒ (Graveline). But this is not a “cure”, simply alleviation of a symptom or sign, a common result of many so-called “cures”. A recent paper (JAMA Intern Med. Published online January 19, 2016. doi:10.1001/jamainternmed.2015.7655) in the conclusions state: In a contemporary, community-based cohort, bradycardia was generally not associated with incident CVD or mortality except for a potential adverse association between bradycardia among those taking H[eart]R[ate]-modifying drugs, my eg, ACE-inhibitors like lisinopril, confirmed by MHRA – arrythmia
The second point relates to meta-analyses: As with all meta-analyses, the main limitation of this work relates to publication bias. If this includes “selection bias” it is absolutely true. SELECTION in statistics is a no-no. And this true of papers as sample units as Ravnskov has demonstrated. They are, of course, for increasing “N” and therefore the probability of a “significant” response, undetected in the individual studies.
Dear Dr Kendrick
I am sure I am not alone in thinking that as you battle for truth and change you subject yourself to the kind of potential stress that whistle-blowers and the bullied endure. Do hope that the goodwill of all your bloggers helps.
Thank you, but I am fairly robust. I am reminded of a comment made to me some time ago. ‘You know you are over the target when the flak is at its greatest.’ Thus, I welcome attacks, and the more the merrier. It means that I am exactly where I need to be.
One more try, then I’ll go back to my seat and watch from afar. I think it all goes back to the initial post asking why RBCs are found in atherosclerotic plaque. It seems microvascularisation of the plaque may be useful, or at least benign, however, when the vascularisation becomes leaky, RBCs get into the intima, and this sets off a whole bunch of nasty stuff with the eventual rupture of the thrombus. So, without leaky microvascularisation, no CVD—just benign atherosclerosis like is seen in the Massai. I’m guessing there’s a common trait to patients with RA, SLE, Kawasaki, and those on Avastin, or people with T2DM or coal miners, etc, that causes the microvasculature inside their plaque to become leaky. This would be the cause, no?
Interesting discussion. The autopsy pathology, at least in dead folks, rarely shows a clot. Maybe they are microscopic and not visible to the naked eye. Most people with coronary artery disease also have hypertrophy of the heart muscle, related to hypertension. These folks usually do not die until they suddenly go into ventricular fibrillation. If an infarction occurs first, and if the victim survives long enough, a spectrum from coagulation necrosis to acute inflammation to granulation tissue to scar tissue in the myocardium is seen depending on length of survival.
Not exactly true. Calcification can make its identification difficult. In my experience in the non-calcified artery patient transverse slicing identified a thrombus in the majority of cases.
Dr. Pfalzgraf,
I, for one, am delighted to see MDs on this blog.
Most people with coronary artery disease also have hypertrophy of the heart muscle, related to hypertension.
Would I be correct in assuming that hypertrophy of heart muscle is a feature of Congestive Heart Failure?(CHF) I ask because some years ago both the US CDC and the NHBLI announced that there was an epidemic of CHF with a graph to prove the point. When I saw it that the rise in incidence seemed to follow the rise in cholesterol lowering therapies, including the early years of statin use (1987 onwards) but it was rapidly removed without trace from both websites. I asked the CDC why it was taken down but they deigned not to reply. I have been assured by a US cardiologist that this disappearing epidemic is very much alive and well.
I must say that in my experience, epidemics rise, peak and then frequently fall; they never disappear on the rise! In this instance one suspects that there is an association between myopathy and statin use, , something that Big Pharma would not like to see and with the “revolving door” system in the US……….Well! Also, in that muscular adverse reactions are more severe and common in athletes and the heart being a very active muscle, one wonders. A lot of astroturfing going on perhaps.
The tunica media injury appears to be a common thread among the aforementioned associated conditions. Medium sized artery involvement is also a common thread. Is mechanical injury (such as prolonged hyperextension of the arterial wall as in chronic hypertension), chemical (direct injury to the smooth muscle), inability to protect the tunica media from intimal injury, or an autoimmune attack to the muscle the specific area of concern? The location of the origination of plaque (bifurcation of artery) must play some role, though why are carotid and coronaries especially susceptible.
I found this article :
https://dash.harvard.edu/bitstream/handle/1/23031209/Requiem_Final.pdf?sequence=1
Basically it’s now more common to see the fibrous cap intact after an MI, so a burst “vunerable plaque” was not the cause of the event. I’m wondering if it’s more a change in our observation rather than some miracle change in plaques over 10 years …
Thanks for the link. I too wonder; I hope that the truth will out but often such research is stubbornly ignored.
A common problem I see in my practice is diabetic retinopathy both in Type 1 and 2 diabetes. Causes include oxidative stress from reactive oxygyen and nitrogen species (ROS/RNS) as well as ischemia from small blood vessel disease. Microaneurysms and micro hemorrhages are seen early prior to symptoms and neovascularization as an end result. AntiVEGF drugs are increasingly being used with considerable efficacy in these patients. These patients are at increased risk for incident MI and stroke independent of other risk factors. Common micro and macro vascular pathophysiology between retinopathy and CVD appears to be the case.
Ref:
Diabetic Retinopathy and the Risk of Coronary Heart Disease DIABETES CARE, VOLUME 30, NUMBER 7, JULY 2007
Dr Caldem
Causes include oxidative stress from reactive oxygyen and nitrogen species (ROS/RNS)
I thank you for the link.
I am intrigued with the possible association of diabetic retinopathy and MI and stroke with ROS since statins through the depletion of CoQ10 may well reduce the Total Antioxidant Capacity(TAC) of blood. Diabetics tend to have a lower level of TAC than non-diabetics,(http://www.knightscientific.com contact Dr Jan Knight) which suggests higher ROS, thus supporting your views
Caldem,
Before we, on our own without a shadow of a doubt, 6 years ago, realised that my wife was seriously diabetic she had consulted several doctors about her severe IBS, her very severe peripheral neuropathy, her lost night vision and the glaucoma she then was diagnosed with. No one though suggested diabetes or a standard glucose test. In hindsight I think this is almost unbelievably ignorant.
Anyway we decided from one day to the next to cut all carbs, going strict LCHF.
The result.
– In THREE DAYS her 30 year old problems with the IBS disappeared.
– In half a year her night vision returned so she was able to drive her car in darkness.
– In one year her peripheral neuropathy had completely resolved.
– In one year they couldn’t find any traces of the glaucoma.
– Her blood sugar values are today just perfect
– And no medicine whatever.
– But with any carb mistakes her diabetic is back – doesn’t seem to go away.
Isn’t my wife just an “unbelievable” anecdote and since no “science” is involved it can easily be dismissed by Big Pharma?
But of course I can never never prove that it was our Hippocratic approach ,”Let the food be your medicine and your medicine your food!”, that worked “wonders”.
I forgot about the blood pressure – today amazingly steady at 110/60 for both me and my wife.
Wonder if life expectancy changes are to be expected, with the love of sugar – post war and post coupons.
TS,
I guess this is the problem if I understand you right.
It is tough to change your lifestyle if you are not utterly convinced that you have. If a doctor tells ‘why don’t you take a pill instead’ instead of challenging your sweet tooth most people are easy victims of self delusions.
Cancer. It’s very good at providing for its own blood supply. I worry for those on therapy that blocks angiogenesis. The treatment would also cut their prospective “collateral circulation” lifeline, would it not?
A rock and a hard place.
Atrial fibrillation leads to clots within the left atrium due to blood chemistry changes and endocardial remodelling. This has been the recipe.
Lone atrial fibrillation is the name given to AF without “known” cause or underlying heart conditions.
The more that is discovered about AF, the more it seems there is no such thing as “lone”.
It seems that what you are (hopefully!) about to reveal as the cause of CVD will also apply, downstream, to AF.
Dr Kendrick’s latest post leaves me puzzled and worried. My husband age 66 was diagnosed with AF around 5 years ago purely by chance (routine echocardiogram before hernia op) Asymptomatic, aside from slight breathlessness on long distance running. 3 years ago he had a stroke (from which he is fully recovered.) and slight awareness of palpitations on occasion. As all the heart investigations reveal heart function and appearance as clean as a whistle, I always assumed it was lone AF. He ran ultra marathons in his youth and there seems a strong correlation with this and lone AF. I argued strenuously with his GPs and consultants who kept trying to put him on statins, aided very substantially with Dr Kendrick’s material, that statins would not only not help his condition but actually endanger him by raising risk of haemorrhagic stroke. (Now they have given up pushing the statins, but his latest lipid tests prompted them to send him a very low fat diet sheet because of his “slightly raised” TC: viz 7! Never mind that his glucose levels, trigs are 0.82, HDL 2.1 and ratios 3.3. i.e all completely fine. )
Question for Dr Kendrick: What tests of the heart have they missed, if you say there is always some evidence of CVD after stroke? He has repeat echocardiograms, ECTs etc and had an MRI immediately after the stroke and gets a clean bill of health on all.
He is on warfarin (which I worry, in the absence of any K2 supplements, will ironically increase risk of calcification of arteries.) He had ablation, which did not cure or improve the AF.
As Malcolm hasn’t answered yet, I will. What Malcolm means is that with stroke due to Arterial disease, there is very frequently (but I can add, not always) arterial disease in the heart. On the other hand, if the stroke is due to atrial fibrillation, which in many cases is not due to arterial disease, then arterial disease of the heart would not be necessarily present at all.
I’m a retired pathologist.
Thanks for your prompt response. I did read Dr Kendrick’s preliminary statement re AF but was then confused by this:
“We studied the risk of heart disease following a stroke in those patients with no cardiac history, thinking that this overrode the first comment and applied to all stroke patients with no cardiac history. ”
Thanks for clearing that up.
To: Dr. Malcolm Kendrick’s remark on Dr. Dwight Lundell
“He saw inflammation. He didn’t ask what caused it.”
Here is more from Dr. Dwight Lundell on the linked web site
Inflammation is not complicated — it is quite simply your body’s natural defence to a foreign invader such as a bacteria, toxin or virus. The cycle of inflammation is perfect in how it protects your body from these bacterial and viral invaders. However, if we chronically expose the body to injury by toxins or foods the human body was never designed to process,a condition occurs called chronic inflammation. Chronic inflammation is just as harmful as acute inflammation is beneficial.
What are the biggest culprits of chronic inflammation? Quite simply, they are the overload of simple, highly processed carbohydrates (sugar, flour and all the products made from them) and the excess consumption of omega-6 vegetable oils like soybean, corn and sunflower that are found in many processed foods.
Blood sugar is controlled in a very narrow range. Extra sugar molecules attach to a variety of proteins that in turn injure the blood vessel wall. This repeated injury to the blood vessel wall sets off inflammation. When you spike your blood sugar level several times a day, every day, it is exactly like taking sandpaper to the inside of your delicate blood vessels. On veg oils – If the balance shifts by consuming excessive omega-6, the cell membrane produces chemicals called cytokines that directly cause inflammation.
Dr. Lundell believes that statin drugs are NOT the solution to heart disease and that drug companies are already aware of this. “Big Pharma won’t promote alternate solutions because they have no profit motive.”
Second opinions – Gabe Mirkin M.D. DOXYCYCLINE FOR HEART DISEASE A study from the Beth Israel Medical Center in New York shows that very low-doses of the antibiotic, doxycycline, reduce blood levels of C-reactive protein (CRP) by nearly 50 percent in patients hospitalized for blocked arteries leading to their hearts.
A study in The New England Journal of Medicine showed that women with high levels of a blood test called C-reactive protein (CRP) which measures inflammation are twice as likely as those with high cholesterol to die from heart attacks and strokes.
Dr. Paul Ridker of Brigham and Women’s Hospital in Boston found that CRP did a better job of predicting heart disease risk than cholesterol, which tells us that inflammation is more important than blood fat levels in predicting heart attacks. This study followed 28,000 women for eight years. Seventy-seven percent of those who had heart attacks or strokes had cholesterol in the normal range and 45 percent were in the ideal range. The fatty plaque buildup that lines blood vessels often becomes inflamed because your white blood cells attack your own tissue rather than just germs.
Ridker found that inflammation was increased in those at risk of CVD. People with inflamed and swollen ankles are at high risk of ligament damage. I would advise checking that you have got your causal chain the right way round.
Creases in the earlobe are very close to 100% correlated with CVD. Also, people over 50 tend to have creases in their earlobes.
I think we need a drug to keep earlobes from creasing, people will stop having heart attacks.
Galectin-3 blockade eases cardiac inflammation and fibrosis. (Dr. Jose Jalife) Seems like a neat fix, but where does the galectin-3 come from in the first place?
It seems curious to me that insulin hasn’t made an on-stage appearance in the main posts or any of the comments yet, especially since chronically elevated insulin seems so heavily associated with all things CVD, as well as lots of other bad stuff. I know that association is not cause, however I thought Dwight Lundell among others has pointed put that insulin is part of activating cellular pathways that allow inflammatory processes to take hold in the endothelium.
I’m really looking forward to parts three and beyond, just like everyone else! I’m going to search your older posts for insulin references…
Because I am talking about process at the moment, not causes (except indirectly)
High insulin level appears to be involved in many conditions but the NHS does not seem concerned. They do not generally measure insulin in patients because “the treatment iis the same in all cases (presumably all diabetes cases) irrespective of insulin levels. Odd but there it is!
Not so much on the build up and cause, though I believe it could be helpful with prevention, I’ve been reading about our bodies electrical system and how our body uses it to signal and program healing. One of the pioneers in this work was Dr. Robert Becker. He was somewhat well known in the past. He wrote a few books about his work in regeneration. He basically was interested in studying why it was a human could typically regenerate bone, but with other tissue, scar tissue formed. What Dr. Becker learned is that all tissue can regenerate under proper conditions. He also wrote about his great disgust with the corruption he saw in the research field.
One of his better known book was The Body Electric
“The Body Electric: Electromagnetism And The Foundation Of Life”
He has a chapter in this book on regenerating damaged hearts. He says he was able to heal the hearts in animals where damage had occurred. He was confident the same could be done with the human heart. He complains that he and others that performed similar heart healing regeneration work were having difficulty being believed and published, which I can imagine to be true.
Because the belief that a clot is the sole reason for CVD MI (as opposed to arrhythmia or severe spasm of the coronaries causing ischemia) must these clots form in the collateral circulation since these are the vessels that are likely supplying the bulk of the O2 to the heart muscle? Occluding the stenotic main vessels over time will often lead to no untoward effects if sufficient collaterals have become established. Another reason why preventive stents and CABG are so ineffectual?
Sorry about the flight of ideas, but your posts are so damned interesting.
Might this be appropriate to get your idea out there?
http://www.onebraveidea.com/about/
Another paper showing microbial connection (fungal DNA was unfortunately not checked for in this study). Though microbial biofilms are usually a result of co-operative work of fungi and bacteria.
Bacteria Present in Carotid Arterial Plaques Are Found as Biofilm Deposits Which May Contribute to Enhanced Risk of Plaque Rupture (Lanter, 2014)
“The association of bacteria with atherosclerosis has been only superficially studied, with little attention focused on the potential of bacteria to form biofilms within arterial plaques. In the current work, we show that bacteria form biofilm deposits within carotid arterial plaques, and we demonstrate that one species we have identified in plaques can be stimulated in vitro to undergo a biofilm dispersion response when challenged with physiologically relevant levels of norepinephrine in the presence of transferrin. Biofilm dispersion is characterized by the release of bacterial enzymes into the surroundings of biofilm microcolonies, allowing bacteria to escape the biofilm matrix. We believe these enzymes may have the potential to damage surrounding tissues and facilitate plaque rupture if norepinephrine is able to stimulate biofilm dispersion in vivo. This research, therefore, suggests a potential mechanistic link between hormonal state and the potential for heart attack and stroke. ”
and the iron link:
” We believe that in an atheroma, a biofilm dispersion event could result from a sudden increase in the availability of free iron, an essential nutrient, released from its bound state by elevated levels of norepinephrine. The induction of a biofilm dispersion response within an atheroma may, therefore, have the potential to induce collateral tissue damage resulting from the localized release of degradative enzymes by the participating bacteria. This response, in turn, could influence the integrity of the surrounding arterial tissues, leading to an enhanced risk of plaque rupture and thrombogenesis.”
Hi Diana, thank you for the links and explanations.
Maybe there is a causal link between the sinusitis, biofilm breakdown and stroke.
E.g. http://www.nextavenue.org/surprising-connection-between-your-sinuses-and-stroke/ notes an increase in the odds of suffering a stroke (observational ?) in those suffering from chronic (34%) and occasional acute (39%) sinusitis. The article doesn’t make the connection but, if you suffer from sinusitis the chances are that you reach for a decongestant which typically enhances norepinephrine (Quote from wiki “The vast majority of decongestants act via enhancing norepinephrine (noradrenaline) and epinephrine (adrenaline) or adrenergic activity by stimulating the α-adrenergic receptors.”).
As a former sufferer of chronic sinus trouble over many years (polyps etc) I can tell you the level of stress it causes on daily basis is enough to cause a stroke, no trouble at all. Basically, you can’t breathe,sleep or eat – basic necessities of healthy living. Or think straight. And you generally have a headache. Really not so surprising!
Stephen Rhodes
“Maybe there is a causal link between the sinusitis, biofilm breakdown and stroke.”
Isn’t sinusitis another example of (pathogenic) microbial biofilm? Because there are “good” biofilms, mind you.
Re noradrenaline. Think interkingdom signalling. Microbes are listening and reacting to the stress hormones produced by the host.
Hormones and drugs act via (gut) microbial flora, so do statins.
Dr. Kendrick,
I must say I was surprised by your comments of “boys and their toys” relating to stenting of the heart.
I had three stents inserted in November 2014 after having previously been misdiagnosed by a Cardiologist as having “a stiffening of the heart” which they could do nothing about, being discharged and sent home to ponder on that. Thank goodness someone else reviewed my file at a later date and contacted me after finding that something could certainly be done.
After being examined by the Head Registrar he set the ball rolling for an angiogram, followed quite quickly by the angioplasty. After laying on the theatre table for roughly an hour and a half for the procedure, which I am sure you are familiar with, I was shown the before and after xray pictures which astounded me. An artery (LAD) which before was more or less completely blocked was now clear again. A bit of a miracle in my estimation, performed by dedicated medical staff who are doing a wonderful job.
The breathlessness which had troubled me for a very long time was now eased, and although I have an erratic heartbeat, which is handled by medication, I am pretty fit for my age but who knows what I would have been like without the stents?.
I love your blog Dr. Kendrick; it encouraged me to stop taking statins after suffering dreadful side effects, but I was disappointed by your comments regarding stents.
Sincerely, Sylvia Brooke.
On Thu, Jan 21, 2016 at 6:56 PM, Dr. Malcolm Kendrick wrote:
> Dr. Malcolm Kendrick posted: “[By heart disease I mean, the development of > atherosclerotic plaques in large arteries. Mainly the coronary arteries > (supplying blood to the heart) and carotid arteries (supplying blood to the > brain). This, I will refer to as Cardiovascular Disease CVD. N” >
Sylvia,
My LAD i also completely blocked since 16 years and the other two coronary arteries are blocked as well so there was “no use” in “playing with the stents” as they told me. My case was a typical three main arteries significant CVD as stated in the angiographic report. Thus a comprehensive by-pass grafting was the obvious offer to me which I however courteously turned down together with all the medications but which I didn’t do before having done my own proper “research”.
What, to my surprise, I then arrived at, all those years ago, about these two types of medical interventions that there was very little to be achieved but mostly only medical negatives.
I didn’t doubt the technical skill employed in the surgical procedures; “great impressive toys” even appreciated by an engineer as myself. There was however no guarantees for any relief from my angina, a 10 % typical toll on my mental capacity was forecast due to the turn off of the heart during the operation and of course, as Dr Kendrick pointed out, you introduce ‘foreign’ pieces of tissue which your immune system naturally tries to reject if you don’t suppress your immune system severely by medication all the rest of your life. You enter a down hill medical slope and the grafting procedure typically has to be renewed every eight years and in my case I would by now have been in for a third round although not very many survives more than two open heart surgeries but of course Big Pharma would benefit greatly.
So I had to change my way of life instead.
Anyway I am now, after my morning ‘bullet coffee’, to continue with my sharpened chain saw on those two large trees I downed yesterday and to chop them up in the following month to get dry firewood for the next winter. But my arteries are still blocked so I can not work as hard as before my heart attack 16 years ago.
This is still a life to enjoy together with a Scotch, well seasoned, whisky now and then in front of my fireplace.
Gosh, I very much doubt there are many people who would be brave enough to do what you have done Dr Sjoberg. It’s one thing to review your lifestyle and change it for the for the better, but most would do that after they’ve had the medical intervention, whatever that may be, not instead of!
Regardless of my firm convictions I’m sure I’d just wither in front of a cardiologist or cardiac surgeon. I’d then live in fear because I’m sure my instincts would be telling me I’d done the wrong thing – stuff of nightmares.
I so admire the courage you have had in your own convictions.
Peggy,
Thank you for your kind regards!
I think you are right again.
Few dare confront the medical “experts”. In all history from the early shamans on to the present day doctors they have been trusted as to know what they are supposed to know. We are talking about religious beliefs from both sides and the high priests (read Big Pharma) are establishing the dogmas to follow.
Nothing to do with science only money.
And now the trees are ready for chopping.
Well done, Goran.
I believe I would do the same and I admire your refusal to be a good patient and unquestioningly take what they wanted to give. My attitude changed after my step-mother had a serious operation that the surgeons deemed a success, but the poor woman never had another day worth living. She’d entered hospital full of life and left in an ambulance and attached to an oxygen cylinder. I began to wonder at the medical definition of success.
May be of interest
DOI: http://dx.doi.org/10.1016/S0140-6736(15)00727-8
The Lancet $31.50 to read???
Revascularisation is recommended for most patients presenting with acute coronary syndromes,[1,2] with percutaneous coronary intervention the most common procedure. Besides dual antiplatelet treatment with aspirin and a platelet P2Y12 blocker (eg, clopidogrel, prasugrel, or ticagrelor), parenteral anticoagulation is mandatory in patients undergoing this procedure. Heparin, low-molecular-weight heparin, and the specific thrombin (factor II) blocker bivalirudin are currently used for anticoagulation.
To read this article in full you will need to make a payment No Open Access here; $31.50 for two pages.
And from the Lancet paper
Odds Ratio Confidence Interval Calculation For 2×2 Contingency Table
The Lancet13 August 1988, Vol.332(8607):349–360
S + A = streptokinase plus aspirin as decribed
S + A Placebo
Dead 343 568 911
Alive 4292 3732 8024
Check 0
Total 4635 4300 8935 0
Odds ratio 0.525083
95% confidence interval from 0.456018 to 0.60461
p = 1.63E-19
Paper simply ignored but 1987-88 was the time that statins were starting to be used.
mikecawdery
Remember that statins also effect the same pathway as NFkB, sterols, Heme A, as well as cholesterol and uqiquinones. The small subset of patients who actually may have benefited from statin therapy likely were affected by one of these other pathways (NFkB particularly). On another note I am still amazed at how many docs prescribe statins without CoQ10 or any mention of it!
I am well aware that statins disrupt the very ancient mevalonate (back to the cenancestor) pathway, thereby distrupting the metabolism of many vital molecules as you say and others such as the selenoproteins, dolichols. What annnoys me is that Merck was well aware of the problem of increasing ROS through statin use when they took out patents for combining CoQ10 with both their statins. This reluctance to admit the importance of anti-oxidants is reflected in the HPS study (a 2×2 factorial design) where the second treatment was an anti-oxidant cocktail MINUS CoQ10 despite their simvastatin/cCoQ10 patent!
It all goes back to money and status – the patients are nuisance -they develop adverse reactions, don’t respond as required (5 tImes as many died, despite therapy, as were saved) . The 1988 Lancet paper was more effective but was ignored – no money in aspirin and streptokinase!
I have no clue about any of this, so instead I made a list and I am now ready to play buzzword bingo when Dr K starts his long-awaited explanation:
*acute vs chronic inflammation
*autoimmunity
*cortisol actions: insulin antagonist, anti-inflammatory, opposes increased capillary permeability of acute inflammation, increased leukocytes, reverses macrophage activation
*HPA axis, steroid use down-regulation and cortisol dysfunction
*NOS isoforms: endothelial and neuronal vs inducible
*macrophage activation and NO release
*upregulated NO, reduced cortisol, hyperimmune vicious circle
*blood pressure differences arteries/veins
*endothelial injury
*importance of inflammation for healing / disruption of natural repair caused by anti-inflammatories
*Role of vitamins (C,D,B12)
*Two types of SLE: with plaque/without plaque; antibody levels, chronic low grade inflammation/aggressive autoimmune treated with potent immunosuppression
I give up as my attempts are laughable. It’s summat to do with cortisol and inflammation and repair and antibodies and autoimmunity and nitric oxide and blood pressure.
or not.
Don’t make us wait too long Dr K.
The pressure of all those blood bits being forced against the walls of the vessels by the tension of the vessels themselves. All that turbulence. All that wear & tear. Gotta heal that and reinforce it somehow. Cholesterol. Calcification. But why that extra blood pressure in the first place?
Neovascularization?
I can’t wait to read part III
I hope this time my comment is published instead of deleted.
“Excessive intimal hyperplasia in human coronary arteries before intimal lipid depositions is the initiation of coronary atherosclerosis and constitutes a therapeutic target” (link)
Thank you for your reply. It’s interesting you mentioned swollen ankles. A good friend of mine developed swollen ankles without insult and shortly after had a heart attack.
Any theory on CVD I believe needs to factor the following. These slides from Peter Attia MD website.
http://high-fat-nutrition.blogspot.ca/search/label/Arteriosclerosis%20%281%29%20in%201957
Notice the picture of the coronary artery of an infant who was 4 days old among others His comment – To me it’s really weird how a cardiologist can think that LDL causes this, and that statins might stop it.
I believe this blows vessel wall tension to hydrostatic pressure etc. (BP) out the window for all cases.
old adage, “the best cholesterol number is one which hasn’t been measured…”
Not Peter Attia. Petro Dobromylskyj, always known as Peter.
Re Hyperlipid’s post: the Prussian blue staining showing GAGs in 1957 study is VERY interesting. Does it possibly have anything to do with so called “primo vascular” system? PVS is a novel threadlike system of ducts running often inside, or along the blood and lymph vessels. Hyaluronan is a PVS marker too!
50 Years of Bong-Han Theory and 10 Years of Primo Vascular System
http://www.hindawi.com/journals/ecam/2013/587827
Evidence for the Primo Vascular System above the Epicardia of Rat Hearts
http://www.hindawi.com/journals/ecam/2013/510461/
I just came to wonder if our energy metabolism may have an important role in the “process” now at charge.
Anyway I got an interesting newletter this morning from Mercola with an interview with Rhonda Patrick, PhD and a biomedical scientist, who stresses the importance of “healthy” mitochondria to fight the “ageing” of tissues – interesting!
A lack of “healthy mitochondria” really is aging, more-or-less, at the tissue level, and considering a long-term average (decline). For an introduction and some clues see “Power, Sex, Suicide: Mitochondria and the meaning of life” by Nick Lane, or certain of his papers (which are available from his eponymous web site). The summary is: energy -mostly produced by mitochondria in health cells is vital, sex is needed to match mitochondrial and nuclear DNA, and apoptosis which is of mitochondrial origin is necessary to manage cooperation in multi-cellular organisms.
This all relates to what I was getting at in my earlier reply about NO (which is clearly related to processes in the arteries) and mitochondria. While aging is the long term trend, the mitochondria in a tissue can recover, through either competition of mitochondria within cells, or apoptosis of the cells with the weakest mitochondria and replacement from stem cells with (hopefully) better, undamaged mitochondria. Eventually, however, even the strongest mitochondria in some tissues are too weak, and that is old age (and brings the diseases of age). Insulin (one example among many) accelerates this aging process. Thomas Seyfried will tell you how the presence of weak mitochonria in a tissue is the usual route to cancer. There are lots of dots to join of course.
I suspect that a lot of the variation in response to chronic disease is due to whether the tissue(s) concerned have, by sheer chance, ended up with stronger or weaker mitochondria from the egg. Even genetic twins differ in that.
Ken
Which brings us back to ROS damage through depleted CoQ10 of mitochondrial DNA and even nuclear DNA. Dr. Graveline has researched this as I remember.
ROS, yes, but not only due to depleted CoQ10, rather resulting from anything that causes a similar imbalance of the redox potential in complex I.
As just one example, and the reason I mention insulin, I have in mind something broadly along the lines of the ideas in “Role of Insulin Resistance in Endothelial Dysfunction” by Muniyappa and Sowers – Rev Endocr Metab Disord. 2013 Mar; 14(1): 5–12. (open access). This paper has a perfect set of keywords for the context: Nitric Oxide; Insulin Resistance; Endothelial Dysfunction; Metabolic Syndrome.
Of course this is only the tiniest part of the story, but I can’t help but think it matters.
Ken
Including the seleno-proteins, another casualty of statin therapy
I find it interesting that a ketogenic diet reduces CVD risk as I know that cells that create energy through fermentation rather than oxidative phosphorylation escape apoptosis. Is part of the process that these cells that have changed to adapt to a low oxygen environment and can’t contract, don’t die? i.e. there’s no apoptosis?
Dont know the answer to that, but it sounds plausible
Did anyone see Trust me I’m a doctor this week, in which it claimed olive oil, virgin or not improved markers in heart disease. About 20 ml a day, raw was recommended. Other oils did nor show the changes. When you consider how beautiful this tree is, drove through such groves in Thassos, with family, including my lost brother in law, stopped at a taverna for a simple lunch, olive oil included of course. Day I won’t forget. Sorry have gone all nostalgic.
Sylvia, I read about it and hope it’s true. I use olive oil most days on my salad, butter for my vegetables and coconut oil with my yoghurt and cream.
SURROGATE markers ? T t t !
Olive oil is part of the traditional Mediterranean diet the whole of which has been proven to decrease mortality in myocardial infarction survivors, and patient, (not patent) oriented outcomes in everyone. Period. We shouldn’t even listen to surrogate markers.
re: Other oils did not show the changes.
Having read a number of fish oil papers, the majority of trials don’t use enough (less than 2 grams/day of DHA+EPA) and/or don’t shift at least some of the participants off the official full-time glycemic diets loaded with other toxic industrial oils. Be suspicious of oily papers.
On olive oil, I suspect it’s not as health-giving as fish oil, and the market is awash in fraud and adulteration. Without some independent testing to rely on, there’s a good chance any random brand of OO consists largely, if not mostly, of the inflammatory Omega 6 PUFAs you may be actively avoiding.
Largely agree with comments on oils, it is nor entirely new data. Mercury and other toxins in fish, so that is also a worry. Unless we are eating food from Highgrove it is a bit Russian roulette.
“Look up the PIMA Indians and their production of insulin and their risk of CVD” – Dr Kendrick, Jan 23 (10:17).
Dr. Kendrick, I’m assuming that you are referring to the studies where the PIMA Indians where reported as having higher rates of T2D but lower rates of CVD than the white population such as:
Click to access 987.full.pdf
http://diabetes.diabetesjournals.org/content/25/7/561
I’ve read about the PIMA Indians and the apparent paradox of a high incidence of T2D but a lower than expected CVD/CHD and, to borrow an expression from your book – put it on the upper shelf. For those of us that are not in a position to see the raw data, or in a position to do our own research other than by reading, then when something is reported that goes completely against massive observation evidence my reaction is to assume (until proven wrong) that there is a mistake. Unless there is some fundamental difference in the PIMA Indians biochemistry then CVD/CHD and T2D go hand-in-hand.
I think the SHS is the study that most people interested in the PIMA Indians are likely to turn to and here we find that the conclusions from earlier studies re CVD/CHD and the white American population are now recognised to be wrong. Quote:
“When this study began, people thought that American Indians were somehow protected from heart disease and had lower rates,” said Barbara Howard, Ph.D., a principal investigator for the study and a researcher with the MedStar Health Research Institute in Hyattsville, Maryland. A review of records from the Indian Health Service from the 1960s showed very low rates of heart disease, noted Dr. Howard, who is also a professor of medicine at Georgetown University School of Medicine in Washington, D.C.
“The Strong Heart Study proved that these earlier assumptions were wrong,” she said. “Heart disease is no longer a rarity in the American Indian population and more intensive efforts are now needed to prevent and reduce its burden.”
Source http://www.nhlbi.nih.gov/news/spotlight/fact-sheet/strong-heart-study-targets-high-rate-heart-disease-among-american-indians
For those that are interested a link to SHS http://strongheart.ouhsc.edu/ and a couple of reports https://www.nhlbi.nih.gov/files/docs/public/heart/shs_db.pdf http://strongheart.ouhsc.edu/S-3.pdf
My original interest in the role of insulin was sparked by a Dr. Mercola article many years ago http://articles.mercola.com/sites/articles/archive/2001/07/14/insulin-part-one.aspx. (This will strike a chord with Dr. Göran). This was followed up by others (link not obvious from the first so here’s the second http://articles.mercola.com/sites/articles/archive/2001/07/14/insulin2.aspx).
I very much look forward to reading your understanding of the fundamental process of CHD/CVD. Linus Pauling/ Dr. Rath and many others such as Chris Masterjohn (natty little slideshow here http://www.slideshare.net/ancestralhealth/ahs-slideschris-masterjohn) have detailed the process as they see it.
You’re correct that many of us here, including me, have focused on cause rather than process partly because it is difficult for the lay person to find sufficient information or have an adequate understanding of the biochemistry involved to do otherwise (if confusion/disagreement reigns within the professional world after billions of expenditure then Joe Public doesn’t stand much chance). However, in my opinion, it is not necessary to know the full story when there is massive observational evidence available to indicate what represents the greatest risk e.g. You do not need an understanding of how an automotive engine fails if it loses all of its oil as there is a clear link between no oil and a failed engine.
Don’t get me wrong. I don’t like insulin (except in the correct amounts in the correct places). However, the PIMA Indians are interesting from many aspects. Firstly, they over-produce insulin before they are obese and/or diabetic. Secondly, they did have a much lower rate of CHD than the surrounding population. The rate in the surrounding population has now fallen, to match the PIMA Indians.
Dr Kendrick …reading the last chapter again and I’m starting to look at the stress process and getting my head around so much …. So can stress cause hormones to release? Causing bacteria/infection causing arterial plaque to fragment/infect (pseudomonas aeruginosa) and biofilms disperse when exposed to free Iron? So can the stress hormone (norepinephrine) release Iron? Causing this? …. can increased levels of Iron be brought on by stress causing P aeruginosa to excrete enzymes the break up the polymer matrix that hold the biofilms together which then causes stable plaque to break off causing arteries to block? Thank you ….
The effect of pancreatic glucagon release on the heart, giving a positive inotropic and chronotropic effect when stress affects the hypothalamus and adrenal glands?
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3281544/ (Fig 1 is very good to look at.)
Sylvia, Dr Kendrick made his remarks about stents in reply to my question.
I can imagine it must be disquieting to hear a negative view of a treatment you’ve had, but I want the truth, however uncomfortable. Otherwise we continue to do the same thing whether it makes sense or not. I’m afraid I agree that ‘boys’ and ‘toys’ seems appropriate when we continue to put people through a stressful procedure when there’s no evidence or trial to support it. Several other sources have given the same information, including NHS cardiologist Dr Aseem Malhotra in the talk I’ve linked. The talk is about sugar but he refers to stents and statins after 27.30 minutes.
My attitude is that I would only submit myself to an operation if the benefit is clear. I’m in Goran’s camp on this and grateful for the clarity of Dr Kendrick’s answer. I truly hope you’ve benefited from your stent, but I doubt you would want the doctor’s replies to mislead those of us who might face this choice in the future in order to comfort those treated in the past.
Stephen,
This Malhotra’s talk is really great!
He nails both the food and the medical industry as I do myself in my own lectures. I will give second talk to a small group of interested people in a couple of weeks. My first had the focus on our vicious food environment on CVD and my upcoming talk will entirely be on the medical industry and their villainous cholesterol/statin nonsense.
In my present relaxed state of my life I have now the pleasure to use the time in my own interest of “understanding” the fundamental science of “life” and not only on chopping wood to increase my blood flow.
My “bible” on the science of life, since a couple of years now, is here to me the great, 1300 pages textbook, “Molecular Biology of THE CELL”. Every page i just loaded with no-nonsense scientific understanding of what life basically is all about. An epitome trait, which indicate science to me, is that it constantly admit how utterly ignorant we are about the complex interactions between the hundreds of thousands of building blocks of life, the proteins, in every one of our 40 000 000 000 000 body cells.
One of the thousands of figures in the present sixth edition specifically caught my eye. It is a figure in the third chapter, “PROTEIN FUNCTION”, figure 3-80, “A network of proteinbinding interactions in a yeast cell.” where lines are drawn between interacting proteins presented as dots.
As the text elaborates.
“When hundreds of thousands of proteins are displayed on the same map, the network diagram becomes bewilderingly complicated, serving to illustrate the enormous challenges that face the scientists attempting to understand the cell.”
To me such an attitude is synonymous with science and serves to refute most categorical dogmas about life.
Dr Göran,
The Cell – a great book and one of my reference sources. When you consider the work of the many that made such a book and the knowledge it contains possible it saddens me that many in the medical profession still support and recommend treatments that are clearly alien to our biochemistry (statins being the obvious one with respect to this blog) in the light of such knowledge. That poor medical advice is backed by poor dietary advice just compounds the problem.
I am afraid that you missed a point which is ischemia. Global ischemia of the heart resulting from tight three vessels diseases could lead to infarction in areas where the supply of oxygen isbelow the threshold of cell life. It is less frequent in the brain but does exist too.
Regional ischemia could result of atheromatous or cardiac emboli in smaller vessels after plaque rupture or thrombus formation on a plaque in thrombotic states. In those cases the fate of cells relies only on collateral circulation which is very poor in the brain where distal arteries are terminal sometimes more developed in the limbs or in some territories of the heart.
Ischemia leads to necrosis as cells couldn’t suffer severe hypoxia without damage.
Dr Kendrick your post has left me puzzled and worried. You seem to suggest there is no such thing as lone AF. My husband, now 66, was diagnosed with AF around 5-6 years ago purely by chance (routine echocardiogram before a hernia op.) Asymptomatic, aside from slight breathlessness during long distance running and conscious of slight palpitations sometimes. I assumed lone AF, which is strongly correlated to his history of ultramarathons. No meds, but had stroke around 3 years ago- appears to have made quick and complete recovery. MRI and other tests immediately post stroke showed heart as clean as a whistle. All repeat echocardiograms, ECGs etc show clean bill of heart health. Has bee on warfarin since the stroke (I worry warfarin will ironically cause calcification if he does not take K2).
Thanks to Dr Kendrick’s information, we have been able to counter and refute all the urging by the GP and some of his consultants to put him on statins. They have given up, and the GP made do with sending him a dreadful very low fat diet sheet because his recent tests showed “slightly raised” TC i.e 7! (trigs 0.82, HDL 2.1, and ratio 3.3: i.e all fine!)
Question: if you say there is always CVD co present with stroke, what tests have the doctors missed?
I don’t think I said this. I think that there can be lone AF.
Any honest electrophysiologist will tell you that Atrial Fibrillation is barely understood.
I mentioned above that researchers are now favoring the idea that there is always an underlying cause, that AF is never lone.
For example, it seems that marathoners have more-or-less five times the chance of presenting with AF compared to the general public.
Also, there’s a paper that associates calcification with AF:
http://circimaging.ahajournals.org/content/8/12/e003786.abstract
Believe me, you have no idea what your CAC Agatston score might be till you do the scan.
The NOACs don’t have warfarin’s Vitamin K problems.
Thanks.
Hi, Not sure if you can help but I have a conundrum:
My Mum (90) has just had an angiogram as Angina was suspected ( she is also SOB and taken Anatenalol for 14 yrs following a TIA) and been told from that and other tests that her heart is fine, but has been sent home from hosp with 6 lots pills – 1st two she went in taking for the Angina -(Nincorandil) a vascodialator, (Bisoprolol) beta blocker, now has a Very high dose Statin (Atrovsastin 80mg!! not recommended for over 70’s) – she’s never had one b4 and her chol is low! also Amlodipine 2.5mg for HBP – hers is not high and Omeprozole as they think maybe she has a resperitory problem with the SOB but that is a side effect of the Anatenalol I believe. So my question must be WHY all these? no explanation given by hospital: are they trying to kill her off. We are hoping to go privately to see her heart specialist or Doctor but would love your take on it……
I love reading you articles even though I am not a doctor, these and your Doctoring Data book gave me the information I needed to stop my statin – which was casuing me a lot of aches and muscle problems… Many thanks.
Kind Regards
Jan