I've noticed that there are many comments on my post which take the viewpoint that either
1) LDL/apo B is not important in the development of ASCVD
2) Statins don't reduce the risk of ASCVD
Clearly, if you believe these 2 points, there is no point in doing CAC
When I became the skeptical cardiologist in 2013 I systematically challenged all that I had been taught about ASCVD. At that time, the hypothesis that lowering LDL would invariably lead to reduced ASCVD in my mind was not fully established. Since then it has been. Basic scientific investigation, prospective longitudinal cohorts, mendelian randomization and randomized clinical trials have all established that apo B is the particle that triggers atherosclerosis and that drugs that lower apo B reduce or eliminate atherosclerotic plaque formation and its consequences including heart attack and stroke.
"despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial and primary prevention more serously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs"
We have the ability to eliminate ASCVD, the biggest killer of humans in the world.
CAC is how we identify subclinical atherosclerosis.
We now have multiple very safe and effective medications beyond statins that lower apo B/LDL and reduce the devastation of ASCVD.
The only serious scientific question at this point is how aggressive to be without pharmacologic treatment in the individual sitting in front of us in the office
You’ve cited supposed knowns - and the vast majority of experts out there believe these claims - but calcium and cholesterol share something really interesting:
Role of UBIAD1 in Intracellular Cholesterol Metabolism and Vascular Cell Calcification
This enzyme is essential for the on-site biosynthesis of menaquinone-4, a hormone. MK- 4 is the most prevalent form of VK2 in our bodies and, in rodents, it is highest in thyroids (over other tissues/organs), but it is unknown how this translates to humans. I mentioned that T3 creation, its gene, directly relates to creation of matrix gla protein, which, upon activation, is the most potent anti-calcification substance known. In arteries, in endothelial cells, MGP has the role of preventing inappropriate calcium deposition. It prevents arterial ossification, noted to increase with age, and previously viewed as inevitable, but which can now be seen as a process over which we may have more control than previously appreciated.
It’s important to believe in one’s integrity, in one’s ability to accurately identify true cause and effect and interpret data correctly, and I am sure that you truly believe these statements to which I am responding. I am showing that there really are other ways to interpret what you state, but they question dogma and are contrary to A LOT of what we do and have been doing in medicine (and nutrition). Is CAC a way to ID subclinical atherosclerosis or is it an indicator of calcium dysregulation? Instead of lipids, what if it’s really calcium dysregulation that causes the “…biggest killer of humans in the world?” PS We will all die.
After all:
A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a prospective follow-up of 9715 individuals
Since statins increase CAC, a scan after taking them is not advised. And a very small reduction in events - artificially inflated by using RR instead of AR - by taking statins is cited as success. But, are these drugs, reducing serum LDLc, the BEST way? I think not. The best way is to prevent plaque and I’m showing that plaque etiology may well be initiated via calcium dysregulation, which just happens to share that enzyme, UBIAD1, with cholesterol. Reducing serum cholesterol has been observed with supplemental VK (and insulin sensitivity is increased), but good RCTs are called for, obviously:
“To test this theory, he ran a small pilot trial giving vitamin K supplements to a few subjects and found it lowered LDL or the bad cholesterol, triglycerides and total cholesterol comparably to lipid-lowering medications.”
Yes, anecdotal, not RCT, but there are more similar findings and supportive data*, but the sheer enormity of money, careers, inertia make for focusing on certain biomarkers and seeing them rather linearly, not holistically, and certainly Dear Peter Toth…how you see this is much like
1) menarche is earlier these days bc of our better nutrition
2) obesity is caused by greater energy intake than expenditure
3) excessive cholesterol causes plaques/CVD and not meeting guidelines by way of drugs is killing folks (poor Toth thinks this, apparently)
[Evidence for these are missing, but these are stories we have embraced/medical societies have embraced]
CAC, if used in trials, would be an interesting biomarker bc of this. In medical practice, facing people with events, symptoms, and all the data published so far, it’s risky to go against this Titanic of thought that we must use certain drugs and meet certain biomarkers , but just look into what I am showing. Look at calcium dysregulation as found in concomitant diseases: CVD, T2D, CKD, obesity, dementia, hypertension. Not tons of data, but they are increasing daily.
This is an entirely different paradigm, it connects the various diseases that tend to be concomitant, it truly questions guidelines/dogma bc: statins increase CAC, beta cells of pancreas have newly discovered vitamin K-dependent proteins that control calcium via carboxylation, those who eat more VK2 have fewer cardiovascular events/weigh less, kidney disease and calcium dysregulation co-exist.
I've noticed that there are many comments on my post which take the viewpoint that either
1) LDL/apo B is not important in the development of ASCVD
2) Statins don't reduce the risk of ASCVD
Clearly, if you believe these 2 points, there is no point in doing CAC
When I became the skeptical cardiologist in 2013 I systematically challenged all that I had been taught about ASCVD. At that time, the hypothesis that lowering LDL would invariably lead to reduced ASCVD in my mind was not fully established. Since then it has been. Basic scientific investigation, prospective longitudinal cohorts, mendelian randomization and randomized clinical trials have all established that apo B is the particle that triggers atherosclerosis and that drugs that lower apo B reduce or eliminate atherosclerotic plaque formation and its consequences including heart attack and stroke.
As Peter Toth has as written recently (https://www.sciencedirect.com/science/article/pii/S2666667722000551)
"despite the enormous number of clinical trials which support the need for reducing the burden of atherogenic lipoprotein in blood, the percentage of high and very high-risk patients who achieve risk stratified LDL-C target reductions is low and has remained low for the last thirty years. Atherosclerosis is a preventable disease. As clinicians, the time has come for us to take primordial and primary prevention more serously. Despite a plethora of therapeutic approaches, the large majority of patients at risk for ASCVD are poorly or inadequately treated, leaving them vulnerable to disease progression, acute cardiovascular events, and poor aging due to loss of function in multiple visceral organs"
We have the ability to eliminate ASCVD, the biggest killer of humans in the world.
CAC is how we identify subclinical atherosclerosis.
We now have multiple very safe and effective medications beyond statins that lower apo B/LDL and reduce the devastation of ASCVD.
The only serious scientific question at this point is how aggressive to be without pharmacologic treatment in the individual sitting in front of us in the office
Dr P
Dear Skeptical Cardiologist,
Thank you.
You’ve cited supposed knowns - and the vast majority of experts out there believe these claims - but calcium and cholesterol share something really interesting:
the enzyme UBIAD1.
https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0149639
Role of UBIAD1 in Intracellular Cholesterol Metabolism and Vascular Cell Calcification
This enzyme is essential for the on-site biosynthesis of menaquinone-4, a hormone. MK- 4 is the most prevalent form of VK2 in our bodies and, in rodents, it is highest in thyroids (over other tissues/organs), but it is unknown how this translates to humans. I mentioned that T3 creation, its gene, directly relates to creation of matrix gla protein, which, upon activation, is the most potent anti-calcification substance known. In arteries, in endothelial cells, MGP has the role of preventing inappropriate calcium deposition. It prevents arterial ossification, noted to increase with age, and previously viewed as inevitable, but which can now be seen as a process over which we may have more control than previously appreciated.
It’s important to believe in one’s integrity, in one’s ability to accurately identify true cause and effect and interpret data correctly, and I am sure that you truly believe these statements to which I am responding. I am showing that there really are other ways to interpret what you state, but they question dogma and are contrary to A LOT of what we do and have been doing in medicine (and nutrition). Is CAC a way to ID subclinical atherosclerosis or is it an indicator of calcium dysregulation? Instead of lipids, what if it’s really calcium dysregulation that causes the “…biggest killer of humans in the world?” PS We will all die.
After all:
A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a prospective follow-up of 9715 individuals
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4537357/#:~:text=CAC%3D0%20confers%20a%2015,unaffected%20by%20age%20or%20gender.
Since statins increase CAC, a scan after taking them is not advised. And a very small reduction in events - artificially inflated by using RR instead of AR - by taking statins is cited as success. But, are these drugs, reducing serum LDLc, the BEST way? I think not. The best way is to prevent plaque and I’m showing that plaque etiology may well be initiated via calcium dysregulation, which just happens to share that enzyme, UBIAD1, with cholesterol. Reducing serum cholesterol has been observed with supplemental VK (and insulin sensitivity is increased), but good RCTs are called for, obviously:
https://www.augustachronicle.com/story/lifestyle/health-fitness/2016/10/06/vitamin-k-tested-diabetes-high-cholesterol/14279990007/
“To test this theory, he ran a small pilot trial giving vitamin K supplements to a few subjects and found it lowered LDL or the bad cholesterol, triglycerides and total cholesterol comparably to lipid-lowering medications.”
Yes, anecdotal, not RCT, but there are more similar findings and supportive data*, but the sheer enormity of money, careers, inertia make for focusing on certain biomarkers and seeing them rather linearly, not holistically, and certainly Dear Peter Toth…how you see this is much like
1) menarche is earlier these days bc of our better nutrition
2) obesity is caused by greater energy intake than expenditure
3) excessive cholesterol causes plaques/CVD and not meeting guidelines by way of drugs is killing folks (poor Toth thinks this, apparently)
[Evidence for these are missing, but these are stories we have embraced/medical societies have embraced]
CAC, if used in trials, would be an interesting biomarker bc of this. In medical practice, facing people with events, symptoms, and all the data published so far, it’s risky to go against this Titanic of thought that we must use certain drugs and meet certain biomarkers , but just look into what I am showing. Look at calcium dysregulation as found in concomitant diseases: CVD, T2D, CKD, obesity, dementia, hypertension. Not tons of data, but they are increasing daily.
This is an entirely different paradigm, it connects the various diseases that tend to be concomitant, it truly questions guidelines/dogma bc: statins increase CAC, beta cells of pancreas have newly discovered vitamin K-dependent proteins that control calcium via carboxylation, those who eat more VK2 have fewer cardiovascular events/weigh less, kidney disease and calcium dysregulation co-exist.
* More info available, just ask
I’m interested in learning more about effective alternatives to statins. That they exist is new to me.
So many.
Ezetimibe.
Repatha/Praluent. PCSK9inhibitors
Bempedoic Acid