By now, you've probably noticed that I'm a bit anti-statin. The "problem" with statins is that they reduce cholesterol synthesis in the liver by reducing the conversion of HydroxyMethylGlutarate (HMG) Co-enzyme A (CoA) into Mevalonate by inhibiting the enzyme HMG CoA reductase.
Reducing Mevalonate reduces lots of other things e.g. Coenzyme Q10 synthesis, terpenoid synthesis, protein prenylation, cell membrane maintenance, hormones, protein anchoring, N-glycosylation and steroid biosynthesis which leads to cholesterol synthesis. Paradoxically, although cholesterol synthesis is reduced, Vitamin D level is increased. See also Atorvastatin increases 25-hydroxy vitamin D concentrations in patients with polycystic ovary syndrome.
Some of the above changes are undesirable in terms of all-cause mortality, so what would be ideal is a drug that just reduces serum cholesterol without doing anything else. Enter....Squalestatin a.k.a. Zaragozic Acid. This reduces the conversion of Farnesyl Pyrophosphate into Squalene by inhibiting the enzyme Squalene synthase. This has no effect on Mevalonate, or any of the substances listed in the above paragraph. Perfect!
A Squalene synthase inhibitor called Lapaquistat (a.k.a. TAK-475) was developed and tested by Takeda Pharmaceutical Company Limited in 2008. So, why is this wonder drug not on the market today? According to Limited press release - Discontinuation of Development of TAK-475, A Compound for Treatment of Hypercholesterolemia:- " the profile of the compound is not superior to existing marketed drugs from both efficacy and safety viewpoints".
So, just reducing serum cholesterol without changing anything else is not superior to reducing serum cholesterol and changing loads of other things. Maybe statins reduce CHD mortality a bit because they change loads of other things, not because they reduce serum cholesterol. See Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein.
Statins are anti-inflammatory. So is Vitamin D3. I'd take Vitamin D3 instead of statins any day.
Tampilkan postingan dengan label Statins. Tampilkan semua postingan
Tampilkan postingan dengan label Statins. Tampilkan semua postingan
How many working brain cells do drug company lackeys have?
In Elvis lives!, I referred to the study Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study*, which came to the conclusion:
"Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD."
I then pointed out the following teensy-weensy flaw in the conclusion:
"What the abstract failed to mention was the fact that there were 26 more deaths in the 80mg Atorvastatin group than in the 10mg group. What's worse? Having a major cardiovascular event or being dead?"
On a Mean Forum far away, I pointed out this teensy-weensy flaw in the conclusion and was told "are you really that retarded?" Funnily enough, I never got an answer from that person as to how the conclusion in red was justified by the data in green. I helpfully suggested that it might have something to do with the fact that Atorvastatin 80mg is a 700% increase in sales compared to Atorvastatin 10mg.
I then received an e-mail from Pfizer ® Customer Service with a spoofed sending address (it was fairly obvious that it was spoofed as it was my e-mail address!). There was the usual helpful Outlook Express "Some pictures have been blocked to help prevent the sender from identifying your computer. Click here to download pictures" message. I didn't click. Well, would you? I deleted the e-mail. I've now enabled comment moderation just in case this 'tard feels like spamming my Blog.
Pfizer manufactures Atorvastatin. Ho-hum!
*Funding for the study was provided by Pfizer Inc., New York, New York. Dr. Shepherd has received consulting fees from AstraZeneca, GlaxoSmithKline, Merck, Oxford Biosensors, Pfizer Inc., and Schering-Plough, and lecture fees from AstraZeneca, Merck, and Schering-Plough. Dr. Kastelein has received consulting fees and lecture fees from Pfizer Inc., AstraZeneca, Merck, and Schering-Plough, and grant support from Pfizer Inc. and AstraZeneca. Dr. Bittner has received consulting fees from CV Therapeutics, Novartis, Pfizer Inc., Abbott, and Reliant, and grant support from Pfizer Inc., Atherogenics, Merck, Kos Pharmaceuticals, Abbott, CV Therapeutics, and the National Institutes of Health. Dr. Deedwania has received consulting fees and lecture fees from Pfizer Inc. and AstraZeneca. Dr. Breazna, Dr. Wilson, and Dr. Zuckerman are all employees of Pfizer Inc. Mr. Dobson is an employee of Envision Pharma Ltd., which was a paid consultant to Pfizer Inc. in connection with the development of the manuscript. Dr. Wenger has received consulting fees from CV Therapeutics, Sanofi-Aventis, Schering-Plough, AstraZeneca, Abbott, Merck, and Pfizer Inc., and grant support from Pfizer Inc., Merck, and the National Heart, Lung, and Blood Institute.
"Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD."
I then pointed out the following teensy-weensy flaw in the conclusion:
"What the abstract failed to mention was the fact that there were 26 more deaths in the 80mg Atorvastatin group than in the 10mg group. What's worse? Having a major cardiovascular event or being dead?"
On a Mean Forum far away, I pointed out this teensy-weensy flaw in the conclusion and was told "are you really that retarded?" Funnily enough, I never got an answer from that person as to how the conclusion in red was justified by the data in green. I helpfully suggested that it might have something to do with the fact that Atorvastatin 80mg is a 700% increase in sales compared to Atorvastatin 10mg.
I then received an e-mail from Pfizer ® Customer Service with a spoofed sending address (it was fairly obvious that it was spoofed as it was my e-mail address!). There was the usual helpful Outlook Express "Some pictures have been blocked to help prevent the sender from identifying your computer. Click here to download pictures" message. I didn't click. Well, would you? I deleted the e-mail. I've now enabled comment moderation just in case this 'tard feels like spamming my Blog.
Pfizer manufactures Atorvastatin. Ho-hum!
*Funding for the study was provided by Pfizer Inc., New York, New York. Dr. Shepherd has received consulting fees from AstraZeneca, GlaxoSmithKline, Merck, Oxford Biosensors, Pfizer Inc., and Schering-Plough, and lecture fees from AstraZeneca, Merck, and Schering-Plough. Dr. Kastelein has received consulting fees and lecture fees from Pfizer Inc., AstraZeneca, Merck, and Schering-Plough, and grant support from Pfizer Inc. and AstraZeneca. Dr. Bittner has received consulting fees from CV Therapeutics, Novartis, Pfizer Inc., Abbott, and Reliant, and grant support from Pfizer Inc., Atherogenics, Merck, Kos Pharmaceuticals, Abbott, CV Therapeutics, and the National Institutes of Health. Dr. Deedwania has received consulting fees and lecture fees from Pfizer Inc. and AstraZeneca. Dr. Breazna, Dr. Wilson, and Dr. Zuckerman are all employees of Pfizer Inc. Mr. Dobson is an employee of Envision Pharma Ltd., which was a paid consultant to Pfizer Inc. in connection with the development of the manuscript. Dr. Wenger has received consulting fees from CV Therapeutics, Sanofi-Aventis, Schering-Plough, AstraZeneca, Abbott, Merck, and Pfizer Inc., and grant support from Pfizer Inc., Merck, and the National Heart, Lung, and Blood Institute.
Elvis lives!
This bloke said he saw Elvis down the chip shop. What? You mean he was mistaken or lying? Surely not!
Regularly, you read or hear:- "Aspartame gives you cancer!" "Meat gives you cancer!" "Crisps give you cancer!" "Coffee gives you cancer!" "Coffee doesn't give you cancer!" "Coffee gives you cancer!" and so on and so forth...... What are we to believe?
In terms of Diet & Nutritional information, there's a hierarchy of credibility. Here's a rough list of credibility, starting with the least credible and ending with the most credible.
Inexpert Opinion. Basically, anyone can say anything (especially on the internet) but that doesn't make it true. This includes anything that I say, which is why I try to back up what I say with evidence from higher up the pile.
Anecdote/Testimonial. Just because it worked for Joe or Josephine doesn't mean that it'll work for anyone else. There's also the placebo effect e.g. Nothing acts faster than Anadin (so I use nothing!)
Expert opinion. Even "experts" with lots of letters after their names get things wrong and have personal biases, hence the controversies over MMR, HIV/AIDS, Cholesterol etc.
In Vitro (in glass) studies. What happens in Petri dishes/test-tubes etc doesn't necessarily happen in humans.
In Vivo (in life) Animal studies. What happens in rats/monkeys etc doesn't necessarily happen in humans.
Epidemiological (population) Human studies. A being associated with B doesn't necessarily mean that A caused B, as the association may have been due to random chance or due to both being caused by C, D, E........Z etc.
Case studies. The number of subjects is usually quite small and often just 1.
Small and/or non-randomised and/or unblinded and/or non-placebo-controlled and/or non-crossover trials.
Large, Randomised, Double-blinded, Placebo-controlled Crossover trials with a decent Washout.
Meta-studies of large, randomised, double-blinded, placebo-controlled crossover trials.
Even the last two in the list aren't perfect. Study outcomes can be manipulated by tweaking the methodology (e.g. using pre-trial screening) or statistical jiggery-pokery. If a trial is funded by (a) drugs company(ies), the methods used & the results obtained should be scrutinised very carefully.
EDIT: Systematic Reviews & Meta-studies can be manipulated by including studies with completely different input & output ranges, so as to dilute the data and force a null result. See Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease and Low Carbohydrate versus Isoenergetic Balanced Diets for Reducing Weight and Cardiovascular Risk: A Systematic Review and Meta-Analysis.
Abstracts can misrepresent the data. See Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study.
"Conclusion: Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD."
There was a 15-32% reduction in major cardiovascular events. Wow, that's impressive! What the abstract failed to mention is the fact that there were 26 more deaths in the 80mg group, than in the 10mg group. What's worse? Having a major cardiovascular event or being dead?
In conclusion, when you read something in the media, do some research of your own before accepting it as fact. Use Google, Wikipedia, PubMed and the Cochrane Library.
Regularly, you read or hear:- "Aspartame gives you cancer!" "Meat gives you cancer!" "Crisps give you cancer!" "Coffee gives you cancer!" "Coffee doesn't give you cancer!" "Coffee gives you cancer!" and so on and so forth...... What are we to believe?
In terms of Diet & Nutritional information, there's a hierarchy of credibility. Here's a rough list of credibility, starting with the least credible and ending with the most credible.
Inexpert Opinion. Basically, anyone can say anything (especially on the internet) but that doesn't make it true. This includes anything that I say, which is why I try to back up what I say with evidence from higher up the pile.
Anecdote/Testimonial. Just because it worked for Joe or Josephine doesn't mean that it'll work for anyone else. There's also the placebo effect e.g. Nothing acts faster than Anadin (so I use nothing!)
Expert opinion. Even "experts" with lots of letters after their names get things wrong and have personal biases, hence the controversies over MMR, HIV/AIDS, Cholesterol etc.
In Vitro (in glass) studies. What happens in Petri dishes/test-tubes etc doesn't necessarily happen in humans.
In Vivo (in life) Animal studies. What happens in rats/monkeys etc doesn't necessarily happen in humans.
Epidemiological (population) Human studies. A being associated with B doesn't necessarily mean that A caused B, as the association may have been due to random chance or due to both being caused by C, D, E........Z etc.
Case studies. The number of subjects is usually quite small and often just 1.
Small and/or non-randomised and/or unblinded and/or non-placebo-controlled and/or non-crossover trials.
Large, Randomised, Double-blinded, Placebo-controlled Crossover trials with a decent Washout.
Meta-studies of large, randomised, double-blinded, placebo-controlled crossover trials.
Even the last two in the list aren't perfect. Study outcomes can be manipulated by tweaking the methodology (e.g. using pre-trial screening) or statistical jiggery-pokery. If a trial is funded by (a) drugs company(ies), the methods used & the results obtained should be scrutinised very carefully.
EDIT: Systematic Reviews & Meta-studies can be manipulated by including studies with completely different input & output ranges, so as to dilute the data and force a null result. See Meta-analysis of prospective cohort studies evaluating the association of saturated fat with cardiovascular disease and Low Carbohydrate versus Isoenergetic Balanced Diets for Reducing Weight and Cardiovascular Risk: A Systematic Review and Meta-Analysis.
Abstracts can misrepresent the data. See Intensive lipid lowering with atorvastatin in patients with coronary heart disease and chronic kidney disease: the TNT (Treating to New Targets) study.
"Conclusion: Aggressive lipid lowering with atorvastatin 80 mg was both safe and effective in reducing the excess of cardiovascular events in a high-risk population with CKD and CHD."
There was a 15-32% reduction in major cardiovascular events. Wow, that's impressive! What the abstract failed to mention is the fact that there were 26 more deaths in the 80mg group, than in the 10mg group. What's worse? Having a major cardiovascular event or being dead?
In conclusion, when you read something in the media, do some research of your own before accepting it as fact. Use Google, Wikipedia, PubMed and the Cochrane Library.
Cholesterol And Coronary Heart Disease
Cholesterol & coronary heart disease are mentioned a lot in the media. Unfortunately, most of what you see & hear is either completely wrong, or dumbed-down so much that it's inaccurate.
Fat & cholesterol don't stick to the insides of artery walls like grease on the inside of a drainpipe. This article explains what cholesterol is, how arteries get blocked and how to minimise the risk of having a heart attack or ischaemic stroke.
What is cholesterol?
Cholesterol is a large, waxy molecule (C27H45OH) consisting of a hydrocarbon (fat-soluble) tail, a middle section consisting of four carbon rings (the steroid bit) and an alcohol (water-soluble) group on the end. Cholesterol is a powerful anti-oxidant and is what bile acids, mineralcorticoids, glucocorticoids and sex hormones are made from.
Cholesterol is "chauffeured" around the body in lipoprotein "limousines". Lipoproteins are lipo (fat-soluble) at one end, protein (water-soluble) at the other end and they form a spherical shell around their contents with the lipo end pointing inwards and the protein end pointing outwards. The shell is like the body of the limousine. In the shell, there are apo(lipo)proteins which are like the chauffeur, as they determine where the particles are taken up. HDL has apo A in its shell which makes it get taken up by receptors in the liver. LDL has apo B in its shell which makes it get taken up by receptors in cells, artery walls etc. The passengers are cholesterol, cholesteryl esters, phospholipids and triglycerides. These limousines have different types, like chylomicrons, VLDL, LDL, IDL & HDL, the difference being the type & amount of apo(lipo)protein and the relative proportions of cholesterol & the other passengers. There are also sub-groups of each type.
The different variants are affected by serum triglycerides. High serum triglycerides (caused by a chronic over-consumption of sugary & starchy carbohydrates for activity level) result in cholesterol-depleted, triglyceride-rich particles and low serum triglycerides result in cholesterol-rich, triglyceride-depleted particles. As cholesterol is a powerful antioxidant, small cholesterol-depleted particles (Type B) oxidise faster than large cholesterol-rich ones (Type A).
Oxidised LDL particles are "bad cholesterol" and are swallowed by scavenger macrophages. These expand into foam cells, which become embedded in the intima of artery walls. Other processes occur which cause cholesterol & calcium to accumulate as a plaque inside the media of artery walls. To see a cross-section through an artery wall, click HERE and scroll down to the bottom of the page. Unoxidised LDL particles are not swallowed by scavenger macrophages, so unoxidised LDL particles are not "bad cholesterol". In young people, plaques of cholesterol with no calcium can accumulate within artery walls, making Coronary Artery Calcium (CAC) scans ineffective. See Stenosis Can Still Exist in Absence of Coronary Calcium.
Plaques force the inner artery wall inwards, making the artery narrower, impeding the flow of blood through it. This can cause angina pectoris (pain in the chest) as the heart is starved of oxygen, or vascular dementia as the brain is starved of blood. The cap covering the plaque may rupture, causing chunks of plaque to circulate and block coronary arteries (causing a heart attack), or cerebral arteries (causing an ischaemic stroke).
It's possible to reduce serum triglycerides significantly by eating lots of long-chain omega-3 fats from oily fish. These inhibit the conversion of glucose into triglycerides. Inhibiting the conversion of glucose into triglycerides can result in increased blood glucose levels (not good - see below) if sugary/starchy carbohydrate intake is too high. Solution? Reduce sugary/starchy carbohydrate intake to suit activity level.
Why do foam cells embed themselves into the intima of artery walls?
Arteries are elastic, muscular tubes which stretch a bit each time the heart pumps and contract again between beats. They also relax & constrict to control the flow of blood through them. When you get cold, they constrict to reduce the flow of blood to the skin to prevent excessive heat loss. When you get hot, they open to increase the flow of blood to the skin to increase heat loss.
Foam cells don't go just anywhere. They embed themselves into damaged areas of artery walls. This is a good thing, otherwise damaged artery walls could rupture, causing a haemorrhage.
What damages artery walls?
Chronically-high blood pressure.
Chronically-high blood glucose.
Chronically-high blood free radicals.
Chronically-high blood homocysteine.
Chronically-low blood antioxidants.
Chronically-high blood pro-oxidants.
Chronically-low blood anti-inflammatories.
Chronically-low Vitamin K2.
Chronically-high LDL due to hypothyroidism or other factors.
How can I reduce damage to my artery walls?
1) Have blood pressure (BP) tested regularly. There's one problem with having your BP taken in a GP's surgery and that is 'white-coat hypertension' where the stress of having your arm squeezed by the cuff sends your BP up! If you buy your own BP monitor (Lloyds pharmacy sell a fully automatic BP monitor with standard cuff for £9.99), you can become accustomed to using it and overcome white-coat hypertension. 5,000iu/day of Vitamin D3 can reduce BP by making artery walls more elastic. 4g/day of Epsom Salts provides 400mg/day of Magnesium, which acts as a smooth muscle relaxant, reducing BP & cardiac arrhythmias.
2) Have blood glucose (BG) tested regularly. If you're lucky, you may be able to get a HbA1c test. This shows accumulated damage to red blood cells by blood glucose.
3) Don't smoke! Apart from lung cancer, chronic obstructive pulmonary disease & emphysema, smoking speeds the oxidation of LDL.
4) Take a B-complex containing B6, B12 & folic acid, which lowers serum homocysteine levels.
5) Eat a diet rich in anti-oxidants from coloured veggies (beta-carotene), fruits (Vitamin C + bioflavonoids), tomatoes (lycopene), nuts & seeds (gamma-tocopherol & copper), Brazil nuts (selenium), beer/wine in moderation (muscle relaxant), green tea (polyphenols), cocoa/dark chocolate (polyphenols & copper), onions/garlic (quercetin) etc. See Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50.
6) In men and non-menstruating women, too much iron in the blood relative to copper is pro-oxidant, so don't supplement with iron. Menstruating women have the opposite problem.
7) Take about 2g/day of long-chain omega-3 fats from oily fish, or about 20g/day of flaxseed oil if male, or about 10g/day of flaxseed oil if female. Please note that tinned tuna contains virtually zero omega-3 fats. See Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care.
8) Eat a diet rich in Vitamin K2, to make calcium go into bones & teeth, instead of into artery walls, kidneys & brain. For good sources of Vitamin K2, see HERE. Note: Warfarin/Coumadin works by depleting Vitamin K, so lots of Vitamin K2 makes Warfarin/Coumadin ineffective.
9) If you're feeling tired and are gaining weight for no obvious reason, get serum thyroid hormone levels tested (TSH, FT4 & FT3 preferably), as low thyroid hormones down-regulate LDL receptors, resulting in LDL particles lingering in the blood for longer than usual. This increases LDL-C, LDL-P (particle count) and the oxidation of the particles. See Neovascularization of coronary tunica intima (DIT) is the cause of coronary atherosclerosis. Lipoproteins invade coronary intima via neovascularization from adventitial vasa vasorum, but not from the arterial lumen: a hypothesis.
What about Benecol & Flora Pro-Activ?
These yoghurts & spreads contain plant sterols/stanols, which reduce total serum cholesterol by up to 15%. However, LDL quality is more important than LDL quantity (up to a point) and there is no evidence that these foods save lives.
What about statins?
Statins (HydroxyMethylGlutarate Coenzyme-A Reductase inhibitors) reduce serum cholesterol. They also have anti-inflammatory & anti-clotting effects by reducing levels of the non-sterol derivative mevalonate and subsequent products. Click HERE to see the cholesterol synthesis pathway. Statins save lives in people who have had a heart attack and in men between the ages of 30 and 60. However, younger & older men and women do not get a significant reduction in deaths, (though heart-attack deaths may be reduced) and there can be undesirable side-effects (muscle pains, memory loss etc). I strongly recommend that anyone taking statins, supplements with at least 100mg/day of Co-Q10, as the synthesis of this vital substance is reduced. Note that fish oils have anti-inflammatory, anti-clotting and anti-arrhythmia actions, but don't suppress the production of Co-Q10.
What about dietary cholesterol?
When cholesterol is eaten, the liver produces less cholesterol. An average egg contains about 250mg of cholesterol. The vast majority of people (who don't have genes for familial hypercholesterolaemia) can eat two eggs a day without significantly affecting their serum cholesterol & triglyceride levels. See Effect of dietary egg on human serum cholesterol and triglycerides, and Eat Whole Eggs All Day and Throw Your Statins Away? 375x Increased Dietary Cholesterol Intake From Eggs Reduces Visceral Fat & Promotes Healthy Cholesterol Metabolism. People with the ApoE4/E4 polymorphism are more sensitive to dietary fat & cholesterol raising serum LDL, and cannot eat fat & cholesterol willy-nilly.
There are a couple of sites that have CVD risk calculators, JBS2 and QRISK®2-2013. The National Institute for Clinical Excellence (NICE) no longer recommends the use of JBS2, as it's overly-pessimistic. Note that CVD mortality isn't the same thing as overall mortality. Slightly higher-than-"normal" total cholesterol level is associated with lower overall mortality, according to Research finds ‘raised’ cholesterol to be associated with a reduced risk of death.
Fat & cholesterol don't stick to the insides of artery walls like grease on the inside of a drainpipe. This article explains what cholesterol is, how arteries get blocked and how to minimise the risk of having a heart attack or ischaemic stroke.
What is cholesterol?
Cholesterol is a large, waxy molecule (C27H45OH) consisting of a hydrocarbon (fat-soluble) tail, a middle section consisting of four carbon rings (the steroid bit) and an alcohol (water-soluble) group on the end. Cholesterol is a powerful anti-oxidant and is what bile acids, mineralcorticoids, glucocorticoids and sex hormones are made from.
Cholesterol is "chauffeured" around the body in lipoprotein "limousines". Lipoproteins are lipo (fat-soluble) at one end, protein (water-soluble) at the other end and they form a spherical shell around their contents with the lipo end pointing inwards and the protein end pointing outwards. The shell is like the body of the limousine. In the shell, there are apo(lipo)proteins which are like the chauffeur, as they determine where the particles are taken up. HDL has apo A in its shell which makes it get taken up by receptors in the liver. LDL has apo B in its shell which makes it get taken up by receptors in cells, artery walls etc. The passengers are cholesterol, cholesteryl esters, phospholipids and triglycerides. These limousines have different types, like chylomicrons, VLDL, LDL, IDL & HDL, the difference being the type & amount of apo(lipo)protein and the relative proportions of cholesterol & the other passengers. There are also sub-groups of each type.
The different variants are affected by serum triglycerides. High serum triglycerides (caused by a chronic over-consumption of sugary & starchy carbohydrates for activity level) result in cholesterol-depleted, triglyceride-rich particles and low serum triglycerides result in cholesterol-rich, triglyceride-depleted particles. As cholesterol is a powerful antioxidant, small cholesterol-depleted particles (Type B) oxidise faster than large cholesterol-rich ones (Type A).
Oxidised LDL particles are "bad cholesterol" and are swallowed by scavenger macrophages. These expand into foam cells, which become embedded in the intima of artery walls. Other processes occur which cause cholesterol & calcium to accumulate as a plaque inside the media of artery walls. To see a cross-section through an artery wall, click HERE and scroll down to the bottom of the page. Unoxidised LDL particles are not swallowed by scavenger macrophages, so unoxidised LDL particles are not "bad cholesterol". In young people, plaques of cholesterol with no calcium can accumulate within artery walls, making Coronary Artery Calcium (CAC) scans ineffective. See Stenosis Can Still Exist in Absence of Coronary Calcium.
Plaques force the inner artery wall inwards, making the artery narrower, impeding the flow of blood through it. This can cause angina pectoris (pain in the chest) as the heart is starved of oxygen, or vascular dementia as the brain is starved of blood. The cap covering the plaque may rupture, causing chunks of plaque to circulate and block coronary arteries (causing a heart attack), or cerebral arteries (causing an ischaemic stroke).
It's possible to reduce serum triglycerides significantly by eating lots of long-chain omega-3 fats from oily fish. These inhibit the conversion of glucose into triglycerides. Inhibiting the conversion of glucose into triglycerides can result in increased blood glucose levels (not good - see below) if sugary/starchy carbohydrate intake is too high. Solution? Reduce sugary/starchy carbohydrate intake to suit activity level.
Why do foam cells embed themselves into the intima of artery walls?
Arteries are elastic, muscular tubes which stretch a bit each time the heart pumps and contract again between beats. They also relax & constrict to control the flow of blood through them. When you get cold, they constrict to reduce the flow of blood to the skin to prevent excessive heat loss. When you get hot, they open to increase the flow of blood to the skin to increase heat loss.
Foam cells don't go just anywhere. They embed themselves into damaged areas of artery walls. This is a good thing, otherwise damaged artery walls could rupture, causing a haemorrhage.
What damages artery walls?
Chronically-high blood pressure.
Chronically-high blood glucose.
Chronically-high blood free radicals.
Chronically-high blood homocysteine.
Chronically-low blood antioxidants.
Chronically-high blood pro-oxidants.
Chronically-low blood anti-inflammatories.
Chronically-low Vitamin K2.
Chronically-high LDL due to hypothyroidism or other factors.
How can I reduce damage to my artery walls?
1) Have blood pressure (BP) tested regularly. There's one problem with having your BP taken in a GP's surgery and that is 'white-coat hypertension' where the stress of having your arm squeezed by the cuff sends your BP up! If you buy your own BP monitor (Lloyds pharmacy sell a fully automatic BP monitor with standard cuff for £9.99), you can become accustomed to using it and overcome white-coat hypertension. 5,000iu/day of Vitamin D3 can reduce BP by making artery walls more elastic. 4g/day of Epsom Salts provides 400mg/day of Magnesium, which acts as a smooth muscle relaxant, reducing BP & cardiac arrhythmias.
2) Have blood glucose (BG) tested regularly. If you're lucky, you may be able to get a HbA1c test. This shows accumulated damage to red blood cells by blood glucose.
3) Don't smoke! Apart from lung cancer, chronic obstructive pulmonary disease & emphysema, smoking speeds the oxidation of LDL.
4) Take a B-complex containing B6, B12 & folic acid, which lowers serum homocysteine levels.
5) Eat a diet rich in anti-oxidants from coloured veggies (beta-carotene), fruits (Vitamin C + bioflavonoids), tomatoes (lycopene), nuts & seeds (gamma-tocopherol & copper), Brazil nuts (selenium), beer/wine in moderation (muscle relaxant), green tea (polyphenols), cocoa/dark chocolate (polyphenols & copper), onions/garlic (quercetin) etc. See Antioxidant state and mortality from coronary heart disease in Lithuanian and Swedish men: concomitant cross sectional study of men aged 50.
6) In men and non-menstruating women, too much iron in the blood relative to copper is pro-oxidant, so don't supplement with iron. Menstruating women have the opposite problem.
7) Take about 2g/day of long-chain omega-3 fats from oily fish, or about 20g/day of flaxseed oil if male, or about 10g/day of flaxseed oil if female. Please note that tinned tuna contains virtually zero omega-3 fats. See Clinical nutrition: 4. Omega-3 fatty acids in cardiovascular care.
8) Eat a diet rich in Vitamin K2, to make calcium go into bones & teeth, instead of into artery walls, kidneys & brain. For good sources of Vitamin K2, see HERE. Note: Warfarin/Coumadin works by depleting Vitamin K, so lots of Vitamin K2 makes Warfarin/Coumadin ineffective.
9) If you're feeling tired and are gaining weight for no obvious reason, get serum thyroid hormone levels tested (TSH, FT4 & FT3 preferably), as low thyroid hormones down-regulate LDL receptors, resulting in LDL particles lingering in the blood for longer than usual. This increases LDL-C, LDL-P (particle count) and the oxidation of the particles. See Neovascularization of coronary tunica intima (DIT) is the cause of coronary atherosclerosis. Lipoproteins invade coronary intima via neovascularization from adventitial vasa vasorum, but not from the arterial lumen: a hypothesis.
What about Benecol & Flora Pro-Activ?
These yoghurts & spreads contain plant sterols/stanols, which reduce total serum cholesterol by up to 15%. However, LDL quality is more important than LDL quantity (up to a point) and there is no evidence that these foods save lives.
What about statins?
Statins (HydroxyMethylGlutarate Coenzyme-A Reductase inhibitors) reduce serum cholesterol. They also have anti-inflammatory & anti-clotting effects by reducing levels of the non-sterol derivative mevalonate and subsequent products. Click HERE to see the cholesterol synthesis pathway. Statins save lives in people who have had a heart attack and in men between the ages of 30 and 60. However, younger & older men and women do not get a significant reduction in deaths, (though heart-attack deaths may be reduced) and there can be undesirable side-effects (muscle pains, memory loss etc). I strongly recommend that anyone taking statins, supplements with at least 100mg/day of Co-Q10, as the synthesis of this vital substance is reduced. Note that fish oils have anti-inflammatory, anti-clotting and anti-arrhythmia actions, but don't suppress the production of Co-Q10.
What about dietary cholesterol?
When cholesterol is eaten, the liver produces less cholesterol. An average egg contains about 250mg of cholesterol. The vast majority of people (who don't have genes for familial hypercholesterolaemia) can eat two eggs a day without significantly affecting their serum cholesterol & triglyceride levels. See Effect of dietary egg on human serum cholesterol and triglycerides, and Eat Whole Eggs All Day and Throw Your Statins Away? 375x Increased Dietary Cholesterol Intake From Eggs Reduces Visceral Fat & Promotes Healthy Cholesterol Metabolism. People with the ApoE4/E4 polymorphism are more sensitive to dietary fat & cholesterol raising serum LDL, and cannot eat fat & cholesterol willy-nilly.
There are a couple of sites that have CVD risk calculators, JBS2 and QRISK®2-2013. The National Institute for Clinical Excellence (NICE) no longer recommends the use of JBS2, as it's overly-pessimistic. Note that CVD mortality isn't the same thing as overall mortality. Slightly higher-than-"normal" total cholesterol level is associated with lower overall mortality, according to Research finds ‘raised’ cholesterol to be associated with a reduced risk of death.