Thursday, 18 December 2008

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, see the top of this 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.


ProudDaddy said...

Another superb post, young man! I always noted that fish oil raised my fasting glucose. Every study I found that was published before 2000 verified it, and every study after 2000 disputed it. I have learned that you can always find a study to prove almost anything, so I really appreciate folks like you who make sense of it all!

Nigel Kinbrum said...

Young man? I'm fifty-*cough*. I don't reveal my age on-line. I like to maintain a little mystery!

ProudDaddy said...

Yes, young man it is, said the 70+ dude.