Coronary Heart Disease And The Diet

Coronary heart disease is sometimes called arteriosclerotic heart disease because the primary disorder is in the arteries. The heart muscle depends for its nourishment and "breathes" through the coronary arteries that form a crown ("corona") around the heart before they plunge down into the heart muscle to bring fresh blood to every cell. Any interference with this blood supply is dangerous and can be quickly fatal. Such interference can be produced by atherosclerosis, that is, deposits of cholesterol and associated cellular changes in the wall of the artery, or by blood clots (coronary thrombosis) which block the blood passage. These clots or thrombi generally form only in an artery with arteriosclerosis.

The most important point about the diet in this connection is that the fats we eat have a major effect on the amount of cholesterol in the blood, and it is this cholesterol which is deposited in the walls of the arteries. The more common fats in modern diets - meat and dairy fat, margarine and cooking fat - tend to raise the blood cholesterol. On the other hand, most common oils (liquid fats) generally have no such effect or may even work in opposition.

Fats in the diet have another effect that may be related to the production of clots in the arteries. A fatty meal tends to make the blood clot more easily in certain tests. Of course, what happens in the arteries may not be the same as what we see in the test tube, but we wonder whether it may not be wise to play safe by avoiding fat-loaded meals.

cholesterol level and the development of coronary heart disease. Most populations that seem to have relatively little coronary disease live on diets that are rather high in leafy vegetables and fruits as well as being low in sugar and in meat and dairy fats. Experiments with diets of this kind indicate that some part of their cholesterol-lowering action cannot be explained solely by the amounts of fat in the diet.

Atherosclerosis and its Results Arteriosclerosis is a generic term that means "hardening of the arteries", a process formerly thought to be simply the inevitable consequence of ageing. In a limited sense this is true in that as age progresses the tough yet pliable tubes that are the arteries tend to become more rigid and less elastic and, eventually, may become impregnated with "lime" (calcium) deposits until they are stiff and stony. But this kind of hardening of the arteries that affects mainly the middle coat ("media") of the artery wall, though often troublesome in the arms and legs of old people, is not our real concern when we are talking about "arteriosclerotic" or, better, coronary heart disease.

The kind of arteriosclerosis we worry about in the heart has a special name, "atherosclerosis". It involves mainly the inner layer of the arterial wall, the "intima". Calcium deposits are only an inconstant and late feature of the tissue change, and the artery is not necessarily really hard, though there is some loss of elasticity. The name "atherosclerosis" refers to the Greek word atheros, meaning porridge or gruel, because the inner layer of the artery looks as though it contains bits of porridge. The "porridge" turns out to be a mixture of cholesterol and the ordinary fats of the blood deposited not on the wall in direct contact with the lumen but just under the inner surface of the artery wall itself. Such spots are called atheromas, literally "porridge bodies".

Cholesterol is a material which is associated with fat. It is not a true fat but a waxy substance resembling fat in being insoluble in water and easily dissolved in ether and other fat solvents. It is a non-poisonous, chemically rather stable substance that may do its mischief in the arteries simply by its passive physical presence. A deposit in the artery wall of cholesterol, or anything else for that matter, tends to diminish the lumen through which the blood must flow, but more important is the effect on the adjacent cells. The cells of the artery wall are crowded so they are ill-nourished, and this condition is accentuated by the tendency for connective tissue to grow and wall off the deposit. Eventually, some of the cells actually die, producing tiny areas of ulceration which are healed by something like scar tissue that still further chokes the normal cells of the wall. Such places in the arteries can grow until the lumen for blood flow is seriously reduced. Perhaps even more dangerous, conditions are set for a local blood clot to form and thus totally occlude the vessel by thrombosis.

These atherosclerotic changes may take place in arteries in several parts of the body, especially in the aorta and its main trunks and in the brain, but in the coronary arteries the result can be most quickly catastrophic because the heart muscle is absolutely dependent on the blood supply through the coronary arteries; if this fails, the muscle is quickly exhausted and it stops working.

It is rare for all the coronary blood supply to be blocked at the same time, but if any one main coronary artery branch is occluded the part of the muscle it supplies is affected at once. At best, the heartbeat is temporarily disordered, some local muscle cells die, and these are gradually replaced by scar tissue; the end result after a few weeks is a scar in the heart, a "healed infarct", and disability can range from being a complete cardiac cripple to having no symptoms at all.

There are three kinds of outcome to the "heart attack" that are worse. The amount of heart muscle affected may be so great that the remainder cannot pump enough blood to prevent serious congestion of the lungs or for the elementary needs of the body, particularly of the brain which is most sensitive to an interruption in blood supply. Or because one part of the heart muscle is dying, the contractions of the rest of the heart become wildly disordered, its rhythm runs away and the entire heart muscle is soon fatally exhausted. Finally, in a small percentage of cases the area where the local muscle cells are dead may give way under the pressure of the blood inside the heart, the heart ruptures and there is massive, uncontrollable haemorrhage inside the body.

These tragic events have their origin in the diseased arterial wall, and if atherosclerosis could be prevented there would be little cause to worry about coronary heart disease. So what causes atherosclerosis? The full story is as yet unknown, but the facts already available are highly significant. The cholesterol that turns up to such dangerous effect in the artery wall comes from the blood, and other things being equal, judging from animal experiments, the more cholesterol in the blood the more tendency for it to deposit in the artery. The atherosclerotic development tends to proceed over a long period of time so the cholesterol concentration in the blood at a given moment is not necessarily very important; much more consequential is the average over the months and years.

An old theory has been revived lately by Professor J. Duguid of Newcastle. This holds that the start of atherosclerosis may be from tiny fragments of blood clots that stick to the walls of the arteries and become the focus of the cholesterol deposits and local cell changes we call atherosclerosis. While the pathologists argue about this we merely note that even in the experiments (on animals) offered in support of theory, a large elevation of blood cholesterol has been required in every case to produce the atherosclerosis - and this has always been produced in the diet!

Of course the cholesterol concentration in the blood, even its average over the years, is not the sole factor in the production of atherosclerosis. Local abnormalities in the structure of the arterial wall or in the way in which the arteries branch may favour the formation of atherosclerosis even if the concentration of cholesterol in the blood is not very high. Such abnormalities may be inherited or may be produced, by causes unknown, during early development. If they are present they increase the danger associated with any given level of cholesterol in the blood. Then, too, a severe degree of atherosclerosis, with much cholesterol deposited in the artery wall, does not always produce coronary heart disease, while on the other hand a single spot in a strategic location may be the site of a fatal clot. None of this lessens the importance of atherosclerosis or the cholesterol in the blood that promotes it.

Finally, people differ in their serum cholesterol levels even on the same diet. There is a general tendency for the level to rise from youth until the fifties or sixties and then to decline at still older ages. It is interesting that this age trend in the blood has a counterpart in the arteries where the rate of development of atherosclerosis is similarly related to age, rising from early adulthood until late middle age with not much new atherosclerosis developing thereafter. This suggests that as we get older, dietary control becomes increasingly important, at least until the years of old age.

Besides this general age trend, there is a great deal of variability between individuals of the same age. If you are 40 years old and living on an ordinary middle-class diet, the chances are that you have a blood serum cholesterol concentration between 220 and 270 milligrams per 100 cubic centimetres, but you may be in the 300-plus class or, on the other hand, among the fortunate few with an average value less than 200. There is no explanation at present for these differences in most cases. It is known that both diabetes and deficient function of the thyroid gland raise the cholesterol, while excessive activity of the thyroid sometimes produces unusually low levels. But attempts to regulate the cholesterol with thyroid hormone are both unsuccessful and undesirable unless there is real evidence of thyroid disorder.

So the importance of the diet is not the same for everyone. From cholesterol measurements in the blood of thousands of persons all over the world, we know that not many adults in those countries where heart disease is common have serum cholesterol values as low as the averages in populations who have relatively low susceptibility to coronary heart disease. But some people are in this class and we see no reason why these individuals should change their present diet. You can if you like arrange for a doctor to carry out your blood analysis. Of course your serum cholesterol concentration is far from being an infallible indicator of your coronary future. You must not let your life insurance lapse just because your report comes back "cholesterol 180 mg. %". (This is a low figure.) Similarly, the finding of a high value is not necessarily a cause for alarm, although it may properly produce determination to do something about it.

This brings up the thorny question of defining "high" and "low" cholesterol values. The interpretation of your blood analysis should be the responsibility of your own doctor, but we shall hazard the opinion that no value above 225 milligrams of total cholesterol per 100 cubic centimetres of serum should be a cause for rejoicing and that all values above 250 are definitely undesirable. For persons under 30 years of age these limits might be set 25 to 30 milligrams lower. In populations in which coronary heart disease is really uncommon not many values over 200 are found even in middle-aged men; perhaps we should set our cholesterol goal at the same low level.

Cholesterol, Lipoproteins or "Giant Molecules" Cholesterol is carried in the blood, which is a watery medium, yet it is not soluble in water. Actually, there is little if any plain cholesterol in the blood; it is combined with proteins and fats in so-called "giant molecules" - the lipoproteins - which are water-soluble. And this also explains how water-insoluble fats can be carried in solution in the blood. The significant point is that cholesterol is an essential part of the lipoproteins - it is needed to form the combination that puts fats into a water-soluble form. Cholesterol, therefore, is not an abnormal or useless substance in the blood but plays a necessary role in making it possible to transport and use fats in the body.

The whole story of what happens to fats from the time they are eaten until they are burned in the body to provide useful energy is complicated and many details are still unknown, but the main features can be outlined in a rather over-simplified version to show how cholesterol fits into the picture. First, after we eat fats they are absorbed into the blood, causing the plasma (the liquid part of the blood) to turn cloudy or, if there is much fat, opaque and creamy. The plasma at this stage is an emulsion like milk, with countless tiny droplets of fat suspended in it. The fat cannot be used by the cells of the body in this form, and anyway there is a temporary surplus of fuel after a meal. But after a few hours the plasma becomes clear again, not because the fat has been burned up but because the liver has been busy.

Much fat can be stored as such in the liver and this is what happens, temporarily, to a good deal of the fat we absorb. This gets the fat out of the way but it does not solve the problem of utilizing it, of providing the fat as a steady supply of fuel to the tissues all over the body. One answer would be to put fat back into the blood but in solution, not in suspension. And so lipoproteins are formed and released into the blood. The net effect is an increase in the amount of cholesterol in the blood. If there is any shortage of cholesterol, the liver promptly makes as much as is needed, and some of the fat, after being broken down part way, can be used for this synthesis of cholesterol. As for the protein needed to make the lipoproteins, this is normally at hand.

Lipoproteins are useful in fat transport in the body but they also create a new problem. The fats in the lipoproteins are valuable fuels, but when they are burned the protein and cholesterol in these lipoprotein molecules remain. The proteins present no problem; they can replace the proteins lost from the cells by "wear and tear", they are readily burned as fuel, and, in any case, they are water-soluble and hence not liable to pile up as deposits. But the cholesterol cannot be so burned and it is a water-insoluble remnant, useless or worse. It is not surprising, then, that some of the cholesterol tends to be deposited in the tissues it finds itself in, particularly in the intima of the arteries.

The liver, which so obligingly makes cholesterol to match the amount of fat to be converted into lipoproteins, also is efficient in disposing of excess cholesterol by excreting it in the bile both as cholesterol and in the slightly altered form of the bile salts. Aside from the occasional danger of forming gallstones (cholesterol is a major constituent of gallstones) this is a satisfactory means of disposal, but the cholesterol must be in the liver to be handled in this way; cholesterol elsewhere in the body has to be brought back to the liver and this is not easy because, again, of the problem of water insolubility.

But what about the cholesterol in the foods we eat? Egg yolks contain a great deal of cholesterol, and there is some cholesterol associated with all of the animal fats in the diet. Does this pile up in the blood and tend to deposit in the tissues? This readily happens in rabbits and chickens but not in rats or dogs, the difference depending on the efficiency of the liver in excreting excess cholesterol in the bile. In this respect man resembles rats and dogs far more than rabbits or chickens, and, short of being confronted with enormous experimental doses of cholesterol that never occur in any ordinary diet, the blood cholesterol in man is quite independent of the amount of cholesterol in the diet. If the human diet is loaded with cholesterol, it is either not absorbed or it is excreted; if the diet contains little cholesterol, the liver makes whatever is needed to match the fats in the manufacture of lipoproteins.

Not all of the fats transported around the body are in the form of lipoproteins. Some droplets of plain fat persist in the blood for many hours after absorption, especially after heavy fat meals. Delayed clearing of the blood is often observed also in coronary patients, indicating that such people are prone to have difficulty in handling fats. A heavy burden of fat droplets in the blood may make the blood sticky, harder to pump and likely to cause the red cells to clump together. Altogether, forming an emulsion in the blood does not seem to be a good way to transport fat.

Another way of transporting fat in the blood involves a partial breakdown of the fat molecule. The true fats consist of fatty acids combined with a little glycerol, commonly known as glycerine, three molecules of fatty acids being joined with one of glycerol to form a fat molecule. The first step in the breakdown of the fat is to release the fatty acids. The glycerol, which is water-soluble, is an acceptable fuel, and the fatty acids are avidly taken as fuel by the cells. These unattached fatty acids, called NEFA (short for non-esterified fatty acids), are not found in the blood except in very low concentrations and only a minute fraction of the fat in the body can ever be in this form at one time. However, because NEFA seem to be a preferred fuel, a good deal of the fat we burn goes through the stage of NEFA in the blood.

It is unknown whether these NEFA have any effect on the development of atherosclerosis; they are still an obscure chapter in the fat story. Since NEFA are just about as water-insoluble as are ordinary fats, it is a mystery as to how they are carried in the blood; somehow they are associated with the albumin in the blood to make a water-soluble complex.

The latest evidence, including our own experiments on man, indicates that perhaps the main and primary effect of the diet on the blood cholesterol (and eventually on the deposits in the arteries) is through the production and excretion of the bile salts, the changes in the blood cholesterol being secondary. One of the main functions of the liver is to produce bile which is primarily a mixture of cholesterol and the bile salts, compounds closely related to cholesterol and, in fact, made from it. When we eat fats, bile pours from the liver by way of the gall bladder into the upper part of the intestine where it greatly aids the digestion and absorption of the fats eaten. Lower down in the intestine, part of the cholesterol and bile salts are reabsorbed, circulate around in the blood and come back to the liver, but a good deal of these substances from the bile are excreted in the stools.

If we measure the amount of cholesterol and bile salts excreted in this way we find that when we change from saturated to higher unsaturated fats in the diet the amount of them excreted is greatly increased. And, by indirect calculation, we conclude that the synthesis of cholesterol by the liver is, at the same time or a little later, actually increased. But, the increased excretion of cholesterol and its derivatives resulting from this change from saturated to unsaturated fats is so great that the total supply in the body is decreased, in spite of the liver actually making more cholesterol. It appears, then, that the loss of these materials in the bile stimulates the liver to make more of the present compound (cholesterol) but as this is only secondary, the net result is a decrease of blood cholesterol - it is leaving the body via the bile faster than the liver can make it.

This sounds complicated; it is complicated. But we can sum up simply. All fats stimulate the liver to make cholesterol but the poly-unsaturated fats help the body to get rid of it even faster. Saturated fats, however, lack this action so cholesterol piles up and the blood level rises.

All this complication may be bewildering, though actually we have, as promised, only given a summary of part of a complex picture that still holds many puzzles for the biochemist. But it should be clear enough that there is a real connection between dietary fats and cholesterol in the blood, and we are not dealing with pure speculation or a complete mystery. Further, it is obvious that cholesterol and lipoproteins are not independent substances, as is sometimes implied. Cholesterol is a major and essential ingredient in the lipoproteins.

There are several kinds of lipoproteins differing in size, density, and their content of cholesterol. "Beta" lipoprotein has a higher concentration of cholesterol in it than the "alpha" type and appears to be much the more dangerous in regard to depositing cholesterol in the arteries. Most of the blood cholesterol is in the beta lipoprotein, and it is this type that is readily affected by the fats in the diet.

There are arguments as to which method of blood analysis best reveals the threat of future coronary heart disease. We can measure the total fats, the total cholesterol, or the total lipoproteins in the blood; we can estimate the lipoprotein fractions separately or the cholesterol in the separate fractions. And for each of these measurements there are several different methods which yield similar but not identical results. Which method is most likely to single out the persons who are in the greatest danger and, therefore, in most need of such prophylactic and corrective measures as can be applied? This question has produced a vast deal of heated debate, but it now appears that several of these methods that are most passionately espoused differ relatively little in their predictive value. They all have high statistical value in comparing groups of people; no particular measurement, or even all methods put together, is very reliable in predicting the fate of an individual. We are personally inclined to think that the measurement of cholesterol in the beta lipoprotein fraction of the blood serum is a little more informative than the others. But this complicated and expensive procedure is at most only a trifle better than the simple total cholesterol measurement. Other methods of estimating the lipoproteins, such as with the ultracentrifuge, seem to be less useful for this purpose in spite of the propaganda from some laboratories which offer commercial analyses and promise a report on the "atherogenic index".