HEPARIN AND ATHEROSCLEROSIS
by John H. Olwin, MD
The most frequent cause of death in Western civilization is cardiovascular disease, and within this category the greatest killer is atherosclerosis – the narrowing of arteries by the deposition of fatty plaques on their linings and within their walls. When the early Greek physicians opened the arteries of their departed patients, they observed a gruel-like (athero) "mush," which was quite hard (sclerotic), hence our term "atherosclerosis." It is obviously a metabolism gone awry, and while we know a number of factors that aggravate it, such as obesity, smoking, industrial pollution, diet, and lack of physical exercise, there are still influences that are unclear. There are primitive tribes that have a low incidence of the disease. Eskimos who eat largely ocean fish are relatively free from it. With increasing industrialization, the incidence and mortality rates go up. Heredity may play an important role. Recent demographic reports relate the level of low-density-lipoprotein cholesterol and the severity of atherosclerosis. Not a few children are found to have an elevated cholesterol. Atherosclerosis appears to be related to the blood-clotting mechanism; in many patients with coronary artery disease, increased clotting tendencies can be demonstrated.
A number of local factors contribute to the process of atherosclerosis:
All of the foregoing events result in the formation of the "fatty plaques" that proliferate and finally clog the arteries.
Heparin is a naturally occurring substance in most mammalian species. Best known for its anticoagulant property, it plays an important role in maintaining the balance between abnormal bleeding and abnormal clotting. It has a variety of other functions, however, which have had much less publicity, one of its little-known ones being that of a powerful antihistaminic. For instance, some migraine headaches in which histamine plays a prominent role can be prevented by 20,000 units of heparin given intravenously at the onset of the prodromal symptoms. It has also been used successfully in the treatment of other allergy conditions. It aids in the destruction of clots (fibrinolysis), hastens the return of a negative charge to the lining (intima) of blood vessels after injury, lowers the tendency of platelets to stick together (agglutinate) and to stick to the blood-vessel wall, aids in the digestion of fats (lipolytic effect), inhibits smooth-muscle-cell proliferation in blood vessel walls, decreases blood viscosity, and enhances the action of the lipemia (abnormally high fat in blood)-clearing factor (lipoprotein lipase). Increased lipema also diminishes the tissue oxygen supply, which is important in atherogenesis and heart muscle deficiency. Heparin reduces the absorption of fat from the intestine and also neutralizes the effect of lipema on the diffusion of oxygen into tissues. Space does not allow a discussion of these many functions of heparin or of others not mentioned, but it is obvious that it is a tremendously important factor in many metabolic activities. For our purposes, it is significant that it neutralizes all of the above factors and others having to do with the development and progress of atherosclerosis.
It is not surprising, then, that there is an extensive literature on the use of heparin to retard the process of atherosclerosis. Before 1971, ten studies demonstrating this effect were done on animals. Five clinical trials, the results of which were published between 1956 and 1987, all showed a reduction in cardiac deaths with the long-term use of very low doses of heparin. Such doses were much lower than those required to demonstrate anticoagulant effect. Although complications – osteoporosis, depression of platelet formation, and abnormal bleeding – have been reported from the long-term use of heparin, few to none of these have been observed in the studies in which low-dose heparin was used to neutralize the atherogenic influence.
Heparin, whether produced within the body or introduced from the outside, is stored largely in the lining of the blood vessels and is released as required by the body. Presently accepted doctrine holds that heparin is ineffective when taken orally; it is usually administered today by subcutaneous or intravenous injection. It may also be inhaled by means of the aerosol nebulizer. Effects resulting from intake by this latter route may persist for up to two weeks – longer than by any other method of administration.
With such background and evidence, it is amazing that heparin is not in general use the world over. Delays in acceptance by the medical profession of "new," even though patently effective and safe, procedures are not uncommon. The classic example is the lapse of 93 years between Edward Jenner’s report of his technic and results for smallpox vaccination and the appointment by the British government of a commission to investigate their possible validity. It has been only 30 years since the first reports of the anti-atherogenic effects of heparin appeared.
The above material is based largely on the following papers. They and the many references cited by the authors are recommended reading.
Shulman, A.G., "Heparin for Prevention of Atherosclerosis," New England Journal of Medicine 319: 1154-55, October 27, 1988.
Jaques, L.B., "Drug Prophylaxis in Atherosclerosis," Artery 14(4): 209-15, 1987.
Engelberg, H., "Heparin and the Atherosclerotic Process," Pharmacological Reviews 36: 91-110, 1984.
Jaques, L.B., "Heparins – Anionic Polyelectrolyte Drugs," Pharmacological Reviews 31: 99-166, 1980.
Jaques, L.B., J. Mahadoo, and L.W. Kavanagh, "Intrapulmonary Heparin A New Procedure for Anticoagulant Therapy," Lancet 2: 1157-61, 1976.
Article from NOHA NEWS, Vol. XIV, No. 2, Spring 1989, pages 3-4.