The Environmental Aspects of Cardiovascular Disease

William J. Rea, MD, FACS, Environmental Control Unit, Brookhaven Medical Center, Dallas, TX, USA
 
 

Over the past century, since the development of the germ theory, physicians have shown much interest in the treatment and prevention of infectious diseases. Now that most of these can be controlled, we are able to delve deeper into the reasons why certain individuals lack resistance and are prone to recurrent infections or to the development of noninfectious inflammatory diseases. The weight of the individual=s environmental burden upon the body=s homeostatic mechanisms appears to be an overwhelmingly important factor in the breakdown of resistance. In this article, I shall attempt to explain the numerous ways in which environmental overload can trigger disease processes concentrating on disease of the cardiovascular system.

Environmental triggering agents for cardiovascular responses, excluding infectious agents, have rarely been reported. However, Hare,1 in the early 1900s, described vasoactive phenomena in patients after food challenges and showed that there was an increase in heart rate in some. In 1925, Lichtwitz2 demonstrated what was probably the first causal relationship between food and a case of angina pectoris. In the next decade numerous case reports and small series showed a direct cause-and-effect relationship between the ingestion of food and arrhythmias.2 Harkavy3 demonstrated that in some patients angina could be triggered by cigarette smoke. Using a semi-controlled environment, T.G. Randolph (personal communication) has been able to demonstrate a whole spectrum of arrhythmias in patients challenged with synthetic chemicals.

Recently, much has been written about the ill effects produced by aerosols and fluorocarbons. This may have been stimulated by Taylor and Hern=s4 report of a cardiac death in a 16-year-old boy due to sniffing an aerosol. The harmful effects of fluorocarbons were brought home by Spizer and his colleagues,5 who reported an increase in arrhythmias with an increase in length of exposure to fluorocarbons.

Certainly Nour-Elden=s6 studies showing that the vascular tree has an increased affinity for phenol, coupled with Yevick=s7 demonstration of inflammatory and fibrotic changes in the cardiovascular system of sea animals exposed to oil spills, add weight to the possibility that excessive pollution has an adverse effect on the heart.

More recently, Finn8 has also shown that arrhythmias can be caused by foods, and I have had experience of several cases in which arrhythmias have apparently been triggered by environmental incitants.9
 
 

FUNDAMENTAL OBSERVATIONS AND CONCEPTS When considering whether an environmental trigger may be a factor in a patient=s illness, the clinician must bear certain facts and concepts in mind. Technological lag Medical ecology lags about 100 years behind environmental technology, and this hampers us in diagnosing and treating diseases caused by noninfectious processes. Moreover, the public, as well as the medical profession, is generally aware of potential environmental triggering agents. These substances are found in such abundance in homes, workplaces, and even in hospitals that at times they may bring to naught all attempts at treatment. Total body load Total body load refers to the sum of all the incitants that the body has to handle in order to function; it is the total of the pollutants in air (Table 1), water and food. The concept seems simple until we realize just how extensively our environment is pollutedCand how insidiously this has come about. The total body load tends to distort many of the body=s homeostatic mechanisms10 and often becomes too great for persons with certain hereditary or acquired tendencies to handle; the result is an individual susceptibility to inflammatory diseases.
Table 1

Degree of Air Pollution in Different Areas

Sea air 0 (excluding salt particles)
Desert air 10 x
Towns (>2500 population) 35 x
Urban 150 x (good days)

1,000C4,000 x (average to bad days)


 

Masking or adaptation

The concept of masking or adaptation11 is as follows (Table 2) : An individual comes into contact with a potentially harmful substance but sustains no apparent harm because there is no immediate reaction. This occurs if he is exposed daily or more frequently. However, should he then avoid the substance for four days he becomes unmasked. If he now takes the suspect substance into his body, there will be an immediate and clearly definable reaction if the substance is, in fact, harmful to him. Cause and effect are now easy to establish. Often, however, food sensitivities are missed because the individual eats the offending food daily, thus masking the symptoms. When this happens the patient no longer perceives the harmful effects and remains healthy until eventually inflammatory disease developsCwhen the time comes, the cause of the illness is obscured because of the masking effect.

Table 2

The Masking or Adaptation Concept

Stage I Stage II Stage III
Alarm Resistance Exhaustion
Nonadapted Adapted Maladapted
Unmasked Masked  Overload

 

Bipolarity

Another concept is that of bipolarity.12 Often an individual is initially stimulated and feels the substance is not harming him but actually doing him good. However, after a period of timeCbe it minutes, months, or yearsChis body=s defenses break down and he develops disabling withdrawal symptoms. Although this is a well-recognized occurrence among cigarette, narcotic, and/or alcohol addicts, it is by no means as well known (despite being just as prevalent) among plastic workers, painters, food addicts, and many other individuals who constantly inhale or ingest a toxic substance. Biochemical individuality The final concept is that of biochemical individuality.13 Each individual possesses a finite number of enzymes quantitatively different from the next. One person may have a superabundance while the next may have too few to fight off pollution.
 
 
ORGAN INVOLVEMENT Many organs appear to be targets for environmentally triggered diseaseCin fact, anywhere that smooth muscle exists might represent a possible target. As well as the cardiovascular system, the systems most likely to become involved are the respiratory, the gastrointestinal, and the genitourinary. In addition, the skin is involved in many patients.

When the cardiovascular system is involved, symptoms can be widespread. Such entities as nontraumatic phlebitis,14 nonarteriosclerotic arrhythmias,15 and large or small vessel vasculitis16 can occur. Raynaud=s disease and phenomenon are often observed.17 Arthritis,18 arthralgia, myositis, fibrositis, and myalgia are frequently present. Perhaps myocardial infarctions and strokes are triggered.

A symptom complex is often seen which may give a lead to the possibility of an environmental trigger. It consists of acneiform lesions, petechiae, and/or spontaneous bruising and purpura, peripheral coldness and cyanosis, and peripheral and periorbital edema. The acneiform lesions usually occur on the face and shoulders and may number from one to thousands. Localized edema or urticaria occasionally occurs, but the more generalized peripheral and periorbital edema is much more common. However, this is often subtle and may be overlooked. People almost accept swelling of their fingers to the point that rings cannot be removed as normal and expect edema to occur cyclically around the eyes and in the feet. Should the blood vessels leak further, extravasation of red cells leads to the appearance of bruising, purpura, and petechiae. Peripheral spastic phenomena, in the absence of cold, occur when the body is challenged with chemicals and foods. If the physician keeps in mind the possibility that any or all of the major systems containing smooth muscle may be involved, he will be better able to diagnose and treat environmentally triggered disease.
 
 

Proposed Mechanisms of Vascular Pathophysiology There are many ways in which inflammatory disease may develop.19 Basically, however, triggering acts on the homeostatic mechanism through the immune and nonimmune systems (by an effect on the immunoglobulins or by the activation of complement, either directly or via the alternate pathway, or by other mediators17 such as kinin or prostaglandin20). Occasionally, trauma can trigger the entire chain of events. Regardless of the pathway involved, the final result is increased membrane permeability with leakage of fluid and eventually of cells also. This produces edema and probably local cell hypoxia with consequent lactic acidosis. Edema, localized or general, seems to be the initial pathological event observed in most individuals sensitive to environmental incitants.

Once blood vessels become inflamed, a myriad of symptoms becomes possible. If the inflammation is generalized, edema occurs. If it is localized, urticaria is seen. If the vessels leak further or even rupture, there is bruising, purpura, and petechiae. Biopsy of these lesions reveals either the leukocytoclastic type of vasculitis with invasion by polymorphonuclear leukocytes, the lymphocytic infiltrative type or the perivascular lymphocytic infiltrative type. Occasionally, the eosinophilic type is seen. As the pathological derangement progresses, clotting occurs and the disease process becomes much more fixed. When diseases become fixed and, therefore, usually irreversible, they are recognized as entities such as necrotizing or hypersensitivity angiitis, giant cell arteritis, Wegener=s granuloma, temporal arteritis or vasculitis, connective tissue disease such as systemic lupus erythematosus, or rheumatoid arthritis, and so on. Finally, should local necrosis not occur, healing takes place by the formation of granulomas of plaques.

Levi21 has proposed a mechanism for the triggering of vascular disease. This, theoretically, holds true even for the triggering of infarctions or strokes. Often environmental triggering involves only the heart and can be responsible for very severe symptoms. Frequently, these are suppressed by medication and can continue for years before death occurs. However, some patients are unable to tolerate even the medication and they become seriously incapacitated.

I have been able to stop and reproduce many arrhythmias, including ventricular tachycardia, in 20 patients in the hospital under environmental control. These patients were usually seen to have normal large vessels on coronary angiography. Some, however, had coronary artery spasm. A few had plaque formation and apparently suffered from arteriosclerosis in addition to vasculitis.
 
 

METHODS OF STUDY Study on patients suspected of suffering from environmentally triggered diseases can only be done under the proper rigidly controlled conditions. For example, investigation for food and chemical susceptibility must be done in meticulous detail in order to discriminate and define clearly the particular incitants. The methods used are refinements of established techniques.22, 23 Each category of pollutantCair, food, and waterCmust be considered in all its aspects and all aspects must be considered as of equal importance if we are to diagnose and treat patients with environmentally triggered diseases.

Our original and baseline studies are done in a specially constructed wing of the hospital. Here, city air can be depolluted not only for particulates but also for gases. The wing is constructed of glass, steel, porcelain, and stone. Most inner materials are of natural fibers decontaminated for synthetic chemicals. Analytical measurements of the air are carried out using gas chromatography, mass spectrometry and portable counters, organoleptic monitors (usually emotionally stable sensitized human beings who respond to chemical contamination of the environment), and biological responses in environmentally sensitive individuals not receiving medication (when in the clean environment of the Unit their eosinophils, gamma globulin, complement, and T lymphocytes show a return to normal values). Inorganic pollutantsCsuch as carbon monoxide, nitrogen dioxide, sulphur dioxide, hydrogen cyanide, chlorine, and chlorine dioxideCare reduced by 70-100% in the Unit when compared to outside air and in other parts of the hospital. Organic pollutantsCsuch as formaldehyde, petroleum alcohol, pesticide (2,4 DNP), phenol, xylene, hexanes, and alkabenzenes are reduced by 90-100% in the Unit as compared to the rest of hospital and the home environment. Particulates are reduced five-fold compared to the rest of the hospital. Spring and distilled waters are used in place of piped city water.

Chemically less contaminated foods grown, stored, and prepared in the relative absence of petrochemicals are also used in order to have proper controls for reproducible studies in patients sensitive to foodstuffs.

Laboratory investigations Many laboratory investigations are now available to help to define changes in the body=s homeostatic mechanisms when a patient is exposed to incitants. Not all are specific but these measurements sometimes can be an aid in confirming the diagnosis of environmentally triggered disease.

Eosinophil cell count. This is usually depressed in patients with environmentally triggered disease. In a consecutive series of more than 300 patients presenting to our Unit with a food and chemical susceptibility, the eosinophil cell count was below 3.5 x 10?/? Cnormal range in our laboratory, 50-200/mm3) in 90%. The 10% of the patients who had an eosinophilia were usually those with asthma or dermatitisCand they were definitely in the minority of patients presenting with those conditions. Once the patient was in the basal state and his peripheral eosinophil cell count had returned to normal, he was challenged with incitants. Frequently, the count was found to be depressed in serial blood specimens drawn during the reaction. If the count was low on admission, it would be low on challenge. If it was elevated on admission, it would rise on challenge.

Peripheral IgG. This was depressed on admission in 15% of our patients. Usually, levels returned to control values without treatment other than avoidance. Often depression recurred upon challenge. The reason for this is unexplained since the body usually contains a large pool of IgG.

Complement. Total hemolytic serum complement CH50 and CH100 has been measured in more than 300 of our patients, as have the C3 and C4 components. Thirty-five percent of the patients appeared to have total complement levels outside the two standard deviation ranges of 80-120%, most being below 70% of control values. Incitant challenge depressed the total complement. The C3 level, when abnormal, may be depressed, whereas C4 was usually elevated. All nine complement components were assayed in 75 patients who presented with initial depression of their total complement levels and frequently C? was also found to be depleted. In 75% of cases, the depressed levels returned to control values by the time the patients had achieved an adequate and consistent program of avoidance.

T and B lymphocytes. B lymphocytes were rarely outside the normal range of 20-40%. However, in 50% of the patients, the total lymphocyte count was below the 60% range, and in most cases the absolute T lymphocyte count was below 1 x 103/L? (1000/mm3). T lymphocytes thus appear to be sensitive indicators in these patients and frequently their levels fall on challenge.

Blastogenesis. Lymphocyte transformation as a result of stimulation with pokeweed mitogen and phytohemagglutinin has been measured in more than 200 patients. Different concentrations have been found to be important in assessing sensitivity, as stimulation may occur only at specific levels. Twenty percent of our patients showed low levels of transformation. These are the most difficult to work with and the slowest to respond to treatment. However, as treatment progresses, the response is reflected in a general increase in transformation.

C-Reactive protein. This was elevated in 10% of our patients but often returned to normal as the inflammation subsided.

IgE. Since IgE was isolated by Ishikawa and his colleagues,26 it has been regarded as the carrier immunoglobulin in allergy. IgE has been measured in more than 400 patients with a food and/or chemical problem: 10% had levels over 100 times the control. Although IgE levels are popularly thought to be elevated in individuals with pollen, dust, and mold allergies, they appear to be of much less significance in the total assessment of patients with environmentally triggered disease. Certainly, when IgE levels are elevated, skin tests will be positive and radioallergosorbent tests (RAST) will also show raised values; the patient will respond to injection therapy. These patients usually are easy to treat by hyposensitization, with the optimum dose best being worked out by skin tests employing serial dilution titration. However, caution is imperative when treating patients with low IgE levels and negative RAST results as they may well be extremely sensitive to inhalant antigens, probably through an abnormality in another as yet undefined mechanism.

IgA. Reports have indicated that low surface IgA levels may occur. However, fewer than 1% of our patients had low IgA levels. At present, therefore, we have been unable to correlate the apparent depletion of this immunoglobulin with clinical entities as have some other authors.

IgM and IgD. No correlation has been seen in more than 400 patients in whom these immunoglobulin levels have been determined.

Leukocyte inhibitory factor. Using the food to which the patient is sensitive on challenge, tests for this factor have been done on more than 400 patients with environmentally triggered disease. Food is placed in the patient=s fresh blood, and the number of leukocytes inhibited after incubation is counted. However, this test appears to be only about 60% accurate.

Cytotoxic food test. This test is not completely reliable. In some individuals the correlation is almost 100%, but in others there seems to be little correlation.
 
 

METHOD OF DIAGNOSIS Traditionally, diagnosis is made by withdrawal and challenge; however, in many cases quantitative skin tests can be used for diagnosis.
 
 
TREATMENT The whole patient should be considered over a period of years. Many measures, though satisfactory in the short term, may be detrimental in the long term. It is becoming increasingly apparent that, if treated early, allergic-like manifestations can be prevented from developing into measurable end-stage cardiovascular disease. It is being shown that patients may do well for a few months to several years with injection therapy for pollen, dust, and mold and food sensitivities and then suddenly start deteriorating. They may even lose their inhalant or food sensitivity but develop a chemical sensitivity. It is not certain why this spreading phenomenon occurs, but it appears to be due to an overload of synthetic chemicals. Though symptomatic treatment may help for a short time, and in some patients for long periods of time, it is clear that removal of incitant triggers is the best mode of therapy if they can be identified. Pollen, dust, mold Avoidance techniques. Certainly avoidance is the best method of dealing with these pollutants, but injection therapy usually must be used simultaneously. Cleanliness in the home is most important. Most cleansing agents should be nontoxic: borax and baking soda are the primary safe cleaners. Nontoxic soaps are available. Antidust sprays should not be used. Antimold treatment (for instance, washing the room with formaldehyde and keeping some in the room) is mentioned only to condemn it, since many patients can develop a chemical sensitivity as a result. Synthetic mattresses and covers are also mentioned only to be condemned. Although they decrease the amount of dusts and molds in the environment, they increase the risk of the allergic patient=s developing a chemical sensitivity due to the constant fuming of the synthetic materials. It is much better to strip the bed to the springs and then build up the area with cotton blankets and cover with a closely woven cotton sheet made from surgical barrier cloth. The mattress can thus be taken apart at any time and washed thoroughly. If a cotton mattress is already available, one can place the barrier cloth over the mattress as a cover. The mattress must not be fireproofed with a chemical retardant or mildew proofed.

Hyposensitization. Usually pollen, dust, and mold hyposensitization is used, bearing in mind the precautions mentioned above. Sensitivity to phenol and glycerine appears to be an increasing problem. It has been my experience that many patients who have been intolerant to phenol or glycerine can be treated if these substances are omitted from the injections. Unfortunately, the extracts are then more hazardous as they have to be kept frozen except when in use.

Food Avoidance techniques. A diversified rotation diet should be adopted both for treatment and for prophylaxis. A five-day rotation is adequate for some individuals; others may need a seven-day or 10-day rotation; still others will have to rotate at up to 30 days with some foods. Some foods must be totally avoided.

Neutralization. Food neutralization injection therapy as advocated by Miller27 seems to be an excellent adjunct to the rotation diet. In our Unit, there is a high correlation between challenge testing and skin wealing in moderately sensitive patients. After neutralization, approximately 75% of the foods could be included in the rotation diet at least once every seven days. Some foods could be eaten without impunity but, more often, repetition led to loss of tolerance for that particular food.

Although this series was small and testing was not done in a double-blind manner, it was clear that repeated challenge consistently resulted in reactions to the food. When daily injections of the neutralizing dose of a food were given, the patient could eat the food on rechallenge. When the injections were withheld, sensitivity to the food rapidly returned. These tests were done under controlled conditions.

Physicians have been using neutralization techniques for food for long enough to realize that injection therapy may fail at any time. Although there is a multitude of reasons for this, chemical overload in food-sensitive patients appears to be the prime cause. As our environment steadily deteriorates, so the problem of chemical sensitivity increases.

Chemicals Treatment for chemical sensitivity is complex, since this mostly consists of avoidance. Some individuals respond intermittently or briefly to neutralization therapy with phenol, ethanol, formaldehyde, and various other synthetic extracts; but these appear to be only >cheater doses= and are effective for only a few hours.

The principles of chemical avoidance can be discussed only briefly here. Those who wish more details can consult Randolph,12 Dickey,19 or Golos.28 The book by Natalie Golos is of particular value to physician and patient alike.

Patients must use safe water. Usually, charcoal-filtered water is adequate if all devices are made of stainless steel. The filter will not remove fluoride, however. Frequently, one of the many available spring waters is best, but even this must be kept in glass containers or the sensitive patient will not tolerate it. A few patients tolerate distilled water. Approximately 1% of the chemically sensitive patients can tolerate no water and are extremely difficult to manage.

Food with a low level of chemical contamination is most important for those with a chemical susceptibility. There is now a sufficient number of patients in all major cities in the USA to make the formation of cooperatives a worthwhile undertaking. We have found it necessary to ask farmers to grow chemically less contaminated foods in order to have a constant and safe supply. Reliance upon health food stores is difficult because many foods sold there are contaminated.

The home environment is the most important place to maintain free of pollution. There should be no gas appliances in the house. If coal or petroleum products are used, they should be kept away from the house and boilers used for heating; the hot water can then be pumped into the central system and the heat carried throughout the house. Lower temperature electric heating appears to be tolerated by many patients. The bedroom should be the main sanctuary. Bedding should be 100% cotton or linen, as previously described. Curtaining of the windows should be either 100% cotton or metal blinds. All clothing except that which the patient can tolerate must be removed from wardrobes, cupboards, and drawers. Articles remaining in the bedroom and/or en suite bathroom should be kept to a minimum; all plastics, cosmetics, and cleaning agents should be removed.

All clothing should be of washable cotton, linen, or silk. Since formaldehyde is often used in conditioning cotton materials, care should be taken to process new clothing before it is worn. A vinegar soak followed by laundering with sodium bicarbonate is the best method for removing substances used in the chemical treatment of cotton. This process may have to be repeated several times for the sensitive patient.

Finally, no pesticides, herbicides, fertilizers, or the like should be used in or around the house.
 
 

REFERENCES

1. Hare, F. (1905). The Food Factor in Disease. London: Longmans.

2. Lichtwitz, cited in Harkavy.

3. Harkavy, J. (1963). Vascular Allergy and Its Systemic Manifestations. Washington: Butterworths.

4. Taylor, G.S., and Hern, W.S. (1970). Cardiac arrhythmias due to aerosol propellants. Journal of the American Medical Association 219:8.

5. Spizer, F.E., Wegerman, D.H., and Ramiers, A. (1975). Palpitation rate associated with fluorocarbon exposure in a hospital setting. New England Journal of Medicine 292:624.

6. Nour-Elden, R. (1970). Uptake of phenol by vascular and brain tissue. Microvascular Research 2:224. 7. Yevick, P. (1975). Oil pollutants in marine life. Eighth Advanced Seminar. Society of Clinical Ecology Instatape, Tape 11. 8. Finn, R. (1979). Food allergy. Lancet 2:249.

9. Rea, W.J. (1979). Environmentally triggered cardiac disease. Annals of Allergy 40:243.

10. Rea, W.J. (1979). Diagnosing food and chemical susceptibility. Continuing Education 16:47.

11. Rinkel, H., Randolph, T.G., & Zellner, M. (1946). Food Allergy. Springfield, IL: Thomas.

12. Randolph, T.G. (1962). Human Ecology and Susceptibility to the Chemical Environment. Springfield, IL: Thomas. 13. Williams, R.J. (1963). Biochemical Individuality. New York: Wiley.

14. Rea, W.J. (1976). Environmentally triggered thrombophlebitis. Annals of Allergy 37:101.

15. Rea, W.J. (1978). Environmentally triggered cardiac disease. Annals of Allergy 40:243.

16. Rea, W.J. (1977). Environmentally triggered small vessel vasculitis. Annals of Allergy 38:245.

17. Rea, W.J. (1979). The environmental aspects of ear, nose and throat disease, Part I. Journal of Continuing Education ??????????? 18. Dickey, L. (1975). Clinical Ecology. Springfield, IL: Thomas. 19. Zeek, P.M. (1953). P?????nodosa and other forms of necrotizing ?????. New England Journal of Medicine 248:764. 20. Bussert, P.D., ???????????? Lancet 1:906. 21. Levi, R. (1979). Is cardiac anaphylaxis a cause of sudden death? American Heart Association presentation. January 1979.

22. Rowe, A. H., and Rowe A, Jr. (1979). Food Allergy: Its Manifestations and Control and the Elimination Diets. A Compendium. Springfield, IL: Thomas.

23. Coca, A.F. (1902). Familial Nonreagenic Food Allergy. Springfield, IL: Thomas. 24. Randolph, T.G. (1960). Food susceptibility (food allergy). In Current Therapy, Ed. H. Conn, p. 416. Philadelphia: Saunders.

25. Rinkel, H.J., Lee, C.H., Brown, D.W., Jr., Willoughby, J.W., & Williams, J.E. (1964). The diagnosis of food allergy. Archives of Otolaryngology 79:71.

26. Ishikawa, K., Ishikawa, T., & Hornbrook, M.M. (1966). Phys-co-chemical properties of human reaginic antibody IV. Presence of a unique immunoglobulin as a carrier of reaginic activity. Journal of Immunology 97:78.

27. Miller, J.B. (1972). Food Allergy: Provocative Testing and Injection Therapy. Springfield, IL: Thomas.

28. Golos, N. (1975). The Management of Complex Allergies. Chicago: Human Action League.