Predictive Medicine XIV. Results

ABSTRACT: Much has been written about the nature and causes of the aging process. For purposes of a predictive medicine program the following points serve as a reasonable base: 1) old people report more symptoms and signs, 2) the old die more readily than the young, and 3) old people with many symptoms and signs die more readily than old people with few such manifestations. Thus it is highly desirable to use all the techniques possible to reduce the number of clinical findings to a minimum.
A predictive medicine program can anticipate classical disease. One example is given to show that the supposed inevitable increase of cardiovascular symptoms and signs with age can be thwarted by dietary means (vitamin E). Another example is given to indicate that, partly by exercise or diet, people may be made younger at heart.

 

“When your work speaks for itself, don’t interrupt.” – Henry J. Kaiser

 

The purpose of the thirteen earlier reports¹ was to establish concepts and set the stage for an operational predictive medicine program. Broadly speaking, prediction is possible when two variables significantly coexist. For prognostic purposes, one factor need not be the cause of the other. In the earlier publications¹ scores of such relationships were described. Nevertheless, it is helpful when there is a cause-and-effect relationship for only then can one variable be changed by altering the other.

The purposes of this, the fourteenth report in the series, are twofold. First, to illustrate the changes which are possible during the early, amorphous incubation period of chronic disease. Second, by so doing, to resolve the oft-repeated question regarding the effectiveness of multiple-testing programs.

Therapeutic Techniques

The surgical separation of a leg or the removal of a kidney stone are painful procedures. The pre- and postsurgical periods, therefore, require potent medication (e.g., morphine). However, under much less serious circumstances, several million people in this country take sedatives, analgesics and hypnotics on a regular basis. If one were to start with the assumption that the real indication for aspirin, for example, is aspirin deficiency, then very few truly therapeutic agents would be in use. In practical terms, the real need is to add resistance agents and thus discourage the onset of chronic disease and minimize susceptibility factors which favor the development of pathosis. In this perspective, diet and physical activity represent the simplest and most practical therapeutic modalities.

For these reasons, this report concerns the changes in clinical state, performance, biochemical status, and enzyme levels made possible by modifying the diet and altering physical activity.

Early Cardiovascular Symptoms and Signs

As suggested in report No. XI of this series,¹ man may be viewed as a lamellated sphere. The most peripheral layers represent the clinical state as judged by symptoms and signs. The point also was made in report No. IV¹ that chronic disease commences with a few isolated findings which, with time, increase until a classical diagnosis is possible.

To demonstrate the effect of diet upon the clinical state, 171 dental practitioners and 128 wives were studied on one occasion in terms of the reported daily consumption of vitamin E and the reported symptoms and signs of cardiovascular disease.² In this group, a second clinical-dietary comparison was made on 58 males and 37 females approximately one year later. Four items warrant special mention. First, the data confirm the well-established clinical observation that, with advancing age, there is an increase in the frequency of cardiovascular findings (Fig. 1). Second, an examination of the relationship between age and the reported cardiovascular findings in both males (Fig. 2) and females (Fig. 3) shows that the increase in clinical findings paralleled age only in the subjects consuming less than the Recommended Dietary Allowance [RDA] for vitamin E. Third, the difference with respect to the number of cardiovascular symptoms and signs was most sharply evident in the relatively oldest subjects. Fourth, a review of the clinical change during the experimental year revealed that the decrease in cardiovascular findings occurred only in the group of subjects characterized by an increase in the daily intake of vitamin E (Fig. 4).

Fig 1. The relationship of age to the frequency of reported cardiovascular findings. In both the male and female groups, there was a low but statistically significant correlation. (In this and subsequent figures, the bracketed numbers below the columns indicate the sample size.)

Fig. 2. The relationship of age and reported cardiovascular findings in terms of the reported daily vitamin-E intake (black columns denote less than 30 I.U., and stippled columns more than 30 I.U.) in male subjects. With advancing age, there was a statistically significant (r = +0.197, P < 0.05) increase in cardiovascular symptoms and signs only in the group consuming less than 30 I.U. of vitamin E daily, which is below the Recommended Dietary Allowances. Intragroup examination by age showed a statistically significant difference (t = 2.740, P<0.01) only in the oldest age category (50+ years).

Fig. 3. The relationship of age and reported cardiovascular findings in terms of the reported daily vitamin-E intake (black columns denote less than 25 I.U., and stippled columns more than 25 I.U.) in female subjects. With advancing age, there was a statistically significant (r = +0.253, P<0.05) increase in cardiovascular symptoms and signs only in the group consuming less than 25 I.U. daily, which is below the Recommended Dietary Allowances. Intragroup examination by age showed a statistically significant difference (t = 2.781, P<0.01) only in the oldest age category (50+ years).

Fig 4. The relationship of change in reported daily vitamin-E intake (left side) to change in reported cardiovascular symptoms and signs (right side) in subjects who increased daily vitamin-E intake (group I) and who decreased daily vitamin E (group III). Only in group I was there a reduction (1.3 to 0.9 complaints per person) in cardiovascular findings of statistical import (t = 2.602, P <0.025).

 

It is significant that early cardiovascular signs and symptoms can be reduced or eliminated before the onset of classical heart disease, and also that this reversal can be accomplished by relatively simple dietary techniques. Most importantly, it demonstrates the effectiveness of a predictive medicine multiple-testing program.

Early Electrocardiographic Evidence of Disease

With advancing age, the electrocardiographic P-R interval lengthens.³ Figure 5 shows the duration of P-R, in different age groups. Is this particular characteristic of the aging process “normal” or is it “physiologic”? The subject has been reviewed in report No. VI of this series.¹ On the assumption that normal is synonymous with average, it is indeed normal for the P-R interval to lengthen with age. However, it is possible to show that it is not a physiologic phenomenon.

Fig. 5. The relationship of the P-R interval (seconds) to age in 872 normal persons [Lepeschkin³]. With time, the P-R interval lengthens.

 

Two hundred and fifty dentists and their wives were participants in a multiple-testing program: (a) in Florida under the auspices of the Southern Academy of Clinical Nutrition, (b) in Los Angeles under the aegis of the Southern California Academy of Nutritional Research, and (c) in Columbus under the sponsorship of the Ohio Academy of Clinical Nutrition.⁴ A standard three-limb lead electrocardiogram was obtained on each subject. The P-R interval was measured carefully under magnification. The Florida contingent, comprising about one-fourth of the entire sample, has been studied for five years. The majority of the subjects, from Ohio and California, have been under investigation for two years. In the initial study, dietary surveys were obtained as well as information concerning exercise, vitamin supplementation, and coffee/tea, alcohol and tobacco consumption.

After completion of the initial studies, the groups were exposed to a series of health-evaluation lectures; the topics included their current diets, the merits and shortcomings of their food intake, and how the diet could be improved. Similar discussions were held regarding physical activity, vitamin supplementation, and coffee/tea, alcohol and tobacco consumption.

Electrocardiograms, dietary surveys and records of physical activity and the foregoing dietary intakes were repeated almost annually. This enabled us to ascertain the electrocardiographic changes in relation to diet and exercise.

Figure 6 shows the P-R values (stippled columns) previously denoted in Figure 5 for 872 normal persons [Lepeschkin³]. Superimposed (black columns) are the findings for the group of 250 seemingly healthy dentists and their wives. Two points are evident: 1) in the dental group there is a lengthening of the P-R interval with time; and 2) the mean value at each temporal point is lower for the dentists and their wives than for the Lepeschkin group of normal persons.

Fig. 6. The relationship of age and the P-R interval in 872 normal persons [Lepeschkin³] (stippled columns) versus 250 presumably healthy dentists and their wives (black columns). In both groups, the P-R interval lengthens with time. However, the rate is much slower in the professional group.

 

After the initial observations, the dietary habits of the group were discussed. It was found that, in general, the refined carbohydrate intake was high, the protein intake low, and the vitamin-mineral intake suboptimal when compared with the Recommended Dietary Allowances outlined by the Food and Nutrition Board of the National Research Council. Also, a significant number of persons reported no daily physical activity. The defects were pointed out to the group and discussions were held about how to improve the diet and to encourage exercise. Subsequently, dietary surveys demonstrated that a large segment of the group had altered their food intake significantly and were consuming, as judged by less refined carbohydrate food substances, greater quantities of protein and more vitamins and minerals. The data also revealed that a large number of the group had begun to take some form of daily exercise.

Figure 7 shows the baseline P-R data of Lepeschkin³ on 872 normal persons (stippled columns). Superimposed are cross-hatched columns showing the mean P-R values for 238 dentists and their wives at the start of the experimental period, and black bars showing the mean P-R values after the series of the health education lectures. Two items are noteworthy: 1) with time, the P-R interval lengthened in each category, and 2) at each temporal point, the mean P-R interval was less after the health education lectures than before.

Fig. 7. The relationship of age and the P-R interval in 872 normal persons [Lepeschkin³] (stippled columns) and in 238 dentists and their wives before (cross-hatched columns) and after (black columns) health education lectures.

 

The evidence demonstrates that the P-R intervals in the dentists and their wives were better (shorter) than in Lepeschkin’s series of normal persons. As pointed out elsewhere,⁵ this is likely due to the fact that it is the health-conscious dentist who tends to participate in a health evaluation program. The data suggesting that the P-R interval may be lowered following health educational lectures are charted in another manner in Figure 8. The oldest group of subjects (60+ years) after health education lectures showed a mean P-R interval of 0.157 second. This was less than the P-R interval (0.158 second) before health education instruction for the 45-60 age group. A similar reversal is shown for age 35-45 versus age 20-35. In every age group, the P-R interval after health education lectures was reduced to that found in persons 15 to 20 years younger.

Fig. 8. Lines a-a and b-b show that, following health education lectures, the mean P-R interval shortens. Apparently, as the group became chronologically older, it became electrocardiographically younger.

 

It is recognized that health and disease are multifactorial problems in a study of this type. It is impossible to develop strict controls. Thus, the changes in the P-R interval are likely due to a combination of changes in the habits of the group.

With regard to the effects of exercise,⁶ Figure 9 shows four groups: 1) those who carried out daily exercise at the beginning and the end of the experimental period, 2) those who started exercise after the initial studies, 3) those who discontinued exercise during the experimental period, and 4) those who engaged in no physical activity during the entire period. The only statistically significant reduction in the P-R interval occurred in the group who started physical activity during the survey period. This is at least circumstantial evidence of the cause-and-effect relationship between physical activity and one electrocardiographic measurement.

Fig. 9. The relationship between a change in physical activity and a change in the electrocardiographic P-R interval duration during a one-year period. No significant change occurred in the groups characterized by: 1) daily exercise at the beginning and end of the year, 2) no daily exercise during the experiment, or 3) those who stopped daily physical activity. There was a statistically significant reduction in the P-R interval only in the group that started to exercise following the initial study.

 

References Cited:

1. Cheraskin, E., and Ringsdorf, W. M., Jr.: “Predictive medicine.” (I.) Alabama J. Med. Sc. 7: 444, 1970; (II.) J. Am. Geriatrics Soc. 19: 448, 1971; (III.) Ibid., p. 505; (IV.) Ibid., p. 511; (V.) Ibid., p. 721; (VI.) Ibid., p. 729; (VII) Ibid., p. 802; (VIII.) Ibid., p. 887; (IX.) Ibid., p. 962; (X.) Ibid., p. 969; (XI.) Ibid. 19: 1000, 1971; (XII.) Ibid. 20:–, 1972; (XIII.) Ibid. 20:–, 1972.
2. Cheraskin, E:, and Ringsdorf, W. M., Jr.: “Daily vitamin E consumption and reported cardiovascular findings,” Nutr. Rep. Internat. 2: 107 (Aug.) 1970.
3. Lepeschkin, E.: Modern Electrocardiography. Baltimore, The Williams & Wilkins Co., 1951, p. 153.
4. Cheraskin, E., and Ringsdorf, W. M., Jr.: “Younger at heart; a study of the P-R interval,” J. Am. Geriatrics Soc. 19: 271 (March) 1971.
5. “Editorial: ADA Health Screening Program,” J.A.D.A. 79: 235 (Aug.) 1969.
6. Cureton, T. K.: The Physiological Effects of Exercise Programs on Adults. Springfield, Illinois, Charles C Thomas, Publisher, 1963, pp. 64, 78, 84.