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TEN-YEAR EXPERIENCE OF MODIFIED-FAT DIETS ON YOUNGER MEN WITH CORONARY HEART-DISEASE
1404
Requests for reprints should be addressed to the Boston Collaborative Drug Surveillance Programme, 400 Totten Pond Road, Waltham, Massachusetts 02154, U.S.A.
group had group.
17%
a
greater survival-rate than the control
Introduction
REFERENCES
Vessey, M. P., Doll, R. Br. med. J. 1968, ii, 199. Vessey, M. P., Doll, R. ibid. 1969, ii, 651. Sartwell, P. E., Masi, A. T., Arthes, F. G., Greene, G. R., Smith, H. E. Am. J. Epidemiol. 1969, 90, 365. 4. Drill, V. A. J. Am. med. Ass. 1972, 219, 583. 5. Preston, S. N. Am. J. Obstet. Gynec. 1971, 111, 994. 6. Friedman, G. D., Kannel, W. B., Dawber, T. R. J. chron. Dis. 1966, 19, 273. 7. Newman, H. F., Northup, J. D. Int. Abstr. Surg. 1959, 109, 1. 8. Kaye, M. D., Kern, F. Lancet, 1971, i, 1228. 9. Sampliner, R. E., Bennett, P. H., Comess, L. J., Rose, F. A., Burch, T. A. New Engl. J. Med. 1970, 283, 1358. 10. Robertson, H. E., Dochat, G. R. Int. Abstr. Surg. 1944, 78, 193. 11. Robertson, H. E. ibid. 1945, 80, 1. 12. Hertz, R. Cancer, 1969, 24, 1140. 13. Vessey, M. P., Doll, R., Sutton, P. M. Br. med. J. 1972, iii, 719. 14. Arthes, F. G., Sartwell, P. E., Lewison, E. F. Cancer, 1971, 28, 1391. 15. Sartwell, P. E., Arthes, F. G., Tonascia, J. A. New Engl. J. Med. 1973, 288, 551. 16. Mantel, N., Haenszel, W. J. natn. Cancer Inst. 1959, 22, 719. 17. Bottiger, L. E., Westerholm, B. Acta med. scand. 1971, 190, 455. 18. Inman, W. H. W., Vessey, M. P., Westerholm, B., Engelund, A. Br. med. J. 1970, ii, 203. 19. Dugdale, M., Masi, A. T. J. chron. Dis. 1971, 23, 775. 20. Aronson, H. B., Magora, F., Schenker, J. G. Am. J. Obstet. Gynec. 1971, 110, 997. 21. Oski, F. A., Lubin, B., Buchert, E. D. Ann. intern. Med. 1972, 77, 1. 2. 3.
419. 22. Zuck, T. F., Bergin, J. J., Raymond, J. T., Dwyre, W. R., Corby, D. G. Thromb. Diath. hœmorrh. 1971, 26, 426. 23. Poller, L., Priest, C. M., Thomson, J. M. Br. med. J. 1969, iv, 273. 24. Poller, L., Tabiowo, A., Thomson, J. M. ibid. 1968, iii, 218. 25. Poller, L., Thomson, J. M., Tabiowo, A., Priest, C. M. ibid. 1969,
i, 554. 26. Hedlin, A. M., Monkhouse, F. C. Obstet. Gynec. 1971, 37, 225. 27. Small, D. M., Rapo, S. New Engl. J. Med. 1970, 283, 53. 28. Small, D. M. Adv. intern. Med. 1970, 16, 243. 29. Tritapepe, R., Cesana, A., Gandini, R., Trivellini, G. Panminerva med. 1969, 11, 410. 30. Potter, J. F., Slimbaugh, W. P., Woodward, S. C. Ann. Surg. 1968, 167, 829. 31. Warren, S. Surgery Gynec. Obstet. 1940, 71, 257. 32. MacMahon, B., Cole, P., Lin, T. M., Lowe, C. R., Mirra, A. P., Ravnihar, B., Salber, E. J., Valaoras, V. G., Yuasa, S. Bull. Wld Hlth Org. 1970, 43, 209. 33. Hougie, C. Am. Heart J. 1973, 85, 538.
have shown a relation between diet, serum-lipids, and the incidence of The aetiology of coronary coronary heart-disease. heart-disease has been shown to be multifactorial,8-11 and diet is one of the contributing factors. Many of the risk factors have been elucidated by the FramingEPIDEMIOLOGICAL studies
ham study. 12
Low-fat, relatively unsaturated diets have been successfully used to lower serum-cholesterol in several primary prevention studies.l3-15 In a 12-year secondary prevention study, Morrison 16 reported a significant decrease in the mortality-rate among subjects on a controlled diet who had already had myocardial infarction. Similar results were obtained by Nelson,1’ Lyon et al.,18 and Leren.19 However, a research committee to the Medical Research Council 20 did not find a significant difference in mortality under similar conditions in a secondary prevention study in London, while Dayton et al.,21 in a primary prevention study, reported a lower incidence of fatal atherosclerotic events but not of total mortality in a group on a diet high in unsaturated fat compared to a control group. In an earlier 5-year report, Bierenbaum et al.22
reported a significant lowering in serum cholesterol and triglyceride in a diet-managed group of young men with coronary heart-disease, as compared to a control group, with a concomitant lowering in the reinfarction-rate in the diet-managed group. We report the results of 10 years’ experience in a prospective study which compared the effect of two controlledfat diets, one containing relatively unsaturated fat and the other containing saturated fat, and determined the morbidity and mortality from coronary heartdisease, according to diet group, in young men who had already had at least one confirmed myocardial
TEN-YEAR EXPERIENCE OF MODIFIED-FAT DIETS ON YOUNGER MEN WITH CORONARY HEART-DISEASE
infarction.
ALAN I. FLEISCHMAN MARVIN L. BIERENBAUM THOMAS HAYTON ROBERT I. RAICHELSON B. WATSON PORTIA
small groups
Atherosclerosis Research Group, Saint Vincent’s Montclair, New Jersey 07042, U.S.A.
Hospital,
1-7
Methods A
study
hundred men was assembled in period of 18 months. Table i shows the of the study and control groups. All
group of
a
over a
age-distribution
individuals had experienced electrocardiographically confirmed myocardial infarctions, with the presence of a Q wave being a prerequisite. They were referred by their own physicians, under whose care they remained throughout the
Summary
One hundred men, 30-50 years old, with confirmed coronary-artery disease
and past myocardial infarction, were placed on a 28% fat diet after weight reduction. This group was matched with a similar group not under dietary management. Over a period of 10 years there were significant reductions in serum-lipids in the diet-managed group compared with the control group. In this pre-
study period. Dietary pilot studies
used a 28% fat diet limited in diet consisted of relatively unsaturated fat and the other consisted of saturated fat. There was no difference in serum-cholesterol value between the two diet
cholesterol;
one
TABLE I-AGE-DISTRIBUTION OF
SUBJECTS
UPON ENTRY INTO STUDY
dominantly lipoprotein-phenotype-IV group, using a diet containing less than 9% of calories as saturated fat and less than 400 mg. exogenous cholesterol daily, the degree of unsaturation of the diet did not appear to influence either serum-lipid values or mortality-rates. After 10 years, the diet-managed
*
Total in age-groups 30-44. age-groups 45-54.
t Total in
1405 TABLE II-COMPARABILITY OF STUDY AND CONTROL GROUPS BEFORE START OF STUDY
* Means.n.
t Classified according
to recommendation of functional capacity by the New York Heart Association.2s
groups.23 Subsequently, a control group was matched to the diet groups already under study. We are fully aware that by continuing to study the original diet groups we made it impossible to have a randomised control series. We recognised that socioeconomic factors of uncertain importance might not be balanced in the subjects and controls, despite their selection from the same area, and that other sources of bias might obtain in the sequential entry of such a comparison group to the study. However, controls with coronary disease were recruited from industry over a 2-year period, with the help of the factory physicians, who collected the necessary data. These men had similar The comgroup characteristics to the study subjects. parability of the two groups with respect to several of these factors is shown in table 11. There are several obvious imbalances between the two groups-i.e., higher serumcholesterol level, more subjects with a family history of coronary heart-disease, and more severe angina in the study group, while there were more smokers in the control Since there were more unfavourable factors in group. the dieted group, we felt that any bias would tend to weigh against favourable results, and, if these results were statistically significant, it would add further to the strength of the data. The grounds for acceptance or exclusion from the study have been reported. 24, 2á All individuals in this study were followed up for 10 years. No subject was lost to the study for any reason except death. On entry to the study, subjects who previously had been consuming a normal American diet were assigned on an alternating basis to one of two diets distinguished by the degree of unsaturation of the dietary fats. The low ratio of polyunsaturated to saturated fat (P/S’) in diet 2 (table III) was first intended to serve as the control for the study * TABLE III-APPROXIMATE COMPOSITION OF DIETS 1 AND 2*
since this P/S pattern closely approximated that of the usual American diet. After a complete history and physical examination, blood-lipids were assayed for 3 consecutive weeks to establish a pre-experimental level before the assigned diet or weight reduction was initiated. Seventythree overweight subjects were placed on a 1200 calorie diet until the desired weight was attained. 233 Thereafter, they joined their assigned diet group. Their pre-diet lipid levels are used in the analysis. Both diets contained approximately 28% calories from fat and 260 mg. per day and 395 mg. per day exogenous cholesterol, respectively (table III). Diet 1 contained 1 ounce of a 50% mixture of corn-safflower oil as part of the daily fat allowance, while diet 2 contained 1 ounce of a 50% mixture of coconut/peanut oil (a somewhat unfortunate choice in view of the recent extensive work showing the qualitative difference in serum-cholesterol effects of coconut oil). To enable the men to adhere more easily to the prescribed diet for protracted periods, specially prepared frozen dinners, including pies, an ice-cream substitute, and oil, were obtained from the " project store at reduced prices. Members of the control group were referred by industrial physicians and remained under their care. The controls had no known dietary manipulation during the study, and at the yearly medical and nutritional evaluation efforts were made to avoid inadvertently giving information. Laboratory analysis of control blood-samples was performed in the same laboratory and at the same time as blood-samples from the diet-managed group. Serum total lipids, phospholipids, total cholesterol, TABLE IV-COMPARISON OF SERUM-LIPIDS IN TWO DIETARY GROUPS
*
Mean -L standard deviation.
triglycerides, and free fatty acids were assayed by previously described procedures.26 Dietary adherence was evaluated subjectively by interview and objectively by gas-liquid chromatography of the serum-triglycerides,27 serum-freefatty-acids, 211 and subcutaneous fat .29 Electrocardiograms were
read blind by three cardiologists at the start of the any clinical episode, and annually.
study, after
Statistical analysis of morbidity and mortality data used life-table techniques. 300 Analysis of lipid data was based upon an assumed normal distribution and used the t test.3l Results
in the diet group required Of these, only forty-four were successful and the remainder were only partially successful in attaining the ideal weight. There was a transitory decrease in serum-cholesterol during weight reduction, but over a 2-year period decreases in serum-cholesterol due to weight reduction were not
Seventy-three
men
weight reduction.
statistically significant. A comparison of serum-lipids
in the two dietary the controlled-fat diets is shown in table iv. The degree of unsaturation of the diets did not significantly influence serum-lipids. Analysis of the groups
*
At 2000 calories per
day.
on
1406 TABLE V-CUMULATIVE INCIDENCE OF FATAL MYOCARDIAL INFARCTION IN MEN UNDER 45 AT ENTRY INTO STUDY
At the end of the 10-year study, the group under dietary management had a survival-rate of 0-84, while in the matched control group it was 0-72. This difference in survival-rate
groups is
was
data indicated that in this group the degree of unsaturation of the diet did not influence cardiovascular disease mortality. For this reason, and despite continuation of the two dietary fat patterns, the data from the two dietary groups were combined before comparison with the data from the control group. Table v shows the cumulative incidence of fatal reinfarctions in both the study and control groups for subjects who were less than 45 years of age on entry to the study. Of forty-two men at risk in the study group, four had a fatal myocardial infarction, while in the control group twelve men had a fatal infarction out of forty-nine men at risk. The cumulative incidences for the study and control groups of men 45 years or over at age of entry are compared in table vi. There were twelve fatal reinfarctions out of fifty-eight men at risk in the study group, against sixteen fatal reinfarctions out of fifty-one at risk in the control group. A life-table analysis 80 of both the study and control TABLE VI-CUMULATIVE INCIDENCE OF FATAL MYOCARDIAL INFARCTION IN MEN OVER 45 AT ENTRY INTO STUDY
TABLE VII-LIFE-TABLE COMPARISON
*
Differences significant
at
95 % confidence level (p < 0-05) for
t
> 2.
given in table
VII.
significant (P<0-05).
Discussion In earlier reports,2 23, 3it was noted that on diets with a 28% fat content, an exogenous cholesterol level below 400 mg. per day, and a P/S ratio of either 2-6/1 or 1/2-9, the cholesterol-lowering effects after 5 years were identical. There was no significant difference in serum-cholesterol levels between men To attain the 28% fat on the two diets (table iv). diet, the reduction in fat from that found in the usual American diet necessitated reduction of the saturated fat. Thus the final saturated fat content of both diets and the content of exogenous cholesterol were com-
Stamler,33 Erikson et al.,34 Keys et al,,3536 Reiser 36 reported that if the exogenous cholesterol and is below 400 mg. per day and the amount of saturated fat in the diet is controlled, the effect of the P/S ratio of the diet on lowering cholesterol levels is lessened. The 10% reduction in serum-cholesterol noted in the present study is similar to that found by Jolliffe et al. 13 and by Page and Brown. 87 Fleischman et al. 81 and Albrink 38 reported that serum-triglyceride may be as important a coronary risk factor as serum-cholesterol. This is particularly important in view of the work of Fredrickson and Lees 39 on the classification and dietary management of hyperlipoproteinsemias. Kuo 4has demonstrated that dietary management of the hypertriglyceridasmic requires weight reduction and carbohydrate control rather than control of exogenous fats. Upon examination, Kuo’s diet-managed group was found to consist of 74% type-iv men, 24% type-ll men, and 2% normolipidsemic men. The reduction in serumtriglyceride in the diet-managed group, from an initial mean serum triglyceride of 205 mg. per 100 ml. to the final value of 152 mg. per 100 ml., was the result of weight reduction. When the men achieved an ideal weight, there was no further significant variation Antonis and Bersohn" in serum-triglycerides. for a that men on high-fat diet, alteration of reported oil patterns caused alteration of serum-triglycerides. In the present study, in which fat contributed 28% of the calories, the P/S ratio of the diet did not significantly affect serum-triglycerides (table iv). The mean serum-triglycerides in the control group did not vary significantly from 187 mg. per 100 ml. during the entire study. The preponderance of lipoprotein-phenotype-iv individuals in our diet-managed group probably explains the variation between the19 results we obtained and those obtained by Leren and the M.R.C. 20 study on serum-cholesterol reduction. Although the lipoprotein phenotype distribution was not reported in either study, from the higher pre-experimental serum-cholesterol values reported by both studies 19,20 it seems highly probable that a much larger proportion of their groups were lipoprotein phenotype II, and as such would be much more susceptible to control by the unsaturated-fat diet. In addition, in the M.R.C. study, both the study and
parable.
1407
control groups underwent previous weight reduction before starting controlled-fat diets. This very probably produced similar serum-triglyceride levels in both M.R.C. groups and eliminated a potentiallymostimpora cohort probably containing many hyperlipoproteinasmic patients. This may explain the similar morbidity and mortality found in the M.R.C. study and control groups. The combined effects of weight control and dietary management produced a 17% difference in the survivalrate between the study and the control group (table This is especially true of the younger vn) (P<0’05). men, who were under 45 years when they entered the study. In this under-45-group, incidence was over twice as high in the control group as in the study
tant
ANTIHYPERTENSIVE TREATMENT AND THE COURSE OF ESTABLISHED CEREBRAL VASCULAR DISEASE D. G. BEEVERS* M. HAMILTON
risk factor in
type-iv
group. Even in the over-45 group, the incidence in the control group was one-third higher than in the study group. From the present study it appears that dietary management may markedly improve the 10-year prognosis of men who have already had an initial coronary insult, particularly those under 45. However, other reports, in keeping with the trend in our study, suggest that dietary change instituted after 45 may still be beneficial. Variations between the results of different studies may be related to degree of severity of disease and limitations in sample size. It seems that dietary management, if it is to have the most beneficial effect on morbidity and mortality, should be started as early in life as possible in those susceptible to or already affected by coronary disease. This study was supported in part by grant H-5905 from the National Heart and Lung Institute, and by grant-in-aid, contract no. 26, from the New Jersey State Department of Health. Requests for reprints should be addressed to M. L. B., Atherosclerosis Research Group, 48 Plymouth Street, Montclair, New Jersey 07042, U.S.A. REFERENCES
Kinsell, L. W., Partridge, J., Boling, L., Margen, S., Michaels, G. J. clin. Endocr. Metab. 1952, 12, 909. 2. Katz, L. N., Stamler, J., Pick, R. in Nutrition and Atherosclerosis (edited by L. N. Katz); p. 148. Philadelphia, 1958. 3. Stamler, J. J. Am. diet. Ass. 1958, 34, 701, 814, 929, 1053, 1060. 4. Jolliffe, N., Archer, M. J. chron. Dis. 1959, 9, 636. 5. Keys, A., Kimura, N., Kusakawa, A., Bronte-Stewart, B., Larsen, N. P., Keys, M. H. Fedn Proc. 1957, 16, 204. 6. Toor, M., Katchalsky, A., Agmom, J., Allalouf, O. Circulation, 1960, 22, 265. 7. Miller, D. C., Trulson, M. F., McCann, M. B., White, P. D., Stare, F. J. Ann. intern. Med. 1958, 49, 1178. 8. Mann, G. V., Pearson, G., Gordon, T. Fedn Proc. 1959, 18, 535. 9. Zukel, W. J., Lewis, R. H., Enterline, P. E., Painter, R. C., Ralston, L. S., Fawcett, R. M., Meredith, A. P., Peterson, B. Am. J. publ. Hlth, 1959, 49, 1630. 10. Bouchier, I. A. D., Bronte-Stewart, B. Lancet, 1961, i, 363. 11. Brown, D. F., Heslin, A. S., Doyle, J. T. New Engl. J. Med. 1961, 264, 733. 12. Kannel, W. B., Dawber, T. R., Kagan, A., Revotskie, N., Stokes, J. Ann. intern. Med. 1961, 55, 33. 13. Jolliffe, N., Rinzler, S. H., Archer, M. Am. J. clin. Nutr. 1959, 7,
M.
J. FAIRMAN† J. E. HARPUR
Chelmsford Group of Hospitals In a group of 162 hypertensive patients who had recovered from a stroke, the recurrence-rate of stroke was closely related to the adequacy of control of hypertension. This was in sharp contrast to the frequency of myocardial infarction and angina pectoris, which did not show a similar relationship. The frequency of cardiac failure was significantly higher in patients with poor control of
Summary
hypertension. Introduction IT is now generally accepted that treatment of moderate and severe hypertension in the young and middle-aged prevents certain complications of hypertension, especially stroke. I, There has been reluctance,
however,
to
prescribe long-term antihypertensive
in patients with established cerebrovascular disease. The observations of Adams3 who in a large series of elderly hemiplegics found no evidence of a critical need to lower the blood-pressure in those patients found to be hypertensive after a stroke, lent support to this view. Subsequently, Merrett and Adams 4 in a comparison of mortality-rates in elderly hypertensive and normotensive patients could not confirm any adverse effect of hypertension. Different conclusions were reached by Marshall and Kaeser treatment
Present address: Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow. t Present address: Department of Medicine, Leeds General Infirmary. *
1.
451. 14. Stamler, J. Prog. cardiovasc. Dis. 1960, 3, 56. 15. Pilkington, T. R. E., Stafford, J. L., Hankin, V. S., F. M., Koerselman, H. B. Br. med. J. 1960, i, 23. 16. Morrison, L. M. J. Am. med. Ass. 1960, 173, 884. 17. Nelson, A. M. N.W. Med., Seattle, 1956, 55, 643. 18. Lyon, T. P., Yankley, A., Gofman, J. W., Strisower, B.
Simmonds,
Calif. Med.
1956, 84, 325. 19. Leren, P. Acta med. scand. 1966, suppl. 466, 1. 20. Research Committee to the Medical Research Council. Lancet, 1968, ii, 693. 21. Dayton, S., Pearce, M. L., Goldman, H., Harnish, A., Plotkin, D., Shickman, M., Winfield, M., Zager, A., Dixon, W. ibid. p. 1060.
Bierenbaum, M. L., Fleischman, A. I., Green, D. P., Raichelson, R. I., Hayton, T., Watson, P. B., Caldwell, A. B. Circulation, 1970, 42, 943. 23. Bierenbaum, M. L., Green, D. P., Gherman, C., Florin, A., Caldwell, A. B. J. chron. Dis. 1963, 16, 1073. 24. Bierenbaum, M. L., Green, D. P., Caldwell, A. B., Kelly, E. H. J. med. Soc. New Jers. 1961, 58, 134. 25. Criteria Committee, New York Heart Association; p. 112. Boston, 22.
1964. 26. Fleischman, A. I., Hayton, T., Bierenbaum, M. L., Wildrick, E. Automation in Analytical Chemistry; p. 21. New York, 1968. 27. Fleischman, A. I., Hayton, T., Bierenbaum, M. L. Am. J. clin. Nutr. 1967, 20, 333. 28. Fleischman, A. I., Hayton, T., Bierenbaum, M. L. ibid. 1964, 15, 299. 29. Hirsch, J., Farquhar, J. W., Ahrens, E. H., Jr., Peterson, M. L., Stoffel, W. ibid. 1960, 8, 499. 30. University of California Publications in Automatic Computation, No. 3. B.M.D. Biomedical Computer Programs, X-Series Supplement (edited by W. J. Dixon) (Program B.M.D. X76). 31. Dixon, W. J., Massey, F. J. Introduction to Statistical Analysis; p. 136. New York, 1968. 32. Fleischman, A. I., Hayton, T., Bierenbaum, M. L. J. Am. diet. Ass. 1967, 50, 112. 33. Stamler, J. Am. J. publ. Hlth, 1960, 3, 14. 34. Erickson, B. A., Coots, R. H., Mattson, F. H., Kligman, A. M. J. clin. Invest. 1964, 43, 2017. 35. Keys, A., Anderson, J. T., Grande, F. Lancet, 1957, ii, 959. 36. Reiser, R. J. Am. Oil Chem. Soc. 1966, 43, 112A. 37. Page, I. H., Brown, H. B. Circulation, 1968, 37, 313. 38. Albrink, M. J. Archs intern. Med. 1962, 109, 345. 39. Fredrickson, D. S., Lees, R. S. Circulation, 1965, 31, 321. 40. Kuo, P. T. J. Am. med. Ass. 1967, 201, 87. 41. Antonis, A., Bersohn, I. Am. J. clin. Nutr. 1962, 10, 484.
Requests for reprints should be addressed to the Boston Collaborative Drug Surveillance Programme, 400 Totten Pond Road, Waltham, Massachusetts 02154, U.S.A.
group had group.
17%
a
greater survival-rate than the control
Introduction
REFERENCES
Vessey, M. P., Doll, R. Br. med. J. 1968, ii, 199. Vessey, M. P., Doll, R. ibid. 1969, ii, 651. Sartwell, P. E., Masi, A. T., Arthes, F. G., Greene, G. R., Smith, H. E. Am. J. Epidemiol. 1969, 90, 365. 4. Drill, V. A. J. Am. med. Ass. 1972, 219, 583. 5. Preston, S. N. Am. J. Obstet. Gynec. 1971, 111, 994. 6. Friedman, G. D., Kannel, W. B., Dawber, T. R. J. chron. Dis. 1966, 19, 273. 7. Newman, H. F., Northup, J. D. Int. Abstr. Surg. 1959, 109, 1. 8. Kaye, M. D., Kern, F. Lancet, 1971, i, 1228. 9. Sampliner, R. E., Bennett, P. H., Comess, L. J., Rose, F. A., Burch, T. A. New Engl. J. Med. 1970, 283, 1358. 10. Robertson, H. E., Dochat, G. R. Int. Abstr. Surg. 1944, 78, 193. 11. Robertson, H. E. ibid. 1945, 80, 1. 12. Hertz, R. Cancer, 1969, 24, 1140. 13. Vessey, M. P., Doll, R., Sutton, P. M. Br. med. J. 1972, iii, 719. 14. Arthes, F. G., Sartwell, P. E., Lewison, E. F. Cancer, 1971, 28, 1391. 15. Sartwell, P. E., Arthes, F. G., Tonascia, J. A. New Engl. J. Med. 1973, 288, 551. 16. Mantel, N., Haenszel, W. J. natn. Cancer Inst. 1959, 22, 719. 17. Bottiger, L. E., Westerholm, B. Acta med. scand. 1971, 190, 455. 18. Inman, W. H. W., Vessey, M. P., Westerholm, B., Engelund, A. Br. med. J. 1970, ii, 203. 19. Dugdale, M., Masi, A. T. J. chron. Dis. 1971, 23, 775. 20. Aronson, H. B., Magora, F., Schenker, J. G. Am. J. Obstet. Gynec. 1971, 110, 997. 21. Oski, F. A., Lubin, B., Buchert, E. D. Ann. intern. Med. 1972, 77, 1. 2. 3.
419. 22. Zuck, T. F., Bergin, J. J., Raymond, J. T., Dwyre, W. R., Corby, D. G. Thromb. Diath. hœmorrh. 1971, 26, 426. 23. Poller, L., Priest, C. M., Thomson, J. M. Br. med. J. 1969, iv, 273. 24. Poller, L., Tabiowo, A., Thomson, J. M. ibid. 1968, iii, 218. 25. Poller, L., Thomson, J. M., Tabiowo, A., Priest, C. M. ibid. 1969,
i, 554. 26. Hedlin, A. M., Monkhouse, F. C. Obstet. Gynec. 1971, 37, 225. 27. Small, D. M., Rapo, S. New Engl. J. Med. 1970, 283, 53. 28. Small, D. M. Adv. intern. Med. 1970, 16, 243. 29. Tritapepe, R., Cesana, A., Gandini, R., Trivellini, G. Panminerva med. 1969, 11, 410. 30. Potter, J. F., Slimbaugh, W. P., Woodward, S. C. Ann. Surg. 1968, 167, 829. 31. Warren, S. Surgery Gynec. Obstet. 1940, 71, 257. 32. MacMahon, B., Cole, P., Lin, T. M., Lowe, C. R., Mirra, A. P., Ravnihar, B., Salber, E. J., Valaoras, V. G., Yuasa, S. Bull. Wld Hlth Org. 1970, 43, 209. 33. Hougie, C. Am. Heart J. 1973, 85, 538.
have shown a relation between diet, serum-lipids, and the incidence of The aetiology of coronary coronary heart-disease. heart-disease has been shown to be multifactorial,8-11 and diet is one of the contributing factors. Many of the risk factors have been elucidated by the FramingEPIDEMIOLOGICAL studies
ham study. 12
Low-fat, relatively unsaturated diets have been successfully used to lower serum-cholesterol in several primary prevention studies.l3-15 In a 12-year secondary prevention study, Morrison 16 reported a significant decrease in the mortality-rate among subjects on a controlled diet who had already had myocardial infarction. Similar results were obtained by Nelson,1’ Lyon et al.,18 and Leren.19 However, a research committee to the Medical Research Council 20 did not find a significant difference in mortality under similar conditions in a secondary prevention study in London, while Dayton et al.,21 in a primary prevention study, reported a lower incidence of fatal atherosclerotic events but not of total mortality in a group on a diet high in unsaturated fat compared to a control group. In an earlier 5-year report, Bierenbaum et al.22
reported a significant lowering in serum cholesterol and triglyceride in a diet-managed group of young men with coronary heart-disease, as compared to a control group, with a concomitant lowering in the reinfarction-rate in the diet-managed group. We report the results of 10 years’ experience in a prospective study which compared the effect of two controlledfat diets, one containing relatively unsaturated fat and the other containing saturated fat, and determined the morbidity and mortality from coronary heartdisease, according to diet group, in young men who had already had at least one confirmed myocardial
TEN-YEAR EXPERIENCE OF MODIFIED-FAT DIETS ON YOUNGER MEN WITH CORONARY HEART-DISEASE
infarction.
ALAN I. FLEISCHMAN MARVIN L. BIERENBAUM THOMAS HAYTON ROBERT I. RAICHELSON B. WATSON PORTIA
small groups
Atherosclerosis Research Group, Saint Vincent’s Montclair, New Jersey 07042, U.S.A.
Hospital,
1-7
Methods A
study
hundred men was assembled in period of 18 months. Table i shows the of the study and control groups. All
group of
a
over a
age-distribution
individuals had experienced electrocardiographically confirmed myocardial infarctions, with the presence of a Q wave being a prerequisite. They were referred by their own physicians, under whose care they remained throughout the
Summary
One hundred men, 30-50 years old, with confirmed coronary-artery disease
and past myocardial infarction, were placed on a 28% fat diet after weight reduction. This group was matched with a similar group not under dietary management. Over a period of 10 years there were significant reductions in serum-lipids in the diet-managed group compared with the control group. In this pre-
study period. Dietary pilot studies
used a 28% fat diet limited in diet consisted of relatively unsaturated fat and the other consisted of saturated fat. There was no difference in serum-cholesterol value between the two diet
cholesterol;
one
TABLE I-AGE-DISTRIBUTION OF
SUBJECTS
UPON ENTRY INTO STUDY
dominantly lipoprotein-phenotype-IV group, using a diet containing less than 9% of calories as saturated fat and less than 400 mg. exogenous cholesterol daily, the degree of unsaturation of the diet did not appear to influence either serum-lipid values or mortality-rates. After 10 years, the diet-managed
*
Total in age-groups 30-44. age-groups 45-54.
t Total in
1405 TABLE II-COMPARABILITY OF STUDY AND CONTROL GROUPS BEFORE START OF STUDY
* Means.n.
t Classified according
to recommendation of functional capacity by the New York Heart Association.2s
groups.23 Subsequently, a control group was matched to the diet groups already under study. We are fully aware that by continuing to study the original diet groups we made it impossible to have a randomised control series. We recognised that socioeconomic factors of uncertain importance might not be balanced in the subjects and controls, despite their selection from the same area, and that other sources of bias might obtain in the sequential entry of such a comparison group to the study. However, controls with coronary disease were recruited from industry over a 2-year period, with the help of the factory physicians, who collected the necessary data. These men had similar The comgroup characteristics to the study subjects. parability of the two groups with respect to several of these factors is shown in table 11. There are several obvious imbalances between the two groups-i.e., higher serumcholesterol level, more subjects with a family history of coronary heart-disease, and more severe angina in the study group, while there were more smokers in the control Since there were more unfavourable factors in group. the dieted group, we felt that any bias would tend to weigh against favourable results, and, if these results were statistically significant, it would add further to the strength of the data. The grounds for acceptance or exclusion from the study have been reported. 24, 2á All individuals in this study were followed up for 10 years. No subject was lost to the study for any reason except death. On entry to the study, subjects who previously had been consuming a normal American diet were assigned on an alternating basis to one of two diets distinguished by the degree of unsaturation of the dietary fats. The low ratio of polyunsaturated to saturated fat (P/S’) in diet 2 (table III) was first intended to serve as the control for the study * TABLE III-APPROXIMATE COMPOSITION OF DIETS 1 AND 2*
since this P/S pattern closely approximated that of the usual American diet. After a complete history and physical examination, blood-lipids were assayed for 3 consecutive weeks to establish a pre-experimental level before the assigned diet or weight reduction was initiated. Seventythree overweight subjects were placed on a 1200 calorie diet until the desired weight was attained. 233 Thereafter, they joined their assigned diet group. Their pre-diet lipid levels are used in the analysis. Both diets contained approximately 28% calories from fat and 260 mg. per day and 395 mg. per day exogenous cholesterol, respectively (table III). Diet 1 contained 1 ounce of a 50% mixture of corn-safflower oil as part of the daily fat allowance, while diet 2 contained 1 ounce of a 50% mixture of coconut/peanut oil (a somewhat unfortunate choice in view of the recent extensive work showing the qualitative difference in serum-cholesterol effects of coconut oil). To enable the men to adhere more easily to the prescribed diet for protracted periods, specially prepared frozen dinners, including pies, an ice-cream substitute, and oil, were obtained from the " project store at reduced prices. Members of the control group were referred by industrial physicians and remained under their care. The controls had no known dietary manipulation during the study, and at the yearly medical and nutritional evaluation efforts were made to avoid inadvertently giving information. Laboratory analysis of control blood-samples was performed in the same laboratory and at the same time as blood-samples from the diet-managed group. Serum total lipids, phospholipids, total cholesterol, TABLE IV-COMPARISON OF SERUM-LIPIDS IN TWO DIETARY GROUPS
*
Mean -L standard deviation.
triglycerides, and free fatty acids were assayed by previously described procedures.26 Dietary adherence was evaluated subjectively by interview and objectively by gas-liquid chromatography of the serum-triglycerides,27 serum-freefatty-acids, 211 and subcutaneous fat .29 Electrocardiograms were
read blind by three cardiologists at the start of the any clinical episode, and annually.
study, after
Statistical analysis of morbidity and mortality data used life-table techniques. 300 Analysis of lipid data was based upon an assumed normal distribution and used the t test.3l Results
in the diet group required Of these, only forty-four were successful and the remainder were only partially successful in attaining the ideal weight. There was a transitory decrease in serum-cholesterol during weight reduction, but over a 2-year period decreases in serum-cholesterol due to weight reduction were not
Seventy-three
men
weight reduction.
statistically significant. A comparison of serum-lipids
in the two dietary the controlled-fat diets is shown in table iv. The degree of unsaturation of the diets did not significantly influence serum-lipids. Analysis of the groups
*
At 2000 calories per
day.
on
1406 TABLE V-CUMULATIVE INCIDENCE OF FATAL MYOCARDIAL INFARCTION IN MEN UNDER 45 AT ENTRY INTO STUDY
At the end of the 10-year study, the group under dietary management had a survival-rate of 0-84, while in the matched control group it was 0-72. This difference in survival-rate
groups is
was
data indicated that in this group the degree of unsaturation of the diet did not influence cardiovascular disease mortality. For this reason, and despite continuation of the two dietary fat patterns, the data from the two dietary groups were combined before comparison with the data from the control group. Table v shows the cumulative incidence of fatal reinfarctions in both the study and control groups for subjects who were less than 45 years of age on entry to the study. Of forty-two men at risk in the study group, four had a fatal myocardial infarction, while in the control group twelve men had a fatal infarction out of forty-nine men at risk. The cumulative incidences for the study and control groups of men 45 years or over at age of entry are compared in table vi. There were twelve fatal reinfarctions out of fifty-eight men at risk in the study group, against sixteen fatal reinfarctions out of fifty-one at risk in the control group. A life-table analysis 80 of both the study and control TABLE VI-CUMULATIVE INCIDENCE OF FATAL MYOCARDIAL INFARCTION IN MEN OVER 45 AT ENTRY INTO STUDY
TABLE VII-LIFE-TABLE COMPARISON
*
Differences significant
at
95 % confidence level (p < 0-05) for
t
> 2.
given in table
VII.
significant (P<0-05).
Discussion In earlier reports,2 23, 3it was noted that on diets with a 28% fat content, an exogenous cholesterol level below 400 mg. per day, and a P/S ratio of either 2-6/1 or 1/2-9, the cholesterol-lowering effects after 5 years were identical. There was no significant difference in serum-cholesterol levels between men To attain the 28% fat on the two diets (table iv). diet, the reduction in fat from that found in the usual American diet necessitated reduction of the saturated fat. Thus the final saturated fat content of both diets and the content of exogenous cholesterol were com-
Stamler,33 Erikson et al.,34 Keys et al,,3536 Reiser 36 reported that if the exogenous cholesterol and is below 400 mg. per day and the amount of saturated fat in the diet is controlled, the effect of the P/S ratio of the diet on lowering cholesterol levels is lessened. The 10% reduction in serum-cholesterol noted in the present study is similar to that found by Jolliffe et al. 13 and by Page and Brown. 87 Fleischman et al. 81 and Albrink 38 reported that serum-triglyceride may be as important a coronary risk factor as serum-cholesterol. This is particularly important in view of the work of Fredrickson and Lees 39 on the classification and dietary management of hyperlipoproteinsemias. Kuo 4has demonstrated that dietary management of the hypertriglyceridasmic requires weight reduction and carbohydrate control rather than control of exogenous fats. Upon examination, Kuo’s diet-managed group was found to consist of 74% type-iv men, 24% type-ll men, and 2% normolipidsemic men. The reduction in serumtriglyceride in the diet-managed group, from an initial mean serum triglyceride of 205 mg. per 100 ml. to the final value of 152 mg. per 100 ml., was the result of weight reduction. When the men achieved an ideal weight, there was no further significant variation Antonis and Bersohn" in serum-triglycerides. for a that men on high-fat diet, alteration of reported oil patterns caused alteration of serum-triglycerides. In the present study, in which fat contributed 28% of the calories, the P/S ratio of the diet did not significantly affect serum-triglycerides (table iv). The mean serum-triglycerides in the control group did not vary significantly from 187 mg. per 100 ml. during the entire study. The preponderance of lipoprotein-phenotype-iv individuals in our diet-managed group probably explains the variation between the19 results we obtained and those obtained by Leren and the M.R.C. 20 study on serum-cholesterol reduction. Although the lipoprotein phenotype distribution was not reported in either study, from the higher pre-experimental serum-cholesterol values reported by both studies 19,20 it seems highly probable that a much larger proportion of their groups were lipoprotein phenotype II, and as such would be much more susceptible to control by the unsaturated-fat diet. In addition, in the M.R.C. study, both the study and
parable.
1407
control groups underwent previous weight reduction before starting controlled-fat diets. This very probably produced similar serum-triglyceride levels in both M.R.C. groups and eliminated a potentiallymostimpora cohort probably containing many hyperlipoproteinasmic patients. This may explain the similar morbidity and mortality found in the M.R.C. study and control groups. The combined effects of weight control and dietary management produced a 17% difference in the survivalrate between the study and the control group (table This is especially true of the younger vn) (P<0’05). men, who were under 45 years when they entered the study. In this under-45-group, incidence was over twice as high in the control group as in the study
tant
ANTIHYPERTENSIVE TREATMENT AND THE COURSE OF ESTABLISHED CEREBRAL VASCULAR DISEASE D. G. BEEVERS* M. HAMILTON
risk factor in
type-iv
group. Even in the over-45 group, the incidence in the control group was one-third higher than in the study group. From the present study it appears that dietary management may markedly improve the 10-year prognosis of men who have already had an initial coronary insult, particularly those under 45. However, other reports, in keeping with the trend in our study, suggest that dietary change instituted after 45 may still be beneficial. Variations between the results of different studies may be related to degree of severity of disease and limitations in sample size. It seems that dietary management, if it is to have the most beneficial effect on morbidity and mortality, should be started as early in life as possible in those susceptible to or already affected by coronary disease. This study was supported in part by grant H-5905 from the National Heart and Lung Institute, and by grant-in-aid, contract no. 26, from the New Jersey State Department of Health. Requests for reprints should be addressed to M. L. B., Atherosclerosis Research Group, 48 Plymouth Street, Montclair, New Jersey 07042, U.S.A. REFERENCES
Kinsell, L. W., Partridge, J., Boling, L., Margen, S., Michaels, G. J. clin. Endocr. Metab. 1952, 12, 909. 2. Katz, L. N., Stamler, J., Pick, R. in Nutrition and Atherosclerosis (edited by L. N. Katz); p. 148. Philadelphia, 1958. 3. Stamler, J. J. Am. diet. Ass. 1958, 34, 701, 814, 929, 1053, 1060. 4. Jolliffe, N., Archer, M. J. chron. Dis. 1959, 9, 636. 5. Keys, A., Kimura, N., Kusakawa, A., Bronte-Stewart, B., Larsen, N. P., Keys, M. H. Fedn Proc. 1957, 16, 204. 6. Toor, M., Katchalsky, A., Agmom, J., Allalouf, O. Circulation, 1960, 22, 265. 7. Miller, D. C., Trulson, M. F., McCann, M. B., White, P. D., Stare, F. J. Ann. intern. Med. 1958, 49, 1178. 8. Mann, G. V., Pearson, G., Gordon, T. Fedn Proc. 1959, 18, 535. 9. Zukel, W. J., Lewis, R. H., Enterline, P. E., Painter, R. C., Ralston, L. S., Fawcett, R. M., Meredith, A. P., Peterson, B. Am. J. publ. Hlth, 1959, 49, 1630. 10. Bouchier, I. A. D., Bronte-Stewart, B. Lancet, 1961, i, 363. 11. Brown, D. F., Heslin, A. S., Doyle, J. T. New Engl. J. Med. 1961, 264, 733. 12. Kannel, W. B., Dawber, T. R., Kagan, A., Revotskie, N., Stokes, J. Ann. intern. Med. 1961, 55, 33. 13. Jolliffe, N., Rinzler, S. H., Archer, M. Am. J. clin. Nutr. 1959, 7,
M.
J. FAIRMAN† J. E. HARPUR
Chelmsford Group of Hospitals In a group of 162 hypertensive patients who had recovered from a stroke, the recurrence-rate of stroke was closely related to the adequacy of control of hypertension. This was in sharp contrast to the frequency of myocardial infarction and angina pectoris, which did not show a similar relationship. The frequency of cardiac failure was significantly higher in patients with poor control of
Summary
hypertension. Introduction IT is now generally accepted that treatment of moderate and severe hypertension in the young and middle-aged prevents certain complications of hypertension, especially stroke. I, There has been reluctance,
however,
to
prescribe long-term antihypertensive
in patients with established cerebrovascular disease. The observations of Adams3 who in a large series of elderly hemiplegics found no evidence of a critical need to lower the blood-pressure in those patients found to be hypertensive after a stroke, lent support to this view. Subsequently, Merrett and Adams 4 in a comparison of mortality-rates in elderly hypertensive and normotensive patients could not confirm any adverse effect of hypertension. Different conclusions were reached by Marshall and Kaeser treatment
Present address: Medical Research Council Blood Pressure Unit, Western Infirmary, Glasgow. t Present address: Department of Medicine, Leeds General Infirmary. *
1.
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