POLYUNSATURATED FAT AND CORONARY HEART DISEASE

344 POLYUNSATURATED FAT AND CORONARY HEART DISEASE

Sip,—The article by Sonja Connor and colleagues (May 31, p 1229), describing a cholesterol/saturated fat index (CSI) of the hypercholesterolaemic and atherogenic potential of foods, is welcome in that it deals with everyday items of food. However, it may be misleading if it gives the impression that the Portland, Oregon, team ignores the well-known effect of polyunsaturated fats in lowering serum cholesterol. Indeed Dr W. E. Connor’s own studies have demonstrated the profound effect of dietary cholesterol on levels of serum cholesterol and its synergism with saturated fat in producing hyperlipidaemia. This paper may have been written for an American readership, since the "Western diet" referred to reflects current US patternsie, 31 g saturated fat(14% of calories), 18gpolyunsaturedfat(8°oof calories), and 400 mg cholesterol, with a P/S ratio 0-57. If, for some reason, it is undesirable to increase polyunsaturates above 8%, lowering serun cholesterol will depend on reducing saturated fat and cholesterol. In the UK the pattern is very different (table). Our National Food Survey (domestic consumption only) shows 41 g saturated and only 12 g polyunsaturated fat in the diet (19 °,and 5 °o of calories, respectively) with a cholesterol intake of 400 mg per day

FAT COMPOSITION OF USA AND UK DIETS

polyunsaturates have

been examined’"" and have not been

substantiated. Cardiac Department, Western General Hospital, Edinburgh EH4 2XU

A. H. KITCHIN R. W. D. TURNER

1. Hornstra G, Lewis B, Chait A, Turpeinen O, Karvonen MJ, Vergroesen AJ Influence of dietary fat on platelet function in man. Lancet 1973; i. 1155-57. 2. O’Brien JR, Etherington MD, Jamieson S. Effect of a diet of polyunsaturated fats on some platelet-function tests. Lancet 1976; ii: 995-97. 3. Lowe GDO, Johnston RV, Drummond MM, Forbes CD, Prentice CRM. Induction of a circulating platelet-aggregates in healthy subjects by a saturated fat meal. Thromb Res 1979; 16: 565-68. 4. Editorial. Lipids, platelets and atherosclerosis. Lancet 1980; i. 464-65. 5. Crawford MA. The role of essential fatty acids and prostaglandins. Postgrad Med J 1980; 56: 557-62. 6. Homstra G. Dietary prevention of coronary heart disease. Effect of dietary fats on arterial thrombosis. Postgrad Med J 1980; 56: 563-70. 7. Sinclair HM. Prevention of coronary heart disease: the role of essential fatty acids Postgrad Med J 1980; 56: 579-84. 8. Logan RL, Riemersma RA, Thomson M, et al. Risk factors for ischaemic heart disease in normal men aged 40. Lancet 1978; i: 949-55. 9. Katan MB, Beynen AC. Linoleic add consumption and coronary heart disease in USA and UK. Lancet 1981; ii: 371. 10. Liu K, Stamler J, Moss D, Garside D, Persky V, Soltero I. Dietary cholesterol, fat and fibre and colon cancer mortality. Lancet 1979; ii: 782-85. 11. Goodnight SH, Harris WJ, Connor WE, Illingworth DR. Polyunsaturated fatty acids hyperlipidaemia and thrombosis. Arteriosclerosis 1982; 2: 87-113.

(ISOCALORIC)* AND OF

PROPOSED DIETARY GOALS

*2000 kcal/day. tWestern--Connor

et al; UK (NFS) = National Food Survey 1984 (domestic consumption only); prudent == Amencan Heart Association/National Institutes of Health prudent diet; UK (COMA) diet recommended by Committee on Medical Aspects of Food Policy (ranges shown) =

P/S ratio of 0-30. Average serum cholesterol levels are above those in the USA and it seems clear that in the UK the lipid lowering effect of increased polyunsatuated fats as well as decreased saturated fat and cholesterol are required. Yet official Department of Health advice, via its Committee on Medical Aspects of Food Policy, is that polyunsaturated fat in the diet should be in the range 10-17g and not exceed this level, which is well below current intake in the USA; no reduction in cholesterol consumption is advised. In the 1960s USA dietary composition resembled that in the UK when both countries had very high levels of CHD mortality. Both continue to have an undesirably high fat intake (42°° of calories), but in the USA the balance of saturated and polyunsaturated fats in the diet has altered greatly, so that the P/S ratio is now about 0-6. This change has been accompanied by a 35-40% drop in CHD mortality. In the UK meanwhile similar changes in dietary composition and in CHD mortality have been slow and small. Besides its effect on serum lipids, relative deficiency of

and

polyunsaturated fatty acids (including the essential fatty acids) may be implicated in CHD through, for example, effects on platelet function and aggregation, thrombogenesis, and the structure and function of the endothelial wall.1-7 The low UK average intake of

polyunsaturated fatty acids, especially linoleic, which is reflected in adipose tissue composition,8.9 may be an additional factor in Britain’s high CHD mortality. The

American Heart recommends that Association polyunsaturated fats should not be increased above 10% of calories in the diet. Since this is double current UK consumption there is clearly considerable room for increase before this caveat operates. It is in any case based, reasonably, on a cautious approach to dietary change and not on firm evidence of harm. Suggestions of a possible increase in colonic cancer in populations taking a diet high in

SIR,-By attempting to reduce the complex arguments of the diet-fat theory to a single score (the CSI or cholesterol/saturated fat index) Sonja Connor and her colleagues are joining together orthodox with more controversial doctrines, and may create a dangerously plausible shorthand dogma, which, like calorie counting, will be used as a substitute for more specific nutritional advice. Reduction of saturated fat in the diet (which is usually of animal origin and contained in the same foodstuffs as most dietary cholesterol) is generally recommended by expert committees.’ More controversial are the independent contribution to serum cholesterol and to coronary risk of foodstuffs containing disproportionate dietary cholesterol with little saturated fat (such as eggs and shellfish), and whether or not to substitute polyunsaturated for saturated fats. The independent effect of dietary cholesterol on serum cholesterol has been a matter of controversy for 25 years; there is now much good evidence that it does have an effect, but this varies considerably between individuals and appears to be non-linear, with a diminishing effect as quantities increase.2The heavy and implied linear weighting given to dietary cholesterol in the derivation of the CSI therefore put Connor and colleagues towards one extreme of the argument. Less controversial than the serum-cholesterol-raising effect of dietary cholesterol is the lowering effect of polyunsaturated fats.’’ Consumption of large quantities of these is probably unwise, for the reasons Connor et al give. However, their typical "Western diet" with 18 g of polyunsaturated fat and 31 g of saturated fat, contains considerably more polyunsaturated fat than is present in many Western diets, such as those in the UK, and the arguments for some substitution in the latter both on practical and theoretical grounds is at least as good as that for the specific substitution by omega-3 fatty acids, cited with approval by Connor et al. Omission of polyunsaturates from the CSI units does lead to positive scores, which means that the units measure potential harm alone, rather than any benefit; avoidance of high scores does not help the user to know what he or she should be substituting. Thus, replacement of liver

or meat with either nothing, sugar, complex carbohydrates, vegetable protein, monounsaturated, or polyunsaturated fat, would all count as equally creditable by this system-leading, without full nutritional advice, to potentially bizarre diets. The scatter diagram of the CSI measure of diet versus ischaemic heart disease mortality in different countries, adduced as evidence for this index, contributes little that is new; Connor et al admit that correlations of this mortality with CSI units, with saturated fat

345

alone, or with the Hegsted formulawhich includes this and dietary cholesterol and polyunsaturated fat, are virtually identical. CSI units, despite their arguable derivation, may be of value on the West Coast of the USA where polyunsaturates and shellfish are eaten in quantity, but in other places, less far West, we suspect they will raise as many problems as they are intended to solve, and will not prove a short-cut to good dietary advice. HUGH TUNSTALL-PEDOE W. C. S. SMITH Cardiovascular Epidemiology Unit, I. K. CROMBIE Ninewells Hospital and Medical School, M. THOMSON Dundee DD1 9SY on Medical Aspects of Food Policy—COMA. Diet and cardiovascular disease. London: HMSO, 1984. 2. Keys A. Serum cholesterol response to dietary cholesterol. Am J Clin Nutr 1984; 40: 351-59. 3. Connor SL, Connor WE. The importance of dietary cholesterol in coronary heart disease. Prev Med 1983; 12: 115-23. 4. Keys A, Anderson JT, Grande F. Serum cholesterol response to changes in the diet. Metabolism 1965; 14: 747-87. 5 Hegsted DM, McGandy RB, Myers ML, Stare FJ. Quantitative effect of dietary fat on serum cholesterol in man. Am J Clin Nutr 1965; 17: 281-95.

1. Committee

Mitogenic activity in platelet-rich plasma-derived serum from 7 normal subjects and 14 patients with myeloproliferative disorders.

SIR,-We have tested the cholesterol/saturated-fat index (CSI) insulin-dependent diabetics, a population at increased risk of atherosclerosis. 50 diabetics (age 31 ± 12 years, range 19-61), selected at random, had 7 day dietary recalls in 1982 and in 1986 by the same dietitian. During this period, they were educated about in

dietary recommendations introduced in the 1980s. The CSI (in Mcal per day) was 32.2 in 1982, falling to 24.3 (p < 0°001). The Keys score (in Mcal per day) fell from 65 ± 16 to 46±16 (p < 0°001). The polyunsaturated/saturated fat ratio rose from 0°32 026 to 0-62 ±0-3 (p< 0-001). CSI and Keys scores were positively correlated (r = 0-86, p < 0-001) as were the CSI and P/S ratio (r=0-65, p<0-001). The dietary changes included reduced consumption of saturated fatty acids (55-2±20-4 to 39-8 ± 19-3 g per day) and cholesterol (500 ± 180 to 417±154 mg per day) and an increased intake of polyunsaturated fatty acids (15 11 to 212 f 8°8 g per day. Weight and calorie intake were unchanged. The serum cholesterol fell from 4,96 ± 1-03 to 4-6 ± 0,8 mmol/1 (p < 0’02) but the individual falls were not correlated with changes in CSI or Keys score. These data confirm that the usual diet of diabetic patients has high atherogenic potential even if serum cholesterol levels are normal. After intensive dietary training, the patients doubled their dietary P/S ratios but the CSI remained high. The P/S ratio and cholesterol intake seem insufficient for evaluating the atherogenic risks of food in diabetics. We must persuade diabetic patients to less animal foods. This goal should be achievable because our results show that nutritional education can lead to reduced lipid intake. The CSI will be very useful for providing nutrition advice for diabetics, especially if a table of the CSIs of foods were to be consume

published. Department of Endocrinology and Metabolism, Centre Hospitalier Universitaire, 29285 Brest, France

DOMINIQUE TATER FRANÇOISE LE GALL JEAN PIERRE BERCOVICI

patients with myeloproliferative disorders than from controls. No differences were found in platelet-poor-plasma-derived serum. Several factors could be responsible for platelet-derived mitogenic activity. Platelets contain proteins able to stimulate the growth of different cell types. The best characterised among these factors are platelet-derived growth factor (PDGF)epidermal growth factor (EGF), and p-transforming growth factor (&bgr;- TGF).4 The heat resistance (100°C for 5 min) of the mitogenic activity we measured strongly suggests a major involvement ofPDGF.s The defect observed could be the result of abnormalities in the maturation of megakaryoblasts of the transformed clone.6 On the other hand, mitogenic factor(s) could be released into the circulation as a consequence of coagulative events common in patients with myeloproliferative disorders? The physiopathological relevance of this new defect in platelets from patients with myeloproliferative disorders remains to be established. A mitogenic factor with characteristics similar to those of PDGF, released in the bone marrow from impaired megakaryoblasts, could be of importance in the development of myelofibrosis.8 The reduced mitogenic activity in platelets from patients with myeloproliferative disorders could serve as a peripheral marker of

events

in the bone marrow.

Mario Negri Institute for Pharmacological Research, Via Eritrea 62, 20157 Milano, Italy Division

of Haematology, Ospedali Riumiti di Bergamo, Bergamo, Italy

M. ROMANO A. POGGI M. B. DONATI S. CORTELAZZO P. VIERO T. BARBUI

T, Cortellazzo S, Viero P, Bassan R, Dini E, Semeraro N. Thrombohaemorrhagic complications in 101 cases ofmyeloproliferative disorders relationship to platelet number and function Eur J Cancer Clin Oncol 1983; 19:

1. Barbui

REDUCED PLATELET MITOGENIC ACTIVITY IN MYELOPROLIFERATIVE DISORDERS

SIR,-Many abnormalities have been described in platelets from patients with myeloproliferative disorders.’ We measured plateletderived mitogenic activity in 14 patients with myeloproliferative disorders (5 had chronic myeloid leukaemia, 2 idiopathic myelofibrosis, 2 polycythaemia vera, and 5 essential thrombocythaemia), and in 7 normal subjects. Mitogenic activity was measured as an increase of 3H-thymidine incorporation by NIH 3T3 cells upon stimulation with platelet-rich-plasma-derived serum, platelet-poor-plasma-derived serum and platelet extract.2 Mitogenic activity was significantly lower in platelet-richplasma-derived serum (see figure) and in platelet extracts from

1593-99. 2.

Poggi A, Rucinski B, James P, Holt JC, Niewiarowski S. Partial purification and characterization of porcine platelet-derived growth factor (PDGF). Exp Cell Res 1984; 150: 436-41.

3. Ross R. The pathogenesis of atherosclerosis. An update. N Engl J Med 488-500. 4. Spom MB, Roberts AB. Autocrine growth factors and cancer. Nature

1986; 314: 1985;

313:

745-47. 5. Deuel TF, Huang JS. Platelet derived growth factor. Structure, function and roles in normal and transformed cells. J Clin Invest 1984; 74: 669-76. 6. Rabellino EM, Levene RB, Nachman RL, Leung LLK. Human megakaryocytes III. Characterisation in myeloproliferative disorders. Blood 1984; 63: 615-22. 7. Schafer AI. Bleeding and thrombosis in the myeloproliferative disorders. Blood 1984; 64: 1-12. 8. Castro-Malaspina H, Rabellino EM, Yen A, Nachman RL, Moore MAS. Human megakaryocyte stimulation of proliferation of bone marrow fibroblasts. Blood 1981; 57: 781-87.