- Email: [email protected]
PREVENTION OF CORONARY HEART DISEASE
894
SIR,-Dr Flynn and colleagues judged zinc status by the total zinc in blood plasma measured by flame atomic absorption. They found a significantly lower total plasma zinc in the alcoholic women. However, this may not reveal the truth about total body zinc status. Zinc is bound to several serum roteins, including albumin, so that alterations in the a2-macroglobulin, and concentrations of these proteins change the total plasma zinc. This is analogous to the situation with thyroid status: fluctuations in thyroxine binding globulin make measurements of total T4 (thyroxine) of limited value, hence the widespread use of triiodothyronine uptake tests. In alcoholic subjects, albumin is characteristically reduced and could well account for the reduced concentrations of zinc in plasma described. The alterations in the other binding proteins also need to be taken into account. Only 1% of body zinc is present in plasma and of this over 9007o is bound to plasma components, such as albumin. Plasma levels of zinc are therefore potentially misleading.
transferrin, P3
Immuno Diagnostic Research Laboratory, Department of Immunology, University of Birmingham, Medical School, Birmingham B15 2TJ
SIR,-Your editorial (Nov. 22, p. 1117) and the letter from Professor Whitehead and his colleagues (March 21, p. 663) refer to the fact that a high intake of alcohol is not the only cause of raised serum y-glutamyltranspeptidase (GGT) levels. We pointed this out in a previous paper,’ since when our study has been extended from 146 to 209 healthy adult males. Of these, 16 (7 -7%) had high levels attributable to alcohol but, intermittently or persistently, raised GGT levels were found in another 16 (7’7%) in all of whom, as far as could be ascertained, alcohol intake was negligible; this is a higher proportion than we previously reported (2 -7%). No medication or other obvious factor appeared to be related yet electrophoresis indicated that the enzyme was probably hepatic in origin. In 5 of the 16 the serum aspartate transaminase was also intermittently slightly raised. There are clearly factors, apart from alcohol, at present unidentified, which provoke increases in GGT and other hepatic enzymes. Study of these subjects continues and may possibly throw light on hepatic cellular damage which is neither viral, autoimmune, nor alcoholic in origin. ROSANNA PENN D.J.WORTHINGTON WORTHINGTON C. A. CLARKE A. G. W. WHITFIELD
CA
SIR,-Professor Whitehead and colleagues (March 21,
p.
663)
limitations of y-glutamyltranspeptidase (GGT) as a for alcoholism but these are of little practical test screening importance. Increased GGT levels are not exclusive to alcoholism. Liver disease, whatever the cause, accounts for many high GGT values, but in most such cases the GGT activity parallels that of alkaline phosphatase (AP) since both enzymes tend to respond to cholestasis. In non-alcoholic pancreatitis, if cholestasis supervenes as a result of pancreatic oedema or associated cholelithiasis, the GGT may also be increased, as Whitehead et al. state, but so will the AP value. A raised GGT with normal or near normal AP level suggests a different mechanism, as in chronic alcohol intake or the administration of drugs, such as barbiturates, that stimulate the some
1 Scott 2.
BJ, Walker BE, Bradwell AR. How should serum zinc concentrations be interpreted? Clin Sci 1979; 56: 27p. Prasad AS, Oberleas D. Binding of zinc to ammo acids and serum proteins ’in vitro’ J
Lab Clin Med 1970; 76: 416. EL, Durieux M, Schechter PJ A study of zinc distribution in human serum. Bioinorg Chem 1976; 5: 211. 4. Whitehead TP, Clarke CA, Whitfield AGW. Biochemical and haematological markers of alcohol intake. Lancet 1978; i: 978-81.
3. Giroux
Ciudad Sanitaria del Valle Hebrón,
BARBARA J. SCOTT ARTHUR R. BRADWELL
ALCOHOL INTAKE
suggest
Department of Internal Medicine, Barcelona, Spain
GAMMA-GLUTAMYLTRANSPEPTIDASE AND
Medical Services Study Group of the Royal College of Physicians, 126 Albert Street, London NW1 7NF
synthesis of some liver enzymes. If a careful medical history is taken these false positives can be avoided. In our experience, a hver enzyme pattern of isolated or predominant increased GGT is found in about 80% of heavy drinkers who are admitted to hospital for whatever reason, including most cases of alcoholic liver disease. Since false positives are easily discarded by the findings of a concomitant increase in AP or by history taking, the true limitation of the GGT as a screening test for alcoholism lies in the 20% of heavy drinkers who have normal levels and in the rare patient with alcohol related cholestasis (alcoholic cholestatic hepatitis and pancreatitis with secondary cholestasis) in whom AP will also be strikingly increased. Even these limitations may in part be solved by the combined determination of GGT levels and mean corpuscular volume, a combination which, in our experience, detects almost 100% of chronic alcoholics. R. PÉREZ-SOLER C. TORNOS SALOMÓ
PREVENTION OF CORONARY HEART DISEASE
SIR,-In your editorial on prostacyclins in therapeutics (March 21) you state that in the prevention of myocardial infarction the therapeutic scene is barren. You consider that the main goal for clinicians and the pharmaceutical industry is to prevent and treat atheroma and superimposed arterial thrombosis, yet appear to assume that prophylaxis by drugs is the main course to pursue. This assumption must be challenged. To concentrate on this line alone, in view of the disappointing results from drugs over the past 20 years, and to neglect the growing evidence that changes in lifestyle are far more important, is surely a mistaken policy. Although controlled trials on man’s behaviour are more difficult to undertake than controlled drug trials, the evidence is impressive. Within 5 years doctors below the age of 55 who stopped smoking markedly reduced their risk of fatal coronary attacks compared with those who continued to smoke. Patients who are persuaded to stop
smoking after an infarct suffer between a half and two-thirds the relapse rate of those who continue to smoke, as at least four different trials have now shown. These results do not constitute proof, but are strongly suggestive. No drug or operation for coronary disease has yet shown such success. You state that dietary changes have not convinced clinicians, yet fail to note that the evidence has convinced many authorities, including the D. H. S. S., that at least the reduction of saturated fat is likely to reduce the incidence of coronary heart disease (CHD) in the nation. Ten years ago the CHD mortality rate for middle-aged men in the United States was 40% above the rate for England and Wales and today has fallen below our own which has increased by 14% during this period. This has not been achieved by drugs. Although proof is not possible it is likely that changes in the American diet (including an increase of polyunsaturated fat), in their smoking and exercise habits, and, probably, their efforts at blood pressure control are
partly responsible.
As a result of long term trials, new drugs might help to reduce coronary deaths in those found to be at high risk on screening. But this of itself would be a costly exercise and would only identify a proportion of those who would develop fatal heart attacks. If doctors would use their concerted influence to help patients to stop cigarette smoking, promote sensible eating ,habits, and detect and treat hypertension, a reduction in coronary death rate could take place very soon. We might then see similar reductions in our coronary mortality to those now occurring not only in the United States but also in Finland, Canada, Belgium, Australia, and New Zealand. Research into prostacyclins may shed further light on the mechanisms of arterial thrombosis and assist the discovery of new drugs, but it should not delay action on more immediate issues Middlesex
Hospital Medical School, Department of Community Medicine, Central Middlesex Hospital, London NW10 7NS
KEITH BALL
SIR,-Dr Flynn and colleagues judged zinc status by the total zinc in blood plasma measured by flame atomic absorption. They found a significantly lower total plasma zinc in the alcoholic women. However, this may not reveal the truth about total body zinc status. Zinc is bound to several serum roteins, including albumin, so that alterations in the a2-macroglobulin, and concentrations of these proteins change the total plasma zinc. This is analogous to the situation with thyroid status: fluctuations in thyroxine binding globulin make measurements of total T4 (thyroxine) of limited value, hence the widespread use of triiodothyronine uptake tests. In alcoholic subjects, albumin is characteristically reduced and could well account for the reduced concentrations of zinc in plasma described. The alterations in the other binding proteins also need to be taken into account. Only 1% of body zinc is present in plasma and of this over 9007o is bound to plasma components, such as albumin. Plasma levels of zinc are therefore potentially misleading.
transferrin, P3
Immuno Diagnostic Research Laboratory, Department of Immunology, University of Birmingham, Medical School, Birmingham B15 2TJ
SIR,-Your editorial (Nov. 22, p. 1117) and the letter from Professor Whitehead and his colleagues (March 21, p. 663) refer to the fact that a high intake of alcohol is not the only cause of raised serum y-glutamyltranspeptidase (GGT) levels. We pointed this out in a previous paper,’ since when our study has been extended from 146 to 209 healthy adult males. Of these, 16 (7 -7%) had high levels attributable to alcohol but, intermittently or persistently, raised GGT levels were found in another 16 (7’7%) in all of whom, as far as could be ascertained, alcohol intake was negligible; this is a higher proportion than we previously reported (2 -7%). No medication or other obvious factor appeared to be related yet electrophoresis indicated that the enzyme was probably hepatic in origin. In 5 of the 16 the serum aspartate transaminase was also intermittently slightly raised. There are clearly factors, apart from alcohol, at present unidentified, which provoke increases in GGT and other hepatic enzymes. Study of these subjects continues and may possibly throw light on hepatic cellular damage which is neither viral, autoimmune, nor alcoholic in origin. ROSANNA PENN D.J.WORTHINGTON WORTHINGTON C. A. CLARKE A. G. W. WHITFIELD
CA
SIR,-Professor Whitehead and colleagues (March 21,
p.
663)
limitations of y-glutamyltranspeptidase (GGT) as a for alcoholism but these are of little practical test screening importance. Increased GGT levels are not exclusive to alcoholism. Liver disease, whatever the cause, accounts for many high GGT values, but in most such cases the GGT activity parallels that of alkaline phosphatase (AP) since both enzymes tend to respond to cholestasis. In non-alcoholic pancreatitis, if cholestasis supervenes as a result of pancreatic oedema or associated cholelithiasis, the GGT may also be increased, as Whitehead et al. state, but so will the AP value. A raised GGT with normal or near normal AP level suggests a different mechanism, as in chronic alcohol intake or the administration of drugs, such as barbiturates, that stimulate the some
1 Scott 2.
BJ, Walker BE, Bradwell AR. How should serum zinc concentrations be interpreted? Clin Sci 1979; 56: 27p. Prasad AS, Oberleas D. Binding of zinc to ammo acids and serum proteins ’in vitro’ J
Lab Clin Med 1970; 76: 416. EL, Durieux M, Schechter PJ A study of zinc distribution in human serum. Bioinorg Chem 1976; 5: 211. 4. Whitehead TP, Clarke CA, Whitfield AGW. Biochemical and haematological markers of alcohol intake. Lancet 1978; i: 978-81.
3. Giroux
Ciudad Sanitaria del Valle Hebrón,
BARBARA J. SCOTT ARTHUR R. BRADWELL
ALCOHOL INTAKE
suggest
Department of Internal Medicine, Barcelona, Spain
GAMMA-GLUTAMYLTRANSPEPTIDASE AND
Medical Services Study Group of the Royal College of Physicians, 126 Albert Street, London NW1 7NF
synthesis of some liver enzymes. If a careful medical history is taken these false positives can be avoided. In our experience, a hver enzyme pattern of isolated or predominant increased GGT is found in about 80% of heavy drinkers who are admitted to hospital for whatever reason, including most cases of alcoholic liver disease. Since false positives are easily discarded by the findings of a concomitant increase in AP or by history taking, the true limitation of the GGT as a screening test for alcoholism lies in the 20% of heavy drinkers who have normal levels and in the rare patient with alcohol related cholestasis (alcoholic cholestatic hepatitis and pancreatitis with secondary cholestasis) in whom AP will also be strikingly increased. Even these limitations may in part be solved by the combined determination of GGT levels and mean corpuscular volume, a combination which, in our experience, detects almost 100% of chronic alcoholics. R. PÉREZ-SOLER C. TORNOS SALOMÓ
PREVENTION OF CORONARY HEART DISEASE
SIR,-In your editorial on prostacyclins in therapeutics (March 21) you state that in the prevention of myocardial infarction the therapeutic scene is barren. You consider that the main goal for clinicians and the pharmaceutical industry is to prevent and treat atheroma and superimposed arterial thrombosis, yet appear to assume that prophylaxis by drugs is the main course to pursue. This assumption must be challenged. To concentrate on this line alone, in view of the disappointing results from drugs over the past 20 years, and to neglect the growing evidence that changes in lifestyle are far more important, is surely a mistaken policy. Although controlled trials on man’s behaviour are more difficult to undertake than controlled drug trials, the evidence is impressive. Within 5 years doctors below the age of 55 who stopped smoking markedly reduced their risk of fatal coronary attacks compared with those who continued to smoke. Patients who are persuaded to stop
smoking after an infarct suffer between a half and two-thirds the relapse rate of those who continue to smoke, as at least four different trials have now shown. These results do not constitute proof, but are strongly suggestive. No drug or operation for coronary disease has yet shown such success. You state that dietary changes have not convinced clinicians, yet fail to note that the evidence has convinced many authorities, including the D. H. S. S., that at least the reduction of saturated fat is likely to reduce the incidence of coronary heart disease (CHD) in the nation. Ten years ago the CHD mortality rate for middle-aged men in the United States was 40% above the rate for England and Wales and today has fallen below our own which has increased by 14% during this period. This has not been achieved by drugs. Although proof is not possible it is likely that changes in the American diet (including an increase of polyunsaturated fat), in their smoking and exercise habits, and, probably, their efforts at blood pressure control are
partly responsible.
As a result of long term trials, new drugs might help to reduce coronary deaths in those found to be at high risk on screening. But this of itself would be a costly exercise and would only identify a proportion of those who would develop fatal heart attacks. If doctors would use their concerted influence to help patients to stop cigarette smoking, promote sensible eating ,habits, and detect and treat hypertension, a reduction in coronary death rate could take place very soon. We might then see similar reductions in our coronary mortality to those now occurring not only in the United States but also in Finland, Canada, Belgium, Australia, and New Zealand. Research into prostacyclins may shed further light on the mechanisms of arterial thrombosis and assist the discovery of new drugs, but it should not delay action on more immediate issues Middlesex
Hospital Medical School, Department of Community Medicine, Central Middlesex Hospital, London NW10 7NS
KEITH BALL