- Email: [email protected]
Hormone replacement therapy and mammography
CORRESPONDENCE
heterophilic antibodies against these species. The awareness of heterophilic antibodies as a possible source of false positive assays is not very widespread among clinicians. Past publications about heterophilic antibodies were published mainly in specialised journals for clinical chemistry and laboratory medicine.2–4 Clinically important markers, such as C-reactive protein and cTnI were affected, but clinicians still tend to see some markers as magic bullets, especially when they are known to have a high specificity. We do not agree with Rotmensch and Cole that in the described cases “the physicians . . . had no reason to question the . . . hCG results”. Neither the clinical picture nor the imaging results clearly supported the diagnosis, but lack of communication with clinical chemists led to unnecessary aggressive treatment in these cases. The reported cases emphasise the necessity to confirm nearly all raised markers with other easy diagnostic methods before proceeding to invasive diagnostic or therapeutic options. *Christoph G Dietrich, Hugo Stiegler, Vincent M Brandenberg, Jochen Riehl Departments of *Internal Medicine III/II and Clinical Chemistry and Pathobiochemistry of the Technical University of Aachen, D-52074 Aachen, Germany 1
2
3
4
Rotmensch S, Cole LA. False diagnosis and needless therapy of presumed malignant disease in women with false-positive human chorionic gonadotropin concentrations. Lancet 2000; 355: 712–15. Yeo KJ, Storm CA, Li Y, et al. Performance of the enhanced Abbott AxSYM Cardiac Troponin I reagent in patients with heterophilic antibodies. Clin Chim Acta 2000; 292: 13–23. Fitzmaurice TF, Brown C, Rifai N, Wu AH, Yeo KT. False increase of cardiac troponin I with heterophilic antibodies. Clin Chem 1998; 44: 2212–14. Benoist JF, Orbach D, Biou D. False increase in C-reactive protein attributable to heterophilic antibodies in two renal transplant patients treated with rabbit antilymphocyte globulin. Clin Chem 1998; 44: 1980–85.
Injections and pain Sir—Bruno Simini (March 25, p 1076)1 showed that although most patients expected a spinal puncture to hurt more than an intravenous and an intramuscular injection, they actually found the opposite to be true. Based on these findings he suggests that patients’ veins should be anaesthetised before inserting a cannula, and intramuscular injections should not be used. There are some considerations, however, that may challenge the interpretation of his results. Pain felt after an injection depends on the size and gauge of the needle,
1726
and on the substance or drug that is being injected, its concentration (or dilution), the volume injected, the site of the injection, and the ability of the healthcare provider to carry out the procedure. Those who were ever given an intramuscular injection of benzathine penicillin are unlikely to have forgotten this experience, contrary to other less painful intramuscular injections. Because the same drug was not injected in all injection sites, the comparisons made in his study may be valid for the drugs used by him, but not necessarily for other drugs. Lumbar puncture was done after an injection of benzodiazepine, which is known to impair memory, so judgment of pain could have been impaired. Even if Simini is correct in his interpretation that spinal punctures are less painful than intramuscular and intravenous injections, this does not necessarily mean that any of these procedures requires or benefits from local anaesthesia, since this question was not addressed in his study. I believe that the points raised above question Dr Simini’s recommendations, that may well be correct, but were not demonstrated by his findings. Sergio de A Nishioka Centro de Ciencias Biomedicas, Universidade Federal de Uberlandia, Uberlandia, Brazil; *Al Sosthenes Guimaraes 667, 38411-160 Uberlandia MG, Brazil (e-mail: [email protected]) 1
Simini B. Patients’ perceptions of pain with spinal, intramuscular, and venous injections. Lancet 2000; 355: 1076.
Author’s reply Sir—Sergio de A Nishioka’s concerns regarding needle size, nature and concentration of the drug injected, injection site, and technique are well founded and are certainly not ignored in my study, some of them are addressed in it. But I do concede that I was imprudent to generalise conclusions which are strictly speaking valid only for the three specific procedures described. Regarding amnesia possibly resulting from previous intramuscular benzodiazepine administraiton, patients were asked about pain immediately after receiving the lumbar puncture, which in turn was given not more than a few minutes after the intravenous cannula was inserted. Most patients said the injections they received first (intramuscular and intravenous) hurt most—drug-induced memory impairment would be expected to cause the opposite—ie, to forget how painful the first injections were. Bruno Simini Ospedale, 55100 Lucca, Italy
Hormone replacement therapy and mammography Sir—Anne Kavanagh and colleagues (Jan 22, p 270)1 reported on the accuracy of mammographic screening in women taking hormone replacement therapy (HRT). While we agree with their general conclusions certain questions remain insufficiently addressed by the investigators. The investigators state that there is a sensitivity reduction in HRT users compared with non-users in those aged 50–69 years. While this is consistent with previous findings as stated,2,3 in this study the CIs for sensitivities overlap in all age groups except in the 60–69 years age group. Hence, a real difference appears to relate to this older age group only (table 2). A reduction in sensitivity in HRT users compared with non-users of 10% at the 1-year interval and 15% at 2 years is stated. Again, this is consistent with previous findings,2,3 however, from the data, the adjusted odds ratio for sensitivity analysis at one year is nonsignificant but is significant at the 2-year interval only (table 3). The investigators did not find a significant difference in the small cancer detection rate between the two groups. This finding is somewhat at odds with the overall reduction in sensitivity of cancer detection in those on HRT and we are surprised it is not addressed and explained by the investigators in their discussion. *Catherine Hayes, Patricia Fitzpatrick, Jane Buttimer Breast Check, Irish National Breast Screening Programme, Dublin 2, Ireland (e-mail: [email protected]) 1
2
3
Kavanagh AM, Mitchell H, Giles GG. Hormone replacement therapy and accuracy of mammographic screening. Lancet 2000; 355: 270–74. Litherland JC, Stallard S, Hole D, Corinder C. The effect of hormone replacement therapy on the sensitivity of screening mammograms. Clin Radiol 1999; 54: 285–88. Seradour B, Esteve J, Heid P, Jacquemier J. Hormone replacement therapy and screening mammography: analysis of the results of the Bouches du Rhone programme. J Med Screen 1999; 6: 99–102.
Authors’ reply Sir—The statistical modelling we used shows an overall reduction in sensitivity to mammographic screening for women on HRT; once the data are stratified into different age categories, statistical power is reduced. The point estimates provide an indication of the magnitude of the effects in the different age groups. Only in the 50–59 years and 60–69 years categories were there clinically significant reductions in the
THE LANCET • Vol 355 • May 13, 2000
CORRESPONDENCE
sensitivity of mammography with HRT use (7·6% and 20·4%, respectively). The 50–59 years and 60–69 years age groups were combined because they are the target group for mammographic screening in Australia. For that combined age group, there was a 15% reduction in the sensitivity of mammography with HRT use over a 2-year interval. Our statement about the 10% reduction in the sensitivity of mammography over a 1-year screening interval refers to women aged 50–69 years and the logistic regression analysis included all age groups. Among women aged 50–69 years at screening who had cancer diagnosed during a 1-year interval, the women on HRT were more likely to have a false negative than non-users of HRT (adjusted odds ratio 2·65 [1·34–5·21]). In the entire age group, the 95% CIs for the adjusted odds ratio of 1·72 are 0·98 to 3·03. Although these limits include the null value of one, and hence do not attain significance at the 5% level, it would be wrong to conclude that this indicates a lack of effect. Rather than acting as de-facto significance tests, CIs provide information about the size and precision of estimates.1 The important point in this instance is that the magnitude of the effect over the 1-year interval is similar to that found in the 2-year interval and is consistent with the findings of other studies.2,3 Catherine Hayes and colleagues ask us why we did not find a significant reduction in the small cancer detection rate in HRT users The small cancer detection is dependent on at least two parameters: the sensitivity of mammography, and the underlying rate of invasive breast cancer in the population group. While we found that sensitivity was reduced in HRT users, which would decrease the small cancer detection rate, these women could also have a higher risk of breast cancer,4 which would have the opposite effect. Anne M Kavanagh, Heather Mitchell, Graham G Giles Australian Research Centre in Sex, Health, and Society, Faculty of Health Sciences, La Trobe University, Melbourne 3000, Australia. 1
2
3
Rothman K, Greenland S. Modern epidemiology, 2nd edn. Lippincott and Raven Publishers; Philadelphia, 1998. Séradour B, Estève J, Heid P, Jacquemier J. Hormone replacement therapy and screening mammography: analysis of the results of the du Rhône programme. J Med Screening 1999; 6: 99–102. Rosenberg R, Hunt W, Williamson M, et al. Effects of age, breast density, ethnicity, and estrogen replacement therapy on the sensitivity and cancer stage at diagnosis: review of 183 134 screening mammograms in Albuquerque, New Mexico. Radiology 1998; 209: 511–18.
THE LANCET • Vol 355 • May 13, 2000
4
Collaborative Group on Hormonal Factors and Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. Lancet 1997; 350: 1047–59.
poverty, poor educational standards, and poor health. Economic prosperity is the key to healthy living and longevity. *P Ghosh, S A Khan Care of the Elderly Directorate, North Herts NHS Trust, Lister Hospital, Stevenage SG1 4AB, UK
Coronary heart disease in Indian Asians Sir—John Chambers and colleagues (Feb 12, p 523)1 suggest that Indian Asians living in the UK have low levels of vitamin B12 and folic acid in their diet and therefore increased plasma homocysteine concentrations, which in turn contributes to coronary heart disease. Conventional risk factors, such as increased total cholesterol, hypertension, and smoking, have failed to explain the increased incidence of coronary heart disease in this group. Type-2 diabetes mellitus, insulin resistance, and central obesity have been suggested as possible risk factors.2 While searching for a medical cause for atherogenesis, one should not ignore the fact that there is a strong association between poverty and poor health. In the UK, Indian Asians generally have lower income and live in poor housing. In addition, the language barrier hampers their access to health services, social care, and health information, particularly amongst the elderly. Mortality from coronary heart disease amongst Indian Asians is 20% higher when compared with the general population. 3 The highest proportional mortality ratio is in excess of 70% in the Bangladeshi immigrant population.4 In 1970–85, the mortality rates associated with coronary heart disease increased by 8% in men and 14% in women from this community, while the overall mortality in all western countries had fallen. This trend was also noted in the second generation, who were born and raised in the UK.2 Life expectancy has a positive correlation with gross national product per head, gross income of the poor in the society, and public expenditure, particularly in health care. Better basic education and access to health care contribute to an improved life expectancy. In the USA, African Americans seem to have a lower life expectancy than their white compatriots. Their life expectancy is even worse than the Chinese and Indians from the state of Kerala.5 This trend is also noted amongst the Aboriginal population in Australia. There seems to be an association between ethnicity, real and relative
1
2
3
4 5
Chambers JC, Obeid OA, Refsum H, et al. Plasma homocysteine concentration and risk of coronary heart disease in the UK Indian Asian and European men. Lancet 2000; 355: 523–27. Gupta S, de Belder A, Hughes L. Avoiding premature coronary deaths in Asians in Britain. BMJ 1995; 311: 1035–36. McKeigue PM, Marmot MG. Mortality from coronary heart disease in Asian communities in London. BMJ 1988; 297: 903. Fox KM, Shapiro LM. Heart disease in Asians in Britain. BMJ 1988; 297: 311–12. Sen A. Economics and health. Lancet 1999; 354: 20.
Sir—The study by John Chambers of plasma and colleagues 1 homocysteine concentrations in UK Indian Asians is interesting but may not reflect the full picture of coronary heart disease in the Indian subcontinent. Many Asians are vegetarians, a diet associated, to differing extents, with reductions in plasma LDL. A vegetarian diet is also associated with reduced folate and vitamin B12 and, therefore, with hyperhomocysteinaemia.2 This type of diet could be a significant confounding element in the study because a strict vegetarian diet is rare among Europeans. A comparison of the non-vegetarian Indian Asian group with Europeans would be helpful in determining the role of plasma homocysteine as a cardiovascular risk factor, independent of the generally cardioprotective effects of a vegetarian diet. Also, the study investigated Asians of North Indian descent, in whom homocysteinaemia has been shown to be common,3 and an east London Bangladeshi/Bengali population, in whom rates of smoking have been found to be higher than in west London Asians of Gujerati descent. There are also substantial differences in diet, including saturated and unsaturated fat intakes, between various ethnic subgroups in India, which are likely to be carried over to the UK.4 In contrast to the findings of this study, a study of 114 individuals of Sri Lankan (Tamil) origin showed no association of methylene tetrahydrofolate reductase (MTHFR) genotype and homocysteinaemia. The MTHFR 677T allele frequency was
1727
heterophilic antibodies against these species. The awareness of heterophilic antibodies as a possible source of false positive assays is not very widespread among clinicians. Past publications about heterophilic antibodies were published mainly in specialised journals for clinical chemistry and laboratory medicine.2–4 Clinically important markers, such as C-reactive protein and cTnI were affected, but clinicians still tend to see some markers as magic bullets, especially when they are known to have a high specificity. We do not agree with Rotmensch and Cole that in the described cases “the physicians . . . had no reason to question the . . . hCG results”. Neither the clinical picture nor the imaging results clearly supported the diagnosis, but lack of communication with clinical chemists led to unnecessary aggressive treatment in these cases. The reported cases emphasise the necessity to confirm nearly all raised markers with other easy diagnostic methods before proceeding to invasive diagnostic or therapeutic options. *Christoph G Dietrich, Hugo Stiegler, Vincent M Brandenberg, Jochen Riehl Departments of *Internal Medicine III/II and Clinical Chemistry and Pathobiochemistry of the Technical University of Aachen, D-52074 Aachen, Germany 1
2
3
4
Rotmensch S, Cole LA. False diagnosis and needless therapy of presumed malignant disease in women with false-positive human chorionic gonadotropin concentrations. Lancet 2000; 355: 712–15. Yeo KJ, Storm CA, Li Y, et al. Performance of the enhanced Abbott AxSYM Cardiac Troponin I reagent in patients with heterophilic antibodies. Clin Chim Acta 2000; 292: 13–23. Fitzmaurice TF, Brown C, Rifai N, Wu AH, Yeo KT. False increase of cardiac troponin I with heterophilic antibodies. Clin Chem 1998; 44: 2212–14. Benoist JF, Orbach D, Biou D. False increase in C-reactive protein attributable to heterophilic antibodies in two renal transplant patients treated with rabbit antilymphocyte globulin. Clin Chem 1998; 44: 1980–85.
Injections and pain Sir—Bruno Simini (March 25, p 1076)1 showed that although most patients expected a spinal puncture to hurt more than an intravenous and an intramuscular injection, they actually found the opposite to be true. Based on these findings he suggests that patients’ veins should be anaesthetised before inserting a cannula, and intramuscular injections should not be used. There are some considerations, however, that may challenge the interpretation of his results. Pain felt after an injection depends on the size and gauge of the needle,
1726
and on the substance or drug that is being injected, its concentration (or dilution), the volume injected, the site of the injection, and the ability of the healthcare provider to carry out the procedure. Those who were ever given an intramuscular injection of benzathine penicillin are unlikely to have forgotten this experience, contrary to other less painful intramuscular injections. Because the same drug was not injected in all injection sites, the comparisons made in his study may be valid for the drugs used by him, but not necessarily for other drugs. Lumbar puncture was done after an injection of benzodiazepine, which is known to impair memory, so judgment of pain could have been impaired. Even if Simini is correct in his interpretation that spinal punctures are less painful than intramuscular and intravenous injections, this does not necessarily mean that any of these procedures requires or benefits from local anaesthesia, since this question was not addressed in his study. I believe that the points raised above question Dr Simini’s recommendations, that may well be correct, but were not demonstrated by his findings. Sergio de A Nishioka Centro de Ciencias Biomedicas, Universidade Federal de Uberlandia, Uberlandia, Brazil; *Al Sosthenes Guimaraes 667, 38411-160 Uberlandia MG, Brazil (e-mail: [email protected]) 1
Simini B. Patients’ perceptions of pain with spinal, intramuscular, and venous injections. Lancet 2000; 355: 1076.
Author’s reply Sir—Sergio de A Nishioka’s concerns regarding needle size, nature and concentration of the drug injected, injection site, and technique are well founded and are certainly not ignored in my study, some of them are addressed in it. But I do concede that I was imprudent to generalise conclusions which are strictly speaking valid only for the three specific procedures described. Regarding amnesia possibly resulting from previous intramuscular benzodiazepine administraiton, patients were asked about pain immediately after receiving the lumbar puncture, which in turn was given not more than a few minutes after the intravenous cannula was inserted. Most patients said the injections they received first (intramuscular and intravenous) hurt most—drug-induced memory impairment would be expected to cause the opposite—ie, to forget how painful the first injections were. Bruno Simini Ospedale, 55100 Lucca, Italy
Hormone replacement therapy and mammography Sir—Anne Kavanagh and colleagues (Jan 22, p 270)1 reported on the accuracy of mammographic screening in women taking hormone replacement therapy (HRT). While we agree with their general conclusions certain questions remain insufficiently addressed by the investigators. The investigators state that there is a sensitivity reduction in HRT users compared with non-users in those aged 50–69 years. While this is consistent with previous findings as stated,2,3 in this study the CIs for sensitivities overlap in all age groups except in the 60–69 years age group. Hence, a real difference appears to relate to this older age group only (table 2). A reduction in sensitivity in HRT users compared with non-users of 10% at the 1-year interval and 15% at 2 years is stated. Again, this is consistent with previous findings,2,3 however, from the data, the adjusted odds ratio for sensitivity analysis at one year is nonsignificant but is significant at the 2-year interval only (table 3). The investigators did not find a significant difference in the small cancer detection rate between the two groups. This finding is somewhat at odds with the overall reduction in sensitivity of cancer detection in those on HRT and we are surprised it is not addressed and explained by the investigators in their discussion. *Catherine Hayes, Patricia Fitzpatrick, Jane Buttimer Breast Check, Irish National Breast Screening Programme, Dublin 2, Ireland (e-mail: [email protected]) 1
2
3
Kavanagh AM, Mitchell H, Giles GG. Hormone replacement therapy and accuracy of mammographic screening. Lancet 2000; 355: 270–74. Litherland JC, Stallard S, Hole D, Corinder C. The effect of hormone replacement therapy on the sensitivity of screening mammograms. Clin Radiol 1999; 54: 285–88. Seradour B, Esteve J, Heid P, Jacquemier J. Hormone replacement therapy and screening mammography: analysis of the results of the Bouches du Rhone programme. J Med Screen 1999; 6: 99–102.
Authors’ reply Sir—The statistical modelling we used shows an overall reduction in sensitivity to mammographic screening for women on HRT; once the data are stratified into different age categories, statistical power is reduced. The point estimates provide an indication of the magnitude of the effects in the different age groups. Only in the 50–59 years and 60–69 years categories were there clinically significant reductions in the
THE LANCET • Vol 355 • May 13, 2000
CORRESPONDENCE
sensitivity of mammography with HRT use (7·6% and 20·4%, respectively). The 50–59 years and 60–69 years age groups were combined because they are the target group for mammographic screening in Australia. For that combined age group, there was a 15% reduction in the sensitivity of mammography with HRT use over a 2-year interval. Our statement about the 10% reduction in the sensitivity of mammography over a 1-year screening interval refers to women aged 50–69 years and the logistic regression analysis included all age groups. Among women aged 50–69 years at screening who had cancer diagnosed during a 1-year interval, the women on HRT were more likely to have a false negative than non-users of HRT (adjusted odds ratio 2·65 [1·34–5·21]). In the entire age group, the 95% CIs for the adjusted odds ratio of 1·72 are 0·98 to 3·03. Although these limits include the null value of one, and hence do not attain significance at the 5% level, it would be wrong to conclude that this indicates a lack of effect. Rather than acting as de-facto significance tests, CIs provide information about the size and precision of estimates.1 The important point in this instance is that the magnitude of the effect over the 1-year interval is similar to that found in the 2-year interval and is consistent with the findings of other studies.2,3 Catherine Hayes and colleagues ask us why we did not find a significant reduction in the small cancer detection rate in HRT users The small cancer detection is dependent on at least two parameters: the sensitivity of mammography, and the underlying rate of invasive breast cancer in the population group. While we found that sensitivity was reduced in HRT users, which would decrease the small cancer detection rate, these women could also have a higher risk of breast cancer,4 which would have the opposite effect. Anne M Kavanagh, Heather Mitchell, Graham G Giles Australian Research Centre in Sex, Health, and Society, Faculty of Health Sciences, La Trobe University, Melbourne 3000, Australia. 1
2
3
Rothman K, Greenland S. Modern epidemiology, 2nd edn. Lippincott and Raven Publishers; Philadelphia, 1998. Séradour B, Estève J, Heid P, Jacquemier J. Hormone replacement therapy and screening mammography: analysis of the results of the du Rhône programme. J Med Screening 1999; 6: 99–102. Rosenberg R, Hunt W, Williamson M, et al. Effects of age, breast density, ethnicity, and estrogen replacement therapy on the sensitivity and cancer stage at diagnosis: review of 183 134 screening mammograms in Albuquerque, New Mexico. Radiology 1998; 209: 511–18.
THE LANCET • Vol 355 • May 13, 2000
4
Collaborative Group on Hormonal Factors and Breast Cancer. Breast cancer and hormone replacement therapy: collaborative reanalysis from 51 epidemiological studies of 52 705 women with breast cancer and 108 411 women without breast cancer. Lancet 1997; 350: 1047–59.
poverty, poor educational standards, and poor health. Economic prosperity is the key to healthy living and longevity. *P Ghosh, S A Khan Care of the Elderly Directorate, North Herts NHS Trust, Lister Hospital, Stevenage SG1 4AB, UK
Coronary heart disease in Indian Asians Sir—John Chambers and colleagues (Feb 12, p 523)1 suggest that Indian Asians living in the UK have low levels of vitamin B12 and folic acid in their diet and therefore increased plasma homocysteine concentrations, which in turn contributes to coronary heart disease. Conventional risk factors, such as increased total cholesterol, hypertension, and smoking, have failed to explain the increased incidence of coronary heart disease in this group. Type-2 diabetes mellitus, insulin resistance, and central obesity have been suggested as possible risk factors.2 While searching for a medical cause for atherogenesis, one should not ignore the fact that there is a strong association between poverty and poor health. In the UK, Indian Asians generally have lower income and live in poor housing. In addition, the language barrier hampers their access to health services, social care, and health information, particularly amongst the elderly. Mortality from coronary heart disease amongst Indian Asians is 20% higher when compared with the general population. 3 The highest proportional mortality ratio is in excess of 70% in the Bangladeshi immigrant population.4 In 1970–85, the mortality rates associated with coronary heart disease increased by 8% in men and 14% in women from this community, while the overall mortality in all western countries had fallen. This trend was also noted in the second generation, who were born and raised in the UK.2 Life expectancy has a positive correlation with gross national product per head, gross income of the poor in the society, and public expenditure, particularly in health care. Better basic education and access to health care contribute to an improved life expectancy. In the USA, African Americans seem to have a lower life expectancy than their white compatriots. Their life expectancy is even worse than the Chinese and Indians from the state of Kerala.5 This trend is also noted amongst the Aboriginal population in Australia. There seems to be an association between ethnicity, real and relative
1
2
3
4 5
Chambers JC, Obeid OA, Refsum H, et al. Plasma homocysteine concentration and risk of coronary heart disease in the UK Indian Asian and European men. Lancet 2000; 355: 523–27. Gupta S, de Belder A, Hughes L. Avoiding premature coronary deaths in Asians in Britain. BMJ 1995; 311: 1035–36. McKeigue PM, Marmot MG. Mortality from coronary heart disease in Asian communities in London. BMJ 1988; 297: 903. Fox KM, Shapiro LM. Heart disease in Asians in Britain. BMJ 1988; 297: 311–12. Sen A. Economics and health. Lancet 1999; 354: 20.
Sir—The study by John Chambers of plasma and colleagues 1 homocysteine concentrations in UK Indian Asians is interesting but may not reflect the full picture of coronary heart disease in the Indian subcontinent. Many Asians are vegetarians, a diet associated, to differing extents, with reductions in plasma LDL. A vegetarian diet is also associated with reduced folate and vitamin B12 and, therefore, with hyperhomocysteinaemia.2 This type of diet could be a significant confounding element in the study because a strict vegetarian diet is rare among Europeans. A comparison of the non-vegetarian Indian Asian group with Europeans would be helpful in determining the role of plasma homocysteine as a cardiovascular risk factor, independent of the generally cardioprotective effects of a vegetarian diet. Also, the study investigated Asians of North Indian descent, in whom homocysteinaemia has been shown to be common,3 and an east London Bangladeshi/Bengali population, in whom rates of smoking have been found to be higher than in west London Asians of Gujerati descent. There are also substantial differences in diet, including saturated and unsaturated fat intakes, between various ethnic subgroups in India, which are likely to be carried over to the UK.4 In contrast to the findings of this study, a study of 114 individuals of Sri Lankan (Tamil) origin showed no association of methylene tetrahydrofolate reductase (MTHFR) genotype and homocysteinaemia. The MTHFR 677T allele frequency was
1727