Homocysteine and heart disease in Indian Asians

CORRESPONDENCE

may increase homocysteine include: prolonged heating of vegetables, which is commonly done in Indian cooking, which destroys most folate; bread, cakes, and cookies consumed freely are prepared from refined, preserved, or processed cereals—poor sources of vitamin B6; and Asians in the study may have been consuming fibrates to lower triglycerides—fibrates cause a rise in homocysteine.5 Raised values of homocysteine may be a marker of insulin resistance. In that case, comprehensive nutritional intervention, rather than simple vitamin supplementation may be required to lower CHD risk. Studies are needed to test this hypothesis. *Bihari S Raheja, Manisha Talim All India Institute of Diabetes, Mahim, Mumbai 400 016, India 1

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Chambers JC, Obeid O, Refsum H, et al. Plasma homocysteine concentrations and risk of coronary heart disease in UK Indian Asians and European men. Lancet 2000; 355: 523–27. Raheja BS. Indians, diet and heart disease. Lancet 1986; ii: 228–29. Raheja BS, Sadikot SM, Phatak RB, Rao MB. Significance of the N6/N3 ratio for insulin action in diabetes. Ann N Y Acad Sci 1993; 683: 258–71. British Nutrition foundation task force. Repeat on unsaturated fatty acids. Chapman and Hall: London, 1992. Dierkes J, Westphal S, Luley C. Serum homocysteine increases after therapy with fenafibrate or bezafibrate. Lancet 1999; 354: 219–20.

Authors’ reply Sir—Lars Brattström asks whether impaired renal function might have contributed to raised plasma homocysteine concentrations in patients with CHD. In our study, renal impairment (creatinine >150 ␮mol/L) was defined prospectively as an exclusion criterion for cases and controls. Mean concentrations for creatinine were similar in Indian Asian and European white controls (86 [SD 12] vs 87 [12] ␮mol/L, respectively, p=0·08). and were higher in patients with CHD compared with respective controls (Indian Asians 90 [14] ␮mol/L, Europeans 9 [14] ␮mol/L, both p<0·001). In regression analysis, raised homocysteine concentrations in patients with CHD were not explained by creatinine concentrations, implying that the association between homocysteine and CHD was not explained by differences in renal function. We concluded that plasma homocysteine is raised in Indian Asians compared with Europeans, and may contribute to their increased CHD risk. We also found that homocysteine concentrations in Indian Asians were

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explained by their reduced vitamin B12 and folate intake. These conclusions were based on the comparisons between Indian Asian and European white controls. Brattström draws attention to raised folate concentrations in Indian Asian patients with CHD compared with controls. Reasons underlying high folate in patients with CHD are not known, but we speculate that this may be secondary to dietary modification, since there was parallel evidence of lifestyle change, with higher smoking cessation rates in cases compared with controls. Increased folate would be expected to lower homocysteine concentrations,1 and to diminish the association of homocysteine with casecontrol status. Therefore, we may have underestimated the strength of homocysteine as a risk factor for CHD in Indian Asians. Helen Baker and colleagues suggest that adjustment for family history, physical activity, and social class would have allowed a more accurate assessment of the impact of homocysteine on CHD. However, the principal aim of our study was to examine whether homocysteine was raised in Indian Asians, and was a risk factor for CHD in this population. We additionally sought to examine whether raised homocysteine in Indian Asians was accounted for by reduced intake of B vitamins, since these are recognised as major determinants of homocysteine concentrations.1 Previous studies have not shown a clear association between homocysteine concentrations and the factors suggested by Baker and colleagues. We agree that our results of raised homocysteine underlying increased CHD risk in Indian Asians are limited to men. However, such men represent over 90% of Indian Asians with premature CHD.2 It is likely that homocysteine concentrations are also raised in Indian Asian women, since they are recognised to have reduced intake and serum concentrations of B vitamins.3,4 Maximilian Ledochowski and colleagues suggest that fructose malabsorption may be a major determinant of reduced plasma folate, and thus leads to raised plasma homocysteine concentrations. This is an interesting proposition, and needs to be examined formally, as part of a separate study in the two racial groups. Bihari Raheja and Manisha Talim suggest that raised plasma homocysteine concentrations may reflect underlying insulin resistance. In our study, raised homocysteine concentrations in Indian Asians compared with Europeans, and in cases compared with controls, were not accounted for by indices of insulin

resistance including glucose, blood pressure, HDL cholesterol, and triglycerides. Furthermore, previous studies in Europeans have failed to find an association between homocysteine and insulin sensitivity.5 John C Chambers, *Jaspal S Kooner Cardiology Department, Hammersmith Hospital, London W12 0HS, UK 1

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Boushey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 1995; 274: 1049–57. Balarajan R. Ethnicity and variations in mortality from coronary heart disease. Health Trends 1996; 28: 45–51. Abraham R, Brown MC, North WR, McFadyen IR. Diets of Asian pregnant women in Harrow: iron and vitamins. Hum Nutr Appl Nutr 1987; 41: 164–73. Michie CA, Chambers J, Abramsky L, Kooner JS. Folate deficiency, neural tube defects, and cardiac disease in UK Indians and Pakistanis. Lancet 1998; 351: 1105. Abbasi F, Facchini F, Humphreys MH, Reaven GM. Plasma homocysteine concentrations in healthy volunteers are not related to differences in insulin-mediated glucose disposal. Atherosclerosis 1999; 146: 175–78.

Migraine revolution and sumatriptan Sir—In his March 11 commentary1 D Nicholas Bateman presents a wellbalanced account of the revolution in migraine treatment that began with the introduction of sumatriptan nearly 10 years ago. The availability of sumatriptan has brought patients fast and effective relief of migraine pain and associated symptoms. As with most pharmaceutical breakthroughs, what begins as a single agent becomes one of Studies

Zolmitriptan Gallagher R. Cephalalgia 1999; 19: 358. Rizatriptan Tflet-Hansen P, et al. Headache 1998; 38: 748–55. Goldstein J, et al. Headache 1998; 38: 737–47. Lines C, et al. Headache 1997; 37: 319–20. Visser WH, et al. Arch Neurol 1996; 53: 1132–37. Eletripan Pitman V, et al. Headache 1999; 39: 374.

Drug doses

% patients with headache response*

100 mg

64%

100 mg

62%

50 mg

67%

50 mg

68%

100 mg†

46%

50 mg† 100 mg†

53% 54%

*Moderate or severe predose pain reduced to mild to no pain post dose, 2 h after sumatriptan dose. †Encapsulated sumatriptan used.

Percentages of patients with headache response 2 h after dosing with sumatriptan tablets in comparator trials

THE LANCET • Vol 355 • June 24, 2000

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