Public Health Sciences, The University of Edinburgh Medical School, Edinburgh EH8 9AG Scotland
Kain et al. (1) studied fibrinogen in South Asians. We question their observation that fibrinogen levels are higher in South Asian than comparison White populations and their statement that "elevated fibrinogen levels may be contributing to the increased risk of cardiovascular disease in South Asians" (1, p. 178).
Kain et al.s paper (1) cites four studies as evidence that fibrinogen levels are higher in South Asians (25). One (2) is by these same authors, and we would be interested to know the extent to which participation overlapped with the present study. Contrary to the authors assertion, the paper by Meade et al. (3) did not report higher fibrinogen levels in South Asians, but it indicated that levels were similar in Whites and "blacks." The ethnic origin of the "black" group in Meade et al.s study was not defined in the paper cited but was probably African and Caribbean rather than South Asian. Although Anand et al. (5) found higher levels of fibrinogen in a population-based study of South Asians living in Canada, the difference did not reach conventional statistical significance (p = 0.10). Markovitz et al. (4) found significantly higher fibrinogen levels among Asian Indians in Alabama. However, the sample size was small and the sample was not population based. Are South Asian populations living in North America comparable to those in the United Kingdom in terms of the determinants of their increased cardiovascular risk?
Kain et al. (1) did not discuss the fibrinogen levels reported in five much larger population-based studies conducted in the United Kingdom (610), although they cited the Newcastle Heart Project (6). In the studies by Bhopal et al. (6), McKeigue et al. (9), and Miller et al. (10), fibrinogen levels were lower in South Asians; in the study by Cook et al. (7), they were lower in South Asian men. Levels were similar in the 1999 Health Survey of England (8) and among women in Cook et al.s study. Is it possible that the unusual finding of high fibrinogen levels in the study by Kain et al. (1) is a result of bias?
Fibrinogen levels in South Asians are associated with age, height, body mass index, heart rate, smoking, and use of hormone replacement therapy (7). Conflicting results might be explained by the lack of adjustment for confounding variables (other than age) in most studies. However, adjustment for these covariates did not substantially alter the ethnic differences reported by Kain et al. (1). Cook et al. found that fibrinogen levels were similar in South Asians and Europeans even after considering age, body mass index, height, heart rate, and smoking (7). With the kind permission of the study investigators, who are listed elsewhere (6), we carried out a further analysis of the Newcastle Heart Project data (6), which showed that after adjustment for age, body mass index, smoking status, and resting pulse rate, fibrinogen levels were slightly, but not significantly lower in South Asians than in Europeans (difference: 0.12 g/liter in women, 95 percent confidence interval: 0.29, 0.04 and 0.08 g/liter in men, 95 percent confidence interval: 0.23, 0.08).
Kain et al. (1) discussed evidence from the Newcastle Heart Project (6) that the cardiovascular risk profile in South Asians (Indians, Pakistanis, and Bangladeshis) is heterogeneous, but they concluded that the lack of significant differences between the ethnic subgroups in their own study justified combining them for analysis. The small numbers in individual ethnic groups in their study make it unlikely that they would have been able to detect clinically significant differences. Contrary to Kain et al.s approach (1), the data from Bhopal et al. (6) and the Health Survey for England (8) both suggest some degree of ethnic heterogeneity in fibrinogen levels.
We conclude that comparatively high fibrinogen levels are an unlikely explanation for the increased cardiovascular risk in South Asians, which requires further study of the prevalence and susceptibility to risk factors (11).
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