To the Editor: In their review of observational studies of postmenopausal hormone replacement therapy (HRT), Dr Nelson and colleagues1 incorrectly claim that our findings from the Nurses' Health Study (NHS)2 - 3 failed to control for education or socioeconomic status (SES) in analyzing postmenopausal HRT use and risk of coronary heart disease (CHD). Because all NHS participants are registered nurses, with nearly identical education, we adjusted for education using stratification.2 - 3 The authors also incorrectly state that studies controlling for alcohol intake or physical activity failed to observe a lower risk of CHD among HRT users. We recently reported a relative risk (RR) of CHD of 0.64 (95% confidence interval, 0.54-0.76) for current vs never HRT users, after adjustment for alcohol and physical activity (in addition to other covariates).2
Nelson et al cited 4 studies that controlled for SES and yielded nonsignificant results for risk of CHD. However, these studies do not support the contention that control for SES explains these results. Sidney et al4 stated that adjustment of their results for education resulted in minimal changes in the RR estimate of CHD risk, from 0.92 to 0.96. Rosenberg et al5 stated that adjustment for factors other than age at and type of menopause had little impact on their RR estimates for CHD. Croft and Hannaford6 reported an unadjusted RR of 0.8 for HRT use and CHD risk, which was entirely unchanged after adjustment for social class (and other covariates). Thus, it is clear from these study results that adjustment for education did not affect results for CHD risk.
Finally, Nelson et al only presented separate meta-analyses by SES adjustment for CHD, although most of the other diseases examined also are strongly associated with SES. If confounding by SES were truly the explanation for the CHD results, it is unlikely that such confounding would not be crucial for other diseases as well. Indeed, the NHS and other observational studies yielded RRs for osteoporotic fracture, breast cancer, colon cancer, venous thromboembolism, and stroke nearly identical to the results of the Women's Health Initiative,7 suggesting a lack of important confounding. Moreover, the Women's Health Initiative trial addressed a different issue than the observational studies; that is, postmenopausal women using continuous combined HRT initiated many years after the onset of menopause. This difference may be particularly important for the outcome of heart disease. Mikkola and Clarkson8 demonstrated in trials of monkeys that HRT begun only at the onset of menopause showed cardiovascular protection. The sparse data available in humans suggest a similar phenomenon. We believe that biologically based hypotheses are more likely to explain the apparent divergence in findings for CHD than the supposed confounding by SES.
Country-Specific Mortality and Growth Failure in Infancy and Yound Children and Association With Material Stature
Use interactive graphics and maps to view and sort country-specific infant and early dhildhood mortality and growth failure data and their association with maternal
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