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Serum ferritin and death from all causes and cardiovascular disease: the NHANES II Mortality Study. National Health and Nutrition Examination Study.

PURPOSE
The purpose of this study was to assess the association between serum ferritin and death from all causes, cardiovascular diseases (CVD), CHD and myocardial infarction (MI). Positive body iron stores have been proposed as a risk factor for coronary heart disease (CHD). While most epidemiologic studies using serum ferritin and other measures of body iron stores have not found an association between iron and heart disease risk, the hypothesis remains controversial. As a result, we examined the relationship of serum ferritin, the principle blood measure of body iron stores, to risk of death in a cohort with a standardized exam and long follow-up.


METHODS
The baseline data for this prospective cohort study were collected in 1976-1980 as part of the second National Health and Nutrition Examination Study (NHANES II) with mortality follow-up using the National Death Index (NDI) through December 31, 1992. The analytic sample (n = 1604) consisted of 128 black men, 658 white men, 100 black women and 718 white women 45-74 years of age at baseline who, based on self-reported data, were free of coronary heart disease at baseline and had no missing data. The main outcome measures were the relative risk of death for persons with serum ferritin levels: <50 microg/L; or 100-199 microg/L; or > or =200 microg/L was compared to persons with serum ferritin levels of 50-99 microg/L adjusted for possible confounding using the Cox proportional hazards model.


RESULTS
Most of the deaths were among white men (n = 254) and women (n = 168). There were relatively few deaths among black men (n = 50) and too few in women (n = 23) to reliably model. The largest number of CVD (n = 119), CHD (n = 82), and MI (n = 49) deaths were in white men while there were 69 CVD, 45 CHD and 13 MI deaths in white women. Black men with a serum ferritin level of <50 microg/L had a significantly higher adjusted risk of death from all causes (RR = 3.1 with 95% confidence limits of 1.5-6.5). There were no other statistically significant associations for all causes mortality for the other three race/sex groups. Additionally, there were no statistically significant associations between serum ferritin and any of the cardiovascular endpoints for any of the groups. There was an apparent but nonsignificant u-shaped association between serum ferritin and all causes mortality in black men and between serum ferritin and CVD death in white women. However, in both cases very wide confidence limits preclude further interpretation.


CONCLUSIONS
Overall, the results do not support the hypothesis that positive body iron stores, as measured by serum ferritin, are associated with an increased risk of CVD, CHD or MI death or between serum ferritin and all causes mortality. Most of the research to date with serum ferritin has been conducted in European men or in European American men. Our results are consistent with the primarily negative results for that race/sex group. More research is needed in women and minority groups, including an explanation of why such an association would exist in these groups but not in white men before an association can be established in them.