Parity and total, ischemic heart disease and stroke mortality. The Adventist Health Study, 1976–1988

In a prospective study with information about life style and reproductive factors, we assessed the relationship between parity and total, ischemic heart disease, and stroke mortality. The large majority of the 19,688 California Seventh-day Adventist women included did not smoke or drink alcohol, 31 percent never ate meat and physical activity was relatively high. Cox proportional hazard analysis was conducted with parity as the main independent variable and with adjustment for a number of other possible confounders. During follow-up from 1976 through 1988, there were 3,122 deaths; 782 deaths from ischemic heart disease and 367 deaths due to stroke. There were no relationships between parity and total mortality (P-value for overall effect of parity = 0.32). Grand multiparous women (>4 children) had somewhat increased ischemic heart disease mortality (MRR = 1.45, 95% CI: 1.15, 1.84) before adjustment for educational level. After adjustment for educational level and marital status, there were no relationship with mortality from ischemic heart disease (P = 0.29) or stroke (P = 0.72). In parous women, there were, after adjustment for age at first delivery, some suggestions of an increased total mortality in women with one child. For ischemic heart disease and stroke mortality, no associations were found. Stratified and adjusted analyses confirmed these results. Thus, we found no consistent relationships between parity and total, ischemic heart disease or stroke mortality. However, a longer follow-up would have been helpful and the conclusions may be somewhat influenced by the lifestyle of the women included

Iron Behaving Badly: Inappropriate Iron Chelation as a Major Contributor to the Aetiology of Vascular and Other Progressive Inflammatory and Degenerative Diseases

The production of peroxide and superoxide is an inevitable consequence of aerobic metabolism, and while these particular "reactive oxygen species" (ROSs) can exhibit a number of biological effects, they are not of themselves excessively reactive and thus they are not especially damaging at physiological concentrations. However, their reactions with poorly liganded iron species can lead to the catalytic production of the very reactive and dangerous hydroxyl radical, which is exceptionally damaging, and a major cause of chronic inflammation. We review the considerable and wide-ranging evidence for the involvement of this combination of (su)peroxide and poorly liganded iron in a large number of physiological and indeed pathological processes and inflammatory disorders, especially those involving the progressive degradation of cellular and organismal performance. These diseases share a great many similarities and thus might be considered to have a common cause (i.e. iron-catalysed free radical and especially hydroxyl radical generation). The studies reviewed include those focused on a series of cardiovascular, metabolic and neurological diseases, where iron can be found at the sites of plaques and lesions, as well as studies showing the significance of iron to aging and longevity. The effective chelation of iron by natural or synthetic ligands is thus of major physiological (and potentially therapeutic) importance. As systems properties, we need to recognise that physiological observables have multiple molecular causes, and studying them in isolation leads to inconsistent patterns of apparent causality when it is the simultaneous combination of multiple factors that is responsible. This explains, for instance, the decidedly mixed effects of antioxidants that have been observed, etc...Comment: 159 pages, including 9 Figs and 2184 reference