Age at menarche and heart failure risk: The EPIC-NL study.

AIMS: Early age at menarche has been reported to be associated with increased risks of developing type 2 diabetes (T2D) and coronary heart disease (CHD) in adulthood, but a late menarche has also been found to be associated with an increased risk of CHD. Both T2D and CHD are important risk factors for developing heart failure (HF). We examined the relationship between age at menarche (AAM) and HF incidence in women from the European Prospective Investigation into Cancer and Nutrition - Netherlands (EPIC-NL) cohort study. METHODS AND RESULTS: The EPIC-NL cohort comprised 28,504 women aged 20-70 years at baseline (1993-1997). Mean age at menarche was 13.3 (standard deviation 1.6) years. During a median follow-up of 15.2 years HF occurred in 631 women. Cox proportional hazard regression models, stratified by cohort and adjusted for potential confounders, were used to investigate the associations between AAM and HF incidence. After confounder adjustment, each year of older age at menarche was associated with a 5% lower risk of HF (hazard ratio 0.95 (95% CI, 0.91-1.00), p-value 0.048). Further adjusting for body mass index (BMI), prevalent CHD, hypertension, or prevalent T2D as potential mediators between early menarche and risk of HF attenuated the associations between AAM and risk of HF to non-significance. CONCLUSION: Older AAM reduced the risk of HF in this study. BMI, prevalent CHD, hypertension and prevalent T2D seemed to mediate this association. Future research with a longer follow-up should establish whether there is an independent effect of AAM on HF risk. Also, further phenotyping of HF cases is necessary to enable whether the associations differ for the various subtypes of HF.

Progesterone and environmental tobacco smoke act synergistically to exacerbate the development of allergic asthma in a mouse model.

BACKGROUND: Asthma affects males and females differently. Females have a higher incidence than males after the onset of puberty. This suggests a hormonal component to the development of the disease. Progesterone, a female hormone, has previously been shown to illicit a T-helper type 2 (TH2) immune response similar to that seen in allergic asthma. Previous studies performed by our laboratory have shown that exposure to environmental tobacco smoke (ETS) enhances the immune response to allergens. OBJECTIVE: To determine if the combination of exposure to ETS and progesterone would further exacerbate the immune response in a mouse model of allergic asthma. METHODS: Female mice were ovariectomized and then implanted with time-release progesterone pellets. Mice were housed in either filtered air (FA) or ETS chambers and half were exposed to aerosolized house dust mite allergen (HDMA). Bronchoalveolar lavage was performed for cell differentials; lung and spleen cells were harvested to compare IL-4 and IFN-gamma production by ELISPOT. RESULTS: Progesterone pellet implantation resulted in increased serum progesterone levels (28.3+/-8.43 vs. 13.5+/-7.22 ng/mL in placebo-treated mice, P<0.0001). Serum total IgE levels were significantly greater in progesterone vs. non-progesterone treated animals that were also exposed to HDMA. ETS exposure enhanced total IgE levels as well. Lung homogenate cells from HDMA/progesterone-treated animals stimulated with Concavalin A produced significantly more IL-4 compared with HDMA/placebo-treated animals (200+/-17.6 vs. 146+/-17.5 spots/well, P<0.01 in ETS exposed animals and 221+/-28.9 vs. 167+/-23.4 spots/well, P<0.01 in animals housed in FA). HDMA/ETS-treated animals had higher eosinophilia in lavage than all other groups. CONCLUSION: Increased serum progesterone levels exacerbate the allergic asthmatic phenotype in a mouse model. These effects are further exacerbated by the addition of environmental tobacco smoke. Progesterone provides a major contribution to the gender differences seen in the development and elicitation of the asthmatic response.

Intraregional decline in case-fatality and hospital use after occlusive stroke in the Southeastern United States.

OBJECTIVE: To identify changes in mortality and hospital use among patients admitted for ischemic stroke in Alabama. BACKGROUND: The decline in stroke mortality in the Southeast is greater than in other US regions. Whether this decline in a result of decreased incidence or improved case-fatality rates is unknown. METHODS: We examined Medicare hospitalization data from approximately 625,000 beneficiaries and identified patients admitted for ischemic stroke between January 1992 and December 1994. The search was carried out using International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) codes pertinent to all diagnoses related to ischemic stroke. Data relevant to mortality and length of stay (LOS) were collected, and comparisons were made of the average case-fatality rate and LOS in each of the 3 years. RESULTS: No significant difference was found in the incidence of ischemic stroke during the 3 years. The number of admissions was 4438 for 1992, 4124 for 1993, and 4762 for 1994. Conversely, the average LOS showed a significant decline, with values of 10.05, 9,36, and 8.72 days, respectively (P<.0003). A significant decline in mortality, with average case-fatality rates of 11.72%, 11.56%, and 9.71%, respectively (P<.003), was also found. CONCLUSION: These data suggest that the decline in stroke mortality in the Southeast is because of improved patient survival after stroke, rather than decreased incidence. Although several factors may be contributing to the decreased case-fatality rates, improved care of hospitalized stroke patients is likely of primary importance. Additionally, decreased mortality associated with decreased LOS suggests more efficient hospital use.

A randomized trial of aspirin or heparin in hospitalized patients with recent transient ischemic attacks. A pilot study.

In a randomized pilot study we compared the efficacy of temporary anticoagulation with intravenous heparin sodium to the efficacy of aspirin in preventing cerebral infarction in hospitalized patients with recent (less than 7 days) transient ischemic attacks (TIAs). Fifty-five patients (33 men, 22 women) aged 36-81 (mean 62.7) years met entry criteria and agreed to participate. Symptoms prompting hospitalization were referable to the carotid distribution in 43 patients (34 hemispheric, nine retinal); 12 patients had vertebrobasilar distribution TIAs. Twenty-seven patients received heparin and 28 received aspirin. Patients were treated until surgery or until long-term medical therapy was instituted, 3-9 (mean 5.5) days in the heparin group and 3-15 (mean 5.8) days in the aspirin group. Recurrent TIAs occurred in eight patients given heparin and in seven treated with aspirin. Infarction occurred in one patient in the heparin group and in four patients in the aspirin group (three brain, one retinal infarction). Initial symptoms in these five patients were referable to the carotid distribution in two and to the vertebrobasilar distribution in three. All patients but the one with a retinal infarction had recurrent TIAs prior to stroke. Our pilot study suggests that hospitalized patients with recent TIAs are at high risk for recurrent TIAs (15 of 55, 27%) and brain infarction (five of 55, 9%) and that patients with recent vertebrobasilar distribution TIAs have a marginally significantly higher risk (odds ratio 6.83, 95% confidence interval 0.65-88.66) of infarction than patients with recent carotid distribution TIAs.