No abstract

We observed an overall significant association between younger age at menopause and higher risk of CHD among women who experienced natural menopause and never used hormone therapy. This increased risk was observed among current smokers but not among never smokers. The apparent elevated risk of CHD with decreased age at natural menopause among smokers might reflect residual confounding by smoking.

No abstract

Objective To compare surgical outcomes and occult cancer rates at risk-reducing salpingo-oophorectomy in BRCA carriers and high-risk women who had not undergone genetic testing.Design Prospective cohort study.Setting Tertiary high-risk familial gynaecological cancer clinic.Population Women undergoing risk-reducing salpingooophorectomy between January 2005 and November 2009.Methods Women at high-risk of ovarian/tubal cancer were identified on the basis of the inclusion criteria for the UK Familial Ovarian Cancer Screening Study. Risk management options discussed with 1456 high-risk women included risk-reducing salpingo-oophorectomy. A strict histopathological protocol with serial slicing was used to assess tubes and ovaries.Results In total, 308 high-risk women (191 with unknown mutation status; 117 known BRCA1/BRCA2 carriers) chose risk-reducing surgery; 94.5% of procedures were performed laparoscopically. The surgical complication rate was 3.9% (95% CI 2.0-6.7). Four ovarian and ten tubal occult invasive/in situ cancers were found. The overall occult invasive cancer rate was 5.1% (95% CI 1.9-10.83) in BRCA1/BRCA2 carriers and 1.05% (95% CI 0.13-3.73) in untested women. When tubal in situ cancers were included, the overall rate was 4.55% (95% CI 2.5-7.5). Two untested women with tubal carcinoma in situ were subsequently found to be BRCA carriers. The median ages of BRCA carriers (58 years; IQR 13.4 years) and untested women (49.5 years; IQR 20.6 years) with occult invasive/in situ cancer were not significantly different (P = 0.454).Conclusions Both high-risk women of unknown mutation status and BRCA carriers have a significant (although higher in the latter group) rate of occult invasive/in situ tubal/ovarian cancer, with a similar age distribution at detection. The data has important implications for counselling high-risk women on the likelihood of occult malignancy and perioperative complications at riskreducing salpingo-oophorectomy. Women with occult disease should be offered genetic testing.

Background Uncertainty remains concerning the association of blood cholesterol with the risk of subsequent dementia. Using data from people with lipid measurements in the UK Clinical Practice Research Datalink (CPRD), we examined the association between blood lipid levels and dementia (both vascular and non-vascular, including Alzheimer's disease) by age at first measurement of blood lipids and duration of follow-up. MethodsWe studied a cohort from the UK CPRD of people aged 40 years or older with a first total cholesterol recording between Jan 1, 1992, and Dec 31, 2009. Follow-up was until the first record of dementia, the last data collection date, patient death or transfer out of the practice, or Jan 5, 2015, whichever was earliest. We excluded individuals with a record of dementia before the total cholesterol measurement. We used Poisson regression to examine the association between baseline total cholesterol, LDL cholesterol and HDL cholesterol, and triglycerides and incident dementia diagnosis. Analyses were stratified by age at first measurement (<65 years or ≥65 years) and duration of follow-up (<10 years or ≥10 years). Our primary focus was LDL cholesterol. We adjusted for age, sex, calendar year, country within the UK, socioeconomic status, ethnicity, smoking, alcohol, body-mass index, comorbidities, and prescriptions. Findings 1 853 954 people had a first total cholesterol recording (dementia diagnosis in 49 416 [2•7%] people), including 953 635 [51•4%] people with LDL cholesterol values for analysis (dementia diagnosis in 21 602 [2•3%] people). Overall, we found a modest positive association between LDL cholesterol and dementia, with an adjusted rate ratio (RR) of 1•05 (95% CI 1•03-1•06) per SD increase in LDL cholesterol (1•01 mmol/L or 39 mg/dL increase). Adjusted RRs per 1-SD increase in LDL cholesterol in people younger than 65 years at baseline (n=636 262) were 1•10 (95% 1•04-1•15) for dementia diagnosed in the first 10 years after measurement and 1•17 (1•08-1•27) for dementia diagnosed more than 10 years after measurement. Associations for LDL cholesterol in people aged 65 years or older at baseline (n=317 373) were weaker compared with people younger than 65 years (RR 1•03 [95% CI 1•01-1•05] for dementia diagnosed during the first 10 years of follow-up and 1•07 [1•03-1•13] for dementia diagnosed after 10 years).We observed a weaker association between total cholesterol and dementia incidence and no consistent associations for HDL cholesterol and triglycerides.Interpretation LDL cholesterol measured in mid-life (<65 years) is modestly associated with dementia risk more than 10 years later. LDL cholesterol should be added to the list of modifiable risk factors for dementia.