Effects of cholesterol-lowering with simvastatin on stroke and other major vascular events in 20536 people with cerebrovascular disease or other high-risk conditions.

BACKGROUND: Lower blood cholesterol concentrations have consistently been found to be strongly associated with lower risks of coronary disease but not with lower risks of stroke. Despite this observation, previous randomised trials had indicated that cholesterol-lowering statin therapy reduces the risk of stroke, but large-scale prospective confirmation has been needed. METHODS: 3280 adults with cerebrovascular disease, and an additional 17256 with other occlusive arterial disease or diabetes, were randomly allocated 40 mg simvastatin daily or matching placebo. Subgroup analyses were prespecified of first "major vascular event" (ie, non-fatal myocardial infarction or coronary death, stroke of any type, or any revascularisation procedure) in prior disease subcategories. Subsidiary outcomes included any stroke, and stroke sub-type. Comparisons are of all simvastatin-allocated versus all placebo-allocated participants (ie, "intention-to-treat"), which yielded an average difference in LDL cholesterol of 1.0 mmol/L (39 mg/dL) during the 5-year treatment period. FINDINGS: Overall, there was a highly significant 25% (95% CI 15-34) proportional reduction in the first event rate for stroke (444 [4.3%] simvastatin vs 585 [5.7%] placebo; p<0.0001), reflecting a definite 28% (19-37) reduction in presumed ischaemic strokes (p<0.0001) and no apparent difference in strokes attributed to haemorrhage (51 [0.5%] vs 53 [0.5%]; rate ratio 0.95 [0.65-1.40]; p=0.8). In addition, simvastatin reduced the numbers having transient cerebral ischaemic attacks alone (2.0% vs 2.4%; p=0.02) or requiring carotid endarterectomy or angioplasty (0.4% vs 0.8%; p=0.0003). The reduction in stroke was not significant during the first year, but was already significant (p=0.0004) by the end of the second year. Among patients with pre-existing cerebrovascular disease there was no apparent reduction in the stroke rate, but there was a highly significant 20% (8-29) reduction in the rate of any major vascular event (406 [24.7%] vs 488 [29.8%]; p=0.001). The proportional reductions in stroke were about one-quarter in each of the other subcategories of participant studied, including: those with coronary disease or diabetes; those aged under or over 70 years at entry; and those presenting with different levels of blood pressure or lipids (even when the pretreatment LDL cholesterol was below 3.0 mmol/L [116 mg/dL]). INTERPRETATION: Much larger numbers of people in the present study suffered a stroke than in any previous cholesterol-lowering trial. The results demonstrate that statin therapy rapidly reduces the incidence not only of coronary events but also of ischaemic strokes, with no apparent effect on cerebral haemorrhage, even among individuals who do not have high cholesterol concentrations. Allocation to 40 mg simvastatin daily reduced the rate of ischaemic strokes by about one-quarter and so, after making allowance for non-compliance in the trial, actual use of this regimen would probably reduce the stroke rate by about a third. HPS also provides definitive evidence that statin therapy is beneficial for people with pre-existing cerebrovascular disease, even if they do not already have manifest coronary disease

The clinical effectiveness, acceptability and accessibility of renal satellite units in England and Wales

Available from British Library Document Supply Centre- DSC:DXN062820 / BLDSC - British Library Document Supply CentreSIGLEGBUnited Kingdo

Chemical evolution of waters in the Lansing-Kansas City Groups in western Kansas

Call number: LD2668 .T4 GEOL 1988 S73Master of ScienceGeolog

A comprehensive analysis of APOE genotype effects on human brain structure in the UK Biobank

Alzheimer’s disease (AD) risk is increased in carriers of the apolipoprotein E (APOE) ε4 allele and decreased in ε2 allele carriers compared with the ε3ε3 genotype. The aim of this study was to determine whether: the APOE genotype affects brain grey (GM) or white matter (WM) structure; and if differences exist, the age when they become apparent and whether there are differential effects by sex. We used cross-sectional magnetic resonance imaging data from ~43,000 (28,494 after pre-processing) white British cognitively healthy participants (7,446 APOE ε4 carriers) aged 45–80 years from the UK Biobank cohort and investigated image-derived phenotypes (IDPs). We observed no statistically significant effects of APOE genotype on GM structure volumes or median T2* in subcortical structures, a measure related to iron content. The volume of white matter hyperintensities differed significantly between APOE genotype groups with higher volumes in APOE ε4ε4 (effect size 0.14 standard deviations [SD]) and ε3ε4 carriers (effect size 0.04 SD) but no differences in ε2 carriers compared with ε3ε3 carriers. WM integrity measures in the dorsal (mean diffusivity [MD]) and ventral cingulum (MD and intracellular volume fraction), posterior thalamic radiation (MD and isotropic volume fraction) and sagittal stratum (MD) indicated lower integrity in APOE ε4ε4 carriers (effect sizes around 0.2–0.3 SD) and ε3ε4 (effect sizes around 0.05 SD) carriers but no differences in ε2 carriers compared with the APOE ε3ε3 genotype. Effects did not differ between men and women. APOE ε4 homozygotes had lower WM integrity specifically at older ages with a steeper decline of WM integrity from the age of 60 that corresponds to around 5 years greater “brain age”. APOE genotype affects various white matters measures, which might be indicative of preclinical AD processes. This hypothesis can be assessed in future when clinical outcomes become available

Cumulative reproductive costs on current reproduction in a wild polytocous mammal

Funding Information Marie‐Curie Fellowship UCLA Rocky Mountain Biological Laboratory Research Fellowship NSF. Grant Numbers: IDBR‐0754247, DEB‐1119660, DBI 0242960, DBI 0731346 Natural Environment Research Council. Grant Number: NE/L50175X/1 National Geographic SocietyPeer reviewedPublisher PD