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

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

Older mothers produce more successful daughters

Acknowledgements Marmots were studied under UCLA research protocol ARC 2001-191-01 (approved by the UCLA Animal Care Committee on 13 May 2002 and renewed annually). Permits were issued by the Colorado Division of Wildlife. We are thankful to all marmoteers who contributed to data collection. S.B.K. was supported by the Natural Environment Research Council, J.G.A.M. by a Marie-Curie Fellowship, and D.T.B by the National Geographic Society, UCLA (Faculty Senate and the Division of Life Sciences), a Rocky Mountain Biological Laboratory research fellowship, and the NSF (IDBR-0754247, DEB1119660 and DEB-1557130 to D.T.B., and DBI 0242960, DBI-0731346 and REU1226713 to the Rocky Mountain Biological Laboratory).Peer reviewedPostprin