***TASK*** the task is to summarize an input biomedical literature in six sentences 
    ***INPUT*** the input is a biomedical literature 
    ***OUTPUT*** the output is the summary of an input biomedical literature in six sentences 
    ***DOCUMENTATION*** 
    ***EXAMPLES*** 
    Input: Background and Purpose — Studies suggest a protective role for statins after intracerebral hemorrhage , but many failed to assess statin discontinuation , did not include postdischarge outcomes , or did not account for withdrawal of care . We studied the relationship between preintracerebral hemorrhage statin use and in-hospital statin discontinuation on stroke severity and 30-day mortality . Methods — We analyzed data from the Registry of the Canadian Stroke Network and determined the adjusted ORs for statin use and outcomes , controlling for stroke severity and other covariates . Results — We analyzed 2466 consecutive patients with intracerebral hemorrhage from 2003 to 2008 : median age was 71 years , 53.6 % were male , and 30-day mortality rate was 36.5 % . Overall , 537 ( 21.7 % ) were taking statins before presentation . Compared with nonusers , statin users were less likely to have severe strokes on presentation ( 54.7 % versus 63.3 % ) but had similar rates of poor outcome ( 70 % versus 67 % ) and 30-day mortality ( 36 % versus 37 % ) .  Statins  were discontinued on admission in 158 of 537 ( 29.4 % ) ; these patients were more likely to have severe stroke ( 65 % versus 27 % , P<0.01 ) , poor outcome ( 90 % versus 62 % , P<0.01 ) , and to have died by 30 days ( 71 % versus 21 % , P<0.01 ) . After adjusting for stroke severity , statin discontinuation was still associated with poor outcome ( adjusted OR , 2.4 ; 95 % CI , 1.13–4.56 ) and higher mortality ( adjusted OR , 2.0 ; 95 % CI , 1.30–3.04 ) . However , these associations were attenuated and no longer significant after excluding patients treated palliatively . Conclusions — We found no association between preadmission statin use and outcomes in intracerebral hemorrhage . Statin discontinuation may worsen outcomes or may simply be a marker of worse underlying prognosis BACKGROUND  Soluble CD40L ( sCD40L ) , a substance that maximally reflects in vivo platelet activation , is increased in patients with hypercholesterolemia . We investigated the relation between sCD40L and platelet CD4OL in hypercholesterolemic patients before and after a short-term treatment with atorvastatin . METHODS AND RESULTS Collagen-induced platelet CD40L and plasma levels of sCD40L and prothrombin fragment F1 + 2 , a marker of thrombin generation , were investigated in 30 hypercholesterolemic patients and 20 healthy subjects . Hypercholesterolemic patients were then r and omized to either diet ( n=15 ; group A ) or atorvastatin 10 mg/d ( group B ) ; the aforementioned variables were measured at baseline and after 3 days of treatment . Compared with referents , hypercholesterolemic patients showed higher values of platelet CD40L ( P<0.005 ) , sCD40L ( P<0.005 ) , and F1 + 2 ( P<0.003 ) . Platelet CD40L was significantly correlated with sCD40L ( P<0.001 ) , and the latter was significantly correlated with F1 + 2 ( P<0.001 ) . The intervention trial showed no changes in group A but a significant decrease in platelet CD40L ( P<0.01 ) , sCD40L ( P<0.002 ) , and F1 + 2 ( P<0.03 ) in group B. In vitro studies demonstrated that cholesterol enhanced platelet CD40L and CD40L-mediated clotting activation by human monocytes ; also , atorvastatin dose-dependently inhibited platelet CD40L expression and clotting activation by CD40L-stimulated monocytes . CONCLUSIONS This study shows that , in hypercholesterolemia , platelet overexpression of CD40L may account for enhanced plasma levels of sCD40L and F1 + 2 .  Atorvastatin exerts a direct antithrombotic effect via inhibition of platelet CD40L and CD40L-mediated thrombin generation , independently of its cholesterol-lowering effect Abstract Objective To investigate risk factors , such as heavy alcohol consumption , that might explain any increased risk of  haemorrhagic stroke associated with low blood cholesterol . Design Prospect i ve cohort study . Setting Korea . Participants 787 442 civil servants ( 661 700 men , 125 742 women ) aged 30 - 64 . Main outcome measures Cardiovascular risk factors were assessed at biennial health check . Data on morbidity and mortality were ascertained from 1990 to 2001 using hospital admissions and mortality surveillance systems . Results 6328 cases of ischaemic stroke ( 6021 men , 307 women ) , 3947 cases of haemorrhagic stroke ( 3748 men , 199 women ) , 3170 cases of undefined stroke ( 2902 men , 268 women ) , and 4417 cases of myocardial infa rct ion ( 4305 men , 112 women ) occurred . Ischaemic stroke and myocardial infa rct ion were strongly and positively associated with blood cholesterol ( hazard ratio per 1 mmol/l cholesterol 1.20 ( 95 % confidence 1.16 to 1.24 ) and 1.48 ( 1.43 to 1.53 ) , respectively ) . Haemorrhagic stroke showed an inverse association in fully adjusted models ( 0.91 , 0.87 to 0.95 ) . This inverse association was confined to participants with hypertension . When stratified by concentration of γ glutamyl transferase ( GGT ) , an indicator of alcohol consumption , the association was not seen in participants with low concentrations of GGT , and it was independent of hypertension in those with high concentrations of GGT ( > 80 U/l ) . Conclusion High alcohol consumption may underlie the association between low blood cholesterol and increased risk of haemorrhagic stroke BACKGROUND A recent post hoc analysis of a large r and omized trial in patients with cerebrovascular disease suggested that statins may increase the risk of intracerebral hemorrhage ( ICH ) . OBJECTIVE To examine the association between statins and ICH in patients with recent ischemic stroke in a population -based setting . DESIGN Retrospective propensity-matched cohort study with accrual from July 1 , 1994 , to March 31 , 2008 . SETTING Ontario , Canada . PARTICIPANTS A total of 17 872 patients aged 66 years and older who initiated statin therapy following acute ischemic stroke and were followed for a median of 4.2 years ( interquartile range , 2.4 - 5.0 years ) . To enhance causal inference , we conducted several tests of specificity to exclude healthy user bias in this sample . Main Outcome Measure Hospitalization or emergency department visit for ICH defined using vali date d diagnosis coding . RESULTS Overall , 213 episodes of ICH occurred . In the primary analysis comparing statin users with nonusers , we found no association between statins and ICH ( hazard ratio = 0.87 ; 95 % confidence interval , 0.65 - 1.17 ) . Subgroup and dose-response analyses yielded similar results . In tests of specificity , statin therapy was not associated with bone mineral density testing , vitamin D or B(12 ) screening , gastrointestinal endoscopy , or elective knee arthroplasty , suggesting that results were not due to healthy user bias or differences in quality of care . CONCLUSION Statin exposure following ischemic stroke was not associated with ICH Background and Purpose — The association of total and high-density lipoprotein ( HDL ) cholesterol with stroke risk is unclear , especially regarding hemorrhagic stroke . Methods — We prospect ively investigated the associations of  serum total and HDL cholesterol and total/HDL cholesterol ratio  with total and type-specific stroke incidence among 58 235 Finnish people aged 25 to 74 years and free of coronary heart disease and stroke at baseline . Results — During a mean follow-up period of 20.1 years , 3914 participants developed stroke events ( 3085 ischemic , 497 intracerebral hemorrhage , and 332 subarachnoid hemorrhage ) . The multivariable-adjusted hazard ratios at different levels of total cholesterol ( < 5 [ reference ] , 5–5.9 , 6–6.0 , ≥7.0 mmol/L ) were 1.00 , 1.05 , 1.16 , and 1.22 for total stroke ( Ptrend=0.036 ) and 1.00 , 1.06 , 1.19 , and 1.27 for ischemic stroke ( Ptrend=0.02 ) in men and 1.00 , 0.58 , 0.61 , and 0.50 for intracerebral hemorrhagic stroke ( Ptrend=0.02 ) in women , respectively . Low levels of HDL cholesterol and high total/HDL cholesterol ratio were associated with increased risks of total and ischemic stroke in both men and women . These associations disappeared in men but remained significant in women after further adjustment for body mass index , blood pressure , and history of diabetes . Conclusions — The study showed a positive association between total cholesterol and total and ischemic stroke risks in men and an inverse association between total cholesterol and intrahemorrhagic stroke risk in women . The inverse association of HDL cholesterol and a positive association of total/HDL cholesterol ratio with total and ischemic stroke risks were found in men and women . These associations attenuated after adjustment for body mass index , blood pressure , and history of diabetes 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 r and omised trials had indicated that cholesterol-lowering statin therapy reduces the risk of stroke , but large-scale prospect i ve confirmation has been needed . METHODS 3280 adults with cerebrovascular disease , and an additional 17256 with other occlusive arterial disease or diabetes , were r and omly allocated 40 mg simvastatin daily or matching placebo . Subgroup analyses were prespecified of first " major vascular event " ( ie , non-fatal myocardial infa rct ion 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 is 
    Output:
    
Whether statins indeed increase the risk of intracranial hemorrhage ( ICH ) , as well as the underlying mechanisms for this potential risk , have not been clearly eluci date d. It has been hypothesized that patients treated with lipophilic statins may be more prone to ICH as these cross the blood – brain barrier more freely compared with hydrophilic statins .
In this population -based , nested case-control study conducted in patients who had experienced an ICH within 1 year following an ischemic stroke , the lipophilicity of statins did not influence the risk of hemorrhagic stroke [ 4 ] .