***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 — Long-term therapy with hydroxymethylglutaryl coenzyme A reductase inhibitors ( statins ) has been shown to reduce levels of C-reactive protein ( CRP ) . However , the generalizability , speed of onset , and dose-response characteristics of this effect are uncertain . Methods and Results — We measured CRP , LDL cholesterol ( LDL-C ) , and HDL cholesterol ( HDL-C ) levels among 785 patients with primary hypercholesterolemia at baseline and after 8 weeks of therapy with either 0.4 or 0.8 mg of cerivastatin . Overall , cerivastatin result ed in a 13.3 % reduction in median CRP levels ( P < 0.001 ) and a 24.5 % reduction in mean CRP levels ( P < 0.001 ) . Although LDL-C promptly decreased in a dose-dependent manner ( mean LDL-C reduction , 37.3 % for 0.4 mg and 42.2 % for 0.8 mg of cerivastatin ) , no clear dose-response effect of cerivastatin on CRP was observed , nor was there any substantive correlation between the magnitude of change in CRP and the magnitude of change in LDL-C ( r = −0.08 ) or the magnitude of change in HDL-C ( r = −0.04 ) . Thus , < 2 % of the variance in the percent change in CRP over 8 weeks could be attributed to the percent change in either of these lipid parameters . Further , there was no evidence of correlation between baseline CRP levels and baseline lipid levels or between end-of- study CRP levels and end-of- study lipid levels . Conclusions — Among 785 patients with primary hypercholesterolemia , CRP levels were significantly reduced within 8 weeks of initiating cerivastatin therapy in a lipid-independent manner Mevinolin reduces cholesterol synthesis by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase . The safety and effectiveness of this agent was evaluated in a double-blind , placebo-controlled study in 59 healthy men ( serum cholesterol 3.88 - -7.76 mmol/liter ) in five centers . Subjects maintained their usual diet and activities . Doses of 6.25 , 12.5 , 25 , or 50 mg twice daily for 4 wk produced mean reductions of total serum cholesterol fo 23 - -27 % [ vs. placebo ( 4 % ) , P less than 0.01 ] . Mean low density lipoprotein cholesterol fell 35 - -45 % , while high density lipoprotein and very low density lipoprotein cholesterol , and triglycerides were not significantly affected . Mean apolipoprotein B fell 27 - -34 % . 50 mg was not significantly more effective than 6.25 mg . Mevinolin was generally well tolerated , and no serious clinical or laboratory abnormalities occurred . One subject ( 12.5 mg ) was withdrawn because of abdominal pain and diarrhea . These results suggest that if long-term safety can be demonstrated , inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase are likely to prove useful in the treatment of hypercholesterolemia BACKGROUND Cholesterol-lowering therapy can improve cardiovascular morbidity and mortality in patients with atherosclerosis . Although the mechanisms responsible are unclear , these benefits precede macroscopic changes in the vasculature . Emerging evidence that improvement in endothelial function may occur requires substantiation ; in particular , it is unclear how early any such improvement would be detectable after initiation of therapy . METHODS AND RESULTS This r and omized , double-blind , placebo-controlled crossover study evaluated the effect of simvastatin ( 20 mg daily for 4 weeks ) on endothelium-dependent and endothelium-independent vasodilation and on the response to the inhibitor of nitric oxide synthesis , NG-monomethyl-L-arginine ( L-NMMA ) , in the forearm vasculature of subjects with moderate elevation of total serum cholesterol ( 6.0 to 10.0 mmol/L ) by use of strain-gauge plethysmography . Studies were repeated after 3 more months of open therapy . When the results are expressed as percentage changes in flow in the infused arm relative to the noninfused arm , the vasodilator response to acetylcholine was significantly increased after 4 weeks of treatment with simvastatin ( P < .0005 ) , and this improvement was further enhanced after 3 months ( P < .005 ) . Concurrently , simvastatin augmented the vasoconstrictor response to L-NMMA , an effect that was maintained at 3 months ( P < .0005 ) . The response to the endothelium-independent vasodilator sodium nitroprusside was unaltered . CONCLUSIONS These observations indicate that within 1 month of treatment with simvastatin , both the stimulated and basal nitric oxide dilator functions of the endothelium are augmented , and the benefits of this HMG-coenzyme A reductase inhibitor persist with continued therapy BACKGROUND & AIMS In cirrhosis , an insufficient release of nitric oxide contributes to increased hepatic resistance and portal pressure and enhances the postpr and ial increase in portal pressure . We hypothesized that simvastatin , which enhances Akt-dependent endothelial nitric oxide synthase phosphorylation , may increase hepatic nitric oxide release and decrease hepatic resistance in patients with cirrhosis and portal hypertension . METHODS In protocol 1 , 13 patients had measurements of the hepatic venous pressure gradient , hepatic blood flow , mean arterial pressure , cardiac output , and nitric oxide products before and 30 and 60 minutes after 40 mg of simvastatin . In protocol 2 , 17 patients were r and omized to receive placebo or simvastatin ( 40 mg ) 12 hours and 1 hour before the study . After baseline measurements of the hepatic venous pressure gradient , hepatic blood flow , and nitric oxide products , a st and ard liquid meal was given , and measurements were repeated at 15 , 30 , and 45 minutes . RESULTS In protocol 1 , acute simvastatin did not modify the hepatic venous pressure gradient but increased the hepatic blood flow ( 21 % + /- 13 % at 30 minutes ; P = 0.01 ) and decreased hepatic sinusoidal resistance by 14 % + /- 11 % ( P = 0.04 ) . Nitric oxide product levels significantly increased in hepatic venous blood ( from 31.4 + /- 12.3 nmol . mL(-1 ) to 35.8 + /- 10.7 nmol . mL(-1 ) ; P = 0.04 ) , but not in peripheral blood . Systemic hemodynamics were not modified . In protocol 2 , simvastatin pretreatment significantly attenuated the postpr and ial increase in hepatic venous pressure gradient ( mean peak increase , 10 % + /- 9 % vs. 21 % + /- 6 % in placebo ; P = 0.01 ) . Hepatic blood flow increased similarly in the 2 groups . Hepatic nitric oxide products increased in the simvastatin group but not in the placebo group . CONCLUSIONS Simvastatin administration increases the hepatosplanchnic output of nitric oxide products and decreases hepatic resistance in patients with cirrhosis BACKGROUND Impaired endothelium-mediated relaxation contributes to vasospasm and myocardial ischemia in patients with coronary artery disease . We hypothesized that cholesterol-lowering therapy with the 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor lovastatin could improve endothelium-mediated responses in patients with coronary atherosclerosis . METHODS In a r and omized , double-blind , placebo-controlled trial , we studied coronary endothelial responses in 23 patients r and omly assigned to either lovastatin ( 40 mg twice daily ; 11 patients ) or placebo ( 12 patients ) plus a lipid-lowering diet ( American Heart Association Step 1 diet ) . Patients were studied 12 days after r and omization and again at 5 1/2 months . These patients had total cholesterol levels ranging from 160 to 300 mg per deciliter ( 4.1 to 7.8 mmol per liter ) and were undergoing coronary angioplasty .  At the initial and follow-up studies , patients received serial intracoronary infusions ( in a coronary artery not undergoing angioplasty ) of acetylcholine to assess endothelium-mediated vasodilatation . The responses of the coronary vessels were analyzed with quantitative angiography . RESULTS The patients in the placebo and lovastatin groups had similar responses to acetylcholine at a mean of 12 days of therapy ( expressed as the percentage of change in diameter in response to acetylcholine doses of 10(-9 ) M , 10(-8 ) M , 10(-7 ) M , and 10(-6 ) M ) . In the placebo group , the respective mean ( + /- SE ) changes were 1 + /- 2 , 0 + /- 2 , -2 + /- 4 , and -19 + /- 4 percent ; in the lovastatin group , they were -2 + /- 2 , -4 + /- 4 , -12 + /- 5 , and -16 + /- 7 percent ( P = 0.32 ) . ( Coronary-artery constriction is reflected by negative numbers ) . The responses to acetylcholine in the placebo group after a mean of 5.5 months of therapy were -3 + /- 3 , -1 + /- 2 , -8 + /- 4 , and -18 + /- 5 percent , respectively ; there was significant improvement in the lovastatin group , which had responses of 3 + /- 3 , 3 + /- 3 , 0 + /- 2 , and 0 + /- 3 percent ( P = 0.004 ) . CONCLUSIONS Cholesterol lowering with lovastatin significantly improved endothelium-mediated responses in the coronary arteries of patients with atherosclerosis . Such improvement in the local regulation of coronary arterial tone could potentially relieve ischemic symptoms and signal the stabilization of the atherosclerotic plaque BACKGROUND R and omized , controlled trials demonstrate that HMG CoA reductase inhibition reduces coronary event rates in both primary and secondary prevention . In addition to reducing cholesterol levels , laboratory evidence suggests that statins also have anti-inflammatory activity , a property that may be critical for maintaining plaque stability . Recently , the inflammatory marker high-sensitivity C-reactive protein ( hs-CRP ) has been shown to predict vascular risk in individuals with and without hyperlipidemia . Furthermore , in the Cholesterol and Recurrent Events ( CARE ) trial , the relative efficacy of pravastatin in reducing events was greatest among those with elevated levels of hs-CRP . However , the time course and magnitude of this effect in both primary and secondary prevention is controversial . METHODS PRavastatin Inflammation CRP Evaluation ( PRINCE ) is an investigator-initiated , multicenter , community-based trial that will evaluate the effects of pravastatin on hs-CRP in up to 1182 individuals with coronary artery disease and up to 1702 individuals without coronary artery disease .  Lipid profiles and hs-CRP levels will be obtained at baseline , 12 weeks , and 24 weeks in all study participants . Patients with known coronary artery disease will receive 40 mg/d pravastatin , whereas those without coronary artery disease will be r and omly assigned to receive placebo or 40 mg/d pravastatin . CONCLUSIONS The potential clinical impact of the PRINCE trial is substantial because nearly 50 % of myocardial infa rct ions in the United States occur in persons with normal cholesterol levels , and inflammatory markers such as hs-CRP may provide a means to detect such individuals at high risk who do not currently qualify for statin therapy . The PRINCE trial will determine the time course of effect of this statin on hs-CRP and whether any observed effect on hs-CRP is independent of pravastatin-induced changes in low-density lipoprotein cholesterol BACKGROUND Pleiotropic effects of statins decrease intrahepatic resistance and portal hypertension . AIM We evaluated the effects of simvastatin on hepatic venous pressure gradient ( HVPG ) and azygos vein blood flow in cirrhotic patients . METHODS A 3-month prospect i ve , r and omized , triple-blind trial with simvastatin ( 40 mg/day ) vs. placebo was conducted in patients with cirrhotic portal hypertension . HVPG and azygos blood flow , measured by colour Doppler endoscopic ultrasound , were assessed before and after treatment . The primary endpoint was a decrease in the HVPG of at least 20 % from baseline or to ≤12 mmHg after the treatment . RESULTS 34 patients were prospect ively enrolled , and 24 completed the protocol . In the simvastatin group 6/11 patients ( 55 % ) presented a clinical ly relevant decrease in the HVPG ; no decrease was observed in the placebo group ( p=0.036 ) . Patients with medium/large oesophageal varices and previous variceal bleeding had a higher response rate to simvastatin  . HVPG and 
    Output:
    
: Based on a systematic review and meta‐ analysis , statin use is probably associated with lower risk of hepatic decompensation and mortality , and might reduce portal hypertension , in patients with CLDs .