***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 —Vascular cell adhesion molecule (VCAM)-1 , intercellular adhesion molecule (ICAM)-1 , and E-selectin mediate adhesion and transmigration of leukocytes to the vascular endothelial wall and may promote plaque growth and instability . In a prospect i ve study , we evaluated the effect of soluble adhesion molecules on the risk of future cardiovascular events among patients with angiographically documented coronary artery disease ( CAD ) . Methods and Results —We obtained baseline sample s from a prospect i ve cohort of 1246 patients with CAD . Besides various markers of inflammation ,  soluble VCAM-1 ( sVCAM-1 ) , sICAM-1 , and  sE-selectin  were determined . Follow-up information on cardiovascular events was obtained ( mean , 2.7 ; maximum , 4.1 years ) . Independently higher levels of  sVCAM-1  ( 1932 versus 1128 ng/mL;P < 0.0001 ) ,  sICAM-1  ( 353 versus 287 ng/mL;P = 0.015 ) , and  sE-selectin  ( 81 versus 63 ng/mL;P = 0.003 ) were observed in patients with future death from cardiovascular causes . In a multivariate model , fatal risk was 2.1-fold ( 1.1 to 4.0 ) higher in patients within the top quartile of baseline sVCAM-1 concentrations compared with lower quartiles . This association was present independent of general inflammatory response as reflected by low or high C-reactive protein ( hs-CRP ) levels . In a model that simultaneously controlled for all inflammatory and soluble adhesion markers determined , only sVCAM-1 remained independently significant for future fatal cardiovascular events , with a 2.8-fold increase in risk ( P = 0.003 ) . Conclusions —Soluble adhesion molecules  sVCAM-1  , sICAM-1 , and sE-selectin were significantly related to future death from cardiovascular causes among patients with documented CAD . Especially sVCAM-1 added to the predictive value of classic risk factors and hs-CRP in determining the risk of future cardiovascular death BACKGROUND Interleukin-6 ( IL-6 ) plays a central role in inflammation and tissue injury . However , epidemiological data evaluating the role of IL-6 in atherogenesis are sparse . METHODS AND RESULTS In a prospect i ve study involving 14 916 apparently healthy men , we measured baseline plasma concentration of IL-6 in 202 participants who subsequently developed myocardial infa rct ion ( MI ) and in 202 study participants matched for age and smoking status who did not report vascular disease during a 6-year follow-up .  Median concentrations of IL-6 at baseline were higher among men who subsequently had an MI than among those who did not ( 1.81 versus 1 . 46 pg/mL ; P=0.002 ) . The risk of future MI increased with increasing quartiles of baseline IL-6 concentration ( P for trend < 0.001 ) such that men in the highest quartile at entry had a relative risk 2.3 times higher than those in the lowest quartile ( 95 % CI 1.3 to 4.3 , P=0.005 ) ; for each quartile increase in IL-6 , there was a 38 % increase in risk (P=0.001).This relationship remained significant after adjustment for other cardiovascular risk factors , was stable over long periods of follow-up , and was present in all low-risk subgroups , including nonsmokers . Although the strongest correlate of IL-6 in these data was C-reactive protein ( r=0.43 , P<0.001 ) , the relationship of IL-6 with subsequent risk remained after control for this factor ( P<0.001 ) . CONCLUSIONS In apparently healthy men , elevated levels of IL-6 are associated with increased risk of future MI . These data thus support a role for cytokine-mediated inflammation in the early stages of atherogenesis BACKGROUND Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events . Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol , we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment . METHODS We r and omly assigned 17,802 apparently healthy men and women with low-density lipoprotein ( LDL ) cholesterol levels of less than 130 mg per deciliter ( 3.4 mmol per liter ) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin , 20 mg daily , or placebo and followed them for the occurrence of the combined primary end point of myocardial infa rct ion , stroke , arterial revascularization , hospitalization for unstable angina , or death from cardiovascular causes . RESULTS The trial was stopped after a median follow-up of 1.9 years ( maximum , 5.0 ) . Rosuvastatin reduced LDL cholesterol levels by 50 % and high-sensitivity C-reactive protein levels by 37 % . The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups , respectively ( hazard ratio for rosuvastatin , 0.56 ; 95 % confidence interval [ CI ] , 0.46 to 0.69 ; P<0.00001 ) , with corresponding rates of 0.17 and 0.37 for myocardial infa rct ion ( hazard ratio , 0.46 ; 95 % CI , 0.30 to 0.70 ; P=0.0002 ) , 0.18 and 0.34 for stroke ( hazard ratio , 0.52 ; 95 % CI , 0.34 to 0.79 ; P=0.002 ) , 0.41 and 0.77 for revascularization or unstable angina ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.70 ; P<0.00001 ) , 0.45 and 0.85 for the combined end point of myocardial infa rct ion , stroke , or death from cardiovascular causes ( hazard ratio , 0.53 ; 95 % CI , 0.40 to 0.69 ; P<0.00001 ) , and 1.00 and 1.25 for death from any cause ( hazard ratio , 0.80 ; 95 % CI , 0.67 to 0.97 ; P=0.02 ) . Consistent effects were observed in all subgroups evaluated . The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes . CONCLUSIONS In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels , rosuvastatin significantly reduced the incidence of major cardiovascular events . ( Clinical Trials.gov number , NCT00239681 . Background Patients with chronic HCV infection have increased liver iron . Recently identified protein hepcidin synthesized in the liver , is thought to be a key regulator for iron homeostasis and is induced by infection and inflammation . Lower erythropoietin and iron supplementation requirements were previously reported in HD patients with HCV infection . We investigated the association of prohepcidin with inflammation and iron parameters in HD patients with and without chronic HCV infection . Methods Sixty patients ( 27 male , 33 female , mean age 50 ±15 years ) on chronic HD were included . Parameters related to iron metabolism ( ferritin , serum iron and total iron binding capacity ( TIBC ) ) , inflammation ( hs-CRP , TNF-α and IL-6 ) and prohepcidin levels were measured . The response to treatment ( erythropoiesis-stimulating agent ( ESA ) resistance index ) was assessed from the ratio of the weekly erythropoietin ( rhuEPO ) dose to hemoglobin ( Hb ) per unit weight . Results Serum prohepcidin levels of HCV positive patients ( 135 ± 25 ng/mL ) were significantly lower than HCV negative patients [ 148 ± 18 ng/mL , ( p = 0.025 ) ] . Serum IL-6 levels of HCV positive patients were also significantly lower than HCV negative patients ( p = 0.016 ) . Serum prohepcidin levels were positively correlated with ferritin ( r = 0.405 , p = 0.001 ) and IL-6 ( r = 0.271 , p = 0.050 ) levels in HD patients . In the HCV positive group , serum prohepcidin levels significantly correlated with ferritin levels ( r = 0.514 p = 0.004 ) . In the HCV negative group , serum prohepcidin levels significantly correlated with serum IL-6 levels ( r = 0.418 , p = 0.027 ) . In multiple regression analysis performed to predict prohepcidin in HCV positive patients , serum ferritin was found to be an independent variable ( r = 0.28 , p = 0.008 ) . Conclusions HCV positive HD patients have low levels of serum prohepcidin and IL-6 which might account for iron accumulation together with lower iron and rhuEPO requirements in these patients BACKGROUND Since inflammation is believed to have a role in the pathogenesis of cardiovascular events , measurement of markers of inflammation has been proposed as a method to improve the prediction of the risk of these events . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy postmenopausal women over a mean follow-up period of three years to assess the risk of cardiovascular events associated with base-line levels of markers of inflammation . The markers included high-sensitivity C-reactive protein ( hs-CRP ) , serum amyloid A , interleukin-6 , and soluble intercellular adhesion molecule type 1 ( sICAM-1 ) . We also studied homocysteine and a variety of lipid and lipoprotein measurements .  Cardiovascular events were defined as death from coronary heart disease , nonfatal myocardial infa rct ion or stroke , or the need for coronary-revascularization procedures . RESULTS Of the 12 markers measured , hs-CRP was the strongest univariate predictor of the risk of cardiovascular events ; the relative risk of events for women in the highest as compared with the lowest quartile for this marker was 4.4 ( 95 percent confidence interval , 2.2 to 8.9 ) . Other markers significantly associated with the risk of cardiovascular events were serum amyloid A ( relative risk for the highest as compared with the lowest quartile , 3.0 ) , sICAM-1 ( 2.6 ) , interleukin-6 ( 2.2 ) , homocysteine ( 2.0 ) , total cholesterol ( 2.4 ) , LDL cholesterol ( 2.4 ) , apolipoprotein B-100 ( 3.4 ) , HDL cholesterol ( 0.3 ) , and the ratio of total cholesterol to HDL cholesterol ( 3.4 ) . Prediction models that incorporated markers of inflammation in addition to lipids were significantly better at predicting risk than models based on lipid levels alone ( P<0.001 ) . The levels of hs-CRP and serum amyloid A were significant predictors of risk even in the subgroup of women with LDL cholesterol levels below 130 mg per deciliter ( 3.4 mmol per liter ) , the target for primary prevention established by the National Cholesterol Education Program . In multivariate analyses , the only plasma markers that independently predicted risk were hs-CRP ( relative risk for the highest as compared with the lowest quartile , 1.5 ; 95 percent confidence interval , 1.1 to 2.1 ) and the ratio of total cholesterol to HDL cholesterol ( relative risk , 1.4 ; 95 percent confidence interval , 1.1 to 1.9 ) . CONCLUSIONS The addition of the measurement of C-reactive protein to screening based on lipid levels may provide an improved method of identifying persons at risk for cardiovascular events Tumor necrosis factor-alpha ( TNF-alpha ) plays a central role in the host 's immunomodulatory response to infective agents . To evaluate the TNF-alpha system in patients with chronic hepatitis C virus ( HCV ) infection , plasma , serum , and peripheral blood mononuclear cells ( P BMC ) were prospect ively collected from 53 patients and 33 healthy control subjects . Circulating TNF-alpha and TNF receptors were assayed by their respective enzyme immunoassays . In addition , TNF-alpha mRNA was quantitated in P BMC using a branched DNA assay , and production of TNF-alpha by P BMC with and without lipopolysaccharide was also assessed . Patients with chronic HCV infection had a higher level of circulating TNF-alpha compared to healthy control subjects ( 9.62 + /- 6.01 vs 3.66 + /- 1.23 pg/ml , P < 0.001 ) . They also had higher circulating levels of TNF receptors compared to control ( CD120a :  
    Output:
    
Our review revealed that HCV infection significantly alters serum levels of markers of inflammation , endothelial function , and cardiac dysfunction prior to HCV treatment , and some of which may change in response to HCV therapy .
Current risk stratification tools for development of CVD in the general population may not account for the increased inflammatory markers that appear to be elevated among HCV‐infected patients contributing to increased CVD risk