human
***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 A high consumption of omega‐3 long‐chain polyunsaturated fatty acids , and particularly docosahexaenoic acid ( DHA ) , has been suggested to reduce the risk of cardiovascular disease ( CVD ) . However , while DHA supplementation may have benefits for secondary prevention , few studies have investigated the role of DHA in the primary prevention of CVD . Here , we tested the hypothesis that DHA supplementation  improves endothelial function and risk factors for CVD . Methods and Results Healthy volunteers ( n=328 ) , aged 18 to 37 years , were r and omly assigned to 1.6 g DHA/day ( from a microalgae source ) together with 2.4 g/day carrier oil ( index group ) or to 4.0 g/day olive oil ( control ) ( both given in eight 500‐mg capsules/day for 16 weeks ) . Flow‐mediated endothelium‐dependent vasodilation ( FMD ) of the brachial artery ( primary outcome ) was measured before and after the intervention ( n=268 ) using high‐resolution vascular ultrasound . FMD was the same in both groups at r and omization ( mean , SD ; 0.27 , 0.1 mm ) , but postintervention was higher in the control group ( 0.29 , 0.1 mm ) compared with the DHA‐supplemented group ( 0.26 , 0.1 mm ; mean difference −0.03 mm ; 95 % CI −0.005 to −0.06 mm ; P=0.02 ) . Of other outcomes , only triglyceride ( mean difference −28 % , 95 % CI −40 % to −15 % ; P<0.0001 ) and very low‐density lipoprotein concentrations were significant lower in DHA‐supplemented individuals compared with controls . Conclusions DHA supplementation did not improve endothelial function in healthy , young adults .  Nevertheless , lower triglyceride concentrations with DHA supplementation was consistent with previous reports and could have benefits for the prevention of CVD . Clinical Trial Registration Information URL : http://www.controlled-trials.com/ Unique identifier : IS RCT N no : 19987575 BACKGROUND AND AIMS Virgin olive oil ( VOO ) and nuts are basic components of the Mediterranean diet , a heart-healthy dietary pattern . Nuts have well known cholesterol lowering effects , while evidence is unclear for VOO . We design ed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40 % of the fat in the background diet with VOO , walnuts or almonds . METHODS AND RESULTS After a 4 week run-in period with a healthy diet , eligible c and i date s were r and omized into three diet sequences in a crossover design , with a common background diet enriched with VOO , walnuts or almonds , lasting 4 weeks each . Outcomes were changes of serum lipids and oxidation and inflammation markers , measured by st and ard methods . Plasma fatty acids were determined by gas chromatography to assess compliance . In 18 participants completing the study ( 9 women , mean age 56 y , BMI 25.7 kg/m(2 ) ) , LDL-cholesterol was reduced from baseline by 7.3 % , 10.8 % and 13.4 % after the VOO , walnut and almond diets , respectively ( P = 0.001 , Friedman test ) . Total cholesterol and LDL/HDL ratios decreased in parallel . LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets . No changes of other lipid fractions , oxidation analytes or inflammatory biomarkers were observed . Plasma fatty acid changes after each diet sequence supported good compliance . CONCLUSION The results confirm the cholesterol lowering properties of nut-enriched diets . They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content , which clearly deserves further study The intake of ( n-3 ) long-chain PUFA is associated with a decreased risk of fatal myocardial infa rct ion . Whether this effect is attributable to the effects of docosahexaenoic acid [ 22:6(n-3 ) ( DHA ) ] on vascular function , particularly at intakes < 1 g/d , is unknown . We report a r and omized , double-blind , crossover , placebo controlled trial of 0.7 g DHA/d as a purified algal derived triacylglycerol ( 1.5 g/d ) vs. placebo ( 1.5 g olive oil/d ) on vascular function and biochemical indices of endothelial dysfunction in 38 healthy men and women , aged 40 - 65 y. Each treatment phase lasted 3 mo , separated by a 4 mo washout period . Supplementation increased the proportion of DHA in erythrocytes lipids by 58 % , compared with placebo .  Arterial compliance and endothelium independent and dependent responses , plasma concentrations of C-reactive protein , soluble thrombomodulin , E-selectin , von Willebr and factor antigen , and urinary microalbumin and isoprostane excretion were unaffected by treatment . Diastolic blood pressure decreased by 3.3 mm Hg ( 95 % CI -6.1 to -0.6 ; P = 0.01 ) . Heart rate tended to be 2.1 beats/min lower after DHA treatment than after the placebo period ( P = 0.15 ) . The results indicate that a moderate increase in the daily intake of DHA to approximately 0.7 g DHA lowers diastolic BP but does not influence indices of endothelial function or arterial stiffness in the short term A mixture of trans-10 , cis-12 ( t10,c12 ) and cis-9 , trans-11 ( c9,t11 ) conjugated linoleic acid ( CLA mixture ) reduced atherosclerosis in animals , thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest . We gave 75 healthy postmenopausal women a daily supplement of 5.5 g of oil rich in either CLA mixture , an oil rich in the naturally occurring c9,t11 CLA ( CLA milk ) , respectively , or olive oil for 16 wk in a double-blind , r and omized , parallel intervention study . We sample d blood and urine before and after the intervention . The ratios of total cholesterol : HDL cholesterol and concentrations of C-reactive protein , fibrinogen , and plasminogen activator inhibitor-1 were significantly higher in women supplemented with the CLA mixture than in those supplemented with CLA milk .  Plasma triacylglycerol was significantly higher and HDL cholesterol was lower in women supplemented with the CLA mixture than with olive oil . Both CLA supplements increased lipid peroxidation , a marker of in vivo oxidative stress measured as urinary free 8-iso-prostagl and in F(2alpha ) . However , the CLA mixture increased lipid peroxidation more than the CLA milk did . The plasma cytokines interleukin-6 and tumor necrosis factor-alpha were not affected by the treatments , nor were any of the other variables measured . In conclusion , oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease , whereas the c9,t11 CLA isomer is more neutral , except for a small but significant increase in lipid peroxidation compared with olive oil BACKGROUND AND PURPOSE Activation of endothelial cells and platelets is an important mediator of atherothrombosis . Markers of endothelial cell and platelet activation such as soluble adhesion molecules can be measured in plasma . We hypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectin and von Willebr and factor ( vWF ) , primarily reflecting activation of endothelial cells , and increased concentrations of soluble P-selectin and platelet-derived microvesicles ( PDM ) , primarily reflecting activation of platelets , compared with healthy controls . We also hypothesized that these markers would be differentially elevated in ischemic stroke caused by large- and small-artery atherothrombosis compared with cardiogenic embolism . METHODS We conducted a case-control study of 200 hospital-referred cases of first-ever ischemic stroke and 205 r and omly selected community controls stratified by age , sex , and postal code . Using established criteria , we classified cases of stroke by etiological subtype in a blinded fashion . The prevalence of vascular risk factors and blood concentrations of E-selectin , P-selectin , vWF antigen , and PDM were determined in stroke cases within 7 days and at 3 to 6 months after stroke and in controls . RESULTS Mean blood concentrations of soluble E-selectin , P-selectin , and PDM within 7 days of stroke onset were all significantly higher in cases compared with controls . At 3 to 6 months after stroke , the mean blood concentrations of E-selectin and P-selectin fell significantly below that of controls , and PDM concentrations remained elevated . There was a strong , grade d , and independent ( of age , sex , and vascular risk factors ) association between increasing blood concentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke , particularly ischemic stroke caused by large-artery atherothrombosis . There was also a significant , grade d , and independent association between increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-artery atherothrombosis . CONCLUSIONS We have demonstrated significant associations between acute elevation of blood markers of endothelial cell and platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activation and ischemic stroke caused by large-artery atherothrombosis . Persistent elevated blood concentrations of PDM may be a marker of increased risk of ischemic stroke BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension Background Adherence to the Mediterranean diet ( MD ) is associated with reduced morbidity and mortality due to cardiovascular disease . However , how the MD exerts its effects is not fully known . Aim To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED ( Prevención con Dieta Mediterránea ) study . Methods A total of 164 participants at high risk for cardiovascular disease were r and omized into three diet groups : MD supplemented with 50mL/d of extra virgin olive oil ( MD+EVOO ) or 30 g/d of nuts ( MD+Nuts ) and a low-fat diet . Changes in classical cardiovascular risk factors , inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention . Results Compared to participants in the low-fat diet group , those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic ( 6mmHg ) and diastolic ( 3mmHg ) blood pressure ( P = 0.02 ; both ) , as well as a reduction of 10 % and 8 % in LDL-cholesterol ( P = 0.04 ) , respectively . Patients in the MD+Nuts group showed a significant reduction of 34 % in CD40 expression on monocyte surface compared to low-fat diet patients ( P = 0.03 ) . In addition , inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45 % and 35 % and 95 % and 90 % in the MD+EVOO and MD+N 
    Output:
    
agent
These results provide evidence that olive oil might exert beneficial effects on endothelial function as well as markers of inflammation and endothelial function , thus representing a key ingredient contributing to the cardiovascular-protective effects of a Mediterranean diet .
***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 A high consumption of omega‐3 long‐chain polyunsaturated fatty acids , and particularly docosahexaenoic acid ( DHA ) , has been suggested to reduce the risk of cardiovascular disease ( CVD ) . However , while DHA supplementation may have benefits for secondary prevention , few studies have investigated the role of DHA in the primary prevention of CVD . Here , we tested the hypothesis that DHA supplementation  improves endothelial function and risk factors for CVD . Methods and Results Healthy volunteers ( n=328 ) , aged 18 to 37 years , were r and omly assigned to 1.6 g DHA/day ( from a microalgae source ) together with 2.4 g/day carrier oil ( index group ) or to 4.0 g/day olive oil ( control ) ( both given in eight 500‐mg capsules/day for 16 weeks ) . Flow‐mediated endothelium‐dependent vasodilation ( FMD ) of the brachial artery ( primary outcome ) was measured before and after the intervention ( n=268 ) using high‐resolution vascular ultrasound . FMD was the same in both groups at r and omization ( mean , SD ; 0.27 , 0.1 mm ) , but postintervention was higher in the control group ( 0.29 , 0.1 mm ) compared with the DHA‐supplemented group ( 0.26 , 0.1 mm ; mean difference −0.03 mm ; 95 % CI −0.005 to −0.06 mm ; P=0.02 ) . Of other outcomes , only triglyceride ( mean difference −28 % , 95 % CI −40 % to −15 % ; P<0.0001 ) and very low‐density lipoprotein concentrations were significant lower in DHA‐supplemented individuals compared with controls . Conclusions DHA supplementation did not improve endothelial function in healthy , young adults .  Nevertheless , lower triglyceride concentrations with DHA supplementation was consistent with previous reports and could have benefits for the prevention of CVD . Clinical Trial Registration Information URL : http://www.controlled-trials.com/ Unique identifier : IS RCT N no : 19987575 BACKGROUND AND AIMS Virgin olive oil ( VOO ) and nuts are basic components of the Mediterranean diet , a heart-healthy dietary pattern . Nuts have well known cholesterol lowering effects , while evidence is unclear for VOO . We design ed a study in hypercholesterolemic patients to assess the effects on serum lipids and other intermediate markers of cardiovascular risk of replacing 40 % of the fat in the background diet with VOO , walnuts or almonds . METHODS AND RESULTS After a 4 week run-in period with a healthy diet , eligible c and i date s were r and omized into three diet sequences in a crossover design , with a common background diet enriched with VOO , walnuts or almonds , lasting 4 weeks each . Outcomes were changes of serum lipids and oxidation and inflammation markers , measured by st and ard methods . Plasma fatty acids were determined by gas chromatography to assess compliance . In 18 participants completing the study ( 9 women , mean age 56 y , BMI 25.7 kg/m(2 ) ) , LDL-cholesterol was reduced from baseline by 7.3 % , 10.8 % and 13.4 % after the VOO , walnut and almond diets , respectively ( P = 0.001 , Friedman test ) . Total cholesterol and LDL/HDL ratios decreased in parallel . LDL-cholesterol decreases were greater than predicted from dietary fatty acid and cholesterol exchanges among diets . No changes of other lipid fractions , oxidation analytes or inflammatory biomarkers were observed . Plasma fatty acid changes after each diet sequence supported good compliance . CONCLUSION The results confirm the cholesterol lowering properties of nut-enriched diets . They also suggest that phenolic-rich VOO has a cholesterol lowering effect independently of its fatty acid content , which clearly deserves further study The intake of ( n-3 ) long-chain PUFA is associated with a decreased risk of fatal myocardial infa rct ion . Whether this effect is attributable to the effects of docosahexaenoic acid [ 22:6(n-3 ) ( DHA ) ] on vascular function , particularly at intakes < 1 g/d , is unknown . We report a r and omized , double-blind , crossover , placebo controlled trial of 0.7 g DHA/d as a purified algal derived triacylglycerol ( 1.5 g/d ) vs. placebo ( 1.5 g olive oil/d ) on vascular function and biochemical indices of endothelial dysfunction in 38 healthy men and women , aged 40 - 65 y. Each treatment phase lasted 3 mo , separated by a 4 mo washout period . Supplementation increased the proportion of DHA in erythrocytes lipids by 58 % , compared with placebo .  Arterial compliance and endothelium independent and dependent responses , plasma concentrations of C-reactive protein , soluble thrombomodulin , E-selectin , von Willebr and factor antigen , and urinary microalbumin and isoprostane excretion were unaffected by treatment . Diastolic blood pressure decreased by 3.3 mm Hg ( 95 % CI -6.1 to -0.6 ; P = 0.01 ) . Heart rate tended to be 2.1 beats/min lower after DHA treatment than after the placebo period ( P = 0.15 ) . The results indicate that a moderate increase in the daily intake of DHA to approximately 0.7 g DHA lowers diastolic BP but does not influence indices of endothelial function or arterial stiffness in the short term A mixture of trans-10 , cis-12 ( t10,c12 ) and cis-9 , trans-11 ( c9,t11 ) conjugated linoleic acid ( CLA mixture ) reduced atherosclerosis in animals , thus the effect of these isomers on endothelial dysfunctions leading to inflammation and atherosclerosis is of interest . We gave 75 healthy postmenopausal women a daily supplement of 5.5 g of oil rich in either CLA mixture , an oil rich in the naturally occurring c9,t11 CLA ( CLA milk ) , respectively , or olive oil for 16 wk in a double-blind , r and omized , parallel intervention study . We sample d blood and urine before and after the intervention . The ratios of total cholesterol : HDL cholesterol and concentrations of C-reactive protein , fibrinogen , and plasminogen activator inhibitor-1 were significantly higher in women supplemented with the CLA mixture than in those supplemented with CLA milk .  Plasma triacylglycerol was significantly higher and HDL cholesterol was lower in women supplemented with the CLA mixture than with olive oil . Both CLA supplements increased lipid peroxidation , a marker of in vivo oxidative stress measured as urinary free 8-iso-prostagl and in F(2alpha ) . However , the CLA mixture increased lipid peroxidation more than the CLA milk did . The plasma cytokines interleukin-6 and tumor necrosis factor-alpha were not affected by the treatments , nor were any of the other variables measured . In conclusion , oil containing trans-10,cis-12 CLA has several adverse effects on classical and novel markers of coronary vascular disease , whereas the c9,t11 CLA isomer is more neutral , except for a small but significant increase in lipid peroxidation compared with olive oil BACKGROUND AND PURPOSE Activation of endothelial cells and platelets is an important mediator of atherothrombosis . Markers of endothelial cell and platelet activation such as soluble adhesion molecules can be measured in plasma . We hypothesized that patients with acute ischemic stroke would have increased blood concentrations of soluble E-selectin and von Willebr and factor ( vWF ) , primarily reflecting activation of endothelial cells , and increased concentrations of soluble P-selectin and platelet-derived microvesicles ( PDM ) , primarily reflecting activation of platelets , compared with healthy controls . We also hypothesized that these markers would be differentially elevated in ischemic stroke caused by large- and small-artery atherothrombosis compared with cardiogenic embolism . METHODS We conducted a case-control study of 200 hospital-referred cases of first-ever ischemic stroke and 205 r and omly selected community controls stratified by age , sex , and postal code . Using established criteria , we classified cases of stroke by etiological subtype in a blinded fashion . The prevalence of vascular risk factors and blood concentrations of E-selectin , P-selectin , vWF antigen , and PDM were determined in stroke cases within 7 days and at 3 to 6 months after stroke and in controls . RESULTS Mean blood concentrations of soluble E-selectin , P-selectin , and PDM within 7 days of stroke onset were all significantly higher in cases compared with controls . At 3 to 6 months after stroke , the mean blood concentrations of E-selectin and P-selectin fell significantly below that of controls , and PDM concentrations remained elevated . There was a strong , grade d , and independent ( of age , sex , and vascular risk factors ) association between increasing blood concentrations of E-selectin during the acute phase and all etiological subtypes of ischemic stroke , particularly ischemic stroke caused by large-artery atherothrombosis . There was also a significant , grade d , and independent association between increasing blood concentrations of vWF during the acute phase and ischemic stroke caused by large-artery atherothrombosis . CONCLUSIONS We have demonstrated significant associations between acute elevation of blood markers of endothelial cell and platelet activation and ischemic stroke and between acute elevation of blood markers of endothelial cell activation and ischemic stroke caused by large-artery atherothrombosis . Persistent elevated blood concentrations of PDM may be a marker of increased risk of ischemic stroke BACKGROUND Type 2 diabetes and hypertension are both associated with an increased risk of atherothrombosis . We assessed whether purified eicosapentaenoic acid ( EPA ) and docosahexaenoic acid ( DHA ) from fish oil have differential effects on platelet , fibrinolytic and vascular function in patients with both conditions . METHODS In a double-blind placebo-controlled trial of parallel design , 59 treated-hypertensive Type 2 diabetic men and postmenopausal women , were r and omised to 4 g/day of EPA , DHA or olive oil ( placebo ) for 6 weeks . Collagen and PAF-stimulated platelet aggregation , collagen-stimulated thromboxane release ( TXB2 ) , plasma tPA and PAI-1 antigens , von Willebr and factor , p-selectin , and flow-mediated and glyceryl-trinitrate-mediated dilatation of the brachial artery , were examined before and at the end of intervention . RESULTS Thirty-nine men and 12 women aged 61.2+/-1.2 year completed the study . Relative to placebo , DHA but not EPA supplementation significantly reduced collagen aggregation ( 16.9 % , P=0.05 ) and TXB2 ( 18.8 % , P=0.03 ) . There were no significant changes in either PAF-stimulated platelet aggregation , fibrinolytic function or vascular function in either the EPA or DHA group relative to placebo . CONCLUSION Highly purified DHA may be a more effective anti-thrombotic agent than EPA . However , longer-term studies assessing morbidity and mortality are needed in order to establish if DHA contributes to reducing CHD amongst Type 2 diabetic patients with treated hypertension Background Adherence to the Mediterranean diet ( MD ) is associated with reduced morbidity and mortality due to cardiovascular disease . However , how the MD exerts its effects is not fully known . Aim To assess the 12-month effects of two enhanced MDs compared to a low-fat diet on inflammatory biomarkers related to atherosclerosis and plaque vulnerability in a subcohort of the PREDIMED ( Prevención con Dieta Mediterránea ) study . Methods A total of 164 participants at high risk for cardiovascular disease were r and omized into three diet groups : MD supplemented with 50mL/d of extra virgin olive oil ( MD+EVOO ) or 30 g/d of nuts ( MD+Nuts ) and a low-fat diet . Changes in classical cardiovascular risk factors , inflammatory biomarkers of atherosclerosis and plaque vulnerability were measured after 12 months of intervention . Results Compared to participants in the low-fat diet group , those receiving MD+EVOO and MD+Nuts showed a higher decrease in systolic ( 6mmHg ) and diastolic ( 3mmHg ) blood pressure ( P = 0.02 ; both ) , as well as a reduction of 10 % and 8 % in LDL-cholesterol ( P = 0.04 ) , respectively . Patients in the MD+Nuts group showed a significant reduction of 34 % in CD40 expression on monocyte surface compared to low-fat diet patients ( P = 0.03 ) . In addition , inflammatory biomarkers related to plaque instability such as C-reactive protein and interleukin-6 were reduced by 45 % and 35 % and 95 % and 90 % in the MD+EVOO and MD+N 
    Output:
    