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: Objective To assess the effects of tibolone on climacteric symptoms , endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer OBJECTIVE To assess the effect of tibolone on markers of vascular risk in postmenopausal women who were receiving hemodialysis . DESIGN One-year open-label study . SETTING " Zvezdara " University Medical Center , Bel grade , Serbia . PATIENT(S ) Twenty-eight postmenopausal women undergoing chronic hemodialysis . INTERVENTION(S ) Fifteen women received tibolone 2.5 mg three times per week ; 13 other women served as controls . MAIN OUTCOME MEASURE(S ) Mean arterial pressure and weight were measured at baseline and at 6 and 12 months , and blood was collected for insulin , total cholesterol , low-density lipoprotein , high-density lipoprotein , triglycerides , lipoprotein(a ) , high-sensitivity C-reactive protein ( hs-CRP ) , endothelin-1 ( ET-1 ) , vascular endothelial growth factor ( VEGF ) , and markers of renal function . RESULT ( S ) Mean arterial pressure fell in the tibolone but not in the control group at 6 and 12 months versus baseline ( mean [ SD ] : 93 [ 15 ] vs. 105 [ 11 ] mmHg and 94 [ 10 ] vs. 105 [ 11 ] mmHg , respectively ) . Weight , insulin , lipids , lipoprotein(a ) , hs-CRP , ET-1 , VEGF , and renal function remained unchanged within each group , but high-density lipoprotein concentrations fell in the tibolone group after 12 months ( 1.2 [ 0.3 ] vs. 1.6 [ 0.6 ] mmol/L ) . CONCLUSION ( S ) The effects of tibolone on markers of vascular risk in postmenopausal women who are receiving hemodialysis and healthy women appear to differ . This should be taken into account when tailoring menopausal therapies to the specific requirements of each individual Background : Lipoprotein(a ) ( Lp(a ) ) has been regarded in some studies as an independent risk factor of atherosclerotic vascular disease . However , the use of a baseline plasma Lp(a ) concentration as a screening tool for future acute vascular events ( AVE ) is controversial . We therefore investigated whether progressively increasing change in plasma Lp(a ) concentration is associated with the development of AVE . Methods : We investigated prospect i ve analyses of 985 participants ( 464 women and 521 men ) who had either clinical ly evident vascular disease ( VD group , n=443 ) or its risk factor(s ) ( RF group , n=542 ) .  Blood sample s were taken from all participants every six months to measure inflammatory markers such as Lp(a ) and C-reactive protein during a 10-year follow-up period . Results : During the follow-up , 223 new cases of myocardial infa rct ion , stroke , and peripheral arterial disease were identified . In the RF group , the relative risk of positive ∆ Lp(a ) for predicting AVE was 4.36 ( 95 % confidence interval [ CI ] 1.76 - 10.85 ; P=0.002 ) . In the VD group , the relative risk of positive ∆ Lp(a ) for predicting AVE was 6.35 ( 95 % CI 3.68 - 10.97 ; P<0.001 ) . Conclusions : These results suggest that a progressively increasing change in Lp(a ) concentration has a highly significant predictive value in AVE in both the VD and the RF groups The effects of hormone replacement therapy in hypertensive women are controversial . This r and omised placebo controlled trial assessed the effect of tibolone 2.5 mg on blood pressure and fasting plasma lipids in 29 hypertensive postmenopausal women over 6 months using a 2:1 r and omisation to tibolone . The primary clinical end-point was mean office blood pressure . At 6 months systolic blood pressure declined by 5.30 ± 2.87 % vs4.94 ± 3.37 % whilst diastolic blood pressure declined 5.38 ± 2.65 % vs 0.85 ± 3.69 % on tibolone and placebo respectively . These differences were not statistically significant . Triglycerides decreased by 33.3 ± 6.1 % vs 7.6 ± 7.9 % ( P < 0.01 ) and high-density lipoprotein (hdl)-cholesterol by 21.7 ± 3.8 % vs2.4 ± 2.6 % ( P < 0.01 ) with tibolone as opposed to placebo . no significant differences were observed in total cholesterol , low-density lipoprotein (ldl)-cholesterol and lipoprotein ( a ) . fibrinogen levels were reduced by 13.6 ± 6.8 % on tibolone compared to a 19.3 ± 15.4 % rise ( P < 0.05 ) on placebo . this study suggests that tibolone has no deleterious effect on blood pressure in women with hypertension but has contrasting effects on biochemical risk factors . large-scale studies are required to determine the overall effect of tibolone on cardiovascular morbidity and mortality Tibolone , a synthetic steroid with estrogenic , and rogenic , and progestogenic properties relieves climacteric symptoms and prevents postmenopausal bone loss . The influence of tibolone treatment on coagulation , fibrinolysis , and lipid metabolism was investigated in 91 healthy late postmenopausal women . They were r and omly assigned in a double-blind , placebo-controlled 2-year study to receive either tibolone 1.25 mg ( n = 36 , 29 completed ) or 2.5 mg ( n = 35 , 28 completed ) or placebo ( n = 20 , 13 completed ) . The biochemical markers of lipid metabolism , fibrinolysis , and coagulation were measured every 3 months . In both tibolone groups a similar ( approximately 30 % ) decrease in high density lipoprotein cholesterol and a corresponding lowering of apolipoprotein A-1 ( P < 0.001 ) was detected . Also serum total cholesterol and triglycerides were reduced ( approximately 15 % ; P < 0.01 ) , whereas low density lipoprotein cholesterol , apolipoprotein B , and lipoprotein(a ) were unaffected by tibolone . The two dose levels of tibolone result ed in a similar , marked lowering ( approximately 30 % ) of tissue plasminogen activator and plasminogen activator inhibitor activity as compared with placebo ( P < 0.001 ) . Plasminogen increased ( approximately 15 % ; P < 0.001 ) in both groups . Fibrinogen was lowered ( P < 0.01 ) in the low-dose group , and antithrombin III remained unchanged . The overall effect on hemostatic factors of the present doses of tibolone in healthy , late postmenopausal women tends towards increased fibrinolysis and unchanged coagulation . This may be beneficial and might theoretically counterbalance the potentially negative effect of the decrease in high density lipoprotein cholesterol Background Lipoprotein(a ) [ Lp(a ) ] is a low density lipoprotein-like particle whose apolipoprotein B ( apo B ) moiety is disulfide-linked to apo(a ) , a plasminogen-like inhibitor of fibrinolysis in vitro . We hypothesized that plasma concentrations of Lp(a ) are acutely affected by intravenous tissue-type plasminogen activator ( t-PA ) . Methods and Results Patients with unstable angina were r and omized to receive either intravenous t-PA ( n = 15 ) or placebo ( n = 11 ) . Two-way ANOVA using repeated measures revealed a significant effect of t-PA on concentrations of Lp(a ) ( p=0.026 ) . There was a 48 % fall in Lp(a ) from baseline concentrations in the t-PA group at 12 hours ( p=0.031 ) but not at 72 hours . Lp(a ) in the placebo group was unchanged . Conclusions We conclude that t-PA produces a sharp and substantial but reversible reduction in plasma Lp(a ) . These data suggest that Lp(a ) concentration is not as static in vivo as had been believed and might be acutely modifiable through some mechanism that induces its removal from the freely circulating state Aims The aims of the study were , first , to critically evaluate lipoprotein(a ) [ Lp(a ) ] as a cardiovascular risk factor and , second , to advise on screening for elevated plasma Lp(a ) , on desirable levels , and on therapeutic strategies . Methods and results The robust and specific association between elevated Lp(a ) levels and increased cardiovascular disease (CVD)/coronary heart disease ( CHD ) risk , together with recent genetic findings , indicates that elevated Lp(a ) , like elevated LDL-cholesterol , is causally related to premature CVD/CHD . The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels . Mechanistically , elevated Lp(a ) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a ) resembles both plasminogen and plasmin but has no fibrinolytic activity , or may accelerate atherosclerosis because , like LDL , the Lp(a ) particle is cholesterol-rich , or both . We advise that Lp(a ) be measured once , using an isoform-insensitive assay , in subjects at intermediate or high CVD/CHD risk with premature CVD , familial hypercholesterolaemia , a family history of premature CVD and /or elevated Lp(a ) , recurrent CVD despite statin treatment , ≥3 % 10-year risk of fatal CVD according to European guidelines , and /or ≥10 % 10-year risk of fatal + non-fatal CHD according to US guidelines . As a secondary priority after LDL-cholesterol reduction , we recommend a desirable level for Lp(a ) < 80th percentile ( less than ∼50 mg/dL ) . Treatment should primarily be niacin 1–3 g/day , as a meta- analysis of r and omized , controlled intervention trials demonstrates reduced CVD  by niacin treatment . In extreme cases , LDL-apheresis is efficacious in removing Lp(a ) . Conclusion We recommend screening for elevated Lp(a ) in those at intermediate or high CVD/CHD risk , a desirable level < 50 mg/dL as a function of global cardiovascular risk , and use of niacin for Lp(a ) and CVD/CHD risk reduction Recent published studies have provided increasing evidence that lipoprotein(a ) [ Lp(a ) ] may be a potential causal , genetic , independent risk factor for cardiovascular disease ( CVD ) . Lp(a ) levels > 25 mg/dl are present in ∼30 % of Caucasians and 60 % to 70 % of Blacks . Lp(a ) is composed of apolipoprotein B-100 and apolipoprotein ( a ) [ ( apo(a ) ] . Circulating Lp(a ) levels are primarily influenced by the LPA gene without significant dietary or environmental effects , mediating CVD risk throughout the patient 's lifetime . Recent clinical outcomes studies , meta-analyses , and Mendelian r and omization studies , in which r and omization of Lp(a ) levels is achieved through the r and om assortment of LPA gene variants thereby removing confounders , have shown that genetically determined Lp(a ) levels are continuously and linearly related to risk of CVD . Currently , Lp(a ) pathophysiology is not fully understood , and specifically targeted therapies to lower Lp(a ) are not available . We provide a rationale for increased basic and clinical investigational efforts to further underst and Lp(a ) pathophysiology and assess whether reducing Lp(a ) levels minimizes CVD risk . First , a detailed underst and ing of Lp(a ) synthesis and clearance has not been realized . Second , several mechanisms of atherogenicity are known to varying extent , but the relative contributions of each are not known . Lp(a ) may be atherothrombotic through its low-density lipoprotein moiety , but also through apo(a ) , including its ability to be retained in the vessel wall and mediate pro-inflammatory and proapoptotic effects including those potentiated by its content of oxidized phospholipids , and antifibrinolytic effects . Finally , development of specific Lp(a)-lowering agents to potently lower Lp(a ) will allow testing of mechanistic hypotheses in animal models and the design of r and omized clinical trials to assess reduction in CVD . A convergence of academic , scientific , pharmaceutical , and National Institutes of Health priorities and efforts can make this a reality in the next decade OBJECTIVE To examine the effects of unopposed estrogen ( E ) and tibolone therapy on coagulation and natural anticoagulant systems in surgical menopause . DESIGN A r and omized , double-blind , placebo-controlled study . SETTING University hospital clinic in Turkey . PATIENT(S ) Ninety healthy surgically postmenopausal women . INTERVENTION(S ) Ninety surgically postmenop 
    Output:
    
agent
This meta- analysis shows that oral tibolone treatment significantly lowers circulating Lp(a ) levels in postmenopausal women .
***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: Objective To assess the effects of tibolone on climacteric symptoms , endometrium and serum lipid/lipoproteins in postmenopausal women receiving tamoxifen after surgery for breast cancer OBJECTIVE To assess the effect of tibolone on markers of vascular risk in postmenopausal women who were receiving hemodialysis . DESIGN One-year open-label study . SETTING " Zvezdara " University Medical Center , Bel grade , Serbia . PATIENT(S ) Twenty-eight postmenopausal women undergoing chronic hemodialysis . INTERVENTION(S ) Fifteen women received tibolone 2.5 mg three times per week ; 13 other women served as controls . MAIN OUTCOME MEASURE(S ) Mean arterial pressure and weight were measured at baseline and at 6 and 12 months , and blood was collected for insulin , total cholesterol , low-density lipoprotein , high-density lipoprotein , triglycerides , lipoprotein(a ) , high-sensitivity C-reactive protein ( hs-CRP ) , endothelin-1 ( ET-1 ) , vascular endothelial growth factor ( VEGF ) , and markers of renal function . RESULT ( S ) Mean arterial pressure fell in the tibolone but not in the control group at 6 and 12 months versus baseline ( mean [ SD ] : 93 [ 15 ] vs. 105 [ 11 ] mmHg and 94 [ 10 ] vs. 105 [ 11 ] mmHg , respectively ) . Weight , insulin , lipids , lipoprotein(a ) , hs-CRP , ET-1 , VEGF , and renal function remained unchanged within each group , but high-density lipoprotein concentrations fell in the tibolone group after 12 months ( 1.2 [ 0.3 ] vs. 1.6 [ 0.6 ] mmol/L ) . CONCLUSION ( S ) The effects of tibolone on markers of vascular risk in postmenopausal women who are receiving hemodialysis and healthy women appear to differ . This should be taken into account when tailoring menopausal therapies to the specific requirements of each individual Background : Lipoprotein(a ) ( Lp(a ) ) has been regarded in some studies as an independent risk factor of atherosclerotic vascular disease . However , the use of a baseline plasma Lp(a ) concentration as a screening tool for future acute vascular events ( AVE ) is controversial . We therefore investigated whether progressively increasing change in plasma Lp(a ) concentration is associated with the development of AVE . Methods : We investigated prospect i ve analyses of 985 participants ( 464 women and 521 men ) who had either clinical ly evident vascular disease ( VD group , n=443 ) or its risk factor(s ) ( RF group , n=542 ) .  Blood sample s were taken from all participants every six months to measure inflammatory markers such as Lp(a ) and C-reactive protein during a 10-year follow-up period . Results : During the follow-up , 223 new cases of myocardial infa rct ion , stroke , and peripheral arterial disease were identified . In the RF group , the relative risk of positive ∆ Lp(a ) for predicting AVE was 4.36 ( 95 % confidence interval [ CI ] 1.76 - 10.85 ; P=0.002 ) . In the VD group , the relative risk of positive ∆ Lp(a ) for predicting AVE was 6.35 ( 95 % CI 3.68 - 10.97 ; P<0.001 ) . Conclusions : These results suggest that a progressively increasing change in Lp(a ) concentration has a highly significant predictive value in AVE in both the VD and the RF groups The effects of hormone replacement therapy in hypertensive women are controversial . This r and omised placebo controlled trial assessed the effect of tibolone 2.5 mg on blood pressure and fasting plasma lipids in 29 hypertensive postmenopausal women over 6 months using a 2:1 r and omisation to tibolone . The primary clinical end-point was mean office blood pressure . At 6 months systolic blood pressure declined by 5.30 ± 2.87 % vs4.94 ± 3.37 % whilst diastolic blood pressure declined 5.38 ± 2.65 % vs 0.85 ± 3.69 % on tibolone and placebo respectively . These differences were not statistically significant . Triglycerides decreased by 33.3 ± 6.1 % vs 7.6 ± 7.9 % ( P < 0.01 ) and high-density lipoprotein (hdl)-cholesterol by 21.7 ± 3.8 % vs2.4 ± 2.6 % ( P < 0.01 ) with tibolone as opposed to placebo . no significant differences were observed in total cholesterol , low-density lipoprotein (ldl)-cholesterol and lipoprotein ( a ) . fibrinogen levels were reduced by 13.6 ± 6.8 % on tibolone compared to a 19.3 ± 15.4 % rise ( P < 0.05 ) on placebo . this study suggests that tibolone has no deleterious effect on blood pressure in women with hypertension but has contrasting effects on biochemical risk factors . large-scale studies are required to determine the overall effect of tibolone on cardiovascular morbidity and mortality Tibolone , a synthetic steroid with estrogenic , and rogenic , and progestogenic properties relieves climacteric symptoms and prevents postmenopausal bone loss . The influence of tibolone treatment on coagulation , fibrinolysis , and lipid metabolism was investigated in 91 healthy late postmenopausal women . They were r and omly assigned in a double-blind , placebo-controlled 2-year study to receive either tibolone 1.25 mg ( n = 36 , 29 completed ) or 2.5 mg ( n = 35 , 28 completed ) or placebo ( n = 20 , 13 completed ) . The biochemical markers of lipid metabolism , fibrinolysis , and coagulation were measured every 3 months . In both tibolone groups a similar ( approximately 30 % ) decrease in high density lipoprotein cholesterol and a corresponding lowering of apolipoprotein A-1 ( P < 0.001 ) was detected . Also serum total cholesterol and triglycerides were reduced ( approximately 15 % ; P < 0.01 ) , whereas low density lipoprotein cholesterol , apolipoprotein B , and lipoprotein(a ) were unaffected by tibolone . The two dose levels of tibolone result ed in a similar , marked lowering ( approximately 30 % ) of tissue plasminogen activator and plasminogen activator inhibitor activity as compared with placebo ( P < 0.001 ) . Plasminogen increased ( approximately 15 % ; P < 0.001 ) in both groups . Fibrinogen was lowered ( P < 0.01 ) in the low-dose group , and antithrombin III remained unchanged . The overall effect on hemostatic factors of the present doses of tibolone in healthy , late postmenopausal women tends towards increased fibrinolysis and unchanged coagulation . This may be beneficial and might theoretically counterbalance the potentially negative effect of the decrease in high density lipoprotein cholesterol Background Lipoprotein(a ) [ Lp(a ) ] is a low density lipoprotein-like particle whose apolipoprotein B ( apo B ) moiety is disulfide-linked to apo(a ) , a plasminogen-like inhibitor of fibrinolysis in vitro . We hypothesized that plasma concentrations of Lp(a ) are acutely affected by intravenous tissue-type plasminogen activator ( t-PA ) . Methods and Results Patients with unstable angina were r and omized to receive either intravenous t-PA ( n = 15 ) or placebo ( n = 11 ) . Two-way ANOVA using repeated measures revealed a significant effect of t-PA on concentrations of Lp(a ) ( p=0.026 ) . There was a 48 % fall in Lp(a ) from baseline concentrations in the t-PA group at 12 hours ( p=0.031 ) but not at 72 hours . Lp(a ) in the placebo group was unchanged . Conclusions We conclude that t-PA produces a sharp and substantial but reversible reduction in plasma Lp(a ) . These data suggest that Lp(a ) concentration is not as static in vivo as had been believed and might be acutely modifiable through some mechanism that induces its removal from the freely circulating state Aims The aims of the study were , first , to critically evaluate lipoprotein(a ) [ Lp(a ) ] as a cardiovascular risk factor and , second , to advise on screening for elevated plasma Lp(a ) , on desirable levels , and on therapeutic strategies . Methods and results The robust and specific association between elevated Lp(a ) levels and increased cardiovascular disease (CVD)/coronary heart disease ( CHD ) risk , together with recent genetic findings , indicates that elevated Lp(a ) , like elevated LDL-cholesterol , is causally related to premature CVD/CHD . The association is continuous without a threshold or dependence on LDL- or non-HDL-cholesterol levels . Mechanistically , elevated Lp(a ) levels may either induce a prothrombotic/anti-fibrinolytic effect as apolipoprotein(a ) resembles both plasminogen and plasmin but has no fibrinolytic activity , or may accelerate atherosclerosis because , like LDL , the Lp(a ) particle is cholesterol-rich , or both . We advise that Lp(a ) be measured once , using an isoform-insensitive assay , in subjects at intermediate or high CVD/CHD risk with premature CVD , familial hypercholesterolaemia , a family history of premature CVD and /or elevated Lp(a ) , recurrent CVD despite statin treatment , ≥3 % 10-year risk of fatal CVD according to European guidelines , and /or ≥10 % 10-year risk of fatal + non-fatal CHD according to US guidelines . As a secondary priority after LDL-cholesterol reduction , we recommend a desirable level for Lp(a ) < 80th percentile ( less than ∼50 mg/dL ) . Treatment should primarily be niacin 1–3 g/day , as a meta- analysis of r and omized , controlled intervention trials demonstrates reduced CVD  by niacin treatment . In extreme cases , LDL-apheresis is efficacious in removing Lp(a ) . Conclusion We recommend screening for elevated Lp(a ) in those at intermediate or high CVD/CHD risk , a desirable level < 50 mg/dL as a function of global cardiovascular risk , and use of niacin for Lp(a ) and CVD/CHD risk reduction Recent published studies have provided increasing evidence that lipoprotein(a ) [ Lp(a ) ] may be a potential causal , genetic , independent risk factor for cardiovascular disease ( CVD ) . Lp(a ) levels > 25 mg/dl are present in ∼30 % of Caucasians and 60 % to 70 % of Blacks . Lp(a ) is composed of apolipoprotein B-100 and apolipoprotein ( a ) [ ( apo(a ) ] . Circulating Lp(a ) levels are primarily influenced by the LPA gene without significant dietary or environmental effects , mediating CVD risk throughout the patient 's lifetime . Recent clinical outcomes studies , meta-analyses , and Mendelian r and omization studies , in which r and omization of Lp(a ) levels is achieved through the r and om assortment of LPA gene variants thereby removing confounders , have shown that genetically determined Lp(a ) levels are continuously and linearly related to risk of CVD . Currently , Lp(a ) pathophysiology is not fully understood , and specifically targeted therapies to lower Lp(a ) are not available . We provide a rationale for increased basic and clinical investigational efforts to further underst and Lp(a ) pathophysiology and assess whether reducing Lp(a ) levels minimizes CVD risk . First , a detailed underst and ing of Lp(a ) synthesis and clearance has not been realized . Second , several mechanisms of atherogenicity are known to varying extent , but the relative contributions of each are not known . Lp(a ) may be atherothrombotic through its low-density lipoprotein moiety , but also through apo(a ) , including its ability to be retained in the vessel wall and mediate pro-inflammatory and proapoptotic effects including those potentiated by its content of oxidized phospholipids , and antifibrinolytic effects . Finally , development of specific Lp(a)-lowering agents to potently lower Lp(a ) will allow testing of mechanistic hypotheses in animal models and the design of r and omized clinical trials to assess reduction in CVD . A convergence of academic , scientific , pharmaceutical , and National Institutes of Health priorities and efforts can make this a reality in the next decade OBJECTIVE To examine the effects of unopposed estrogen ( E ) and tibolone therapy on coagulation and natural anticoagulant systems in surgical menopause . DESIGN A r and omized , double-blind , placebo-controlled study . SETTING University hospital clinic in Turkey . PATIENT(S ) Ninety healthy surgically postmenopausal women . INTERVENTION(S ) Ninety surgically postmenop 
    Output:
    