Tibolone: influence on markers of cardiovascular disease. Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies. Effect of tibolone on markers of cardiovascular disease risk in postmenopausal women undergoing hemodialysis: a pilot study. Observational Study on the Efficacy of Tibolone in Counteracting Early Carotid Atherosclerotic Lesions in Postmenopausal Women A 2‐year Study of Lipid and Lipoprotein Changes in Postmenopausal Women With Tibolone and Estrogen‐Progestin Increased plasma concentrations of TGF-beta1 after hormone replacement therapy. Lipoprotein(a) as a cardiovascular risk factor: current status The influence of 5-year therapy with tibolone on the lipid profile in postmenopausal women with mild hypercholesterolemia Predictive value of electrophoretically detected lipoprotein(a) for coronary heart disease and cerebrovascular disease in a community-based cohort of 9936 men and women. Lowering of HDL cholesterol in post-menopausal women by tibolone is not associated with changes in cholesterol efflux capacity or paraoxonase activity. Hormonal regulation of lipoprotein(a) levels: effects of estrogen replacement therapy on lipoprotein(a) and acute phase reactants in postmenopausal women. Effects of either Tibolone or Continuous Combined Transdermal Estradiol with Medroxyprogesterone Acetate on Coagulatory Factors and Lipoprotein(a) in Menopause A prospective evaluation of lipoprotein-associated phospholipase A(2) levels and the risk of future cardiovascular events in women. The EWA (estrogen in women with atherosclerosis) study: a randomized study of the use of hormone replacement therapy in women with angiographically verified coronary artery disease. Characteristics of the study population. Effects on lipids and lipoproteins. A randomised placebo controlled trial of the effects of tibolone on blood pressure and lipids in hypertensive women Atherogenic forms of dyslipidaemia in women with polycystic ovary syndrome. Serum Lp(a) lipoprotein levels in patients with coronary artery disease and the influence of long-term n-3 fatty acid supplementation.
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 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 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 Objective : To study whether tibolone affects lipid profile and diffused intima media thickness ( IMT ) of the common carotid arteries ( CCA ) in postmenopausal women ( PMW ) . Methods : Twenty-two PMW and 20 premenopausal women participated in the study . The PMW were r and omly divided into 11 women who did not receive any treatment and 11 women who received tibolone ( 2.5 mg once a day ) . Results : After 6 months the treated women had lipoprotein(a ) ( Lpa ) , total-cholesterol ( total-C ) , and LDL-cholesterol ( LDL-C ) levels lower than before , while in the non-treated women Lpa was increased . The IMT of CCA was unmodified in the treated women , whereas it increased in non-treated women . Conclusions : This preliminary study suggests that a 6-month tibolone treatment could counteract the increase of the IMT of CCA observed in untreated PMW Objective To assess changes in lipid-lipoprotein profile in postmenopausal women taking tibolone and estrogenprogestin  , compared with untreated controls . Methods Sixty-three women were r and omized to take a combined estrogen-progestin preparation ( n = 31 ) or tibolone ( n = 32 ) , and 50 other women acted as controls . Fasting lipid-lipoprotein levels were measured over 96 weeks . Results The controls , who were older and postmenopausal longer than the therapy subjects , exhibited significant decreases in total ( P < .05 ) and low-density lipoprotein ( LDL ) ( P < .001 ) cholesterol and increases in triglyceride ( P < .05 ) and lipoprotein ( a ) ( P < .001 ) over the 96-week period of study . Lipoprotein ( a ) also decreased significantly in both treated groups ( P < .001 ) . Total and LDL cholesterol decreased and triglyceride increased in the estrogenprogestin group , but , compared with controls , these changes were not significant . Total cholesterol decreased in the tibolone group , although decreases in low- and particularly high-density lipoprotein ( HDL ) ( P < .001 ) cholesterol and parallel decreases in apolipoprotein A1 ( P < .001 ) and B ( P < .01 ) were also observed . There was evidence of a reversion phenomenon in apolipoproteins A1 and B in all groups , and in lipoprotein ( a ) with tibolone . Conclusion Some changes accompanying tibolone may be favorable and may counter its adverse effect on HDL cholesterol . Lowering of lipoprotein ( a ) was the only significant change found with estrogen-progestin OBJECTIVES AND DESIGN Hormone replacement therapy ( HRT ) in postmenopausal women may reduce the cardiovascular risk . A dominant protective role of transforming growth factor beta ( TGF-beta1 ) on coronary arteries has been proposed . Lp(a ) lipoprotein may block the activation of latent TGF-beta1 . Given this background , we examined the effects of HRT on TGF-beta1 and Lp(a ) lipoprotein in 99 postmenopausal women . The women had angiographically documented coronary heart disease ( CHD ) and were r and omized to either sequential transdermal 17beta-oestradiol for 14 weeks and then medroxyprogesterone ( MPA ) for 14 days ( HRT ) or to a control group ( C ) . RESULTS Serum levels of TGF-beta1 were increased in the HRT group compared with the C group after 3 months ' treatment and this effect was sustained after 12 months . There was a significant reduction in Lp(a ) lipoprotein serum levels after 3 months ' treatment in the HRT group compared with the C group . However , after 12 months , no significant difference in changes in Lp(a ) lipoprotein serum levels was detected between the two groups . CONCLUSION The novel observation that transdermal 17beta-oestradiol in postmenopausal women increases levels of TGF-beta1 and lowers the concentration of Lp(a ) lipoprotein suggests yet another possible mechanism for the cardioprotective effect of HRT . Whereas combination therapy of oestradiol and MPA preserves the beneficial effect on TGF-beta1 , it reduces the unopposed oestradiol effects on Lp(a ) lipoprotein 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 Our objective was to investigate the effects of 5-year therapy with tibolone on the lipid profile in postmenopausal women with mild hypercholesterolemia ( total cholesterol , 241 ± 7 mg/dl ; LDL cholesterol , 153 ± 9 mg/dl ) . Eighty-two patients were divided into two groups . Group A ( 53 women ) received 2.5 mg of tibolone per day . Group B ( 29 women ) received no tibolone . Total , low- and high-density lipoprotein cholesterol and lipoprotein(a ) were found to be decreased in the tibolone group , by 17.7 % , 32 % , 15.5 % and 12 % , respectively ( p < 0.01 ) throughout the 5-year treatment , while triglycerides showed no significant change . The lipid profile in the control group remained at its initial values . Menopausal symptoms disappeared in the treatment group within the first 5 months , whereas they deteriorated in the control group during the first 2 years . Although a few unwanted side-effects on hormonedependent tissues were observed ( including vaginal spotting in 11.3 % and febrile hemorrhagic cystic mastopathy in 3.8 % ) long-term therapy with tibolone seemed to be well tolerated , and appeared to have a beneficial effect on the levels of serum lipids BACKGROUND Elevated  lipoprotein(a ) [ Lp(a ) ] levels have been associated with the presence of atherosclerotic disease . However , the results of prospect i ve studies of Lp(a ) and cardiovascular disease have been contradictory . METHODS AND RESULTS From 1968 through 1982 , lipoprotein analysis  was performed in 11,335 Olmsted County residents . Quantitative  cholesterol  and  triglycerides  were obtained along with semiquantitative Lp(a ) levels based on electrophoretic pattern . Lp(a ) b and s were scored from 0 ( absent ) to 3 ( increased ) . A cohort of 4967 men and 4968 women with no prior history of atherosclerotic disease who had baseline Lp(a ) determinations were followed up for 14 years for development of coronary artery disease ( CAD ) and cerebrovascular disease ( CVD ) . During 131,330 person-years of follow-up , there were 1848 CAD events and 841 CVD events . Age , diabetes , hypertension , cholesterol , and triglycerides were significantly and independently associated with an increased risk of CAD and CVD in men and women . There was a significant increase in the adjusted hazards ratio for CAD with increasing Lp(a ) levels for men and women . For Lp(a ) level 3 , the hazard ratio was 1.9 ( range , 1.3 to 2.9 ) in women and 1.6 ( range , 1.0 to 2.5 ) in men . The adjusted hazard ratio for CVD showed an irregular association with Lp(a ) levels in men and no association in women . CONCLUSIONS In this cohort of 9936 men and women initially free of cardiovascular disease who were followed up for 14 years , Lp(a ) was a significant predictor of risk of future CAD . Lp(a ) was a weak risk factor for CVD in men and was not a significant predictor of CVD risk in women Low HDL cholesterol increases the risk of coronary heart disease . Treatment of postmenopausal women with tibolone  lowers  HDL cholesterol . We eluci date d the consequences of this unwanted side effect in a r and omized , double-blind study , where 12 women received 2.5 mg tibolone per day and 6 women , placebo .  Blood sample s were collected on days -1 ( i.e. baseline ) , 28 , 56 , and 84 for the analysis of various parameters of lipid metabolism and HDL function . Compared to placebo , treatment with tibolone led to statistically significant decreases of HDL cholesterol ( -22 % to -32 % ) , apoA-I ( -14 % to -22 % ) , and HDL subclass LpA-I ( -30 % to -40 % ) but to no significant changes in apoA-II and HDL subclass LpA-I , A-II . These changes were not associated with statistically significant changes in the activity of plasma to release 3H-cholesterol from radiolabeled fibroblasts or in the serum activity of the anti-oxidative enzyme paraoxonase/arylesterase . There were no significant changes in either serum levels of triglycerides , LDL cholesterol , apoB , and leptin , or in LDL size . We conclude that changes in insulin do not contribute to the lowering of HDL cholesterol by tibolone . Despite decreased HDL cholesterol , putatively anti-atherogenic activities of HDL remained unchanged Estrogen lowers lipoprotein(a ) [ Lp(a ) ] levels , but the mechanisms involved have not been clarified . To address the relationship between estrogenic effects on Lp(a ) and serum lipids , and on other plasma proteins of hepatic origin , 15 healthy postmenopausal women participated in a r and omized , double-blinded , placebo-controlled , crossover study with 4 weeks of oral conjugated estrogens ( 0.625 mg/d ) and placebo , separated by a 6-week period . Lp(a ) levels decreased during estrogen treatment in 14 of the 15 subjects ( mean decrease , 23 % ; P < .001 ) . In response to estrogen , apolipoprotein A-I ( apoA-I ) , HDL cholesterol , and triglyceride levels increased by 12 % ( P = .001 ) , 11 % ( P < .001 ) , and 10 % ( P = .02 ) , respectively . Apolipoprotein B ( apoB ) and LDL cholesterol levels decreased by 7 % ( P = .01 ) and 12 % ( P = .03 ) , respectively , ApoB , LDL cholesterol , and Lp(a ) levels fell within 1 week of treatment , whereas apoA-I and HDL cholesterol levels rose more slowly . Levels of acid alpha 1-glycoprotein ( AAG ) and haptoglobin ( HPT ) , two hepatically derived acute phase proteins , also decreased during estrogen treatment by 18 % ( P < .001 ) and 25 % ( P = .002 ) , respectively . Although the changes in AAG and HPT in response to estrogen were highly correlated ( r = .67 , P = .009 ) , we were unable to detect a correlation between change in either acute phase protein and change in Lp(a ) ( r = -.14 and -.24 , P = .64 and .41 ) . The lack of correlation between the changes in two acute phase reactants and Lp(a ) suggests different underlying mechanisms for the effects of estrogen on these liver-derived proteins Background / Aim : The aim of this prospect i ve controlled study was to compare the effects of two therapies for menopause on factor VII ( FVII ) and hemostatic variables . Methods : Postmenopausal women were assigned to receive one of the following treatments : transdermal estradiol ( TTS E2 ; 50 μg ) combined in a continuous sequential regimen with oral medroxyprogesterone acetate ( MPA ; 10 mg/day for 12 days ) ( group A ; n = 20 ) , tibolone ( 2.5 mg/day ) ( group B ; n = 21 )  or placebo  ( group C ; n = 19 ) . Sixty women completed the 1-year treatment and underwent follow-up examinations after 3 , 6 and 12 months . Results : TTS E2/MPA induced various changes in procoagulatory factors . At 12 months , fibrinogen , activated FVII ( FVIIa ) and coagulative FVII ( FVIIc ) had increased by 10.7 , 12.9 and 3.7 % , respectively . Among the fibrinolytic factors , plasminogen and α2-antiplasmin increased by 11.3 and 7.2 % , respectively . Lipoprotein(a ) [ Lp(a ) ] and antithrombin III ( ATIII ) did not show any significant variation . Tibolone induced some changes toward a more homogeneous antithrombotic profile . Fibrinogen , FVIIa and FVIIc decreased significantly by 7.5 , 8.1 and 21.3 % , respectively . Plasminogen increased ( by 11.8 % ) and Lp(a ) decreased ( by 28.4 % ) . ATIII was unchanged with tibolone therapy . Conclusion : Our results show that tibolone induces a significant reduction in FVIIc and Lp(a ) and a greater enhancement of factors promoting fibrinolysis than the TTS E2/MPA regimen OBJECTIVES We sought to determine prospect ively whether lipoprotein-associated phospholipase A(2 ) ( Lp-PLA(2 ) ) was a predictor of future cardiovascular risk in women . BACKGROUND Inflammatory markers may help predict cardiovascular risk . Lp-PLA(2 ) levels have recently been hypothesized to be an independent predictor of cardiovascular risk in hypercholesterolemic men . METHODS We conducted a prospect i ve , nested case-control study among 28,263 apparently healthy middle-aged women to assess the risk of death from coronary heart disease , non-fatal myocardial infa rct ion , and stroke associated with baseline levels of Lp-PLA(2 ) over a mean follow-up of three years . RESULTS In univariate analysis , mean levels of Lp-PLA(2 ) correlated strongly with low-density lipoprotein cholesterol ( r = 0.51 ; p = 0.0001 ) , were lower among women currently using hormone replacement therapy ( mean 0.98 mg/l vs. 1.23 mg/l ; p = 0.0001 ) and were significantly higher at baseline among cases ( n = 123 ) than controls ( n = 123 ) ( mean 1.20 mg/l vs. 1.05 mg/l ; p = 0.016 ) . However , the predictive value of Lp-PLA(2 ) was markedly attenuated after adjustment for these and other cardiovascular risk factors . Specifically , the multivariate relative risks of future cardiovascular events for women in the lowest ( referent ) to highest quartiles of Lp-PLA(2 ) were 1.00 , 0.75 , 0.64 and 1.17 , respectively ( all p values non-significant ) . In contrast , the adjusted relative risks of future cardiovascular events for each increasing quartile of C-reactive protein ( another marker of low- grade inflammation ) were 1.00 , 1.78 , 2.02 and 4.66 , respectively ( p-value for trend = 0.002 ) . Inclusion of Lp-PLA(2 ) levels did not significantly attenuate this latter observation . CONCLUSIONS In contrast to prior data among hyperlipidemic men , the current data suggest that Lp-PLA(2 ) is not a strong predictor of future cardiovascular risk among unselected women OBJECTIVES To evaluate the effects of hormone replacement therapy ( HRT ) on lipids and lipoproteins in postmenopausal women with coronary artery disease . SETTING In this single-centre , controlled and r and omized study taking place in a tertiary referral clinic , patients were examined at baseline , and after 3 and 12 months . All analyses were performed examiner-blind . SUBJECTS Postmenopausal women ( n = 118 ) with angiographically verified coronary artery disease were recruited consecutively from patients referred for investigational procedures due to coronary artery disease . INTERVENTIONS The women were r and omized to HRT , i.e. transdermal application of continuous 17-beta oestradiol with cyclic medroxyprogesterone actetate tablets every 3rd month for 14 days , or to a control group . MAIN OUTCOMES Effects on lipids and lipoproteins . RESULTS After 3 months of unopposed oestradiol , triglycerides decreased significantly compared to the control group ( P = 0.006 ) . Sequential administration of medroxyprogesterone caused a decrease in HDL cholesterol ( P = 0.01 ) , concomitantly with a decrease in ApoA1 lipoproteins ( P = 0.007 ) . No other changes in lipids or lipoproteins were observed . After 12 months of therapy , no significant differences were observed between the two groups in lipid or lipoprotein levels . Concomitant statin treatment did not alter the main findings . CONCLUSIONS In postmenopausal women with established coronary artery disease in whom the majority is treated with statins , no additional effect of HRT on lipids or lipoproteins could be observed except for a transient decrease in triglycerides in the initial unopposed oestradiol phase . No deleterious effect could be observed during medroxyprogesterone administration except for a small transient decrease in HDL cholesterol and ApoA1 lipoproteins 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 OBJECTIVE Dyslipidaemia is very common in patients with polycystic ovary syndrome ( PCOS ) but , beyond plasma lipids , atherogenic lipoprotein ( Lp ) and apolipoprotein ( apo ) alterations are still ill defined . DESIGN We measured concentrations of apoB , Lp(a ) and small , dense low-density lipoprotein ( LDL )  in 42 patients with PCOS [ age : 28 + /- 7 years , body mass index ( BMI ): 27 + /- 5 kg/m(2 ) ] vs. 37 age- and BMI -matched healthy controls . METHODS Elevated  Lp(a ) levels  considered were those > 30 mg/dl while elevated apoB concentrations were those > 100 g/l . RESULTS Polycystic ovary syndrome showed increased triglycerides levels ( p = 0.0011 ) and lower high-density lipoprotein (HDL)-cholesterol concentrations ( p = 0.0131 ) while total- and LDL cholesterol were similar . PCOS also showed smaller LDL size ( p = 0.0005 ) , higher levels of total small , dense LDL ( p < 0.0001 ) , higher concentrations of Lp(a ) , as considered as absolute values ( p = 0.0143 ) and log-transformed ( p = 0.0014 ) , while no differences were found in apoB levels . Elevated Lp(a ) concentrations were found in 24 % of PCOS , while elevated apoB levels were relatively uncommon ( 14 % ) . Spearman correlation analysis revealed that Lp(a ) concentrations were weakly correlated only with HDL-cholesterol levels ( r = -0.378 , p = 0.0431 ) . In addition , 36 % of patients with PCOS with normal plasma lipid profile showed elevated levels of Lp(a ) , apoB or small , dense LDL . CONCLUSIONS Atherogenic Lp abnormalities may be found in one-third of women with PCOS who have a normal lipid pattern . Future prospect i ve studies are needed to test to which extent such atherogenic forms of dyslipidaemia may contribute to the increased cardiovascular risk in young women with PCOS The serum levels of  Lp(a ) lipoprotein ( Lp(a ) ) were determined preoperatively in 601 patients with coronary artery disease , undergoing bypass operations .  Compared with a reference group of 99 apparently healthy individuals , the Lp(a ) levels were higher in the patient group ( 7.7 mg dl-1 vs. 5.1 mg dl-1 , p = 0.012 ) . In the patient group , there was a weak , but significant negative correlation between the Lp(a ) levels and age ( r = -0.10 , p = 0.017 ) , and in both groups the women had higher Lp(a ) levels than the men . In the patients we found no significant correlations between Lp(a ) and other serum lipids or lipoproteins , nor between Lp(a ) and variables in the fibrinolytic system . We investigated the long-term effects of supplementation with n-3 polyunsaturated fatty acids ( n-3 PUFAs ) on the Lp(a ) concentrations . Postoperatively , in a r and omized fashion , 280 of the patients received 4 g of an n-3 PUFA concentrate ( containing > 85 % of long-chain n-3 PUFAs ) per day , whereas 269 patients comprised the control group . The fatty acids in serum phospholipids were monitored , and a significant increase in the phospholipid n-3 fatty acids was noted in the n-3 PUFA group , as opposed to the virtually unchanged amounts in the control group . The Lp(a ) levels were determined again after 6 months , and , compared with the control group , n-3 PUFA supplementation had no overall effect on the serum Lp(a ) levels
This meta- analysis shows that oral tibolone treatment significantly lowers circulating Lp(a ) levels in postmenopausal women .
INTRODUCTION Circulating lipoprotein ( a ) ( Lp(a ) ) is a recognized risk factor for cardiovascular disease ( CVD ) .
Tibolone , a synthetic steroid , may lower Lp(a ) levels ; however , evidence of the effects of tibolone on Lp(a ) still remain to be defined .
Therefore , we investigated the effects of tibolone treatment on circulating Lp(a ) levels in postmenopausal women .