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. Differential Effect of Hypolipidemic Drugs on Lipoprotein-Associated Phospholipase A2 Lipoprotein(a) as a cardiovascular risk factor: current status Long term statin treatment reduces lipoprotein(a) concentrations in heterozygous familial hypercholesterolaemia Lipoprotein(a) Concentrations, Rosuvastatin Therapy, and Residual Vascular Risk: An Analysis From the JUPITER Trial (Justification for the Use of Statins in Prevention An Intervention Trial Evaluating Rosuvastatin) Atorvastatin lowers lipoprotein(a) but not apolipoprotein(a) fragment levels in hypercholesterolemic subjects at high cardiovascular risk. Role of lipoprotein(a) and apolipoprotein(a) phenotype in atherogenesis: prospective results from the Bruneck study. Lipoprotein (a) as a predictor of coronary heart disease: the PRIME Study. Serially increasing change in lipoprotein(a) concentration has predictive value in acute vascular events Is lipoprotein(a) a predictor for survival in patients with established coronary artery disease? Results from a prospective patient cohort study in northern Sweden. Effect of niacin and atorvastatin on lipoprotein subclasses in patients with atherogenic dyslipidemia. Lipoprotein(a) and cholesterol levels act synergistically and apolipoprotein A-I is protective for the incidence of primary acute myocardial infarction in middle-aged males. An incident case-control study from Sweden. Effects of gemfibrozil or simvastatin on apolipoprotein-B-containing lipoproteins, apolipoprotein-CIII and lipoprotein(a) in familial combined hyperlipidaemia. Interactions between fibrinolysis, lipoproteins and leptin related to a first myocardial infarction Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials. Lipoprotein (a) and coronary heart disease risk: a nested case-control study of the Helsinki Heart Study participants. Lowering of lipoprotein(a) level under niacin treatment is dependent on apolipoprotein(a) phenotype.
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 — Lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) is a predictor for incident atherosclerotic disease . We investigated the effect of 3 hypolipidemic drugs that exert their action through different mechanisms on plasma and lipoprotein-associated Lp-PLA2 activity and mass . Methods and Results — In 50 patients with Type IIA dyslipidemia were administered rosuvastatin ( 10 mg daily ) , whereas in 50 Type IIA dyslipidemic patients exhibiting intolerance to previous statin therapy were administered ezetimibe as monotherapy ( 10 mg daily ) . Fifty patients with Type IV dyslipidemia were given micronised fenofibrate ( 200 mg daily ) . Low- and high-density lipoprotein ( LDL and HDL , respectively ) subclass analysis was performed electrophoretically , whereas lipoprotein subfractions were isolated by ultracentrifugation . Ezetimibe reduced plasma Lp-PLA2 activity and mass attributable to the reduction in plasma levels of all LDL subfractions . Rosuvastatin reduced enzyme activity and mass because of the decrease in plasma levels of all LDL subfractions and especially the Lp-PLA2 on dense LDL subfraction ( LDL-5 ) . Fenofibrate preferentially reduced the Lp-PLA2 activity and mass associated with the VLDL+IDL and LDL-5 subfractions . Among studied drugs only fenofibrate increased HDL-associated Lp-PLA2 ( HDL-Lp-PLA2 ) activity and mass attributable to a preferential increase in Lp-PLA2 associated with the HDL-3c subfraction . Conclusion — Ezetimibe , rosuvastatin , and fenofibrate reduce Lp-PLA2 activity and mass associated with the atherogenic apoB-lipoproteins . Furthermore , fenofibrate improves the enzyme specific activity on apoB-lipoproteins and induces the HDL-Lp-PLA2 . The clinical implication s of these effects remain to be established 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 Background : Raised plasma lipoprotein(a ) ( Lp(a ) ) is associated with increased risk of cardiovascular disease . It is unknown whether increased Lp(a ) is an additional risk factor for coronary artery disease in familial hypercholesterolaemia ( FH ) or whether statin treatment can reduce Lp(a ) concentrations in the long term . Objective : To investigate Lp(a ) concentrations in relation to statin treatment and the progression of atherosclerosis in a large cohort of FH patients . Design : A two year , r and omised , double blind trial ( the ASAP trial ) . Patients : 325 heterozygous FH patients . Intervention : Treatment with 80 mg atorvastatin or 40 mg simvastatin . Main outcome measure : Change in Lp(a ) concentrations and intima – media thickness of carotid artery segments at one year and two years . Results : At baseline , median Lp(a ) concentrations were 327 mg/l and 531 mg/l in the atorvastatin and simvastatin arms , respectively ( p = 0.03 ) . In the atorvastatin arm , Lp(a ) concentrations decreased to 243 mg/l after one year ( p < 0.001 ) and to 263 mg/l after two years ( p < 0.001 ) . In the simvastatin arm , Lp(a ) concentrations decreased to 437 mg/l after one year ( p < 0.001 ) and to 417 mg/l after two years ( p < 0.001 ) . The difference in Lp(a ) reduction between the two treatment arms was significant after one year ( p = 0.004 ) , but not after two years ( p = 0.086 ) . Lp(a ) concentrations at baseline were not related to cardiovascular events at baseline . There was no correlation between baseline Lp(a ) concentrations and low density lipoprotein cholesterol concentrations or intima – media thickness at baseline . Change in Lp(a ) concentrations was not correlated with change in intima – media thickness after one or two years . Conclusions : Long term statin treatment significantly lowers Lp(a ) in FH patients . However , this reduction was unrelated to changes in intima – media thickness and casts doubt on the importance of Lp(a ) in the progression of atherosclerotic disease in these patients Background — Lipoprotein(a ) [ Lp(a ) ] is a low-density lipoprotein – like particle largely independent of known risk factors and predictive of cardiovascular disease . Statins may offset the risk associated with elevated Lp(a ) , but it is unknown whether Lp(a ) is a determinant of residual risk in the setting of low low-density lipoprotein cholesterol after potent statin therapy . Methods and Results — Baseline and on-treatment Lp(a ) concentrations were assessed in 9612 multiethnic participants in the JUPITER trial ( Justification for the Use of Statins in Prevention : An Intervention Trial Evaluating Rosuvastatin ) before and after r and om allocation to rosuvastatin 20 mg/d or placebo , with outcomes reported for whites ( n=7746 ) .  Lp(a ) concentrations ( median [ 25th–75th percentile ] , in nmol/L ) were highest in blacks ( 60 [ 34–100 ] ) , then Asians ( 38 [ 18–60 ] ) , Hispanics ( 24 [ 11–46 ] ) , and whites ( 23 [ 10–50 ] ; P<0.001 ) . Although the median change in Lp(a ) with rosuvastatin and placebo was zero , rosuvastatin nonetheless result ed in a small but statistically significant positive shift in the overall Lp(a ) distribution ( P<0.0001 ) . Baseline Lp(a ) concentrations were associated with incident cardiovascular disease ( adjusted hazard ratio per 1-SD increment in Ln[Lp(a ) ] , 1.18 ; 95 % confidence interval , 1.03–1.34 ; P=0.02 ) . Similarly , on-statin Lp(a ) concentrations were associated with residual risk of cardiovascular disease ( adjusted hazard ratio , 1.27 ; 95 % confidence interval , 1.01–1.59 ; P=0.04 ) , which was independent of low-density lipoprotein cholesterol and other factors . Rosuvastatin significantly reduced incident cardiovascular disease among participants with baseline Lp(a ) greater than or equal to the median ( hazard ratio , 0.62 ; 95 % confidence interval , 0.43–0.90 ) and Lp(a ) less than the median ( hazard ratio , 0.46 ; 95 % confidence interval , 0.30–0.72 ) , with no evidence of interaction . Similar results were obtained when analyses included nonwhites . Conclusion — Among white JUPITER participants treated with potent statin therapy , Lp(a ) was a significant determinant of residual risk . The magnitude of relative risk reduction with  rosuvastatin was similar among participants with high or low Lp(a ) . Clinical Trials Registration — URL : http://www . clinical trials.gov . Unique identifier : NCT00239681 The effect of statins on Lp(a ) levels is controversial ; furthermore , the potential action of statins on apo(a ) fragmentation is indeterminate . We therefore determined the circulating levels of Lp(a ) and of apo(a ) fragments in hypercholesterolemic patients before and after treatment ( 6 weeks ) with Atorvastatin 10 mg/day ( A10 ) or Simvastatin 20 mg/day ( S20 ) . In a double blind study , hypercholesterolemic patients ( n=391 ) at high cardiovascular risk ( LDL-C>=4.13 mmol/l ; TG<2.24 mmol/l ; 34 % with documented CHD ; 45 % hypertensive ; and 29 % current smokers ) were assigned to treatment with A10 ( n=199 ) or S20 ( n=192 ) . Plasma Lp(a ) and apo(a ) fragment levels ( n=206 ) were measured prior to and after treatment . At baseline , A10 and S20 groups did not differ in plasma levels of lipids , Lp(a ) ( A10 : 0.45+/-0.48 mg/ml , S20 : 0.46+/-0.5 ) , and apo(a ) fragments ( A10 : 3.88+/-5.22 microg/ml ; S20 : 3.25+/-3 ) , and equally in apo(a ) isoform size ( A10 : 26+/-5 kr , S20 : 25.5+/-5.3 ) . After treatment , both statins significantly reduced Lp(a ) levels ( A10 : 0.42+/-0.47 mg/ml , 6 % variation , P<0.001 ; S20 : 0.45+/-0.53 mg/ml , 0.02 % variation , P=0.046 ) . A10 and S20 did not significantly differ in their efficacy to lower Lp(a ) levels . In a multivariate logistic regression analysis , the reduction of Lp(a ) levels was independently associated with Lp(a ) baseline concentration , but not to other variables , including LDL-C reduction . Plasma levels of apo(a ) fragments were not modified by either statin . In conclusion , both A10 and S20 significantly lowered Lp(a ) , although this effect was of greater magnitude in atorvastatin-treated patients BACKGROUND Experimental studies have suggested both atherogenic and thrombogenic properties of lipoprotein(a ) [ Lp(a ) ] , depending on Lp(a ) plasma concentrations and varying antifibrinolytic capacity of apolipoprotein(a ) [ apo(a ) ] isoforms . Epidemiological studies may contribute to assessment of the relevance of these findings in the general population . METHODS AND RESULTS This study prospect ively investigated the association between Lp(a ) plasma concentrations , apo(a ) phenotypes , and the  5-year progression of carotid atherosclerosis assessed by high-resolution duplex ultrasound in a r and om sample population of 826 individuals . We differentiated early atherogenesis ( incident nonstenotic atherosclerosis ) from advanced ( stenotic ) stages in atherosclerosis that originate mainly from atherothrombotic mechanisms . Lp(a ) plasma concentrations predicted the risk of early atherogenesis in a dose-dependent fashion , with this association being confined to subjects with LDL cholesterol levels above the population median ( 3.3 mmol/L ) . Apo(a ) phenotypes were distributed similarly in subjects with and without early carotid atherosclerosis . In contrast , apo(a ) phenotypes of low molecular weight emerged as one of the strongest risk predictors of advanced stenotic atherosclerosis , especially when associated with high Lp(a ) plasma concentrations ( odds ratio , 6.4 ; 95 % CI , 2.8 to 14 . 9 ) . CONCLUSIONS Lp(a ) is one of the few risk factors capable of promoting both early and advanced stages of atherogenesis . Lp(a ) plasma concentrations predicted the risk of early atherogenesis synergistically with high LDL cholesterol . Low-molecular-weight apo(a ) phenotypes with a putatively high antifibrinolytic capacity in turn emerged as one of the leading risk conditions of advanced stenotic stages of atherosclerosis The association of an elevated level of  lipoprotein ( a ) ( Lp(a ) ) with the development of coronary heart disease ( CHD ) remains controversial . Lp(a ) was investigated as a CHD risk factor in the PRIME Study , a prospect i ve cohort study which included 9133 French and Northern Irish men aged 50 - 59 at entry , without a history of CHD and not on hypolipidaemic drugs .  During a follow-up of 5 years , 288 subjects experienced at least one CHD event ( myocardial infa rct ion ( MI ) , coronary death , angina pectoris ) .  Lp(a )  was measured by immunoassay in all subjects on fresh plasma obtained at entry . Traditional cardiovascular risk factors such as low-density lipoproteins (LDL)-cholesterol , HDL-cholesterol , triglycerides , the presence of diabetes , hypertension or smoking were determined . Logistic regression analysis was used to evaluate Lp(a ) level as a CHD risk factor after controlling for the other risk factors . In addition , its possible interaction with LDL- and HDL-cholesterol levels was investigated . Lp(a ) appeared a significant risk factor ( P<0.0006 ) in the whole cohort without between- population interaction , even if the association was not statistically significant in the Belfast sample . The relative risk ( RR ) of CHD events in subjects with Lp(a ) levels in the highest quartile was 1.5 times that of subjects in the lowest quartile ( RR : 1.56 ; 95 % confidence intervals ( CIs ) : 1.10 - 2.21 ) . A high Lp(a ) level was a risk for MI , coronary death and angina pectoris . A significant interaction term between Lp(a ) and LDL-cholesterol levels , however , was found . The relative CHD risk associated with a Lp(a ) level > or = 33 mg/dl in comparison with Lp(a ) <33 mg/dl increasing gradually from 0.82 ( 95 % CI : 0.28 - 2.44 ) in men with LDL-cholesterol in the lowest quartile ( < 121 mg/dl ) to 1.58 ( 95 % CI : 1.06 - 2.40 ) in the highest quartile ( > 163 mg/dl ) . In conclusion , Lp(a ) increased the risk for MI and angina pectoris , especially in men with a high LDL-cholesterol level . This study which analyzed Lp(a ) level using a measurement independent of apolipoprotein ( a ) size on fresh plasma , has confirmed utility of Lp(a ) as a predictor of CHD 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 OBJECTIVES Lipoprotein(a ) [ Lp(a ) ] is a known risk factor for the development of atherosclerosis . The aim of the present study was to test the importance of Lp(a ) as a predictor for the further prognosis in patients with established coronary artery disease . DESIGN A prospect i ve patient cohort study was carried out . SETTING AND SUBJECTS The cohort consists of 1216 patients who were examined with coronary angiography at the University Hospital in Umeå , Sweden , because of stable effort angina . MAIN OUTCOME MEASURES Lipids , Lp(a ) , fibrinogen , antithrombin III ( AT III ) , sedimentation rate and clinical data were registered at angiography . After a mean follow-up time of 6.7 years information on survival was collected from the municipal census lists and death certificates were examined . Total mortality and mortality because of cardiovascular disease were both used as outcome variables in the survival analyses . RESULTS . The total mortality in the patient cohort was 16.4 % . An Lp(a ) level of 300 mg L-1 or more was found in 30 % of the study population and was found to be an independent predictor for death . A high fibrinogen , a low AT III level , a depressed left ventricular function and a high coronary obstruction score were other significant independent predictors of death . Total cholesterol , HDL- and LDL-cholesterol were not related to survival in this study , but a substantial proportion of the population probably received lipid-lowering agents during the study period . CONCLUSIONS An Lp(a ) level exceeding 300 mg L-1 indicates a poor further prognosis and may help to identify patients who probably need powerful secondary prevention programmes to improve their prognosis This study was conducted to determine the efficacy of atorvastatin and niacin on lipoprotein subfractions in patients with atherogenic dyslipidemia . This was a multicenter , r and omized , open-label , parallel- design study of patients with total cholesterol > 200 mg/dl , triglycerides between 200 and 800 mg/dl , and apolipoprotein B > 110 mg/dl . Patients were r and omly assigned to atorvastatin 10 mg or immediate release niacin 3,000 mg daily for 12 weeks following a low-fat diet stabilization period . Lipoprotein subclasses were measured by nuclear magnetic resonance spectroscopy . Atorvastatin and niacin both significantly reduced the concentrations of very low-density lipoprotein ( VLDL ) particles ( -31 % and -29 % , respectively ) and small low-density lipoprotein ( LDL ) particles ( -44 % and -35 % , respectively ) . Niacin increased the concentration of large LDL ( + 75 % ) . Atrovastatin reduced the number of LDL particles more than niacin ( 31 % vs 14 % ) . In patients with atherogenic dyslipidemia , both drugs had important effects on lipoprotein subfractions , which contributed to a reduction in coronary heart disease risk . The drugs equally reduced VLDL subclass levels . Niacin shifted the LDL subclass distribution toward the larger particles , more effectively converted patients from LDL phenotype B to phenotype A , and increased levels of the larger and perhaps more cardioprotective high-density lipoprotein particles . In contrast , atorvastatin preferentially lowered the concentration of small LDL particles without increasing levels of large LDL , and more effectively , reduced LDL particle numbers .  Atorvastatin had a preferred LDL effect , whereas niacin had a preferred high-density lipoprotein effect OBJECTIVE To further establish the importance of total plasma apolipoprotein A-I and lipoprotein(a ) in the prediction of primary acute myocardial infa rct ion ( AMI ) in men . DESIGN An incident case-control study . SETTING The study was nested within the Västerbotten Intervention Program ( VIP ) and the Northern Sweden MONICA cohorts . SUBJECTS A total of 62 male AMI cases and 124 matched controls , r and omly selected from the study cohorts . RESULTS In multivariate logistic regression , significant odds ratios ( OR ) were found for Lp(a ) above 200 mg L-1 , apo A-I below the mean value ( 1136 mg L-1 ) and total cholesterol ( TC ) above 7.8 mmol L-1 . TC interacted significantly with Lp(a ) ; for Lp(a ) above 200 mg L-1 and TC below 6.5 mmol L-1 , OR = 5.6 ; for Lp(a ) above 200 mg L-1 and TC above 6.5 mmol L-1 , OR = 12.6 . To evaluate the potential effect of reducing high levels of Lp(a ) or TC on the incidence of AMI in males , the attributable risk percentage ( ARP ) was calculated when interaction between the two variables was present . ARP is 31 % for Lp(a ) and 21 % for TC , implying that 31 % of the cases are due to high Lp(a ) and 21 % of the cases are due to high TC levels . CONCLUSIONS In the Swedish male population , total apo A-I in plasma is a protective factor and a plasma Lp(a ) level above 200 mg L-1 is a risk factor for AMI in males . A TC level above 6.5 mmol L-1 increased the risk of AMI if the Lp(a ) level was above 200 mg L-1 , suggesting Lp(a ) to be useful in identifying high risk individuals needed to be treated BACKGROUND Familial combined hyperlipidaemia ( FCH ) , characterized by elevated very-low-density lipoprotein ( VLDL ) and /or low-density lipoprotein ( LDL ) , is associated with an increased prevalence of premature cardiovascular disease . Therefore , lipid-lowering is frequently indicated . METHODS We evaluated in a parallel , double-blind r and omized fashion the effect of gemfibrozil ( 1200 mg/day ) ( n = 40 ) or simvastatin ( 20 mg/day ) ( n = 41 ) on lipids , apolipoprotein-B (apo-B)-containing lipoproteins , apo-CIII and lipoprotein(a ) [ Lp(a ) ] , in 81 well-defined FCH patients . RESULTS While both drugs lowered plasma cholesterol and triglyceride levels , gemfibrozil lowered plasma triglycerides more effectively by reduction of triglycerides in VLDL and LDL , whereas simvastatin was more effective in its reduction of total plasma cholesterol by exclusively decreasing LDL cholesterol . High-density lipoprotein ( HDL ) increased to an equal extent on both therapies . Total serum apo-B levels were reduced with both drugs ; however , gemfibrozil decreased apo-B only in VLDL + IDL , whereas simvastatin decreased apo-B in both VLDL + IDL and LDL . In keeping with a more effective reduction of VLDL particles , a more pronounced reduction of apo-CIII also was observed after gemfibrozil , which correlated with the reduction in plasma triglycerides . Baseline concentrations of Lp(a ) showed a wide range in both treatment groups . Median Lp(a ) levels increased after simvastatin , but were not affected by gemfibrozil . CONCLUSION Both therapies exhibited their specific effects , although none of the drugs alone completely normalized the lipid profiles of these patients with FCH . Therefore , the choice of treatment should be based on the most elevated lipoprotein fraction , and in some cases a combination of the two drugs may be indicated Background The summarized importance of haemostatic and metabolic variables ( insulin , lipids including lipoprotein ( a ) [ Lp(a ) ] and leptin ) in predicting first  myocardial infa rct  ion , as well as possible interactions among these variables , have not been reported . Design A prospect i ve case-control study nested within the Northern Sweden Health and Disease Cohort . Methods Sixty-two men diagnosed with a first myocardial infa rct ion were sex- and age-matched with 124 controls .  Conditional logistic regression was conducted including established risk factors , plasma levels of  plasminogen activator inhibitor-1 ( PAI-1 ) , tissue plasminogen activator ( tPA ) mass concentration , von Willebr and factor , insulin , proinsulin , specific insulin , apolipoprotein A-I ( apo A-I ) , Lp(a ) , and leptin . Interaction analysis was also performed for tPA , apo A-I , Lp(a ) , leptin and proinsulin . Results Smoking , low plasma levels of apo A-I and high plasma levels of cholesterol , Lp(a ) , tPA , PAI-1 , proinsulin and leptin were associated with myocardial infa rct ion in univariate conditional logistic regression analysis . High tPA [ odds ratio ( OR ) , 21.3 ; 95 % confidence interval ( CI ) , 2.04 - 222 ] and Lp(a ) ( OR , 7.21 ; 95 % CI , 1.31 - 39.8 ) and low apo A-I ( OR , 0.15 ; 95 % CI , 0.02 - 0.93 ) remained significant risk determinants in multivariate analysis with smoking habits , body mass index , hypertension , cholesterol , and diabetes included as covariates . There were non-significant synergic interactions between high Lp(a ) and leptin and tPA , respectively , and between high Lp(a ) and low apo A-I. Conclusion Plasma levels of tPA , Lp(a ) , and apo A-I are independently associated with subsequent development of a first myocardial infa rct ion in men OBJECTIVES The purpose of this study was assess the effect of  evolocumab  (  AMG 145 ) on lipoprotein (Lp)(a ) from a pooled analysis of 4 phase II trials . BACKGROUND Lp(a ) , a low-density lipoprotein ( LDL ) particle linked to the plasminogen-like glycoprotein apolipoprotein(a ) , shows a consistent and independent positive association with cardiovascular disease risk in epidemiological studies . Current therapeutic options to reduce Lp(a ) are limited . METHODS A pooled analysis of data from 1,359 patients in 4 phase II trials assessed the effects of  evolocumab  , a fully human monoclonal antibody to PCSK9 , on Lp(a ) , the relationship between Lp(a ) and lowering of low-density lipoprotein cholesterol ( LDL-C ) and apolipoprotein B , and the influence of background statin therapy . Lp(a ) was measured using a st and ardized isoform-independent method . RESULTS Evolocumab treatment for 12 weeks result ed in significant ( p < 0.001 ) mean ( 95 % confidence interval ) dose-related reductions in Lp(a ) compared to control : 29.5 % ( 23.3 % to 35.7 % ) and 24.5 % ( 20.4 % to 28.7 % ) with 140 mg and 420 mg , dosed every 2 and 4 weeks , respectively , with no plateau of effect . Lp(a ) reductions were significantly correlated with percentages of reductions in LDL-C ( Spearman correlation coefficient , 0.5134 ; p < 0.001 ) and apolipoprotein B ( Spearman correlation coefficient , 0.5203 ; p < 0 . 001 ) . Mean percentage reductions did not differ based on age or sex but the trend was greater in those patients taking statins . CONCLUSIONS Inhibition of PCSK9 with evolocumab result ed in significant dose-related reductions in Lp(a ) . While the mean percentage of reduction was significantly greater in those patients with baseline Lp(a ) of ≤125 nmol/l , the absolute reduction was substantially larger in those with levels > 125 nmol/l To prospect ively assess the role of lipoprotein(a ) ( Lp(a ) ) as a risk factor for coronary heart disease , the serum Lp(a ) concentration was determined in 130 subjects without coronary events and in 138 patients in whom coronary events ( i.e. fatal and non-fatal myocardial infa rct ion and cardiac death ) occurred during the 5-year Helsinki Heart Study . The participants of this study ( n = 4081 ) were 40 - 55-year-old men who were devoid of coronary heart disease at the beginning of the trial ; half were r and omized to gemfibrozil  and the other half to placebo treatment . In patients with coronary events  blood pressure and total cholesterol were not significant predictors of the events but their LDL cholesterol was higher than compared to the control group in this cohort ( P less than 0.05 ) . The serum Lp(a ) concentration was determined by immunoassay from sample s obtained 3 months after the beginning of the trial and then stored at -20 degrees C until analysed . Studies on the effect of long term storage at -20 degrees C on serum Lp(a ) levels did not reveal significant changes in Lp(a ) concentration in sera stored for up to 8.5 years . The distribution of Lp(a ) concentrations were similar in the men with coronary events and the controls . Nor did the mean or median levels of Lp(a ) differ significantly between the two groups . Measurements of Lp(a ) levels in fresh sample s using 2 different immunoassays did not reveal any significant difference between the participants who had survived a myocardial infa rct ion or participants without cardiac events . Thus , we conclude that in the Helsinki Heart Study cohort the serum Lp(a ) level was not a predictor of future coronary events BACKGROUND Lipoprotein(a ) [ Lp(a ) ] is a cardiovascular risk factor ; in addition to being a low-density lipoprotein (LDL)-like particle , it contains highly heterogeneous apolipoprotein(a ) [ apo(a ) ] . No prior studies have evaluated extended-release ( ER ) niacin effect on Lp(a ) level depending on apo(a ) phenotype . METHODS For this 24-week , prospect i ve , open-label clinical trial we recruited 30 men ( mean age 46.2 ± 7.5 years ) with Lp(a ) levels > 20 mg/dL. No participant had previously received lipid lowering therapy  , and started ER niacin 500 mg with stepwise dose increasing up to 1.5 - 2.0 g. Subjects were evaluated for Lp(a ) , lipids , high-sensitivity C-reactive protein , lipoprotein-associated phospholipase A2 ( Lp-PLA2 ) , and fibrinolytic markers ( plasminogen activator inhibitor-1 , tissue plasminogen activator/plasminogen activator inhibitor-1 complex , plasmin-antiplasmin complex ) . Patients were divided into two groups with major low- ( LMW ) or high-molecular weight ( HMW ) apo(a ) isoforms determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis of plasma under reducing conditions followed by immunoblotting . RESULTS At baseline , groups were comparable in age , lipid , inflammatory and fibrinolytic biomarkers levels . There was a significant difference in baseline Lp(a ) concentrations : 92 ± 29 mg/dL versus 54 ± 46 mg/dL in LMW and HMW apo(a ) groups , respectively , p < 0.01 . During the course of niacin treatment Lp(a ) decreased by 28 % ( p < 0.003 ) , Lp-PLA2 by 22 % ( p < 0.001 ) , C-reactive protein by 24 % ( p = 0.07 ) in LMW apo(a ) group , whereas no changes in Lp(a ) and biomarkers levels were obtained in HMW apo(a ) group . CONCLUSION High-dose ER niacin declines elevated Lp(a ) level in male subjects with low- but not high-molecular weight apo(a ) phenotype
Conclusions Fibrates have a significantly greater effect in reducing plasma Lp(a ) concentrations than statins .
Addition of fibrates to statins can enhance the Lp(a)-lowering effect of statins
Background Raised plasma lipoprotein(a ) ( Lp(a ) ) concentration is an independent and causal risk factor for atherosclerotic cardiovascular disease .
Several types of pharmacological approaches are under evaluation for their potential to reduce plasma Lp(a ) levels .
There is suggestive evidence that statins and fibrates , two frequently employed lipid-lowering drugs , can lower plasma Lp(a ) .
The present study aims to compare the efficacy of fibrates and statins in reducing plasma concentrations of Lp(a ) using a meta- analysis of r and omized head-to-head trials .