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Competing Interests: Conflict of interest: none declared.

Importance: In patients with coronary artery disease, some guidelines recommend initial statin treatment with high-intensity statins to achieve at least a 50% reduction in low-density lipoprotein cholesterol (LDL-C). An alternative approach is to begin with moderate-intensity statins and titrate to a specific LDL-C goal. These alternatives have not been compared head-to-head in a clinical trial involving patients with known coronary artery disease., Objective: To assess whether a treat-to-target strategy is noninferior to a strategy of high-intensity statins for long-term clinical outcomes in patients with coronary artery disease., Design, Setting, and Participants: A randomized, multicenter, noninferiority trial in patients with a coronary disease diagnosis treated at 12 centers in South Korea (enrollment: September 9, 2016, through November 27, 2019; final follow-up: October 26, 2022)., Interventions: Patients were randomly assigned to receive either the LDL-C target strategy, with an LDL-C level between 50 and 70 mg/dL as the target, or high-intensity statin treatment, which consisted of rosuvastatin, 20 mg, or atorvastatin, 40 mg., Main Outcomes and Measures: Primary end point was a 3-year composite of death, myocardial infarction, stroke, or coronary revascularization with a noninferiority margin of 3.0 percentage points., Results: Among 4400 patients, 4341 patients (98.7%) completed the trial (mean [SD] age, 65.1 [9.9] years; 1228 females [27.9%]). In the treat-to-target group (n = 2200), which had 6449 person-years of follow-up, moderate-intensity and high-intensity dosing were used in 43% and 54%, respectively. The mean (SD) LDL-C level for 3 years was 69.1 (17.8) mg/dL in the treat-to-target group and 68.4 (20.1) mg/dL in the high-intensity statin group (n = 2200) (P = .21, compared with the treat-to-target group). The primary end point occurred in 177 patients (8.1%) in the treat-to-target group and 190 patients (8.7%) in the high-intensity statin group (absolute difference, -0.6 percentage points [upper boundary of the 1-sided 97.5% CI, 1.1 percentage points]; P < .001 for noninferiority)., Conclusions and Relevance: Among patients with coronary artery disease, a treat-to-target LDL-C strategy of 50 to 70 mg/dL as the goal was noninferior to a high-intensity statin therapy for the 3-year composite of death, myocardial infarction, stroke, or coronary revascularization. These findings provide additional evidence supporting the suitability of a treat-to-target strategy that may allow a tailored approach with consideration for individual variability in drug response to statin therapy., Trial Registration: ClinicalTrials.gov Identifier: NCT02579499.

Methods: Three hundred thirty-nine patients (230 men, 109 women) treated with lipoprotein apheresis in Saxony, Germany, in 2018 are described in terms of age, lipid pattern, risk factors, cardiovascular events, medication, and number of new admissions since 2014, and the data are compared with figures from 2010 to 2013., Results: Patients were treated by 45.5 physicians in 16 lipoprotein apheresis centers. With about 10 patients per 100 000 inhabitants, the number of patients treated with lipoprotein apheresis in Saxony is twice as high as in Germany as a whole. The median treatment time was 3 years. Almost all patients had hypertension; type 2 diabetes mellitus was seen significantly more often in patients with low Lipoprotein(a). Cardiovascular events occurred in almost all patients before initiation of lipoprotein apheresis, under apheresis therapy the cardiovascular events rate was very low in this high-risk group. For some cardiovascular regions even no events could be observed., Conclusions: The importance of lipoprotein apheresis in Saxony had been increasing from 2010 to 2018., (© 2022 The Authors. Therapeutic Apheresis and Dialysis published by John Wiley & Sons Australia, Ltd on behalf of International Society for Apheresis and Japanese Society for Apheresis.)

Background: Elevated blood lipid level, also known as hyperlipoproteinemia (HLP), is the most common metabolic disorder in the general population. According to US National Heart Institute data, about 36% of adults and 10% of children aged 9 to 12 have elevated cholesterol levels. The risk of ischemic heart disease increases by 2-3% with every 1% increase in total cholesterol levels. Therefore, men aged 55-65 with a 10% increase in total cholesterol have about 38% increased ischemic heart disease mortality. The study's main objective is to determine the occurrence of thrombotic complications in patients in whom first-generation drug-eluting stents are implanted and how these events are influenced by the presence of HLP., Methods: The study is retrospective, clinical, and non-interventional with a five-year follow-up period for each patient. Initially, 800 patients undergoing index percutaneous coronary angioplasty with sirolimus-eluting and paclitaxel-eluting stent implantation were enrolled. Clinical data collected included cardiac disorders, the presence of diabetes mellitus, hyperlipoproteinemia, and smoking as a risk factor. In the examined group of patients, stent thrombosis was monitored according to Academic Research Consortium (ARC) criteria., Results: The study included 800 patients who underwent percutaneous coronary angioplasty index. At the end of the follow-up period, 701 patients (87.6%) completed the clinical trial and were included in the statistical analysis. Stent thrombosis, determined according to ARC criteria, was reported as 'definitive stent thrombosis' in 22 patients (3.06%), 'probable stent thrombosis' in 1 patient (0.14%), and 'possible stent thrombosis' in 1 patient (0.14%). Of the 404 patients with HLP, 120 patients had a total cholesterol value >300 mg/dL. Twenty patients with definitive stent thrombosis had cholesterol >300 mg/dL. Patients with probable and possible stent thrombosis did not have HLP. A comparison of patients with stent thrombosis, with HLP and without HLP, revealed a statistically significant difference (16.67% vs. 1.35%, p <0.001). Comparing patients with unstable angina pectoris, with cholesterol value >300 mg/dL and without HLP, a statistically significant difference was observed (71.7% vs. 17.2%, p <0.001)., Conclusions: We report on the long-term follow up of patients with stent thrombosis after drug-eluting stent insertion with and without HLP. The results suggest that HLP influences the development of coronary disease, with a significant influence on complications following percutaneous coronary intervention., Competing Interests: CONFLICTS OF INTEREST The authors declare that there is no potential conflict of interest regarding the publication of this article., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Congenital disorders of lipid metabolism are characterised by LDL-C concentrations > 190 mg/dl (4.9 mM) and/or triglycerides > 200 mg/dl (2.3 mM) in young individuals after having excluded a secondary hyperlipoproteinemia. Further characteristics of this primary hyperlipoproteinemia are elevated lipid values or premature myocardial infarctions within families or xantelasms, arcus lipoides, xanthomas and abdominal pain. This overview summarises our current knowledge of etiology and pathogenesis of primary hyperlipoproteinemia., Competing Interests: F. U. B. und H. D. geben an, dass kein Interessenkonflikt besteht.W. M. ist leitender Angestellter der Synlab Holding Deutschland GmbH und erklärt den Erhalt von Forschungsunterstützung und/oder Honoraren durch AMGEN GmbH, Sanofi, Amryt Pharmaceuticals, Abbott Diagnostics, Akzea Therapeutics, Novartis Pharma GmbH, Vifor Pharma und Daiichi-Sankyo., (Thieme. All rights reserved.)

Background: Lipoprotein (a) [Lp(a)] is a proven independent risk factor for coronary heart disease. It is also associated with type 2 diabetes mellitus (T2DM). However, the correlation between Lp(a) and T2DM has not been clearly elucidated., Methods: This was a retrospective cohort study involving 9248 T2DM patients and 18,496 control individuals (1:2 matched). Patients were randomly selected from among inpatients in the Second Affiliated Hospital of Nanchang University between 2006 and 2017. Clinical characteristics were compared between the two groups. Spearman rank-order correlation coefficients were used to evaluate the strength and direction of monotonic associations of serum Lp(a) with other metabolic risk factors. Binary logistic regression analysis was used to establish the correlation between Lp(a) levels and T2DM risk., Results: The median Lp(a) concentration was lower in T2DM patients than in controls (16.42 vs. 16.88 mg/dL). Based on four quartiles of Lp(a) levels, there was a decrease in T2DM risk from 33.7% (Q1) to 31.96% (Q4) (P for trend < 0.0001). Then, Lp(a) levels > 28.72 mg/dL (Q4) were associated with a significantly lower T2DM risk in the unadjusted model [0.924 (0.861, 0.992), P = 0.030]. Similar results were obtained in adjusted models 1 [Q4, 0.925 (0.862, 0.993), P = 0.031] and 2 [Q4, 0.919 (0.854, 0.990), P = 0.026]. Furthermore, in the stratified analysis, Q4 of Lp(a) was associated with a significantly lower T2DM risk among men [0.813 (0.734, 0.900), P < 0.001] and those age > 60 years [0.819 (0.737, 0.910), P < 0.001]. In contrast, the low-density lipoprotein cholesterol (LDL-C) levels and coronary heart disease (CHD) did not impact these correlations between Lp(a) and diabetes., Conclusions: There is an inverse association between Lp(a) levels and T2DM risk in the Chinese population. Male patients, especially those aged more than 60 years with Lp(a) > 28.72 mg/dL, are low-risk T2DM individuals, regardless of LDL-C levels and CHD status., (© 2021. The Author(s).)

Background: Lipoprotein apheresis (LA) is a safe method of reducing atherogenic lipoproteins and improving cardiovascular (CV) outcomes. We aimed to assess the reductions in low-density lipoprotein cholesterol (LDL-C) and lipoprotein (a) [Lp(a)] levels in patients undergoing regular LA therapy and to evaluate its influence on the incidence rate of adverse cardiac and vascular events (ACVE) and major adverse cardiac events (MACE)., Methods: A longitudinal study in Poland evaluated the prospective and retrospective observational data of 23 patients with hyperlipoproteinaemia (a) [hyper-Lp(a)] and familial hypercholesterolemia (FH), undergoing 1014 LA sessions between 2013 and 2020. Their pre- and post-apheresis LDL-C and Lp(a) levels were assessed to calculate the acute percent reductions. The time period used to evaluate annual rates of ACVE and MACE before and after initiation of LA was matched in each patient., Results: The pre-apheresis LDL-C and Lp(a) concentrations were 155 (107-228) (mg/dL) (median and interquartile range) and 0.56 (0.14-1.37) (g/L), respectively. LA therapy resulted in a reduction of LDL-C to 50 (30-73.5) (mg/dL) and of Lp(a) to 0.13 (0.05-0.34) (g/L), representing a percent reduction of 70.0% and 72.7% for LDL-C and Lp(a), respectively. We found a significant reduction in the annual rate of ACVE (0.365[0.0-0.585] vs (0.0[0.0-0.265]; P = .047) and MACE (0.365[0.0-0.585] vs 0.0[0.0-0.265]; P = .031)., Conclusions: The findings of our study indicate that LA treatment in patients with hyperlipoproteinaemia (a) and FH on maximally tolerated lipid lowering therapies leads to a substantial reduction in LDL-C and Lp(a) concentrations and lowers CV event rates in Polish patients., (© 2021 Wiley Periodicals LLC.)

Observational studies have identified gout patients are often comorbid with dyslipidemia. However, the relationship between dyslipidemia and gout is still unclear. We first performed Mendelian randomization (MR) to evaluate the causal effect of four lipid traits on gout and serum urate based on publicly available GWAS summary statistics (n ~100,000 for lipid, 69,374 for gout and 110,347 for serum urate). MR showed each standard deviation (SD) (~12.26 mg/dL) increase in HDL resulted in about 25% (95% CI 9.0%-38%, p = 3.31E-3) reduction of gout risk, with 0.09 mg/dL (95% CI: -0.12 to -0.05, p = 7.00E-04) decrease in serum urate, and each SD (~112.33 mg/dL) increase of TG was associated with 0.10 mg/dL (95% CI: 0.06-0.14, p = 9.87E-05) increase in serum urate. Those results were robust against various sensitive analyses. Additionally, independent effects of HDL and TG on gout/serum urate were confirmed with multivariable MR. Finally, mediation analysis demonstrated HDL or TG could also indirectly affect gout via the pathway of serum urate. In conclusion, our study confirmed the causal associations between HDL (and TG) and gout, and further revealed the effect of HDL or TG on gout could also be mediated via serum urate.

Background: High density lipoprotein cholesterol (HDL-C) concentration correlates inversely with atherosclerotic cardiovascular disease (ASCVD) risk and is included in risk calculations. Endothelial lipase (EL) is a phospholipase that remodels HDL. Deficiency of EL due to mutations in its gene, LIPG, is associated with hyperalphalipoproteinemia. The effects of EL on HDL function and ASCVD risk remain poorly understood., Objectives: To determine whether hyperalphalipoproteinemia due to EL deficiency is protective against ASCVD., Methods: We identified LIPG variants amongst patients with severe hyperalphalipoproteinemia (HDL-C >2.5 mmol/L) attending a referral lipid clinic in the Western Cape Province of South Africa. We analysed the clinical and biochemical phenotypes amongst primary hyperalphalipoproteinemia cases (males HDL-C >1.6 mmol/L; females HDL-C >1.8 mmol/L) due to LIPG variants, and the distribution of variants in normal and hyperalphalipoproteinemia ranges of HDL-C., Results: 1007 patients with HDL-C concentration ranging from 1.2 to 4.5 mmol/L were included. Seventeen females had primary hyperalphalipoproteinemia. Vascular disease was prominent, but not associated with HDL-C concentration, LDL-C concentration or carotid artery intima media thickness. Two novel and three known LIPG variants were identified in severe hyperalphalipoproteinemia. Four additional variants were identified in the extended cohort. Two common variants appeared normally distributed across the HDL-C concentration range, while six less-common variants were found only at higher HDL-C concentrations. One rare variant had a moderate effect., Conclusion: Hyperalphalipoproteinemia due to LIPG variants is commoner in females and may not protect against ASCVD. Use of current risk calculations may be inappropriate in patients with hyperalphalipoproteinemia due to EL deficiency. Our study cautions targeting EL to reduce risk., (Copyright © 2020 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: Elevated lipoprotein(a) (Lp(a)) is an inherited lipid disorder and an independent risk factor for cardiovascular (CV) disease. Although its prevalence in the general population has been well-documented, the prevalence of elevated Lp(a) in patients with clinical coronary artery disease (CAD) is less clear. In this study, we hypothesised that there is an over-representation of elevated Lp(a) in patients with early-onset CAD compared to the general population., Methods: Between 6 February and 8 June 2018, we screened consecutive patients aged ≤70 years who presented to the Austin Hospital with any of the following criteria: (1) acute coronary syndrome (ACS); (2) percutaneous coronary intervention (PCI); or (3) coronary artery bypass grafting (CABG). Whilst examining a range of different Lp(a) levels, a dichotomous elevated Lp(a) was defined as concentrations ≥0.5 g/L. Other CV risk factors were documented including hypertension, type 2 diabetes mellitus, and familial hypercholesterolaemia (FH) using the Dutch Lipid Clinic Network Criteria (DLCNC), also incorporating family history and clinical examination., Results: One hundred and fifty-eight (158) patients were screened; 63 (39.9%) were under 60 years of age. Overall, elevated Lp(a) ≥0.5 g/L was identified in 57 patients (36.1%). Of these, nine patients (15.8%) also had probable or definite FH. General population data was obtained from the Copenhagen General Population Study which studied 6,000 men and women and showed that the estimated prevalence of Lp(a) ≥0.5 g/L in the general population was 20%., Conclusions: Elevated Lp(a) is more prevalent in patients with relatively early-onset CAD compared to the general population and may contribute to previously unappreciated residual cardiovascular risk. Patients who present with early-onset CAD, should be routinely screened for elevated Lp(a)., (Copyright © 2020 Australian and New Zealand Society of Cardiac and Thoracic Surgeons (ANZSCTS) and the Cardiac Society of Australia and New Zealand (CSANZ). Published by Elsevier B.V. All rights reserved.)

Determining subclinical Brain stroke (BS) risk factors may allow for early and more operative BS prevention measures to find the main risk factors and moderating effects of survival in patients with BS. In this prospective study, a total of 332 patients were recruited from 2004 up to 2018. Cox's proportional hazard regressions were used to analyze the predictors of survival and the moderating effect by introducing the interaction effects. The survival probability 1-, 5- and 10-year death rates were 0.254, 0.053, and 0. 023, respectively. The most important risk factors for predicting BS were age category, sex, history of blood pressure, history of diabetes, history of hyperlipoproteinemia, oral contraceptive pill, hemorrhagic cerebrovascular accident. Interestingly, the age category and education level, smoking and using oral contraceptive pill moderates the relationship between the history of cerebrovascular accident, history of heart disease, and history of blood pressure with the hazard of BS, respectively. Instead of considerable advances in the treatment of the patient with BS, effective BS prevention remains the best means for dropping the BS load regarding the related factors found in this study.

Background: Lipoprotein apheresis (LA) is a well-established therapy for lowering lipid levels in serious cases of dyslipidaemia, including high levels of lipoprotein(a) [Lp(a)]. This method lowers both LDL cholesterol and Lp(a) by more than 60% in most of patients; however, because randomized clinical studies could be extremely difficult, also other markers of the effect of this procedures on vascular health are of importance. Therefore, in addition to changes in plasma lipids and Lp(a) during LA, we also analysed the response of biomarkers associated with vascular integrity: small non-coding microRNAs (miRNAs)., Materials and Methods: We analysed the changes in miRNAs in two women (age 70 and 72 years) with clinically manifest extensive and progressive atherosclerotic disease and high levels of Lp(a) and with different clinical course who were treated by LA. In both women we analysed changes of 175 circulating plasma miRNAs using pre-defined serum/plasma focus panels at the beginning of and one year after the therapy., Results: In addition to reduced levels of plasma lipids and Lp(a), circulating plasma levels of miR-193a-5p; -215-5p; -328-3p; -130a-3p; -362-3p; -92b-3p decreased, and levels of miR-125a-5p; -185-5p; -106a-5p; -320b; -19a increased (all P < 0.05) in both women. Moderate differences were found between both women with regard to the different course of atherosclerotic disease., Conclusions: Long-term LA substantially changes circulating plasma miRNAs associated with vascular integrity reflected different clinical course in both women. If confirmed, this approach could improve the assessment of the effectiveness of this therapy on an individual basis., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Although lipid-lowering drugs, especially statins, and recently also PCSK9 inhibitors can reduce LDL cholesterol (LDL-C) and decrease the risk for cardiovascular disease (CVD) including coronary artery disease (CAD) events most efficiently, only 5-10% of high-risk cardiovascular patients reach the target values recommended by international guidelines. In patients who cannot be treated adequately by drugs it is possible to reduce increased LDL-C and/or lipoprotein(a) (Lp(a)) values by the use of lipoprotein apheresis (LA) with the potential to decrease severe CVD events in the range of 70%->80%. Even in Germany, a country with well-established reimbursement guidelines for LA, knowledge about this life-saving therapy is unsatisfactory in medical disciplines treating patients with CVD. Starting in 1996 our aim was to offer LA treatment following current guidelines for all patients in the entire region of our clinic as standard of care., Methods: Based on the experience of our large apheresis competence center overlooking now nearly 80,000 LA treatments in the last two decades, we depict the necessary structure for identification of patients, defining indication, referral, implementation and standardisation of therapy as well as for reimbursement. LA is unfamiliar for most patients and even for many practitioners and consultants. Therefore nephrologists performing more than 90% of LA in Germany have to form a network for referral and ongoing medical education, comprising all regional care-givers, general practitioners as well as the respective specialists and insurances or other cost bearing parties for offering a scientifically approved therapeutic regimen and comprehensive care. The German Lipid Association (Lipid-Liga) has implemented the certification of a lipidological competence center as an appropriate way to realize such a network structure., Results: Working as a lipidological and apheresis competence center in a region of 400,000 to 500,000 inhabitants, today we treat 160 patients in the chronic LA program. In spite of the availability of PCSK9 inhibitors since 2015, LA has remained as an indispensable therapeutic option for targeted lipid lowering treatment. An analysis of nearly 37,000 LA treatments in our own center documented a >80% reduction of cardiovascular events in patients treated by regular LA when comparing with the situation before the start of the LA therapy. We have implemented the concept of an apheresis competence center characterised by ongoing medical education with a focus on lipidological and cardiovascular aspects, interdisciplinary networking and referral., Conclusions: Incidence and prevalence of LA patients in our region demonstrate that based on our ongoing patient-centered approach the access of patients in need to LA is substantially above the German average, thus contributing to an extraordinary reduction of cardiovascular events in the population we in particular feel responsible for., (Copyright © 2019. Published by Elsevier B.V.)

Background: Lipoprotein (Lp-) apheresis is a life-long therapy, usually performed in weekly intervals. In some cases, however, atherosclerotic disease progresses despite adequate therapy with weekly Lp-apheresis and maximal lipid lowering medication. In an attempt to improve the effectiveness of therapy, we temporarily shortened treatment intervals of Lp-apheresis in patients with elevated lipoprotein(a) (Lp(a)) and further progression of coronary atherosclerosis despite weekly Lp-apheresis and maximal lipid lowering medication., Methods: We illustrate three case reports of patients with elevated Lp(a), who underwent regular weekly Lp-apheresis treatment for secondary prevention. The intensified treatment protocol contained three therapies in two weeks (alternating 2 per week and 1 per week)., Results: The shortening of treatment intervals achieved a stabilization of atherosclerotic disease in case 1. After a total of 68 therapies in 52 weeks (1.31 sessions/week) the elective coronary angiography revealed excellent long-term results. In case 2, the intensified treatment protocol is still ongoing. The patient reported a decrease in angina pectoris and an increase in exercise capacity since the beginning of more frequent therapy sessions. In some cases, as it is shown in case 3, a fast decision for shortening the treatment intervals is necessary., Conclusions: The intensified treatment regimen resulted in an improvement in clinical symptoms and no further progression of atherosclerosis. In conclusion, shorter therapeutic Lp-apheresis intervals, at least temporarily, should be considered in patients who suffer from clinical and/or angiographic progression of atherosclerosis, despite maximal lipid lowering medication and weekly Lp-apheresis., (Copyright © 2019. Published by Elsevier B.V.)

An elevation of lipoprotein(a) (Lp(a)) is an internationally recognized atherogenic risk factor, documented in epidemiological studies, in studies with Mendelian randomization and in genome-wide association studies (GWAS). At present, no drug is available to effectively reduce its concentration. In Germany, an elevation of Lp(a) associated with progressive cardiovascular diseases is officially recognized as an indication for a lipoprotein apheresis (LA). The number of patients who were treated with LA with this abnormality was steadily increasing in the years 2013-2016 - the official data are reported. In all new patients, who started to be treated at our LA center in 2017 (n = 20) the increased Lp(a) was a main indication for extracorporeal therapy, though some of them also showed clearly elevated LDL cholesterol (LDL-C) concentrations despite being treated with a maximal tolerated lipid-lowering drug therapy. A diabetes mellitus was seen in 5 patients. The higher was the Lp(a) level before the first LA session, the higher was the cardiovascular risk. Lp(a) concentrations measured before LA sessions were usually about 20% lower than those before the start of the LA therapy. Acutely, Lp(a) levels were reduced by about 70%. Following LA sessions the Lp(a) levels increased and in the majority reach pre-session concentrations after one week. Thus a weekly interval is best for the patients, but a few may need two sessions per week to stop the progress of atherosclerosis. The interval mean values were about 39% lower than previous levels. Several papers had been published showing a higher efficiency of LA therapy on the incidence of cardiovascular events in patients with high Lp(a) values when comparing with hypercholesterolemic patients with normal Lp(a) concentrations. Russian specific anti-Lp(a) columns positively affected coronary atherosclerosis. PCSK9 inhibitors reduce Lp(a) concentrations in many patients and in this way have a positive impact on cardiovascular outcomes. In the future, an antisense oligonucleotide against apolipoprotein(a) may be an alternative therapeutic option, provided a clear-cut reduction of cardiovascular events will be demonstrated., (Copyright © 2019. Published by Elsevier B.V.)

Background: In Austria, about 12 patients per 1 million inhabitants are treated currently with lipoprotein (LP-) apheresis. In 2016 it has been suggested, that about 5000 patients were treated worldwide with LP-apheresis, more than half of them in Germany. Regular LP-apheresis aims to decrease apolipoprotein B-rich lipoproteins and to reduce cardiovascular events. In this analysis we present the current situation of LP-apheresis in Austria and we evaluated the cardiovascular event rate 2 years before versus 2 years after starting LP-apheresis., Methods: A retrospective analysis of 30 patients (19 men and 11 women) was performed at Athos Institute, Vienna, Austria. The study period included two years prior versus two years after the beginning of LP-apheresis. Cardiovascular events and interventions were defined as regarding the coronary (MACE) or the non-coronary (peripheral, cerebral or renal) vascular system., Results: The first cardiovascular event before treatment initiation occurred at a mean age of 48.4 years (range 34-73), treatment was started at a mean age of 55.6 years (range 34-73). The mean rate of incidence of cardiovascular events per patient per 2 years before beginning of LP-apheresis (y-2 and y-1) versus 2 years during treatment (y+1 and y+2) was reduced by 77.78% (1.50 versus 0.33 events/patient/2 years, p = 0.003)., Conclusions: The significant reduction in MACE and vascular disease during regular LP-apheresis at weekly intervals is consistent with data from the literature. Difficulties arise in comparing such studies due to different definition of events or interventions and different study durations. However, LP-apheresis is an efficient treatment option and causes significantly prolonged event-free survival for patients at risk., (Copyright © 2019. Published by Elsevier B.V.)

Malignant coronary artery disease (CAD) refers to a severe and extensive atherosclerotic process involving multiple coronary arteries in young individuals (aged <45 years in men and <50 years in women) with a low or no burden of established risk factors. Indians, in general, develop acute myocardial infarction (AMI) about 10 years earlier; AMI rates are threefold to fivefold higher in young Indians than in other populations. Although established CAD risk factors have a predictive value, they do not fully account for the excessive burden of CAD in young Indians. Lipoprotein(a) (Lp(a)) is increasingly recognized as the strongest known genetic risk factor for premature CAD, with high levels observed in Indians with malignant CAD. High Lp(a) levels confer a twofold to threefold risk of CAD-a risk similar to that of established risk factors, including diabetes. South Asians have the second highest Lp(a) levels and the highest risk of AMI from the elevated levels, more than double the risk observed in people of European descent. Approximately 25% of Indians and other South Asians have elevated Lp(a) levels (≥50 mg/dl), rendering Lp(a) a risk factor of great importance, similar to or surpassing diabetes. Lp(a) measurement is ready for clinical use and should be an essential part of all CAD research in Indians., (Copyright © 2019 Cardiological Society of India. Published by Elsevier B.V. All rights reserved.)

The prevalence of calcific aortic valve disease is increasing with aging of the population. Current treatment options for advanced or symptomatic aortic stenosis are limited to traditional surgical or percutaneous aortic valve replacement. Medical therapies that impact the progression of calcific aortic valve disease do not currently exist. New pathophysiological insights suggest that the processes leading to calcific aortic valve disease are metabolically active for many years before and during the clinical expression of disease. The identification of genetic and potentially causal mediators of calcific aortic valve disease allows opportunities for therapies that may slow progression to the point where aortic valve replacement can be avoided. Recent studies suggest that approximately one-third of aortic stenosis cases are associated with highly elevated lipoprotein(a) [Lp(a)] and pathways related to the metabolism of procalcifying oxidized phospholipids. Oxidized phospholipids can be carried by Lp(a) into valve leaflets but can also be formed in situ from cell membranes, lipoproteins, and apoptotic cells. This review will summarize the clinical data implicating the potential causality of Lp(a)/oxidized phospholipids, describe emerging therapeutic agents, and propose clinical trial designs to test the hypothesis that lowering Lp(a) will reduce progression aortic stenosis and the need for aortic valve replacement.

Objective: To evaluate the association of lipoprotein(a) [Lp(a)] level with short- and long-term outcomes after coronary artery bypass grafting (CABG) and to assess the effect of a 12 month course of weekly lipoprotein apheresis on vein graft patency and coronary atherosclerosis course in post-CABG patients with hyperlipidemia., Methods: This study was performed in patients after successful CABG and consisted of three parts: a) a retrospective part with computed tomography assessment of vein graft patency in patients with first-year recurrence of chest pain after CABG (n = 102); b) a prospective trial with evaluation of cardiovascular outcomes during follow up time up to 15 years in relation to baseline Lp(a) levels (n = 356); c) an 12-months interventional controlled study in 50 patients with low-density lipoprotein cholesterol (LDL-C) levels >2.6 mmol/L prior to the operation despite statin treatment that allocated into 2 groups: active (n = 25, weekly apheresis by cascade plasma filtration (CPF) plus atorvastatin), and control (n = 25, atorvastatin alone)., Results: Patients subjected to computed tomography were divided in two groups: 66 (65%) with at least one vein graft occlusion and 36 (35%) without occlusions. Lp(a) levels were significantly higher in patients with occluded grafts with a median (95% confidence intervals (CI)) of 24 (17-42) mg/dL vs. 12 (6-24) mg/dL in patients with patent grafts, p < 0.01. Over a mean of 8.5 ± 3.5 years (range 0.9-15.0 years), the primary and secondary endpoints were registered in 46 (13%) and 107 (30%) patients, respectively. Patients with Lp(a) ≥30 mg/dL were at significantly greater risk for the primary endpoint (hazard ratio (HR) 2.98, 95% confidence interval (CI) 1.76-5.03, p < 0.001) and secondary endpoint (HR 3.47, 95%CI 2.48-4.85, p < 0.001) than patients with Lp(a) values <30 mg/dL. During the CPF procedure LDL-C levels decreased by 59 ± 14%, Lp(a) levels by 49 ± 15. The frequency of vein graft occlusions at study end was 14.3% (11 of 77) in the apheresis group and 27.4% (23 of 84) in the control group, p < 0.05. Progression of atherosclerosis was obtained in 26 (14.2%) segments of native coronary arteries in the apheresis group and in 50 (25.0%) segments of the control group. Regression signs were found in 30 (16.4%) and 19 (9.5%) segments, stabilization in 127 (69.4%) and 131 (65.5%) segments, respectively (χ 2  = 9.37, p < 0.01). A Lp(a) level higher than 30 mg/dL was associated with a three-fold increased risk of vein grafts occlusion during first year after CABG, p < 0.001., Conclusion: Our data suggest that elevated Lp(a) is associated with a significantly increasing rate of one-year vein graft occlusions and adverse long-term cardiovascular outcomes whereas the use of lipoprotein apheresis improves vein graft patency during the first year after CABG., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: Elevated plasma levels of lipoprotein(a) [Lp(a)], referred to as lipoprotein(a)-hyperlipoproteinemia [Lp(a)-HLP], are an independent risk factor for atherosclerosis. Lipoprotein apheresis (LA) enables an effective reduction of Lp(a) plasma levels. The present study investigates the effects of LA in patients with Lp(a)-HLP and peripheral artery disease (PAD)., Methods: Ten patients with isolated Lp(a)-HLP and severe PAD and who had recently undergone a revascularization (index procedure) were prospectively included in this observational single center study. All patients received weekly LA. Ankle-brachial-index (ABI), transcutaneous partial oxygen pressure (tcpO 2 ), pain level, and walking distance were assessed at baseline and at the follow ups scheduled 1, 3, 6, 12, and 24 months after initiation of LA. The number of revascularizations within 12 months prior and within 24 months after the index procedure was determined., Results: As early as 1 month after initiation of LA, all investigated parameters had improved significantly compared to baseline. This improvement was further substantiated under LA throughout the entire follow-up period. Comparing baseline results with the 24-month follow-up, the average ABI increased from 0.53 ± 0.15 to 0.97 ± 0.08 (P < 0.001). The mean tcpO 2 also increased from 42.9 ± 2.3 mmHg to 61 ± 4.6 mmHg (P < 0.001). The improved perfusion led to a reduction of the mean pain level from 7.0 ± 1.5 to 1.1 ± 0.4 (P < 0.001) on a visual analogue scale (VAS) and an extension of the mean walking distance from 87 ± 60 m to 402 ± 119 m (P < 0.001). All patients suffered from severe PAD with a high number of revascularizations in the 12 months prior to the index procedure (35 procedures in 120 patient-months). Since initiation of LA, the number of revascularizations dropped significantly and remained very low during the entire follow-up period (2 procedures in 229 patient-months, P < 0.001)., Conclusion: In patients with Lp(a)-HLP and severe PAD, LA results in sustained improvement of circulation, pain level and walking distance. The number of repeat revascularizations is strongly reduced under LA treatment., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: Lipoprotein(a) (Lp(a)) is an independent cardiovascular (CV) risk factor, predisposing to premature and progressive CV events. Lipoproteinapheresis (LA) is the only efficacious therapy for reducing Lp(a). Data comparing the clinical efficacy of LA with respect to reduction of CV events in subjects with elevated Lp(a) versus LDL-C versus both disorders is scarce. We aimed to perform this comparison in a multicenter observational study., Methods: 113 LA patients from 8 apheresis centers were included (mean age 56.3 years). They were divided into 3 groups: Group I: Lp(a) < 600 mg/l, LDL-C > 2.6 mmol/l, Group II: Lp(a) > 600 mg/l, LDL-C < 2.6 mmol/l, and Group III: Lp(a) > 600 mg/l, LDL-C > 2.6 mmol/l. CV events were documented 2 years before versus 2 years after LA start., Results: Before start of LA Group II showed the highest CV event rate (p 0.001). Group III had a higher CV event rate than Group I (p 0.03). During LA there was a significant reduction of CV events/patient in all vessel beds (1.22 ± 1.16 versus 0.33 ± 0.75, p < 0.001). The highest CV event rate during LA was seen in coronaries followed by peripheral arteries, cerebrovascular events were least common. Greater CV event reduction rates were achieved in patients with isolated Lp(a) elevation (-77%, p < 0.001) and in patients with Lp(a) and LDL-C elevation (-74%, p < 0.001) than in subjects with isolated hypercholesterolemia (-53%, p 0.06)., Conclusion: This study demonstrates that patients with Lp(a) elevation benefit most from LA treatment. Prospective trials to confirm these data are warranted., (Copyright © 2017. Published by Elsevier B.V.)

Background: Dyslipidemia is a well-known risk factor for atherosclerosis and subsequent cardiovascular disease (CVD). While low density lipoprotein cholesterol (LDL-C) is well-established and taken into consideration for risk management and therapy, lipoprotein(a) is another established CVD risk factor frequently not undergoing screening due to a lack of medical treatment options. For patients suffering from CVD due to massive elevation of Lp(a) in presence of normal LDL-C levels, lipoprotein apheresis is the only available treatment option. While this constellation is an accepted indication for lipoprotein apheresis (LA) in Germany, prospective studies including a control group are still lacking., Objective: Primary objective of this trial is to evaluate the clinical benefit of lipoprotein apheresis on myocardial infarction, PCI, CABG and death from cardiovascular disease in subjects with elevated Lp(a). This study evaluates the clinical benefit of weekly LA in subjects with progressive cardiovascular disease, as accepted by the German Federal Joint Committee (treatment group). Comparator will be well-matched subjects under maximum tolerated lipid lowering therapy without access to LA treatment (control group)., Methods: MultiSELECt, is a prospective, multicenter, multinational, two-arm matched-pair cohort study designed to directly compare subjects with significantly elevated Lp(a) approved for LA subsequently undergoing weekly apheresis treatment versus a continuation of maximal medical therapy. The follow-up period will be 2 years after the baseline visit and until at least 60 events of the primary end-point occurred in the control group. A central trial expert committee will review all subjects with respect to their potential indication for LA according to established German guidelines in a blinded fashion. All control subjects will be contacted monthly via telephone visits to compensate for the more frequent visits during apheresis. Approximately 150 matched pairs will be necessary to detect an event reduction of at least 10% in subjects under LA treatment., Conclusion: The MultiSELECt trial provides the unique opportunity to demonstrate the efficiency of LA on CVD in patients with elevated Lp(a) under strongly controlled conditions., (Copyright © 2017 Elsevier B.V. All rights reserved.)

In this article is given the new insight about the affection of stress on the increase of level of low density lipoproteins (LDL) in the blood, which is connected with the disturbance of hydrodynamics in the bloodstream, the attention was paid to the cylindrical cholesterol plaque, and it's classification. The disturbance of hydrodynamics of blood under the stress leads to the formation of a cylindrical cholesterol plaque, which repeats the contour of the vessel, and leads to the ischemic disorders of the heart and brain. The cylindrical cholesterol plaque goes through several stages of development: friable, yielding, dense, old. In the case of destruction of friable, fresh cholesterol plaque, releases a big quantity of low-density lipoproteins. This leads to the pathological increase of level of LDL in the blood. In the case of long disturbance of hydrodynamics, occurs the formation of strong links between low-density lipoproteins. Yielding cholesterol plaque is formed. Further maturation of cylindrical cholesterol plaque, leads to it's densifying and damage. We may emphasize, that short periods of strong contraction and expansion of vessels lead to the increase of level of LDL in the blood. Self-dependent restoration of normal level of LDL in blood occurs in the case of restoration of pressure in the limits of numbers, which are specific for particular person, and which don't exceed the physiological standard. Among patients with long duration of stress, the duration of vasospasm increases. LDL, without having a possibility to crumble, begin to stick together and form the yielding cylindrical plaque. It is characterized by having of not so strong connection with the vascular wall, and maintains only at the expanse of iteration of the vascular wall, it has cylindrical shape, is elastic and yellow. The thickness and length of walls depends on the degree of cross-clamping during the time of formation of yielding cylindrical plaque. In the case of stopping of spasm, yielding cylindrical plaque can resolve slowly. Among hypotensive and individuals, which have normal pressure, the increase of level of LDL isn't noted. There aren't such investigations, where such link was noted. The increasing of level of LDL among these people (especially under the stress) can say about cases of short-term increase of pressure, which could be unnoticed. These patients require pressure monitoring and, accordingly, the adjustment of the state of stress and anger., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

High concentrations of lipoprotein(a) (Lp(a)) represent an important independent and causal risk factor associated with adverse outcome in atherosclerotic cardiovascular disease (CVD). Effective Lp(a) lowering drug treatment is not available. Lipoprotein apheresis (LA) has been proven to prevent cardiovascular events in patients with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP) and progressive CVD. Here we present the course of a male patient with established peripheral arterial occlusive disease (PAOD) at the early age of 41 and coronary artery disease (CAD), who during follow-up developed over 2 years a progressive syndrome of cerebellar and spinal cord deficits against the background of multifactorial cardiovascular risk including positive family history of CVD. Spastic tetraplegia and dependency on wheel chair and nursing care represented the nadir of neurological deficits. All conventional risk factors including LDL-cholesterol had already been treated and after exclusion of other causes, genetically determined Lp(a)-HLP was considered as the major underlying etiologic factor of ischemic vascular disease in this patient including spinal cord ischemia with vascular myelopathy. Treatment with an intensive regimen of chronic LA over 4.5 years now was successful to stabilize PAOD and CAD and led to very impressive neurologic and overall physical rehabilitation and improvement of quality of life.Measurement of Lp(a) concentration must be recommended to assess individual cardiovascular risk. Extracorporeal clearance of Lp(a) by LA should be considered as treatment option for select patients with progressive Lp(a)-associated ischemic syndromes.

General lipoprotein (Lp) (a) screening can help to identify patients at high risk for cardiovascular disease. Non-invasive methods allow early detection of clinically asymptomatic incipient atherosclerotic disease. Medical treatment options are still unsatisfactory. Lp(a) apheresis is an established treatment in Germany for secondary prevention of progressive cardiovascular disease. Statin-based lowering of LDL cholesterol and thrombocyte aggregation inhibitors still represent the basis of medical treatment. Target levels for LDL-cholesterol should be modified in patients with hyperlipoproteinemia (a).

Lipoprotein (a) (Lp (a)) is one risk factor for the development of cardiovascular diseases. Several studies have shown that Lp (a) hyperlipoproteinaemia has a particular influence on the development of coronary heart disease (CHD). A retrospective single-centre observation study was performed to evaluate the effectiveness of lipid apheresis on the basis of consecutively performed percutaneous coronary interventions (PCI) in patients with high Lp (a) values and angiographically documented CHD.In 23 pts (male 18, age 60.04 ± 0.58 years) with angiographically documented CHD (first manifestation 48.00 ± 9.41 years), elevated LDL cholesterol (144.39 ± 92.01 mg/dl) and Lp (a) (133.04 ± 39.68 mg/dl), 49 PCI and 3 coronary artery bypass grafting (CABG) procedures had been performed prior to the initiation of lipid apheresis. Following the initiation of weekly lipid apheresis, LDL cholesterol was 99.43 ± 36.53 mg/dl and Lp (a) 91.13 ± 33.02 mg/dl. In a time interval of 59.87 ± 49.49 months (median 51.00, range 1-153 months) 15 pts did not require an additional PCI. In 8 pts (7 pts 3‑vessel disease, 1 pt 2‑vessel disease) 14 PCI - no CABG - were performed after 69.38 ± 71.67 months (median: 32.50, range 17-232 months). The incidence of PCI could thus be reduced by 71.43%.

Atherosclerosis, as a common arterial disease with high morbidity rate, is reported to be closely associated with adventitia angiogenesis. The present study aimed to investigate the effect of tongxinluo (TXL) on angiogenesis in the carotid adventitia of hyperlipidemic rabbits and the underlying mechanism. A total of 90 experimental rabbits were randomly assigned into the following six groups (n=15 per group): Normal group, model group, low‑dose TXL group, moderate-dose TXL group, high‑dose TXL group and atorvastatin group. The normal group was fed with a standard diet. The model and treatment groups were on a high cholesterol diet for 4 weeks. The serum lipid level of the model group was significantly higher compared with the normal group. TXL serum lipid level compared with the model group. Hematoxylin and eosin, and CD31 staining demonstrated that TXL inhibited adventitia angiogenesis in a dose‑dependent manner. The dihydroethidium probe and fluorescence in situ hybridization results indicated that TXL reduced O2‑ level and positive signal of gp91phox and p22phox mRNA in adventitia. Reverse transcription‑polymerase chain reaction and western blot analysis determined that TXL treatment significantly downregulated the expression levels of the gp91phox, p22phox genes and the vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor-2 (VEGFR-2) proteins compared with the model group. TXL exhibited a dose‑dependent inhibitory effect on angiogenesis in the carotid adventitia of hyperlipidemic rabbits. This may be associated with the downregulation of reactive oxygen species generation in the adventitia and the suppression of VEGF/VEGFR-2 expression.

Peroxisome proliferator activated receptor gamma (PPARγ) is a pleiotropic ligand activated transcription factor that acts in several tissues to regulate adipocyte differentiation, lipid metabolism, insulin sensitivity and glucose homeostasis. PPARγ also regulates cardiomyocyte homeostasis and by virtue of its obligate role in placental development is required for embryonic survival. To determine the postnatal functions of PPARγ in vivo we studied globally deficient neonatal mice produced by epiblast-restricted elimination of PPARγ. PPARγ-rescued placentas support development of PPARγ-deficient embryos that are viable and born in near normal numbers. However, PPARγ-deficient neonatal mice show severe lipodystrophy, lipemia, hepatic steatosis with focal hepatitis, relative insulin deficiency and diabetes beginning soon after birth and culminating in failure to thrive and neonatal lethality between 4 and 10 days of age. These abnormalities are not observed with selective PPARγ2 deficiency or with deficiency restricted to hepatocytes, skeletal muscle, adipocytes, cardiomyocytes, endothelium or pancreatic beta cells. These observations suggest important but previously unappreciated functions for PPARγ1 in the neonatal period either alone or in combination with PPARγ2 in lipid metabolism, glucose homeostasis and insulin sensitivity.

Herein, we describe a 69-year-old Japanese man with massive type III hyperlipoproteinemia (total cholesterol, 855 mg/dL; triglyceride, 753 mg/dL) presenting as a paraneoplastic manifestation of hepatitis B virus-associated hepatocellular carcinoma. The messenger RNA expression of sterol regulatory element-binding protein-2 and proprotein convertase subtilisin/kexin 9 in the tumor tissue was increased by 13-fold and 4-fold, respectively, compared with the non-tumor tissue. Serum level of active form of PCSK9 was 382 ng/mL (reference range: 253 ± 79 ng/mL). The non-tumor tissue had extremely low expression of low-density lipoprotein receptor and low-density lipoprotein receptor-related protein 1. Together, we speculate that marked overexpression of sterol regulatory element-binding protein-2 in the tumor may stimulate the secretion of PCSK9, which inhibits the lipoprotein receptors in the non-tumor tissue, thereby causing paraneoplastic hyperlipoproteinemia., (Copyright © 2016 National Lipid Association. Published by Elsevier Inc. All rights reserved.)

Background: To date, there have been no studies evaluating the effect of isolated lipoprotein(a) (Lp(a)) lowering therapy on carotid atherosclerosis progression., Methods: We enrolled 30 patients who had coronary heart disease (CHD) verified by angiography, Lp(a) level ≥50 mg/dL, and low density lipoprotein cholesterol (LDL-C) level ≤2.6 mmol/L (100 mg/dL) on chronic statin therapy. Subjects were allocated in a 1:1 ratio to receive apheresis treatment on a weekly basis with immunoadsorption columns ("Lp(a) Lipopak"(®), POCARD Ltd., Russia) added to atorvastatin, or atorvastatin monotherapy. The primary efficacy end-point was the change from baseline in the mean intima-media thickness (IMT) of the common carotid arteries., Results: After one month run-in period with stable atorvastatin dose, LDL-C level was 2.3 ± 0.3 mmol/L and Lp(a) - 105 ± 37 mg/dL. As a result of acute effect of specific Lp(a) apheresis procedures, Lp(a) level decreased by an average of 73 ± 12% to a mean of 29 ± 16 mg/dL, and mean LDL-C decreased by 17 ± 3% to a mean of 1.8 ± 0.2 mmol/L. In the apheresis group, changes in carotid IMT at 9 and 18 months from baseline were -0.03 ± 0.09 mm (p = 0.05) and -0.07 ± 0.15 mm (p = 0.01), respectively. In the atorvastatin group no significant changes in lipid and lipoprotein parameters as well as in carotid IMT were received over 18-month period. Two years after study termination carotid IMT increased by an average of 0.02 ± 0.08 mm in apheresis group and by 0.06 ± 0.10 mm in the control group (p = 0.033)., Conclusion: Isolated extracorporeal Lp(a) elimination over an 18 months period produced regression of carotid intima-media thickness in stable CHD patients with high Lp(a) levels. This effect was maintained for two years after the end of study., Trial Registration: Clinicaltrials.gov (NCT02133807)., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Hyperlipoproteinemia(a) [Lp(a)-HLP] is a major risk factor for severe atherosclerosis. The present investigation sought to assess the effect of lipoprotein apheresis (LA) in patients with peripheral artery disease (PAD) and Lp(a)-HLP., Methods: In January 2013, we started a registry for Lp(a)-HLP patients who receive weekly LA in our center. So far, ten patients with severe PAD and isolated Lp(a)-HLP who recently underwent revascularization (index procedure) have been included. Pain level, ankle-brachial-index (ABI), transcutaneous oxygen pressure (tcpO2) and walking distance were determined before, as well as 1, 3, 6 and 12 months after initiation of LA. Furthermore, the mean time interval between revascularizations within the 12 months prior to the index procedure and up to 12 months after the index procedure was assessed., Results: All analyzed parameters significantly improved under LA. When comparing the results before LA with the results after 12 months, the ankle-brachial-index increased from 0.5 ± 0.2 to 0.9 ± 0.1 (P < 0.001). The tcpO2 levels also increased from 42.9 ± 2.3 mmHg to 59.0 ± 8.9 mmHg (P < 0.001). The improved microcirculation was associated with a reduction of the mean pain level from 7.0 ± 1.5 to 2.0 ± 0.8 (P < 0.001) as determined using the visual analog scale. The walking distance increased from 87 ± 60 m to 313 ± 145 m (P < 0.001). Importantly, the frequency of revascularization procedures was strongly decreased under LA. All patients combined underwent 35 revascularizations within the 12 months prior to the index procedure (mean interval between two revascularizations: 104.3 days). Since the index procedure, only one revascularization was necessary within 79 patient-months under LA (mean interval: 2404.5 days, P < 0.001)., Conclusion: LA improves circulation, oxygen supply, level of pain and walking distance in patients with severe PAD and Lp(a)-HLP. The frequency of revascularization procedures is strongly reduced under LA treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Lipoprotein apheresis (LA) can lower LDL-cholesterol and Lp(a) by 60%-70% and is the final escalating option in patients with hyperlipoproteinemias involving LDL or Lp(a) particles. Major therapeutic effect of LA is preventing cardiovascular events. In Germany since 2008 a reimbursement guideline has been implemented accepting to establish the indication for LA not only for familial or severe forms of hypercholesterolemia but also based on Lp(a)-hyperlipoproteinemia associated with a progressive course of cardiovascular disease, that persists despite effective treatment of other concomitant cardiovascular risk factors. The Pro(a)LiFe-study confirmed with a prospective multicenter design that LA can be regarded as an important therapeutic approach to effectively reduce Lp(a) plasma levels and prevent cardiovascular events in this particular high-risk patient group. Results support that Lp(a) may be a major causal factor for precipitating mechanisms of accelerated progression of cardiovascular disease (CVD). Indication for LA based on measurement of Lp(a) as part of risk assessment is supported by the following conditions: progressive CVD as assessed clinically and with imaging techniques, established maximally tolerated lipid lowering drug treatment, recent cardiovascular events despite efficient drug treatment, out of the ordinary frequency of cardiovascular events, early CVD, or positive family history of early CVD. Still existing difficulties with Lp(a) laboratory measurement require a practical approach to establish the indication for LA considering the 60 mg/dl threshold of German guidelines with selecting an Lp(a) assay which has been calibrated for mass., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: In recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system challenged the approval of diagnostic and therapeutic procedures for regular reimbursement, including lipoprotein apheresis therapy. Years before an interdisciplinary German apheresis working group, established by members of both German Societies of Nephrology (Verband Deutsche Nierenzentren (VDN), Deutsche Gesellschaft für Nephrologie (DGfN)), initiated a revision of the indication of lipoprotein apheresis therapy according to current guidelines and recommendations for the treatment of lipid disorders. This working group was convinced, that data derived from a registry would support lipoprotein apheresis as a therapy for severe hyperlipidemic patients suffering from progressive cardiovascular diseases., Methods and Results: In 2009 the working group established the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and scientific knowledge for the registry, which are in line with the reimbursement guidelines. In 2011 financing by sponsors was secured and an internet-based registry was created. A pilot project with 5 apheresis centers finished in 2012 - since then the registry is available to all German apheresis centers., Conclusions: There has been consensus between the medical societies and health care carriers regarding the need for a German Lipoprotein Apheresis Registry (GLAR). The launch of this registry complies with requirements of the Federal Joint Committee (G-BA). Complementing the Pro(a)LiFe-Study, first data from GLAR support the safety of the different apheresis treatment procedures. In addition these first data suggest, with respect to the results of Pro(a)LiFe-Study, effectiveness in preventing cardiovascular progression as well. Here, further data are needed to statistically substantiate these early findings., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

It is well established that Lipoprotein(a) [Lp(a)] is an independent cardiovascular risk factor and predictor of major adverse cardiovascular events. Lipoprotein apheresis is currently the most effective approved treatment available, with minimal effect conferred by conventional lipid lowering agents. A growing body of evidence suggests that aggressively lowering raised Lp(a) may improve cardiovascular and clinical outcomes, although more prospective research is required in this field. Angina which is refractory to conventional medical therapy and revascularisation is extremely challenging to manage. There is a significant unmet need to establish therapeutic options. Our goal is to determine the impact of lipoprotein apheresis on clinical parameters and symptoms of patients with refractory angina secondary to advanced coronary disease and raised Lp(a). Determining whether we should aggressively lower Lp(a) in such patients remains a very important question, which could potentially impact on the management of a large population. We will also gain insight into how this treatment works and the mechanisms via which Lp(a) increases cardiovascular risk. We are currently conducting a prospective, randomised controlled crossover study of patients with refractory angina and raised Lp(a), randomised to undergoing three months of weekly lipoprotein apheresis or sham apheresis. Patients will then crossover to the opposite study arm after a 1 month wash-out phase. We will assess myocardial perfusion, carotid atherosclerosis, endothelial vascular function, thrombogenesis, oxidised LDL and their antibodies, exercise capacity, angina and quality of life at the beginning and end of treatment, to determine the net true treatment effect on the above parameters. This is a novel area of research, as previous studies have not assessed the role of lipoprotein apheresis in patients with refractory angina and raised Lp(a) in a prospective randomised controlled manner., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Lipoprotein(a) (Lp(a)) is a low density lipoprotein-like particle to which apolipoprotein(a) is bound. It is recognized as an atherosclerosis-inducing risk factor. Up to now a detailed description of the effect of Lipoprotein apheresis (LA) on Lp(a) levels in the long run is lacking., Methods: We studied 59 patients with elevated Lp(a) levels who were treated with LA at the Lipoprotein Apheresis Center at the University Hospital Dresden. We analyzed Lp(a) concentrations before the start of the LA treatment and during this extracorporeal therapy., Results: Comparing the Lp(a) levels before the start of LA therapy and pre-apheresis (measured before the LA sessions) Lp(a) levels, we observed a reduction of the Lp(a) levels of about 22.8% in all patients. Lp(a) levels were acutely (comparing post-apheresis with pre-apheresis concentrations) reduced by all 6 available LA methods (by about 70%). A linear regression analysis was performed to differentiate the long term course of pre-apheresis Lp(a) levels. In 30 patients we saw an increase of the pre-apheresis Lp(a) levels over the time, in 15 patients a constancy and in 14 patients a decrease. Patients with a decrease of pre-apheresis Lp(a) levels over the time had significantly higher initial (before the start of the extracorporeal treatment) and pre-apheresis values and they were significantly older. These patients had significantly more severe peripheral arterial disease as well as cardiac valve and carotid stenosis. The patients with the lowest initial Lp(a) levels and an increase of the pre-apheresis Lp(a) levels over the time had the highest percentage of intake of Tredaptive(®)/Niaspan(®) though after stopping the intake of these nicotinic acid preparations no clear increase of Lp(a) concentrations was observed. The applied LA systems did not seem to have a significant influence on the course of pre-apheresis Lp(a) levels. In all patients there was a high variability of Lp(a) concentrations between LA sessions which may in part be due to the inaccuracy of the method used to measure Lp(a) concentrations., Conclusion: Pre-apheresis Lp(a) levels (before the LA sessions) are lower than those before the start of a LA treatment but they behave differently among patients during LA treatment., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Lipoprotein(a) (Lp(a)) was first described by K. Berg and is known for more than 50 years. It is an interesting particle and combines the atherogenic properties of low-density lipoprotein (LDL)-cholesterol as well as the thrombogenic properties of plasminogen inactivation. However, due to technical problems and publication of negative trials the potential role of Lp(a) in atherosclerosis was severely underestimated. In recent years our understanding of the function and importance of Lp(a) improved. Interventional trials with niacin failed to demonstrate any benefit of lowering Lp(a); however, several studies confirmed the residual cardiovascular disease (CVD) risk of elevated Lp(a). LDL/Lp(a) apheresis is able to lower Lp(a) and some new drugs under development should help us to lower Lp(a) in the near future. It will be important to follow this with hard endpoint trials. Until then most clinicians recommend the use of an aggressive LDL-lowering approach in patients with high Lp(a). Since most of these patients with high Lp(a) might have manifested atherosclerosis anyway, we would also consider the use of acetylsalicylic acid.

Elevated lipoprotein(a) (Lp(a)) has emerged as an important independent cardiovascular risk factor, and causal association has been accepted with adverse outcome in atherosclerotic disease. Lipoprotein apheresis (LA) can lower low-density lipoprotein (LDL)-cholesterol and Lp(a) by 60-70 % and is the final escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL or Lp(a) particles. Major therapeutic effect of LA is preventing cardiovascular events. Stabilizing plaque morphology might be an important underlying mechanism of action. In Germany, since 2008, a reimbursement guideline has been implemented to establish the indication for LA not only for familial or severe forms of hypercholesterolemia but also for Lp(a)-HLP associated with a progressive course of cardiovascular disease, that persists despite effective treatment of other concomitant cardiovascular risk factors, i.e. isolated Lp(a)-HLP. The Pro(a)LiFe-study confirmed with a prospective multicenter design that LA can effectively reduce Lp(a) plasma levels and prevent cardiovascular events.

Lipoprotein (a) [Lp(a)] is a modified LDL particle with an additional apolipoprotein [apo(a)] protein covalently attached by a thioester bond. Multiple isoforms of apo(a) exist that are genetically determined by differences in the number of Kringle-IV type-2 repeats encoded by the LPA gene. Elevated plasma Lp(a) is an independent risk factor for cardiovascular disease.The phenotypic diversity of familial Lp(a) hyperlipidemia [Lp(a)-HLP] and familial hypercholesterolemia [FH], as defined risks with genetic background, and their frequent co-incidence with additional cardiovascular risk factors require a critical revision of the current diagnostic and therapeutic recommendations established for isolated familial Lp(a)-HLP or FH in combination with elevated Lp(a) levels.Lp(a) assays still suffer from poor standardization, comparability and particle variation. Further evaluation of the current biomarkers and establishment of novel comorbidity biomarkers are necessary for extended risk assessment of cardiovascular disease in FH or Lp(a)-HLP and to better understand the pathophysiology and to improve patient stratification of the Lp(a) syndrome complex.Lp(a) promotes vascular remodeling, increased lesion progression and intima media thickening through induction of M1-macrophages, antiangiogenic effects (e.g. vasa vasorum) with secretion of the antiangiogenic chemokine CXCL10 (IP10) and CXCR3 mediated activation of Th1- and NK-cells.In addition inhibition of serine proteases causing disturbances of thrombosis/ hemostasis/ fibrinolysis, TGFb-activation and acute phase response (e.g. CRP, anti-PL antibodies) are major features of Lp(a) pathology. Anti-PL antibodies (EO6 epitope) also bind to oxidized Lp(a).Lipoprotein apheresis is used to reduce circulating lipoproteins in patients with severe FH and/or Lp(a)-HLP, particularly with multiple cardiovascular risks who are intolerant or insufficiently responsive to lipid-lowering drugs.

Purpose: The prevalence of systemic atherosclerosis and overactive bladder/detrusor overactivity increases almost simultaneously with age but an association between these diseases has not yet been proved. We evaluated changes in bladder function and morphology, including vascularization, in apoE(-/-)LDLR(-/-) double knockout mice with systemic atherosclerosis but without central nervous system involvement., Materials and Methods: Cystometry was performed in awake, freely moving 60-week-old apoE(-/-)LDLR(-/-) mice and C57BL/6N controls. The mice were sacrificed and perfused with Microfil® contrast medium. The bladder was excised, dissected and scanned by nano-computerized tomography, including 3-dimensional reconstruction. Samples then underwent histomorphological analysis., Results: In apoE(-/-)LDLR(-/-) mice cystometry revealed a significant decrease in the peak-peak interval, micturition interval, functional bladder capacity and micturition volume. However, maximum bladder pressure increased. Nano-computerized tomography revealed a significant reduction in bladder wall thickness, segment volume, vascular volume and the vascular volume fraction. Histomorphologically bladder specimens showed a thickened media of intramural vessels, activated endothelial cells and intramural inflammatory cells., Conclusions: To our knowledge this study presents a new in vivo mouse model of nonneurogenic detrusor overactivity caused by systemic atherosclerosis. Decreased bladder wall vascularization seems to be a major factor for detrusor overactivity onset. Capillaries are rarified with reduced lumina due to thickened media. Activated endothelial cells and the infiltration of inflammatory cells in apoE(-/-)LDLR(-/-) mice underlines once more that atherosclerosis is an inflammatory process that may also be relevant to the onset of detrusor overactivity., (Copyright © 2015 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.)

Treatment with statins to achieve target low-density lipoprotein cholesterol (LDL-C) levels is still associated with residual risk. Lipoprotein subfraction evaluation can provide additional information regarding atherogenicity in these individuals. Patients (n = 40) with hypercholesterolemia (29 females, mean age 63 years), without previous hypolipemic treatment, were treated with atorvastatin 40 mg/d for 3 months. Atorvastatin significantly reduced total cholesterol (6.7 ± 1.0 vs 4.6 ± 1.3 mmol/L, P < .001), LDL-C (4.3 ± 1.0 vs 2.6 ± 0.9 mmol/L, P < .001), triglycerides (1.8 ± 0.9 vs 1.5 ± 1.00 mmol/L, P < .05), small-dense LDL (sdLDL) fraction 3 to 7 (0.22 ± 0.37 vs 0.09 ± 0.16 mmol/L, P < .001), and apolipoprotein B (apoB; 1.0 ± 0.2 vs 0.74 ± 0.2 g/L, P < .001). There was a negative correlation of atherogenic index of plasma (AIP) with buoyant LDL-1 and LDL-2 (r = -.35; P < .05) and positive with sdLDL-3 to sdLDL-7 (r = .52, P < .001). Administration of atorvastatin 40 mg/d in patients with hypercholesterolemia caused a shift in sdLDL subfractions to large, buoyant subfractions. The AIP better correlated with sdLDL than apoB levels., (© The Author(s) 2013.)

High levels of fasting circulating triglycerides (TG) represent an independent risk factor for cardiovascular disease. In western countries, however, people spend most time in postprandial conditions, with continuous fluctuation of lipemia due to increased levels of TG-rich lipoproteins (TRLs), including chylomicrons (CM), very low density lipoproteins (VLDL), and their remnants. Several factors contribute to postprandial lipid metabolism, including dietary, physiological, pathological and genetic factors. The presence of coronary heart disease, type 2 diabetes, insulin resistance and obesity is associated with higher postprandial TG levels compared with healthy conditions; this association is present also in subjects with normal fasting TG levels. Increasing evidence indicates that impaired metabolism of postprandial lipoproteins contributes to the pathogenesis of coronary artery disease, suggesting that lifestyle modifications as well as pharmacological approaches aimed at reducing postprandial TG levels might help to decrease the cardiovascular risk.

Lipoprotein(a) has been shown to be associated with an increased incidence of cardiovascular diseases for decades. However, only recent research revealed more about its physiological function and its role in the development of cardiovascular diseases. The authors summarize the physiological role of lipoprotein(a), causes and treatment of elevated lipoprotein(a) level, and the association between lipoprotein(a) and cardiovascular diseases.

Background: Post-operative atrial fibrillation is an important complication after coronary bypass surgery. As inflammation and oxidative stress were makedly encountered in the etiology, high cholesterol was also defined to provoke atrial fibrillation. In this present study, the relationship between postoperative atrial fibrillation and preoperative serum lipid levels were evaluated., Methods: A total of 100 patients, who were operated at the department of Cardiovascular Surgery of our hospital were included to the study analysis. Patients, who had preoperative atrial fibrillation, thyroid dysfunction, or left atrial dilatation (above 4.5 cm) were excluded from the study. Patients were divided into two groups with postoperative atrial fibrillation development (Group I n = 36), and without atrial fibrillation development (Group II n = 64). Preoperative routine blood analyses, ECG, echocardiography were evaluated. Patients were followed for atrial fibrillation development for one month starting from the intensive care unit at the postoperative period. Serum lipid profiles and thyroid function were measured. For homogenization of inflammatory factors and oxidative stress, treatments other than statins, betablockers, calcium channel blockers, aspirin, ACE inhibitors, and ARB were stopped for 10 days. Atrial fibrillation for at least ≥ 5 minutes in the intensive care unit was accepted as postoperative atrial fibrillation., Results: Demographic data were similiar between groups (p > 0.05). There was no difference in TC levels between groups, whereas LDL-C levels were statistically lower in patients developing post-operative atrial fibrillation (106.67 ± 28.36 vs 118.75 ± 27.75; P < 0.05)., Conclusion: The more lowered is the LDL-C in the preoperative period, the more reduced risk of postoperative atrial fibrillation development. High levels of LDL-C in the preoperative period could be predictor of atrial fibrillation development in the post operative period.