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Oxidative modifications of lipoproteins play a crucial role in the initiation of atherosclerotic cardiovascular diseases (ASCVDs). Nowadays, the one effective strategy for the treatment of patients with hyperlipoproteinemia(a) is lipoprotein apheresis (LA), which has a pleiotropic effect on reducing the risk of ASCVDs. The significance of oxidative susceptibility of the LDL fraction in ASCVDs has been extensively studied. Whether LA alters the susceptibility of lipoprotein(a) to oxidative modifications remains an unresolved issue. In this study, we isolated lipoprotein fractions by ultracentrifugation in patients with hyperlipoproteinemia(a) undergoing apheresis (LA group) at three time points and patients who were qualified for LA but did not consent to the procedure (non-LA group). We performed copper-mediated oxidation of Lp(a) and LDL fractions and determined autotaxin activity. After apheresis, we observed a lower susceptibility to oxidation of the Lp(a) and LDL fractions as expressed by the extended value of oxidation lag time, decreased slope of the oxidation curve, and decreased final concentration of conjugated dienes. No significant differences were found between these parameters before and 7 days after LA. Additionally, both patients undergoing and not undergoing LA had a significant correlation between autotaxin activity and all parameters characterizing susceptibility to oxidation in the Lp(a) fraction. Our results demonstrate that the pleiotropic effect of apheresis may be related to the reduced oxidative susceptibility of Lp(a) and LDL particles, which may influence the reduction in ASCVD risk in patients undergoing apheresis. The results of the rebound effect 7 days after LA will contribute to a better definition of apheresis frequency guidelines.

Introduction: Elevated levels of lipoprotein(a) [Lp(a)] are independently associated with an increased risk of cardiovascular disease (CVD)., Objectives: We aimed to evaluate the levels of Lp(a) among patients of European ancestry referred to outpatient cardiology clinics., Patients and Methods: We analyzed 2475 consecutive patients referred to 2 outpatient cardiology clinics between March 2022 and January 2024. Individuals with atherosclerotic CVD, heart failure, significant valve disease, and aortic aneurysm were excluded., Results: A majority of the study population were women (n = 1724 [69.7%]). The median (interquartile range) age of the participants was 66 (53-73) years. An Lp(a) level greater than or equal to 30 mg/dl (≥75 nmol/l) was recorded in 21.5% and a level greater than or equal to 50 mg/dl (≥125 nmol/l) was recorded in 13.5% of the patients. In univariable analysis, the Lp(a) level was significantly associated with hypertension, sleep apnea, migraine, polycystic ovary syndrome, physical activity level, as well as fasting blood glucose, glycated hemoglobin A1c (HbA1c), low‑density lipoprotein cholesterol (LDL‑C), and non-high‑density lipoprotein cholesterol concentrations. Female sex (β [SE] = 0.06 [0.02]), atrial fibrillation (β [SE] = 0.05 [0.02]), and the levels of HbA1c (β [SE] = 0.14 [0.02]) and LDL‑C (β [SE] = 0.09 [0.02]) were independently related to the level of Lp(a). Atrial fibrillation (odds ratio [OR], 1.8; 95% CI, 1.01-3.19), migraine (OR, 0.51; 95% CI, 0.32-0.83), and hyperlipidemia (OR, 1.56; 95% CI, 1.22-1.99) were related to the Lp(a) level of 30 mg/dl or above (≥75 nmol/l), while female sex (OR, 1.46; 95% CI, 1.10-1.92), hyperlipidemia (OR, 1.49; 95% CI, 1.12-1.97), hypertension (OR, 1.42; 95% CI, 1.1-1.84) and HbA1c concentration (OR, 0.84; 95% CI, 0.72-0.96) were significantly associated with the Lp(a) level greater than or equal to 50 mg/dl (≥125 nmol/l)., Conclusions: The observed prevalence of increased Lp(a) concentration among patients of European ancestry treated at outpatient cardiology clinics was 21.5%. Female sex, hypertension, atrial fibrillation, migraine, and concentrations of LDL‑C and HbA1c were independently related to the level of Lp(a) in this population.

Introduction and Objectives: The association between HDL cholesterol (HDL-C) levels and death from cardiovascular disease follows a U-shaped pattern, increasing at the extremes. The objective of the study was to characterize a sample of subjects with extreme hyperalphalipoproteinemia (HAE)., Material and Methods: 53 cases with HAE were recruited, 24 women (HDL-C>135mg/ dL) and 29 men (HDL-C>116mg/ dL). A detailed medical history was taken and questionnaires on adherence to the Mediterranean diet and physical activity were collected. Carotid ultrasounds were performed to detect the presence of suclinical atherosclerosis., Results: The most prevalent cardiovascular risk factor (CVRF) was dyslipidemia (64%) with no significant differences between men and women, unlike hypertension (21% in women, versus 55% in men, p=0.01) and others CVRF, for example, diabetes. 7% of the series had previous cardiovascular disease, women had higher LDL cholesterol (p=0.002) and HDL-C than men (without significant differences). Plaque was detected in 53% of cases, being more prevalent in men. Patients with plaque were older, drank more alcohol and smoked more (p<0.05)., Conclusions: Men had a higher prevalence of CVRF than women, except for dyslipidemia. Subclinical atherosclerosis occurred in more than half of the series. Age, alcohol consumption and smoking were independently associated with the presence of plaque, however, our data do not show a significant influence of HDL-C levels., (Copyright © 2024. Publicado por Elsevier España, S.L.U.)

Background: In 2012, the German Lipoprotein Apheresis Registry (GLAR) was launched. Real-world data on lipoprotein apheresis (LA) treatment are now available for a time period of 11 years. All patients received the maximally tolerated lipid-lowering therapy, which included statins, ezetimibe, bempedoic acid, and either proprotein convertase subtilisin/kexin type 9 (PCSK9) antibodies or antisense therapy., Methods and Results: During the time period from 2012 to 2022, 92 German apheresis centers collected retrospective and prospective observational data of a total of 2,301 patients undergoing regular lipoprotein apheresis (LA) treatment of hypercholesterolemia or/and Lp(a)-hyperlipoproteinemia suffering from progressive atherosclerotic cardiovascular disease (ASCVD), with complete data sets of 1.125 patients, who were the subject of this analysis. More than 61,500 LA sessions are documented in the database. In 2022, all patients treated with LA demonstrated a significant immediate median reduction rate of LDL-C (68.8 %) and Lp(a) (72.9 %). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to eleven years on LA treatment (y+1 to y+11). During the first two years of LA treatment (y+1 and y+2), a MACE reduction of 73 % was observed and continued to be low during y+3 to y+11, when all LA patients were analyzed. LA patients with only increased Lp(a) levels (Lp(a) ≥ 60 mg/dl (≥120 nmol/l) and an LDL-C < 100 mg/dl (<2.6 mmol/l)) had a higher MACE reduction (85 %; n = 443) in the first two years of LA treatment compared to LA patients with only increased LDL-C-levels (LDL-C ≥ 100 mg/dl (≥2.6 mmol/l); Lp(a) < 60 mg/dl (<120 nmol/l)) (53 %; n = 171). Adverse events of LA remained low (about 5 %) over the eleven years and mainly represented puncture problems (1.0 %). No side effects resulted in termination of LA therapy., Conclusions: The current analysis of GLAR data indicates that regular LA leads to very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid-lowering medication, including proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition. Additionally, LA was safe with a low rate of adverse effects over an 11-year period. The number of enrolled patients and the duration of observation establish GLAR as the largest LA registry worldwide., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: The knowledge on the prevalence of elevated lipoprotein(a) (Lp(a)), patients' characteristics, and nongenetic risk factors is scarce in some regions including Poland, the largest Central and Eastern European country. Thus, we aimed to present the results from the Lp(a) registry established in Poland's 2nd largest, supra-regional hospital - the Polish Mother's Memorial Hospital Research Institute (PMMHRI)., Methods: The PMMHRI-Lp(a)-Registry was established in January 2022. Since that time all consecutive patients of the Departments of Cardiology, Endocrinology, and outpatient cardiology, diabetology and metabolic clinics have been included. The indications for Lp(a) measurement in the registry are based on the 2021 Polish Lipid Guidelines and new Polish recommendations on the management of elevated Lp(a) (2024). Lp(a) was determined using Sentinel's Lp(a) Ultra, an Immunoturbidimetric quantitative test (Sentinel, Milan, Italy), and the results are presented in mg/dL., Results: 511 patients were included in the registry between Jan 2022 and 15th May 2024. The mean age of patients was 48.21 years. Female patients represented 53.42 % of the population. Elevated Lp(a) levels above 30 and 50 mg/dL were detected in 142 (27.79 %), and 101 (19.8 %) patients, respectively. The mean Lp(a) level was 30.45 ± 42.50 mg/dL, with no significant sex differences [mean for men: 28.80 mg/dL; women: 31.89 mg/dL]. There were also no significant differences between those with and without: coronary artery disease (CAD), dyslipidemia, stroke, heart failure, cancer, diabetes, chronic kidney disease, and thyroid disease. The significant Lp(a) level difference was observed in those with a history of myocardial infarction (MI) vs those without (51.47 ± 55.16 vs 28.09 ± 37.51 mg/dL, p < 0.001). However, when we divided those with premature vs no premature MI, no significant difference in Lp(a) level was observed (51.43 ± 57.82 vs 51.52 ± 53.18 mg/dL, p = 0.95). Lipid-lowering therapy (LLT) at baseline did not significantly affect Lp(a) level, with only significant differences for the highest doses of rosuvastatin (p < 0.05) and in those treated with ezetimibe (as a part of the combination therapy; 44.73 ± 54.94 vs 26.84 ± 37.11 mg/dL, p < 0.001). For selected patients (n = 43; 8.42 %) with at least two Lp(a) measurements (mean time distance: 7 ± 5 months, range 1-20 months) we did not observe statistically significant visit-to-visit variability (mean difference: 3.25 mg/dL; r = 0.079, p = 0.616). While dividing the whole population into those with Lp(a) ≤30 mg/dL and > 30 mg/dL, the only hyper-Lp(a)-emia prevalence differences were seen for FH diagnosis (12.88 vs 21.43; p = 0.017), MI prevalence (6.52 vs 16.90 %; p < 0.001), thyroid disease diagnosis (18.14 vs 26.76 %; p = 0.033) and ezetimibe treatment (18.58 vs 30.77 %, p = 0.036). A similar pattern was observed while dividing the whole population on those with Lp(a) ≤50 mg/dL (125 nmol/L) and > 50 mg/dL (125 nmol/L) except for no statistical difference for thyroid disease., Conclusions: These results strongly emphasize that Lp(a) should be measured commonly, as its high level is highly prevalent (even every 3rd patient) in patients at cardiovascular disease (CVD) risk in primary and secondary prevention, requiring risk re-stratification and optimization of the treatment. This is especially important in the regions that characterize baseline high CVD risk, which refers to most CEE countries, including Poland., Competing Interests: Declaration of competing interest Dr Lewek has received a speaker's fee from Amgen, Novartis, Sanofi; Dr. Banach has received research grant(s)/support from Amgen, Daiichi Sankyo, Sanofi and Viatris, and has served as a consultant/received speaker's fee for Amgen, Daiichi-Sankyo, Esperion, Kogen, KRKA, Menarini, MSD, Mylan/Viatris, Novartis, Novo-Nordisk, Polpharma, Sanofi, Servier, Teva, and Zentiva; all other authors have nothing to declare in relation to the results of this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

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.

Importance: Lipoprotein(a) (Lp[a]) is an important risk factor for atherothrombotic cardiovascular disease and aortic stenosis, for which there are no treatments approved by regulatory authorities., Objectives: To assess adverse events and tolerability of a short interfering RNA (siRNA) designed to reduce hepatic production of apolipoprotein(a) and to assess associated changes in plasma concentrations of Lp(a) at different doses., Design, Setting, and Participants: A single ascending dose study of SLN360, an siRNA targeting apolipoprotein(a) synthesis conducted at 5 clinical research unit sites located in the US, United Kingdom, and Australia. The study enrolled adults with Lp(a) plasma concentrations of 150 nmol/L or greater at screening and no known clinically overt cardiovascular disease. Participants were enrolled between November 18, 2020, and July 21, 2021, with last follow-up on December 29, 2021., Interventions: Participants were randomized to receive placebo (n = 8) or single doses of SLN360 at 30 mg (n = 6), 100 mg (n = 6), 300 mg (n = 6), or 600 mg (n = 6), administered subcutaneously., Main Outcomes and Measures: The primary outcome was evaluation of safety and tolerability. Secondary outcomes included change in plasma concentrations of Lp(a) to a maximum follow-up of 150 days., Results: Among 32 participants who were randomized and received the study intervention (mean age, 50 [SD, 13.5] years; 17 women [53%]), 32 (100%) completed the trial. One participant experienced 2 serious adverse event episodes: admission to the hospital for headache following SARS-CoV-2 vaccination and later for complications of cholecystitis, both of which were judged to be unrelated to study drug. Median baseline Lp(a) concentrations were as follows: placebo, 238 (IQR, 203-308) nmol/L; 30-mg SLN360, 171 (IQR, 142-219) nmol/L; 100-mg SLN360, 217 (IQR, 202-274) nmol/L; 300-mg SLN360, 285 (IQR, 195-338) nmol/L; and 600-mg SLN360, 231 (IQR, 179-276) nmol/L. Maximal median changes in Lp(a) were -20 (IQR, -61 to 3) nmol/L, -89 (IQR, -119 to -61) nmol/L, -185 (IQR, -226 to -163) nmol/L, -268 (IQR, -292 to -189) nmol/L, and -227 (IQR, -270 to -174) nmol/L, with maximal median percentage changes of -10% (IQR, -16% to 1%), -46% (IQR, -64% to -40%), -86% (IQR, -92% to -82%), -96% (IQR, -98% to -89%), and -98% (IQR, -98% to -97%), for the placebo group and the 30-mg, 100-mg, 300-mg, and 600-mg SLN360 groups, respectively. The duration of Lp(a) lowering was dose dependent, persisting for at least 150 days after administration., Conclusions and Relevance: In this phase 1 study of 32 participants with elevated Lp(a) levels and no known cardiovascular disease, the siRNA SLN360 was well tolerated, and a dose-dependent lowering of plasma Lp(a) concentrations was observed. The findings support further study to determine the safety and efficacy of this siRNA., Trial Registration: ClinicalTrials.gov Identifier: NCT04606602; EudraCT Identifier: 2020-002471-35.

Objectives: To investigate the prevalence and quantity of aortic valve calcium (AVC) in two large cohorts, stratified according to age and lipoprotein(a) (Lp(a)), and to assess the association between Lp(a) and AVC., Methods: We included 2412 participants from the population-based Rotterdam Study (52% women, mean age=69.6±6.3 years) and 859 apparently healthy individuals from the Amsterdam University Medical Centers (UMC) outpatient clinic (57% women, mean age=45.9±11.6 years). All individuals underwent blood sampling to determine Lp(a) concentration and non-enhanced cardiac CT to assess AVC. Logistic and linear regression analyses were performed to investigate the associations of Lp(a) with the presence and amount of AVC., Results: The prevalence of AVC was 33.1% in the Rotterdam Study and 5.4% in the Amsterdam UMC cohort. Higher Lp(a) concentrations were independently associated with presence of AVC in both cohorts (OR per 50 mg/dL increase in Lp(a): 1.54 (95% CI 1.36 to 1.75) in the Rotterdam Study cohort and 2.02 (95% CI 1.19 to 3.44) in the Amsterdam UMC cohort). In the Rotterdam Study cohort, higher Lp(a) concentrations were also associated with increase in aortic valve Agatston score (β 0.19, 95% CI 0.06 to 0.32 per 50 mg/dL increase)., Conclusions: Lp(a) is robustly associated with presence of AVC in a wide age range of individuals. These results provide further rationale to assess the effect of Lp(a) lowering interventions in individuals with early AVC to prevent end-stage aortic valve stenosis., Competing Interests: Competing interests: SSS, YBdR and ES were supported by Amgen: Lp(a) Ahead Study. ESGS has received research grants/support to his institution from Amgen, Sanofi, Resverlogix and Athera, and has served as a consultant for Amgen, Sanofi, Esperion, Novartis and Ionis Pharmaceuticals., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

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.)

Purpose of Review: Summarize recent recommendations on clinical management of adults and youth with elevated lipoprotein(a) [Lp(a)] who are at-risk of or affected by cardiovascular disease (CVD)., Recent Findings: There is ample evidence to support elevated Lp(a) levels, present in approximately 20% of the general population, as a causal, independent risk factor for CVD and its role as a significant risk enhancer. Several guidelines and position statements have been published to assist in the identification, treatment and follow-up of adults with elevated levels of Lp(a). There is growing interest in Lp(a) screening and strategies to improve health behaviors starting in youth, although published recommendations for this population are limited. In addition to the well established increased risk of myocardial infarction, stroke and valvular aortic stenosis, data from the coronavirus pandemic suggest adults with elevated Lp(a) may have a particularly high-risk of cardiovascular complications. Lp(a)-specific-lowering therapies are currently in development. Despite their inability to lower Lp(a), use of statins have been shown to improve outcomes in primary and secondary prevention., Summary: Considerable differences exist amongst published guidelines for adults on the use of Lp(a) in clinical practice, and recommendations for youth are limited. With increasing knowledge of Lp(a)'s role in CVD, including recent observations of COVID-19-related risk of cardiovascular complications, more harmonized and comprehensive guidelines for Lp(a) in clinical practice are required. This will facilitate clinical decision-making and help define best practices for identification and management of elevated Lp(a) in adults and youth., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

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.)

The treatment of elevated plasma lipids plays an important role in atherosclerosis prevention. Low-density lipoprotein (LDL) cholesterol lowering with statins and, if required, additional inhibition is of the utmost importance. Lifestyle modification plays only a minor role in LDL cholesterol lowering. Absolute cardiovascular risk determines whether and at what intensity lipid lowering therapy should be implemented. Thus, in patients at very high risk, an LDL cholesterol level <55 mg/dl (<1.4 mmol/l) and a 50% reduction from baseline should be achieved. With respect to elevated triglyceride concentrations, treatment goals are less clearly defined, despite the fact that elevated triglyceride concentrations are causally linked to atherosclerotic events. Lifestyle modification can significantly reduce triglyceride concentrations and are often more effective than specific triglyceride lowering medications. New lipid lowering drugs still need to prove their clinical benefit in endpoint trials.

The emergence of pathophysiological, epidemiologic, and genetic data strongly supports the causality for lipoprotein(a) [Lp(a)] in cardiovascular disease (CVD) and calcific aortic valve disease (CAVD). In parallel, novel Lp(a) lowering approaches have been developed that have re-invigorated clinical interest in Lp(a). Because Lp(a) is the most prevalent monogenetic lipid disorder globally, with prevalence of Lp(a) > 50 mg/dL estimated at >1.4 billion people, the rationale for diagnosing and managing Lp(a)-mediated risk is now stronger than ever. Patients with elevated Lp(a) are significantly under-diagnosed and the diagnosis is frequently made ad hoc rather than systematically. Elevated Lp(a) levels are associated with atherothrombotic risk and patients present with varied clinical phenotypes, ranging from stroke in pediatric age groups, to ST-segment elevation myocardial infarction in young males, to CAVD in elderly individuals. A new clinical care paradigm of a dedicated "Lp(a) Clinic" would serve to evaluate and manage such patients who have elevated Lp(a) as the pathophysiological etiology. Such a clinic would include multidisciplinary expertise in lipid metabolism, clinical cardiology, vascular medicine, valvular disease, thrombosis, and pediatric aspects of clinical care. This viewpoint argues for the rationale of an Lp(a) outpatient clinic where patients with elevated Lp(a) and their affected relatives can be referred, evaluated, managed and followed, to ultimately reduce Lp(a)-mediated CVD and CAVD risk., Competing Interests: Declaration of competing interest ST is a co-inventor, receives royalties from patents owned by the University of California San Diego on oxidation-specific antibodies, is a co-founder of Oxitope, Inc and Kleanthi Diagnostics and currently has a dual appointment at UCSD and as an employee of Ionis Pharmaceuticals. ESGS is a consultant for Akcea Therapeutics, Amgen, Sanofi, Esperion, and has received research grants from Sanofi., (Copyright © 2020. Published by Elsevier B.V.)

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: 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: 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.)

Objective: A high level of LDL-C (low-density lipoprotein cholesterol) is a major risk factor for cardiovascular disease. The E3 ubiquitin ligase named IDOL (inducible degrader of the LDLR [LDL receptor]; also known as MYLIP [myosin regulatory light chain interacting protein]) mediates degradation of LDLR through ubiquitinating its C-terminal tail. But the expression profile of IDOL differs greatly in the livers of mice and humans. Whether IDOL is able to regulate LDL-C levels in humans remains to be determined. Approach and Results: By using whole-exome sequencing, we identified a nonsynonymous variant rs149696224 in the IDOL gene that causes a G51S (Gly-to-Ser substitution at the amino acid site 51) from a Chinese Uygur family. Large cohort analysis revealed IDOL G51S carriers (+/G51S) displayed significantly higher LDL-C levels. Mechanistically, the G51S mutation stabilized IDOL protein by inhibiting its dimerization and preventing self-ubiquitination and subsequent proteasomal degradation. IDOL(G51S) exhibited a stronger ability to promote ubiquitination and degradation of LDLR. Adeno-associated virus-mediated expression of IDOL(G51S) in mouse liver decreased hepatic LDLR and increased serum levels of LDL-C, total cholesterol, and triglyceride., Conclusions: Our study demonstrates that IDOL(G51S) is a gain-of-function variant responsible for high LDL-C in both humans and mice. These results suggest that IDOL is a key player regulating cholesterol level in humans.

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.)

Introduction and Objectives: Primary biliary cholangitis (PBC) is a chronic cholestatic autoimmune disease that disrupts the cholesterol metabolism. Our aim was to investigate the frequency of dyslipidemias and to evaluate the risk of cardiovascular events in a historic cohort of patients with PBC., Patients: All patients attended from 2000 to 2009 with histological diagnosis of PBC were included and were compared with healthy controls. The 10-year cardiovascular risk was estimated by the Framingham risk score., Results: Fifty four patients with PBC were included and compared to 106 controls. Differences in total cholesterol (263.8±123.9mg/dl vs. 199.6±40, p=0.0001), LDL-cholesterol (179.3±114.8 vs. 126.8±34.7, p=0.0001), HDL-cholesterol (62.4±36.2mg/dl vs. 47.3±12.3, p=0.0001) and triglycerides (149.1±59.1mg/dl vs. 126.4±55.4, p=0.001) were found. Hypercholesterolemia (>240mg/dl) was found in 52.4% of the patients with PBC vs. 11% in the control group, high LDL-cholesterol (160-189mg/dl) in 45.2% of the patients with PBC vs. 10% in controls and hyperalphalipoproteinemia (HDL-cholesterol >60mg/dl) in 45.2% of the patients with PBC vs. 16% in controls. The 10-year cardiovascular risk was 5.3%±5.9 in the patients with PBC and 4.1%±5.7 in the control group (p=0.723, IC 95%=0.637-1.104). Only one cardiovascular event (stroke) in a patient with PBC was registered in a mean follow up time of 57.9±36.5 months., Conclusions: Marked derangements in serum lipids and a high frequency of dyslipidemias are found in patients with PBC, however, these do not increase the risk of cardiovascular events., (Copyright © 2019. Published by Elsevier España, S.L.U.)

Familial combined hyperlipidemia, which presents as hypercholesterolemia or hypertriglyceridemia, is the commonest form of genetic hyperlipidemia and is associated with premature coronary artery disease. This is a rare case report of a 27 day-old neonate born out of a third-degree consanguineous marriage, with grade III lipemia retinalis secondary to familial-combined hyperlipidemia., Competing Interests: None

Background: Concentrations of circulating apolipoproteins are strongly linked to risk for coronary artery disease (CAD). The relative importance of the additional knowledge of apolipoprotein concentrations within specific lipoprotein species for CAD risk prediction is limited., Objectives: This study sought to evaluate the performance of a high-density lipoprotein (HDL) apolipoproteomic score, based on targeted mass spectrometry of HDL-associated apolipoproteins, for the detection of angiographic CAD and outcomes., Methods: HDL-associated apolipoprotein (apo) A-1, apoC-1, apoC-2, apoC-3, and apoC-4 were measured in 943 participants without prevalent myocardial infarction (MI) referred for coronary angiography in the CASABLANCA (Catheter Sampled Blood Archive in Cardiovascular Diseases) study. A composite HDL apolipoproteomic score (pCAD) was associated with likelihood of obstructive CAD (≥70% lesion in ≥1 vessel) and with incident cardiovascular outcomes over 4-year follow-up., Results: There were 587 (62.2%) patients with coronary stenosis. The pCAD score was associated with the presence of obstructive CAD (odds ratio: 1.39; 95% confidence interval [CI]: 1.14 to 1.69; p < 0.001), independently of conventional cardiovascular risk factors including circulating plasma apoA-1 and apoB. The C-index for pCAD was 0.63 (95% CI: 0.59 to 0.67) for the presence of obstructive CAD. Although pCAD was not associated with cardiovascular mortality among all individuals (hazard ratio: 1.24; 95% CI: 0.93 to 1.66; p = 0.15), there was evidence of association for individuals with obstructive CAD (hazard ratio: 1.48; 95% CI: 1.07 to 2.05; p = 0.019)., Conclusions: An HDL apolipoproteomic score is associated with the presence of CAD, independent of circulating apoA-1 and apoB concentrations and other conventional cardiovascular risk factors. Among individuals with CAD, this score may be independently associated cardiovascular death. (The CASABLANCA Study: Catheter Sampled Blood Archive in Cardiovascular Diseases [CASABLANCA]; NCT00842868)., (Copyright © 2019 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Lipoprotein(a) [Lp(a)] is a genetically determined risk factor for calcific aortic valve stenosis (CAVS) for which transcatheter aortic valve replacement (TAVR) is increasingly utilized as treatment. We evaluated the effect of a program to increase testing of and define the prevalence of elevated Lp(a) among patients undergoing TAVR. Educational efforts and incorporation of a "check-box" Lp(a) order to the preoperative TAVR order set were instituted. Retrospective chart review was performed in 229 patients requiring TAVR between May 2013 and September 2018. Of these patients, 57% had an Lp(a) level measured; testing rates increased from 0% in 2013 to 96% in 2018. Lipoprotein(a) testing occurred in 11% of patients before and in 80% of patients after the "check-box" order set ( P < .001). The prevalence of elevated Lp(a) (≥30 mg/dL) was 35%; these patients had a higher incidence of coronary artery disease requiring revascularization compared with patients with normal Lp(a) (65% vs 47%; P = .047). Patients with Lp(a) ≥30 mg/dL also had higher incidence of paravalvular leak compared with those with normal Lp(a) (13% vs 4%; P = .04). This study defines the prevalence of elevated Lp(a) in advanced stages of CAVS and provides a practice pathway to assess procedural complications and long-term outcomes of TAVR in patients with elevated Lp(a) levels.

Background: Therapeutic apheresis is a term used to describe a group of treatments where blood components are separated in real time, and one component is removed, exchanged, and/or treated to remove pathogenic substances from the circulation. Plasma exchange, which removed all plasma components, and lipid apheresis which selectively removes lipoproteins from circulation, have both been used to treat atherosclerotic vascular diseases., Methods: To review the literature regarding the application of therapeutic apheresis for atherosclerotic vascular diseases., Results: Primarily lipid apheresis is used to treat atherosclerotic vascular diseases, particularly familial hypercholesterolemia, lipoprotein (a) hyperlipoproteinemia and peripheral vascular diseases. Lipid apheresis can be used as first line or second line treatment with a strong evidenced-based recommendation. Its use has decreased atherosclerotic events., Conclusion: Lipid apheresis is an important therapy for the treatment of familial hypercholesterolemia, lipoprotein (a) hyperlipoproteinemia and peripheral vascular diseases. Lipid apheresis does more than remove low-density lipoproteins and other lipoproteins but also decreases inflammatory markers and improves blood flow.

Background and Aims: High levels of lipoprotein(a) [Lp(a)] are associated with increased risk of acute coronary syndrome (ACS). We explored whether Lp(a) exhibits a stronger association with premature ACS., Methods: A case-control study was conducted; 1457 patients with a history of ACS (54.8 ± 13 years, 86% males) and 2090 age-sex matched adults free of cardiovascular disease were enrolled. Bio-clinical characteristics [risk factors, low-density lipoprotein-cholesterol, Lp(a)] were derived through standard procedures., Results: A 10 mg/dL increase in Lp(a) was associated with 4% (95% CI, 1.01 to 1.02) higher likelihood of having ACS in younger (<45 years) and 2% (95% CI, 1.01 to 1.02) higher likelihood in middle-aged (45-60 years) individuals. Adjusting for common risk factors, elevated Lp(a), i.e. >50 mg/dL, was still associated with increased likelihood of ACS in younger adults (<45 years) (OR = 2.88, 95% CI, 1.7 to 4.6) and in middle aged ones (45 and 60 years) (OR = 2.06, 95% CI, 1.4 to 3.2), but not in older participants (>60 years) (OR = 1.31, 95% CI, 0.8 to 2.4)., Conclusions: Lp(a) seems to be an independent risk factor for ACS in individuals <45 years, and high Lp(a) levels increase by ∼3folds the risk for ACS. The association is preserved but is less in middle-aged individuals (45-60 years) and is abolished >60 years., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To examine patterns of non-high-density lipoprotein (HDL) cholesterol in early childhood and identify factors associated with persistent high non-HDL cholesterol in healthy urban children., Study Design: We identified all children enrolled in a primary care practice-based research network called TARGet Kids! (The Applied Research Group for Kids) with ≥3 laboratory measurements of non-HDL cholesterol. Latent class growth model analysis was performed to identify distinct trajectory groups for non-HDL cholesterol. Trajectory groups were then categorized into "normal" vs "persistent-high" non-HDL cholesterol based on guideline cut-off values and logistic regression was completed to examine the association between trajectory group and the presence of anthropometric and cardiometabolic risk factors., Results: A total of 608 children met inclusion criteria for the trajectory analysis (median age at enrolment = 18.3, IQR = 27.9 months). Four trajectory groups were identified with 2 groups (n = 451) categorized as normal non-HDL cholesterol and 2 groups (n = 157) as persistent high non-HDL cholesterol. Family history of high cholesterol (OR 2.04, 95% CI 1.27-3.28) was associated significantly with persistent high non-HDL cholesterol, whereas East/Southeast Asian vs European ethnicity (OR 0.33, 95% CI 0.14-0.78), longer breastfeeding duration (OR 0.96, 95% CI 0.93-1.00), and greater birth weight (OR 0.69, 95% CI 0.48-1.00) were associated with lower odds of persistent high non-HDL cholesterol., Conclusions: Patterns of non-HDL cholesterol are identified during early childhood, and family history of high cholesterol was associated most strongly with persistent high non-HDL cholesterol. Future research should inform the development of a clinical prediction tool for lipids in early childhood to identify children who may benefit from interventions to promote cardiovascular health., (Copyright © 2017 Elsevier Inc. All rights reserved.)

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.)

Lipoprotein apheresis has been shown to improve the cardiovascular outcome in patients with atherosclerotic disease and therapy-refractory hypercholesterolemia or elevated lipoprotein (a) (Lp(a)). An elevated intake of omega-3 polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) has also been associated with a reduced cardiovascular risk. However, until now only little is known about the effect of apheresis treatment on the levels of omega-6 and omega-3 polyunsaturated fatty acids (n-6 PUFA and n-3 PUFA) in patients. Using gas chromatography (GC) the present study analyzed the content of n-6 and n-3 PUFA as well as saturated fatty acids and monounsaturated fatty acids in the plasma of 20 patients with hyperlipidemia undergoing regular lipoprotein apheresis procedures in direct pre- and post-therapy measurements. Lipoprotein apheresis uniformly reduced the concentrations of arachidonic acid (AA), EPA and DHA fatty acids analyzed in the plasma. However, the three different apheresis methods analyzed (heparin precipitation, membrane filtration and direct absorption) had different effects on the fatty acid profile in the plasma. We found that heparin precipitation and direct absorption apheresis procedures led to a significant decrease of plasma n-3 and n-6 PUFA by 40-50%. In contrast, patients undergoing membrane filtration apheresis, levels pre- and post-apheresis did not change significantly, with AA and EPA being only reduced by approximately 10% while levels of DHA were maintained pre- and post-apheresis. In contrast, total triglyceride levels were lowered most potently by membrane filtration apheresis. In summary, heparin precipitation and direct absorption apheresis approaches significantly lowered polyunsaturated fatty acids in plasma, while membrane filtration did not. This might have implications for cardiovascular and inflammatory risk/benefit profiles associated with n-6 and n-3 PUFA levels in the body., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Introduction: Lipoprotein apheresis (LA) represents the only effective therapeutic option for patients with elevated Lipoprotein(a) (Lp(a)) levels. We aimed at analyzing the Lp(a) reduction, rebound rates as well as mean interval values between two weekly apheresis sessions, since this might be important for the prediction of the residual cardiovascular risk and development of individualized approaches for this special therapeutic strategy., Materials and Methods: 20 patients under weekly and 2 patients under twice weekly apheresis were included. We measured serum concentrations of Lp(a), total, LDL-, HDL - cholesterol and triglycerides daily over 7 days after single LA sessions., Results: Mean Lp(a) levels was 158.1 ± 69.82 nmol/l before the LA session, decreased acutely by 76 ± 7% and increased to 97 ± 13% of the baseline value within 7 days in patients under weekly treatment. By mathematical modeling, the acute Lp(a) reduction can be calculated from the function: y (nmol/l) = 3.415 + 0.738 * x (R 2  = 0.970), where x is the baseline Lp(a) value. The recovery rate can be predicted from the equation: y (%) = 22.49 + 18.64 * x - 1.14 * x 2 (R 2  = 0.874), where x is the day after apheresis. The empirical formula for the mean interval value is: y (nmol/l) = x - 12, where x is the absolute reduction in nmol/l., Conclusion: We modeled - for the first time - equations to predict the course of Lp(a) serum levels under weekly LA which are simple, reliable and enable the development of optimal individualized protocols of this costly lipid lowering therapy., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Background and Aims: Dyslipidaemias are associated with cardiovascular mortality and morbidity, driven by unstable atherosclerotic plaques with inflammatory infiltrates. Levels of messenger RNA (mRNA) for pro-inflammatory cytokines have been positively correlated with atherosclerotic disease progression. Therapeutic lipoprotein apheresis (LA) reduces plasma lipid levels and reduces inflammation. We evaluated the effects of LA on expression of mRNA coding for key pro-inflammatory cytokines in patients with dyslipidaemia, homo-/hetero-zygous familial hypercholesterolaemia (HoFH, HeFH) or hyperlipoprotein(a)aemia [hyperLp(a)] and associated coronary artery disease (CAD)., Approach: Ten patients (five males and five females, mean age 47 ± 9.2 years) were enrolled, all with HyperLp(a) or confirmed genetic diagnoses of dyslipidaemia, HoFH, or HeFH; all had associated CAD. mRNA determinations were via reverse transcriptase polymer chain reaction (RT-qPCR)., Results: LA was associated with downregulation of mRNA expression for IL-1α, IL-6 and TNF-α, starting after the first LA session. The observed reduction was progressively enhanced during the interval between the first and second LA sessions to achieve a maximum decrease by the end of the second session (IL-1α: -49%, p < 0.001; IL-6: -35%, p < 0.001; TNF-α: -56%, p < 0.001)., Conclusions: LA suppresses the expression of IL-1α, IL-6 and TNF-α mRNA in patients with dyslipidaemias. This may contribute to the arterial anti-inflammatory effect of LA., (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.)

Purpose of Review: The aim of this study was to review and assess the evidence for low-density lipoprotein cholesterol (LDL-C) treatment goals as presented in current guidelines for primary and secondary prevention of cardiovascular disease., Recent Findings: Different sets of guidelines and clinical studies for secondary prevention have centered on lower absolute LDL-C targets [<70 mg/dL (<1.8 mmol/L)], greater percent reductions of LDL-C (≥50%), or more intense treatment to achieve greater reductions in cardiovascular risk. Population-based risk models serve as the basis for statin initiation in primary prevention. Reviews of current population risk models for primary prevention show moderate ability to discriminate [with c-statistics ranging from 0.67 to 0.77 (95% CIs from 0.62 to 0.83) for men and women] with poor calibration and overestimation of risk. Individual clinical trial data are not compelling to support specific LDL-C targets and percent reductions in secondary prevention. Increasing utilization of electronic health records and data analytics will enable the development of individualized treatment goals in both primary and secondary prevention.

The first experimental model of atherosclerosis (in rabbits) is more than hundred years old. Several animal species have been used to produce hyperlipoproteinemia and possible atherosclerosis. The gene manipulation produced the most used models recently. This review acknowledges the extensive study of atherosclerotic changes in experimental models of hyperlipoproteinemia and atherosclerosis to come to light thus far and the purpose here is not only to summarize the published data but also to try to add some details of our experience in using these models. In addition to rabbit (the old but also improved model by reno-vascular hypertension) dog, birds, pig, hamster, mice, rat and non-human primate's animal models are described. The gene manipulation produced the most used models two decades ago. Germline genetically engineered (without apoE or LDL receptor genes) animals have become the most used models producing atherosclerotic changes in the aorta. Recent new models also producing atherosclerotic changes but without germline genetic manipulation are also described.

Background: Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology and of Lipidologists and completed the data set for the registry according to the current guidelines and the German indication guideline for apheresis in 2009. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data are available over nearly 5 years now., Methods and Results: During the time period 2012-2016, 71 German apheresis centers collected retrospective and prospective observational data of 1435 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-C levels and/or high Lp (a) levels suffering from cardiovascular disease (CVD) or progressive CVD. A total of 15,527 completely documented LA treatments were entered into the database. All patients treated by LA showed a median LDL-C reduction rate of 67.5%, and a median Lp (a) reduction rate of 71.1%. Analog to the Pro(a)LiFe pattern, patient data were analyzed to the incidence rate of coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y‑1) and prospectively two years on LA treatment (y + 1 and y + 2). During two years of LA treatment a MACE reduction of 78% was observed. In the years considered, side effects of LA treatment were low (5.9%) and mainly comprised puncture problems., Conclusions: The data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp (a) levels, progressive CVD, and maximally tolerated lipid lowering medication. In addition, LA treatments were found to be safe with a low rate of side effects.

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.

Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD). Lipoprotein apheresis (LA) is a safe well-tolerated outpatient treatment to lower LDL-C and Lp(a) by 60-70%, and is the ultimate escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing cardiovascular events. Lp(a)-HLP associated with progressive CVD has been approved as indication for regular LA in Germany since 2008. The Pro(a)LiFe-study investigated with a prospective multicenter design the long-term preventive effect of LA on incidence rates of cardiovascular events prospectively over a period of 5 years in 170 consecutive patients who commenced regular LA. During a median period of 4.7 years of the pre-LA period, Lp(a) associated progressive CVD became apparent. Apolipoprotein(a) (apo(a)) isoforms and polymorphisms at the apo(a) gene (LPA) were analyzed to assess hypothetical clinical correlations. 154 patients (90.6%) completed 5‑years follow-up. Significant decline of the mean annual major adverse cardiac event (MACE) rate was observed from 0.41 ± 0.45 two years prior to regular LA to 0.06 ± 0.11 during 5 years with regular LA (p < 0.0001). 95.3% of patients expressed at least one small apo(a) isoform. Calculation of isoform specific concentrations allowed to confirm the equivalence of 60 mg/dl or 120 nmol/l as Lp(a) thresholds of the German LA guideline. Results of 5 years prospective follow-up confirmed that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP and afore progressive CVD.

Background: Recently it has been demonstrated that elevated lipoprotein (a) (LPA) levels are associated with an increased risk of cardiovascular disease across multiple ethnic groups. However, there is only scanty data about the incidence of elevated LPA levels in different patient cohorts. As a consequence, we aimed to examine whether patients with elevated LPA levels might be seen more often in a cardiovascular center in comparison to the general population., Methods: We reviewed LPA concentrations of 52,898 consecutive patients who were admitted to our hospital between January 2004 and December 2014. We subdivided them into different groups according to their LPA levels. Data was compared to available information in medical literature., Results: 26.4% of the patients had LPA levels >30 mg/dl which is in line with the data from literature. Mean level of LPA concentration in our study was twice as high in comparison to the general population (25.8% vs. 13.3%). 4.6% had LPA levels >98 mg/dl (general population <0.3%)., Conclusion: In patients admitted to a cardiovascular center the proportion of LPA >30 mg/dl is comparable to the general population but mean levels over all are twice as high and the proportion of patients with LPA levels of >98 mg/dl is extremely higher.

A high level of lipoprotein(a) (Lp(a)) is recognized as an independent and additional cardiovascular risk factor contributing to the risk of early onset and progressive course of cardiovascular disease (CVD). All lipid lowering medications in use mainly lower low density lipoprotein-cholesterol (LDL-c) with no or limited effect on levels of Lp(a). Niacin, the only component lowering Lp(a), is firstly often poorly tolerated and secondly not available anymore in many countries. A level of <50 mg/dl was recommended recently as the cut off level for clinical use and decision making. Since lipoprotein apheresis (LA) lowers not only LDL-c but also Lp(a) significantly, its use is recommended in some countries in very high-risk patients with early or progressive CVD. Retrospective analyses show that regular LA improves the course of CVD. This is supported by a recent prospective observational trial and data of the German Lipoprotein Apheresis Registry. Despite many treatment options, all too often it is not possible to reduce LDL-c levels to target and to reduce Lp(a) levels sustainably at all. Therefore, new drug therapies are awaited. Some of the lipid modifying drugs in development lower Lp(a) to some extent in addition to LDL-c; the only specific approach is the apoprotein(a) antisense oligonucleotide. Currently LA is the standard of care as a last resort treatment in high-risk patients with elevated Lp(a) and severe CVD despite optimal control of all other cardiovascular risk factors.