scholarly journals Korszerű lipidcsökkentő kezelés

2016 ◽  
Vol 157 (31) ◽  
pp. 1219-1223 ◽  
Author(s):  
György Paragh ◽  
István Karádi
Keyword(s):  
Monoclonal Antibodies ◽  
Cardiovascular Events ◽  
Ldl Cholesterol ◽  
Cholesterol Absorption ◽  
New Agents ◽  
Considerable Evidence ◽  
Cholesterol Levels ◽  
Cholesterol Absorption Inhibitor ◽  
Reasonable Approach ◽  
New Strategies

Considerable evidence suggests that “the lower the better” is a reasonable approach for reducing cardiovascular risk by lowering LDL cholesterol levels. Despite the reduction in cardiovascular events and mortality achieved by statin therapy, significant residual risk remains, especially in severe hereditary hypercholesterolemia, such as familial hypercholesterolemia. Some new strategies to achieve even lower LDL levels are now available, including the addition of cholesterol absorption inhibitor ezetimibe, and the recently available Proprotein convertase subtilisin/kexin type 9 monoclonal antibodies. In addition, new LDL drugs may be effectively administrated in those individuals who are unable to tolerate statins. The authors summarize the efficacy and clinical indications of these new agents and review the currently available guidelines. Orv. Hetil., 2016, 157(31), 1219–1223.

Lipids in health and disease

2004 ◽  
Vol 32 (6) ◽  
pp. 1051-1056 ◽  
Author(s):  
J. Shepherd
Keyword(s):  
Statin Therapy ◽  
Poor Response ◽  
Cholesterol Absorption ◽  
Lipid Lowering ◽  
Cholesterol Lowering ◽  
Cholesterol Levels ◽  
Cholesterol Absorption Inhibitor ◽  
Health And Disease ◽  
Cholesterol Control ◽  
Lipid Lowering Agents

The evidence linking cholesterol levels in the blood to vascular risk is now incontrovertible and the introduction of HMG CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase inhibitor (or statin) therapy into clinical practice has now revolutionized the management of lipid disorders and silenced at a stroke the critics of cholesterol control as a means to vascular disease prevention. Statins were the first lipid-lowering agents, which, within a framework of a clinical trial, actually extended life by mechanisms that probably go beyond cholesterol alone. Their benefits are so impressive that some enthusiasts have been emboldened to write that they ‘are to atherosclerosis what penicillin was to infectious disease’. But is Nature as easily tamed as we might imagine? Some individuals show a modest or even poor response to statin therapy. The recent discovery of ezetimibe, a highly efficient and precise cholesterol absorption inhibitor, has proven to be a very effective cholesterol lowering alternative for them and combining statins with ezetimibe, thereby inhibiting cholesterol absorption and endogenous synthesis, takes us to realms of cholesterol lowering capability that could not have been dreamt of a decade ago.

2980The effect of monoclonal antibodies against PCSK9 on circulating CD34+ progenitor cells interactions with platelets in patients with familial hypercholesterolemia

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A N Tsouka ◽  
E N Liberopoulos ◽  
C V Rizos ◽  
E C Christopoulou ◽  
M S Elisaf ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Progenitor Cells ◽  
Ldl Cholesterol ◽  
Density Lipoprotein ◽  
Cell Types ◽  
Membrane Expression ◽  
Cholesterol Levels ◽  
Cd34 Cells ◽  
Endothelial Phenotype

Abstract Introduction Platelets interact with circulating CD34+ progenitor cells inducing their differentiation into endothelial progenitor cells (EPCs) and further promoting EPC maturation into endothelial cells, an important step for endothelial regeneration and angiogenesis. PSCK9 is a serine protease that may not only play a crucial role in binding to the low density lipoprotein receptor (LDL-R) increasing its endosomal and lysosomal degradation thus inhibiting its recycling to the cell surface, leading to increasing LDL-cholesterol levels in plasma, but may also exhibit several, independent on LDL-R, activities on a plethora of cell types, including platelets. Purpose We investigated whether monoclonal antibodies (mabs) against PCSK9 could affect platelet interaction with CD34+ cells as well as their differentiation into EPCs, in patients with Familial Hypercholestorelemia (FH). Patients and methods Patients with FH (n=11, 8 men and 3 women, mean age 53±10 years) being under statin/ezetimibe therapy (40mg statin/ 10mg ezetimibe) participated in the study. Patients exhibited resisting high LDL-cholesterol levels, therefore following the existing guidelines, they received mab against PCSK9 (7 evolocumab, 140mg/ml and 4 alirocumab, 150mg/ml) every two weeks. Blood samples were drawn before and after 4 doses of the antibody i.e. after two months (Follow-up). In addition to the patients' serum lipid profile, the endothelial phenotype of CD34+ (membrane expression levels of KDR which is a receptor for VEGF and an endothelial phenotype marker) on CD34+ cells (CD34+-KDR+ cells) and the formation of platelet-CD34+ (CD61+-CD34+) and platelet-KDR+ (CD61+-KDR+) conjugates were also determined by flow cytometry on whole blood after dual labelling with anti-VEGFR-R2/KDR-PE, anti-CD61-PerCP and anti-CD34-FITC. The results were expressed as the %gated of CD34+-KDR+ cells, as well as CD61+-CD34+ and CD61+-KDR+ conjugates. Results The baseline LDL-cholesterol levels were significantly reduced from 172±43 mg/dl to 51±17 at follow-up, p=0.0001. Importantly, the formation of CD61+-CD34+ and CD61+-KDR+ conjugates were increased from baseline to follow-up (from 1.39±1.3 to 2.23±2.8, p=0.037) and (from 2.91±4.2 to 5.92±6.01, p=0.014), respectively. The membrane expression of KDR on CD34+ cells was also increased from 0.79±0.9 to 1.36±0.90, p=0.042, which reflects the increase in the CD34+ endothelial phenotype. Conclusion We show for the first time that the mabs against PCSK9, significantly increase the CD34+ endothelial phenotype in FH patients, which may at least partially attributed to the increase in the platelet interaction with CD34+ cells (platelet-CD34+ conjugates). The underlying mechanisms as well as the consequences of this effect at the clinical level for these patients are under investigation.

scholarly journals Consumption of tall oil-derived phytosterols in a chocolate matrix significantly decreases plasma total and low-density lipoprotein-cholesterol levels

2002 ◽  
Vol 88 (5) ◽  
pp. 479-488 ◽  
Author(s):  
Jacqueline de Graaf ◽  
Pernette R. W. de Sauvage Nolting ◽  
Marjel van Dam ◽  
Elizabeth M. Belsey ◽  
John J. P. Kastelein ◽  
...  
Keyword(s):  
Ldl Cholesterol ◽  
Controlled Trial ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Cholesterol Absorption ◽  
Tall Oil ◽  
Double Blind ◽  
Intestinal Cholesterol Absorption ◽  
Primary Hypercholesterolaemia ◽  
Cholesterol Levels

In a randomized, double-blind, placebo-controlled trial we evaluated the effect of dietary chocolates enriched with a wood-based phytosterol–phytostanol mixture, containing 18% (w/w) sitostanol, compared with placebo dietary chocolates in seventy subjects with primary hypercholesterolaemia (total cholesterol levels below 8 mmol/l). For 4 weeks, participants consumed three servings of the phytosterol-enriched chocolate/d that provided 1·8 g unesterified phytosterols/d or a placebo chocolate in conjunction with a low-fat, low-cholesterol diet. Plasma total and LDL-cholesterol levels were statistically significantly reduced by 6·4% (−0·44 mmol/l) and 10·3% (−0·49 mmol/l), respectively, after 4 weeks of phytosterol-enriched-chocolate treatment. Plasma HDL-cholesterol and triacylglycerol levels were not affected. Consumption of phytosterol-enriched chocolates significantly increased plasma lathosterol concentration (+20·7%), reflecting an increased endogenous cholesterol synthesis in response to phytosterol-induced decreased intestinal cholesterol absorption. Furthermore, the chocolates enriched with phytosterols significantly increased both plasma sitosterol (+95·8%) and campesterol (+64·1%) levels, compared with the placebo chocolate group. However, the absolute values of plasma sitosterol and campesterol remained within the normal range, that is, below 10 mg/l. The chocolates with phytosterols were palatable and induced no clinical or biochemical side effects. These findings indicate that dietary chocolate enriched with tall oil-derived phytosterols (1·8 g/d) is effective in lowering blood total and LDL-cholesterol levels in subjects with mild hypercholesterolaemia and thus may be helpful in reducing the risk of CHD in these individuals.

Ease: Ezetimibe Add-on to Statin for Effectiveness Trail

2006 ◽  
Vol 4 (1) ◽  
pp. 32-35
Author(s):  
Linda Brokes
Keyword(s):  
National Cholesterol Education Program ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Cholesterol Absorption ◽  
Adult Treatment ◽  
Adult Treatment Panel ◽  
Community Based ◽  
Cholesterol Absorption Inhibitor ◽  
Additional Reduction

Results from the largest community-based clinical trial to date, involving more than 3000 patients, has shown that adding the cholesterol absorption inhibitor ezetimibe to ongoing stable statin therapy in patients with hypercholesterolemia produces a significant additional reduction in low-density lipoprotein (LDL)- cholesterol compared with adding a placebo.[1] In addition, more patients who added ezetimibe achieved their National Cholesterol Education Program Adult Treatment Panel (NCEP ATP) If LDL-cholesterol targets. The Ezetimibe Add-on to Statin for Effectiveness (EASE) trial included a total of 3030 patients on a stable dose of a statin but not yet at their NCEP ATP III LDLcholesterel goal,[2]

Guideline-oriented ambulatory lipid-lowering therapy of patients at high risk for cardiovascular events by cardiologists in clinical practice: the 2L cardio registry

2009 ◽  
Vol 16 (4) ◽  
pp. 438-444 ◽  
Author(s):  
Anselm K. Gitt ◽  
Claus Juenger ◽  
Christina Jannowitz ◽  
Barbara Karmann ◽  
Juergen Senges ◽  
...  
Keyword(s):  
Clinical Practice ◽  
High Risk ◽  
Cardiovascular Events ◽  
Cholesterol Absorption ◽  
Lipid Lowering ◽  
Target Level ◽  
High Risk Patients ◽  
Total Cohort ◽  
Cholesterol Absorption Inhibitor ◽  
Risk Patients

Background Lipid-lowering treatment has been proven to decrease the rate of cardiovascular events in high-risk patients with manifest coronary artery disease (CAD) or CAD equivalent risk profile. Current treatment guidelines recommend low-density lipoprotein-cholesterol (LDL-C) less than 100 mg/dl (optional < 70 mg/dl) as the target level for this high-risk population. Little is known about the ambulatory treatment of high-risk patients in clinical practice and the achievement of guideline recommended target values. Methods and results In the ‘2L cardio’ registry in Germany, 295 cardiologists enrolled 6711 consecutive patients with known CAD, and/or diabetes mellitus, peripheral arterial disease (summarized as ‘coronary risk equivalent’, CE), on chronic statin treatment. They recorded actual LDL-C values at entry, probable changes in therapy, and the expected LDL-C values using a lipid calculator based on an earlier observational study in a similar setting. The three groups comprised 2618 patients with CAD plus CE (39.0%; median LDL-C 112 mg/dl), 3436 patients with CAD only (51.2%; median LDL-C 108 mg/dl), and 657 with CE only (9.8%; median LDL-C 124 mg/dl). They had LDL-C levels less than 100 mg/dl in 36.2% [95% confidence intervals (CI): 34.3–38.1], 39.7% (CI: 38.0–41.4), and 27.2% (CI: 23.7–30.7), respectively. Statin doses at entry were usually in the lower to intermediate range (e.g. simvastatin median 25 mg/day). Cardiologists switched to another statin in 10.1% (9.4–10.8), increased the dose of statins (if same drug) in 22.2% (CI: 21.1–23.2) and/or added a cholesterol absorption inhibitor in 23.7% (CI: 22.7–24.7) of the patients. The cardiologists’ intervention improved expected LDL-C levels in the total cohort by a mean of 9.0 mg/dl, but the 100 mg/dl LDL-C target was only reached in 51.3% (CI: 50.0–52.5) of the total cohort. CE patients appeared undertreated in terms of antiplatelet drugs. Discussion Through infrequent increases in statin doses and mainly through add-on of a cholesterol absorption inhibitor, cardiologists improved target level attainment. Compared with earlier studies in the outpatient setting, the treatment to target for LDL-C of high-risk CAD patients has improved, but is not satisfactory.

Low-density lipoprotein cholesterol lowering for the prevention of cardiovascular outcomes in patients with ischemic stroke

2019 ◽  
Vol 14 (5) ◽  
pp. 476-482 ◽  
Author(s):  
George Ntaios ◽  
Haralampos Milionis
Keyword(s):  
Ischemic Stroke ◽  
Cardiovascular Events ◽  
Ldl Cholesterol ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Statin Treatment ◽  
Cardiovascular Outcomes ◽  
Stroke Patients ◽  
Pcsk9 Inhibitors ◽  
Cholesterol Levels

Background Low-density lipoprotein (LDL) cholesterol has been long associated with the risk for ischemic stroke, myocardial infarction, and cardiovascular death. For more than a decade, the main pharmacological option to prevent stroke and myocardial infarction through LDL-cholesterol lowering was the use of statins. During the recent years, two novel classes of drugs have proven their efficacy and safety to reduce LDL-cholesterol and prevent cardiovascular events in large, well-conducted randomized controlled trials: ezetimibe and proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors. Aims The present review summarizes the evidence arising from the latest trials of lipid-lowering treatment for cardiovascular outcomes prevention and discusses their implications for secondary prevention strategies in patients with ischemic stroke. Summary of review There is strong evidence which confirms the hypothesis that the lower the LDL-cholesterol, the less frequent the cardiovascular events are and underlines the importance of treating our ischemic stroke patients with intensive statin treatment aiming at low LDL-cholesterol levels. The very low levels of LDL cholesterol seem to be safe, even in the mid/long term but longer follow-up data are needed. Currently there are no tools to reliably predict cardiovascular outcomes in the specific population of ischemic stroke patients. Conclusions Stroke physicians should aim for low LDL-cholesterol levels by intensive statin treatment in all ischemic stroke patients. For those patients who are at the highest risk for recurrent stroke or another cardiovascular event and have unacceptable LDL-cholesterol levels despite intensive statin treatment, PCSK9 inhibitors should be considered.

Abstract 29: PCSK9 Association With Lipoprotein(a)

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Hagai Tavori ◽  
Ilaria Giunzioni ◽  
Calvin Yeang ◽  
Sotirios Tsimikas ◽  
Michael D Shapiro ◽  
...  
Keyword(s):  
Molecular Weight ◽  
Monoclonal Antibodies ◽  
Immune Complexes ◽  
Ldl Cholesterol ◽  
Sandwich Elisa ◽  
Mononuclear Phagocyte ◽  
Lower Plasma ◽  
Ldl Receptors ◽  
Lipoprotein A ◽  
Cholesterol Levels

Monoclonal antibodies (mAb) against PCSK9 lower plasma LDL-cholesterol levels by increasing the lifespan of LDL receptors (LDLR). Significant effects on lipoprotein(a) [Lp(a)] have also been observed, but the mechanism for this is neither known nor intuitive since Lp(a) is not cleared by LDLR. Our and other laboratories have shown that PCSK9 associates with LDL in plasma. Here, we aimed to study whether PCSK9 also associates with Lp(a) particles and whether this association depends on Lp(a) levels and/or apo(a) size. Using sandwich ELISA we determined that plasma PCSK9 is indeed associated with Lp(a) particles in patient with high Lp(a) levels (>30mg/dl). We then isolated LDL and Lp(a) fractions from plasma of 8 patients with high Lp(a) levels, ranging from 36 to 224 mg/dl, and determined PCSK9 and apoB levels as well as apo(a) isoforms. Our results show a 17.8 fold higher PCSK9/apoB ratio for Lp(a) compared with LDL (Fig. 1A), which suggests a preferential distribution of PCSK9 with Lp(a), at least in high Lp(a) individuals. Surprisingly, the preferential association of PCSK9 with Lp(a) was inversely correlated to Lp(a) levels (Fig. 1B) and independent of LDL levels. Since Lp(a) levels are inversely correlated with the size of apo(a), we set out to determine whether PCSK9 association with Lp(a) is related to the molecular weight of apo(a). Using plasma of patients with two distinct apo(a) isoforms, we show that PCSK9 associates exclusively with the higher molecular weight of apo(a) (Fig. 1C). Our results suggest that Lp(a)-bound PCSK9 exists in plasma of patients with high Lp(a) and that this association depends on the size of apo(a). This provides a possible mechanism for the reduction in Lp(a) caused by PCSK9mAb, as immune complexes mAb-PCSK9-Lp(a) may be cleared via the mononuclear phagocyte system.

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