scholarly journals Effect of PCSK9 inhibitor on lipoprotein particles in patients with acute coronary syndromes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Tingting Li ◽  
Yingyi Zhang ◽  
Hongliang Cong

Abstract Background To assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes. Methods A total of 99 consecutive patients with ACS were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140 mg, q2w) and moderate statin (Rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (Rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after 8 weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed. Results In the experimental group, after 8 weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions [VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)] demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL-P 5 + 6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3 + 4) and large-sized LDL-P (LDL-P1 + 2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after 8 weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target (P < 0.01). Conclusions Evolocumab combination treatment for 8 weeks significantly improves the plasma lipid profiles in ACS patients, and significantly decrease the concentration of lipoprotein particles which might contribute to the pathonesis of atherosclerosis.

2020 ◽  
Author(s):  
Tingting Li ◽  
Yingyi Zhang ◽  
Hongliang Cong

Abstract Backgrounds: To assess the effects of proprotein convertase subtilisin/kexin type 9 inhibitor (evolocumab) on lipoprotein particles subfractions with Nuclear Magnetic Resonance spectroscopy in patients with acute coronary syndromes.Methods: A total of 99 consecutive patients with ACS and poor lipid control were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140mg, q2w) and moderate statin (rosuvastatin, 10 mg, qn) was administered in the experimental group, with statin monotherapy (rosuvastatin, 10 mg, qn) in the control group. The therapeutic effects on lipoprotein particle subfractions were assessed with NMR spectroscopy after eight weeks treatment, and the achievement of LDL-C therapeutic target in both groups were analyzed.Results: In the experimental group, after eight weeks of evolocumab combination treatment, the concentrations of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions (VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)) demonstrated therapeutic benefits with statistical significance (P < 0.05). The decrease in total LDL-P concentrations was mainly due to a decreased concentration of small-sized LDL particles (LDL 5+6), which was significantly more prominent than the decrease in medium-sized LDL-P (LDL-P3+4) and large-sized LDL-P (LDL-P1+2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program Expert Consensus in 2019, after eight weeks treatment, 96.3% patients in the experimental group and 13.3% in the control group had achieved the LDL-C therapeutic target(P < 0.01).Conclusions: Evolocumab combination treatment for 8 weeks could significantly improve the plasma lipid profiles in ACS patients with poor lipid control, and significantly decrease the concentration of lipoprotein particles which could result in atherosclerosis.


2020 ◽  
Author(s):  
tingting li ◽  
Hongliang Cong ◽  
yingyi zhang

Abstract ObjectiveTo assess the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (evolocumab) on blood lipid level, lipoprotein particles, and their subfractions with Nuclear Magnetic Resonance (NMR) spectroscopy in patients with acute coronary syndromes(ACS). MethodsA total of 99 consecutive patients with ACS and poor lipid control were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha®, 140mg, q2w) and moderate statin (rosuvastatin, 10 mg, qn) was administered in the experimental group, with moderate statin therapy (rosuvastatin, 10 mg, qn) alone in the control group. The therapeutic effects on blood lipid levels and lipoprotein particle subfractions were assessed with NMR spectroscopy after eight weeks of treatment, and the achievement of LDL-C treatment target in both groups was analyzed. ResultsIn the experimental group, after eight weeks of evolocumab and moderate statin combination therapy, the level of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions (VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)) demonstrated therapeutic benefits with statistical significance (P < 0.05). Lowered level of LDL-P was attributed to the significant decrease of small LDL-P (LDL-P5+6), which was significantly more prominent than the decrease in medium LDL-P (LDL-P3+4) and large LDL-P (LDL-P1+2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program (CCEP) Expert Consensus in 2019, the percentage of patients reaching the treatment target differed significantly between the experimental group and the control group (96.3% and 13.3%, respectively, P < 0.001). ConclusionsPCSK9 inhibitor treatment for 8 weeks could significantly improve the plasma lipid profiles in ACS patients with poor lipid control, and significantly decrease the concentration of lipoprotein particles which could result in atherosclerosis.


2020 ◽  
Author(s):  
tingting li ◽  
Hongliang Cong ◽  
yingyi zhang

Abstract Objective: To assess the effects of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor (evolocumab) on blood lipid level, lipoprotein particles, and their subfractions with Nuclear Magnetic Resonance (NMR) spectroscopy in patients with acute coronary syndromes(ACS).Methods: A total of 99 consecutive patients with ACS and poor lipid control were enrolled and assigned to either the experimental group (n = 54) or the control group (n = 45). The combination therapy of PCSK9 inhibitor (Repatha ® , 140mg, q2w) and moderate statin (rosuvastatin, 10 mg, qn) was administered in the experimental group, with moderate statin therapy (rosuvastatin, 10 mg, qn) alone in the control group. The therapeutic effects on blood lipid levels and lipoprotein particle subfractions were assessed with NMR spectroscopy after eight weeks of treatment, and the achievement of LDL-C treatment target in both groups was analyzed.Results: In the experimental group, after eight weeks of evolocumab and moderate statin combination therapy, the level of blood lipids (TC, LDL-C and its subfractions [LDL-1 to 6], VLDL-C and its subfractions [VLDL-1 to 5], IDL-C, and HDL-C), lipoprotein particles, and their subfractions (VLDL-P, IDL-P, LDL-P, and its subfractions [LDL-P1 to 6], apoB, and LP(a)) demonstrated therapeutic benefits with statistical significance (P < 0.05). Lowered level of LDL-P was attributed to the significant decrease of small LDL-P (LDL-P5+6), which was significantly more prominent than the decrease in medium LDL-P (LDL-P3+4) and large LDL-P (LDL-P1+2) (P < 0.001). According to lipid control target recommended by the latest China Cholesterol Education Program (CCEP) Expert Consensus in 2019, the percentage of patients reaching the treatment target differed significantly between the experimental group and the control group (96.3% and 13.3%, respectively, P < 0.001).Conclusions: PCSK9 inhibitor treatment for 8 weeks could significantly improve the plasma lipid profiles in ACS patients with poor lipid control, and significantly decrease the concentration of lipoprotein particles which could result in atherosclerosis.


1997 ◽  
Vol 77 (02) ◽  
pp. 248-251 ◽  
Author(s):  
Lena Norlund ◽  
Johan Holm ◽  
Bengt Zöller ◽  
Ann-Kristin Öhlin

SummaryEndothelial dysfunction and haemostatic imbalance are believed to be important aetiological factors in the development of acute coronary syndromes. Thrombomodulin (TM) is an integral membrane protein crucial for normal endothelial function and activation of the protein C anticoagulant pathway. We have investigated the importance of a common C/T dimorphism in the TM gene (nucleotide 1418) for development of premature myocardial infarction (MI). The C/T dimorphism predicts an Ala455 to Val replacement in the sixth EGF-like domain of TM. The dimorphism was investigated in 97 MI survivors and 159 healthy controls. The C allele was significantly more frequent among patients than controls (p = 0.035). The allele frequency for the C allele was 0.82 in the patients and 0.72 in the control group. The plasma concentration of TM was investigated among healthy controls but was not related to the C/T dimorphism. In conclusion, the association of the C allele with premature MI, suggests that the TM gene and the C/T dimorphism may be aetiological factors involved in the pathogenesis of MI. Possibly, the Ala455 to Val replacement may affect the function of the TM molecule and the activation of the protein C anticoagulant pathway.


2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
A Jeronimo Baza ◽  
C Salazar ◽  
M.J Perez Vyzcaino ◽  
L Nombela ◽  
P Jimenez Quevedo ◽  
...  

Abstract Introduction Systemic embolism to coronary arteries is one of the mechanisms of acute myocardial infarction (AMI) of non-atherosclerotic cause. However, its clinical profile has not been properly established yet. Purpose To identify clinical predictors and angiographic characteristics of acute coronary syndromes caused by systemic embolism to a principal coronary artery (ACS-E), as well as to describe in-hospital mortality of these patients. Methods 40 patients with ACS-E, admitted between 2003 and 2018 in a tertiary hospital. Epidemiological, clinical and angiographic characteristics of these cases were compared with those from 4989 patients, attended for acute coronary syndrome of atherosclerotic cause (ACS-A) in the same hospital during the same period. Results Patients with ACS-E were younger (28% vs 10% were &lt;45 years old, p&lt;0.001) and had a higher proportion of women (43% vs 22%, p 0.003), atrial fibrillation (40% vs 5%, p&lt;0.001) and neoplasia (18% vs 7%, p 0.009). They had also undergone previous valvular surgery more frequently than patients with ACS-A (13% vs 0.5%, p&lt;0.001) and a higher proportion of them were under treatment with warfarin (15% vs 3%, p&lt;0.001). Variables identified as independent predictors of ACS-E in the multivariate analysis are shown in the table. Regarding clinical presentation, ST elevation AMI was more frequent in ACS-E cases (83% vs 67%, p 0.04). Patients with ACS-E did not present any significative stenosis in other vessels apart from the culprit one (number of other vessels with at least 1 severe stenosis was 0 in the ACS-E group vs 1.33 + 1 in the ACS-A arm, p&lt;0.001). PCI was attempted in 75% of the patients with ACS-E, resulting successful in 80% of the cases. On the other hand, 100% of SCA-A underwent PCI, with a success proportion of 99% (p&lt;0.001). In-hospital mortality in ACS-E group was 15% and 4% in the control group (p&lt;0.001). Conclusions ACS-E and ACS-A have different clinical and angiographic features. Atrial fibrillation, chronic warfarin treatment, previous valvular surgery, presence of any neoplasia and female sex are independent predictors for ACS-E. Funding Acknowledgement Type of funding source: None


2003 ◽  
Vol 22 (4) ◽  
pp. 303-309 ◽  
Author(s):  
Svetlana Ignjatovic

Although the use of troponin to diagnose acute myocardial infarction (AMI) has been previously proposed, the Committee on Standardization of Markers of Cardiac Damage (C-SMCD) of the International Federation of Clinical Chemistry and Laboratory Medicine (IFCC) made a recommendation in 1999 to expand on the enzyme diagnostic criteria for AMI to include cardiac-specific proteins. In September 2000, a joint committee of the European Society of Cardiology and the American College of Cardiology (ESC/ACC) published a new definition of AMI that for first time officially included troponin. According to these criteria, as the best biochemical indicator for detecting myocardial necrosis is "a concentration of cardiac troponin exceeding the decision limit (defined as the 99th percentile of a reference control group) on at least one occasion during the first 24 hours after the onset of clinical event". The use of creatine kinase MB (CK-MB), measured by mass assays, is still considered as an acceptable alternative only if cardiac troponin assays are not available. It is very important to standardize the clinical use of troponin in diagnosis and management of acute coronary syndromes and to clearly define decision thresholds. Two strategies have competed as the most appropriate for the use of new markers. The first relies on the use of a combination of two markers - a rapid rising marker such as myoglobin, and a marker that takes longer to rise but is more specific, such as cardiac troponin - to enable detection of AMI in patients who present early and late after symptom onset. In the second strategy, only measurement of cardiac troponin is suggested. One of the most important problems in the practical use of the cardiac-specific troponin is the right definition of decision limits. As diagnostic cut-off for clinical use, the IFCC C-SMCD recommends for troponin assays a total imprecision, expressed as coefficient of variation (CV), of <10% at the 99th percentile of a reference control group. For troponin assays that cannot presently meet the 10% CV at the 99th percentile value, a predetermined higher concentration that meets this imprecision goal should be used as cut-off for AMI until the goal of a 10% CV can be achieved at the 99th percentile. It is very important that clinically relevant biomarker, such as cardiac troponin, on which critical decisions will rest, can be measured with highly reliable and standardized methods. There are problems in assay standardization, imprecision interference, and of pre-analytical variability. Cardiac troponin is currently the most sensitive and specific biochemical marker of myocardial damage and is the best marker for diagnosis, risk stratification, and guidance of therapy in acute coronary syndromes.


2016 ◽  
Vol 63 (4) ◽  
pp. 183-192 ◽  
Author(s):  
Marijana Popović Bajić ◽  
Violeta Petrović ◽  
Vanja Opačić Galić ◽  
Vesna Danilović ◽  
Vukoman Jokanović ◽  
...  

Summary Introduction Direct pulp capping is an important therapeutic method that has goal to provide formation of dentin bridge and healing process of the pulp. The aim of this study was to investigate the effects of new nanostructural materials based on calcium silicate systems and hydroxyapatite on exposed dental pulp in Vietnamese pigs. Material and Methods The study was conducted on 30 teeth of two Vietnamese pigs (Sus scrofa verus). On buccal surfaces of incisors, canines and first premolars, class V cavities were prepared with a small round bur and pulp horn was exposed. In the first experimental group (10 teeth) the perforation was covered with new nanostructural material based on calcium silicate systems (CS). In the second experimental group, the perforation was covered with compound of calcium silicate systems and hydroxyapatite (HA-CS) (10 teeth). In the control group, exposed pulp was covered with Pro Root MTA® (Dentsply Tulsa Dental, Johnson City, TN, USA) (10 teeth). All cavities were restored with glass ionomer cement (GC Fuji VIII, GC Corporation, Tokyo, Japan). Observation period was 28 days. After sacrificing the animals, histological preparations were done to analyze the presence of dentin bridge, inflammatory reaction of the pulp, pulp tissue reorganization and the presence of bacteria. Results Dentin bridge was observed in all teeth (experimental and control groups). Inflammation of the pulp was mild to moderate in all groups. Neoangiogenesis and many odontoblast like cells responsible for dentin bridge formation were detected. Necrosis was not observed in any case, neither the presence of Gram-positive bacteria in the pulp. Conclusion Histological analysis indicated favorable therapeutic effects of new nanostructural materials based on calcium silicate systems and hydroxyapatite for direct pulp capping in teeth of Vietnamese pigs.


2021 ◽  
Vol 5 (1) ◽  
Author(s):  
Jianyong Gao ◽  
Yi Zhao ◽  
Tinglan Sun ◽  
Weike Liu ◽  
Zhenguo Wang

Objective: To compare the therapeutic effects of acupotomy trinity lysis and traditional acupotomy on cervical spondylotic myelopathy. Methods: A total of 205 patients with cervical spondylotic myelopathy of liver and kidney deficiency syndrome were randomly divided into the experimental group (105 cases) and the control group (100 cases). The experimental group was relaxed with acupotomy in three positions: Heaven (tian), Human (ren) and Earth (di). Traditional acupotomy was used to relax Ashi acupoints of the affected vertebra in the control group. One treatment was conducted in one week, and the duration of one course of treatment was three weeks. The VAS, JOA score and NDI index were observed after treatment.  Results: Before and after treatment, the total treatment efficiency of the treatment group was 95.23%, and that of the control group was 80.00%, there was significant difference between the two groups, P<0.05; Before operation, there was no significant difference in JOA score, NDI index score, and VAS score between the treatment group and the control group (P>0.05); there was no significant difference after 1 week (P>0.05), but there were significant differences between the two groups 2 weeks and 3 weeks after operation (P<0.05). Conclusion: Acupotomy trinity lysis is a safe, effective and economical treatment for cervical spondylotic myelopathy.


2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yan Ding ◽  
Ming An Zhu ◽  
Zhi Xiao Wang ◽  
Jing Zhu ◽  
Jing Bo Feng ◽  
...  

Background. Acute coronary syndromes (ACSs) are clinically cardiovascular events associated with dyslipidemia in common. Single nucleotide polymorphisms (SNPs) and haplotypes in the APOA1/C3/A5 gene cluster are associated with diabetes and familial combined hyperlipidaemia (FCH). Little is known about whether the polymorphisms in these genes affect lipid homeostasis in patients with ACSs. The present paper aimed to examine these associations with 4 SNPs in the APOA1 −75G>A, the APOC3 −455T>C, and APOA5 −1131T>C, c.553G>Tvariant to ACSs in Chinese Han.Methods. Chinese Han of 229 patients with ACSs and 254 unrelated controls were analyzed. Four SNPs in APOA1/C3/A5 cluster were genotyped and lipid was determined.Results. Our data show that minor allelic frequencies of APOC3 −455T>C, APOA5 −1131T>C, and c.553G>Tpolymorphisms in patients with ACSs were significantly higher than control group (P<0.05). Furthermore, the 3 polymorphic sites were strongly of linkage disequilibrium, and minor alleles of 3 SNP sites had higher TG level than wild alleles (P<0.05), APOC3 −455C and APOA5 c.553T allele carriers also had lower level of HDL-C.Conclusions. The minor alleles of APOC3 −455T>C, APOA5 −1131T>C, and c.553G>Tpolymorphisms are closely associated with ACSs.


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