scholarly journals Nuclear Magnetic Resonance (NMR) Spectroscopy on the Effect of PCSK9 Inhibitor on Lipoprotein Particles  in Patients With Acute Coronary Syndromes(ACS)

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.

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 ◽  
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.


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.


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.


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.


2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Ying-zhong Lin ◽  
Shan-he Lu ◽  
Zheng-de Lu ◽  
Ying Huang ◽  
Ying Shi ◽  
...  

Background. Regulatory T (Treg) cells play a protective role in atherosclerosis prone models and are related to the onset of acute coronary syndromes (ACS, including non-ST-elevation ACS (NSTEACS) and ST-elevation acute myocardial infarction (STEAMI)). CD4+LAP+ Treg cells are a novel subset of Tregs that have been found to ameliorate atherosclerosis inApoE-/-mice, and these cells also exist in humans. The present study was designed to investigate whether CD4+LAP+ Treg cells are involved in the onset of ACS.Methods. The frequencies of CD4+LAP+ and CD4+CD25+ Treg cells were detected using flow cytometric analysis, and the plasma IL-10 and TGF-β1 levels were measured using an ELISA in 29 stable angina (SA) patients, 30 NSTEACS patients, 27 STEAMI patients, and a control group (30 cases).Results. The results revealed a significant decrease in the frequencies of CD4+LAP+ and CD4+CD25+ Treg cells and in the levels of IL-10 and TGF-β1 in patients with ACS compared with those in the SA and control groups.Conclusions. The decrease in the frequencies of CD4+LAP+ and CD4+CD25+ Treg cells may play a role in the onset of ACS.


Cardiology ◽  
2015 ◽  
Vol 132 (2) ◽  
pp. 119-123 ◽  
Author(s):  
Damian Dudek ◽  
Wiktor Kuliczkowski ◽  
Jacek Kaczmarski ◽  
Joanna Wiechec ◽  
Edyta Reichman-Warmusz ◽  
...  

Introduction: Oral surgery (OS) in patients on antecedent dual antiplatelet therapy (DAPT) may be associated with extra bleeding risks. Monitoring platelet activity in such patients may be beneficial for safety when performing OS. Objectives: The aim of this study was to assess whether platelet function during DAPT impacted the risk of bleeding following OS in patients with acute coronary syndromes (ACS). Patients and Methods: Patients who required OS on top of DAPT with aspirin and clopidogrel (n = 55) for invasively treated ACS were included. The control group (n = 33) consisted of patients who underwent OS with no antiplatelet agent. Platelet aggregation before OS was assessed with a Multiplate® analyzer. Bleeding during OS and at days 1, 3, 7 and 10 after surgery was serially evaluated. Results: All 88 patients completed the study. An incomplete response to aspirin or clopidogrel was observed in 43.6% of the patients. In 11% of the cases, an excessive response to clopidogrel was demonstrated. No excessive bleeding upon OS was exhibited in either group during the entire follow-up. Platelet aggregation values and the use of DAPT did not impact the performance of OS. Conclusion: Therapy with clopidogrel and aspirin after ACS does not seem to increase the risk of real-life bleeding following OS, regardless of the platelet activity response to DAPT.


2021 ◽  
Author(s):  
Hai-xia Liao ◽  
Lin-lin Meng ◽  
Xin Yu ◽  
Ming Song ◽  
Guo-kai Shang ◽  
...  

Objective: This study is to explore the predictive value of erythrocyte-derived microparticles (ErMPs) in patients with acute coronary syndrome (ACS). Materials & methods: Total 305 subjects were enrolled and divided into the control group and ACS group. Flow cytometry was used to detect the ErMPs. The Gensini score was calculated based on the results of the coronary angiography. Results: Compared with that in the control group, the ErMPs concentration in the ACS group increased significantly and the concentration of ErMPs was correlated with the ACS risk. The concentration of ErMPs and the percentage of ErMPs were positively correlated with the Gensini score. Conclusion: ErMPs may be a new biomarker for predicting the ACS risk and the coronary artery disease severity.


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