Plasma kinetics of mature PCSK9, furin-cleaved PCSK9, and Lp(a) with or without administration of PCSK9 inhibitors in acute myocardial infarction

AbstractCardiac biomarkers are the cornerstone of the biological definition of acute myocardial infarction (AMI). The key role of troponins in diagnosis of AMI is well established. Moreover, kinetics of troponin I (cTnI) and creatine kinase (CK) after AMI are correlated to the prognosis. New technical assessment like high-sensitivity cardiac troponin T (hs-cTnT) raises concerns because of its unclear kinetic following the peak. This study aims to compare kinetics of cTnI and hs-cTnT to CK in patients with large AMI successfully treated by percutaneous coronary intervention (PCI).We prospectively studied 62 patients with anterior AMI successfully reperfused with primary angioplasty. We evaluated two consecutive groups: the first one regularly assessed by both CK and cTnI methods and the second group by CK and hs-cTnT. Modeling of kinetics was realized using mixed effects with cubic splines.Kinetics of markers showed a peak at 7.9 h for CK, at 10.9 h (6.9–12.75) for cTnI and at 12 h for hs-cTnT. This peak was followed by a nearly log linear decrease for cTnI and CK by contrast to hs-cTnT which appeared with a biphasic shape curve marked by a second peak at 82 h. There was no significant difference between the decrease of cTnI and CK (p=0.63). CK fell by 79.5% (76.1–99.9) vs. cTnI by 86.8% (76.6–92.7). In the hs-cTnT group there was a significant difference in the decrease by 26.5% (9–42.9) when compared with CK that fell by 79.5% (64.3–90.7).Kinetic of hs-cTnT and not cTnI differs from CK. The role of hs-cTnT in prognosis has to be investigated.

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Abstract 14556: Is There a Relationship Between Lipoprotein (a) and Proprotein Convertase Subtilisin /keksin Type 9 and Cardiovascular Events After Acute Myocardial Infarction?

Circulation ◽

10.1161/circ.142.suppl_3.14556 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Albert GALYAVICH ◽

Alsu Gimadeeva

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Unstable Angina ◽

Blood Level ◽

Cardiovascular Events ◽

Cardiovascular Death ◽

Blood Levels ◽

Proprotein Convertase ◽

Pcsk9 Inhibitors ◽

Lipoprotein A

Introduction: Lipoprotein (a) (Lp(a)) has atherogenic effects. Proprotein convertase subtilisin /keksin type 9 (PCSK9) involved in the degradation of LDL-C receptors, increasing LDL-C blood level. Hypothesis: Identify the relationship between Lp(a) and PCSK9 blood levels and major cardiovascular events (unstable angina, myocardial infarction, cardiovascular death) after acute myocardial infarction. Methods: The study included 119 patients with acute myocardial infarction (97 men and 22 women aged 50-70 years). Blood samples were taken on the 2nd day of myocardial infarction. The Lp(a) blood level was determined by immunoturbidimetry (RANDOX), the PCSK9 blood level was determined by ELISA (BioVendor). Primary combined endpoint included hospitalization due to myocardial infarction and unstable angina and cardiovascular death. Patient follow-up was 52 weeks. Statistical analysis methods included Mann-Whitney test and non-parametric correlation by Spearman. Results: In 36 (30.2%) patients with acute myocardial infarction the Lp(a) blood levels were higher than 30 mg/dL. In 83 (69.7%) patients the Lp(a) blood level were below 30 mg/dL. Mean values of Lp(a) blood level was 29.26 ± 2.79 (men 27.71 ± 2.82 mg/dL, women 36.07 ± 8.54 mg/dL, p = 0.797). Mean PCSK9 blood level was 479.7 ± 15.4 ng/ml (males 465.6 ± 16.2ng/ml, females 534.9 ± 38.9 ng/ml, p = 0.122). There was no significant correlation of Lp(a) blood level with total cholesterol, LDL-C, triglycerids and PCSK9 blood levels. No significant correlation was found between Lp(a) and PCSK9 blood levels and cardiovascular events within 12 months. In the group of smoking patients (n = 22) there was found negative correlation between PCSK9 and HDL-C blood levels (-0.45, p = 0.039). Conclusions: Due to the fact that there is no relationship between Lp(a) and PCSK9 blood levels and subsequent cardiovascular events within 52 weeks, the effectiveness of the use of PCSK9 inhibitors after acute myocardial infarction is doubtful.

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Release kinetics of early ischaemic biomarkers in a clinical model of acute myocardial infarction

Heart ◽

10.1136/heartjnl-2013-305253 ◽

2014 ◽

Vol 100 (8) ◽

pp. 652-657 ◽

Cited By ~ 16

Author(s):

Christoph Liebetrau ◽

Holger M Nef ◽

Oliver Dörr ◽

Luise Gaede ◽

Jedrzej Hoffmann ◽

...

Keyword(s):

Myocardial Infarction ◽

Acute Myocardial Infarction ◽

Release Kinetics ◽

Hypertrophic Obstructive Cardiomyopathy ◽

Fatty Acid Binding ◽

Continuous Increase ◽

Clinical Model ◽

Additional Information ◽

Coronary Syndrome ◽

Kinetics Of

ObjectiveTo determine the release kinetics of different biomarkers with potential as novel early ischaemic biomarkers in patients with acute coronary syndrome (ACS); it is difficult to establish the detailed release kinetics in patients with acute myocardial infarction (AMI).MethodsWe analysed the release kinetics of soluble fms-like tyrosine kinase (sFlt-1), ischaemia modified albumin (IMA), and heart-type fatty acid binding protein (hFABP) in patients with hypertrophic obstructive cardiomyopathy who were undergoing transcoronary ablation of septal hypertrophy (TASH), a procedure mimicking AMI. Consecutive patients (n=21) undergoing TASH were included. Blood samples were collected before TASH and 15, 30, 45, 60, 75, 90, and 105 min and 2, 4, 8, and 24 h after TASH. sFlt-1 and hFABP were quantified in serum, and IMA was quantified in plasma using immunoassays.ResultssFLT-1 and hFABP increased significantly 15 min after induction of AMI vs baseline as follows: sFlt-1, 3657.5 ng/L (IQR 2302.3–4475.0) vs 76.0 ng/L (IQR 71.2–88.8) (p<0.001); hFABP, 9.0 ng/mL (IQR 7.0–15.4) vs 4.6 ng/mL (IQR 3.4–7.1) (p<0.001). sFlt-1 demonstrated a continuous decrease after the 15th min. hFABP showed a continuous increase until the 8th hour with a decline afterwards. The IMA concentrations increased significantly 30 min after induction of AMI vs baseline, with values of 26.0 U/mL (IQR 21.8–38.6) vs 15.6 U/mL (IQR 10.1–24.7) (p=0.02), and then decreased after 75 min.ConclusionssFlt-1 and hFABP increased very early after induction of myocardial ischaemia, showing different release kinetics. The additional information provided by these findings is helpful for developing their potential combined use with cardiac troponins in patients with suspected AMI.

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