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. 2022 May 20;21(1):80.
doi: 10.1186/s12933-022-01519-3.

Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes

Li Song  1 , Xiaoxiao Zhao  1 , Runzhen Chen  1 , Jiannan Li  1 , Jinying Zhou  1 , Chen Liu  1 , Peng Zhou  1 , Ying Wang  1 , Yi Chen  1 , Hanjun Zhao  2 , Hongbing Yan  3
Affiliations

Association of PCSK9 with inflammation and platelet activation markers and recurrent cardiovascular risks in STEMI patients undergoing primary PCI with or without diabetes

Li Song et al. Cardiovasc Diabetol. .

Abstract

Background: Proprotein convertase subtilisin/kexin type 9 (PCSK9) has been shown to be predictive of cardiovascular outcomes in stable coronary artery disease with diabetes. We aimed to assess the relationship between PCSK9 and major adverse cardiovascular events (MACEs) in ST-segment elevation myocardial infarction (STEMI) patients with or without diabetes, as well as the relationships between PCSK9 and metabolism, inflammation and platelet activation markers.

Methods: A total of 1027 patients with STEMI undergoing primary percutaneous coronary intervention (PCI) and without prior lipid-lowering therapy were consecutively enrolled and the baseline plasma PCSK9 levels were determined by ELISA. Patients were divided into high and low PCSK9 groups according to PCSK9 median. All patients were followed up for the occurrence of MACEs. The associations of PCSK9 with metabolism, inflammation and platelet activation markers and MACEs were evaluated.

Results: PCSK9 levels were positively correlated with triglycerides, high-sensitivity C reactive protein, soluble CD40 ligand and soluble P-selectin levels, and the correlations were stronger in diabetic patients than in non-diabetic patients. In diabetic patients receiving ticagrelor, PCSK9 levels were positively correlated with maximal platelet aggregation measured by light transmittance aggregometry and maximum amplitude of adenosine diphosphate-induced platelet-fibrin clots measured by thrombelastography in the maintenance phase of treatment, whereas no correlations were found in non-diabetic patients. During a median follow-up of 2.0 years, 155 (15.1%) MACEs occurred. The Kaplan-Meier analysis displayed that the patients with high PCSK9 levels had lower event-free survival rate than those with low PCSK9 levels (P = 0.030). When participants were categorized into 4 subgroups according to PCSK9 levels and diabetes status, high PCSK9 levels plus diabetes subgroup had the lowest cumulative event-free survival rate (P = 0.043). Multivariable Cox regression analysis revealed that high PCSK9 levels were independently associated with MACEs in diabetic patients (hazard ratio 2.283, 95% confidence interval: 1.094-4.764, P = 0.028), but not in the whole cohort or non-diabetic patients.

Conclusions: The study showed that high PCSK9 levels were independently associated with MACEs in STEMI patients with diabetes undergoing primary PCI, and the association may be due to stronger correlations of PCSK9 with inflammation and platelet activation markers in diabetic patients.

Keywords: Diabetes mellitus; Inflammation; MACEs; Metabolism; PCSK9; Percutaneous coronary intervention; Platelet activation; STEMI.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Study flow chart. STEMI ST-segment elevation myocardial infarction, PCI percutaneous coronary intervention, PCSK9 proprotein convertase subtilisin/kexin type 9, DM diabetes mellitus, Non-DM non-diabetes mellitus
Fig. 2
Fig. 2
Kaplan–Meier analysis according to different PCSK9 levels (a), diabetic status (b) and status of both PCSK9 levels and diabetic status (c). PCSK9 proprotein convertase subtilisin/kexin type 9, Non-DM non-diabetes mellitus, DM diabetes mellitus
Fig. 3
Fig. 3
Receiver operating characteristic curves of risk models of established risk factors with or without levels of PCSK9 for predicting major adverse cardiovascular events in the whole cohort (a), DM patients (b) and non-DM patients (c). PCSK9 proprotein convertase subtilisin/kexin type 9, DM diabetes mellitus, Non-DM non-diabetes mellitus, AUC area under the curve
See this image and copyright information in PMC

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