Circulating and Regional Matrix Gla Protein Indicating Plaque Calcification and Prognosis of Patients with ST-Segment Elevation Myocardial Infarction

Abstract

Background and Aims

The association between matrix Gla protein (MGP) and vascular calcification has been investigated in recent years; however, studies focusing on MGP with plaque calcification are lacking. In the present study, we aimed to explore the association of circulating and regional levels, as well as polymorphism of MGP with plaque calcification detected by optical coherence tomography (OCT) and adverse clinical outcome in patients with ST-segment elevation myocardial infarction (STEMI).

Methods and Results

A prospective cohort of 1,648 consecutive patients with STEMI were established. Circulating level of dephosphorylated-uncarboxylated MGP (dp-ucMGP) was determined using enzyme-linked immunosorbent assay. The primary outcome was major adverse cardiovascular event (MACE), composite of all-cause death, recurrent myocardial infarction, and ischemic stroke. Plaque calcification of 326 patients in the cohort was analyzed via OCT and MGP single nucleotide polymorphism (SNP) was detected in 1,313 patients. A total of 54 patients with aspirated coronary material undertook immunohistochemical (IHC) staining for quantifying regional MGP expression surrounding culprit lesions. During a median follow-up of 4 years, patients with high dp-ucMGP (≥1128 ng/mL) were associated with higher risk of death (hazard ratio [HR]: 1.41, 95% confidence interval [CI]: 1.02–1.97, p = 0.040), which was sustained in propensity score matching (HR: 1.488, 95% CI: 1.049–2.109, p = 0.026). In OCT observation, patients with annular calcification had higher level of dp-ucMGP than those without calcification (1,273 ng/mL [972.2–2168] vs. 1,079 ng/mL [729.2–1888], p = 0.0136). On IHC examination, patients with culprit plaque calcifications had significantly higher regional MGP expression than those without in their aspirated coronary material (AOD: 0.225 ± 0.021 vs. 0.183 ± 0.021, p < 0.0001). However, MGP variants showed no correlation with plaque calcification or the prognosis of patients in the cohort.

Conclusion

High levels of circulating dp-ucMGP were significantly associated with increased mortality and annular plaque calcification in patients with STEMI. Moreover, higher expression of regional MGP in aspirated coronary material showed more indicative value for patients with culprit lesion calcification. However, MGP variants including rs4236, rs1800801, and rs1800802 in the current study were not significantly correlated with plaque calcification or poorer prognosis.

Keywords

matrix Gla protein - plaque calcification - prognosis - ST-segment elevated myocardial infarction

Data Availability Statement

The datasets used and/or analyzed during this study are available from the corresponding author on reasonable request.

Authors' Contribution

Substantial contributions to conception and design, data acquisition, and data analysis and interpretation: H.Y., J.L., R.C., Y.T., C.L., P.Z., Y.C., L.S. and H.Z. Drafting the article and critically revising it for important intellectual content: J.L. and H.Z. Final approval of the version to be published: J.L., R.C., X.Z., C.L., P.Z., Y.C., L.S., Y.T., H.Y. and H.Z. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of the work are appropriately investigated and resolved: J.L., R.C., X.Z., C.L., P.Z., Y.C., L.S., Y.T., H.Y. and H.Z.

Publication History

Received: 16 December 2024

Accepted: 05 May 2025

Article published online:
23 May 2025

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