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Plasma Dephosphorylated-Uncarboxylated Matrix Gla-Protein in Systemic Sclerosis Patients: Biomarker Potential for
Judith Potjewijd1, Rachid Tobal1, Karin A Boomars2
1Department of Internal Medicine, Division Clinical and Experimental Immunology, Maastricht University Medical Center, 6229 HX Maastricht, The Netherlands.
Insights
Elevated dephosphorylated-uncarboxylated Matrix Gla-protein (dp-ucMGP) levels in systemic sclerosis (SSc) patients predict increased cardiovascular disease (CVD) and mortality risk. This finding highlights dp-ucMGP as a novel biomarker for SSc patients.
Area of Science:
- Cardiovascular Medicine
- Rheumatology
- Biomarker Discovery
Background:
- Systemic sclerosis (SSc) patients have a higher risk of cardiovascular disease (CVD) beyond traditional risk factors.
- Plasma dephosphorylated-uncarboxylated Matrix Gla-protein (dp-ucMGP), an inactive MGP form, is linked to increased CVD risk.
- Vascular smooth muscle cells, key in SSc pathogenesis, produce dp-ucMGP.
Purpose of the Study:
- To assess dp-ucMGP levels in early-diagnosed SSc patients.
- To evaluate dp-ucMGP as a predictor of incident CVD and all-cause mortality in SSc.
- To investigate the relationship between dp-ucMGP and cardiovascular risk factors in SSc.
Main Methods:
- Measured baseline dp-ucMGP levels in 87 SSc patients without prior CVD or dialysis.
- Assessed traditional cardiovascular risk factors concurrently.
- Validated dp-ucMGP levels in a subset of treatment-naive SSc patients.
Main Results:
- SSc patients exhibited significantly elevated median dp-ucMGP levels (634 pmol/L) compared to controls (<393 pmol/L).
- Over a median 10.5-year follow-up, 33.3% of SSc patients experienced a first CVD event, irrespective of traditional risk factors.
- Elevated dp-ucMGP levels (>634 pmol/L) were associated with a higher risk of CVD and/or all-cause mortality.
Conclusions:
- Elevated plasma dp-ucMGP is a novel, independent predictor of CVD and mortality in systemic sclerosis.
- dp-ucMGP may serve as a valuable biomarker for risk stratification in SSc patients.
- Further research into the role of MGP in SSc-related cardiovascular complications is warranted.
Background:
Systemic sclerosis (SSc) patients face an elevated risk of cardiovascular disease (CVD), even when classic cardiovascular risk factors are considered. Plasma dephosphorylated-uncarboxylated Matrix Gla-protein (dp-ucMGP), an inactive form of MGP, is associated with increased CVD risk. Smooth muscle cells, implicated in SSc's development, are the primary dp-ucMGP producers. This study assessed dp-ucMGP levels and initial CVD events in early-diagnosed SSc patients, investigating its potential as a CVD and all-cause mortality predictor over time.
Methods:
In a cohort of 87 SSc patients (excluding those with pre-existing CVD or on dialysis), baseline dp-ucMGP levels were measured, along with cardiovascular risk factors. Validation involved assessing dp-ucMGP in a subset of treatment-naive SSc patients.
Results:
A significantly elevated median dp-ucMGP level of 634 pmol/L (IQR 301) compared with healthy controls (dp-ucMGP < 393 pmol/L; p < 0.001) was observed. Validation in a treatment-naive SSc patient subset yielded similar results (median 589 pmol/L; IQR 370). During a median 10.5-year follow-up among 78 SSc patients, 33.3% experienced their first CVD event, independent of traditional risk factors. Elevated dp-ucMGP levels (>634 pmol/L) correlated with a higher risk of CVD and/or death (log-rank test: p < 0.01).
Conclusions:
In summary, dp-ucMGP emerges as a novel biomarker in SSc patients, with elevated levels indicating an increased risk of CVD and/or mortality in this population.
