AUTHOR=Wei Dongmei , Melgarejo Jesus , Vanassche Thomas , Van Aelst Lucas , Janssens Stefan , Verhamme Peter , Zhang Zhen-Yu 

TITLE=Urinary matrix Gla protein is associated with mortality risk in Flemish population: A prospective study

JOURNAL=Frontiers in Cardiovascular Medicine

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/cardiovascular-medicine/articles/10.3389/fcvm.2022.894447

DOI=10.3389/fcvm.2022.894447

ISSN=2297-055X

ABSTRACT=Background: Vascular calcification is strongly related to the risk of mortality and cardiovascular diseases. In vascular calcification, matrix Gla protein (MGP), a small vitamin K-dependent protein, is an important mineralization inhibitor. Recent studies showed that circulating MGP is associated with mortality risk. However, the longitudinal association between urinary excretion of MGP and all-cause mortality was not established. 
Methods: Urinary MGP was measured in 776 randomly recruited Flemish (mean age: 51.2 years; 50.9% women) at baseline (during 2005-2010) using capillary electrophoresis coupled with mass spectrometry. Plasma inactive MGP (desphospho-uncarboxylated, dp-ucMGP) levels were quantified in 646 individuals by ELISA kits. Mortality status was ascertained through the Belgian Population Registry until 2016. The longitudinal association with mortality was determined by multivariable adjusted Cox proportional hazards regression models. Multivariable linear regression models were used to identify determinants of urinary MGP level.
Results: Over the 9.2 years, 47 (6.06%) participants died, including 15 cardiovascular deaths. For a doubling of urinary MGP, the hazard ratios (HRs) were 1.31 (95% confidence interval [CI]: 1.01–1.69, P = 0.040) for all-cause mortality, 2.05 (95% CI: 1.11–3.79, P = 0.023) for CV mortality with adjustment known risk factors, including estimated glomerular filtration rate and urine microalbumin. The addition of urinary MGP to the basic models improved the reclassification as suggested by the increased net reclassification improvement (64.01% [95% CI: 32.64–98.63]) and integrated discrimination improvement (2.33% [95% CI: 0.24-4.71]). Circulating inactive MGP, total cholesterol, urine microalbumin, and smoking were significantly associated with urinary MGP levels (P ≤ 0.041), independent of sex and age. 
Conclusions: Elevated urinary MGP was associated with an increased risk of all-cause mortality and cardiovascular mortality and improved the risk reclassification for all-cause mortality. These findings suggested that urinary MGP might be useful in mortality risk assessment in the general population. However, these observations need to be replicated in larger studies with a longer follow-up time.