Desphospho-Uncarboxylated Matrix-Gla Protein Is Increased Postoperatively in Cardiovascular Risk Patients

Abstract

Background: Matrix Gla protein (MGP) is an extrahepatic protein that is dependent on glutamate carboxylation, a vitamin K-dependent process. Its dysfunctional form, desphospho-uncarboxylated-MGP, has been associated with increased arterial calcification and stiffness. The aim of this study was to measure the degree of postoperative carboxylation of MGP and two other Gla proteins in patients scheduled for abdominal or orthopaedic surgery. Methods: Forty patients undergoing abdominal or orthopaedic surgery were included. Blood samples were collected preoperatively and four days after the surgery. Desphospho-carboxylated MGP (dp-cMGP), desphospho-uncarboxylated MGP (dp-ucMGP), carboxylated osteocalcin (OC) (cOC), uncarboxylated OC (ucOC), and uncarboxylated prothrombin (PIVKA-II) were analysed. Results: Preoperatively, 29 patients had dp-ucMGP levels above the reference values. Patients with pre-existing cardiovascular comorbidities had higher dp-ucMGP preoperatively compared with patients with no record of cardiovascular disease. Postoperatively, this number increased to 36 patients, and median dp-ucMGP levels increased (p < 0.0001) and correlated to a PIVKA-II increase (r = 0.44). On the other hand, dp-cMGP levels did not significantly alter. Decreased levels of ucOC and cOC were seen after surgery (p = 0.017 and p = 0.0033, respectively). Comorbidities, possible nutritional defects, and complications affecting Gla protein activity and function were identified. Conclusions. Dp-ucMGP was high preoperatively, and had further increased postoperatively. This pattern was linked to several comorbidities, possible nutritional defects, and postoperative complications, which motivates further research about potential interactions between perioperative corrective treatments with vitamin K supplements, cardiovascular biomarkers, and incidents of stroke and myocardial infarction events.

Intravenous Vitamin K1 for the Correction of Prolonged Prothrombin Times in Non-Bleeding Critically Ill Patients: A Prospective Observational Study

“…This effect of vitamin K in higher dosages corroborates results from 2 recent studies [28,29]. Our dp-ucMGP levels are high, but in a previous study on postoperative changes after major surgery, even higher dp-ucMGP levels were measured on day 5 compared to day 1 after surgery [14].…”

“…The delta changes between the time points also demonstrated a stronger return to a normal Owren PT in the group with increased or unchanged SOFA score. Thrombin generation assay, reagent B; 12 Thrombin generation assay, reagent C, for this analysis one sample was missing in the increased or stagnant SOFA score group, calculations are based on 24 patients for this analysis; 13 Rotational thromboelastometry; 14 Clotting time; 15 Clot formation time; 16 Maximal clot firmness; 17 Maximal lysis; 18 C-reactive protein; 19 Greater decrease in the group with decreased SOFA score.…”

“…; 8 Reagent B;9 Reagent C, for this analysis one sample was missing and calculation are based on 51 patients. ; 10 Rotational thromboelastometry;11 Clotting time;12 Clot formation time;13 Maximal clot firmness;14 Maximal lysis;15 Sequential organ failure assessment;16 C-reactive protein;17 Between sampling occasions-calculated intake through enteral or parenteral nutrition;18 Between sampling occasions compared to the United States Food and Drug Administration recommended daily vitamin K1 intake of 120 µg per day; − Value unchanged between samplings; ↓ Value decreased to second sampling; ↑ Value increased to second sampling.…”

Vitamin K2 Needs an RDI Separate from Vitamin K1

“…The hypothesis and data presented in this review further suggest that extrahepatic vitamin K deficiency cannot be alleviated with VK1 supplementation alone [101]. Although it remains a challenge to directly screen VK2, there is a strong argument that patients with osteoporosis, cardiovascular disease, and diabetes are deficient in VK2 [102][103][104]. The MK-7 isoform appears to have the greatest extrahepatic bioavailability [9].…”

Association of the Inactive Circulating Matrix Gla Protein with Vitamin K Intake, Calcification, Mortality, and Cardiovascular Disease: A Review

“…Among 40 patients scheduled for orthopedic or abdominal surgery, serum dpucMGP levels were significantly higher in those with previous history of CVD compared to those with no record, while dpcMGP levels were not significantly different among groups. Post-operatively, only serum dpucMGP (and not dpcMGP) levels were significantly increased in the group with history of CVD [105]. A recent meta-analysis including 7 studies and 3301 patients reported that circulating inactive dpucMGP was a strong independent predictor of overall and CV mortality, but not CVD [106].…”