Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis

Chen, Heng‐Gui; Sheng, Li‐Ting; Zhang, Yanbo; Cao, Anlan; Lai, Yu-Wei; Kunutsor, Setor K; Jiang, Limiao; Pan, An

doi:10.1007/s00394-019-01998-3

Cited by 65 publications

(64 citation statements)

References 64 publications

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“…Measuring levels of dp-ucMGP has previously been proven to be a useful method to assess vitamin K status [22]. Dp-ucMGP inversely relates to mortality and other clinical meaningful endpoints in various cohorts [12,15,[23][24][25][26][27][28][29][30]. Supplementation of vitamin K has a reducing effect on dp-ucMGP levels [22,31], and the opposite holds true with regard of the use of VKAs [22,[32][33][34].…”

Section: Discussionmentioning

confidence: 99%

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Dofferhoff¹,

Piscaer²,

Schurgers³

et al. 2020

Preprint

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Introduction: Coronavirus 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus-2. The majority of patients have at most mild symptoms, however, a significant proportion develops respiratory failure. COVID-19 may also progress beyond the lungs. Coagulopathy and thromboembolism are prevalent in severe COVID-19 and relate to decreased survival. Coagulation is an intricate balance between clot promoting and dissolving processes in which vitamin K plays a well-known role. We hypothesized that vitamin K status is reduced in patients with severe COVID-19. Methods: Vitamin K status was assessed by measuring desphospho-uncarboxylated matrix Gla protein (dp-ucMGP; inversely related to vitamin K status) and the rate of elastin degradation by measuring desmosine. We included 123 patients who were admitted with COVID-19 and 184 controls. Results: Dp-ucMGP levels were significantly elevated in COVID-19 patients (1,673Å}1,584 pmol/L) compared to controls (536±291 pmol/L; p<0.0005). Dp-ucMGP levels were significantly higher in COVID-19 patients with unfavorable outcome compared to those with less severe disease. Furthermore, dp-ucMGP and desmosine levels were significantly associated (r=0.65; p<0.0005). Conclusions: Vitamin K status was reduced in patients with COVID-19 and related to poor prognosis. Also, low vitamin K status seems to be associated with accelerated elastin degradation. An intervention trial is now needed to assess whether vitamin K administration improves outcome in patients with COVID-19.

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Section: Discussionmentioning

confidence: 99%

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Dofferhoff¹,

Piscaer²,

Schurgers³

et al. 2020

Preprint

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“…Moreover, two separate meta-analyses were conducted to investigate the possible association between dp-ucMGP and CV mortality and morbidity. Chen et al included 21 studies and 222,592 participants and reported that high plasma dp-ucMGP was strongly associated with increased risk for all cause and CV mortality [ 32 ]. Similarly, another meta-analysis of 11 studies and 33,289 patients showed that circulating dp-ucMGP was associated with high risk for total mortality (HR = 1.77) and CV mortality (HR = 1.84), whereas no association was found between dp-ucMGP and CV disease [ 33 ].…”

Section: Discussionmentioning

confidence: 99%

The Association of dp-ucMGP with Cardiovascular Morbidity and Decreased Renal Function in Diabetic Chronic Kidney Disease

Roumeliotis

Στάμου

et al. 2020

IJMS

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We aimed to investigate the possible association of the inactive, dephosphorylated, uncarboxylated matrix Gla protein (dp-ucMGP) with oxidized low-density lipoprotein (ox-LDL) and all-cause/cardiovascular (CV) mortality and renal function in diabetic chronic kidney disease (CKD). Ox-LDL and dp-ucMGP were determined in 66 diabetic CKD patients. All patients were prospectively followed for seven years, or until the occurrence of death, or a composite renal outcome of 30% estimated glomerular filtration rate (eGFR) reduction or progression to end-stage renal disease (ESRD) requiring dialysis occurred. Secondary outcomes were the occurrence of CV events. Kaplan–Meier curves showed that patients with plasma dp-ucMGP levels above the median (≥656 pM) had a significantly higher risk for all study endpoints. After adjustment for several well-known cofounders, multivariate Cox analysis showed that high plasma dp-ucMGP levels were associated with all-cause mortality (Hazard ratio-HR = 2.63, 95% Confidence Interval-CI = 1.17–5.94, p = 0.02), CV mortality (HR = 2.82, 95% CI = 1.07–7.49, p = 0.037) and progression of CKD (HR = 4.02, 95% CI = 1.20–13.46, p = 0.024). Circulating dp-ucMGP is associated with mortality and decreased renal function in diabetic CKD.

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“…In agreement with these results, data from the Third National Health and Nutrition Examination Survey (NHANES III) and Prevention of Renal and Vascular End-Stage Disease (PREVEND) studies showed that vitamin K deficiency was a strong, independent predictor of CVD, mortality and incidence of CKD (55,56). Chen et al, conducted a meta-analysis of 21 studies including 222,592 subjects and found that both daily dietary consumption of K1 and K2 were associated with aortic calcification (57). Several studies reported that CKD patients present with a significant -often underdiagnosed-deficiency of vitamin K, which is gradually increased along with deterioration of renal function and is more pronounced in dialysis patients.…”

Section: Vitamin K: the Essential Co-factor Of Mgpmentioning

confidence: 75%

Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein

et al. 2020

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Arterial calcification is highly prevalent in chronic kidney disease (CKD) patients and is associated with cardiovascular (CV) morbidity and mortality. Patients at early CKD stages are more likely to suffer a fatal CV event than to develop end-stage renal disease and require hemodialysis treatment. The heavy CV burden of these patients cannot be solely explained by traditional calcification risk factors. Moreover, the pathophysiologic mechanisms underlying this association are complex and yet not fully understood. Although vascular calcification was regarded as a passive degenerative process for over a century, this theory changed by recent evidence that pointed toward an active process, where calcification promoters and inhibitors were involved. Matrix Gla Protein (MGP) has been established as a strong inhibitor of calcification both in vitro and in vivo. Not only it prevents mineralization of the arterial wall, but it is the only factor that can actually reverse it. To become fully active, MGP must undergo carboxylation of specific protein bound glutamate residues, a process fully dependent on the availability of vitamin K. Low vitamin K status leads to inactive, uncarboxylated forms of MGP and has been repeatedly associated with accelerated vascular calcification. Aim of this review is to present the pathophysiologic mechanisms underlying the activation and function of MGP and review the existing, accumulating data regarding the association between vitamin K, MGP and vascular calcification/CV disease in CKD patients.

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Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis

Abstract: Association of vitamin K with cardiovascular events and all-cause mortality: a systematic review and meta-analysis

Cited by 65 publications

References 64 publications

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

Reduced Vitamin K Status as A Potentially Modifiable Prognostic Risk Factor in COVID-19

The Association of dp-ucMGP with Cardiovascular Morbidity and Decreased Renal Function in Diabetic Chronic Kidney Disease

Vascular Calcification in Chronic Kidney Disease: The Role of Vitamin K- Dependent Matrix Gla Protein

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