vitamin-k-1 and Coronary-Artery-Disease

A protective role for vitamin K in cardiovascular disease (CVD), a leading cause of morbidity and mortality, has been proposed because vitamin K-dependent proteins, such as matrix Gla (γ-carboxyglutamic acid) protein (MGP), are present in vascular tissue. MGP functions as a vascular calcification inhibitor-but only when it is carboxylated, which requires vitamin K. There is more than one naturally occurring form of vitamin K. Phylloquinone (vitamin K1) is found in plant-based foods, whereas menaquinones (vitamin K2) are a class of vitamin K compounds found in animal-based and fermented foods. Phylloquinone and menaquinones are capable of carboxylating MGP and other vitamin K-dependent proteins. In rodent models, high intakes of either phylloquinone or menaquinone reduced vascular calcification. Evidence of the relative importance of phylloquinone and menaquinone to CVD in humans is limited and controversial. In some observational studies, higher dietary menaquinone intake, but not phylloquinone intake, was associated with less coronary artery calcification (a subclinical manifestation of CVD) and a lower risk for clinical CVD events. These findings have led to claims that menaquinones have unique cardiovascular health benefits compared with phylloquinone. However, this claim is not supported by the results of the limited number of intervention trials conducted to date. The purpose of this review is to evaluate the strengths and limitations of the available evidence regarding the role of vitamin K in vascular calcification, CVD, and mortality.

Topics: Animals; Cardiovascular Diseases; Coronary Artery Disease; Humans; Vitamin K; Vitamin K 1; Vitamin K 2

Vitamin K activates matrix Gla protein (MGP), a key inhibitor of vascular calcification. There is a high prevalence of sub-clinical vitamin K deficiency in patients with end-stage kidney disease.. A parallel randomized placebo-controlled pilot trial was designed to determine whether 10 mg of phylloquinone thrice weekly versus placebo modifies coronary artery calcification progression over 12 months in patients requiring hemodialysis with a coronary artery calcium score (CAC) ≥30 Agatston Units (ClinicalTrials.gov identifier NCT01528800). The primary outcome was feasibility (recruitment rate, compliance with study medication, study completion and adherence overall to study protocol). CAC score was used to assess calcification at baseline and 12 months. Secondary objectives were to explore the impact of phylloquinone on vitamin K-related biomarkers (phylloquinone, dephospho-uncarboxylated MGP and the Gla-osteocalcin to Glu-osteocalcin ratio) and events of clinical interest.. A total of 86 patients with a CAC score ≥30 Agatston Units were randomized to either 10 mg of phylloquinone or a matching placebo three times per week. In all, 69 participants (80%) completed the trial. Recruitment rate (4.4 participants/month) and medication compliance (96%) met pre-defined feasibility criteria of ≥4.17 and ≥90%, respectively. Patients randomized to phylloquinone for 12 months had significantly reduced levels of dephospho-uncarboxylated MGP (86% reduction) and increased levels of phylloquinone and Gla-osteocalcin to Glu-osteocalcin ratio compared with placebo. There was no difference in the absolute or relative progression of coronary artery calcification between groups.. We demonstrated that phylloquinone treatment improves vitamin K status and that a fully powered randomized trial may be feasible.

Topics: Calcium-Binding Proteins; Coronary Artery Disease; Extracellular Matrix Proteins; Humans; Osteocalcin; Pilot Projects; Renal Dialysis; Vascular Calcification; Vitamin K; Vitamin K 1; Vitamin K 2

Patients on haemodialysis (HD) exhibit increased cardiovascular mortality associated with accelerated vascular calcification (VC). VC is influenced by inhibitors such as matrix Gla protein (MGP), a protein activated in the presence of vitamin K. HD patients exhibit marked vitamin K deficiency, and supplementation with vitamin K reduces inactive MGP levels in these patients. The VitaVasK trial analyses whether vitamin K1 supplementation affects the progression of coronary and aortic calcification in HD patients.. VitaVasK is a prospective, randomized, parallel group, multicentre trial (EudraCT No.: 2010-021264-14) that will include 348 HD patients in an open-label, two-arm design. After baseline multi-slice computed tomography (MSCT) of the heart and thoracic aorta, patients with a coronary calcification volume score of at least 100 will be randomized to continue on standard care or to receive additional supplementation with 5 mg vitamin K1 orally thrice weekly. Treatment duration will be 18 months, and MSCT scans will be repeated after 12 and 18 months. Primary end points are the progression of thoracic aortic and coronary artery calcification (calculated as absolute changes in the volume scores at the 18-month MSCT versus the baseline MSCT). Secondary end points comprise changes in Agatston score, mitral and aortic valve calcification as well as major adverse cardiovascular events (MACE) and all-cause mortality. VitaVask also aims to record MACE and all-cause mortality in the follow-up period at 3 and 5 years after treatment initiation. This trial may lead to the identification of an inexpensive and safe treatment or prophylaxis of VC in HD patients.

Topics: Antifibrinolytic Agents; Calcium-Binding Proteins; Coronary Artery Disease; Disease Progression; Extracellular Matrix Proteins; Humans; Matrix Gla Protein; Multicenter Studies as Topic; Patient Selection; Prospective Studies; Randomized Controlled Trials as Topic; Renal Dialysis; Tomography, X-Ray Computed; Vascular Calcification; Vitamin K 1

Animal studies have shown that vitamin K treatment reduced vascular calcification, but human data are limited.. We determined the association between vitamin K status and coronary artery calcium (CAC) progression in the Multi-Ethnic Study of Atherosclerosis by using a case-cohort design.. Serum phylloquinone (vitamin K1) was measured in 296 participants with extreme CAC progression and 561 randomly selected participants without extreme CAC progression; all subjects had baseline and follow-up CAC measures (mean follow-up: 2.5 y). A serum vitamin K1 concentration was considered low at <1.0 nmol/L (the distribution median). Outcomes were replicated by using post hoc per-protocol analyses of a vitamin K1 supplementation trial.. The OR (95% CI) for extreme CAC progression for subjects with low serum vitamin K1 compared with subjects without extreme CAC progression was 1.34 (0.94, 1.90; NS) when adjusted for demographics and confounders. A significant interaction between low vitamin K1 and antihypertension medication use was detected (P = 0.016). Hypertension medication users with low serum vitamin K1 were more likely to have extreme CAC progression than were medication users without extreme CAC progression [OR (95% CI): 2.37 (1.38, 4.09)]. In replication, baseline antihypertensive medication users in the supplementation group had less CAC progression than did those in the control group [adjusted mean ± SEM of the 3-y CAC change was +5 ± 20 Agatston units (AU) in the vitamin K1 group (n = 40) and +44 ± 13 AU in the placebo group (n = 49); P < 0.01].. Although the point estimate of our primary analysis suggests low serum vitamin K1 is associated with greater CAC progression, the difference was NS. Low serum vitamin K1 was significantly associated with CAC progression in antihypertension medication users, which, to our knowledge, is a novel finding conditionally replicated by using an independent sample. Intervention trials are needed to determine whether improving serum vitamin K1 reduces CAC progression, especially in hypertensive individuals. This trial was registered at clinicaltrials.gov as NCT00183001.

Topics: Aged; Atherosclerosis; Calcium; Cohort Studies; Coronary Artery Disease; Coronary Vessels; Dietary Supplements; Disease Progression; Double-Blind Method; Ethnicity; Female; Follow-Up Studies; Humans; Male; Middle Aged; Risk Factors; Vascular Calcification; Vitamin K 1

Vitamin K is involved in the formation of coronary artery calcification which is an independent predictor of coronary heart disease. This study aims to explore the association between coronary artery calcification score and serum concentrations of vitamin K1, menaquinone-4 (MK-4) and menaquinone-7 (MK-7) in middle-aged and elderly Chinese population.. A total of 116 patients who underwent CT coronary angiography were consecutively enrolled. Serum concentrations of vitamin K1, MK-4 and MK-7 were determined by high performance liquid chromatography tandem mass spectrometry. The relationships between coronary artery calcification score and serum vitamin K concentrations were analyzed.. Significantly lower serum vitamin K1 concentration was found in the patients with CACS > 400, comparing with the other CACS categories, respectively. Log (CACS + 1) was significantly higher in MK-4 < 0.05 ng/ml group compared with MK-4 ≥ 0.05 ng/ml group [2.03(0.21, 2.58) vs 1.31(0.00, 2.19), P < 0.05]. In subjects with established coronary calcification (defined as CACS > 10), vitamin K1 was found to be an independent factor contributing to higher CACS (r = -0.288, P = 0.013).. In this retrospective analysis, serum vitamin K1 and MK-4 concentrations were significantly lower in middle-aged and elderly cohorts with increasing calcification scores. The significant effect of vitamin K1 on CACS was only found in individuals who already had calcification. Whether the detection of circulating vitamin K in patients with preexisting coronary calcification could guide vitamin K supplementation needs further exploration.

Topics: Aged; Coronary Artery Disease; Humans; Middle Aged; Retrospective Studies; Vascular Calcification; Vitamin K; Vitamin K 1

To investigate the association of plasma phylloquinone concentrations with coronary artery calcification (CAC) and vascular calcification.. In a prospective cohort of 508 postmenopausal women, plasma phylloquinone concentrations were measured by high-pressure liquid chromatography. Calcification was measured in the coronary arteries, aortic valve, mitral valve, and thoracic aorta by multidetector computed tomography. To combine these calcification scores, we dichotomized each of the 4 areas into present or absent. Because of the continuous measurement of CAC, we categorized this as calcification present if Agatston score was >0, and calcification score was calculated as the sum of the calcified areas. Multivariate-adjusted prevalence ratios and odds ratios were estimated using Poisson regression and multinomial logistic regression. After 8.5 years of follow-up, 22% of the women had no calcification, whereas 5% had calcification in all measured areas. Detectable phylloquinone concentrations were associated with increased CAC compared with nondetectable phylloquinone concentrations with a prevalence ratio of 1.34 (95% confidence interval, 1.01-1.77). When dividing women with detectable phylloquinone concentrations into low detectable (>0-0.70 nmol/L) and moderate to high detectable (>0.70 nmol/L) phylloquinone concentrations versus nondetectable phylloquinone concentrations, both were associated with increased CAC with a prevalence ratio of 1.32 (95% confidence interval, 0.99-1.76) and 1.36 (95% confidence interval, 1.02-1.81), respectively. Detectable phylloquinone concentrations were not associated with the number of calcified areas with an odds ratio(no versus ≥ 3 areas calcifications) of 1.60 (95% confidence interval, 0.65-3.99; P=0.31).. Detectable phylloquinone concentrations are not associated with reduced vascular calcification but seemed to be associated with an increased prevalence of CAC.

Topics: Aged; Aortic Diseases; Aortography; Biomarkers; Chromatography, High Pressure Liquid; Coronary Angiography; Coronary Artery Disease; Female; Healthy Volunteers; Humans; Logistic Models; Middle Aged; Multidetector Computed Tomography; Multivariate Analysis; Netherlands; Odds Ratio; Postmenopause; Prevalence; Prospective Studies; Risk Factors; Severity of Illness Index; Vascular Calcification; Vitamin K 1

Coronary artery calcification is a recognised risk factor for ischaemic heart disease and mortality. Evidence is now strong that Mönckeberg's arteriosclerosis, a form of vascular calcification, can be attributable to vitamin K deficiency, but that vitamin K-2, especially the MK-4 form from foods like cheese can be protective. Warfarin blocks the recycling of hepatic and peripheral vitamin K leading to secondary vitamin K deficiency with adverse effects on vasculature, bone, kidneys, brain and other tissues and systems (inflammatory, immune function and neoplasia at least). There is individual susceptibility to vitamin K deficiency and warfarin sensitivity, partly explicable in terms of genetic polymorphisms, epigenetics, diet and pharmacotherapy. The emergence of extensive coronary calcification in a man with atrial fibrillation treated for a decade with warfarin is described by way of illustration and to raise the present clinical management conundrums. Finally, a putative set of recommendations is provided.

Topics: Calcinosis; Coronary Artery Disease; Diet; Factor Xa Inhibitors; Humans; Male; Middle Aged; Monckeberg Medial Calcific Sclerosis; Vitamin K 1; Vitamin K 2; Vitamin K Deficiency; Warfarin

The activity of matrix Gla-protein (MGP), a potent inhibitor of vascular calcification, is dependent on carboxylation using vitamin K as a co-factor. In animals, low intake of total vitamin K has been shown to accelerate vascular calcification via the MGP mechanism. This has led to the hypothesis that low levels of dietary vitamin K intake may be a risk factor for accelerated vascular calcification in humans due to decreased MGP activity. Additionally, some authors have suggested that current recommended daily intake values for vitamin K might be insufficient to fully inhibit vascular calcification via the MGP mechanism. The aim of this study was to examine the relationship between dietary vitamin K1 (the most prevalent dietary form of vitamin K) intake and premature coronary artery calcification (CAC) in an asymptomatic screening population.. We conducted a prospective study of 807 consecutive active-duty US Army personnel, 39-45 years of age, without known coronary heart disease. Vitamin K1 intake was measured with the Block Dietary Questionnaire and CAC was identified using electron-beam computed tomography (EBCT).. We found no significant correlation between CAC score and vitamin K1 intake (r = 0.132, P = 0.106). Multivariate analysis with adjustment for cardiac risk factors showed no association between dietary vitamin K1 intake and CAC.. Dietary vitamin K1 (phylloquinone) intake appears to be unrelated to premature coronary calcification in a screening population. Further investigation into the relationship of vascular calcification and other forms of vitamin K1 (menaquinones) is indicated.

Topics: Adult; Calcinosis; Coronary Artery Disease; Female; Humans; Logistic Models; Male; Middle Aged; Military Personnel; Nutrition Surveys; Prospective Studies; Tomography, X-Ray Computed; Vitamin K 1

Topics: Anticoagulants; Biomedical Research; Coronary Artery Disease; Coronary Disease; Humans; Myocardial Infarction; Phenindione; Placebos; Statistics as Topic; Thromboembolism; Vitamin K 1