Beneficial effects of vitamins D and K on the elastic properties of the vessel wall in postmenopausal women: A follow-up study
Abstract and Figures
Matrix-Gla Protein (MGP) is a strong inhibitor of vascular calcification, the expression of which is vitamin D dependent. MGP contains five gamma-carboxyglutamic acid (Gla)-residues which are formed in a vitamin K-dependent carboxylation step and which are essential for its function. Hence vascular vitamin K-deficiency will result in undercarboxylated, inactive MGP which is a potential risk factor for calcification. In the present study we describe the effects of vitamin K1 and D supplementation on vascular properties in postmenopausal women. In a randomized placebo-controlled intervention study, 181 postmenopausal women were given either a placebo or a supplement containing minerals and vitamin D (MD-group), or the same supplement with vitamin K1 (MDK-group). 150 participants completed the study and analysis was performed on 108 participants. At baseline and after three years, vessel wall characteristics, including compliance coefficient (CC), distensibility coefficient (DC), intima-media thickness (IMT) and the Young's Modulus (E) were measured to assess the effect of the supplements on the change of these parameters. The results showed that the elastic properties of the common carotid artery in the MDK-group remained unchanged over the three-year period, but decreased in the MD- and placebo-group. Comparing the MDK- and placebo-group, there were significant differences in decrease of DC (8.8%; p<0.05), CC (8.6%; p<0.05), and in increase of PP (6.3%; p<0.05) and E (13.2%, p<0.01). There were no significant differences between the MD-group and placebo. No significant differences were observed in the change of IMT between the three groups. It is concluded that a supplement containing vitamins K1 and D has a beneficial effect on the elastic properties of the arterial vessel wall.
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... Studies in patients with CKD will be discussed in the following paragraph. In postmenopausal women, three years of supplementation with vitamin K1 significantly enhanced the compliance and distensibility of the arterial vessel wall [47]. There was no effect, however, on the progression of atherosclerosis quantified by carotid intima-media thickness (cIMT) [47]. ...
... In postmenopausal women, three years of supplementation with vitamin K1 significantly enhanced the compliance and distensibility of the arterial vessel wall [47]. There was no effect, however, on the progression of atherosclerosis quantified by carotid intima-media thickness (cIMT) [47]. In healthy postmenopausal women, three years of supplementation of vitamin K2 was effective in reducing arterial stiffness quantified by PWV [48]. ...
Citation: Piscaer, I.; Janssen, R.; Franssen, F.M.E.; Schurgers, L.J.; Wouters, E.F.M. The Pleiotropic Role of Vitamin K in Multimorbidity of Chronic Obstructive Pulmonary Disease. Abstract: Although defined by the presence of airflow obstruction and respiratory symptoms, patients with chronic obstructive pulmonary disease (COPD) are characterized by multimorbidity. Numerous co-occurring conditions and systemic manifestations contribute to the clinical presentation and progression of COPD; however, underlying mechanisms for multimorbidity are currently not fully elucidated. Vitamin A and vitamin D have been related to COPD pathogenesis. Another fat-soluble vitamin, vitamin K, has been put forward to exert protective roles in COPD. Vitamin K is an unequivocal cofactor for the carboxylation of coagulation factors, but also for extra-hepatic proteins including the soft tissue calcification inhibitor matrix Gla-protein and the bone protein osteocalcin. Additionally, vitamin K has been shown to have anti-oxidant and anti-ferroptosis properties. In this review, we discuss the potential role of vitamin K in the systemic manifestations of COPD. We will elaborate on the effect of vitamin K on prevalent co-occurring chronic conditions in COPD including cardiovascular disorders, chronic kidney disease, osteoporosis, and sarcopenia. Finally, we link these conditions to COPD with vitamin K as a connecting factor and provide recommendations for future clinical studies.
... These T2DM patients with hypovitaminosis D have significant thickening of the common carotid intima compared to those presenting normal serum 25(OH)D levels [49]. However, when 108 healthy postmenopausal women (mean age: 55 years) received a daily supplement containing minerals and vitamin D, no statistical significance was seen for intima-media thickness, compliance coefficient, or distensibility coefficient when compared to a placebo [50]. Oh and colleagues, in an in vitro study, found that 1,25(OH)2D suppressed macrophage foam cell formation in a cultured positive medium by reducing acetylated or oxidized LDL uptake. ...
... There is evidence that vitamin D directly stimulates insulin secretion by pancreatic β cells, and some other indirect actions have been proposed [62]. Additionally, considering the relevance of 25(OH)D in the regulation of the immune system, as suggested by the higher prevalence of hypovitaminosis D in patients with autoimmune diseases (e.g., Crohn's disease, T2DM, rheumatoid arthritis, lupus, and multiple sclerosis) and some types of cancer (e.g., colon, prostate, breast, and pancreas), the possibility was also raised that exacerbation of inflammatory responses, which accompanies hypovitaminosis D states, may contribute to the worsening of insulin resistance [5,49,50,62,63]. ...
Introduction:
Vitamin D has been primarily studied as an important factor influencing bone and calcium metabolism. Metabolites of vitamin D are essential for whole-body calcium homeostasis, maintaining serum calcium levels within a narrow range by regulating this process in the bones and gut. Nevertheless, its deficiency is also related to increased risk of type 2 diabetes mellitus (T2DM), metabolic syndrome (MS), and cardiovascular disease (CVD)-with increased visceral adipose tissue and body mass index (BMI), as well as the frequently associated hypercholesterolemia. It has been reported that vitamin D levels are inversely related to cardiovascular (CV) risk in men and women. However, the effects of vitamin D on distinct outcomes in women and the dose of supplementation needed to improve clinical endpoints have not been established. 25-Hydroxyvitamin D [25(OH)D] reduces systemic inflammatory mediators in CVD and favors the release of anti-inflammatory cytokines from the immune system. In addition, 25(OH)D can be primarily converted into calcitriol (1,25-dihydroxycholecalciferol [1,25(OH)2D]) in the kidneys through the action of the 1-α-hydroxylase enzyme. Calcitriol, through the downregulation mechanism of renin expression, renin-angiotensin-aldosterone system (RAAS) activity, and its interaction with the vitamin D receptor, can bring CV benefits. The calcitriol form also lowers parathyroid hormone (PTH) levels by indirectly causing a reduction in aldosterone and mineralocorticoid synthesis. Elevated plasma aldosterone is related to endothelial dysfunction and CVD in hypovitaminosis D status.
Conclusion:
Vitamin D supplementation may benefit certain risk groups, as it improves metabolic variables, reducing oxidative stress and CV outcomes. More studies are needed to define interventions with vitamin D in men and women.
... There are also intervention studies addressing a possible role for a preventive effect of vitamin K in cardiovascular health. In an intervention study including 121 healthy participants, it was shown that a 3-year vitamin K1 (100 µg/day) supplementation period resulted in maintenance of vascular elasticity, in comparison with a 12% loss of elasticity in the placebo group [95]. In a placebo-controlled human trial of supplementation with vitamin K2 MK7 in postmenopausal women (n = 244), Knapen et al. showed that MK7 supplementation (180 µg/day) for 3 years significantly decreased pulse wave velocity, which is the gold standard for measuring arterial stiffness [96]. ...
The observation that the extent of artery calcification correlates with the degree of atherosclerosis was the background for the alternative treatment of cardiovascular disease with chelator ethylenediamine tetraacetate (EDTA). Recent studies have indicated that such chelation treatment has only marginal impact on the course of vascular disease. In contrast, endogenous calcium chelation with removal of calcium from the cardiovascular system paralleled by improved bone mineralization exerted, i.e., by matrix Gla protein (MGP) and osteocalcin, appears to significantly delay the development of cardiovascular diseases. After post-translational vitamin-K-dependent carboxylation of glutamic acid residues, MGP and other vitamin-K-dependent proteins (VKDPs) can chelate calcium through vicinal carboxyl groups. Dietary vitamin K is mainly provided in the form of phylloquinone from green leafy vegetables and as menaquinones from fermented foods. Here, we provide a review of clinical studies, addressing the role of vitamin K in cardiovascular diseases, and an overview of vitamin K kinetics and biological actions, including vitamin-K-dependent carboxylation and calcium chelation, as compared with the action of the exogenous (therapeutic) chelator EDTA. Consumption of vitamin-K-rich foods and/or use of vitamin K supplements appear to be a better preventive strategy than EDTA chelation for maintaining vascular health.
... [15][16][17] At present, few RCTs have been performed in individuals without manifest CVD. [18][19][20] One RCT in healthy older adults found no overall effect of a 3-year intervention with vitamin K1 on progression of CAC, while among adherent individuals with mild pre-existing CAC, vitamin K reduced CAC progression with 6%. 18 Similar to these findings, 3 years supplementation with 180 µg menaquinone-7 (MK-7) per day significantly improved arterial stiffness in healthy postmenopausal women, with the most pronounced effect seen in women with increased arterial stiffness at baseline. ...
Introduction
Vitamin K has been suggested to have protective effects against progression of vascular calcification and development of cardiovascular disease (CVD). However, few well-powered randomised controlled trials have examined whether vitamin K prevents progression of vascular calcification in individuals from the general population. The aim of the InterVitaminK trial is to investigate the effects of vitamin K supplementation (menaquinone-7, MK-7) on cardiovascular, metabolic, respiratory and bone health in a general ageing population with detectable vascular calcification.
Methods and analysis
The InterVitaminK trial is a randomised, double-blinded, placebo-controlled, trial. A total of 450 men and women aged 52–82 years with detectable coronary artery calcification (CAC), but without manifest CVD, will be randomised (1:1) to receive daily MK-7 (333 µg/day) or placebo tablets for 3 years. Health examinations are scheduled at baseline, and after 1, 2 and 3 years of intervention. Health examinations include cardiac CT scans, measurements of arterial stiffness, blood pressure, lung function, physical function, muscle strength, anthropometric measures, questionnaires on general health and dietary intake, and blood and urine sampling. The primary outcome is progression of CAC from baseline to 3-year follow-up. The trial has 89% power to detect a between-group difference of at least 15%. Secondary outcomes are bone mineral density, pulmonary function and biomarkers of insulin resistance.
Ethics and dissemination
Oral MK-7 supplementation is considered safe and has not been found to cause severe adverse events. The Ethical Committee of the Capital Region (H-21033114) approved the protocol. Written informed consent is obtained from all participants and the trial is conducted in accordance with the Declaration of Helsinki II. Both negative and positive findings will be reported.
Trial registration number
NCT05259046 .
... A recent North Indian case control study of nulliparous women with PE and singleton pregnancies reported serum vitamin D to be significantly lower among PE cases vs. controls at the time of delivery (24.2 +/− 12.4 nmol/L, 36.9 +/− 16.7 nmol/L, respectively; p = 0.0001). Similar vitamin D levels were found in women with mild and severe PE (29) . Two cross-sectional studies report 25(OH)D and 1,25(OH)2D levels to be lower in women with PE in the third trimester. ...
... It has been reported that 25(OH)D level was inversely related to stroke risk, with a non-linear dose response relationship (15). Previous studies have shown that vitamins D and K have a synergistic effect on cardiovascular health (16,17). As noted previously, prospective studies of the association between blood concentrations of vitamin K1 and subsequent stroke are sparse, and additionally, the question remains whether a joint association exists between vitamins D and K1, and stroke. ...
Background
Vitamin K plays a role in preventing vascular calcification and may have a synergetic influence with vitamin D on cardiovascular health. However, whether this relationship applies to stroke, especially in a high-risk population of hypertensive individuals, remains unclear. The present study aims to study the joint association of low vitamin K1 and D status with first stroke in general hypertensive adults.
Methods
This study used a nested, case–control design with data from the China Stroke Primary Prevention Trial. The analysis included 604 first total stroke patients and 604 matched controls from a Chinese population with hypertension. Odds ratios (ORs) and 95% confidence intervals were calculated using conditional logistic regression.
Results
There was a non-linear negative association between plasma vitamin K1 and the risk of first total stroke or ischemic stroke in the enalapril-only group. Compared to participants in vitamin K1 quartile 1, a significantly lower risk of total stroke ( OR = 0.58, 95% CI: 0.36, 0.91, P = 0.020) or ischemic stroke ( OR = 0.34, 95% CI: 0.17, 0.63, P < 0.001) was found in participants in vitamin K1 quartile 2-4 in the enalapril-only group. When further divided into four subgroups by 25(OH)D and vitamin K1, a significantly higher risk of total stroke or ischemic stroke was observed in participants with both low vitamin K1 and 25(OH)D compared to those with both high vitamin K1 and 25(OH)D in the enalapril-only group. No increased risk was observed in the groups low in one vitamin only.
Conclusion
Low concentrations of both vitamin K1 and 25(OH)D were associated with increased risk of stroke.
... Furthermore, vitamin K2 was shown to slightly increase HDL cholesterol and to decrease systemic inflammation [93,94]. Consistently, its supplementation could be supposed to slow vascular damage and prevent atherosclerosis, CVD and stroke [95][96][97][98]. Indeed, a connection between higher estimated menaquinone intake (above 21.6 µg/day) and decreased coronary heart disease-related mortality and aortic calcification was found, but there was no such correlation for phylloquinone [99][100][101]. ...
Chronic kidney disease (CKD) is commonly associated with vitamin K deficiency. Some of the serious complications of CKD are represented by cardiovascular disease (CVD) and skeletal fragility with an increased risk of morbidity and mortality. A complex pathogenetic link between hormonal and ionic disturbances, bone tissue and metabolism alterations, and vascular calcification (VC) exists and has been defined as chronic kidney disease–mineral and bone disorder (CKD-MBD). Poor vitamin K status seems to have a key role in the progression of CKD, but also in the onset and advance of both bone and cardiovascular complications. Three forms of vitamin K are currently known: vitamin K1 (phylloquinone), vitamin K2 (menaquinone), and vitamin K3 (menadione). Vitamin K plays different roles, including in activating vitamin K-dependent proteins (VKDPs) and in modulating bone metabolism and contributing to the inhibition of VC. This review focuses on the biochemical and functional characteristics of vitamin K vitamers, suggesting this nutrient as a possible marker of kidney, CV, and bone damage in the CKD population and exploring its potential use for promoting health in this clinical setting. Treatment strategies for CKD-associated osteoporosis and CV disease should include vitamin K supplementation. However, further randomized clinical studies are needed to assess the safety and the adequate dosage to prevent these CKD complications.
Calcification in the vascular bed relates to the formation of calcium crystals that organize into aggregates and sheet-like lattices that mostly consist of calcium phosphate (hydroxyapatite), but in some rare conditions consist of calcium oxalate.
The appearance of detectable amounts of calcium in atheromatous plaque in the coronary circulation by computerized tomography (CT) scanning marks an inflection point in the natural history of coronary artery disease.
This chapter focuses on how calcification develops in atheromatous plaque and highlights how it differs in nature from calcification in the media of the vessel wall. The distinction is important as the treament varies with the location of calcium. Whereas atherosclerosis is generally widespread in the systemic circulation, calcification in the media is unrelated to the atherosclerosis and is rarely seen in the coronary arteries. Thus, while the detection of coronary calcification by CT scanning is specific for atherosclerosis, vascular calcification beyond the coronary tree may over-estimate the atherosclerotic load that often co-exists with it.
Currently there is no compelling evidence that reducing vascular calcification impacts the natural history of patients with coronary atherosclerosis or peripheral vascular disease. However, it is possible that the measurement of total coronary calcium scores are too blunt as an instrument to measure the potential benefits of therapies that can truly modify the formation and morphology of calcium crystals as they begin to develop in the atherosclerotic matrix.
Background
Vascular calcification (VC) is a complex process that has been linked to conditions including cardiovascular diseases and chronic kidney disease. There is an ongoing debate about whether vitamin K (VK) can effectively prevent VC. To assess the efficiency and safety of VK supplementation in the therapies of VC, we performed a systematic review and meta-analysis of recent studies.
Methods
We searched major databases, including PubMed, the Cochrane Library, Embase databases, and Web of Science up until August 2022. 14 randomized controlled trials (RCTs) describing the outcomes of treatment for VK supplementation with VC have been included out of 332 studies. The results were reported in the change of coronary artery calcification (CAC) scores, other artery and valve calcification, vascular stiffness, and dephospho-uncarboxylated matrix Gla protein (dp-ucMGP). The reports of severe adverse events were recorded and analyzed.
Results
We reviewed 14 RCTs, comprising a total of 1,533 patients. Our analysis revealed that VK supplementation has a significant effect on CAC scores, slowing down the progression of CAC [ I ² = 34%, MD= −17.37, 95% CI (−34.18, −0.56), p = 0.04]. The study found that VK supplementation had a significant impact on dp-ucMGP levels, as compared to the control group, where those receiving VK supplementation had lower values [ I ² = 71%, MD = −243.31, 95% CI (−366.08, −120.53), p = 0.0001]. Additionally, there was no significant difference in the adverse events between the groups [ I ² = 31%, RR = 0.92, 95% CI (−0.79,1.07), p = 0.29].
Conclusion
VK may have therapeutic potential for alleviating VC, especially CAC. However, more rigorously designed RCTs are required to verify the benefits and efficacy of VK therapy in VC.
Vitamin D3 deficiency is common worldwide (Holick, 2006) (1). For example, vitamin D3 deficiency was 77% in the US population (Ginde et al., 2009) (2). According to our data, vitamin D3 deficiency was found in 80% of CHD patients (3). Ecological studies have shown a higher incidence of cardiovascular disease with increasing distance from the equator, suggesting an association with vitamin D insufficiency in regions with less sun exposure (4). Low 25(OH)D concentrations may increase the risk of hypertension, peripheral vascular disease, diabetes, obesity, myocardial infarction, heart failure, and cardiac mortality (4,5,6,7), low 25(OH)D levels are associated with endothelial dysfunction, inflammation, increased vascular stiffness and arterial calcification (8).
Background:
Calcification of the media of peripheral arteries is referred to as Mönckeberg's sclerosis (MS) and occurs commonly in aged and diabetic individuals. Its pathogenesis is unknown, but its presence predicts risk of cardiovascular events and leg amputation in diabetic patients. Several studies have documented expression of bone-associated genes in association with intimal atherosclerotic calcification, leading to the suggestion that vascular calcification may be a regulated process with similarities to developmental osteogenesis. Therefore, we examined gene expression in vessels with MS to determine whether there was evidence for a regulated calcification process in the vessel media.
Methods and results:
In situ hybridization, immunohistochemistry, and semiquantitative reverse-transcription polymerase chain reaction were used to examine the expression of mineralization-regulating proteins in human peripheral arteries with and without MS. MS occurred in direct apposition to medial vascular smooth muscle cells (VSMCs) in the absence of macrophages or lipid. These VSMCs expressed the smooth muscle-specific gene SM22alpha and high levels of matrix Gla protein but little osteopontin mRNA. Compared with normal vessels, vessels with MS globally expressed lower levels of matrix Gla protein and osteonectin, whereas alkaline phosphatase, bone sialoprotein, bone Gla protein, and collagen II, all indicators of osteogenesis/chondrogenesis, were upregulated. Furthermore, VSMCs derived from MS lesions exhibited osteoblastic properties and mineralized in vitro.
Conclusions:
These data indicate that medial calcification in MS lesions is an active process potentially orchestrated by phenotypically modified VSMCs.
The stiffness of the thoracic aorta can be assessed non-invasively. If aortic stiffness can be shown to be related to coronary heart disease, perhaps it can be used to identify which patients with hypercholesterolaemia are most likely to have atheromatous changes and thus to be selected for intensive cholesterol-lowering treatment. Hence the distensibility of the transverse aortic arch was measured by echocardiography of the aortic arch in four groups of patients--symptom-free patients with normal serum cholesterol; symptom-free patients with raised serum cholesterol; patients with coronary heart disease (all with raised serum cholesterol), and post-heart-transplant patients. In all groups distensibility fell with age. The regression slope was steeper (p less than 0.05) for patients with known coronary disease than for either of the disease-free groups, and among cardiac transplant recipients there was also a segregation of distensibility values between those with and without atheroma in their native hearts. The results indicate that aortic distensibility might be an indicator of coronary heart disease and that it might be useful in identifying which symptom-free subjects with modest hypercholesterolaemia should be treated aggressively.
As ultrasonographically assessed carotid arteriosclerosis is being used as a surrogate measure for coronary arteriosclerosis, we performed a prospective longitudinal study of the association of our high-resolution ultrasound assessment of extracranial carotid morphology with the risk of acute coronary events in 1,288 eastern Finnish men. The presence of any structural changes in the common carotid arteries or carotid bulbs was associated with a 3.29-fold (95% confidence interval, 1.31-8.29; p = 0.0074), intimal-medial thickening with a 2.17-fold (95% confidence interval, 0.70-6.74; p = NS), small carotid plaques with a 4.15-fold (95% confidence interval, 1.51-11.47; p less than 0.01), and large ("stenotic") plaques with a 6.71-fold (95% confidence interval, 1.33-33.91; p less than 0.01) risk of acute myocardial infarction compared with men free of any structural changes in the carotid artery wall at baseline. These data confirm the close relation between carotid artery wall morphology and coronary heart disease.
The synthesis of matrix Gla protein (MGP) and bone Gla protein (BGP) have been shown to be mutually exclusive in all osteosarcoma cell lines investigated. In the cell lines that produce the respective proteins, synthesis is stimulated by 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) within the first several hours of hormone treatment. In the present studies we have investigated the effects of longer-term treatment with 1,25(OH)2D3 in the ROS 17/2 cell line, a cell line that synthesizes BGP constitutively but does not synthesize MGP. In agreement with earlier studies, the rate of BGP synthesis increases within 8 hours of hormone treatment, is maximal by 24 hours, and remains at the maximal rate through 48 hours of 1,25(OH)2D3 treatment. The present study is the first to report that the rate of BGP secretion at times beyond 48 hours declines to that of control cultures despite the continued administration of 1,25(OH)2D3, and that MGP synthesis is induced in ROS 17/2 cells by 48 hours of 1,25(OH)2D3 treatment. At this time, MGP mRNA could be detected by northern blot analysis and MGP secretion could be demonstrated by radioimmunoassay of culture medium. Both the level of MGP message per unit total RNA and the rate of MGP secretion into culture medium increased steadily between 2 and 6 days of 1,25(OH)2D3 treatment. The MGP synthesized by the 1,25(OH)2D3-treated ROS 17/2 cells was identical to that found in bone by northern blot analysis of message and by western blot analysis of the media antigen. Half-maximal induction of MGP synthesis was obtained with 0.3 nM 1,25(OH)2D3, a 60-fold higher dosage than was required for the half maximal stimulation of BGP synthesis in these cells. Treatment of ROS 17/2 cells with 24,24-F21,25(OH)2D3 suggests that the observed difference in dose dependence is not due to an increased rate of hormone catabolism.
Vitamin K functions as a cofactor during the posttranslational modification of proteins. The reaction in question is the carboxylation of glutamate (Glu) residues into γ-carboxyglutamate (Gla). The discovery of vitamin K in 1935 and the identification of Gla in the early 1970s have been reviewed elsewhere and will not be detailed in this paper. Here we intend to summarize the recent advances in vitamin K research.
Doppler signal processing cannot only be employed to detect the local blood velocity as function of time, but also to assess transcutaneously the displacement of the arterial walls during the cardiac cycle (distension waveform) and, hence, the time-dependent changes in arterial diameter relative to its initial diameter at the start of a cardiac cycle. The distension waveform normalized with respect to the local pulse pressure provides useful information about the local elasticity of the arterial wall. The displacement of the arterial wall can be obtained by processing the RF-signals within a sample volume coinciding with the arterial wall. To evaluate this method a dedicated high-speed memory system has been developed storing the RF-signal, as obtained with a conventional echo-imager in M-mode, over a number of successive sweeps covering a selected depth range. The data are transferred line after line to a personal computer (PC) and processed on the fly, thereby relieving the memory requirements of the PC. It can be concluded that a RF-signal memory in combination with a PC provides a useful tool to extract detailed diameter waveforms from the RF-signals obtained. Although the system does not process the signals in real-time the process can be considered to be on-line since the results become available within one minute after the acquisition of the data is completed.
We investigated the progression of carotid atherosclerosis in a population-based sample of 100 Eastern Finnish men aged 42, 48, 54 or 60 years. A high-resolution B-mode ultrasonographic examination was repeated after a follow-up of 24 months for each subject. The intimal-medial thickness (IMT) in the common carotid artery increased by -0.06 mm to 0.90 mm (mean 0.12 mm, SD 0.20 mm). Age (standardised partial coefficient, beta = 0.325, P = 0.0003), serum LDL cholesterol concentration (beta = 0.229, P = 0.0011), pack-years of smoking (beta = 0.274, P = 0.0023), blood leukocyte count (beta = 0.201, P = 0.0239), and platelet aggregability (beta = 0.165, P = 0.0646), measured at baseline, were the strongest predictors of atherosclerosis progression. Neither hypertension, current blood pressure level, serum HDL cholesterol nor serum HDL2 cholesterol concentration at the baseline examination had any association with the change of IMT over 2 yrs.
To determine whether vitamin K administration affects urinary calcium excretion in postmenopausal women.
Before- and after-trials with a 2-week treatment period.
Healthy postmenopausal women (55 to 75 years old) were recruited from the convents in and around Maastricht. Controls (25 to 40 years old) were healthy premenopausal volunteers.
Daily administration of 1 mg of vitamin K for 2 weeks.
Serum immunoreactive osteocalcin: hydroxylapatite binding (HAB) capacity of serum immunoreactive osteocalcin; excretion of calcium, hydroxyproline, and creatinine in the urine during the last 2 h of a 16-h fasting period.
In premenopausal women, no effect of vitamin K administration was seen. In the postmenopausal group, vitamin K induced increased serum immunoreactive osteocalcin concentration; normalization of the HAB capacity of serum immunoreactive osteocalcin (this marker was less than 50% that of the controls in the pretreatment samples); a decrease in urinary calcium excretion, notably in the "fast losers" of calcium; and a parallel decrease in urinary hydroxyproline excretion in the fast losers of calcium.
The serum immunoreactive osteocalcin level may vary with vitamin K status. This variance should be taken into consideration if osteocalcin is used as a marker for osteoblast activity. Vitamin K is one factor that may play a role in the loss of bone mass in postmenopausal osteoporosis.
The static elastic properties of arterial tree (abdominal aorta and common carotid artery) were studied in 19 normal subjects and in 49 patients with myocardial infarction with an ultrasonic phase-locked echo-tracking system that allows continuous transcutaneous measurement of the arterial diameter. The stiffness index beta, which represented the mechanical properties in the arterial wall, was calculated from the relation between systemic blood pressure and the diameter of the artery. Patients with myocardial infarction underwent coronary angiography in their convalescent period to determine involved vessels. In 11 patients, coronary artery was patent; 15 patients had one-vessel disease, 12 had two-vessel disease, and the remaining 11 patients had three-vessel disease. In normal subjects, increasing age was associated with an increase in arterial stiffness. An average value of the stiffness index of the abdominal aorta was 8.58 +/- 3.02 (mean +/- SD) and that of common carotid artery was 9.17 +/- 2.22. In patients with three-vessel disease, these values were significantly higher (22.37 +/- 4.29 in abdominal aorta and 13.17 +/- 4.56 in common carotid artery) than those in normal subjects. Stiffness index of patients with two- or one-vessel disease was also increased but lower than those in patients with three-vessel disease (p less than 0.05). Forty-four of 49 patients with infarction had an arterial stiffness index of abdominal aorta higher than the 95% confidence limits of the normal data (p less than 0.05). Twenty-eight patients were outside the nomogram of common carotid artery (p less than 0.05). The mechanical properties of these elastic arteries provided sufficiently reliable information on changes caused by atherosclerosis.