Impact of menaquinone-4 supplementation on coronary artery calcification and arterial stiffness: an open label single arm study.
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ABSTRACT:
SUBMITTER: Ikari Y
PROVIDER: S-EPMC4866409 | biostudies-other | 2016
REPOSITORIES: biostudies-other
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Project description:Coronary artery calcification (CAC) develops early in the pathogenesis of atherosclerosis and is a strong and independent predictor of cardiovascular disease (CVD). Arterial calcification is caused by an imbalance in calcification regulatory mechanisms. An important inhibitor of calcification is vitamin K-dependent matrix Gla protein (MGP). Both preclinical and clinical studies have shown that inhibition of the vitamin K-cycle by vitamin K antagonists (VKA) results in elevated uncarboxylated MGP (ucMGP) and subsequently in extensive arterial calcification. This led us to hypothesize that vitamin K supplementation may slow down the progression of calcification. To test this, we designed the VitaK-CAC trial which analyses effects of menaquinone-7 (MK-7) supplementation on progression of CAC. The trial is a double-blind, randomized, placebo-controlled trial including patients with coronary artery disease (CAD). Patients with a baseline Agatston CAC-score between 50 and 400 will be randomized to an intervention-group (360 microgram MK-7) or a placebo group. Treatment duration will be 24 months. The primary endpoint is the difference in CAC-score progression between both groups. Secondary endpoints include changes in arterial structure and function, and associations with biomarkers. We hypothesize that treatment with MK-7 will slow down or arrest the progression of CAC and that this trial may lead to a treatment option for vascular calcification and subsequent CVD.
| S-EPMC4663571 | biostudies-literature
Project description:BackgroundThere is a very high prevalence of subclinical vitamin K deficiency in patients requiring hemodialysis (HD), and this problem is associated with vascular calcification and arterial stiffness. Vitamin K2 (MK-7) supplementation can improve vitamin K status in HD patients. However, the benefits of vitamin K supplementation on arterial stiffness have still not been established. The present study was conducted to evaluate the efficacy of menaquinone-7 (MK-7) supplementation on arterial stiffness in chronic HD patients.MethodsThis open-label multicenter randomized clinical trial was conducted in 96 HD patients who had arterial stiffness, defined by high carotid femoral pulse wave velocity (cfPWV ≥ 10 m/s). The patients were randomly assigned to receive oral MK-7 (375 mcg once daily) for 24 weeks (n = 50) or standard care (control group; n = 46). The change in cfPWV was the primary outcome.ResultsBaseline parameters were comparable between the two groups. There was no significant difference in the change in cPWV at 24 weeks between the MK-7 group and standard care [-6.0% (-20.2, 2.3) vs. -6.8% (-19.0, 7.3), p = 0.24]. However, we found that MK-7 significantly decreased cPWV in patients with diabetes [-10.0% (-15.9, -0.8) vs. 3.8% (-5.8, 11.6), p = 0.008]. In addition, the MK-7 group had a lower rate of arterial stiffness progression, compared to controls (30.2% vs. 39.5%, p = 0.37), especially in diabetes patients (21.4% vs. 72.7%, p = 0.01). No serious adverse events were observed during the 24 weeks.ConclusionVitamin K supplements provided a beneficial impact in lowering the rate of arterial stiffness progression in chronic hemodialysis patients with diabetes. Possible benefits on cardiovascular outcomes require further investigation.
| S-EPMC10255064 | biostudies-literature
Project description:BackgroundThe triglyceride and glucose (TyG) index has been linked to various cardiovascular diseases. However, it's still unclear whether the TyG index is associated with arterial stiffness and coronary artery calcification (CAC).MethodsWe conducted a systematic review and meta-analysis of relevant studies until September 2022 in the PubMed, Cochrane Library, and Embase databases. We used a random-effects model to calculate the pooled effect estimate and the robust error meta-regression method to summarize the exposure-effect relationship.ResultsTwenty-six observational studies involving 87,307 participants were included. In the category analysis, the TyG index was associated with the risk of arterial stiffness (odds ratio [OR]: 1.83; 95% CI 1.55-2.17, I2 = 68%) and CAC (OR: 1.66; 95% CI 1.51-1.82, I2 = 0). The per 1-unit increment in the TyG index was also associated with an increased risk of arterial stiffness (OR: 1.51, 95% CI 1.35-1.69, I2 = 82%) and CAC (OR: 1.73, 95% CI 1.36-2.20, I2 = 51%). Moreover, a higher TyG index was shown to be a risk factor for the progression of CAC (OR = 1.66, 95% CI 1.21-2.27, I2 = 0, in category analysis, OR = 1.47, 95% CI 1.29-1.68, I2 = 41% in continuity analysis). There was a positive nonlinear association between the TyG index and the risk of arterial stiffness (Pnonlinearity < 0.001).ConclusionAn elevated TyG index is associated with an increased risk of arterial stiffness and CAC. Prospective studies are needed to assess causality.
| S-EPMC10183133 | biostudies-literature
Project description:ObjectiveCoronary artery calcified plaque is a marker for atheromatous plaque burden and predicts future risk of cardiovascular events. The relationship between calcium plus vitamin D (calcium/D) supplementation and coronary artery calcium (CAC) has not been previously assessed in a randomized trial setting. We compared CAC scores after trial completion between women randomized to calcium/vitamin D supplementation and women randomized to placebo.MethodsIn an ancillary substudy of women randomized to calcium carbonate (1,000 mg of elemental calcium daily) plus vitamin D3 (400 IU daily) or placebo, nested within the Women's Health Initiative trial of estrogen among women who underwent hysterectomy, we measured CAC with cardiac CT in 754 women aged 50 to 59 years at randomization. Imaging for CAC was performed at 28 of 40 centers after a mean of 7 years of treatment, and scans were read centrally. CAC scores were measured by a central reading center with masking to randomization assignments.ResultsPosttrial CAC measurements were similar in women randomized to calcium/D supplementation and those receiving placebo. The mean CAC score was 91.6 for women receiving calcium/D and 100.5 for women receiving placebo (rank test P value = 0.74). After adjustment for coronary risk factors, multivariate odds ratios for increasing CAC score cutpoints (CAC >0, > or =10, and > or =100) for calcium/D versus placebo were 0.92 (95% CI, 0.64-1.34), 1.29 (0.88-1.87), and 0.90 (0.56-1.44), respectively. Corresponding odds ratios among women with a 50% or higher adherence to study pills and for higher levels of CAC (>300) were similar.ConclusionsTreatment with moderate doses of calcium plus vitamin D3 did not seem to alter coronary artery calcified plaque burden among postmenopausal women. Whether higher or lower doses would affect this outcome remains uncertain.
| S-EPMC2940244 | biostudies-literature
Project description:Vascular calcification is a risk factor that predicts adverse cardiovascular complications of several diseases including atherosclerosis. Reduced dietary potassium intake has been linked to cardiovascular diseases such as hypertension and incidental stroke, although the underlying molecular mechanisms remain largely unknown. Using the ApoE-deficient mouse model, we demonstrated for the first time to our knowledge that reduced dietary potassium (0.3%) promoted atherosclerotic vascular calcification and increased aortic stiffness, compared with normal (0.7%) potassium-fed mice. In contrast, increased dietary potassium (2.1%) attenuated vascular calcification and aortic stiffness. Mechanistically, reduction in the potassium concentration to the lower limit of the physiological range increased intracellular calcium, which activated a cAMP response element-binding protein (CREB) signal that subsequently enhanced autophagy and promoted vascular smooth muscle cell (VSMC) calcification. Inhibition of calcium signals and knockdown of either CREB or ATG7, an autophagy regulator, attenuated VSMC calcification induced by low potassium. Consistently, elevated autophagy and CREB signaling were demonstrated in the calcified arteries from low potassium diet-fed mice as well as aortic arteries exposed to low potassium ex vivo. These studies established a potentially novel causative role of dietary potassium intake in regulating atherosclerotic vascular calcification and stiffness, and uncovered mechanisms that offer opportunities to develop therapeutic strategies to control vascular disease.
| S-EPMC5841863 | biostudies-literature
Project description:BackgroundSubclinical atherosclerosis detected by increased coronary artery calcium (CAC) or arterial stiffness as reflected by cardio-ankle vascular index (CAVI) has been associated with major adverse cardiovascular events (MACEs). However, comparative data from these two assessments in the same population are still limited.MethodsFrom 2005 to 2013, patients with stable coronary artery disease (CAD), both asymptomatic and symptomatic who underwent both coronary computed tomography and CAVI were enrolled and followed for occurrence of MACEs (cardiovascular [CV] death, nonfatal myocardial infarction [MI], and nonfatal stroke) until December 2019. A cause-specific hazard model was applied to assess the associations of CAC score, and CAVI with long-term MACEs.ResultsA total of 8687 patients participated. Of them, CAC scores were 0, 1-99, 100-399, and ≥400 in 49.7%, 31.9%, 12.3%, and 6.1%, respectively. Arterial stiffness (CAVI ≥ 9.0) was associated with the magnitude of CAC in 23.8%, 36.3%, 44.5%, and 56.2%, respectively. During an average of 9.9 ± 2.4 years follow-up, MACEs occurred in 8.0% (95% CI: 7.4%, 8.6%) of subjects. After adjusting for covariables, CAC scores of 100-399 and ≥400, and CAVIs of ≥9.0 were found to independently predict the occurrence of MACEs with the hazard ratios (95% CI) of 1.70 (1.13, 1.98), 1.87 (1.33, 2.63), and 1.27 (1.06, 1.52), respectively. Other risk predictors were hypertension, diabetes mellitus (DM), chronic kidney disease (CKD), aspirin, and statin therapy.ConclusionsA CAC score ≥100 or a CAVI ≥ 9.0 predicts the long-term occurrence of MACEs in both asymptomatic and symptomatic patients with stable CAD. These two noninvasive tests can be used as screening tools to guide treatment for the prevention of future CV events.
| S-EPMC9933115 | biostudies-literature
Project description:BACKGROUND:There is increasing evidence that breast arterial calcification (BAC), an incidental finding on 3-29% of mammograms, could be used to screen for coronary artery disease (CAD). We conducted a systematic review to assess the associations between BAC and CAD and its risk factors (hypertension, hypercholesterolemia, diabetes mellitus and smoking). METHODS AND FINDINGS:MEDLINE and EMBASE databases and references of relevant papers were searched up to 18 February 2020 for English language studies that evaluated the associations of BAC and CAD and its risk factors. A single reviewer extracted all data and assessed study quality with verification by another independent reviewer, if required. Across 31 studies (n = 35,583; 3 longitudinal and 28 cross-sectional studies) that examined the association of BAC and CAD, the OR was 2.61 (95% CI 2.12-3.21; I2 = 71%). Sub-analysis of studies that graded BAC severity using the 4- (4 studies) or 12-point scale systems (3 studies) revealed an association with CAD and moderate-severe BAC (OR 4.83 (95%CI 1.50-15.54) and OR 2.95 (95%CI 1.49-5.84), respectively) but not mild BAC (OR 2.04 (95%CI 0.82-5.05) and OR 1.08 (95%CI 0.42-2.75), respectively). BAC was associated with hypertension (42 studies; n = 32,646; OR 1.80; 95% CI 1.47-2.21; I2 = 85%) and diabetes mellitus (51 studies; n = 53,464; OR 2.17; 95% CI 1.82-2.59; I2 = 75%) but not with hypercholesterolemia (OR 1.31; 95%CI 0.97-1.77; I2 = 67%). Smoking was inversely associated with BAC (35 studies; n = 40,002; OR 0.54; 95% CI 0.42-0.70; I2 = 83%). Studies mostly included symptomatic women. Marked heterogeneity existed and publication bias may be present. CONCLUSIONS:BAC is associated with CAD, diabetes mellitus and hypertension and inversely associated with smoking. Whether BAC could screen for CAD cannot be determined from current published data due to the lack of larger prospective studies. A consensus approach to quantifying BAC may also facilitate further translation into clinical care. PROSPERO: CRD42020141644.
| S-EPMC7386618 | biostudies-literature
Project description:BackgroundCardiac surgery-associated acute kidney injury (CSA-AKI) is a serious postoperative complication of cardiac surgery, an episode of which impacts on patient morbidity and mortality. Pulse wave velocity (PWV; a non-invasive measurement tool to assess arterial stiffness) has been shown to predict kidney disease progression, and cardiovascular and all-cause mortality in patients with chronic kidney disease. We hypothesised that PWV would also predict acute kidney injury in subjects who have undergone non-valve repair elective coronary artery bypass graft (CABG) surgery .MethodsThis was a prospective, observational, exploratory study. PWV was determined with a Vicorder device, together with standard clinical and biochemical parameters. AKI staging was defined according to the Kidney Disease Improving Global Outcomes (KDIGO) Clinical Practice Guidelines.Results137 patients were included in the study. 85% were male, and mean age was 66.3 years (SD = 9.7 years). There were 40 episodes (29%) of CSA-AKI. Each 1 unit increase in PWV score was associated with a 1.5 fold greater odds of a CSA-AKI event (p = 0.006(odds ratio = 1.5; confidence interval:1.13-2.10). A 1 unit increase in estimated glomerular filtration rate resulted in an estimated 85% decrease in the odds of developing AKI, each year, men have an odds reduction of 15% of developing AKI compared with females and each 1 year increase in age lowered the odds of developing AKI by 87%.ConclusionsThis pilot exploratory study revealed that PWV, assessed prior to non-valve repair elective CABG surgery, independently predicts CSA-AKI events. PWV is a simple, non-invasive technique that could potentially be used to risk stratify for CSA- AKI following elective cardiac surgery.Trial registrationClinTrial.Gov NCT02364427 . Registered 18 February 2015.
| S-EPMC6407199 | biostudies-literature
Project description:ObjectiveArterial hemodynamics and vascular calcification are associated with increased risk for cardiovascular disease, but their inter-relations remain unclear. We sought to examine the associations of arterial stiffness, pressure pulsatility, and wave reflection with arterial calcification in individuals free of prevalent cardiovascular disease.Approach and resultsFramingham Heart Study Third Generation and Offspring Cohort participants free of cardiovascular disease underwent applanation tonometry to measure arterial stiffness, pressure pulsatility, and wave reflection, including carotid-femoral pulse wave velocity, central pulse pressure, forward wave amplitude, and augmentation index. Participants in each cohort (n=1905, 45±6 years and n=1015, 65±9 years, respectively) underwent multidetector computed tomography to assess the presence and quantity of thoracic aortic calcification, abdominal aortic calcification, and coronary artery calcification. In multivariable-adjusted models, both higher carotid-femoral pulse wave velocity and central pulse pressure were associated with greater thoracic aortic calcification and abdominal aortic calcification, whereas higher augmentation index was associated with abdominal aortic calcification. Among the tonometry measures, carotid-femoral pulse wave velocity was the strongest correlate of all calcification measures in multivariable-adjusted models (odds ratio per SD for thoracic aortic calcification, 2.69 [95% confidence interval, 2.17-3.35]; abdominal aortic calcification, 1.47 [95% confidence interval, 1.26-1.73]; and coronary artery calcification, 1.48 [95% confidence interval, 1.28-1.72]; all P<0.001, respectively). We observed stronger relations of carotid-femoral pulse wave velocity, central pulse pressure, and forward wave amplitude with nearly all continuous calcification measures in the younger Third Generation Cohort as compared with the Offspring Cohort.ConclusionsIn community-dwelling individuals without prevalent cardiovascular disease, abnormal central arterial hemodynamics were positively associated with vascular calcification and were observed at younger ages than previously recognized. The mechanisms of these associations may be bidirectional and deserve further study.
| S-EPMC4199901 | biostudies-literature
Project description:AimTo assess the prevalence of breast arterial calcification (BAC) in patients who also underwent routine surveillance mammography, and to determine the association with cardiovascular risk factors, coronary artery calcification, and coronary artery disease on coronary computed tomography angiography (CCTA).Materials and methodsFour hundred and five female participants were identified who had undergone CCTA and subsequent mammography in the SCOT-HEART randomised controlled trial of CCTA in patients with suspected stable angina. Mammograms were assessed visually for the presence and severity of BAC.ResultsBAC was identified in 93 (23%) patients. Patients with BAC were slightly older (63±7 versus 59±8 years, p<0.001), with a higher cardiovascular risk score (19±11 versus 16±10, p=0.022) and were more likely to be non-smokers (73% versus 49%, p<0.001). In patients with BAC, coronary artery calcification was present in 58 patients (62%; relative risk [RR] 1.26, 95% confidence intervals [CI]: 1.04, 1.53; p=0.02), non-obstructive coronary artery disease in 58 (62%; RR 1.27, 95% CI: 1.04 to 1.54, p=0.02), and obstructive coronary artery disease in 19 (20%; RR 1.62, 95% CI: 0.98, 2.66; p=0.058). Patients without BAC were very unlikely to have severe coronary artery calcification (negative predictive value 95%) but the diagnostic accuracy of BAC to identify coronary artery disease was poor (AUC 0.547).ConclusionAlthough BAC is associated with the presence and severity of coronary artery calcification, the diagnostic accuracy to identify patients with coronary artery disease or obstructive coronary artery disease is poor.
| S-EPMC6512949 | biostudies-literature