Cardiovascular Risk Predictors High Sensitivity C-Reactive Protein and Plasminogen Activator Inhibitor-1 in Women with Lean Phenotype of Polycystic Ovarian Syndrome: A Prospective Case-Control Study.

Objective Accumulating evidence suggests increased cardiovascular risk in women with polycystic ovarian syndrome (PCOS) due to a cluster of factors, such as obesity, lipid abnormalities, impaired glucose tolerance (IGT), and hypertension. Markers such as high-sensitivity C-reactive protein (hs-CRP) and plasminogen activator inhibitor-1 (PAI-1) can provide an adjunctive method for the assessment of cardiovascular risk and can indicate future coronary heart diseases in women with lean PCOS. Materials and Methods In this prospective case-control study, women clinically diagnosed with PCOS ( n = 25) with normal body mass index (BMI) and age and BMI-matched healthy controls ( n = 75) were enrolled. The quantitative data were expressed as mean ± standard deviation (SD). Unpaired Student's t -test was used to compare the values (PCOS vs. controls) and Pearson's correlation coefficient was used to elucidate the relationship between the variables. Results The mean level of fasting blood sugar, serum total cholesterol, low-density lipoprotein (LDL), thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), luteinizing hormone (LH), prolactin (PRL), hs-CRP, and PAI-1 were significantly increased in PCOS patients ( p < 0.000) compared with the control patients. Of the reported cases, 54.16% had hs-CRP levels greater than 3 mg/L. When the cases were further divided into normal ( n = 20) and IGT ( n = 5), hs-CRP values were significantly higher in IGT group as compared with normal glucose tolerance (NGT) group. On bivariate correlation analysis, hs-CRP had significant correlations with PAI-1 ( r = 0.41, p < 0.000), waist-to-hip ratio (WHR; r = 0.23, p = 0.02), fasting blood sugar (FBS; r = 0.26, p = 0.009), LDL ( r = 0.20, p = 0.03), TSH ( r = 0.42, p < 0.000), and LH-to-FSH ratio ( r = 0.24, p = 0.01). Conclusion Women with lean phenotype of PCOS suffer from many metabolic abnormalities such as abdominal obesity, dyslipidemia, hyperandrogenemia, and insulin resistance. The findings of the study suggest that environment of ongoing low-grade inflammation due to infiltration further exacerbates the metabolic derangements and cardiovascular risk. The investigations as hs-CRP and PAI-1 will help in early identification, diagnosis, and management of cardiovascular diseases associated with lean type of PCOS. These markers can prove to be beneficial in monitoring any unfavorable changes in cardiometabolic profile of such patients.

Association of neutrophil gelatinase associated lipocalin, ischemia modified albumin with uric acid in the etiopathogenesis of preeclampsia.

OBJECTIVES: Preeclampsia is a multisystem illness that manifests in the third trimester of pregnancy after 20 weeks of gestation and is marked by proteinuria and hypertension (PE). Changes in lifestyle, such as eating a high-calorie diet and delaying delivery, have raised the likelihood of developing PE. Eclampsia, abrupt renal failure, thromboembolic episodes leading to cardiac and brain problems, pulmonary embolism, and coagulopathy associated with HELLP syndrome are a few of the complications that might follow preeclampsia in pregnant moms. The objects of this study is to estimate and correlate the levels of NGAL (neutrophil gelatinase associated lipocalin), IMA (ischemia modified albumin) and Uric acid in prreclampsia. METHODS: 40 diagnosed cases of preeclampsia and 40 healthy age and gestational age matched healthy controls were included in the study. Blood samples were collected from them and serum NGAL, IMA and Uric acid levels were estimated. Estimation of NGAL (neutrophil gelatinase associated lipocalin), IMA (ischemia modified albumin) was done by commercially available ELISA kits standard spectrophotometry methods in autoanalyzer Mind ray BS300 using commercially available kits. RESULTS: The parameters of NGAL and IMA were significantly increased in patients with PE (p<0.001) when compared with the healthy control subjects. γ-glutamyl transferases and OPN were found in patients with ALD (p<0.001) when compared with the control subjects. OPN showed significant positive correlations with AST (r=0.76, p<0.001), ALT (r=0.64 p<0.001), ALP (r=0.68, p<0.001), and GGT (r=0.61, p<0.001). CONCLUSIONS: The current study focuses on the roles of NGAL and IMA, two sensitive markers of kidney injury that are particularly useful in identifying widespread endothelial dysfunction. As a result, the pattern of elevated NGAL and IMA levels can be useful for diagnosis.

Level of non-conventional lipid parameters and its comparative analysis with TSH in subclinical hypothyroidism.

OBJECTIVES: The objective of this study is to estimate lipid parameters in subclinical hypothyroidism and correlate it with TSH. METHODS: Forty newly diagnosed cases of subclinical hypothyroidism and Forty age and gender-matched healthy controls were recruited for the study. Blood samples were collected from them and serum lipid profile (i.e. HDL, LDL, TG, serum total cholesterol) of the subjects was estimated by standard photometric methods in a fully auto-analyzer (MINDRAY BS-300) using commercially available kits and VLDL cholesterol was calculated using the Friedewald's formula. While serum Ox-LDL, Lipoprotein A, Apolipoprotein A1 and Apo B were estimated by using commercial kit based on enzyme-linked immmunosorbent assay. RESULTS: The parameters such as Oxidized low-density lipoprotein (Ox-LDL), lipoprotein (a), apolipoprotein A1, apolipoprotein B and small dense lipoprotein (sd LDL) were significantly increased in subclinical hypothyroid cases when compared with the control subjects (p<0.0001). In present study results showed significant positive correlations of serum thyroid stimulating hormone (TSH) with Ox-LDL (r=0.85, p<0.01), sd LDL (r=0.71, p<0.01). CONCLUSIONS: The present study focuses on the role of Ox-LDL, sd-LDL Lipoprotein A, Apolipoprotein A1 and Apo B that are sensitive indicators of atherogenic dyslipidemia in subclinical hypothyroidism and can serve as a better & novel risk factor for CAD.

A Study on the Serum γ-Glutamyltranspeptidase and Plasma Osteopontin in Alcoholic Liver Disease.

Background Alcoholic liver disease (ALD) is a major source of alcohol-related morbidity and mortality. Heavy drinkers and alcoholics may progress from fatty liver to alcoholic hepatitis to cirrhosis. The enzyme γ-glutamyltranspeptidase (GGT) is a membrane-bound glycoprotein which catalyzes the transfer of the γ-glutamyl group from γ-glutamyl peptides to other peptides, amino acids, and water. Serum GGT activity mainly attributed to hepatobiliary system and thus is an important marker of ALD. Hence the present study is conducted to estimate and correlate the levels of GGT and osteopontin (OPN) in ALD. Aims and Objectives The objective of this study is to estimate and correlate the levels of GGT and OPN in ALD. Materials and Methods Sixty clinically diagnosed cases of ALD and sixty age- and gender-matched healthy controls were recruited for the study. Blood samples were collected from them and serum aspartate aminotransferase, serum alanine transaminases (ALTs), serum ALP levels, and plasma OPN levels were measured. Estimation of serum aspartate transaminases (AST), ALTs, and alkaline phosphatase (ALP) was assayed by standard photometric methods in autoanalyzer ERBA-XL (EM-200) using commercially available kits. OPN was estimated by using commercial kit based on enzyme-linked immunosorbent assay. Results The parameters of the liver function tests such as AST, ALT, and ALP were significantly increased in patients with ALD ( p < 0.001) when compared with the healthy control subjects. In the present study, significantly increased levels of γ-glutamyl transferases and OPN were found in patients with ALD ( p < 0.001) when compared with the control subjects. OPN showed significant positive correlations with AST ( r = 0.76, p < 0.001), ALT ( r = 0.64, p < 0.001), ALP ( r = 0.68, p < 0.001), and GGT ( r = 0.61, p < 0.001). Conclusion The present study focuses on the role of GGT and OPN that are sensitive indicators of liver cell injury and are most helpful in recognizing hepatocellular diseases such as ALD, hepatitis, and liver cirrhosis. Hence, the pattern of the GGT and OPN levels elevation can be helpful diagnostically.

A study on lipoprotein-a and PAI-1 in women with polycystic ovary syndrome.

OBJECTIVES: PCOS is the most common endocrinological disorder amongst women of reproductive age. The consequences of PCOS extend beyond the reproductive axis and may lead to the development of metabolic syndrome leading to a high risk for hypertension and cardiovascular disease. Therefore, a more comprehensive evaluation of biochemical markers that reflect the cardiovascular risk is required for further understanding of pathophysiologic mechanisms, diagnosis and management. METHODS: In this case-control study, women diagnosed with PCOS (n=100) in the age group (18-35 years) years were taken as cases and age matched healthy controls (n=100) were enrolled. Estimations of fasting plasma Glucose, serum total cholesterol (TC), triglycerides (TG) and High-density lipoprotein (HDL) concentrations were assayed while Low-density lipoprotein (LDL) was calculated by using Fredrickson Friedwald's formula. Serum Lipoprotein-a (Lp-a) was estimated using ELISA (Enzyme Linked Immunosorbent Assay). The quantitative data were expressed as Mean ± Standard Deviation (SD). Unpaired Student's t-test was used to compare the values (PCOS vs Controls) and Pearson's correlation coefficient was used to elucidate the relationship between the variables. RESULTS: FBS and all lipid parameters were significantly increased in PCOS patients compared to control subjects. On the other hand, HDL-C was significantly decreased as compared to the control subjects. The hormones TSH, LH, FSH, PRL and LH/FSH ratio were significantly increased in PCOS patients compared to control subjects. Lipoprotein-a and PAI-1 was significantly increased in PCOS patients compared to the control subjects. Upon bivariate correlation analysis, Lp(a) had significant correlations with PAI-1 (r=0.35, p=0.000), WHR (r=0.25, p=0.000), LDL (r=0.52, p=0.000) and TSH (r=0.24, p=0.000). While the correlations with FBS (r=-0.008, p=0.91) and LH/FSH ratio (r=-0.004, p=0.95) were statistically insignificant. CONCLUSIONS: The evaluation of serum biomarkers such as Lp-a, PAI-1 and lipid profile routinely in PCOS patients may have diagnostic role in the early detection of metabolic abnormalities and endocrine derangements and timely management of comorbid Diabetes and Cardiovascular disease in PCOS females.

Association of inflammatory biomarker abnormalities with mortality in COVID-19: a meta-analysis.

Background: COVID-19 outbreak has engulfed different parts of the world, affecting more than 163 million people and causing more than 3 million deaths worldwide due to human transmission. Thus, it has become critical to identify the risk factors and laboratory parameters to identify patients who have high chances of worsening clinical symptoms or poor clinical outcomes. Therefore, the study aims to identify inflammatory markers that can help identify patients at increased risk for progression to critical illness, thus decreasing the risk of any mortality. Our study focussed on the predictive utility of C-reactive protein, Interleukin-6, D-dimer and Procalcitonin in assisting the management of COVID-19 patients with adverse clinical effects. Through literature search in electronic databases, we included the retrospective studies that evaluated the biomarkers among confirmed COVID-19 patients before initiation of treatment and who had a definite outcome (dead or discharged). Biomarkers were expressed in standardized difference in mean value, calculated based on study sizes and mean values between survivors and non-survivors considered the effect size. We carried out a meta-regression analysis to identify the causes of the heterogeneity between the studies. Results: Number of studies eligible for C-reactive protein, D-dimer and Interleukin-6 markers were eight, seven and four, respectively. Using random effect model revealed that the overall effect size with 95% confidence interval (CI) for C-reactive protein, D-dimer and Interleukin-6 were 1.45 (0.79-2.12) milligrams/litre, 1.12 (0.64-1.59) micrograms/millilitre Fibrinogen Equivalent Units and 1.34 (0.43-2.24) picograms/millilitre respectively was statistically significant (P < 0.05) inferring that the mean scores of these marker were significantly higher among the non-survivors compared to the survivors. Two studies were eligible for Procalcitonin marker and there was no heterogeniety (I 2-statistics = 0) between these studies. Therefore, fixed-effect model revealed that the overall effect size (95% CI) for Procalcitonin was 0.75 (0.30-1.21) Nanograms/millilitre was also high among non-survivors. Conclusions: The study found that serum levels of C-reactive protein, Interleukin-6 and D-dimer showed significant elevation in non-survivors compared to survivors. Raised inflammatory markers aid in the risk stratification of COVID-19 patients and their proper management.

A study on serum homocysteine and oxidized LDL as markers of cardiovascular risk in patients with overt hypothyroidism.

OBJECTIVES: Hypothyroidism is the most common endocrine disorder worldwide. Hypothyroisim increases cardiovascular risk, thus the study focuses on the assessment of cardiovascular risk factors such as serum Homocysteine, serum Oxidized LDL and Lipid profile and their correlation with TSH levels. Timely evaluation of these risk predictors would help in reducing cardiovascular disease morbidity and mortality in hypothyroidism. METHODS: This was a hospital based cross-sectional study consisting of Forty newly diagnosed patients with overt hypothyroidism in the age group of 20-60 years attending Medicine OPD were included as cases and Fifty healthy age and gender matched healthy controls participated as controls in the study. A written and informed consent to all the participants of both the groups was taken after explaining the purpose and details of the study. The Thyroid profile was assessed by CLIA-based MAGLUMI- 1000 analyzer and Serum total cholesterol, triglycerides and high-density lipoproteins were analyzed in Fully automated clinical chemistry analyzer EM-200 by using commercially available kits. LDL was calculated indirectly using Friedwalds equation. Commercially available ELISA-based kits were used for analysis of serum Homocysteine and serum oxidized-LDL. RESULTS: Elevated levels of serum homocysteine (p<0.0001), Oxidized LDL (p<0.0001) were found in newly diagnosed overt hypothyroid patients as compared to controls whereas significant elevated levelsof TC, TG, LDL, and VLDL (p<0.0001) and decrease in HDLcholesterol (p<0.0001) were reported in newly diagnosed newly diagnosed overt hypothyroid patients. CONCLUSIONS: We concluded that the association of hyperhomocysteinemia and lipid abnormalities occurring in hypothyroidism may represent a dynamic atherogenic state and thyroid hormone failed to completely normalize Hcy levels. Thus, elevated plasma homocysteine levels may be an independent risk factor for the accelerated atherosclerosis seen in hypothyroidism. In addition, we found that the circulating ox-LDL levels were elevated in untreated hypothyroidism and they tend to be higher in thyroid dysfunction.

Diagnostic measures comparison for ovarian malignancy risk in Epithelial ovarian cancer patients: a meta-analysis.

Epithelial ovarian cancer has become the most frequent cause of deaths among gynecologic malignancies. Our study elucidates the diagnostic performance of Risk of Ovarian Malignancy Algorithm (ROMA), Human epididymis secretory protein 4 (HE4) and cancer antigen (CA125). To compare the diagnostic accuracy of ROMA, HE-4 and CA125 in the early diagnosis and screening of Epithelial Ovarian Cancer. Literature search in electronic databases such as Medicine: MEDLINE (through PUBMED interface), EMBASE, Google Scholar, Science Direct and Cochrane library from January 2011 to August 2020. Studies that evaluated the diagnostic measures of ROMA, HE4 and CA125 by using Chemilumincence immunoassay or electrochemiluminescence immunoassay (CLIA or ECLIA) as index tests. Using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS-2). We included 32 studies in our meta-analysis. We calculated AUC by SROC, pooled estimated like sensitivity, specificity, likelihood ratio, diagnostic odds ratio (DOR), Tau square, Cochran Q through random effect analysis and meta-regression. Data was retrieved from 32 studies. The number of studies included for HE4, CA125 and ROMA tests was 25, 26 and 22 respectively. The patients with EOC were taken as cases, and women with benign ovarian mass were taken as control, which was 2233/5682, 2315/5875 and 2281/5068 respectively for the markers or algorithm. The pooled estimates of the markers or algorithm were sensitivity: ROMA (postmenopausal) (0.88, 95% CI 0.86-0.89) > ROMA (premenopausal) 0.80, 95% CI 0.78-0.83 > CA-125(0.84, 95% CI 0.82-0.85) > HE4 (0.73, 95% CI 0.71-0.75) specificity: HE4 (0.90, 95% CI 0.89-0.91) > ROMA (postmenopausal) (0.83, 95% CI 0.81-0.84) > ROMA (premenopausal) (0.80, 95% CI 0.79-0.82) > CA125 (0.73, 95%CI 0.72-0.74), Diagnostic odd's ratio ROMA (postmenopausal) 44.04, 95% CI 31.27-62.03, ROMA (premenopausal)-18.93, 95% CI 13.04-27.48, CA-125-13.44, 95% CI 9.97-18.13, HE4-41.03, 95% CI 27.96-60.21 AUC(SE): ROMA (postmenopausal) 0.94(0.01), ROMA (premenopausal)-0.88(0.01), HE4 0.91(0.01), CA125-0.86(0.02) through bivariate random effects model considering the heterogeneity. Our study found ROMA as the best marker to differentiate EOC from benign ovarian masses with greater diagnostic accuracy as compared to HE4 and CA125 in postmenopausal women. In premenopausal women, HE4 is a promising predictor of Epithelial ovarian cancer; however, its utilisation requires further exploration. Our study elucidates the diagnostic performance of ROMA, HE4 and CA125 in EOC. ROMA is a promising diagnostic marker of Epithelial ovarian cancers in postmenopausal women, while HE4 is the best diagnostic predictor of EOC in the premenopausal group. Our study had only EOC patients as cases and those with benign ovarian masses as controls. Further, we considered the studies estimated using the markers by the same index test: CLIA or ECLIA. The good number of studies with strict inclusion criteria reduced bias because of the pooling of studies with different analytical methods, especially for HE4. We did not consider the studies published in foreign languages. Since a few studies were available for HE4 and CA125 in the premenopausal and postmenopausal group separately, data were inadequate for sub-group analysis. Further, we did not assess these markers' diagnostic efficiency stratified by the stage and type of tumour due to insufficient studies.

Body Composition, Natriuretic Peptides, and Adverse Outcomes in Heart Failure With Preserved and Reduced Ejection Fraction.

OBJECTIVES: The purpose of this study was to determine the relationship between body composition, N-terminal B-type natriuretic peptide (NT-proBNP) levels, and heart failure (HF) phenotypes and outcomes. BACKGROUND: Abnormalities in body composition can influence metabolic dysfunction and HF severity; however, data assessing fat distribution and skeletal muscle (SM) size in HF with reduced (HFrEF) and preserved EF (HFpEF) are limited. Further, whether NPs relate more closely to axial muscle mass than measures of adiposity is not well studied. METHODS: We studied 572 adults without HF (n = 367), with HFrEF (n = 113), or with HFpEF (n = 92). Cardiac magnetic resonance was used to assess subcutaneous and visceral abdominal fat, paracardial fat, and axial SM size. We measured NT-proBNP in 334 participants. We used Cox regression to analyze the relationship between body composition and mortality. RESULTS: Compared with controls, pericardial and subcutaneous fat thickness were significantly increased in HFpEF, whereas patients with HFrEF had reduced axial SM size after adjusting for age, sex, race, and body height (p < 0.05 for comparisons). Lower axial SM size, but not fat, was significantly predictive of death in unadjusted (standardized hazard ratio: 0.63; p < 0.0001) and multivariable-adjusted analyses (standardized hazard ratio = 0.72; p = 0.0007). NT-proBNP levels more closely related to lower axial SM rather than fat distribution or body mass index (BMI) in network analysis, and when simultaneously assessed, only SM (p = 0.0002) but not BMI (p = 0.18) was associated with NT-proBNP. However, both NT-proBNP and axial SM mass were independently predictive of death (p < 0.05). CONCLUSIONS: HFpEF and HFrEF have distinct abnormalities in body composition. Reduced axial SM, but not fat, independently predicts mortality. Greater axial SM more closely associates with lower NT-proBNP rather than adiposity. Lower NT-proBNP levels in HFpEF compared with HFrEF relate more closely to muscle mass rather than obesity.

Axial Muscle Size as a Strong Predictor of Death in Subjects With and Without Heart Failure.

Background The impact of skeletal muscle size, quantified using simple noninvasive images routinely obtained during cardiac magnetic resonance imaging studies on mortality in the heart failure ( HF ) population is currently unknown. Methods and Results We prospectively enrolled 567 subjects without HF (n=364), with HF with reduced ejection fraction (n=111), or with HF with preserved ejection fraction (n=92), who underwent a cardiac magnetic resonance imaging. Skeletal muscle cross-sectional area was assessed with manual tracing of major thoracic muscle groups on axial chest magnetic resonance images. Factor analysis was used to identify a latent factor underlying the shared variability in thoracic muscle cross-sectional area. Cox regression was used to assess the relationship between these measurements and all-cause mortality (median follow up, 36.4 months). A higher overall thoracic muscle area factor assessed with principal component analysis was independently associated with lower mortality (standardized hazard ratio, 0.51; P<0.0001). The thoracic muscle area factor was predictive of death in subjects with HF with preserved ejection fraction, HF with reduced ejection fraction, and those without HF . Among all muscle groups, the pectoralis major cross-sectional area was the most representative of overall muscle area and was also the most robust predictor of death. A higher pectoralis major cross-sectional area predicted a lower mortality (standardized hazard ratio, 0.49; P<0.0001), which persisted after adjustment for various confounders (standardized hazard ratio, 0.55; P=0.0017). Conclusions Axial muscle size, and in particular smaller size of the pectoralis major, is independently associated with higher risk of mortality in patients with and without HF . Further work should clarify the role of muscle wasting as a therapeutic target in patients with HF .

Left Atrial Phasic Function by Cardiac Magnetic Resonance Feature Tracking Is a Strong Predictor of Incident Cardiovascular Events.

BACKGROUND: The prognostic importance of left atrial (LA) dysfunction is increasingly recognized. Magnetic resonance imaging can provide excellent visualization of the LA wall. We aimed to study the association of LA dysfunction measured using feature-tracking magnetic resonance imaging with incident adverse cardiovascular events among subjects with or without heart failure (HF) at baseline. METHODS AND RESULTS: We prospectively studied 640 adults without HF (n=419), HF with preserved ejection fraction (n=101), or HF with reduced ejection fraction (n=120). We measured phasic LA function by volumetric and feature-tracking methods to derive longitudinal strain. The composite outcome of incident HF hospitalization or death was adjudicated during a median follow-up of 37.1 months. Measures of LA phasic function were more prominently impaired in subjects with HF with reduced ejection fraction than among subjects with HF with preserved ejection fraction. In unadjusted Cox proportional hazards models, all measures of phasic LA function and volumes (maximum, minimum, and diastatic) were associated with the composite outcome. However, in analyses that adjusted for clinical risk factors, HF status, maximum LA volume, left ventricular mass, and left ventricular ejection fraction, measures of conduit and reservoir LA function, but not booster-pump function, were associated with the composite outcome. The strongest associations were observed for conduit longitudinal strain (standardized hazard ratio, 0.66; 95% CI, 0.49-0.88; P=0.004), conduit strain rate (standardized hazard ratio, 1.59; 95% CI, 1.16-2.16; P=0.0035), and reservoir strain (standardized hazard ratio, 0.68; 95% CI, 0.52-0.89; P=0.0055). CONCLUSIONS: Phasic LA function measured using magnetic resonance imaging feature tracking is independently predictive of the risk of incident HF admission or death, even after adjusting for LA volume and left ventricular remodeling.

Circulating Dephospho-Uncarboxylated Matrix Gla-Protein Is Associated With Kidney Dysfunction and Arterial Stiffness.

BACKGROUND: Large artery stiffening is increased in advanced chronic kidney disease (CKD) but likely develops progressively in earlier stages of CKD. Active matrix Gla-protein (MGP) is a potent vitamin K-dependent inhibitor of vascular calcification. A recent animal model demonstrated intrinsic abnormalities in vitamin K metabolism even in early CKD, but whether early human CKD is associated with vascular vitamin K deficiency is unknown. METHODS: We enrolled 137 adults without HF with varying degrees of renal function: normal estimated glomerular filtration rate (eGFR; >90 ml/min; n = 59), mildly reduced eGFR (stage 2 CKD: eGFR = 60-89 ml/min; n = 53) or at least moderately reduced eGFR (stage 3-5 CKD; eGFR < 60 ml/min; n = 25). Carotid-femoral pulse wave velocity (CF-PWV) was measured with carotid and femoral tonometry. Dephospho-uncarboxylated matrix gla-protein (dp-ucMGP) was measured with enzyme-linked immunosorbent assay (ELISA) (VitaK; Maastricht University; The Netherlands). RESULT: Dp-ucMGP levels were progressively increased with decreasing renal function (eGFR ≥ 90: 247 pmol/l; eGFR 60-89: 488 pmol/l; eGFR < 60: 953 pmol/l; P < 0.0001). These differences persisted after adjustment for multiple potential confounders (eGFR ≥ 90: 314 pmol/l; eGFR 60-89: 414 pmol/l; eGFR < 60: 770 pmol/l; P < 0.0001). In a multivariable model adjusted for various confounders, dp-ucMGP was a significant independent predictor of CF-PWV (ß = 0.21; P = 0.019). In formal mediation analyses, dp-ucMGP mediated a significant relationship between eGFR and higher CF-PWV (ß = -0.16; P = 0.005), whereas no significant dp-ucMGP-independent relationship was present (ß = -0.02; P = 0.80). CONCLUSIONS: CKD is associated with increased (inactive) dp-ucMGP, a vitamin K-dependent inhibitor of vascular calcification, which correlates with large artery stiffness. Further studies are needed to assess whether vitamin K2 supplementation represents a suitable therapeutic strategy to prevent or reduce arterial stiffening in CKD.