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Circulating 25-hydroxyvitamin D (25(OH)D) is the generally accepted indicator of vitamin D status. Since hydroxylation of 25(OH)D to 24-25-dihydroxyvitamin D (24,25(OH)2D) is the first step of its catabolism, it has been suggested that a low 24,25(OH)D level and a low vitamin D metabolite ratio (VMR), i.e., 24,25(OH)2D divided by 25(OH)D, may indicate high vitamin D requirements and provide additional diagnostic information beyond serum 25(OH)D. We, therefore, evaluated whether the classification of "functional vitamin D deficiency", i.e., 25(OH)D below 50 nmol/L, 24,25(OH)2D below 3 nmol/L and a VMR of less than 4%, identifies individuals who benefit from vitamin D supplementation. In participants of the Styrian Vitamin D Hypertension trial, a randomized controlled trial (RCT) in 200 hypertensive patients with serum 25(OH)D below 75 nmol/L, who received either 2.800 international units of vitamin D per day or placebo over 8 weeks, 51 participants had functional vitamin D deficiency. In these individuals, there was no treatment effect of vitamin D supplementation on various parameters of bone metabolism and cardiovascular risk except for a significant effect on parathyroid hormone (PTH) and expected changes in vitamin D metabolites. In conclusion, a low vitamin D metabolite profile did not identify individuals who significantly benefit from vitamin D supplementation with regard to bone markers and cardiovascular risk factors. The clinical significance of functional vitamin D deficiency requires further evaluation in large vitamin D RCTs.

Accumulating evidence suggests an association of the tryptophan−kynurenine (TRP-KYN) pathway with atherosclerosis and cardiovascular risk factors. In this cross-sectional analysis we investigated whether TRP-KYN pathway parameters are associated with 24 h blood pressure (BP) and other risk factors in patients with arterial hypertension from a tertiary care centre. In 490 participants, we found no significant and independent association of 24 h systolic and diastolic BP with parameters of the TRP-KYN pathway. However, linear regression analyses of HDL as dependent and TRP, KYN and quinolinic acid (QUIN) as explanatory variables adjusted for BMI and sex showed significant associations. These were found for KYN, BMI and sex (unstandardised beta coefficient −0.182, standard error 0.052, p < 0.001; −0.313 (0.078), p < 0.001; −0.180 (0.024), p < 0.001, respectively) as well as for QUIN, BMI and sex (−0.157 (0.038), p < 0.001; −0.321 (0.079), p < 0.001; −0.193 (0.024), p < 0.001, respectively). Smokers had significantly lower levels of KYN (2.36 µmol/L, IQR 2.01−2.98, versus 2.71 µmol/L, IQR 2.31−3.27, p < 0.001), QUIN (384 nmol/L, IQR 303−448, versus 451 nmol/L, IQR 369−575, p < 0.001) and KYN/TRP ratio (38.2, IQR 33.7−43.2, versus 43.1, IQR 37.5−50.9, p < 0.001) compared to non-smokers. We demonstrated that TRP/KYN pathway metabolites are associated with some cardiovascular risk factors, warranting further studies to elucidate the diagnostic and therapeutic potential of the TRP-KYN pathway for cardiovascular diseases.

Introduction: Systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) are risk factors for cardiovascular mortality (CVM). Pulse pressure (PP) is an easily available parameter of vascular stiffness, but its impact on CVM in chronic dialysis patients with diabetes is unclear., Methods: Therefore, we have examined the predictive value of baseline, predialytic PP, SBP, DBP, and MAP in the German Diabetes and Dialysis (4D) study, a prospective, randomized, double-blind trial enrolling 1,255 patients with type 2 diabetes on hemodialysis in 178 German dialysis centers., Results: Mean age was 66.3 years, mean blood pressure 146/76 mm Hg, mean time suffering from diabetes 18.1 years, and mean time on maintenance dialysis 8.3 months. Considered as continuous variables, PP, MAP, SBP, and DBP could not provide a significant mortality prediction for either cardiovascular or all-cause mortality. After dividing the cohort into corresponding tertiles, we also did not detect any significant mortality prediction for PP, SBP, DBP, or MAP, both for all-cause mortality and CVM after adjusting for age and sex. Nevertheless, when comparing the HR plots of the corresponding blood pressure parameters, a pronounced U-curve was seen for PP for both all-cause mortality and CVM, with the trough range being 70-80 mm Hg., Discussion: In patients with end-stage renal disease and long-lasting diabetes mellitus predialytic blood pressure parameters at study entry are not predictive for mortality, presumably because there is a very high rate of competing mortality risk factors, resulting in overall very high rates of all-cause and CVM that may no longer be significantly modulated by blood pressure control., (© 2023 The Author(s). Published by S. Karger AG, Basel.)

Although neurohormones and Renin-Angiotensin-Aldosterone-System (RAAS) components are important predictors of cardiovascular mortality (CVM), their importance for predicting outcomes in patients with/without RAAS-blockers and different degrees of arterial stiffness is less understood. We therefore analyzed long-term data from the Ludwigshafen Risk and Cardiovascular Health (LURIC) study in 3316 patients subdivided according to pulse pressure (PP) and RAAS-blocker use. Patients on RAAS-inhibition had higher renin and noradrenaline, lower aldosterone and aldosterone/renin quotient (ARQ). Renin and noradrenaline significantly predicted CVM in patients without RAAS-blocker (HR = 1.17, 1.15) and in patients receiving angiotensin-converting-enzyme (ACE) inhibitors (HR = 1.17, 1.29), whereas aldosterone predicted CVM only in patients receiving ACE-inhibitors (HR = 1.13). CVM was predicted independently from PP by renin, noradrenaline and angiotensin II. Independently from RAAS inhibition renin decreased and ARQs increased with rising PP. Furthermore, noradrenaline increased with PP, but only without ACE-inhibition. The HR for CVM in the ACE-inhibitor group were 1.29, 1.28, 1.29 for renin in the first, second and third PP quartiles and 1.22, and 1.19 for aldosterone in the second and fourth quartile. Furthermore, we showed that noradrenaline predicts CVM in all PP quartiles in patients with ACE-inhibition. In the RAAS-blocker-free group, the HR for renin for CVM were 1.36 and 1.18 in the third and fourth PP quartiles, but neither aldosterone nor noradrenaline were predictive for CVM within the PP quartiles. Renin and noradrenaline are strong predictors of CVM regardless of RAAS blockade, whereas aldosterone is predictive only in the ACE-inhibitor group. Catecholamines but not renin are associated with rising PP., (© 2022 The Authors. The Journal of Clinical Hypertension published by Wiley Periodicals LLC.)

Low serum concentrations of the amino acid homoarginine (HA) are associated with increased cardiovascular mortality by incompletely understood mechanisms. This study sought to assess the influence of HA on cardiac remodeling in rats undergoing either transaortic banding or inhibition of nitric oxide synthesis by Nω-Nitro-L-arginine methyl ester hydrochloride (L-NAME). Male Wistar rats (n = 136) underwent sham operation (SH) or aortic banding (AB). Both groups were equally divided into 14 subgroups, receiving different doses of HA alone or in combination with lisinopril, spironolactone, or L-NAME for 4 weeks. HA treatment in AB animals resulted in a dose-dependent improvement of cardiac function up to a concentration of 800 mg·kg -1 ·day -1 . Combining 800 mg·kg -1 ·day -1 HA with spironolactone or lisinopril yielded additional effects, showing a positive correlation with LV ejection fraction (+33%, p = 0.0002) and fractional shortening (+41%, p = 0.0014). An inverse association was observed with collagen area fraction (-41%, p < 0.0001), myocyte cross-sectional area (-22%, p < 0.0001) and the molecular markers atrial natriuretic factor (-74%, p = 0.0091), brain natriuretic peptide (-42%, p = 0.0298), beta-myosin heavy chain (-46%, p = 0.0411), and collagen type V alpha 1 chain (-73%, p = 0.0257) compared to placebo-treated AB animals. Co-administration of HA and L-NAME was found to attenuate cardiac remodeling and prevent NO-deficient hypertension following AB. HA treatment has led to a dose-dependent improvement of myocardial function and marked histological and molecular changes in cardiac remodeling following AB. Combining HA with standard heart failure medication resulted in additional beneficial effects boosting its direct impact on heart failure pathophysiology., (© 2022 The Authors. Fundamental & Clinical Pharmacology published by John Wiley & Sons Ltd on behalf of Société Française de Pharmacologie et de Thérapeutique.)

Uromodulin (UMOD) is a major risk gene for monogenic and complex forms of kidney disease. The encoded kidney-specific protein uromodulin is highly abundant in urine and related to chronic kidney disease, hypertension, and pathogen defense. To gain insights into potential systemic roles, we performed genome-wide screens of circulating uromodulin using complementary antibody-based and aptamer-based assays. We detected 3 and 10 distinct significant loci, respectively. Integration of antibody-based results at the UMOD locus with functional genomics data (RNA-Seq, ATAC-Seq, Hi-C) of primary human kidney tissue highlighted an upstream variant with differential accessibility and transcription in uromodulin-synthesizing kidney cells as underlying the observed cis effect. Shared association patterns with complex traits, including chronic kidney disease and blood pressure, placed the PRKAG2 locus in the same pathway as UMOD. Experimental validation of the third antibody-based locus, B4GALNT2, showed that the p.Cys466Arg variant of the encoded N-acetylgalactosaminyltransferase had a loss-of-function effect leading to higher serum uromodulin levels. Aptamer-based results pointed to enzymes writing glycan marks present on uromodulin and to their receptors in the circulation, suggesting that this assay permits investigating uromodulin's complex glycosylation rather than its quantitative levels. Overall, our study provides insights into circulating uromodulin and its emerging functions.

Accumulating evidence suggests that potential cardiovascular benefits of vitamin D supplementation may be restricted to individuals with very low 25-hydroxyvitamin D (25(OH)D) concentrations; the effect of vitamin D on blood pressure (BP) remains unclear. We addressed this issue in a post hoc analysis of the double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011−2014) with 200 hypertensive patients with 25(OH)D levels <30 ng/mL. We evaluated whether 2800 IU of vitamin D3/day or placebo (1:1) for 8 weeks affects 24-hour systolic ambulatory BP in patients with 25(OH)D concentrations <20 ng/mL, <16 ng/mL, and <12 ng/mL and whether achieved 25(OH)D concentrations were associated with BP measures. Taking into account correction for multiple testing, p values < 0.0026 were considered significant. No significant treatment effects on 24-hour BP were observed when different baseline 25(OH)D thresholds were used (all p-values > 0.30). However, there was a marginally significant trend towards an inverse association between the achieved 25(OH)D level with 24-hour systolic BP (−0.196 per ng/mL 25(OH)D, 95% CI (−0.325 to −0.067); p = 0.003). In conclusion, we could not document the antihypertensive effects of vitamin D in vitamin D-deficient individuals, but the association between achieved 25(OH)D concentrations and BP warrants further investigations on cardiovascular benefits of vitamin D in severe vitamin D deficiency.

Background and Aims: Animal and cell models indicated that vitamin D modulates inflammatory activity, which is considered relevant in the pathogenesis of arterial hypertension and cardiovascular diseases. We therefore aimed to investigate the effect of vitamin D supplementation on systemic markers of inflammation in a cohort of hypertensive patients., Methods and Results: The Styrian Vitamin D Hypertension Trial is a single-centre, double-blind, placebo-controlled study conducted from 2011 to 2014 in Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxy-vitamin-D (25(OH)D) concentration below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D 3 per day or placebo for 8 weeks. The present investigation is a post-hoc analysis using analysis of co-variance (ANCOVA). Outcome measures were biomarkers of inflammation including CRP, leukocytes including subtypes and leukocyte-to-lymphocyte ratio, leucine and kynurenic acid. A total of 187 participants (mean age 60.1 ± 11.3years; 47% women; mean baseline 25(OH)D 21.1 ± 5.6 ng/mL) completed the trial. ANCOVA revealed a mean treatment effect for none of the respective outcomes and no significant results were detected in various subgroup analyses., Conclusion: Vitamin D 3 supplementation in hypertensive patients with insufficient 25(OH)D concentrations has no significant effect on lowering markers of systemic inflammation. Further studies investigating the effect of vitamin D on other inflammatory pathways and in populations with severe vitamin D deficiency and a significant inflammatory burden are required., Registration: ClinicalTrials.gov Identifier: NCT02136771; EudraCT No. 2009-018,125-70. Start Date: 2011-04-06., Competing Interests: Declaration of competing interest The authors have nothing to disclose., (Copyright © 2021. Published by Elsevier B.V.)

Systolic (SBP) and diastolic blood pressure (DBP) and mean arterial pressure (MAP) are risk factors for cardiovascular mortality (CVM). Pulse pressure (PP) is considered as an easily available marker of vascular stiffness and the double product (DP) as a marker of cardiac workload. Therefore, we have examined the predictive value of PP and DP in the Ludwigshafen Risk and Cardiovascular Health study, a monocentric cohort study of 3316 patients referred to coronary angiography. An increase of SBP or PP by 1mmHg increased the risk of CVM with hazard ratios of 1.009 (95% CI, 1.005-1.012) and 1.016 (1.012-1.020), respectively. Increasing DP by 100 mm Hg/min was associated with a 1.010 (1.007-1.013) higher risk of CVM. In patient subgroups with coronary artery disease (CAD) and heart failure (HF), PP and DP predicted CVM better than SBP or MAP. In a multivariate analysis adjusted for sex, BMI, diabetes, eGFR, hazard ratios for CVM for z-standardized PP, DP, SBP, and HR were 1.20, 1.16, 1.12, and 1.14. After adding age to the multivariate analysis, only DP and HR remained significant. We provide evidence that PP and DP are powerful predictors of CVM and all-cause mortality in a CV medium- to high-risk population, especially in patients with CAD and HF. While DP proved to be an independent predictor of cardiovascular and all-cause mortality also in multivariate analysis, PP was no independent predictor in our cohort with widespread antihypertensive treatment (>85%). PP is associated with age, presence of diabetes, obesity, and impaired renal function., (© 2020 Wiley Periodicals LLC.)

Epidemiology studies suggested that low birthweight was associated with a higher risk of hypertension in later life. However, little is known about the causality of such associations. In our study, we evaluated the causal association of low birthweight with adulthood hypertension following a standard analytic protocol using the study-level data of 183,433 participants from 60 studies (CHARGE-BIG consortium), as well as that with blood pressure using publicly available summary-level genome-wide association data from EGG consortium of 153,781 participants, ICBP consortium and UK Biobank cohort together of 757,601 participants. We used seven SNPs as the instrumental variable in the study-level analysis and 47 SNPs in the summary-level analysis. In the study-level analyses, decreased birthweight was associated with a higher risk of hypertension in adults (the odds ratio per 1 standard deviation (SD) lower birthweight, 1.22; 95% CI 1.16 to 1.28), while no association was found between genetically instrumented birthweight and hypertension risk (instrumental odds ratio for causal effect per 1 SD lower birthweight, 0.97; 95% CI 0.68 to 1.41). Such results were consistent with that from the summary-level analyses, where the genetically determined low birthweight was not associated with blood pressure measurements either. One SD lower genetically determined birthweight was not associated with systolic blood pressure (β = - 0.76, 95% CI - 2.45 to 1.08 mmHg), 0.06 mmHg lower diastolic blood pressure (β = - 0.06, 95% CI - 0.93 to 0.87 mmHg), or pulse pressure (β = - 0.65, 95% CI - 1.38 to 0.69 mmHg, all p > 0.05). Our findings suggest that the inverse association of birthweight with hypertension risk from observational studies was not supported by large Mendelian randomization analyses.

Background: Marinobufagenin (MBG) is an endogenous cardiotonic steroid (CTS) that inhibits the Na+/K+-ATPase. Human MBG is significantly increased in end-stage renal disease and immunization against MBG attenuates cardiovascular fibrosis in a rat model of uremic cardiomyopathy. Mineralocorticoid antagonists (MRA) block MBG binding sites and decrease proteinuria in chronic kidney disease (CKD) patients. We therefore aimed to investigate the association of MBG and albuminuria, as a marker of renal damage, as well as MBG and decline of glomerular filtration rate (GFR)., Methods: The Graz endocrine causes of hypertension (GECOH) study is a single center study of adults routinely referred for screening of endocrine hypertension. Plasma MBG was measured by an enzyme-linked immunoassay, and in a post-hoc analysis, follow-up creatinine levels were obtained. Patients with proteinuria >3.5g/day at baseline were excluded from further evaluation., Results: We measured MBG concentrations in 40 hypertensive subjects and excluded one patient due to pre-existing proteinuria. Plasma MBG was significantly correlated with albuminuria (Spearman ρ = .357; p = .028) and proteinuria (ρ = .336; p = .039). In linear regression analysis, the association remained significant after adjustment for age, sex, and BMI (β = .306; p = .036), and for mean systolic blood pressure (β = .352; p = .034). In follow-up analyses (N = 30), MBG was significantly associated with decline in GFR after adjustment for time-to-follow-up (β = -.374; p = .042)., Conclusion: The findings suggest that MBG plasma concentrations were associated with albuminuria as well as decline in kidney function. Whether MBG predicts hard renal endpoints warrants further investigations., Competing Interests: The authors have declared that no competing interests exist.

Patients with primary hyperparathyroidism are at increased risk for high blood pressure, vascular stiffening, and left ventricular hypertrophy, but previous studies have failed to demonstrate the direct associations with circulating parathyroid hormone (PTH) levels. The authors investigated cross-sectional relationships between PTH and 24-hour pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index in patients with primary hyperparathyroidism who were treatment-naive with cinacalcet, renin-angiotensin-aldosterone-system inhibitors, and thiazide or loop diuretics. In 76 patients, mean±SD of pulse wave velocity, nocturnal systolic blood pressure, and left ventricular mass index values were 9.3±1.8 m/s, 116.6±17.0 mm Hg, and 92.8±23.0 g/m². In multivariate linear regression analyses with adjustment for potentially confounding parameters, PTH was independently associated with nocturnal systolic blood pressure (adjusted ß coefficient=.284, P=.040), mean 24-hour pulse wave velocity (ß=.199, P=.001), and left ventricular mass index (ß=.252, P=.025). PTH may promote vascular and cardiac remodeling in primary hyperparathyroidism. Interventional trials are needed to test the antihypertensive and cardioprotective effects of PTH-inhibitory treatment strategies., (©2017 Wiley Periodicals, Inc.)

It is unclear whether genetic markers interact with risk factors to influence atrial fibrillation (AF) risk. We performed genome-wide interaction analyses between genetic variants and age, sex, hypertension, and body mass index in the AFGen Consortium. Study-specific results were combined using meta-analysis (88,383 individuals of European descent, including 7,292 with AF). Variants with nominal interaction associations in the discovery analysis were tested for association in four independent studies (131,441 individuals, including 5,722 with AF). In the discovery analysis, the AF risk associated with the minor rs6817105 allele (at the PITX2 locus) was greater among subjects ≤ 65 years of age than among those > 65 years (interaction p-value = 4.0 × 10 -5 ). The interaction p-value exceeded genome-wide significance in combined discovery and replication analyses (interaction p-value = 1.7 × 10 -8 ). We observed one genome-wide significant interaction with body mass index and several suggestive interactions with age, sex, and body mass index in the discovery analysis. However, none was replicated in the independent sample. Our findings suggest that the pathogenesis of AF may differ according to age in individuals of European descent, but we did not observe evidence of statistically significant genetic interactions with sex, body mass index, or hypertension on AF risk.

Increasing evidence describes a possible interplay between vitamin D insufficiency with increased aldosterone. The authors sought to evaluate the effect of vitamin D supplementation on plasma aldosterone concentration (PAC) in patients with hypertension and 25-hydroxyvitamin D[25(OH)D] insufficiency. The Styrian Vitamin D Hypertension Trial was a single-center, double-blind, placebo-controlled randomized clinical trial conducted from 2011 to 2014. Two hundred patients with arterial hypertension and 25(OH)D levels <30 ng/mL were enrolled. Study participants were randomized to receive either 2800 IU of vitamin D3 or placebo. The present investigation is a post hoc analysis using analysis of covariance adjusting for baseline differences. A total of 188 participants (mean±standard deviation age, 60.1±11.3 years; 47% women; 25(OH)D, 21.2±5.6 ng/mL) completed the trial. Mean differences between baseline and follow-up PAC in the control and intervention arm were +3.3 ng/dL and +0.9 ng/dL, respectively (P=.04). The findings indicate that vitamin D3 supplementation significantly decreases PAC in patients with arterial hypertension and 25(OH)D insufficiency., (© 2016 Wiley Periodicals, Inc.)

High parathyroid hormone (PTH) has been linked with high blood pressure (BP), but the relationship with 24-hour ambulatory blood pressure monitoring is largely unknown. The authors therefore analyzed cross-sectional data of 292 hypertensive patients participating in the Styrian Hypertension Study (mean age, 61±11 years; 53% women). Median plasma PTH (interquartile range) determined after an overnight fast was 49 pg/mL (39-61), mean daytime BP was 131/80±12/9 mm Hg, and mean nocturnal BP was 115/67±14/9 mm Hg. In multivariate regression analyses adjusted for BP and PTH-modifying parameters, PTH was significantly related to nocturnal systolic and diastolic BP (adjusted β-coefficient 0.140 [P=.03] and 0.175 [P<.01], respectively). PTH was not correlated with daytime BP readings. These data suggest a direct interrelationship between PTH and nocturnal BP regulation. Whether lowering high PTH concentrations reduces the burden of high nocturnal BP remains to be shown in future studies., (©2015 Wiley Periodicals, Inc.)

Aldosterone is considered to exert direct effects on the myocardium and the sympathetic nervous system. Both QT time and heart rate (HR) variability (HRV) are considered to be markers of arrhythmic risk and autonomous dysregulation. In this study, we investigated the associations between aldosterone, QT time, and HRV in patients with arterial hypertension.We recruited 477 hypertensive patients (age: 60.2 ± 10.2 years; 52.3% females) with a mean systolic/diastolic 24-hour ambulatory blood pressure monitoring (ABPM) value of 128 ± 12.8/77.1 ± 9.2 mmHg and with a median of 2 (IQR: 1-3) antihypertensive agents. Patients were recruited from the outpatient clinic at the Department of Internal Medicine of the Medical University of Graz, Austria. Blood samples, 24-hour HRV derived from 24-hour blood pressure monitoring (ABPM) and ECG's were obtained. Plasma aldosterone and plasma renin concentrations were measured by means of a radioimmunoassay. Twenty-four-hour urine specimens were collected in parallel with ABPM.Mean QTc was 423.3 ± 42.0 milliseconds for males and 434.7 ± 38.3 milliseconds for females. Mean 24H-HR and 24H-HRV was 71.9 ± 9.8 and 10.0 ± 3.6 bpm, respectively. In linear regression analyses adjusted for age, sex, body mass index, ABPM, and current medication, aldosterone to active renin ratio (AARR) was significantly associated with the QTc interval, a marker for cardiac repolarization abnormalities (mean = 426 ± 42.4 milliseconds; β-coefficient = 0.121; P = 0.03) as well as with the 24-hour heart rate variability a surrogate for autonomic dysfunction (median = 9.67 [IQR = 7.38-12.22 bpm]; β-coefficient = -0.133; P = 0.01).In hypertensive patients, AARR is significantly related to QTc prolongation as well as HRV. Further studies investigating the effects of mineralocorticoid receptor blocker and aldosterone synthase inhibitors on QTc and HRV are warranted.

Unlabelled: Vitamin D deficiency is a risk factor for arterial hypertension, but randomized controlled trials showed mixed effects of vitamin D supplementation on blood pressure (BP). We aimed to evaluate whether vitamin D supplementation affects 24-hour systolic ambulatory BP monitoring values and cardiovascular risk factors. The Styrian Vitamin D Hypertension Trial is a single-center, double-blind, placebo-controlled study conducted from June 2011 to August 2014 at the endocrine outpatient clinic of the Medical University of Graz, Austria. We enrolled 200 study participants with arterial hypertension and 25-hydroxyvitamin D levels below 30 ng/mL. Study participants were randomized to receive either 2800 IU of vitamin D3 per day as oily drops (n=100) or placebo (n=100) for 8 weeks. Primary outcome measure was 24-hour systolic BP. Secondary outcome measures were 24-hour diastolic BP, N-terminal-pro-B-type natriuretic peptide, QTc interval, renin, aldosterone, 24-hour urinary albumin excretion, homeostasis model assessment-insulin resistance, triglycerides, high-density lipoprotein cholesterol, and pulse wave velocity. A total of 188 participants (mean [SD] age, 60.1 [11.3] years; 47% women; 25-hydroxyvitamin D, 21.2 [5.6] ng/mL) completed the trial. The mean treatment effect (95% confidence interval) for 24-hour systolic BP was -0.4 (-2.8 to 1.9) mm Hg (P=0.712). Triglycerides increased significantly (mean change [95% confidence interval], 17 [1-33] mg/dL; P=0.013), but no further significant effects were observed for secondary outcomes. Vitamin D supplementation in hypertensive patients with low 25-hydroxyvitamin D has no significant effect on BP and several cardiovascular risk factors, but it was associated with a significant increase in triglycerides., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02136771., (© 2015 American Heart Association, Inc.)

Background: The cardiotonic steroid marinobufagenin (MBG) is increasingly suggested to be responsible for some of the cardiovascular injury that has been previously attributed to aldosterone. We examined the clinical correlates of circulating MBG concentrations in hypertensive patients and tested the hypothesis that MBG serves as a reliable diagnostic tool for detecting primary aldosteronism (PA)., Methods: Plasma MBG concentrations (mean: 0.51±0.25 nmol/l) were measured in the morning fasting samples in 20 patients with PA and 20 essential hypertensive (EH) controls matched for age, sex, body mass index, renal function, urinary sodium and intake of antihypertensive medication (mean age: 51.6 years; 52.2% women)., Results: Overall, plasma MBG was directly correlated with plasma aldosterone, aldosterone to active renin ratio (AARR), diastolic blood pressure, mean carotid intima-media thickness, serum sodium, urinary protein to creatinine ratio and inversely with serum potassium levels. Plasma MBG levels were significantly higher in patients with PA compared to EH (mean: 0.68±0.12 versus 0.35±0.24 nmol/l; p<0.001). ROC analysis yielded a greater AUC for plasma MBG compared to the AARR, PAC and serum potassium levels for detecting PA. Youden's Index analyses yielded the optimal plasma MBG cut-off score for diagnosing PA at >0.49 nmol/l with specificity and sensitivity values of 0.85 and 0.95, respectively, which were higher than those at the optimum AARR cut-off at >3.32 ng/dl/µU/ml., Conclusions: In a well-characterized cohort, values of plasma MBG were significantly related to clinical correlates of cardiovascular and renal disease. Plasma MBG emerged as a valuable alternative to the AARR for screening of PA.

The current study assessed which measure of heart rate (HR) is most associated with inflammatory activity. Among 368 hypertensive patients (mean age±standard deviation, 60.6±10.8; 52.9% women), mean daytime (from 6 am to 10 pm), nighttime (from 10 pm to 6 am), and 24-hour HR were recorded using a continuous 24-hour ambulatory blood pressure monitoring portable device. Associations of daytime, nighttime, and 24-hour HR with leukocytes, platelets, C-reactive protein (CRP), and 25-hydroxyvitamin D were calculated using multivariate linear regression, reporting unstandardized coefficients (B) with standard errors (SEs). Mean daytime, nighttime, and 24-hour HR were 73, 64, and 71 beats per minute, respectively. All HR measures were positively associated with leukocytes after adjustment. Nighttime HR was additionally related with higher CRP. When all HR measures were simultaneously added to a single multivariate model, only the positive associations of nighttime HR with leukocytes (B [SE]=0.06 [0.03], P=.04), as well as with CRP (B [SE]=0.20 [0.07], P=.005), persisted. Nighttime HR was more closely associated with inflammatory activity. These observations lend some insight toward the pathophysiological mechanisms that implicate HR in cardiovascular risk and provide valuable direction for forthcoming investigations., (Copyright © 2014 Wiley Periodicals, Inc.)

Background: Low plasma 25-hydroxyvitamin D (25[OH]D) concentration is associated with high arterial blood pressure and hypertension risk, but whether this association is causal is unknown. We used a mendelian randomisation approach to test whether 25(OH)D concentration is causally associated with blood pressure and hypertension risk., Methods: In this mendelian randomisation study, we generated an allele score (25[OH]D synthesis score) based on variants of genes that affect 25(OH)D synthesis or substrate availability (CYP2R1 and DHCR7), which we used as a proxy for 25(OH)D concentration. We meta-analysed data for up to 108 173 individuals from 35 studies in the D-CarDia collaboration to investigate associations between the allele score and blood pressure measurements. We complemented these analyses with previously published summary statistics from the International Consortium on Blood Pressure (ICBP), the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and the Global Blood Pressure Genetics (Global BPGen) consortium., Findings: In phenotypic analyses (up to n=49 363), increased 25(OH)D concentration was associated with decreased systolic blood pressure (β per 10% increase, -0·12 mm Hg, 95% CI -0·20 to -0·04; p=0·003) and reduced odds of hypertension (odds ratio [OR] 0·98, 95% CI 0·97-0·99; p=0·0003), but not with decreased diastolic blood pressure (β per 10% increase, -0·02 mm Hg, -0·08 to 0·03; p=0·37). In meta-analyses in which we combined data from D-CarDia and the ICBP (n=146 581, after exclusion of overlapping studies), each 25(OH)D-increasing allele of the synthesis score was associated with a change of -0·10 mm Hg in systolic blood pressure (-0·21 to -0·0001; p=0·0498) and a change of -0·08 mm Hg in diastolic blood pressure (-0·15 to -0·02; p=0·01). When D-CarDia and consortia data for hypertension were meta-analysed together (n=142 255), the synthesis score was associated with a reduced odds of hypertension (OR per allele, 0·98, 0·96-0·99; p=0·001). In instrumental variable analysis, each 10% increase in genetically instrumented 25(OH)D concentration was associated with a change of -0·29 mm Hg in diastolic blood pressure (-0·52 to -0·07; p=0·01), a change of -0·37 mm Hg in systolic blood pressure (-0·73 to 0·003; p=0·052), and an 8·1% decreased odds of hypertension (OR 0·92, 0·87-0·97; p=0·002)., Interpretation: Increased plasma concentrations of 25(OH)D might reduce the risk of hypertension. This finding warrants further investigation in an independent, similarly powered study., Funding: British Heart Foundation, UK Medical Research Council, and Academy of Finland., (Copyright © 2014 Vimaleswaran et al. Open Access article distributed under the terms of CC BY. Published by .. All rights reserved.)

The objective of the present study was to review previous investigations on the association of haplotypes in the G-protein β3 subunit (GNB3) gene with representative cardiovascular risk factors/phenotypes: hypertension, overweight, and variation in the systolic and diastolic blood pressures (SBP and DBP, respectively) and as well as body mass index (BMI). A comprehensive literature search was undertaken in Pubmed, Web of Science, EMBASE, Biological Abstracts, LILACS and Google Scholar to identify potentially relevant articles published up to April 2011. Six genetic association studies encompassing 16,068 participants were identified. Individual participant data were obtained for all studies. The three most investigated GNB3 polymorphisms (G-350A, C825T and C1429T) were considered. Expectation-maximization and generalized linear models were employed to estimate haplotypic effects from data with uncertain phase while adjusting for covariates. Study-specific results were combined through a random-effects multivariate meta-analysis. After carefully adjustments for relevant confounding factors, our analysis failed to support a role for GNB3 haplotypes in any of the investigated phenotypes. Sensitivity analyses excluding studies violating Hardy-Weinberg expectations, considering gender-specific effects or more extreme phenotypes (e.g. obesity only) as well as a fixed-effects "pooled" analysis also did not disclose a significant influence of GNB3 haplotypes on cardiovascular phenotypes. We conclude that the previous cumulative evidence does not support the proposal that haplotypes formed by common GNB3 polymorphisms might contribute either to the development of hypertension and obesity, or to the variation in the SBP, DBP and BMI.

Objective: Accumulating evidence supports a potential role for dopamine in the regulation of insulin secretion. We examined the association between circulating dopamine and C-peptide concentrations using data from the Graz Endocrine Causes of Hypertension (GECOH) study., Research Design and Methods: After 12 h of fasting, we measured plasma dopamine and serum C-peptide levels and established determining factors of insulin secretion in 201 nondiabetic hypertensive patients (mean age 48.1 ± 16.0 years; 61.7% women)., Results: Mean dopamine and C-peptide concentration were 33.4 ± 38.6 pg/mL and 3.1 ± 2.7 ng/mL, respectively. A strong and inverse correlation was observed between dopamine and C-peptide levels (r = -0.423, P < 0.001). There was no significant relationship between C-peptide, plasma epinephrine, and norepinephrine. C-peptide levels decreased steadily and significantly from tertile 1 of dopamine (3.6 ng/mL [95% CI 2.9-4.1]) to tertile 3 (1.6 ng/mL [1.5-2.7], P < 0.001) after multivariate adjustment., Conclusions: The inverse association between dopamine and C-peptide highlights the need to evaluate whether dopamine could be effective for modulating endocrine pancreatic function.

Introduction: Medical societies have developed guidelines for the detection, treatment and control of hypertension (HTN). Our analysis assessed the extent to which such guidelines were implemented in Germany in 2003 and 2001., Methods: Using standardized clinical diagnostic and treatment appraisal forms, blood pressure levels and patient questionnaires for 55,518 participants from the cross-sectional Targets and Essential Data for Commitment of Treatment (DETECT) study (2003) were analyzed. Physician's diagnosis of hypertension (HTN(doc)) was defined as coding hypertension in the clinical appraisal questionnaire. Alternative definitions used were physician's diagnosis or the patient's self-reported diagnosis of hypertension (HTN(doc,pat)), physician's or patient's self-reported diagnosis or a BP measurement with a systolic BP ≥ 140 mmHg and/or a diastolic BP ≥ 90 (HTN(doc,pat,bp)) and diagnosis according to the National Health and Nutrition Examination Survey (HTN(NHANES)). The results were compared with the similar German HYDRA study to examine whether changes had occurred in diagnosis, treatment and adequate blood pressure control (BP below 140/90 mmHg) since 2001. Factors associated with pharmacotherapy and control were determined., Results: The overall prevalence rate for hypertension was 35.5% according to HTN(doc) and 56.0% according to NHANES criteria. Among those defined by NHANES criteria, treatment and control rates were 56.0% and 20.3% in 2003, and these rates had improved from 55.3% and 18.0% in 2001. Significant predictors of receiving antihypertensive medication were: increasing age, female sex, obesity, previous myocardial infarction and the prevalence of comorbid conditions such as coronary heart disease (CHD), hyperlipidemia and diabetes mellitus (DM). Significant positive predictors of adequate blood pressure control were CHD and antihypertensive medication. Inadequate control was associated with increasing age, male sex and obesity., Conclusions: Rates of treated and controlled hypertension according to NHANES criteria in DETECT remained low between 2001 and 2003, although there was some minor improvement.

The intentions of our investigation were (1) to search for atherogenic risk factors and signs of incipient atherosclerosis in children and adolescents with type 1 diabetes (T1DM) in comparison to well-matched control subjects, (2) to evaluate risk factor associations with carotid intima media thickness (cIMT) in diabetic patients and control subjects, and (3) to acquire a better knowledge of early atherogenesis in children and adolescents with and without T1DM. 94 diabetic children (age median 12.3 years, HbA1c median 7.7%) and 40 non-diabetic controls (age median 12.3 years) were investigated. Mean cIMT was determined using high-resolution B-mode ultrasound with an automated contour identification procedure. Compared to controls, subjects with diabetes had significantly elevated cIMT (p = 0.041) and systolic BP (p = 0.007) but showed a less atherogenic lipid profile. Most markers of inflammation, endothelial function and fibrinolytic activity were higher in diabetic subjects than in controls. Multiple linear regression analysis revealed a significant relationship (r = 0.53, p = 0.036) between bilateral mean cIMT and diverse risk factors in patients with T1DM. Spearman rank correlation showed that diabetes duration (rho = 0.32, p = 0.029), systolic BP (rho = 0.32, p = 0.004), weight (rho = 0.257, p = 0.022), and height (rho = 0.265, p = 0.018) significantly correlated with bilateral mean cIMT in the 94 diabetic patients. In conclusion, in well-controlled type 1 diabetic children systolic BP may be of greater importance than dyslipidaemia in early atherogenesis. BMI, markers of sustained inflammation, endothelial dysfunction and fibrinolytic activity are increased in diabetic versus non-diabetic children but none of them correlates significantly with cIMT. Their prognostic value remains to be determined.

Objective: The oral antidiabetic agent pioglitazone improves insulin sensitivity and glycemic control and appears to lower atherogenic dense LDL in type 2 diabetes. Insulin resistance may occur frequently in nondiabetic patients with hypertension. This study is the first to report the effect of pioglitazone on LDL subfractions in normolipidemic, nondiabetic patients with arterial hypertension., Research Design and Methods: We performed a monocentric, double-blind, randomized, parallel-group comparison of 45 mg pioglitazone (n = 26) and a placebo (n = 28), each given once daily for 16 weeks. Fifty-four moderately hypertensive patients (LDL cholesterol, 2.8 +/- 0.8 mmol/l; HDL cholesterol, 1.1 +/- 0.3 mmol/l; triglycerides, 1.4 mmol/l (median; range 0.5-7.1) were studied at baseline and on treatment., Results: At baseline, dense LDLs were elevated (apolipoprotein [apo]B in LDL-5 plus LDL-6 >250 mg/l) in 63% of all patients. Sixteen weeks of treatment with pioglitazone did not significantly change triglycerides, total, LDL, and HDL cholesterol. However, pioglitazone reduced dense LDLs by 22% (P = 0.024). The mean diameter of LDL particles increased from 19.83 +/- 0.30 to 20.13 +/- 0.33 nm (P < 0.001 vs. placebo), whereas the mean LDL density decreased from 1.0384 +/- 0.0024 to 1.0371 +/- 0.0024 kg/l (P = 0.005 vs. placebo). The effect of pioglitazone on LDL size and density was independent of fasting triglycerides and HDL cholesterol at baseline and of changes in fasting triglycerides and HDL cholesterol., Conclusions: The prevalence of atherogenic dense LDL in nondiabetic, hypertensive patients is similar to patients with type 2 diabetes. Pioglitazone significantly reduces dense LDL independent from fasting triglycerides and HDL cholesterol. The antiatherogenic potential of pioglitazone may thus be greater than that expected from its effects on triglycerides, LDL, and HDL cholesterol alone.

Disorders of the lipoprotein metabolism are a major cause of endothelial dysfunction that may result in hypertension and proteinuria, clinical hallmarks of preeclampsia (PE). Lipoproteins and low-density lipoprotein (LDL) subfractions were investigated in 15 women with severe PE and compared with 23 women with a normal course of pregnancy. Compared with normal pregnancy, in PE apolipoprotein (apo)B in very low-density lipoprotein was increased by 76% (P = 0.008), and the triglyceride content of intermediate dense lipoproteins (IDL) was increased by 51% (P < 0.001); cholesterol and apoB in LDL were decreased by 26% (P = 0.005) and 23% (P = 0.016), respectively. Although not significant, the LDL profile was dominated by the most buoyant LDL-1. ApoB in the most dense LDL (dLDL), namely LDL-5 and LDL-6, was significantly decreased by 49% (P < 0.001) and 55% (P < 0.001), respectively. Diastolic blood pressure was positively correlated with the triglyceride content of IDL (r = 6.31; P < 0.001 and r = 0.352; P = 0.033 by partial correlation controlling for the presence or absence of PE) and negatively correlated with the concentration of apoB in dLDL (r = -0.500; P = 0.002). In addition, IDL triglycerides correlated negatively with infant birth weight percentile (r = -0.373; P = 0.027) and positively with proteinuria (r = 0.430; P = 0.014). Low birth weight was associated with high IDL triglycerides and low rather than high concentrations of dLDL. Triglyceride-rich remnants are known to cause endothelial dysfunction. Because the triglyceride content of IDL was positively correlated with elevated blood pressure and proteinuria, triglyceride-rich remnant lipoproteins might contribute to the pathophysiology of PE.

Introduction: Short telomeres have been associated with adverse lifestyle factors, cardiovascular risk factors and age-related diseases, including cardiovascular disease (CVD), myocardial infarction, atherosclerosis, hypertension, diabetes, and also with mortality. However, previous studies report conflicting results. Objectives: The aim of the present study has been to investigate the involvement of telomere length in all-cause and CVD mortality in subjects hospitalized for diagnostic coronary angiography of the Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Methods: Relative telomere length (RTL) was measured with a Q-PCR based method in 3,316 participants of the LURIC study. Age-corrected RTL was calculated as the ratio between RTL and age. Median follow-up was 9.9 years. Cox regression and Kaplan-Maier analyses were performed to evaluate the role of RTL for all-cause and cardiovascular mortality. Results: RTL correlated negatively with age (r = -0.09; p<0.001). In surviving patients the correlation between age and RTL was statistically significant (r = -0.088; p<0.001), but not in patients who died during follow-up (r = -0.043; p = 0.20). Patients in quartiles 2–4 of RTL had a lower hazard ratio for all-cause mortality (HR:0.822; 95%CI 0.712–0.915; p = 0.008) and CVD-mortality (HR:0.836; 95%CI 0.722–0.969; p = 0.017) when compared to those in the 1st quartile. Adjustment for major cardiovascular risk factors did not change this result, however additional adjustment for age attenuated this effect. Patients in the 4th quartile of age-corrected RTL compared to those in the 1st quartile had a lower hazard ratio for all-cause mortality, even with adjustment for major cardiovascular risk factors. Conclusions: The present study supports the hypothesis that short telomere length increases the risk of all-cause and CVD mortality. Age appears to be an important co-variate that explains a substantial fraction of this effect. It remains unclear whether short telomeres contribute directly to the increase in mortality or if they are simply a surrogate marker for other adverse processes of aging. [ABSTRACT FROM AUTHOR]

Background: Vitamin D deficiency may be a risk factor for mortality but previous meta-analyses lacked standardization of laboratory methods for 25-hydroxyvitamin D (25[OH]D) concentrations and used aggregate data instead of individual participant data (IPD). We therefore performed an IPD meta-analysis on the association between standardized serum 25(OH)D and mortality. Methods: In a European consortium of eight prospective studies, including seven general population cohorts, we used the Vitamin D Standardization Program (VDSP) protocols to standardize 25(OH)D data. Meta-analyses using a one step procedure on IPD were performed to study associations of 25(OH)D with all-cause mortality as the primary outcome, and with cardiovascular and cancer mortality as secondary outcomes. This meta-analysis is registered at ClinicalTrials.gov, number NCT02438488. Findings: We analysed 26916 study participants (median age 61.6 years, 58% females) with a median 25(OH)D concentration of 53.8 nmol/L. During a median follow-up time of 10.5 years, 6802 persons died. Compared to participants with 25(OH)D concentrations of 75 to 99.99 nmol/L, the adjusted hazard ratios (with 95% confidence interval) for mortality in the 25(OH)D groups with 40 to 49.99, 30 to 39.99, and <30 nmol/L were 1.15 (1.00–1.29), 1.33 (1.16–1.51), and 1.67 (1.44–1.89), respectively. We observed similar results for cardiovascular mortality, but there was no significant linear association between 25(OH)D and cancer mortality. There was also no significantly increased mortality risk at high 25(OH)D levels up to 125 nmol/L. Interpretation: In the first IPD meta-analysis using standardized measurements of 25(OH)D we observed an association between low 25(OH)D and increased risk of all-cause mortality. It is of public health interest to evaluate whether treatment of vitamin D deficiency prevents premature deaths. [ABSTRACT FROM AUTHOR]

Epidemiological evidence suggests that circulating 25-hydroxyvitamin D (25OHD) levels are inversely associated with hemoglobin (Hb) levels and anemia risk. We evaluated whether vitamin D supplementation improves Hb levels and reduces anemia risk in hypertensive patients. Two hundred patients with 25OHD levels <75 nmol/L who attended the Styrian Vitamin D Hypertension Trial were included, of whom 188 completed the trial. Patients randomly received 2800 IU vitamin D3 daily or a matching placebo for eight weeks. Initially, the prevalence of anemic status (Hb levels <12.5 g/dL) and deficient 25OHD levels (<30 nmol/L) was 6.5% and 7.5%, respectively. All anemic patients had 25OHD levels >50 nmol/L. The mean (95% confidence interval) vitamin D effect on Hb levels was 0.04 (−0.14 to 0.22) g/dL (P=0.661). Moreover, vitamin D treatment did not influence anemic status significantly (P>0.999). Likewise, vitamin D had no significant effect on Hb levels in the subgroups of anemic patients or in patients with initial 25OHD levels <30 nmol/L. In conclusion, a daily vitamin D supplement of 2800 IU for eight weeks did not improve Hb levels or anemic status in hypertensive patients. Future trials should focus on anemic patients with deficient 25OHD levels (e.g., <30 nmol/L). This trial is registered with clinicaltrials.gov [NCT02136771]. [ABSTRACT FROM AUTHOR]

Background: Owing to a growing interest in vitamin D, there has been an increasing demand for 25-hydroxyvitamin D (25[OH]D) measurements over the past few years warranting a critical evaluation of laboratory methods for 25(OH)D determinations. Therefore, the aim of this study was to compare four of the most frequently used routine assays for 25(OH)D. Methods: In 106 hypertensive patients (53±14 years; 59% females), derived from the Graz Endocrine Causes of Hypertension (GECOH) study, we measured 25(OH)D in serum and plasma by means of four automated immunoassays (DiaSorin Liaison, IDS iSYS, Abbott ARCHITECT, and Roche Cobas). Results: We observed a poor comparability between assay results with Pearson correlation coefficients between the different methods ranging from 0.57 to 0.85. Using a value of ≤20 ng/mL (50 nmol/L) as the cut-off for vitamin D deficiency, the percentages of vitamin D deficient patients was significantly different depending on the assay method: 79.2% (Abbott ARCHITECT), 50.0% (DiaSorin Liaison), 28.3% (IDS iSYS), and 23.6% (Roche Cobas). Conclusions: By comparing four frequently used automated immunoassays for 25(OH)D, we observed remarkable differences with a significant impact on vitamin D status classification. Clinicians and researchers must be aware of these assay differences and must aim for standardization of 25(OH)D measurements. [ABSTRACT FROM AUTHOR]

Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Copyright of Journal of Laboratory Medicine / Laboratoriums Medizin is the property of De Gruyter and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Angiotensinogen and its cleaved forms angiotensin I and angiotensin II are important regulators of blood pressure. The gene for angiotensinogen (AGT) carries two common polymorphisms, T207M and M268T (previously described as T174M and M235T). To investigate the role of haplotypes formed by these polymorphisms for angiotensinogen levels we examined blood pressure, coronary artery disease (CAD), myocardial infarction (MI), andAGTgenotypes and haplotypes in 2,575 patients with angiographically documented CAD and 731 individuals in whom CAD had been ruled out by angiography. Three haplotypes, designated as Hap1 (T207, M268), Hap2 (T207, T268) and Hap3 (M207, T268), accounted for more than 99% of alleles. TheAGTHap2 haplotype was significantly associated with angiotensinogen levels; one additional Hap2 allele accounted for an approx. 8% increase in angiotensinogen. This association was stronger than that of either single polymorphism.AGTgenotypes or haplotypes were not related to hypertension, CAD or MI. We conclude that a common haplotype of the angiotensinogen gene is linked to angiotensinogen levels but has no major impact on blood pressure, hypertension, or cardiovascular risk. [ABSTRACT FROM AUTHOR]

Nitric oxide (NO) synthesis markers, comprising L-homoarginine, asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA), are significantly associated with cardiovascular events and mortality. Being involved in NO pathways, they may be of high importance regulating vascular tone and arterial hypertension, but data on this topic are sparse and controversial. In this study, we evaluated whether these NO synthesis markers are associated with blood pressure values and pulse wave velocity (PWV). This analysis was based on the data of the Styrian Vitamin D Hypertension Trial, which included adults with arterial hypertension. We analyzed correlations of NO synthesis markers with 24 h ambulatory blood pressure values and PWV (primary outcomes), as well as with anthropometric and laboratory data. A total of 509 patients were included in the present analysis. The mean age was 61.2 ± 10.5 years, mean PWV was 8.6 ± 2.4 m/s, mean 24 h systolic blood pressure was 127.5 ± 13.8 mmHg and mean 24 h diastolic blood pressure was 76.4 ± 9.5 mmHg. In bivariate analyses, there was a significant positive correlation between homoarginine and 24 h diastolic blood pressure (r = 0.1; p = 0.02), which was revealed to be no longer significant after adjustment for age, gender and glomerular filtration rate (GFR) in multivariate regression analysis. No other significant correlations of any NO synthesis markers with blood pressure or PWV were observed. In line with previous studies, there were inverse associations between homoarginine and age and between ADMA or SDMA and GFR (p < 0.05 for all). This study did not reveal a significant association between homoarginine, ADMA or SDMA and blood pressure or PWV in hypertensive adults. These results suggested that the associations of these parameters with adverse outcome may not be mediated by hypertension and/or endothelial dysfunction. [ABSTRACT FROM AUTHOR]

Background Vitamin D deficiency is associated with an unfavorable lipid profile, but whether and how vitamin D supplementation affects lipid metabolism is unclear. Objective To examine the effects of vitamin D supplementation on lipid and lipoprotein parameters. Methods This is a post hoc analysis of the single-center, double-blind, randomized, placebo-controlled Styrian Vitamin D Hypertension Trial (2011–2014). Two hundred individuals with arterial hypertension and 25-hydroxyvitamin D concentrations of <75 nmol/L were randomized to 2800 IU of vitamin D daily or placebo for 8 weeks. Results One hundred sixty-three participants (62.2 [53.1–68.4] years of age; 46% women) had available lipid data and were included in this analysis. Vitamin D supplementation significantly increased total cholesterol, triglycerides, very-low-density lipoprotein (VLDL) triglycerides, low-density lipoprotein (LDL) triglycerides, high-density lipoprotein (HDL) triglycerides, apolipoprotein B (ApoB), LDL-ApoB, ApoCII, ApoCIII, phospholipids, and ApoE ( P < .05 for all). Except for ApoCII and ApoCIII and HDL-triglycerides, all other treatment effects remained statistically significant after adjustment for multiple testing with the Benjamini and Hochberg false discovery rate method. There was a nonsignificant increase in LDL cholesterol. Furthermore, no significant effects were seen on free fatty acids, lipoprotein (a), ApoAI, ApoAII, VLDL cholesterol, VLDL–ApoB, HDL cholesterol, LDL diameter, and VLDL diameter. Conclusions The effects of vitamin D on lipid metabolism are potentially unfavorable. They require further investigation in view of the wide use of vitamin D testing and treatment. [ABSTRACT FROM AUTHOR]