scholarly journals Increased Sclerostin, but Not Dickkopf-1 Protein, Is Associated with Elevated Pulse Wave Velocity in Hemodialysis Subjects

2019 ◽  
Vol 44 (4) ◽  
pp. 679-689 ◽  
Author(s):  
Eirini Stavrinou ◽  
Pantelis A. Sarafidis ◽  
Charalampos Koumaras ◽  
Charalampos Loutradis ◽  
Panagiotis Giamalis ◽  
...  

Background: Sclerostin and Dickkopf-1 (Dkk-1) proteins are inhibitors of the canonical Wnt/β-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in chronic kidney disease (CKD), but data on the effects of Dkk-1 are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. Methods: A total of 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central blood pressure (BP), and wave reflections evaluated with applanation tonometry (Sphygmocor) on a midweek non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, comorbid, laboratory, and drug parameters were used in the analyses. Results: Subjects with PWV >9.5 m/s (high arterial stiffness group, n = 40) were older, had higher BMI, higher prevalence of hypertension, diabetes, and coronary heart disease, and higher peripheral systolic BP, central systolic BP, C-reactive protein, and serum sclerostin (p = 0.02), but similar Dkk-1, compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63 ± 2.71 vs. 9.77 ± 3.13, p = 0.048). Increased sclerostin (>200 pg/mL) was significantly associated with increased PWV (>9.5 m/s; HR 2.778, 95% CI 1.123–6.868 per pg/mL increase); this association remained significant after stepwise adjustment for Dkk-1, intact parathyroid hormone, and calcium × phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR 1.000, 95% CI 0.416–2.403). Conclusion: Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast, Dkk-1 has no association with arterial stiffness and is not pathophysiologically involved in relevant vascular changes.

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
EIRINI STAVRINOU ◽  
Panteleimon Sarafidis ◽  
Charalampos Koumaras ◽  
Charalampos Loutradis ◽  
Panagiotis Giamalis ◽  
...  

Abstract Background and Aims Sclerostin and Dickkopf-1 (Dkk-1) protein are inhibitors of the canonical Wnt/β-catenin bone pathway. Pilot data suggest that sclerostin may be involved in vascular changes in CKD, but data on Dkk-1 effects are scarce. This is the first study investigating simultaneously the associations of sclerostin and Dkk-1 with arterial stiffness in hemodialysis patients. Method 80 patients on chronic hemodialysis had carotid-femoral pulse wave velocity (PWV), central BP and wave reflections evaluated with applanation tonometry (Sphygmocor) in a mid-week non-dialysis day. Serum levels of sclerostin and Dkk-1 were measured with ELISA. A large set of demographic, co-morbid, laboratory and drug parameters were used in the analyses. Results Subjects with PWV>9.5 m/sec (high arterial stiffness group, n=40) were older, had higher BMI, higher prevalence of hypertension, diabetes and coronary-heart-disease and higher peripheral SBP, central SBP, C- reactive protein and serum sclerostin (p=0.02), but similar Dkk-1 compared to subjects with low PWV. When dichotomizing the population by sclerostin levels, those with high sclerostin had higher PWV than patients with low sclerostin levels (10.63±2.71 vs 9.77±3.13, p=0.048). Increased sclerostin (>200 pg/ml) was significantly associated with increased PWV (>9.5 m/s) (HR:2.778, 95%CI:1.123-6.868, per pg/ml increase); this association remained significant after stepwise adjustment for Dkk-1, iPTH and calcium x phosphate product. In contrast, no association was noted between Dkk-1 and PWV (HR: 1.000, 95%CI: 0.416-2.403). Conclusion Serum sclerostin is associated with PWV independently of routine markers of CKD-MBD in hemodialysis patients. In contrast Dkk-1 has no association with arterial stiffness and is rather not pathophysiologically involved in relevant vascular changes.


Author(s):  
V. V. Genkel ◽  
R. G. Portnova ◽  
T. V. Antipina ◽  
I. I. Shaposhnik

Aim.  To study muscular (brachial and radial arteries) and elastic (aorta) regional arterial stiffness in IBD patients in comparison with those without IBD, as well as to establish the relationship between arterial stiffness and the characteristics of the IBD course (the duration of illness, severity of attack, activity of systemic inflammation). Materials and methods. The study included 21 IBD patients and 30 patients in the comparison group. The values of regional aortic and muscular arterial stiffness were measured by applanation tonometry. The carotid–femoral pulse wave velocity (cfPWV) and the carotid-radial pulse wave velocity (crPWV) were determined. The laboratory research plan included the analysis of complete blood count, biochemical parameters, fibrinogen and a high sensitivity  C-reactive protein (hsCRP).Results. crPWV, similar to cfPWV, was not significantly different between the groups. At the same time, the proportion of individuals with an increase in the cfPWV of more than 10 m/s was higher in the group of IBD patients. However, these differences did not reach the level of statistical significance. According to the results of the correlation analysis, the increase in cfPWV was associated with an increase in patient age (r = 0.564; p = 0.01), the duration of IBD history (r = 0.628; p = 0.003), fasting plasma glucose (r = 0.367; p = 0.034) and GFR decrease (r = -0.482; p = 0.031). The crPWV also directly correlated with the IBD duration (r = 0.630; p = 0.003). According to the results of the regression analysis, an increase in the IBD duration by 1 year is associated with an increase in cfPWV by 0.205 m/s, i.e. the increase in the IBD duration by 5 years is associated with an increase in the cfPWV of approximately 1 m/s.Conclusion. In IBD patients, the duration of the disease directly correlated with an increase in cfPWV and crPWV. The increase in the IBD duration by 1 year was associated with an increase in cfPWV by 0.205 m/s. The muscular and elastic regional arterial stiffness was not statistically significantly different between IBD patients and the comparison group. 


Angiology ◽  
2008 ◽  
Vol 60 (1) ◽  
pp. 82-86 ◽  
Author(s):  
Oladipupo Olafiranye ◽  
Ghazanfar Qureshi ◽  
Louis Salciccioli ◽  
Kinda Vernon-Jones ◽  
Charles Philip ◽  
...  

Background increased arterial stiffness is a predictor of cardiovascular events. The stroke volume (SV) to pulse pressure (PP) ratio is an estimate of arterial capacitance. Pulse wave velocity (PWV) is a measure of arterial stiffness. This study evaluated the effect of left ventricular (LV) SV on the SV/PP–PWV relationship. Methods 97 patients had applanation tonometry and echocardiography to measure arterial capacitance (SV/PP), PWV, and central aortic pressure. Results 50 patients had normal SV and 47 had low SV. For all patients, PWV inversely correlated with SV/PP. PWV and SV/PP correlated more strongly in the normal SV group than in the low SV group. Aortic PP was significantly correlated with PWV in all patients, in the normal SV group, and in the low SV group. Conclusion effective arterial capacitance correlates with PWV. The presence of decreased SV weakens the relationship.


2004 ◽  
Vol 37 (8) ◽  
pp. 1639-1643
Author(s):  
Jun Shiota ◽  
Koji Ito ◽  
Yuji Nakamura ◽  
Masaharu Katae ◽  
Hideaki Tomita ◽  
...  

2011 ◽  
Vol 15 (3) ◽  
pp. 326-333 ◽  
Author(s):  
Serena TORRACA ◽  
Maria Luisa SIRICO ◽  
Pasquale GUASTAFERRO ◽  
Luigi Francesco MORRONE ◽  
Filippo NIGRO ◽  
...  

2012 ◽  
Vol 35 (5) ◽  
pp. 518-522 ◽  
Author(s):  
Lucia Di Micco ◽  
Serena Torraca ◽  
Maria Luisa Sirico ◽  
Domenico Tartaglia ◽  
Biagio Di Iorio

2018 ◽  
Vol 16 (3) ◽  
pp. 281-288 ◽  
Author(s):  
Hsin-Yu Yang ◽  
Du-An Wu ◽  
Ming-Chun Chen ◽  
Bang-Gee Hsu

Background: Sclerostin and Dickkopf-1 are extracellular inhibitors of the canonical Wnt/β-catenin signalling pathway, which is implicated in the development of arterial stiffness. However, the correlation between aortic stiffness and sclerostin or Dickkopf-1 levels in patients with type 2 diabetes mellitus is unknown. Methods: Fasting blood samples were collected from 125 patients with type 2 diabetes mellitus. Aortic stiffness was measured by carotid–femoral pulse wave velocity, and high aortic stiffness was defined by a carotid–femoral pulse wave velocity of >10 m/s. The serum sclerostin and Dickkopf-1 concentrations were determined using commercially available enzyme-linked immunosorbent assays. Results: In total, 46 patients with type 2 diabetes mellitus (36.8%) had high levels of aortic stiffness. Compared to the control group without aortic stiffness, this group was significantly older, had higher systolic and diastolic blood pressures, had higher blood urea nitrogen, creatinine, urinary albumin-to-creatinine ratio and serum sclerostin levels, and had significantly lower high-density lipoprotein cholesterol levels and estimated glomerular filtration rates. After adjusting for confounders, serum sclerostin [odds ratio = 1.005 (1.002–1.007), p = 0.002] levels remained an independent predictor of aortic stiffness. Multivariate analysis showed that the serum sclerostin level ( β = 0.374, adjusted R2 change = 0.221, p < 0.001) was positively associated with carotid–femoral pulse wave velocity. Conclusion: Serum levels of sclerostin, but not Dickkopf-1, are positively correlated with carotid–femoral pulse wave velocity and independently predict aortic stiffness in patients with type 2 diabetes mellitus.


1985 ◽  
Vol 13 (5) ◽  
pp. 1237-1243
Author(s):  
Susumu YUKAWA ◽  
Kazuo MORI ◽  
Osamu NISHIKAWA ◽  
Hiroshi NOMOTO ◽  
Noriko NISHIKAWA ◽  
...  

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