Serum levels of sclerostin as a potential biomarker in central arterial stiffness among hypertensive patients

Abstract

BackgroundSclerostin is known to be a canonical Wnt/β-catenin signaling pathway inhibitor, while the Wnt/β-catenin signaling pathway is proposed to be involved in the development of arterial stiffness. This study aims to investigate the relationship between serum sclerostin levels and carotid–femoral pulse wave velocity (cfPWV) among hypertensive patients.MethodsFasting blood samples were obtained from 105 hypertensive patients. Patients with cfPWV values of > 10 m/s were classified in the high arterial stiffness group, whereas those with cfPWV values of ≤10 m/s were assigned to the low arterial stiffness group. Serum sclerostin and Dickkopf-1 (DKK1) levels were quantified using commercially available enzyme-linked immunosorbent assays.ResultsThirty-six hypertensive patients (34.3%) who belonged to the high arterial stiffness group were generally older (p < 0.001), presented with lower estimated glomerular filtration rates (eGFR, p = 0.014), higher incidence of diabetes mellitus (p = 0.030), average systolic blood pressures (SBP, p = 0.013), pulse pressure (p = 0.026), serum creatinine levels (p = 0.013), intact parathyroid hormone levels (iPTH, p = 0.003), and sclerostin levels (p < 0.001) than their counterparts in the low arterial stiffness group. A multivariable logistic regression analysis identified sclerostin as an independent predictor of arterial stiffness in hypertensive patients (odds ratio, 1.042; 95% confidence interval (CI), 1.017–1.068; p = 0.001). Multivariable forward stepwise linear regression analysis also showed that serum sclerostin level (β = 0.255, adjusted R2 change: 0.146, p = 0.003) was positively associated with cfPWV values in patients with hypertension.ConclusionsIn this study, serum sclerostin level, but not DKK1, is found to be positively correlated with cfPWV values and is identified as an independent predictor of arterial stiffness in hypertensive patients after adjusting for significant confounders.

Higher Plasma Sclerostin and Lower Wnt Signaling Gene Expression in White Adipose Tissue of Prediabetic South Asian Men Compared with White Caucasian Men

“…Whether these higher sclerostin levels are due to increased production by osteocytes or decreased renal or hepatic elimination, is unknown. Of note, as sclerostin is suggested to be involved in arterial stiffness and vascular calcifications [23,24], we critically looked at the plasma sclerostin values of the three South Asian participants with well-controlled hypertension, but these were well within the range of the study population. Interestingly, previous studies showed that circulating sclerostin levels are higher in individuals with prediabetes and diabetes compared with normoglycemic individuals, and that sclerostin levels positively correlate with HbA1c and HOMA-IR [13,[25][26][27][28][29], albeit we could not reproduce this in our study.…”

Serum Sclerostin Is Associated with Peripheral and Central Systolic Blood Pressure in Pediatric Patients with Primary Hypertension

“…The same authors revealed a negative relationship between augmentation index and sclerostin concentration in 67 healthy adults [15]. However, one should not forget that some authors have shown a positive relationship between the concentration of circulating sclerostin and cIMT and arterial stiffness in adults [12,20,33]. The latter may indicate the complexity of the interaction between the Wnt/beta-catenin system and arterial wall.…”

“…The exclusion criteria were: secondary forms of hypertension, the coexistence of known bone pathology, abnormalities in biochemical parameters of calcium-phosphate metabolism, diabetes mellitus, chronic inflammatory disease, or acute infectious disease. Based on available literature on sclerostin, assuming a delta of 4.5 (effect size: 0.50), a 0.05 alpha level, and 80% power, we estimated the sample size at 60 patients [13,14,16,[18][19][20]; 20 age-and sex-matched healthy subjects were included in the control group. In the statistical analysis, the control group was smaller than the study group due to the comparable variance of key parameters in both groups.…”

Serum Osteoprotegerin and Carotid Intima-Media Thickness Are Related to High Arterial Stiffness in Heart Failure with Reduced Ejection Fraction

“…However, the exact relationship of sclerostin and vascular calcification is yet to be established since some publications state a negative [ 51 ], while others no correlation [ 52 ] or a positive correlation between the two [ 53 ]. In the study of Chang et al, which was performed on 105 hypertensive patients, serum sclerostin proved to be an independent predictor of AS in a model containing age, intact parathyroid hormone levels, systolic blood pressure, diabetes, and GFR [ 54 ]. Sclerostin was different in the low and high AS groups, and the cfPWV values were similar to those measured in our study in both groups.…”