Aneta Mankowska-Cyl

25-hydroxyvitamin D, biomarkers of endothelial dysfunction and subclinical organ damage in adults with hypertension.

BACKGROUND The mechanism that underlies the association between low 25-hydroxyvitamin D [25(OH)D] and hypertension is not well understood; it seems to involve regulation of the renin-angiotensin-aldosterone system and the impact on endothelial function, cardiac remodeling, and subclinical organ damage. Vitamin D supplementation presents an ambiguous effect on endothelial function and arterial stiffness. We assess serum 25(OH)D3, biomarkers of endothelial dysfunction (soluble intercellular adhesion molecule [sICAM], C-reactive protein [CRP], homocysteine [Hcy]) and subclinical organ damage in adults with newly diagnosed untreated hypertension. METHODS Patients were classified based on ambulatory blood pressure monitoring: 98 had hypertension, whereas in 60 persons BP was normal. Laboratory assays including serum 25(OH)D3, hsCRP, Hcy, sICAM, glucose, insulin, lipids, echocardiography, pulse wave velocity (PWV), intima-media thickness (IMT), and left-ventricular mass (LVM) measurements were performed. RESULTS 25(OH)D3 was significantly lower in hypertensive patients. The logistic regression analysis indicated that 25(OH)D3 reduced the probability of hypertension occurrence after adjusting for body mass index (BMI). 25(OH)D3 in those with hypertension correlated significantly with systolic BP (SBP; r = -0.39), PWV, IMT (r = -0.33), and diastolic BP (r = -0.26). Multiple regression analysis in patients with hypertension revealed that 25(OH)D3 and sICAM accounted for up to 27% of SBP variation after adjusting for age, BMI, and smoking. 25(OH)D3 and either PWV or IMT accounted for 23% of SBP variation. The impact of 25(OH)D3 was 10%. CONCLUSION The impact of 25(OH)D3 on SBP variation, mediated by its effect on endothelial dysfunction and subclinical organ damage, is modest but significant.

25(OH)D3 in patients with ovarian cancer and its correlation with survival.

OBJECTIVES The aim of this study was to examine vitamin 25(OH)D3 concentration in ovarian cancer patients in relation to a pathological subtype of the tumor, FIGO stage, grading, menopause status and overall 5-year survival. DESIGN AND METHODS 72 epithelial ovarian cancer patients aged 37-79, who undergone optimal cytoreductive surgery were enrolled to the study group. Serum 25(OH)D3 concentration was measured using an electrochemiluminescence immunoassay before surgery. Serum concentration of 25(OH)D3 was also measured in a group of 65 healthy non-obese women aged 35-65 years. RESULTS In patients with ovarian cancer serum concentration of 25(OH)D3 was lower than in the reference group (12.5±7.75 ng/mL vs 22.4±6.5 ng/mL). No significant correlation was found between serum 25(OH)D3 concentration and histological subtype, grading, FIGO stage and menopausal status. The study group was divided into two subgroups and the survival curves were analyzed. Overall 5-year survival rate was significantly higher in the subgroup of patients with 25(OH)D3 concentration over 10 ng/mL compared to women with concentration below 10 ng/mL. CONCLUSIONS Low 25(OH) D3 concentration associated with lower overall survival rate might suggest for the important role of severe deficiency in more aggressive course of ovarian cancer. Testing for 25(OH)D in the standard procedure could help to find ovarian cancer patients with worse prognosis, who would benefit of special attention and supplementation.

Serum Inhibin A and Inhibin B Levels in Epithelial Ovarian Cancer Patients

The aim of our study was to examine serum inhibin A and inhibin B concentrations in ovarian cancer patients in relation to clinicopathological features and 5-year survival. Material and Methods We enrolled 90 epithelial ovarian cancer patients in our study, aged 45–81 years, who underwent optimal cytoreductive surgery. In all patients, serum inhibin A and inhibin B concentrations were measured using a two-step sandwich type enzyme immunoassay before surgery. Results In the group of patients with ovarian cancer median serum concentration of inhibin A was 3.87 pg/mL (0.96–10.09) and inhibin B was 13.9 pg/mL (5.1–45.0). Median concentrations of inhibin A and B in relation to FIGO stage and histological subtype did not differ significantly. Inhibin A levels were significantly higher in patients with lower grading (G1 and G2) in comparison to those with higher grade G3 (p = 0.001). There were no differences in inhibin B concentrations in relation to grading. The Kaplan-Meier analyses demonstrated no differences in survival rate in relation to inhibin A levels, while there was a stepwise impairment of 5-years survival with increased inhibin B level. In the group of patients with inhibin B levels higher than 20 pg/ml the survival rate was lower (p = 0,00625, log-rank test). Conclusion 1. Higher inhibin A serum levels were found in patients with highly differentiated ovarian carcinoma compared to the group of patients with a poorly differentiated cancer, which may confirm the influence of inhibin A on cell proliferation processes. 2. A significant importance of inhibin B was demonstrated in the prediction of death within less than a five year period. The probability of survival in patients featuring high inhibin B levels was lower with statistical significance. This may indicate the need for further studies on how to block the inhibin B activation pathway in the ovarian carcinoma therapy.

A-FABP and its association with atherogenic risk profile and insulin resistance in young overweight and obese women

AIM We evaluated the association of A-FABP with proatherogenic risk profile and insulin resistance (IR) in young, nondiabetic, overweight/obese women. MATERIALS & METHODS Serum A-FABP, high-sensitivity CRP, adiponectin, glucose, insulin, lipids and apolipoproteins were measured in 104 women (aged 20-45 years; BMI ≥25 kg/m(2)) and age-matched healthy controls (n = 76; BMI <25 kg/m(2)). All patients underwent blood pressure and anthropometric measurements. RESULTS A-FABP concentration was related to IR, and anthropometric and atherogenic indices. A-FABP was an independent predictor of triglyceride:high-density lipoprotein cholesterol, explaining 42% of its variation in overweight/obese women. At a cutoff level of 16 ng/ml, A-FABP discriminated between controls and overweight/obese (area under curve = 0.96) with high sensitivity and specificity. A-FABP predicted atherogenic risk, with an odds ratio of 11.2 (95% CI: 3.7-34.2), 7.1 (1.9-27.2) and 6.7 (2.6-17.2) for having elevated triglyceride:high-density lipoprotein cholesterol, apoB and CRP, respectively, and IR with an odds ratio 5.6 (1.8-17.2). CONCLUSION A-FABP seems to be a valuable predictor of atherogenic risk profile; if elevated it contributes to cardiovascular disease beyond its effect on IR.

Serum Anti-Müllerian Hormone Levels in Patients with Epithelial Ovarian Cancer

Objectives. The aim of our study was to examine serum anti-Müllerian hormone (AMH) concentration in ovarian cancer patients in relation to clinicopathological features, such as a pathological subtype of the tumor, (FIGO) stage, grading, and overall 5-year survival. Material and Methods. We enrolled 72 epithelial ovarian cancer patients in our study, aged 45–79 years, who underwent optimal cytoreductive surgery. In all patients, serum AMH concentration was measured using a two-step sandwich type enzyme immunoassay before surgery. As a reference value for women over 45 years we accepted anti-Müllerian hormone concentration below 1 ng/mL. Results. In the whole group of patients with ovarian cancer, median serum concentration of AMH was 0.07 (0.0–0.37) ng/mL, whereas in the group of those with positive AMH values (≥0.14 ng/mL) it was 0.31 (0.15–0.73) ng/mL. No significant correlation was found between serum AMH levels and FIGO stage, histological subtype, or grading (P > 0.05). The analysis of five-year survival rate related to AMH levels showed no statistically significant differences. There were no differences in survival rates between patients with positive or negative serum AMH levels. Conclusion. Measurement of serum anti-Müllerian hormone levels was not useful in predicting clinicopathological features and survival in patients with ovarian cancer.

Amyloid β Peptides and Cognitive Functions in Patients with Pseudoexfoliation Syndrome

Abstract Purpose: The aim of this study was to evaluate if there is any relation between the Alzheimer’s peptides (amyloid β-40 and β-42) concentration in plasma and aqueous humor as well as cognitive functions with pseudoexfoliation syndrome (PEX). Methods: One-hundred forty-two patients with PEX have been included for this study; median age: 75 years (Q1 = 71,5; Q3 = 80,0). Control group comprised 93 subjects aged 74 years (Q1 = 68,0; Q3 = 80,0). Amyloid β-40 and β-42 (Aβ-40, Aβ-42) concentrations were assessed in plasma in 73 PEX patients and 49 controls. Aβ-40 concentration in aqueous humor was measured in 31 patients from each group. Mini Mental State Examination (MMSE) and Clock Drawing Tests were performed in 83 PEX patients and 36 controls. Results: The differences between amyloid concentrations both in plasma and in aqueous humor in PEX and control groups were not statistically significant. There were no differences in MMSE and Clock Drawing Tests between groups. Conclusion: Our results do not indicate any relation between PEX and Alzheimer’s amyloids or cognitive functions in cataract patients.

Lipids and C-reactive protein as vascular risk markers in pseudoexfoliation syndrome.

the right eye was entirely normal. A full-field electroretinography (ERG) following ISCEV standards was performed, showing an obvious asymmetry between the two eyes. As the responses were entirely normal on the right eye, the scotopic and photopic amplitudes were reduced by approximately 50% (if compared to the right eye) and flicker implicit time was subnormally increased in the left eye. A multifocal ERG of the left eye showed temporal abnormalities with cone-driven responses being considerably reduced with prolonged implicit times (Fig. 1D,E). Visual field test demonstrated unchanged dense temporal scotoma. The loss of retinal function correlated with the structural changes in the outer retina and the diagnosis of AZOOR was made. The diagnosis of AZOOR is not always easily established, mainly because of minimal or absent fundoscopic changes, and many times after other conditions have been ruled out. In the original series presented by Gass, affected patients typically presented with acute onset of photopsia, scotomas and abnormal ERG but minimal fundoscopic changes. The abnormal ERG is essential for the diagnosis of AZOOR. Gass et al. (2002) reported that the electroretinographic amplitude was depressed in all affected eyes. We would like to emphasize the importance of multimodal imaging, namely OCT, wide-angle FAF and ERG allowing to establish the diagnosis of AZOOR. The present case indicates that it might be challenging to make a timely diagnosis of AZOOR and that some patients may suffer from symptoms for many years. We would also like to increase awareness among ophthalmologists of how multimodal imaging and electrophysiological testing can help to avoid costly, lengthy and maybe even invasive neurological and systemic investigations in patients with AZOOR.

Response to “The Putative Role of Vitamin D in Essential Hypertension: Stepping Into the Light?”

To the Editor: In their letter, “The Putative Role of Vitamin D in Essential Hypertension: Stepping Into the Light?,” Gkaliagkousi et al. seem to question the use of traditional circulating biomarkers such as soluble intercellular adhesion molecule (sICAM), C-reactive protein (CRP), and homocysteine (Hcy) for the evaluation of endothelial dysfunction. They point out the latest position statement1 and recent European Society of Hypertension guidelines2 as a source of information on methods for the evaluation of endothelial dysfunction. It is obvious, however, that guidelines do not explicitly define which biomarkers should be used, and the position statement presents different methods for evaluating endothelial function, including the measurement of biomarkers we used,3 with the special focus on emerging biomarkers. We strongly disagree with Gkaliagkousi et al.’s criticism because we measured the circulating biomarkers that are widely and commonly used by others as determinants of endothelial dysfunction.4–6 Serum biomarkers of the endothelial origin reflect endothelial function; higher levels are thought to mirror the endothelial activation or damage.4 It has been reported that activated endothelial cells show enhanced expression and release of cell-surface adhesion molecules. sICAM-1 concentration correlates with its cell expression and was confirmed recently to be a sensitive marker of inflammatory vascular activation in hypertensive adolescents.7 Within the past 10 years the association between CRP and other inflammatory markers (including s-ICAM-1, Hcy) with prehypertension, hypertension, and arterial stiffness has been demonstrated.5 CRP is not only a biomarker of inflammation but, as recently unraveled,6 also actively and directly participates in the development of the endothelial dysfunction, which stands in stark contrast to the criticism of Dr Gkaliagkousi. Besides an array of traditional biomarkers, several modern but expensive methods may be used to assess the endothelial status: imaging methods and measurement of endothelial progenitor cells, circulating endothelial cells, and endothelial-derived microparticles (EMPs).1 Interestingly, a recent study8 demonstrated that sICAM-1 correlated significantly with EMPs measured by flow cytometry, which unequivocally substantiates its use as a surrogate marker of endothelial dysfunction. The emerging evidence suggests that blood EMPs may serve as both specific markers and contributors to pathology; however, their accurate quantification is a substantial challenge. EMPs and ECPs (endothelial progenitor cells) may be attractive biomarkers, but their measurement by multicolor flow cytometry or proteomic analysis by mass spectrometry is not widely available. Furthermore, progress in standardization of measurement of the emerging biomarkers is crucial to establish their clinical interest for the assessment of endothelial dysfunction. In the recent European Society of Hypertension guidelines, the term “BP variability” obviously refers to visit-tovisit blood pressure variability or blood pressure variability assessed by ambulatory blood pressure measurement. The mathematical definition of “variation” describes a function that relates the values of one variable to those of other variables, and in this sense we assessed variables of significance for the prediction of systolic blood pressure variation that was adjusted for possible confounders. In fact, both terms “variation” and “variability” are used interchangeably, which does not necessarily have to be correct because the R2 value explains the variability in the statistics. 25-Hydroxyvitamin D might mediate various biological effects, and it regulates physiological functions such as the expression of adhesion molecules and endothelium-dependent vasoconstriction. The endothelial dysfunction was associated with 25(OH) D deficiency; moreover, 25(OH)D deficiency was propounded to promote endothelial dysfunction. We presented potential mechanisms relating to the role of 25(OH)D and its influence on the endothelial dysfunction in hypertension. The putative causal relationships remain to be elucidated.

Chosen Vascular Risk Markers in Pseudoexfoliation Syndrome: An Age-Related Disorder

Purpose To evaluate lipids and C-reactive protein serum levels in patients with pseudoexfoliation syndrome (PEX) in the Polish population. Methods 96 patients were studied with PEX and 79 control subjects. Total cholesterol, triglycerides, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein (LDL)-cholesterol, non-HDL-cholesterol and CRP serum levels, and TG/HDL-C and TC/HDL-C indexes were assessed. Results There were no significant differences in concentration of lipids and values of TC/HDL-C, TG/HDL-C, and non-HDL-C between PEX and control groups. High-sensitivity C-reactive protein was not increased in patients with PEX. Conclusions Our results cast doubt on the opinion on the possible PEX and vascular diseases relation. Further studies on this subject are mandatory.

Gamma-glutamyltransferase activity as a surrogate biomarker of metabolic health status in young nondiabetic obese women

AIM We investigated the association of gamma-glutamyltransferase (GGT) activity with atherogenic risk factors and metabolic health status in young nondiabetic obese women. METHODS & RESULTS In 140 obese women GGT activity was independently associated with BMI, triglyceride to high-density cholesterol ratio and homeostasis model assessment. Metabolically healthy but obese women had significantly lower GGT activity, associated with a normal insulin sensitivity, favorable lipid profile and apolipoprotein B to apolipoprotein AI ratio. GGT activity showed good diagnostic accuracy to distinguish between metabolically healthy but obese and obese women at risk (77.8% sensitivity and 60% specificity). GGT activity >17 U/l can predict atherogenic risk and insulin resistance. CONCLUSION GGT activity may serve as a potential surrogate biomarker of atherogenic risk and metabolic health status.