Changes in kidney function in a population with essential hypertension in real life settings

Introduction. Hypertension has been identified as one of the commonest modifiable determinants for chronic kidney disease progression. A variety of antihypertensive drugs are available and their effect on kidney function has been investigated by a large number of randomized controlled trials. Observational studies, although scarcely been used, outpatient can reflect everyday practice, where drug exposures vary over time, and may provide an alternative for detecting longitudinal changes in kidney function. Materials and Methods. We applied mixed model repeated measures analysis to investigate the effect of antihypertensive drug categories and their combinations on kidney function change over time in a cohort of 779 patients with essential hypertension, using the data from a Greek hypertension outpatient clinic. Antihypertensive drugs were grouped in 5 categories. Their effect was evaluated and their combinations with and without renin-angiotensin-system inhibitors (RASI) to each other. In addition, the combination of RASI with calcium channel blockers (CCBs) was studied. Results. Diuretics, RASI, CCBs, and beta-blockers had a significant renoprotective and blood pressure lowering effect. Combinations with RASI had a smaller beneficial effect on kidney function compared to CCBs (0.75 mL/min/1.73 m2 per year of drug use versus 0.97 mL/min/1.73 m2). There was no additional effect when combining RASI with CCBs. However, the lowering effect on systolic blood pressure was greater (-0.83 mm Hg per year of drug use, P < .001). Conclusions. RASI were found to have a smaller, although significant, renoprotective effect. There was no additional effect on kidney function when combining RASI with CCBs

Association of antihypertensive monotherapy with serum sodium and potassium levels in Chinese patients

<b>Background</b> International guidelines on management of hypertension recommend any major classes of antihypertensive drugs. However, the low prescribing rate of thiazides has been attributed to concerns about electrolyte disturbances and studies between antihypertensive drug classes and hyponatremia/hypokalemia among Chinese patients were scarce. <p></p> <b>Methods</b> From clinical databases we included 2,759 patients who received their first-ever antihypertensive monotherapy from January 2004 to June 2007 in a large territory of Hong Kong. We studied the plasma sodium and potassium levels 8 weeks after prescriptions and factors associated with hyponatremia and hypokalemia by multivariable regression analyses. <p></p> <b>Results</b> Among major antihypertensive drug classes, thiazide users had the lowest sodium level (139.6 mEq/l, 95% confidence interval (CI) 139.3, 140.0, P < 0.001) and patients-prescribed calcium channel blockers (CCBs; 3.92 mEq/l, 95% CI 3.89, 3.95) or thiazide diuretics (3.99 mEq/l, 95% CI 3.93, 4.04) had the lowest potassium levels (P < 0.001). Multivariate analysis reported that advanced age (>/=70 years, odds ratio (OR) 7.49, 95% CI 2.84, 19.8, P < 0.001), male gender (OR 2.38, 95% CI 1.45, 3.91, P < 0.001), and thiazide users (OR 2.42, 95% CI 1.29, 4.56, P = 0.006) were significantly associated with hyponatremia, while renin-angiotensin system (RAS) (OR 0.31, 95% CI 0.13, 0.73, P = 0.008) and beta-blockers (BBs) (OR 0.35, 95% CI 0.23, 0.54, P < 0.001) users were less likely to present with hypokalemia. However, the proportions having normonatremic (95.1%) and normokalemic (89.4%) levels were high. <p></p> <b>Conclusions</b> In view of the low prevalence of hyponatremia and hypokalemia associated with thiazides, physicians should not be deterred from prescribing thiazide diuretics as first-line antihypertensive agents as recommended by most international guidelines

Anti-diabetic effect of a preparation of vitamins, minerals and trace elements in diabetic rats: a gender difference

BACKGROUND: Although multivitamin products are widely used as dietary supplements to maintain health or as special medical food in certain diseases, the effects of these products were not investigated in diabetes mellitus, a major cardiovascular risk factor. Therefore, here we investigated if a preparation of different minerals, vitamins, and trace elements (MVT) for human use affects the severity of experimental diabetes. METHODS: Two days old neonatal Wistar rats from both genders were injected with 100 mg/kg of streptozotocin or its vehicle to induce diabetes. At week 4, rats were fed with an MVT preparation or vehicle for 8 weeks. Well established diagnostic parameters of diabetes, i.e. fasting blood glucose and oral glucose tolerance test were performed at week 4, 8 and 12. Moreover, serum insulin and blood HbA1c were measured at week 12. RESULTS: An impaired glucose tolerance has been found in streptozotocin-treated rats in both genders at week 4. In males, fasting blood glucose and HbA1c were significantly increased and glucose tolerance and serum insulin was decreased at week 12 in the vehicle-treated diabetic group as compared to the vehicle-treated non-diabetic group. All of the diagnostic parameters of diabetes were significantly improved by MVT treatment in male rats. In females, streptozotocin treatment resulted in a less severe prediabetic-like phenotype as only glucose tolerance and HbA1c were altered by the end of the study in the vehicle-treated diabetic group as compared to the vehicle-treated non-diabetic group. MVT treatment failed to improve the diagnostic parameters of diabetes in female streptozotocin-treated rats. CONCLUSION: This is the first demonstration that MVT significantly attenuates the progression of diabetes in male rats with chronic experimental diabetes. Moreover, we have confirmed that females are less sensitive to STZ-induced diabetes and MVT preparation did not show protection against prediabetic state. This may suggest a gender difference in the pathogenesis of diabetes

Suppression of SIRT1 in Diabetic Conditions Induces Osteogenic Differentiation of Human Vascular Smooth Muscle Cells via RUNX2 Signalling

Vascular calcification is associated with significant morbidity and mortality within diabetes, involving activation of osteogenic regulators and transcription factors. Recent evidence demonstrates the beneficial role of Sirtuin 1 (SIRT1), an NAD+ dependant deacetylase, in improved insulin sensitivity and glucose homeostasis, linking hyperglycaemia and SIRT1 downregulation. This study aimed to determine the role of SIRT1 in vascular smooth muscle cell (vSMC) calcification within the diabetic environment. An 80% reduction in SIRT1 levels was observed in patients with diabetes, both in serum and the arterial smooth muscle layer, whilst both RUNX2 and Osteocalcin levels were elevated. Human vSMCs exposed to hyperglycaemic conditions in vitro demonstrated enhanced calcification, which was positively associated with the induction of cellular senescence, verified by senescence-associated β-galactosidase activity and cell cycle markers p16 and p21. Activation of SIRT1 by SRT1720 reduced Alizarin red staining by a third, via inhibition of the RUNX2 pathway and prevention of senescence. Conversely, inhibition of SIRT1 via Sirtinol and siRNA increased RUNX2 by over 50%. These findings demonstrate the key role that SIRT1 plays in preventing calcification in a diabetic environment, through the inhibition of RUNX2 and senescence pathways, suggesting a downregulation of SIRT1 may be responsible for perpetuating vascular calcification in diabetes

The burden of obesity on blood pressure is reduced in older persons: The SardiNIA study

Introduction: Being overweight or obese increases the risk of elevated blood pressure. However differences of their effects on blood pressure in different age groups are not clear. Objective: The aim of the present study was to evaluate differences of the effects of adiposity on the odds of having hypertension in different age groups. Design and Methods: Three thousand fifty-six subjects (1,532 women and 1,524 men) consist of the drug naive subjects from the SardiNIA study. Logistic regression models with backward elimination were used to determine and compare the association between categories of obesity on hypertension within young (â¤39), middle aged (40-59), and older (60+) subjects. Additional terms controlled for in the model were smoking and alcohol intake status. Results: The relationship of body mass index (BMI) on hypertension differed by age, as indicated by the significant interaction term of age with BMI (P <0.01). Older subjects had higher odds of having hypertension than younger subjects but these odds were lower for obese than for lean subjects (OR 10.45, 95% CIs 4.58-23.85 in obese versus OR 33.89, 95% CIs 17.94-64.02 in lean subjects). A similar trend was also observed in middle aged subjects. Conclusions: This study shows that among men and women, older age was associated with a lesser effect of BMI on the odds of having hypertension

Aggravated Dental and Periodontal Status in Patients with Sickle Cell Disease and Its Association with Serum Ferritin

Aim: The present study aimed to evaluate the possible consequences of sickle cell disease (SCD) on dental and periodontal health in middle-aged patients and to examine the association of certain cardiovascular parameters and serum ferritin with the dental and periodontal status. Materials and methods: Thirty-seven patients (mean age 43.2 years old) with SCD and 30 non-SCD and otherwise healthy individuals (mean age 38.9 years old) were examined for caries experience and periodontal status in addition to cardiovascular characteristics and ferritin level in serum. Results: Compared to controls, SCD patients exhibited higher plaque and gingival bleeding scores, higher prevalence of periodontal diseases, and higher caries experience. Multiple stepwise linear regression analysis showed that caries experience was predominantly determined by the presence of SCD and the age, while major determinants of periodontitis were the ferritin levels and the male gender. The results reveal an aggravation of oral health in SCD patients regarding both caries and periodontal diseases. Conclusion: A potential role of the increased central inflammatory response, reflected by the elevated ferritin level in serum, is suggested for the impaired periodontal health of SCD patients. Clinical significance: Compliance with precautionary dental checks and early management of dental complications is of great importance in order to improve oral health status and prevent general health complications in SCD patients. © The Author(s). 2021 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (https://creativecommons. org/licenses/by-nc/4.0/), which permits unrestricted use, distribution, and non-commercial reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated

Wave reflections and systemic vascular resistance are stronger determinants of pulse pressure amplification than aortic stiffness in drug-naïve hypertensives

Background: Aortic-to-brachial pulse pressure (PP) amplification is a novel biomarker that prognosticates the cardiovascular risk above and beyond central aortic and brachial blood pressure. This phenomenon is modulated by left ventricular contractility and chronotrophy, large-artery stiffness and reflecting properties of microcirculation. However, the relative importance of these parameters as hemodynamic determinant of PP amplification remains elusive. Methods: A total of 88 consecutive drug-naïve hypertensives underwent a non-invasive assessment of central and peripheral hemodynamics via impedance cardiography and pulse wave analysis. Participants were classified into tertiles according to the magnitude of PP amplification. Hemodynamic determinants of low PP amplification were explored in univariate and multivariate regression analysis. Results: Compared with the high tertile, patients within the low PP amplification tertile were older and more commonly female and had lower height, weight and heart rate. Augmentation index (AIx) and systemic vascular resistance index (SVRI) were higher among patients within the low PP amplification tertile, whereas aortic pulse wave velocity (PWV) did not differ among groups. In multivariate analysis, higher AIx (OR: 1.27; 95% CI: 1.09–1.48) and higher SVRI were independently associated with higher odds for low PP amplification, whereas higher heart rate was the only parameter related to lower odds for low PP amplification (OR: 0.84; 95% CI: 0.71–0.99). Conclusion: This study shows that among newly-diagnosed drug-naïve hypertensives, elevated wave reflections and systemic vascular resistance are stronger determinants of PP amplification than aortic stiffness. © 2019, © 2019 Taylor & Francis

Changes of circulating MicroRNAs in response to treatment with teriparatide or denosumab in postmenopausal osteoporosis

Context: Expression of microRNAs (miRs) related to bone metabolism in the serum may be affected by antiosteoporotic treatment. Objective: To investigate the effect of two antiosteoporotic agents with opposite effects on bone metabolism on miR expression profile in the serum. Design: Observational, open label, nonrandomized clinical trial. Setting: The outpatient clinics for Metabolic Bone Diseases of 424 General Military Hospital, Thessaloniki, Greece. Patients and Interventions: Postmenopausal women with low bone mass were treated with either teriparatide (TPTD; n = 30) or denosumab (n = 30) for 12 months. Main Outcome Measures: Changes in the serum expression of selected miRs linked to bone metabolism at 3 and 12 months of treatment. Secondary measurements: associations of measured miRs with changes in bone mineral density (BMD) at 12 months and the bone turnover markers (BTMs) C-terminal cross-linking telopeptide of type I collagen and procollagen type I N-terminal propeptide at 3 and 12 months. Results: We found significantly decreased relative expression of miR-33-3p at 3 months (P = 0.03) and of miR-133a at 12 months (P = 0.042) of TPTD treatment. BMD values at 12 months of TPTD treatment were significantly and inversely correlated with miR-124-3p expression at 3 months (P = 0.008). Relative expression of miR-24-3p and miR-27a was correlated with changes in BTMs during TPTD treatment and of miR-21-5p, miR-23a-3p, miR-26a-5p, miR-27a, miR-222-5p, and miR-335-5p with changes in BTMs during denosumab treatment. Conclusions: Circulating miRs are differentially affected by treatment with TPTD and denosumab. TPTD affects the relative expression of miRs related to the expression of RUNX-2 (miR-33) and DKK-1 gene (miR-133). Copyright © 2018 Endocrine Society

Validity and reproducibility of HOMA-IR, 1/HOMA-IR, QUICKI and McAuley's indices in patients with hypertension and type II diabetes

The aim of this study was to evaluate the validity and reliability of homeostasis model assessment-insulin resistance (HOMA-IR) index, its reciprocal (1/HOMA-IR), quantitative insulin sensitivity check index (QUICKI) and McAuley's index in hypertensive diabetic patients. In 78 patients with hypertension and type II diabetes glucose, insulin and triglyceride levels were determined after a 12-h fast to calculate these indices, and insulin sensitivity (IS) was measured with the hyperinsulinemic euglycemic clamp technique. Two weeks later, subjects had again their glucose, insulin and triglycerides measured. Simple and multiple linear regression analysis were applied to assess the validity of these indices compared to clamp IS and coefficients of variation between the two visits were estimated to assess their reproducibility. HOMA-IR index was strongly and inversely correlated with the basic IS clamp index, the M-value (r = 0.572, P < 0.001), M- value normalized with subjects' body weight or fat-free mass and every other clamp-derived index. 1/HOMA-IR and QUICKI indices were positively correlated with the M- value (r = 0.342, P < 0.05 and r = 0.456, P < 0.01, respectively) and the rest clamp indices. McAuley's index generally presented less strong correlations ( r = 0.317, P < 0.05 with M- value). In multivariate analysis, HOMA-IR was the best fit of clampderived IS. Coefficients of variation between the two visits were 23.5% for HOMA-IR, 19.2% for 1/HOMA-IR, 7.8% for QUICKI and 15.1% for McAuley's index. In conclusion, HOMA- IR, 1/HOMA-IR and QUICKI are valid estimates of clamp-derived IS in patients with hypertension and type II diabetes, whereas the validity of McAuley's index needs further evaluation. QUICKI displayed better reproducibility than the other indices