Maria Pikilidou

Oral Magnesium Supplementation Reduces Ambulatory Blood Pressure in Patients With Mild Hypertension

BACKGROUND Accumulating evidence implicates a role of Mg(2+) in the pathophysiology of essential hypertension. Previous studies evaluating the antihypertensive efficacy of Mg(2+) supplementation gave contradictory results. This study aimed to investigate the effect of oral Mg(2+) supplementation on 24-h blood pressure (BP) and intracellular ion status in patients with mild hypertension. METHODS A total of 48 patients with mild uncomplicated hypertension participated in the study. Among them, 24 subjects were assigned to 600 mg of pidolate Mg(2+) daily in addition to lifestyle recommendations for a 12-week period and another 24 age- and sex-matched controls were only given lifestyle recommendations. At baseline and study-end (12 weeks) ambulatory BP monitoring, determination of serum and intracellular ion levels, and 24-h urinary collections for determination of urinary Mg(2+) were performed in all study subjects. RESULTS In the Mg(2+) supplementation group, small but significant reductions in mean 24-h systolic and diastolic BP levels were observed, in contrast to control group (-5.6 +/- 2.7 vs. -1.3 +/- 2.4 mm Hg, P < 0.001 and -2.8 +/- 1.8 vs. -1 +/- 1.2 mm Hg, P = 0.002, respectively). These effects of Mg(2+) supplementation were consistent in both daytime and night-time periods. Serum Mg(2+) levels and urinary Mg(2+) excretion were significantly increased in the intervention group. Intracellular Mg(2+) and K(+) levels were also increased, while intracellular Ca(2+) and Na(+) levels were decreased in the intervention group. None of the intracellular ions were significantly changed in the control group. CONCLUSION This study suggests that oral Mg(2+) supplementation is associated with small but consistent ambulatory BP reduction in patients with mild hypertension.

Insulin sensitivity increase after calcium supplementation and change in intraplatelet calcium and sodium-hydrogen exchange in hypertensive patients with Type 2 diabetes

Aims/hypothesis  To investigate the effect of oral calcium (Ca2+) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca2+ ([Ca2+]i) and the transmembrane sodium–hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension.

24-Hour Intraocular Pressure and Blood Pressure Levels with Latanoprost/Timolol Fixed Combination Versus Timolol

Purpose: To evaluate 24-hr intraocular pressure (IOP) and blood pressure (BP) with timolol or latanoprost/timolol fixed combination (LTFC). Methods: Patients with primary open-angle glaucoma or ocular hypertension with normal blood pressure were randomized to LTFC, dosed each evening, or timolol dosed twice daily in a cross-over design for 8 weeks and the opposite medicine for 8 weeks. IOP was measured at 02:00, 06:00, 10:00, 14:00, 18:00 and 22:00 hours in the sitting position with Goldmann applanation tonometry and BP monitoring every 30 min while awake and every hour while asleep at the end of each 8-week treatment period. Results: Twenty-nine patients had a 24-hr baseline IOP of 26.3 ± 2.5 mmHg, systolic BP (SBP) of 121.4 ± 12.4 mmHg, diastolic BP (DBP) 72.9 ± 7.1 mmHg, and ocular perfusion pressure (OPP) of 33.9 ± 5.7 mmHg. No statistical differences were found between untreated and treated 24-hr SBP, DBP, mean BP (MBP), heart rate, or nocturnal BP dipping status with either medication. LTFC lowered IOP more at each timepoint compared to timolol (difference between treatments 2.7 mmHg, p = 0.0002). Conclusions: Neither timolol or evening-dosed LTFC reduced SBP, DBP, MBP, OPP, or increased nocturnal dipping. LTFC was more effective than timolol in decreasing IOP.

Blood Pressure Reduction and Secondary Stroke Prevention: A Systematic Review and Metaregression Analysis of Randomized Clinical Trials.

Current recommendations do not specifically address the optimal blood pressure (BP) reduction for secondary stroke prevention in patients with previous cerebrovascular events. We conducted a systematic review and metaregression analysis on the association of BP reduction with recurrent stroke and cardiovascular events using data from randomized controlled clinical trials of secondary stroke prevention. For all reported events during each eligible study period, we calculated the corresponding risk ratios to express the comparison of event occurrence risk between patients randomized to antihypertensive treatment and those randomized to placebo. On the basis of the reported BP values, we performed univariate metaregression analyses according to the achieved BP values under the random-effects model (Method of Moments) for those adverse events reported in ≥10 total subgroups of included randomized controlled clinical trials. In pairwise meta-analyses, antihypertensive treatment lowered the risk for recurrent stroke (risk ratio, 0.73; 95% confidence interval, 0.62–0.87; P<0.001), disabling or fatal stroke (risk ratio, 0.71; 95% confidence interval, 0.59–0.85; P<0.001), and cardiovascular death (risk ratio, 0.85; 95% confidence interval, 0.75–0.96; P=0.01). In metaregression analyses, systolic BP reduction was linearly related to the lower risk of recurrent stroke (P=0.049), myocardial infarction (P=0.024), death from any cause (P=0.001), and cardiovascular death (P<0.001). Similarly, diastolic BP reduction was linearly related to a lower risk of recurrent stroke (P=0.026) and all-cause mortality (P=0.009). Funnel plot inspection and Egger statistical test revealed no evidence of publication bias. The extent of BP reduction is linearly associated with the magnitude of risk reduction in recurrent cerebrovascular and cardiovascular events. Strict and aggressive BP control seems to be essential for effective secondary stroke prevention.

The effect of antihypertensive drugs on chronic kidney disease: a comprehensive review

Data from randomized clinical trials and epidemiological evidence identify systemic hypertension as the second most common modifiable risk factor for chronic kidney disease (CKD) progression after diabetes mellitus. CKD may progress silently over the years and early diagnosis and control of hypertension is of major importance in delaying renal function decline. Recent guidelines for the treatment of hypertension suggest the use of a variety of antihypertensive drugs in order to achieve the desired blood pressure levels. Renin–angiotensin system inhibitors have been undoubtedly studied the most and are suggested by guidelines and experts as first choice in patients with hypertension and renal injury, particularly in those with diabetes, as they have repeatedly shown to significantly reduce proteinuria. Other classes of antihypertensive drugs have been studied to a lesser extent and they have their own unique properties and effects. However, it is now common knowledge that adequate blood pressure control is the most important factor for the preservation of renal function, so every drug that effectively lowers hypertension is believed to be renoprotective. The present article will review the latest data on the role and properties of each class of antihypertensive drugs on CKD.

Blood Pressure and Serum Potassium Levels in Hypertensive Patients Receiving or Not Receiving Antihypertensive Treatment

Objective. Serum potassium has a fundamental role in blood pressure (BP) regulation, and there is evidence highlighting the importance of potassium homeostasis in hypertension. The aim of this study was to determine the relationship between serum potassium levels and office BP in untreated essential hypertensives and the effect of antihypertensive medication on serum potassium levels. Setting and Participants. In a retrospective analysis, we collected data for consecutive patients first visiting our Hypertension Clinic from 1999–2004. From this population, we first selected patients who were not taking any antihypertensive medication. Patients who had conditions that could affect potassium metabolism, such as history of arrhythmias treated with digitalis, diabetes mellitus under insulin treatment, and hypo- and hyperthyroidism, were excluded from the study. From the remaining patients, those who had impaired renal function (serum creatinine ≥1.6 mg/dL for men and ≥1.4 mg/dl for women) and patients with secondary forms of hypertension were also excluded. The final population consisted of 817 subjects. Multivariate linear regression analysis was applied, and models were created associating serum potassium with systolic BP, diastolic BP, mean BP, or pulse pressure. The population for the second part of the study consisted of patients first visiting our Hypertension Clinic who were on one antihypertensive agent. This second group included 757 patients, 218 of whom were on β-blockers, 42 on diuretics, 187 on angiotensin-converting enzyme (ACE) inhibitors, 287 on calcium channel blockers (CCBs), and 28 on angiotensin receptor blockers (ARBs). Results. After adjusting for age, gender, and body mass index, significant negative correlations were found between serum potassium levels and systolic BP (R = −0.093, p = 0.007), diastolic BP (R = −0.078, p = 0.03), mean BP (R = −0.122, p = 0.002), and pulse pressure (R = −0.071, p = 0.044). The levels of potassium were found to be significantly lower among patients receiving diuretics than those receiving one of the other four drug categories of antihypertensive (p < 0.05 for β-blockers, ACE inhibitors, and CCBs; p < 0.001 for ARBs). In addition, hypokalemia was found to be significantly more prevalent in the group using diuretics than the other groups. Conclusions. The observed reverse relation between serum potassium and BP supports a close pathophysiological connection between serum potassium and essential hypertension. Moreover, diuretic therapy is a significant cause of hypokalemia and requires systematic monitoring.

The Contribution of Osteoprogenitor Cells to Arterial Stiffness and Hypertension

Hypertension, the major cause of cardiovascular disease, is bidirectionally linked to arterial stiffness. Evidence shows that vascular calcification, either medial or intimal, induces arterial stiffening further worsening hypertension parallel to substantially increasing cardiovascular risk. The disturbance in the bone-vascular axis that leads to the increase of calcium deposition in the arterial wall may be the result of a shift in the functionality of bone marrow-derived circulating stem cells with a calcifying potential, namely osteoprogenitor cells. These cells deposit bone matrix proteins in the vascular wall that can subsequently become mineralized. The current notion is that these cells derive from diverse cell lines. The present review summarizes the current knowledge on the role of progenitor cells with a calcifying potential on arterial calcification, stiffness and hypertension.Hypertension, the major cause of cardiovascular disease, is bidirectionally linked to arterial stiffness. Evidence shows that vascular calcification, either medial or intimal, induces arterial stiffening further worsening hypertension parallel to substantially increasing cardiovascular risk. The disturbance in the bone-vascular axis that leads to the increase of calcium deposition in the arterial wall may be the result of a shift in the functionality of bone marrow-derived circulating stem cells with a calcifying potential, namely osteoprogenitor cells. These cells deposit bone matrix proteins in the vascular wall that can subsequently become mineralized. The current notion is that these cells derive from diverse cell lines. The present review summarizes the current knowledge on the role of progenitor cells with a calcifying potential on arterial calcification, stiffness and hypertension.

Bone Quality Assessment as Measured by Trabecular Bone Score in Patients With End-Stage Renal Disease on Dialysis

Patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD) exhibit osteoporosis and increased fracture risk. Dual-energy X-ray absorptiometry scan measurements and calculation of fracture risk assessment toll score underestimate fracture risk in these patients and do not estimate bone quality. Trabecular bone score (TBS) has been recently proposed as an indirect measure of bone microarchitecture. In this study, we investigated alterations of bone quality in patients with ESRD on HD, using TBS. Fifty patients with ESRD on HD, with a mean age 62 years, and 52 healthy individuals matched for age, body mass index, and gender, were enrolled. All participants had a bone mineral density (BMD) measurement by dual-energy X-ray absorptiometry scan at the lumbar spine, femoral neck, total hip, and 1/3 radius. TBS was evaluated using TBS iNsight. Serum fetuin-A and plasma fibroblast growth factor-23 (FGF-23) (C-terminal) were also measured. Patients on dialysis had significantly lower BMD values at all skeletal sites measured. Plasma FGF-23 levels significantly increased and serum fetuin-Α significantly decreased in patients on dialysis compared with controls. TBS was significantly reduced in patients on dialysis compared with controls (1.11 ± 0.16 vs 1.30 ± 0.13, p < 0.001, respectively) independently of age; BMD; duration of dialysis; and serum levels of alkaline phosphatase, 25-OH-vitamin D, parathyroid hormone, fetuin-A, or plasma FGF-23. Patients on HD who were diagnosed with an osteoporotic vertebral fracture had numerically lower TBS values, albeit without reaching statistical significance, compared with patients on dialysis without a fracture (1.044 ± 0.151 vs 1.124 ± 0.173, respectively, p = 0.079). Bone microarchitecture, as assessed by TBS, is significantly altered in ESRD on patients on HD independently of BMD values and metabolic changes that reflect chronic kidney disease-mineral and bone disorder.

Oral Calcium Supplementation Ambulatory Blood Pressure and Relation to Changes in Intracellular Ions and Sodium-Hydrogen Exchange

BACKGROUND Calcium (Ca2+) supplementation has been shown paradoxically to reduce intracellular Ca2+ and induce vascular relaxation. The aim of the study was to assess 24-h blood pressure (BP) change after Ca2+ supplementation and to investigate its relation to changes in intracellular ions and the activity of the first isoform of sodium-hydrogen exchange (NHE-1) in subjects with hypertension and type 2 diabetes. METHODS This parallel, randomized controlled, single-blinded trial, consisted of 31 patients with type 2 diabetes, and hypertension who were allocated to receive 1,500 mg of Ca2+ per day (n = 15) or no treatment (n = 16) for 8 weeks. RESULTS In the Ca2+ group a decrease of 1.7 +/- 2.7 mm Hg (mean +/- SE) P = 0.52 for mean 24-h systolic BP (SBP) and 2.1 +/- 1.5 mm Hg, P = 0.19 for mean 24-h diastolic BP (DBP) was recorded. Whereas in the control group an increase of 1.4 +/- 2.7 mm Hg, P = 0.59 for mean 24-h SBP and 1.2 +/- 2.8 mm Hg, P = 0.83 for mean 24-h DBP was observed. Intraplatelet Ca2+ decreased whereas intraplatelet magnesium (Mg2+) and erythrocyte K+ increased in the intervention group. Change in mean 24-h SBP in the pooled group correlated with both change in intraplatelet Ca2+ (r = 0.49, P < 0.05) and NHE-1 activity (r = 0.6, P < 0.001). The contribution of intraplatelet Ca2+ was attenuated when both parameters were entered in a multivariate regression model. CONCLUSIONS The present study shows a weak, statistically nonsignificant trend towards association of Ca2+ supplementation on 24-h BP in hypertensive subjects with type 2 diabetes. However, our results indicated an interrelation of [Ca2+]i levels and NHE-1 activity on BP in patients with hypertension and type 2 diabetes.

Postprandial response of bone turnover markers in patients with Crohn's disease.

AIM To investigate the postprandial response of bone turnover markers in patients with Crohns disease (CD). METHODS Fifty nine patients with CD aged 38 ± 14 years, and 45 healthy individuals matched for age and body mass index were included in the study. All participants underwent an oral glucose tolerance test (OGTT) after an overnight fast and serum levels of the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX-I) and the bone formation marker procollagen type I N propeptide were measured. Activity of the disease was assessed by calculation of the Crohns disease activity index (CDAI). RESULTS Serum CTX-I was significantly higher in patients compared to controls (CTX-I: 453 ± 21 pg/mL vs 365 ± 25 pg/mL, P = 0.008), and values were significantly correlated with the activity of the disease (r = 0.435, P = 0.001). Results from OGTT-induced suppression of CTX-I showed two different trends. Patients with more active disease (assessed as CDAI > 150) had a more excessive suppression of CTX-I compared to controls (55% vs 43% P < 0.001), while patients on remission (assessed as CDAI < 150) demonstrated an attenuated CTX-I suppression (30% vs 43% P < 0.001). In line with this, CTX-I suppression after oral glucose load was significantly correlated with the activity of the disease (r = 0.913, P < 0.001). CONCLUSION The physiological skeletal response of postprandial suppression of bone resorption is maintained in patients with CD and is strongly dependent to the activity of the disease.