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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.

The long interdialytic interval in thrice-weekly hemodialysis is associated with excess cardiovascular risk. However, the mechanisms behind these adverse consequences are not fully understood. This study investigated the interdialytic changes in right and left ventricular function during the 2- and 3-day intervals.Observational study with 2 random crossover sequences of recordings: 3-day followed by 2-day interval or vice versa.41 stable patients with end-stage renal disease on standard thrice-weekly hemodialysis therapy.3-day (long) versus 2-day (short) interdialytic interval.Interdialytic change in echocardiographic indexes of left and right ventricular function.2-dimensional echocardiographic and tissue Doppler imaging studies were performed with a Vivid 7 cardiac ultrasound system at the start and end of the 3- and 2-day interdialytic intervals.During both intervals studied, elevations in cardiac output, stroke volume, left ventricular mass index, and peak early diastolic velocities of the left ventricle were evident. Interdialytic weight gain (3.0±1.7 vs 2.4±1.3 [SD] kg) and inferior vena cava diameter increase (0.54±0.3 vs 0.25±0.3) were higher during the 3-day versus the 2-day interval (P0.001). Left ventricular systolic and diastolic function indexes were generally no different between interdialytic intervals. In contrast, interdialytic increases in left and right atrial volume, right ventricular systolic pressure (RVSP; 15.3±10.2 vs 4.7±5.2mmHg; P0.001), and tricuspid regurgitation maximum velocity (0.46±0.45 vs 0.14±0.33m/s; P=0.001) were significantly greater during the 3- versus the 2-day interval. Multivariable analysis suggested that changes in interdialytic weight gain, right ventricle diastolic function, and pulmonary vascular resistance were determinants of the change in RVSP.Observational study design.Excess volume accumulation over the long interdialytic interval in hemodialysis patients results in higher left and right atrial enlargement and RVSP elevation, which clinically corresponds to pulmonary circulation overload, providing one plausible pathway for the excess mortality risk during this period.

Background/Aims: The hypothesis that dialytic modality affects arterial stiffness was never investigated. This study includes comparative evaluation of hemodiafiltration versus hemodialysis on arterial function during first and second weekly dialysis sessions. Methods: 24 patients receiving hemodiafiltration and another 24 age- and sex-matched controls receiving hemodialysis were included. Patients were evaluated before and after first and second weekly dialysis sessions. Applanation tonometry of peripheral arteries was applied to determine aortic and brachial pulse wave velocity and heart rate-adjusted augmentation index (AIx(75)). Results: Hemodiafiltration and hemodialysis reduced AIx(75), but not aortic and brachial pulse wave velocity. Intradialytic reductions in AIx(75) did not differ between hemodiafiltration and hemodialysis in first and mid-week dialysis. In multivariate linear regression, predictors of intradialytic reduction in AIx(75) were changes in body weight and central aortic systolic blood pressure, but not dialytic modality. Conclusion: This study showed that hemodiafiltration has similar effects with hemodialysis on wave reflections and stiffness.

BACKGROUND Increased arterial stiffness is a common finding and independent predictor of mortality in end-stage renal disease (ESRD) patients. A long interdialytic interval was associated with increased risk of cardiovascular death in patients receiving conventional haemodialysis (HD). This is the first study to examine the effects of a long (3-day) versus short (2-day) interdialytic period on arterial elasticity in HD patients. METHODS Seventy ESRD patients receiving standard HD three times per week were studied at the start and end of a 3-day and a 2-day interdialytic interval. At each time point, applanation tonometry of peripheral arteries was performed to assess arterial stiffness and wave reflection parameters. Aortic and brachial pulse wave velocities (PWV) were recorded as measures of arterial stiffness and augmentation index (AIx) as a measure of wave reflections. RESULTS AIx, heart-rate-adjusted AIx and augmentation pressure were significantly increased during both interdialytic intervals, whereas aortic and brachial PWVs remained unchanged. The interdialytic increases in all the three AIx parameters were significantly higher during the 3-day interval in comparison to the 2-day interval (P < 0.001 for all comparisons). In contrast, no significant differences in interdialytic changes of aortic (P = 0.355) and brachial (P = 0.319) PWVs were noted between the two intervals. Mixed linear model analysis revealed that central aortic systolic blood pressure (SBP) and body weight, but not aortic or brachial PWV, were independent determinants of the change in heart-rate-adjusted AIx throughout the study. CONCLUSIONS AIx is increased between HD sessions, whereas arterial elasticity is not. This interdialytic increase in central wave augmentation is more pronounced during the 3-day interval, suggesting a mechanism possibly involved in the elevated cardiovascular risk of HD patients at this time point.

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.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.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).RASI were found to have a smaller, although significant, renoprotective effect. There was no additional effect on kidney function when combining RASI with CCBs.

We present the case of a young patient with hypertension and unprovoked symptomatic hypokalemia. His workup uncovered secondary aldosteronism, moderate proteinuria, and, quite unusually, concurrent chronic hepatitis B. Detailed investigations, including renal angiography, renal vein sampling, and kidney biopsy, showed unilateral renin hypersecretion due to intrarenal arterial stenoses and mesangioproliferative glomerulonephritis, presumed to be secondary to hepatitis B infection. Targeted pharmacotherapy reversed all clinical manifestations, normalizing blood pressure and serum potassium level and achieving full remission of proteinuria and loss of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg), and a dramatic decrease in viral load.

Among several beneficial cardiovascular actions of statins, experimental studies have suggested that statins may also induce a mild blood pressure (BP) reduction. However, clinical data were controversial and the potential hypotensive statin effect remains uncertain. This study aimed to investigate the effect of atorvastatin on ambulatory BP in patients with mild hypertension and hypercholesterolaemia. A total of 50 patients with mild hypertension and hypercholesterolaemia participated in this double-blind, randomized, placebo-controlled study. Patients were randomized to either 10 mg atorvastatin or placebo for 26 weeks. Background antihypertensive treatment, if any, remained unchanged during follow-up. At baseline and study-end (26 weeks), ambulatory BP monitoring and blood sampling for determination of standard biochemical and safety parameters were performed in all participants. BP loads were defined as the percentage of BP measurements exceeding the hypertension threshold of 140/90 mm Hg for daytime and 125/75 mm Hg nighttime period. Atorvastatin significantly reduced 24-h systolic and diastolic BP (DBP; median (range)) as compared with placebo (-5.0 (-21.0, 4.0) vs +1.0 (-6.0, 7.0) mm Hg, P0.001 and -3.0 (-16.0, 2.0) vs +0.1 (-7, 4) mm Hg, P0.01, respectively). Reductions in systolic and DBP loads during follow-up were also evident in the atorvastatin, but not in the placebo group. BP-lowering effects of atorvastatin were consistent in both daytime and nighttime periods. This study shows a mild, but consistent throughout the 24-h period BP-lowering effect of atorvastatin in patients with mild hypertension and hypercholesterolaemia. This beneficial effect of atorvastatin on BP may represent another pathway through which this drug class provides cardiovascular risk reduction.

Systemic Sclerosis (SSc) is a multisystem connective tissue disease characterized by fibrosis of the skin and internal organs and extensive vasculopathy. We report a case of a 41 year-old white woman with a 10 year-history of limited scleroderma, who developed the rare combination of Scleroderma Renal Crisis (SRC) and Systemic Sclerosis related Pulmonary Arterial Hypertension (SScPAH) in the same time. Although the patient received the proposed antihypertensive treatment, the renal function did not recover, and she initiated on renal replacement therapy. SRC and SScPAH are two aspects of SSc vasculopathy characterized by endothelial dysfunction mediated by endothelin-1 and other vasoactive hormones. Further new studies with therapies directed towards the underlying mechanisms of SRC (i.e. endothelin-receptor antagonists), which are proven helpful in SScPAH, should take place to establish new therapeutic options and improve prognosis of these patients, for which our therapeutic armamentarium is currently poor.

Background Because of the major clinical and economic burden of diabetic nephropathy, new therapeutic tools to delay its progression are needed. Recent studies suggest that thiazolidinediones have renal benefits. We aimed to evaluate the effect of thiazolidinediones on urinary albumin and protein excretion in patients with diabetes mellitus. Study Design Systematic review and meta-analysis by searching MEDLINE/PubMed, EMBASE, and Cochrane CENTRAL databases (1991 to September 2009). Setting & Population Patients with diabetes mellitus. Selection Criteria for Studies Randomized controlled trials. Intervention Thiazolidinediones (rosiglitazone and pioglitazone) compared with placebo or other antidiabetic agents. Outcomes Weighted (WMDs) and standardized mean differences (SMDs) for changes in urine albumin or protein excretion between the thiazolidinedione and control groups. Results Of 171 originally identified articles, 15 studies (5 with rosiglitazone and 10 with pioglitazone) involving 2,860 patients were included in the analysis. In participants with baseline normo- or microalbuminuria, the WMD of proportional changes between the thiazolidinedione and control groups in urinary albumin excretion measured using time-specified collections was −64.8% (95% CI, −75.6 to −53.9) and the WMD of changes in albumin-creatinine ratio was −24.8% (95% CI, −39.6 to −10.0). Overall, in participants with normo- and microalbuminuria, thiazolidinedione treatment was associated with a significant decrease in urinary albumin excretion (SMD, −0.6 units of standard deviation [SD]; 95% CI, −0.8 to −0.4). Similarly, thiazolidinediones were associated with a significant decrease in urinary protein excretion in patients with proteinuria (SMD, −1.1 units of SD; 95% CI, −1.8 to −0.4). Limitations Significant heterogeneity across included studies in several subgroup analyses; patient-level data not available. Conclusions Treatment with thiazolidinediones significantly decreases urinary albumin and protein excretion in patients with diabetes. This finding calls for clinical trials with hard renal outcomes to elucidate the potential benefits of thiazolidinediones on diabetic nephropathy.

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+], levels and NHE-1 activity on BP in patients with hypertension and type 2 diabetes. (Less)

To investigate the effect of oral calcium (Ca(2+)) supplementation on insulin sensitivity measured by the euglycaemic hyperinsulinaemic clamp, intraplatelet cationic concentration of Ca(2+) ([Ca(2+)](i)) and the transmembrane sodium-hydrogen exchanger (NHE) activity in erythrocytes in subjects with Type 2 diabetes and hypertension.In this parallel randomized controlled single-blinded trial, 31 patients were allocated to receive either 1500 mg of Ca(2+) orally, daily (n = 15) or no treatment (n = 16) for 8 weeks. At baseline and at the end of the 8-week period insulin sensitivity, [Ca(2+)](i) and the first isoform of NHE (NHE-1) activity were measured.At the end of the study, subjects who received Ca(2+) supplementation showed higher insulin sensitivity (Delta M-value 0.32 +/- 0.5 mmol/min P0.05) and lower [Ca(2+)](i) (125.0 +/- 24.7 to 80.4 +/- 10.6 nmol/l, P0.05, mean +/- sem) and NHE-1 activity (79.5 +/- 10.0 to 52.1 +/- 6.4 mmol Na/l red cell/h, P0.05). None of the above parameters were changed in the control group. Simple regression analysis demonstrated the change in [Ca(2+)](i) significantly determined insulin sensitivity change (beta = -0.36, P0.05).Oral Ca(2+) supplementation improves insulin sensitivity in patients with Type 2 diabetes and hypertension. These changes are likely to be mediated by changes in intracellular ionic Ca(2+). NHE-1 activity was also reduced after Ca(2+) supplementation but its role in insulin sensitivity requires further investigation.

To evaluate 24-hr intraocular pressure (IOP) and blood pressure (BP) with timolol or latanoprost/timolol fixed combination (LTFC).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.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).Neither timolol or evening-dosed LTFC reduced SBP, DBP, MBP, OPP, or increased nocturnal dipping. LTFC was more effective than timolol in decreasing IOP.

BACKGROUND In contrast to previous studies, recent data questioned the ability of renin-angiotensin-aldosterone system (RAAS) blockers to delay progression of diabetic nephropathy. This study evaluated the effect of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) in patients with diabetic nephropathy. METHODS A systematic literature search of MEDLINE/PubMed and EMBASE databases was performed to identify randomized trials published up to June 2007 comparing the effects of ACEIs or ARBs with placebo and/or a regimen not including a RAAS blocker on the incidence of end-stage renal disease (ESRD), doubling of serum creatinine (DSC), or death from any cause in patients with diabetic nephropathy. Treatment effects were summarized as relative risks (RRs) using the Mantel-Haenszel fixed-effects model. RESULTS Of the 1,028 originally identified studies, 24 fulfilled the inclusion criteria (20 using ACEIs and 4 using ARBs). Use of ACEIs was associated with a trend toward reduction of ESRD incidence (RR 0.70; 95% confidence interval (CI) 0.46-1.05) and use of ARBs with significant reduction of ESRD risk (RR 0.78; 95% CI 0.67-0.91). Both drug classes were associated with reduction in the risk of DSC (RR 0.71; 95% CI 0.56-0.91 for ACEIs and RR 0.79; 95% CI 0.68-0.91 for ARBs) but none affected all-cause mortality (RR 0.96; 95% CI 0.85-1.09 for ACEIs and RR 0.99; 95% CI 0.85-1.16 for ARBs). CONCLUSION Treatment of patients with diabetic nephropathy with a RAAS blocker reduces the risks of ESRD and DSC, but does not affect all-cause mortality. These findings are added to the evidence of a renoprotective role of RAAS blockers in such patients.

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

The "pleiotropic" effects of statins have been the centre of a considerable research activity. Among the numerous experimental and clinical studies of this field, some focused on the effects of statins on blood pressure (BP), while others reported data on BP together with other parameters. Some of the animal or human studies do not show an association between statin treatment and BP changes, whereas others usually report mild but significant reductions. Among the latter, all clinical studies using ambulatory BP recordings show a significant drop in both systolic and diastolic BP in hypertensive patients. In addition, accumulating evidence has identified a number of statin actions that may be involved in BP lowering. Overall, current evidence suggests that statins can be associated with a mild beneficial effect on BP, but further research is needed to clarify the exact magnitude of this action, as well as its clinical relevance.

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.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 creatinineor = 1.6 mg/dL for men andor = 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 beta-blockers, 42 on diuretics, 187 on angiotensin-converting enzyme (ACE) inhibitors, 287 on calcium channel blockers (CCBs), and 28 on angiotensin receptor blockers (ARBs).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 (p0.05 for beta-blockers, ACE inhibitors, and CCBs; p0.001 for ARBs). In addition, hypokalemia was found to be significantly more prevalent in the group using diuretics than the other groups.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 metabolic syndrome is a cluster of disturbances such as type 2 diabetes mellitus, hypertension, central obesity, dyslipidemia, and others for which insulin resistance and compensatory hyperinsulinemia have been proposed to be the underlying disorders. Several possible mechanisms linking insulin resistance and compensatory hyperinsulinemia with hypertension have been described, such as renal sodium reabsorption enhancement, sympathetic nervous system activation, and blunted insulin-mediated vasodilation caused by endothelial dysfunction. Peroxisome proliferator-activated receptors-gamma agonists or thiazolidinediones (TZD) are a class of agents for the treatment of type 2 diabetes mellitus that act through improvement of insulin sensitivity. In parallel to their antihyperglycemic action, these drugs were found to exert beneficial effects on other components of the metabolic syndrome. For example all TZD have been shown to reduce blood pressure (BP) levels in both animal and human studies. In addition a considerable number of in vitro and in vivo studies report actions of TZD on the cardiovascular system that could explain this blood pressure-lowering effect of TZD, such as restoration of blunted endothelium-mediated vasodilation, attenuation of sympathetic overactivity, inhibition of intracellular Ca(2+) increase, and proliferation of vascular smooth muscle cells and others. This review summarizes the current evidence about these actions of TZD that could positively influence BP, representing possible mechanisms of BP amelioration.

Thiazolidinediones are antidiabetic agents that decrease insulin resistance. Emerging evidence indicates that they present beneficial effects for the vasculature beyond glycemic control. The aim of this open-label observational study was to determine the effect of the thiazolidinedione rosiglitazone on novel cardiovascular risk factors, namely, lipoprotein(a) [Lp(a)], C-reactive protein (CRP), homocysteine, and fibrinogen in patients with type 2 diabetes and hypertension. A total of 40 type 2 diabetic patients already on treatment with 15 mg of glibenclamide daily and with poorly controlled or newly diagnosed hypertension were included in the study. Twenty of them received 4 mg of rosiglitazone daily as added-on therapy, whereas the rest remained on the preexisting antidiabetic treatment for 26 weeks. At baseline and the end of the study, subjects gave blood tests for the determination of Lp(a), CRP, homocysteine, fibrinogen, serum lipids, apolipoprotein (apo) A-I, and apo B. At the end of the study, rosiglitazone treatment was associated with significant reductions in Lp(a) (10.5 [8.9-54.1] to 9.8 [8.0-42.0] mg/dL, P

Background In the 2003 European Society of Hypertension–European Society of Cardiology (ESH-ESC) guidelines, it is concluded that the major classes of antihypertensive agents are suitable for the initiation and maintenance of antihypertensive therapy. The aim of this study was to compare the cost-effectiveness of each one of the major antihypertensive agents as monotherapy in the management of mild-to-moderate hypertension in Greece, when following the 2003 ESH-ESC guidelines. Methods We performed a cost-effectiveness analysis based on numbers needed to treat. A decision analysis model was developed to compare chlorthalidone, propranolol, amlodipine, enalapril and losartan. Clinical inputs were derived from a meta-analysis and randomized controlled trials and cost data from public sources. The evaluation of the cost of managing hypertension includes the cost of drug therapy, monitoring, treating side effects, poor compliance and switching. All costs were calculated from a public insurance system perspective, in 2004 Euros. Future costs and clinical benefits were discounted at 5%. The time frame was 5 years. Extensive sensitivity analyses were also performed. Results The cost (in Euros) of uncomplicated hypertension treatment for 5 years was 485.87, 567.66, 851.44, 607.45, and 1279.88 for chlorthalidone, propranolol, amlodipine, enalapril, and losartan, respectively. The estimated total cost (in Euros) to prevent one death was 60230.71, 70369.96, 105596.72, 75301.40, and 158659.35, respectively. Conclusions In mild-to-moderate uncomplicated hypertension chlorthalidone is the most cost-effective agent. If it was the drug of choice to initiate treatment of uncomplicated hypertension, it would probably save the public insurance system organizations a great amount of expenses for benefit of the insured patients.

Background: Thiazolidinediones are antidiabetic agents that improve insulin sensitivity (IS). Accumulating data indicate that these agents provide beneficial effects beyond glycemic control, such as improvement in vascular function. The aim of this study was to determine the effect of rosiglitazone on urine albumin excretion (UAE) in patients with type 2 diabetes mellitus (DM) and hypertension. Methods: The study involved 20 subjects with type 2 DM who were already on 15 mg glibenclamide daily but were achieving poor glycemic control and who had either poorly controlled or newly diagnosed hypertension. In these patients, rosiglitazone (4 mg daily) was added to the existing therapeutic regimen for 26 weeks. At baseline and the end of the treatment, subjects gave a 24-h urine collection for direct measurement of albumin and a spot specimen for determination of the albumin-to-creatinine ratio (ACR). Subjects also had a hyperinsulinemic euglycemic clamp and an ambulatory blood pressure (BP) monitoring. Results: At the end of the study, UAE was significantly reduced versus baseline, as measured either directly in the 24-h collection (22.4 +/- 4.6 v 13.8 +/- 3.0 mg/day, P

Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance.To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension.In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters.Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 +/- 2.6 to 41.9 +/- 3.2 micromol/min per kg per nmol/l, P0.001) and the HOMA-IR index significantly decreased (6.34 +/- 0.39 versus 4.40 +/- 0.33, P0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 +/- 1.8 versus 129.9 +/- 1.7 mmHg, P0.001 for systolic BP and 76.0 +/- 1.6 versus 71.9 +/- 1.6 mmHg, P0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = -0.78, P0.01 and r = -0.68, P0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 +/- 0.41 versus 7.55 +/- 0.31 mmol/l, P0.001), insulin (94.0 +/- 0.41 versus 79.5 +/- 5.6 pmol/l, P0.01) and HbA1c (8.15 +/- 0.24 versus 7.24 +/- 0.19%, P0.001).Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.

Diabetic nephropathy is the most serious problem among current issues in nephrology, as 40% of the cases of end-stage renal disease are due to this entity. The close relationship between type 2 diabetes and hypertension makes the problem even more severe. The knowledge of the intrarenal effects of angiotensin II and the greater effect of angiotensin converting enzyme inhibitors (ACEI) on reducing albuminuria suggested in the past a trend toward preferable use of these drugs in diabetic nephropathy. The first relevant clinical trials yielded rather poor conclusions because of lack of blind randomization and short duration. Subsequent double-blind studies with adequate numbers of patients and sufficient duration underlined the importance of blood pressure (BP) control as well as the rather poor response of diabetic nephropathy to any treatment. In most of these studies, the changes in albuminuria or microalbuminuria were a substitute end point for the renal function. Three clinical trials using angiotensin II receptor blockers (ARB), planned specifically to monitor the progression of renal damage, have been recently published. They showed better renal protection by ARB, as compared with placebo or calcium channel blockers (CCB), beyond or independently of the BP reduction. Nevertheless, these recent trials, like the previous ones with similar results, invariably demonstrate slightly better control of BP in the groups of the active drug. Another issue is that the vast majority of the patients need so many nonstudy drugs to keep their pressure under control, that the isolation of advantageous effects of certain drugs seems unrealistic.

Wave reflections and arterial stiffness are independent cardiovascular risk factors in ESRD. Previous studies in this population included only static recordings before and after dialysis. This study investigated the variation of these indices during intra- and interdialytic intervals and examined demographic, clinical, and hemodynamic variables related to arterial function in patients undergoing hemodialysis.Between February 2013 and May 2014, a total of 153 patients receiving maintenance hemodialysis in five dialysis centers of northern Greece underwent ambulatory BP monitoring with the newly introduced Mobil-O-Graph device (IEM, Stolberg, Germany) over a midweek dialysis session and the subsequent interdialytic period. Mobil-O-Graph is an oscillometric device that records brachial BP and pulse waves and estimates, via generalized transfer function, aortic BP, augmentation index (AIx) as a measure of wave reflections, and pulse wave velocity (PWV) as an index of arterial stiffness.AIx was lower during dialysis than in the interdialytic period of dialysis-on day (Day 1) (mean±SD, 24.7%±9.7% versus 26.8%±9.4%; P0.001). In contrast, PWV remained unchanged between these intervals (9.31±2.2 versus 9.29±2.3 m/sec; P=0.60). Both AIx and PWV increased during dialysis-off day (Day 2) versus the out-of-dialysis period of Day 1 (28.8%±9.8% versus 26.8%±9.4% [P0.001] and 9.39±2.3 versus 9.29±2.3 m/sec [P0.001]). Older age (odds ratio [OR], 1.09; 95% confidence interval [95% CI], 1.02 to 1.15), female sex (OR, 7.56; 95% CI, 1.64 to 34.81), diabetic status (OR, 8.84; 95% CI, 1.76 to 17.48), and higher mean BP (OR, 1.17; 95% CI, 1.09 to 1.27) were associated with higher odds of high AIx; higher heart rate was associated with lower odds (OR, 0.71; 95% CI, 0.63 to 0.80) of high AIx. Older age (OR, 2.04; 95% CI, 1.61 to 2.58) and higher mean BP (OR, 1.15; 95% CI, 1.05 to 1.27) were independent correlates of high PWV.This study showed a gradual interdialytic increase in AIx, whereas PWV was only slightly elevated during Day 2. Future studies are needed to elucidate the value of these ambulatory measures for cardiovascular risk prediction in ESRD.

Background/Aims: Elevated wave reflections and arterial stiffness, as well as ambulatory blood pressure (BP) are independent predictors of cardiovascular risk in end-stage-renal-disease. This study is the first to evaluate in hemodialysis patients the validity of a new ambulatory oscillometric device (Mobil-O-Graph, IEM, Germany), which estimates aortic BP, augmentation index (AIx) and pulse wave velocity (PWV). Methods: Aortic SBP (aSBP), heart rate-adjusted AIx (AIx(75)) and PWV measured with Mobil-O-Graph were compared with the values from the most widely used tonometric device (Sphygmocor, ArtCor, Australia) in 73 hemodialysis patients. Measurements were made in a randomized order after 10 min of rest in the supine position at least 30 min before a dialysis session. Brachial BP (mercury sphygmomanometer) was used for the calibration of Sphygmocor's waveform. Results: Sphygmocor-derived aSBP and AIx(75) did not differ from the relevant Mobil-O-Graph measurements (aSBP: 136.3 ± 19.6 vs. 133.5 ± 19.3 mm Hg, p = 0.068; AIx(75): 28.4 ± 9.3 vs. 30.0 ± 11.8%, p = 0.229). The small difference in aSBP is perhaps explained by a relevant difference in brachial SBP used for calibration (146.9 ± 20.4 vs. 145.2 ± 19.9 mm Hg, p = 0.341). Sphygmocor PWV was higher than Mobil-O-Graph PWV (10.3 ± 3.4 vs. 9.5 ± 2.1 m/s, p < 0.01). All 3 parameters estimated by Mobil-O-Graph showed highly significant (p < 0.001) correlations with the relevant measurements of Sphygmocor (aSBP, r = 0.770; AIx(75), r = 0.400; PWV, r = 0.739). The Bland-Altman Plots for aSBP and AIx(75) showed acceptable agreement between the two devices and no evidence of systemic bias for PWV. Conclusion: As in other populations, acceptable agreement between Mobil-O-Graph and Sphygmocor was evident for aSBP and AIx(75) in hemodialysis patients; PWV was slightly underestimated by Mobil-O-Graph.

The ASCEND study was a large, international trial that aimed to assess the effects of avosentan on diabetic nephropathy. To the disappointment of the nephrology community who had anticipated that the trial would demonstrate beneficial effects of this treatment, ASCEND was terminated early owing to excessive rates of adverse events, such as congestive heart failure associated with avosentan use.

The purpose of this study was to reveal the unique sound characteristics of the bruit produced by arteriovenous fistulae (AVF), using a computerized method. An electronic stethoscope (20 Hz to 20 000 Hz sensitivity) was used, connected to a portable laptop computer. Forty prevalent hemodialysis patients participated in the study. All measurements were made with patients resting in supine position, prior to the initiation of mid-week dialysis session. Standard color Doppler technique was used to estimate blood flow. Clinical examination revealed the surface where the perceived bruit was more intense, and the recording took place at a sample rate of 22 000 Hz in WAV lossless format. Fast Fourier Transform (FFT) mathematical algorithm, was used for the sound analysis. This algorithm is particularly useful in revealing the periodicity of sound data as well as in mapping its frequency behavior and its strength. Produced frequencies were divided into 40 frequency intervals, 250 Hz apart, so that the results would be easier to plot and comprehend. The mean age of the patients was 63.5 ± 14 years; the median time on dialysis was 39.6 months (mean 1 month, max. 200 months). The mean blood flow was 857.7 ± 448.3 ml/min. The mean sound frequency was approximately 5 500 Hz ± 4 000 Hz and the median, which is also expressing the major peak of sound data, was 750 Hz, varying from 250 Hz to 10 000 Hz. A possible limitation of the study is the relatively small number of participants.

Prospective observational studies have shown that arterial stiffness is a strong and independent predictor of cardiovascular disease in hemodialysis patients. Recent evidence further supports that arterial hardening predicts cardiovascular and all-cause mortality in peritoneal dialysis patients, renal transplant recipients and patients with chronic kidney disease (CKD) not on dialysis. Of note, dissociation of arterial stiffness with blood pressure reduction were related to worsened cardiovascular outcome in kidney disease patients, suggesting that arterial stiffness may not only be a predictor, but also a true risk factor, representing a specific and potentially reversible pattern of outward arterial remodeling in these individuals. On this basis, arterial stiffness has emerged as a novel therapeutic target for cardiovascular risk reduction in patients with CKD; specific interventions, such as renin-angiotensin-system blockade, use of statins, and decrease of calcium- phosphate product may delay the progression of arteriosclerotic process. This article summarizes the accumulated evidence from clinical and epidemiological studies regarding the prognostic significance of arterial stiffening on cardiovascular outcomes and provides insights on possible treatment strategies for arterial stiffness attenuation in patients with CKD.

Experimental and clinical data suggest that statins exert anti-inflammatory and antiproliferative actions on vasculature beyond their lipid-lowering properties. Whether these pleiotropic effects of statins translate into a beneficial effect on arterial stiffness is not clear. This study aimed to evaluate the potential effects of low-dose atorvastatin treatment on arterial stiffness and central arterial pressure waveforms in patients with mild hypertension and hypercholesterolemia.In a double-blind, randomized, placebo-controlled fashion, 50 hypertensive and hypercholesterolemic patients were allocated to receive 10 mg of atorvastatin or placebo for 26 weeks. Arterial stiffness was assessed by aortic pulse-wave velocity (PWV) using a Sphygmocor device. Central arterial pressure waveform parameters were estimated by radial artery applanation tonometry. Heart rate-adjusted augmentation index (AIx(75)) was used as measure of wave reflections.At study end, aortic PWV (9.0 ± 1.5 vs. 10.9 ± 2.6 m/sec; P0.001) and AIx(75) (24.9% ± 9.7% vs 28.8% ± 11.8%; P0.001) were significantly lower in the atorvastatin group than that placebo group. Furthermore, decreases in central aortic systolic blood pressure and pulse pressure were evident at study-end with atorvastatin but not with placebo (130 ± 8 vs. 138 ± 6 mm Hg, P0.001; 48 ± 7 vs. 53 ± 6 mm Hg, P0.05, respectively). Atorvastatin-induced reductions in aortic PWV during follow-up showed significant associations with changes in AIx(75) and central aortic systolic blood pressure and pulse pressure.This study shows that low-dose atorvastatin treatment improves arterial stiffness and exerts a reduction on central aortic pressures. These effects may represent a potential mechanism of cardiovascular risk reduction observed with statin use.ClinicalTrials.gov Database Identifier Number: NCT01126684.

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.

Diabetes mellitus is an established risk factor for cardiovascular disease and the leading cause of end-stage renal disease in the Western World. Thiazolidinediones (TZDs) represent a class of antidiabetic agents that exert their glucose-lowering effects by reducing insulin resistance, through stimulation of a type of nuclear receptor, called peroxisome proliferator-activated receptor-γ. Apart from improving glycemic control, TZDs were shown to exert beneficial effects on several components of the metabolic syndrome and cardiovascular risk markers. Furthermore, background and human studies have shown that TZDs reduce urinary albumin and protein excretion and interfere with most of the pathogenentic pathways involved in the development and progression of diabetic nephropathy. On the other hand, currently used TZDs have side effects, most important of which is fluid retention leading to wait gain and heart failure deterioration. With regards to cardiovascular outcomes, the anticipated benefit of TZDs was demonstrated for pioglitazone, whereas a series of previous meta-analyses linking rosiglitazone treatment with increased risk of myocardial infarction and cardiovascular death raised uncertainty around the cardiovascular safety of rosiglitazone. This article will discuss the effects of TZDs on established and emerging cardiovascular risk factors, the data on possible beneficial renal effects of these compounds, and the existing evidence from large-scale clinical trials and meta-analyses on their effects on cardiovascular outcomes, aiming to provide an overview of the cardio- and renoprotective properties of these drugs.

The aim of this study is to assess the effect of hospital admission on 24-h ambulatory blood pressure (ABP) in hypertensive subjects. Treated or untreated hypertensive adults with open-angle glaucoma underwent inpatient and outpatient 24-h ABP monitoring in a random order 4 weeks apart. Awake ambulatory hours, awake in-bed hours and sleep hours were reported by participants. The nighttime-to-daytime ABP dip (%) and the sleeping-to-awake dip (ambulatory and in-bed) were determined using the two ABP recordings. A total of 40 subjects were analyzed (mean age 65.7 ± 8.4 (s.d.) years, n=19 men). Daytime systolic BP (SBP) was lower in the hospital than in the outpatient setting (mean difference 4.3 ± 10.4 mm Hg, P=0.01), as was the awake ambulatory SBP (mean difference 5.0 ± 11.1 mm Hg, P=0.008). No differences were detected in 24 h, nighttime or sleeping SBP or in any of the respective diastolic outpatient vs. inpatient ABP measurements. The nighttime SBP dip (vs. daytime) was larger in the outpatient setting (8.9 ± 7.5% and 5.2 ± 4.7%, respectively; P=0.003). Sleeping SBP dip (vs. awake ambulatory and awake in-bed) was also larger in the outpatient setting (11.1 ± 7.3 and 7.8 ± 5.9%, respectively; P=0.02) with no difference in diastolic ABP. These data suggest that inpatient 24-h ABP monitoring does not reflect the usual BP level during routine daily life, nor does it represent the usual diurnal pattern of an individual. Relying on the 24-h ABP monitoring performed in the hospital environment may lead to an underestimation of ABP and an overdiagnosis of non-dippers. Therefore, 24-h ABP monitoring for decision making regarding diagnosis and treatment of hypertension should be performed only in the routine daily conditions of each individual.

Epidemiological studies have associated low dietary Mg2+ intake with insulin resistance (IR) and increased risk for metabolic syndrome; however, the effect of Mg2+ supplementation on IR has not been adequately investigated. This study aimed to investigate the effects of oral Mg2+ supplementation on insulin sensitivity (IS) and serum lipids.br /Forty-eight patients with mild uncomplicated hypertension participated in the study. Among them, 24 subjects were assigned to 600 mg of pidolate Mg2+ 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, blood sampling for determination of fasting glucose and insulin levels, serum lipids and other standard laboratory tests, as well as an oral glucose tolerance test (OGTT) for estimation of IS indices, were performed in all subjects.br /In the Mg2+ supplementation group the OGTT-derived IS indices of Stumvoll, Matsuda and Cedercholm in were increased between baseline baseline and study-end. In contrast, none of these parameters were changed in the control group. Reductions in total cholesterol, LDL-cholesterol and triglyceride levels, along with a parallel increase in HDL-cholesterol levels, were evident at study-end in the intervention group, but not in the control group.br /This study suggests that oral Mg2+ supplementation improves IS and lipid profile in mildly hypertensive patients. These potential beneficial effects of Mg2+ on associated metabolic factors could be helpful for patients with hypertension in terms of overall cardiovascular risk reduction.

As with all potent therapeutic agents, the use of diuretic compounds has been linked with several adverse effects that may reduce quality of life and patient compliance and, in some cases, may be associated with considerable morbidity and mortality. Among the various types of adverse effects, disturbances of electrolyte and acid-base balance are perhaps the most common, and some of them are the aetiological factors of other side effects (i.e., hypokalaemia causing ventricular arrhythmias or glucose intolerance). The mechanism and site of action and, therefore, the pharmacological effects of each diuretic class largely determine the specific electrolyte or acid-base abnormalities that will accompany the use of each diuretic agent.This article reviews the major electrolyte disturbances (hypokalaemia, hyperkalaemia, hyponatraemia, disorders of magnesium and calcium balance), as well as the acid-base abnormalities complicating the use of the various diuretic agents.The reader will gain insights into the pathogenesis of the diuretic-induced electrolyte and acid-base disorders together with considerations for their prevention and treatment.Knowledge of the pharmacologic properties of each diuretic class and appropriate monitoring of patients under diuretic treatment represent the most important strategies to prevent the development of diuretic-related adverse events and their consequences.

Diuretics are among the most important drugs of our therapeutic armamentarium and have been broadly used for50 years, providing important help towards the treatment of several diseases. Although all diuretics act primarily by impairing sodium reabsorption in the renal tubules, they differ in their mechanism and site of action and, therefore, in their specific pharmacological properties and clinical indications. Loop diuretics are mainly used for oedematous disorders (i.e., cardiac failure, nephrotic syndrome) and for blood pressure and volume control in renal disease; thiazides and related agents are among the most prescribed drugs for hypertension treatment; aldosterone-blockers are traditionally used for primary or secondary aldosteronism; and other diuretic classes have more specific indications.This article discusses the mechanisms of action, pharmacological effects and clinical indications of the various diuretic classes used in everyday clinical practice, with emphasis on recent knowledge suggesting beneficial effects of certain diuretics on clinical conditions distinct from the traditional indications of these drugs (i.e., heart protection for aldosterone blockers).Reader will gain insights into the effective use of diuretic agents for various medical conditions, representing their established or emerging therapeutic indications.Knowledge of the pharmacologic properties and mechanisms of action of diuretic agents is a prerequisite for the successful choice and effective clinical use of these compounds.

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.

Recent population studies suggest that insulin resistance and hyperinsulinemia, as well as the presence of the cardiometabolic syndrome, are associated with increased risk of chronic kidney disease. A considerable number of background studies support this association, proposing several mechanisms through which insulin resistance and hyperinsulinemia can harm the normal kidney. Current knowledge suggests that activation of the endothelin system can be an important factor contributing to the development of renal injury. Moreover, data from in vitro and in vivo studies have clearly shown that hyperinsulinemia stimulates the production and action of endothelin-1, an effect that is sustained in insulin-resistant states. Thus, insulin-mediated activation of the endothelin system can be another important pathway linking insulin resistance with kidney injury. This article discusses the existing data on the interactions between insulin resistance, hyperinsulinemia, and endothelin and how these can lead to renal damage in patients with the cardiometabolic syndrome.

We examined the effect of familial burden of hypertension on blood pressure (BP) levels, insulin resistance (IR), and intracellular ions in healthy offspring of Greek families with one, two, or no hypertensive parents. A total of 118 adolescents and young adults were recruited. Three groups were formed: Group A, both parents were normotensive (N-N); Group B, one parent normotensive and one hypertensive (N-H); and Group C, both parents hypertensive (H-H). BP levels, homeostasis assessment model-IR (HOMA-IR) index, and intracellular Na(+), K(+), Ca(2+), and Mg(2+) were compared in the three groups. Also, multiple regression analyses were used to create models with BP parameters and HOMA-IR as dependent variables. Offspring of H-H parents had higher body mass index (BMI) (mean difference, 4.3 +/- 0.9 kg/m(2); 95% confidence interval [CI], 2.0-6.5), higher systolic blood pressure (SBP) (mean difference, 13.2 +/- 3.1 mm Hg; 95% CI, 5.8-20.7), increased levels of intraerythrocyte Ca(2+) (mean difference, 0.02 +/- 0.01 mmol/l; 95% CI, 0.05-0.1), and fasting blood glucose (mean difference, 0.31 +/- 0.10 mmol/l; 95% CI, 0.05-0.56) when compared with those with no parental history of hypertension. In the regression model, SBP was found to be significantly affected by BMI (beta = 0.43; P < .001), iK(+) (beta = -0.224; P < .01), and gender (beta = -0.298; P < .001). The addition of the parental history showed a significant independent association of H-H parental history with SBP (beta = 0.27; P < .05). HOMA-IR was significantly determined by BMI (beta = 0.511; P < .05), iNa(+) (beta = 0.211; P < .05), and iMg(2+) (beta = -0.205; P < .05). Parental history of hypertension did not influence the HOMA-IR index. This study highlights the relative importance and contribution of environmental and genetic influences on the development of high BP. Both these influences possibly alter the intracellular ionic environment. However, nurture rather than familial hypertension burden is the key factor of IR in Greek offspring.

Cardiovascular morbidity and mortality in patients with type 2 diabetes are a major problem in clinical practice. Thiazolidinediones (TZDs) are agonists of the peroxisome proliferator-activated receptor gamma which improve glycaemic control by reducing insulin resistance. TZDs also seem to have beneficial effects on various cardiovascular risk factors and consequently may have the potential to reduce the risk of cardiovascular disease (CVD). Although the first large-scale clinical trial evaluating the effect of a TZD on secondary prevention of major adverse cardiovascular outcomes supported this hypothesis, a recently published meta-analysis raised substantial uncertainty about the cardiovascular safety of rosiglitazone. This article summarises the evidence from completed and ongoing outcome trials with TZDs, as well as the recent meta-analytic data on their cardiovascular safety, aiming to provide an up-to-date and balanced view of a very important field. Data from clinical trials consistently indicate that treatment with glitazones significantly increase the risk of heart failure. Despite the fact that rosiglitazone and pioglitazone have much more similarities than differences with regards to their effects on cardiovascular risk factors, pioglitazone seems to have more favourable effects on major cardiovascular outcomes. This issue also highlights the potential hazards involved in using surrogate end-points for drug approval.

The aim of this study was to estimate the cost-effectiveness of renin-angiotensin-aldosterone system blockers in patients with diabetic nephropathy. A cost-effectiveness analysis was performed based on a meta-analysis of studies investigating the effect of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) as part of a treatment regimen on the incidence of end-stage renal disease (ESRD) in patients with diabetic nephropathy. The primary outcome was the cost to prevent 1 patient from developing ESRD. Cost analysis was performed from a third-party payer perspective in 2006 US dollars. As part of a treatment regimen, ARBs significantly reduced the incidence of ESRD and doubling of serum creatinine concentration (P

In addition to the lipid-lowering effects of statins, several basic and clinical studies in recent years have examined the effects of these agents on other cardiovascular parameters. Some of these studies investigated the general impact of a statin on blood pressure (BP) among various other factors, while others were specifically designed to determine this effect. Data from animal studies are conflicting but the majority of human studies in the field report a beneficial effect, and most available statin compounds are reported to lower BP levels. Recent clinical studies using ambulatory BP measurements support these findings. Although the exact actions of statins involved in this effect are unknown, several possible mechanisms can be hypothesized. This review summarizes existing data on the effect of statins on BP, aiming to give an overview of the current knowledge and to provide perspectives for future research in the field.

The objective of this study was to examine the prevalence and the levels of awareness, control, and treatment of hypertension in workers, technicians and clerks of factories of the city of Naoussa. A total of 1976 employees in 19 units were examined. From those, 1937 (1045 men and 892 women), 15-73 years of age, were included in the analysis. Every employee was examined twice with 1 week's interval between the two examinations. Analysis was performed using the 140/90 mmHg hypertension threshold. In every visit, three blood pressure (BP) measurements were taken with at least 1-min interval between them. In the analysis only the average BP of the second clinic visit was used. In total, hypertension prevalence was 30.5% (32.1% for men and 28.7% for women respectively, P=0.10). The levels of awareness, treatment, and control of hypertension in hypertensive patients were 18.6%, 11.8%, and 2.2%, respectively. The levels of awareness and treatment differed significantly between men and women (13.4 vs 25.4%, P0.001 and 9.6 vs 14.8%, P0.05), but there was no difference in the levels of control (1.5 vs 3.1%, P=0.18). Hypertension prevalence, awareness, and treatment differed also between patients45 andor =45 years of age (22.0 vs 53.2%, P0.001, 9.7 vs 28.4%, P0.001 and 6.5 vs 17.7%, P0.001, respectively). In conclusion, the prevalence of hypertension in our study's population is high, while the levels of awareness, treatment, and control are disappointing and should be significantly improved. There is also a difference in awareness and treatment in favour of women compared to men and in favour of patients/=45 years of age compared to those45 years of age.