A comparison study of brachial blood pressure recorded with Spacelabs 90217A and Mobil-O-Graph NG devices under static and ambulatory conditions.

Ambulatory blood pressure monitoring is an important tool in hypertension diagnosis and management. Although several ambulatory devices exist, comparative studies are scarce. This study aimed to compare for the first time brachial blood pressure levels of Spacelabs 90217A and Mobil-O-Graph NG, under static and ambulatory conditions. We examined 40 healthy individuals under static (study A) and ambulatory (study B) conditions. In study A, participants were randomized into two groups that included blood pressure measurements with mercury sphygmomanometer, Spacelabs and Mobil-O-Graph devices with reverse order of recordings. In study B, simultaneous 6-h recordings with both devices were performed with participants randomized in two sequences of device positioning with arm reversal at 3 h. Finally, all the participants filled in a questionnaire rating their overall preference for a device. In study A, brachial systolic blood pressure (117.2±10.3 vs 117.1±9.8 mm Hg, P=0.943) and diastolic blood pressure (73.3±9.4 mm Hg vs 74.1±9.4 mm Hg, P=0.611) did not differ between Spacelabs and Mobil-O-Graph or vs sphygmomanometer (117.8±11.1 mm Hg, P=0.791 vs Spacelabs, P=0.753 vs Mobil-O-Graph). Similarly, no differences were found in ambulatory systolic blood pressure (117.9±11.4 vs 118.3±11.0 mm Hg, P=0.864), diastolic blood pressure (73.7±7.4 vs 74.7±8.0 mm Hg, P=0.571), mean blood pressure and heart rate between Spacelabs and Mobil-O-Graph. Correlation analyses and Bland-Altman plots showed agreement between the monitors. Overall, the participants showed a preference for the Mobil-O-Graph. Spacelabs 90217A and Mobil-O-Graph NG provide practically identical measurements during the static and ambulatory conditions in healthy individuals and can be rather used interchangeably in clinical practice.

Low-dose atorvastatin reduces ambulatory blood pressure in patients with mild hypertension and hypercholesterolaemia: a double-blind, randomized, placebo-controlled study.

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, P<0.001 and -3.0 (-16.0, 2.0) vs +0.1 (-7, 4) mm Hg, P<0.01, 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.

Epigenetic mechanisms and kidney diseases.

In recent years, molecular research has brought to light a series of mechanisms involved in the regulation of gene function without altering the DNA sequence. These mechanisms are described with the term "epigenetics" and include modifications in the structure of the human genome, leading to heritable and potentially reversible changes in gene expression. There is now increasing evidence suggesting that several characteristic features of chronic kidney disease such as hyperhomocysteinemia, subclinical inflammation, increased oxidative stress and others may affect the human epigenome. In addition, animal studies have suggested a possible link between nutrition and environmental exposure during the periconceptional period and epigenetic changes in the expression of major genes implicated in kidney organogenesis; these changes result in a diminished number of nephrons in the developing kidney, which predisposes to an increased risk for hypertension and chronic kidney disease in future life. The understanding of the role of epigenetic phenomena in the pathogenesis of chronic kidney disease opens new avenues for future therapeutic strategies, through the development of pharmaceutical agents that target directly with the changes in the human epigenome. Such epigenetic drugs are already in clinical use for the treatment of cancer as well as under investigation for the use in other diseases. This review will summarize the existing data on the link between epigenetic mechanisms and chronic uremic milieu, as well as the promising results of ongoing research in the field of epigenetic drugs that could represent additional options in our therapeutic armamentarium for patients with chronic kidney disease.

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.

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 (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. PATIENTS AND METHODS: 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. RESULTS: 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 P < 0.05) and lower [Ca(2+)](i) (125.0 +/- 24.7 to 80.4 +/- 10.6 nmol/l, P < 0.05, mean +/- sem) and NHE-1 activity (79.5 +/- 10.0 to 52.1 +/- 6.4 mmol Na/l red cell/h, P < 0.05). 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, P < 0.05). CONCLUSIONS/INTERPRETATION: 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.

Quantitative evaluation of the systemic effects of transposed basilic vein to brachial artery arteriovenous fistula: a prospective study.

BACKGROUND: The transposed basilic vein to brachial artery arteriovenous fistula (BBAVF) constitutes an alternative autogenous vascular access (VA) site for chronic hemodialysis (HD); however, the hemodynamic effects of this procedure have not been adequately studied. The purpose of this study is to evaluate the effects of BBAVF on systemic arterial pressure, cardiac function, and upper limb ischemia (ischemic steal syndrome) utilizing reproducible quantitative methods. METHODS: Ten consecutive patients (eight males; mean age: 65.10+/-2.87 yrs) scheduled to undergo a brachial-basilic vein transposition were included, excluding patients with cardiac failure. Blood flow volume at the level of the AVF, systemic arterial pressure (SAP), cardiac output (CO) and digital brachial index (DBI) were measured intra-operatively, before and after the creation of the BBAVF, and post-operatively on the 30th post-operative day and on the 3rd post-operative month. RESULTS: SAP and DBI at 30 days and 3 months post-operatively were significantly lower compared to baseline. CO at 30 days and 3 months post-operatively was significantly higher compared to baseline; however, none of the patients developed cardiac failure. DBI remained >or=0.6 at 3 months, except in one case (0.59). Blood flow volume at the level of the AVF was positively correlated with CO levels on the 30th post-operative day. Mean clinical follow-up was 12 months (range: 4-15 months). In two cases (20%) the AVF was thrombosed (4th and 10th post-operative month). CONCLUSION: This prospective quantitative study proves that the BBAVF does impact significantly upon SAP, CO, and DBI; however, it is safe in terms of high-output cardiac failure and ischemic steal syndrome. The authors state that they do not have any commercial, proprietary, or financial interest in any products or companies described in this article.

Cost-effectiveness of losartan in diabetic nephropathy: a Greek perspective.

BACKGROUND: Diabetic nephropathy is the primary cause of end-stage renal disease (ESRD), which involves substantial economic burden. The primary objective of this study was to estimate the potential effect of losartan on the costs associated with ESRD in patients with diabetic nephropathy in a Greek setting. A secondary aim was to approximate the direct health care cost of renal replacement therapy (RRT) in Greece. METHODS: A cost-effectiveness analysis was performed to compare losartan with placebo in patients with type 2 diabetes and nephropathy. Clinical data were derived from the RENAAL study. All costs were calculated from the perspective of the Greek social insurance system, in 2003 euros. Future costs were discounted at 3%. The time horizon was 3.5 years. Extensive sensitivity analyses were performed. RESULTS: The reduction in the number of ESRD days over 3.5 years in patients treated with losartan reduced ESRD-related costs by 3,056.54 euros, resulting in net cost savings of 1,665.43 euros per patient. Net cost savings increase thereafter, increasing to 2,686.48 euros per patient over a period of 4.0 years. The results were robust under a wide range of plausible assumptions. The weighted mean daily cost of RRT was estimated at 90.97 euros per patient. The total economic burden of RRT for the year 2003 has been estimated at 304.773 million euros. CONCLUSIONS: This study demonstrated that treatment of patients with diabetic nephropathy in Greece with losartan is cost-effective, as it leads to important savings for the social insurance system by slowing the progression to ESRD.

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 clamp-derived 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.

Non-esterified fatty acids and blood pressure elevation: a mechanism for hypertension in subjects with obesity/insulin resistance?

The prevalence of hypertension in individuals with obesity or type II diabetes is substantially elevated. Increased levels of non-esterified fatty acids (NEFAs) in abdominally obese subjects were reported to contribute in the development of various disturbances related to the metabolic syndrome, such as hepatic and peripheral insulin resistance (IR), dyslipidaemia, beta-cell apoptosis, endothelial dysfunction and others. However, the involvement of NEFAs in the development of hypertension has been much less studied in comparison to other mechanisms linking IR and central obesity with blood pressure (BP) elevation. This article reviews the existing evidence on the relation between NEFA and hypertension in an attempt to shed a light on it. In vivo data from both animal and human studies support that acute plasma NEFA elevation leads to increase in BP levels, whereas epidemiological evidence suggests a link between increased NEFA levels and hypertension. Further, accumulating data indicate the existence of several pathways through which NEFAs could promote BP elevation, that is alpha(1)-adrenergic stimulation, endothelial dysfunction, increase in oxidant stress, stimulation of vascular cell's growth and others. The above data support a possible important role of NEFA in hypertension development in patients with obesity and the metabolic syndrome and raise hypotheses for future research.

Proteinuria: natural course, prognostic implications and therapeutic considerations.

In individuals with normally functioning kidneys a small amount of proteins are secreted in the urine everyday. However, urinary albumin excretion (UAE) above 30 mg/day is considered abnormal; UAE levels between 30-300 mg/day are considered as microalbuminuria, whereas every albumin or protein excretion above 300 mg/day represents macroalbuminuria or clinical proteinuria. The prevalence of proteinuria in the general population is rather low, but it increases considerably in patients with diabetes or hypertension. The natural course of proteinuria is also different in patients with diabetic or nondiabetic nephropathy; however its prognostic implications for renal and cardiovascular endpoints are the same, independently from the underlying kidney disease. Recent population studies and post hoc analyses of outcome trials have shown a continuous association between the level of UAE and the risk for cardiovascular events, as well as cardiovascular and overall mortality. Thus, both microalbuminuria and proteinuria today are considered risk factors for cardiovascular disease. Moreover, proteinuria is a typical manifestation of overt nephropathy and is associated with faster decline of renal function. These roles of proteinuria are further supported by the fact that interventions that reduce UAE have been associated with slower decline in renal function and decrease in the risk of cardiovascular events. This article will discuss data on the prevalence and natural history of proteinuria, its prognostic implications for chronic kidney disease and cardiovascular disease, as well as on therapeutic approaches to reduce its impact, with special focus on blood pressure control.

Protection of the kidney by thiazolidinediones: an assessment from bench to bedside.

The global epidemic of diabetes mellitus has led to a continuous increase in the prevalence of diabetic nephropathy over the past years. Thus, diabetic nephropathy is currently the number one cause of end-stage renal disease in the Western world. It represents a major public health problem for which more effective prevention and treatment strategies are needed. Thiazolidinediones (TZDs) are a class of agents that lower blood glucose through reduction of insulin resistance in patients with type 2 diabetes. Growing evidence support the concept that TZDs have several beneficial effects on the cardiovascular system beyond their effects on glycemic control. These benefits include: blood pressure lowering, triglyceride reduction, high-density lipoprotein-cholesterol elevation, and reduction in subclinical vascular inflammation. Moreover, data from several animal and human studies support the notion that TZDs reduce urine albumin excretion and may prevent development of renal injury. The relative lack of evidence, however, demonstrating the effects of TZDs on hard renal outcomes mandates the need for well-designed trials with this particular objective. This paper summarizes all the data from clinical and experimental studies relevant to a possible renoprotective effect of TZDs and discusses actions of these compounds that may contribute toward this effect.

Antihypertensive treatment with beta-blockers and the spectrum of glycaemic control.

Hypertension and type 2 diabetes mellitus (DM) are major cardiovascular risk factors, and often cluster in the same individual in the context of the metabolic syndrome. Management of hypertension in the diabetic patient is extremely important, and agents from all major antihypertensive classes are effective towards this goal. Conventional beta-blockers are associated with detrimental effects on insulin sensitivity, glycaemic control, and the incidence of type 2 DM and thus are less often used in hypertensive patients with DM. In contrast, the newer vasodilating beta-blockers appear to be free of adverse effects on the above metabolic parameters, and could be a valuable tool for hypertension treatment in patients with DM or the metabolic syndrome. This review summarizes the evidence on the effects of antihypertensive treatment with both traditional and vasodilating beta-blockers on parameters related to carbohydrate metabolism, and discuss the pathophysiological mechanisms that may be responsible.

Prevalence, awareness, treatment and control of hypertension in employees of factories of Northern Greece: the Naoussa study.

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%, P<0.001 and 9.6 vs 14.8%, P<0.05), 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 patients <45 and > or =45 years of age (22.0 vs 53.2%, P<0.001, 9.7 vs 28.4%, P<0.001 and 6.5 vs 17.7%, P<0.001, 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 those <45 years of age.