Reduction Of Elevated Blood Pressure Research Articles

Formulation and Characterization of Mouth Dissolving Films of Amlodipine using Natural Polymer

Amlodipine is a BCS class I oral hypertensive drug widely prescribed for the management of severe hypertension. The need of rapid reduction of elevated blood pressure makes designing of drug delivery systems that can release the drug in systemic circulation in very short span of time very significant. In the present study an endeavor was made to formulate mouth dissolving films (MDFs) containing amlodipine using a natural polymer, xanthan gum as the film forming polymer. Solvent casting method was utilized to formulate the MDFs. A 32 factorial approach was used for preparing the films with concentration of polymer and plasticizer as the independent variables. All the formulations demonstrated quick drug release, rapid disintegration and optimal mechanical strength. The formulations were also found to be able to release almost complete drug content within a period of 10 minutes. The maximum amount of drug was released by AF4 (97%) while AF5 released the lowest amount of drug (90%) in the same period. The results of accelerated stability study exhibited that all the batches of prepared films were stable under the storage conditions.

A RANDOMIZED CONTROLLED TRIAL OF INDIVIDUALIZED HOMOEOPATHIC TREATMENT TO REDUCE ANGER & THEREBY REDUCING HYPERTENSION

Objective: Despite improved detection and treatments, rates of hypertension (HT) are not decreasing. More and more people experience increased anger, anxiety, depression brought on by globalisation and stress leading to high-risk behaviours. There is the possibility that blood pressure (BP) may positively correlate with anger variables leading to essential hypertension (EHT). Homoeopathy works holistically, helping the patient to cope up with these changes. The study aims to demonstrate the efficacy of similimum on mild to moderate essential hypertension by modifying the underlying anger state, trait, and expressions, thus making the patient more capable of coping with the changing life situations than standard care treatment. Design and method: 172 patients (108 males and 64 females) between 18–65 years were enrolled after consent. They were allocated to the placebo and intervention groups by simple randomisation. Thorough homoeopathic case-taking was done, and the STAXI-2 scale was applied at the beginning and after a 6-months study period to measure the change in anger. Regular follow up was done every two weeks to evaluate the subjective and objective parameters. Results: After six months, in the control arm 16%, had to be prescribed standard AHT. Whereas in the intervention arm, the BP of all patients were maintained on similimum. The patients on standard AHT, in the control arm 98%, continued with the same dose of their medicines. However, standard AHT stopped in 33% of patients in the intervention group, and in 28%, the dose was reduced. Reduction in blood pressure and anger variables at the end of the study period was statistically significant (p = 0.001) in both arms. However, the difference was significantly more in all variables in the intervention arm than in the control arm. Conclusions: Most hypertension patients, especially with a family history of HT, suppress their anger & hostile impulses. Individualised homoeopathic treatment reduces anger & thereby have a reduction in elevated BP. Also, it relieves associated ailments.

Buchu (Agathosma betulina and A. crenulata): Rightfully Forgotten or Underutilized?

Today, the term buchu refers to the two species in commerce, Agathosma betulina (P.J.Bergius) Pillans and Agathosma crenulata (L.) Pillans (Rutaceae). Its traditional use in urinary tract infections and related ailments made it a popular remedy, specifically in the US, in 19th century, but with the advent of antibiotics it became largely obsolete. Recent focus is on technological use and on the essential oil for use in the perfume and food-flavouring industry. A review of the scarce pharmacological research revealed moderate antimicrobial activity for a leaf extract but not the essential oil of both species in the MIC assay. In the 5-lipoxygenase (5-LO) assay the essential oil of both species revealed IC50 values of 50.37 ± 1.87 μg/ml and 59.15 ± 7.44 μg/ml, respectively. In another study 98% inhibitory activity was determined for 250 μg/ml of an ethanolic extract of A. betulina on cyclooxygenase (COX)-1 and a 25% inhibitory activity on COX-2. Analgesic activity of an ethanolic extract of A. betulina was shown in mice. Moderate antioxidant activity was determined for methanol:dichlormethane extracts of A. betulina and A. crenulata and an aqueous extract of A. betulina showed a Trolox equivalent antioxidant capacity (TEAC) of 11.8 µM Trolox. Recent in vitro studies with a commercial aqueous extract of buchu revealed increased uptake of glucose added to 3T3-L1 cell line, significant inhibition of the respiratory burst of neutrophils and monocytes, reduction in the expression of adhesion molecules and inhibition of the release of IL-6 and TNF-α. In diabetic rats the ingestion of aqueous buchu extract completely normalized the glucose level and in rats receiving a high fat diet the consumption of aqueous buchu extract resulted in less weight gain and less intraperitoneal fat gain as well as reduction of elevated blood pressure to normal associated with cardioprotective effects. Limitations in the hitherto conducted research lie in the undisclosed composition of the buchu extracts used and the difficulty in extrapolating data from animal studies to humans. Health claims for buchu products need to be substantiated by randomized, double-blind and placebo-controlled studies. Only then can they be promoted for their true therapeutic potential.

Acute hypotensive effect of EET‐A, a stable analog of epoxyeicosatrienic acid (EET), in spontaneously hypertensive rats: dependence on endogenous EETs activity

IntroductionArterial hypertension and related disorders are one of the main mortality causes world‐wide. Recent evidence points to epoxyeicosatrienoic acids (EETs) as significant factors in blood pressure regulation. These cytochrome P‐450 dependent metabolites of arachidonic acid, exhibit vasodilator and natriuretic activity. Therefore EETs might contribute to reduction of elevated blood pressure and have therapeutic potential. In our spontaneously hypertensive rats (SHR), potential hypotensive efficiency was examined of EET‐A (disodium (S)‐2‐(13‐(3‐entyl)ureido)‐tridec‐8(Z)‐enamido) succinate), a stable 14,15‐EET analog. EET‐A effects were studied in animals that were or were not pretreated with c‐AUCB (cis‐4‐[4‐(3‐adamantan‐1‐yl‐ureido)‐ cyclohexyloxy]‐benzoic acid), an inhibitor of soluble epoxide hydrolase (sEH) which prevents degradation of EETs. Inhibition of sEH increases endogenous EETs levels.MethodsAnesthetized SHR aged 16 weeks (established hypertension) received 1‐hour infusion of EET‐A (5 mg/kg BW iv) or its solvent. These acute experiments were performed in rats pretreated for 14 days with oral c‐AUCB (8.5 mg/kg/24 h, in drinking water) or in untreated rats receiving c‐AUCB solvent. Throughout experiments mean arterial blood pressure (MABP) and left kidney total blood flow (RBF, renal artery probe) and perfusion of the cortex, outer‐ and inner medulla (CBF, OMBF, IMBF; laser‐Doppler fluxes) were measured, along with renal excretion of water (V), total solute (UosmV), and sodium (UNaV).ResultsBasal MABP measured after chronic treatments tended to be lower after c‐AUCB compared to solvent‐treated group; otherwise no meaningful between‐group differences in renal hemodynamics and excretion parameters were seen. In control group pretreated with c‐AUCB‐solvent, EET‐A administration was followed by a delayed significant progressive decrease in MABP, down to a value 6% below control (p=0.01). In AUCB‐pretreated group no significant post‐EET‐A change in MABP was seen. During EET‐A infusion RBF and CBF significantly and fairly rapidly increased, to 130% and 124% of the control levels, respectively, comparably in untreated and c‐AUCB pretreated group and became almost always significant within the first 30 minutes of EET‐A infusion.SummaryIn acute experiments with anesthetized SHR, administration of EET analog (EET‐A) caused a significant delayed reduction of MABP. Not unexpectedly, previous enhancement of endogenous EETs activity after sEH blockade tended to reduce baseline MABP and virtually abolished the pressure reduction in response to exogenous EET analog. Irrespective of the baseline endogenous EET activity, EET‐A invariably induced renal vasodilation. The data indicate that in adult SHR a hypotensive effect can be obtained both by administration of EET analog and by enhancing endogenous EETs activity. On the other hand, only EET‐A treatment was found to improve renal hemodynamics.Support or Funding InformationNational Science Centre 2017/26/M/NZ5/00367

Xiao-Qing-Long Tang Prevents Cardiomyocyte Hypertrophy, Fibrosis, and the Development of Heart Failure with Preserved Ejection Faction in Rats by Modulating the Composition of the Gut Microbiota.

Background Changes in the gut microbiota are associated with cardiovascular disease progression. Xiao-Qing-Long Tang (XQLT), a traditional herbal formula, has an anti-inflammatory effect and regulates the steady state of the immune system, which is also associated with the progression of heart failure with preserved ejection faction (HFpEF). In this study, we investigated whether XQLT could contribute to prevent the development of HFpEF and whether the modulation of the gut microbiota by this herbal formula could be involved in such effect. Methods The gut microbiota, SCFAs, the histology/function of the heart, and systolic blood pressure were examined to evaluate the effect of XQLT on the gut microbiota and the progression of HFpEF after oral administration of XQLT to model rats. Furthermore, we evaluated, through fecal microbiota transplantation experiments, whether the favorable effects of XQLT could be mediated by the gut microbiota. Results Oral administration of XQLT contributed to the reduction of elevated blood pressure, inflammation, and compensatory hypertrophy, features that are associated with the progression of HFpEF. The gut microbiota composition, SCFA levels, and intestinal mucosal histology were improved after treatment with XQLT. Moreover, fecal transfer from XQLT-treated rats was sufficient to prevent the progression of HFpEF. Conclusions These data suggested that XQLT prevented the development of HFpEF in model rats by regulating the composition of the gut microbiota.

KDOQI US Commentary on the 2017 ACC/AHA Hypertension Guideline

Hypertension is a modifiable risk factor for cardiovascular morbidity and mortality and reduction of elevated blood pressure (BP) remains an important intervention for slowing kidney disease progression. Over the past decade, the most appropriate BP target for initiation and titration of BP-lowering medications has been an area of intense research and debate within the clinical community. In 2017, the American College of Cardiology and the American Heart Association (ACC/AHA) in conjunction with several other professional societies released new hypertension guidelines based on data from a systematic review of clinical trials and observational data. While many of the recommendations in the ACC/AHA hypertension guideline are relevant to nephrology practice, BP targets and management strategies for patients receiving dialysis are not discussed. This Kidney Disease Outcomes Quality Initiative (KDOQI) commentary focuses largely on recommendations from the ACC/AHA hypertension guidelines that are pertinent to individuals at risk of chronic kidney disease or with non-dialysis-dependent chronic kidney disease. This KDOQI commentary also includes a brief discussion of the consensus statement regarding hypertension diagnosis and management for adults receiving maintenance dialysis published by the European Renal and Cardiovascular Medicine Working Group of the European Renal Association-European Dialysis and Transplant Association (ERA-EDTA) and the Hypertension and the Kidney working group of the European Society of Hypertension. Overall, we support the vast majority of the ACC/AHA recommendations and highlight select areas in which best diagnosis and treatment options remain controversial.

Protective effect of sitagliptin and rosuvastatin combination on vascular endothelial dysfunction in type-2 diabetes.

The present investigation aimed to evaluate the protective effects of sitagliptin, glimepiride, rosuvastatin and their combinations on oxidative stress and endothelial dysfunction in the aortic tissues in fructose-fed type-2 diabetic rats. Sitagliptin (20 mg/kg, p.o.), glimepiride (2 mg/kg, p.o.), rosuvastatin (5 mg/kg, p.o.) and their combinations were administered for 6 w after induction of diabetes by fructose (66%, w/v solution, p.o. for 8 w) in wistar rats. The effects were examined on body weight, serum glucose, triglyceride, cholesterol, blood pressure, heart rate, nitric oxide and antioxidant defensive enzymes. After completion of treatment schedule, the blood pressure was determined by invasive method and vascular reactivity was tested with adrenaline, noradrenaline and phenylephrine. Endothelial dysfunction was determined by acetylcholine and sodium nitroprusside-induced vasorelaxation studies on isolated rat aortas. Long term treatments significantly decreased body weight gain, serum glucose, triglyceride and cholesterol levels; normalize the heart rate, and blood pressure in fructose fed rats. The treatments significantly improved vascular reactivity to catecholamines with reduction in elevated blood pressure in type-2 diabetic rats. The significant improvement in the relaxant response to acetylcholine and sodium nitroprusside was obtained on isolated aortas. All the treatments were effective in restoring defensive antioxidant enzymes. Sitagliptin and rosuvastatin were able to reverse endothelial dysfunction in type-2 diabetes, but better ameliorating potential was found when used in combination.

Effect of Justicia spicigera extract plant on oxidative and nitrosative stress in hypertensive rat kidney mitochondria (960.2)

Hypertension is a major risk factor for cardiovascular, Reno vascular disease. Reduction of elevated blood pressure significantly reduces the risk of cardiovascular events. Kidney synthesizes reactive oxygen species (ROS), which under pathological conditions play an important role in renal dysfunction. Evidence indicates that increased oxidative and nitrosative stress are mediators of Reno vascular injury in cardiovascular pathologies. Herbal medicines are being used by about 80% of the world population for the primary health care including hypertension. Recent data demonstrated that Justicia spicigera (muicle) a Mexican medicinal plant, has a potential to reduce the blood pressure in L‐NAME rats through the chloroform extract, hence the main purpose of this work was to elucidate if the oxidative and nitrosative stress are related with the antihypertensive effect of Justicia spicigera, however our results indicate that the stress levels assayed by lipid peroxidation, nitric oxide and protein nitration (S‐nitrosylation) are no different in hypertensive and control groups. In conclusion, part of the mechanism by which muicle reduces blood pressure is not mediated by ROS. Acknowledgements: We appreciated the partial economic support from the grants of: CIC‐UMSNH (2.10 to RSG; 2.16 to ASM; 2.33 to SMA) and CONACYT (169093 to ASM). EEG is a CIC‐UMSNH Postdoctoral Fellow.

Association between blood pressure and disability-free survival among community-dwelling elderly patients receiving antihypertensive treatment

A reduction of elevated blood pressure (BP) is an important treatment goal in elderly hypertensive patients. However, excessive reduction of systolic BP (SBP) and/or diastolic BP (DBP) might be harmful in such patients. We investigated whether this was the case with regard to risk of incident disability or death in community-dwelling elderly subjects. We analyzed 570 patients receiving antihypertensive treatment aged 65-94 years. The endpoint was the composite outcome of incident disability, defined as first certification of a support/care need or death. Relationships among each of the four classes of SBP or DBP and the risk of incident disability or death were estimated using the Cox proportional hazards model. Over four years, 77 (13.5%) incident disabilities or deaths occurred. After adjustment for age, sex and variables selected according to their univariate analysis P-value <0.20, the risk of events was significantly higher in subjects with baseline SBP<120 mm Hg (hazard ratio (HR)=2.81, P=0.023) and ⩾160 mm Hg (HR=4.32, P<0.001), compared with subjects with baseline SBP of 140-159 mm Hg, who showed the lowest incidence of events. This J-curve relationship was observed in very elderly patients (⩾75 years) but not in younger patients. Patients with SBP<120 mm Hg tended to have a higher risk of incident disability caused by cerebral events, and those with SBP⩾160 mm Hg had a higher risk of incident disability caused by falls/bone fractures. These observations indicate that excessive BP reduction could cause discontinuance of disability-free survival in community-dwelling elderly patients.

Arterial Stiffness as a Risk Factor for Coronary Artery Disease

Hypertension is a major modifiable risk factor, and clinical trials have demonstrated that successful reduction of elevated blood pressure to target levels translates into decreased risk for the development of coronary artery disease, stroke, heart failure, and renal failure. The arterial system had previously been regarded as a passive conduit for the transportation of arterial blood to peripheral tissues. The physiologic role the arterial system was greatly expanded by the recognition of the central role of the endothelial function in a variety of physiologic processes. The role of arterial function and structure in cardiovascular physiology was expanded with the development of a variety of parameters that evaluate arterial stiffness. Markers of arterial stiffness have been correlated with cardiovascular outcomes, and have been classified as an emerging risk factor that provides prognostic information beyond standard stratification strategies involving hypertension, diabetes, obesity, dyslipidemia and smoking. Multiple epidemiologic studies have correlated markers of arterial stiffness such as pulse-wave velocity, augmentation index and pulse pressure with risk for the development of fatal and nonfatal cardiovascular events. Additionally, measurements of arterial stiffness had clarified the results of clinical trials that demonstrated differing impacts on clinical outcomes, despite similar reductions in blood pressure, as measured by brachial and sphygmomanometry.

Blood Pressure Control for Spontaneous Intracerebral Hemorrhage

Blood Pressure Control for Spontaneous Intracerebral Hemorrhage

Practitioner's Trial on the Efficacy of Antihypertensive Treatment in Elderly Patients with Hypertension II (PATE‐Hypertension II study) in Japan

Reduction of elevated blood pressure (BP) has been an important treatment goal in elderly hypertensive patients. However, it has been reported that an excessive reduction of systolic BP to less than 120mmHg might be harmful in such patients. We investigated whether this was the case in a study which assessed long-term antihypertensive efficacy, tolerability and impact on cardiovascular/cerebrovascular (CV) morbidity/mortality in a large cohort of Japanese patients. This study was performed at general practitioners' offices nationwide with a target sample size of 1500 patients. Hypertensive patients aged 60years or more who achieved successful BP control with candesartan monotherapy, and who tolerated the treatment for at least 8weeks, were enrolled into the study and followed for 3years. BP was maintained below the target level of 140/90mmHg over the 3-year period. The incidence of CV events during the study period was 20.4/1000person-years. Investigation of the relationship between BP and the incidence of CV events revealed that patients with higher BP generally had a higher incidence of events. However, very elderly patients (≥75years) with a systolic BP (SBP) of less than 120mmHg also had a higher incidence of CV events compared with those with an SBP of 120-139mmHg. This study demonstrated that treatment with candesartan maintained long-term control of BP in elderly hypertensive patients without serious adverse events. CV events demonstrated a J-curve relationship with SBP in patients aged 75years or older, which suggests that excessive BP reductions might be harmful for very elderly patients.

Feasibility of electrical impedance tomography in haemorrhagic stroke treatment using adaptive mesh

EIT has been proposed for acute stroke differentiation, specifically to determine the type of stroke, either ischaemia (clot) or haemorrhage (bleed) to allow the rapid use of clot-busting drugs in the former (Romsauerova et al 2006) . This addresses an important medical need, although there is little treatment offered in the case of haemorrhage. Also the demands on EIT are high with usually no availability to take a 'before' measurement, ruling out time difference imaging. Recently a new treatment option for haemorrhage has been proposed and is being studied in international randomised controlled trial: the early reduction of elevated blood pressure to attenuate the haematoma. This has been shown via CT to reduce bleeds by up to 1mL by Anderson et al 2008. The use of EIT as a continuous measure is desirable here to monitor the effect of blood pressure reduction. A 1mL increase of haemorrhagic lesion located near scalp on the right side of head caused a boundary voltage change of less than 0.05% at 50 kHz. This could be visually observed in a time difference 3D reconstruction with no change in electrode positions, mesh, background conductivity or drift when baseline noise was less than 0.005% but not when noise was increased to 0.01%. This useful result informs us that the EIT system must have noise of less than 0.005% at 50 kHz including instrumentation, physiological and other biases.

Effects of Dark Chocolate on Cardiovascular Risk

Cocoa is rich in polyphenols, a subgroup of dietary flavonoids, which seems to be able to reduce cardiovascular risk. Since dark chocolate is popular in Europe and the United States, and it is a potent source of polyphenols, there is increasing interest on its potential effects on cardiovascular risk. Evidence suggests that dark chocolate has some beneficial effects on cardiovascular risk factors, particularly on atherogenic dyslipidemia. Beneficial effects include the reduction of elevated blood pressure in hypertensive subjects, the increase in vasodilatation with improved endothelial function, as well as the inhibition of platelet activation and function. In addition, dark chocolate seems to reduce C-reactive protein concentrations and to modulate atherogenic dyslipidemia, reducing plasma total-cholesterol, LDL-cholesterol and triglyceride levels, with a concomitant increase in HDL-cholesterol concentrations. Yet, further studies are needed before recommending habitual dark chocolate consumption for the reduction of cardiovascular risk. I N T R O D U C T I O N Dark chocolate is a potent source of flavonoids, which have been proposed as a key protective dietary component able to reduce cardiovascular risk. These agents are polyphenolic compounds ubiquitous in fruits and vegetables, and appear in higher concentrations in the form of flavonols in cocoa, with beneficial antioxidant effects. In addition, flavonoids are known to suppress inflammation, by inhibiting the cyclooxygenase-2, an enzyme that up-regulates during inflammation, as well as some types of tumor formation. Recent evidence also suggests that some flavanols may inhibit atherogenesis, by the interaction with beta-platelet derived growth factor. Further beneficial effects include the reduction of elevated blood pressure in hypertensive subjects, the increase in vasodilatation with improved endothelial function, as well as the inhibition of platelet activation and function. In addition, dark chocolate seems to reduce C-reactive protein concentrations and to modulate atherogenic dyslipidemia, reducing plasma total-cholesterol, low-density lipoprotein (LDL)-cholesterol and triglyceride levels, with a concomitant increase in high-density lipoprotein (HDL)-cholesterol concentrations. This represents a very important point, since atherogenic dyslipidemia is strongly associated with cardiovascular risk. EDITORIAL Department of Internal Medicine and Emerging Diseases, University of Palermo, Italy HOSPITAL CHRONICLES 2010, 5(2): 56–58

Hypertension and Cognitive Function

Arterial hypertension, cerebrovascular disease, and dementia are related pathologies. This paper has reviewed comparatively the incidence of arterial hypertension and adult-onset dementia disorders. Hypertension is associated with cerebrovascular disease, which is in turn associated with dementia. It is the most important modifiable risk factor for stroke, which is a recognized cause of vascular dementia. In terms of pathophysiology of hypertensive brain damage, several hypotheses were developed, such as that vascular alterations induced by hypertension can induce lacunar or cortical infarcts and leucoaraiosis, that hypertension is responsible for cerebrovascular disease and acts into the contest of a pre-existing subclinic Alzheimer's disease (AD), that hypertension determines neurobiologic alterations (such as β-amyloid accumulation) resulting in neuropathologic damage, and that aging and cerebrovascular risk factors act together to cause cerebral capillary degeneration, mitochondrial disruption, reduced glucose oxidation, and reduced ATP synthesis. The consequence of these alterations are neuronal death and dementia. Macroscopic results of these mechanisms are the so-called white matter lesions (WML), the significance of which is analyzed. Increasing clinical evidence suggests a close relationship between the reduction of elevated blood pressure and countering of both vascular dementia and AD. Antihypertensive treatment probably influences cognitive performances and prevents cognitive function alterations and the development of dementia. It is therefore important to evaluate as soon as possible cognitive functions of hypertensive patients.

Nitric Oxide in Hypertension

Hypertension is a major risk factor for cardiovascular disease, and reduction of elevated blood pressure significantly reduces the risk of cardiovascular events. Endothelial dysfunction, which is characterized by impairment of nitric oxide (NO) bioavailability, is an important risk factor for both hypertension and cardiovascular disease and may represent a major link between the conditions. Evidence suggests that NO plays a major role in regulating blood pressure and that impaired NO bioactivity is an important component of hypertension. Mice with disruption of the gene for endothelial NO synthase have elevated blood pressure levels compared with control animals, suggesting a genetic component to the link between impaired NO bioactivity and hypertension. Clinical studies have shown that patients with hypertension have a blunted arterial vasodilatory response to infusion of endothelium-dependent vasodilators and that inhibition of NO raises blood pressure. Impaired NO bioactivity is also implicated in arterial stiffness, a major mechanism of systolic hypertension. Clarification of the mechanisms of impaired NO bioactivity in hypertension could have important implications for the treatment of hypertension.

Vitamin D insufficiency in congestive heart failure: Why and what to do about it?

This article gives an overview of the current knowledge on vitamin D status in patients with congestive heart failure (CHF). A serum 25-hydroxyvitamin D level below 50 nmol/l (20 ng/ml) is generally regarded as insufficient. Available data indicate that the majority of CHF patients have 25-hydroxyvitamin D levels in the insufficiency range. Skin synthesis of vitamin D after solar ultraviolet B exposure is the most important vitamin D source for humans. However, CHF patients have relatively low outdoor activities. Consequently, a disease-related sedentary lifestyle is an important cause for the insufficient vitamin D status in CHF patients. There is also evidence from a recently performed case-controlled study that indicators of ultraviolet B exposure are already reduced in CHF patients during childhood, adolescence, and early adulthood compared to healthy controls. We present results indicating that an insufficient vitamin D status may contribute to the etiology/pathogenesis of CHF. Data include a vitamin D-mediated reduction of elevated blood pressure as well as a vitamin D-mediated prevention of enhanced parathyroid hormone levels, a pathophysiological state that contributes to cardiovascular disease. Based on population attributable risks, hypertension and cardiovascular disease have a high impact, accounting for the majority of CHF events.Theoretically, vitamin D status can be improved by adequate skin synthesis of vitamin D and/or adequate oral vitamin D intake. At present, daily oral intake of 50-100 microg vitamin D seems to be the most effective way to improve vitamin D status in CHF patients.

Extracellular Volume Changes and Blood Pressure Levels in Hemodialysis Patients

Despite the use of highly efficient antihypertensive drugs (AHD), blood pressure (BP) is poorly controlled in the vast majority of hemodialysis (HD) patients. Many of them show no reduction in nocturnal BP, a finding that is associated with left ventricular hypertrophy. The aim of the study was to investigate the effect of the removal of a fluid overload on BP by monitoring the ambulatory BP during 48 hours in 16 hypertensive HD patients treated with AHD. Our aim was to obtain a gradual reduction in post-HD body weight (BW) over a period of 3 to 4 months. During a period of 3-4 months, the postdialysis BW was reduced as the minimal tolerable BW was gradually achieved by slightly increasing the ultrafiltration volume. The Na concentration in the dialysate was reduced from 143-141 mmol/L to 139-138 mmol/L. Extracellular volume (ECV) was measured with a multiple-frequency bioimpedance analyzer (Xitron 4000B, Xitron Technologies Inc., San Diego, CA, USA). Based on the change in ECV, the patients were subdivided into two groups: group 1 with a reduction in ECV (n = 10), and group 2 with no reduction (n = 6). At the start of the study, BW, BP, and AHD in group 1 and group 2 were virtually identical. Group 1 showed a significant reduction during the entire 48-hour period in systolic (156 +/- 16 mmHg vs. 140 +/- 14 mmHg, P = 0.030) and diastolic BP (97 +/- 12 mmHg vs. 87 +/- 9 mmHg, P = 0.026) as well as in mean arterial pressure (MAP, 117 +/- 13 vs. 105 +/- 10 mmHg, P = 0.027). This reduction was more marked during the night (systolic BP 156 +/- 15 mmHg vs. 138 +/- 14 mmHg, P = 0.007; diastolic BP 97 +/- 12 mmHg vs. 85 +/- 9 mmHg, P = 0.009) than during the day (157 +/- 18 mmHg vs. 142 +/- 15 mmHg, P = 0.067; diastolic BP 97 +/- 13 mmHg vs. 90 +/- 9 mmHg, P = 0.126). A significant reduction in systolic load also occurred during the entire 48-hour period (76 +/- 24% vs. 46 +/- 28%, P = 0.043) as well as in night systolic load (75 +/- 21% vs. 41 +/- 30%, P = 0.015) and night diastolic load (67 +/- 32% vs. 39 +/- 31%, P = 0.030). AHD were stopped in eight and reduced in two patients. There were no significant reductions in BP and AHD in group 2. The removal of excess fluid is necessary for adequate BP control and especially for the reduction in elevated BP during the night.

Blood pressure-independent impact of antihypertensive agents on cardiovascular and renal disease.

Reduction of elevated blood pressure clearly protects against target organ damage, but the different targets do not necessarily benefit to the same degree. There is considerable debate over whether or not there is a drug-specific benefit above and beyond that conferred by blood pressure reduction alone. We performed a Medline search to identify recent randomized clinical trials including 300 or more patients who were followed for at least 2 years. We critically reviewed these papers to find like trials for comparisons. There was too much dissimilarity to perform a meaningful meta-analysis. We found that the literature does not support a definitive conclusion either in favor of or against an overall drug-specific protective effect. However, by grouping like trials, it is possible to support an additional protective effect by angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers on reducing the rate of decline in renal function and in reducing proteinuria.

Role of ACE inhibitors in treating hypertensive diabetic patients.

Cardiovascular disease (CVD) is a major determining factor of morbidity and mortality in type 2 diabetic patients. Hypertension, which accompanies diabetes in more than 70% of cases, contributes to increased prevalence of CVD events in this group of patients. Results from the United Kingdom Prospective Diabetes Study (UKPDS) indicated that reduction of elevated blood pressure might decrease CVD morbidity and mortality more than reduction of hyperglycemia. Activation of circulating and tissue renin-angiotensin system (RAS) contributes to the development of both hypertension and insulin resistance in patients with the cardiometabolic syndrome. Angiotensin-converting enzyme (ACE) inhibitor therapy in patients with the cardiometabolic syndrome may improve insulin action as well as lessen CVD. In clinical trials, ACE inhibitors have been shown to be more efficient than other antihypertensive medications (i.e., calcium channel blockers) in the reduction of CVD morbidity and mortality in hypertensive diabetics. In this article, we summarize possible mechanisms by which ACE inhibition may improve insulin resistance, coagulation/clotting, and vascular function abnormalities, and postpone or even prevent the development of type 2 diabetes in hypertensive patients.