Fall In BP Research Articles

Značaj dobre regulacije krvnog pritiska u sekundarnoj prevenciji koronarne bolesti

After an acute coronary event, control of any hypertension (HT) reduces the recurrence rate and coronary mortality by 20%. An isolated fall in BP with treatment does not completely reduce the risk of coronary heart disease (CHD) in essential HT. This confirms the complexity of the relationship between CHD and HT since numerous factors other than HT are implicated. Treatment of HT in patients with CHD must be more aggressive than in the absence of CHD. Indeed, the risk of a recurrent coronary event in this population is very high, and all efforts should be expended in order to lower BP, especially since we may expect a better compliance with treatment after a coronary event. The latest 'update' version of the guide for secondary prevention of coronary heart disease and other vascular diseases was appeared in November of 2011. Emphasis is placed on the lifestyle modification with the use of non-pharmacological measures that may lead to a reduction of the KP and the impact on other associated risk factors (dyslipidemia, physical inactivity, obesity, etc.). Antihypertensive therapy is useful in patients with arterial hypertension and coronary heart disease. As first-line medicines in the European and American guidelines are recommended: In hypertensive patients with stable coronary heart disease, beta-blocker or long acting calcium antagonist, whereas in hypertensive patients after myocardial infarction, beta blocker and/ or ACE inhibitor. The results are still contradictory, regarding the target value of BP in these patients and therefore the final recommendation is that the most reasonable is to keep the BP values of 130-139 for systolic and 85-89 mmHg KP for KP diastolic.

A marked fall in nocturnal blood pressure is associated with the stage of primary open-angle glaucoma in patients with arterial hypertension

Introduction. The aim of this study was to assess blood flow in the vessels of the eyeball and changes in the optic nerve in patients with arterial hypertension and primary open-angle glaucoma. Material and Methods. The patients were divided into groups: 1 (night blood pressure, BP, fall, NBPF, not more than 10%; non-dippers); 2 (NBPF 10–15%, dippers) and 3 (NBPF>15%; extreme dippers). Results. In the group of dippers and extreme dippers, perfusion pressure was significantly lower than that in the non-dippers group, there was reduced thickness of the nerve fibers and a greater decrease in the visual field. Significant relationships between peak systolic, end-diastolic flow in the ophthalmic and central retinal arteries and night perfusion pressure, thickness of nerve fibers, and a loss of visual field were observed. Conclusion. In patients with glaucoma and well-controlled hypertension, a nocturnal BP fall of more than 10% is associated with a greater visual field defect and greater degeneration of the optic nerve fibers. Low minimum diastolic pressure and the level of nocturnal BP fall, but not the absolute value of average arterial BP at night, should be included in the group of specific risk factors in patients with hypertension and open-angle glaucoma. These findings also suggest avoiding excessive lowering of BP at night in this group.

Comparison of atrial electromechanical coupling interval and P-wave dispersion in non-dipper versus dipper hypertensive subjects

Background. The lack of nocturnal BP fall less than 10% of the daytime, called non-dipper hypertension, is associated with increased cardiovascular morbidity and mortality. The aim of our study was to investigate atrial conduction time in patients with non-dipper hypertension using electromechanical coupling interval and P-wave dispersion (PWD), measured with the surface electrocardiogram and tissue Doppler echocardiographic imaging (TDI). Methods. Age- and sex-matched 43 dipper hypertensive patients (19 male, 24 female, mean age: 53.9 ± 10.5 years), 40 non-dipper patients (18 male, 22 female, mean age 54.3 ± 9.6 years) and 46 healthy subjects (22 male, 24 female, mean age: 52.8 ± 9.6 years) were included in the study. The difference between the maximum and minimum P-wave durations was calculated and defined as PWD. Atrial electromechanical coupling (PA), inter-atrial and intra-atrial electromechanical delays were measured with TDI. Results. PWD was significantly higher in patients with non-dippers compared with dippers (p <0.02) and controls (p <0.001). The inter-atrial conduction time was delayed in non-dippers compared with dippers (p <0.01) and controls (p <0.001). There was a positive correlation between left atrial (LA) diameter and inter-atrial conduction times (r = 0.46, p <0.001). LA diameter was also correlated with PWD (r = 0.44, p <0.001). Conclusion. The patients with non-dipper hypertension have higher P-wave duration, PWD and delayed inter-atrial electromechanical coupling intervals compared with those of dippers and controls. This indicates that these subjects may be more prone to atrial rhythm disturbances.

DIPPING SUB-CLASSIFICATION CARRIES NO ADDITIONAL PROGNOSTIC IMPORTANCE AMONG SUBJECTS WITH NOCTURNAL HYPERTENSION: PP.3.116

Objectives: Both nocturnal hypertension and non-dipping status have been associated with increased rates of target organ damage and adverse cardiovascular outcomes. We assessed the role of dipping sub-classification in development of subclinical target organ damage among subjects with nocturnal hypertension. Design and Methods: From a population of 278 consecutive untreated subjects with essential hypertension, we selected 167 nocturnal hypertensives on the basis of ambulatory BP monitoring, night- time BP >or = 120/70 mmHg. These subjects were subdivided into dippers (n = 105) and non- dippers (n = 62) according to a nocturnal BP reduction of >or = 10% or <10% respectively. All subjects underwent echocardiographic examination and determination of pulse wave velocity (PWV) determination and urine albumin to creatinine ratio ACR). Results: Non- dipper as compared to dipper nocturnal hypertensives were older by 4.4 years (p = 0.001) while they did not differ regarding body mass index, waist to hip ratio and gender (p = NS for all cases). No differences between the two groups were observed regarding left ventricular mass index (LVMI) (89.2 ± 21 vs 92.6 ± 22 g/m2), tissue Doppler imaging derived indices of diastolic function Em (0.06 ± 0.002 vs 0.07 ± 0.003 m/s) and Em/Am (0.72 ± 0.1 vs 0.75 ± 0.2), PWV (8.26 ± 1.2 vs 8.25 ± 1.5 m/s) and ACR (27.3 vs 29.8 mg/g) (p = NS, in all cases). In nocturnal hypertensives nighttime systolic BP and male gender were prognosticators of LVMI (R2 = 0.37, p < 0.0005), 24 h PP, age and male gender were prognosticators of PWV (R2 = 0.24, p < 0.0005), and 24 h PP and PWV was the prognosticator of ACR (R2 = 0.18, p < 0.0005). Nocturnal BP fall did not constitute an independent predictor for none of the above assessed indices of target organ damage. Conclusion: Among subjects with nocturnal hypertension, dippers compared to non-dippers did not differ regarding LVMI, PWV and ACR. This finding implies a distinct prognostic role of nocturnal hypertension which abolishes the value of the dipping classification in the risk stratification of hypertensives at least in this setting.

Non-dipping phenomenon in patients with essential hypertension with renal cysts

Dear Editor, Afsar et al. [1] concluded that the presence of simple renal cysts is related to higher ambulatory blood pressure and with non-dipping phenomenon in patients with essential hypertension. Evidence has been shown about association of hypertension and simple renal cysts [2]. The actual and independent association of simple renal cysts and non-dipping phenomenon in essential hypertension is still unclear from this study. Non-dipping blood pressure profile is usually defined as a nocturnal BP fall of less than 10% [3]. Its association with salt-sensitive forms of hypertension, renal function impairment and mineralocorticoidinduced forms of hypertension has been postulated [3]. Evidence suggests that these confounding variables have to be taken into consideration before final conclusions can be drawn. Furthermore, a larger sample size may help delineate these associations which would enhance the clinical and statistical significance of these findings.

New Developments in the Field of RAS Inhibition

The renin-angiotensin system (RAS) was extensively investigated and characterized throughout the first half of the 20th century. However, its contribution to the maintenance of high blood (BP) in essential hypertension and to the development of hypertensive cardiac complications remained under debate until the advent of the first pharmacologic probes capable of blocking its actions, namely the angiotensin receptor blocker (ARB) saralasin and the angiotensin-converting enzyme inhibitor (ACEI) teprotide in the early 1970’s. Using these probes, we could demonstrate that even in normal-renin and low-renin hypertension, blockade of the RAS produced a fall in BP. And this fall was maximized if the patient had been previously submitted to sodium depletion by diuretics or low salt diet, which might produce only a small and possibly insignificant BP fall by itself, but rendered the hypertension RAS-dependent and far more responsive to RAS blockade. In parallel, we had found that excess angiotensin II, either exogenous (in experimental animals) or endogenous, in various clinical settings, could produce significant cardiac and renal tissue damage, because the vasculature of these organs is particularly sensitive to the constricting effects of angiotensin. In particularly, angiotensin excess was shown to produce widespread foci of necrosis and scarring of the myocardium, leading to replacement of myocardial tissue by fibrotic tissue, eventually progressing to ischemic cardiomyopathy and heart failure. Early clinical trials found that treatment of heart failure with ACEIs or ARBs leads to significant hemodynamic improvement in terms of increased cardiac output, decreased peripheral arterial resistance, decreased heart rate, increased coronary blood flow and diminished myocardial oxygen consumption. Subsequent large randomized long-term outcome trials with ACEIs or ARBs, such as the HOPE, EUROPA, LIFE, CHARM, etc., confirmed the functional and structural benefits of these therapeutic approaches and have now established treatment with an ACEI or ARB as mandatory therapy for patients with ischemic heart disease, as well as congestive or chronic heart failure. It is also now universally accepted that initiation of RAS-suppressing therapy with an ACEI or ARB in patients with multiple cardiovascular risk factors, even not necessary including hypertension, offers long-term protection from ischemic heart disease, diastolic and systolic cardiac dysfunction, arrhythmias, as well as protection from renal insufficiency, cerebrovascular accidents and new onset type 2 diabetes mellitus. Drugs that inhibit the RAS now include, in addition to the ACEIs and ARBs, a new class, the direct renin inhibitors (DRIs), of which only aliskiren is commercially available to date. Several clinical trials have shown aliskiren to be equally effective to ACEIs and ARBs in terms of BP lowering, cardioprotection and nephroprotection. A large body of literature has now reported additional benefits of ACEI+ARB combination in selected patients, i.e., those with resistant hypertension on multidrug ATHENS CARDIOLOGY UPDATE 2010

The Effect Of Pulmonary Rehabilitation on Arterial Stiffness in Patients with Chronic Obstructive Pulmonary Disease (COPD)

Background: We have previously shown increased arterial stiffness using aortic pulse wave velocity (PWV) in patients with COPD. Pulmonary rehabilitation (PR) (exercise, education and nutritional advice) has respiratory and functional benefits, though effects on cardiovascular (CV) risk have not been explored. We hypothesised PWV would improve with PR. Methods: 22 (8 male) clinically stable patients, free from overt CV disease had BP, PWV, spirometry (FEV1), shuttle walk (ISWT) and fasting glucose and lipids performed pre and post PR. 20 age and gender matched controls were studied for baseline comparison. Results: Median (range) age for patients was 62.5 (54-79) years, mean (SD) FEV1 was 44.9 (15.6)% predicted. Aortic PWV, cholesterol and BP reduced with PR. 3 of 11 patients no longer met the criteria for hypertension. The fall in aortic PWV was attributable to the fall in BP. Conclusions: PR improves the haemodynamic profile of subjects with COPD. Longer term CV effects of PR should now be investigated.

Intradialytic hypertension in maintenance hemodialysis patients

Objectives To study the intradialytic (RABP) and interdialytic (ERBP) behaviour of blood pressure in maintenance hemodialysis (MHD) patients (pts). Method Conventional blood pressure recording was done before, after and at half hourly intervals during each dialysis session of 4 h in 60 stable hemodialysis patients involving 898 dialysis sessions over a period of 3 months. Results ERBP was categorized as: Group A: normotensive in interdialytic period (n=9 pts), Group B: hypertensive in interdialytic period (n=41 pts), and Group C: indeterminate pattern (n=10 pts). RABP in groups A and B was subclassified as: Type X: no significant intradialytic change in BP (δ<20 mm Hg), Type Y: >20 mm Hg rise in BP in intradialytic period (↑ RABP), and Type Z: >20 mm Hg fall in BP in intradialytic period (↓ RABP). 70% of our MHD patients (41/60) arrive hypertensive predialysis at our unit. In groups A+B (n=50), 50% had Type Y behaviour, 28% patients had Type Z behaviour while 22% had Type X behaviour. Patients in Group C could not be analysed. 22% of all dialysis sessions (196/898) were complicated by >20 mm Hg rise in BP during the dialysis session. Conclusions We note an unexpectedly high incidence of intradialytic hypertension. Adverse events attributable to ↑ RABP such as worsening LVF, headache, convulsions, angina etc. can be frequently encountered during dialysis. Intradialytic hypertension appears to occur irrespective of whether the interdialytic pressure is under control or not. The causative factors for ↑ RABP need to be identified and corrected. Objectives To study the intradialytic (RABP) and interdialytic (ERBP) behaviour of blood pressure in maintenance hemodialysis (MHD) patients (pts). Method Conventional blood pressure recording was done before, after and at half hourly intervals during each dialysis session of 4 h in 60 stable hemodialysis patients involving 898 dialysis sessions over a period of 3 months. Results ERBP was categorized as: Group A: normotensive in interdialytic period (n=9 pts), Group B: hypertensive in interdialytic period (n=41 pts), and Group C: indeterminate pattern (n=10 pts). RABP in groups A and B was subclassified as: Type X: no significant intradialytic change in BP (δ<20 mm Hg), Type Y: >20 mm Hg rise in BP in intradialytic period (↑ RABP), and Type Z: >20 mm Hg fall in BP in intradialytic period (↓ RABP). 70% of our MHD patients (41/60) arrive hypertensive predialysis at our unit. In groups A+B (n=50), 50% had Type Y behaviour, 28% patients had Type Z behaviour while 22% had Type X behaviour. Patients in Group C could not be analysed. 22% of all dialysis sessions (196/898) were complicated by >20 mm Hg rise in BP during the dialysis session. Conclusions We note an unexpectedly high incidence of intradialytic hypertension. Adverse events attributable to ↑ RABP such as worsening LVF, headache, convulsions, angina etc. can be frequently encountered during dialysis. Intradialytic hypertension appears to occur irrespective of whether the interdialytic pressure is under control or not. The causative factors for ↑ RABP need to be identified and corrected.

Comparison of Midazolam, Nalbuphine Combination with Propofol for Sedation during ERCP

Purpose: Midazolam is fast-acting benzodiazepine, with anxiolytic, amnesic, hypnotic, anticonvulsant, muscle relaxant and sedative properties. It is used for sedation during diagnostic and therapeutic endoscopic procedures, but its sedative and amnestic effects are not sufficient for longer procedures such as ERCP. Opioids are added, but questions have been raised about benefit of this combination. Propofol is rapid acting anesthetic and has advantages over benzodiazepines and narcotics because of more rapid onset of action and rapid recovery to alertness without residual sedative effects or amnesia. Study was planned to investigate the effectiveness of Midazolam/Nalbuphine combination with Propofol for sedation during ERCP in terms of effectiveness of sedation, frequency of possible complications and quality of recovery from sedation. Methods: 60 patients were enrolled in two groups. Group A (n=30) received Midazolam (0.07mg/Kg body weight over 30 seconds and then increments given after every two min as needed) and Nalbuphine (2mg stat followed by 2mg every 5 min as needed). Group B (n=30) received Propofol Lipuro (1.5mg/Kg body wt) over 30 sec with 10 mg dosing after every two min as needed). Patient's BP, heart rate, R/R and 02 saturation were monitored preinduction and after every three min. ECG was monitored continuously. During recovery patients were assessed for duration of full orientation in time and place, and were interviewed after 10, 20, and 30 minutes. Aldrete scoring was used for this purpose. Results were analyzed using t-tests and one way analysis of variance (ANOVA). Fischer exact test was used to determine significance of changes from baseline in each group and differences between groups. Significant covariates were entered into a multivariate stepwise logistic regression model to identify those that contained independent information. P-value of < 0.05 was taken significant. Results: Both treatment groups were similar in age, gender, weight and for duration of procedure. Cardiopulmonary assessment revealed more fall of BP, R/R and rise of heart rate in Group A (p-value <0.05). Also there was more fall of 02 saturation in Midazolam group as compared to Propofol group (pvalue<0.05). Multivariate stepwise logistic regression analysis was done for patient's acceptability of procedure, which revealed higher level of patient comfort (x 2 = 5.3, p < 0.05), and a quicker patient recovery time (x2 = 19.5, p < 0.01; × 2 = 52.1, p <0.01; x2 = 58.4, p < 0.01 for Aldrete in 10 min, 20 min, and 30 min, respectively). Conclusion: Propofol as compared to Midazolam/Nalbuphine combination is well tolerated, has more acceptable and effective sedation and has early recovery from sedation.Table: Cardiopulmonary assessment (Midazolam)Table: Cardiopulmonary assessment (Propofol)

Effects of high sodium intake and diuretics on the circadian rhythm of blood pressure in type 2 diabetic patients treated with an angiotensin II receptor blocker

The inhibition of the renin-angiotensin system in the diabetic condition was reported to enhance the sodium sensitivity of blood pressure. In patients with sodium-sensitive hypertension, high sodium intake reduces the nocturnal fall in blood pressure. Therefore, we examined the effects of the amount of sodium intake or diuretics in patients with diabetes treated with an angiotensin receptor blocker. We recruited 32 Japanese type 2 diabetic patients with base line blood pressure > or =130/80 mmHg and treated with valsartan (80 mg daily). At baseline, 24-h ambulatory blood pressure and 24-h urinary excretion of sodium were measured. The patients were then randomly assigned to take either combination therapy with 50 mg of losartan plus 12.5 mg of hydrochlorothiazide or monotherapy with 160 mg of valsartan for 24 weeks. At baseline, 22 of 32 (69%) patients were classified as non-dippers, and the night/day ratio of mean arterial pressure was significantly correlated with 24-h urinary sodium excretion. The combination therapy resulted in a significantly higher fall than the monotherapy in 24-h mean, daytime, night-time and morning blood pressures. The night/day ratio of mean arterial pressure was significantly reduced from the baseline at the end of the study in the combination therapy group, but not in the monotherapy group. In non-dipper patients, the diminished nocturnal fall in blood pressure was restored by the combination therapy. Excessive intake of salt causes non-dipping and diuretics restored nocturnal BP fall in type 2 diabetic patients treated with angiotensin 2 receptor blockers.

Are current recommendations to diagnose orthostatic hypotension in Parkinson's disease satisfactory?

We interviewed 50 Parkinson's disease (PD) patients using a questionnaire to verify the reliability of orthostatic symptoms in warning the presence of orthostatic hypotension (OH). OH is defined as 20 mm Hg systolic or 10 mm Hg diastolic BP fall within 3 min of tilting or standing but if this fall occurs after 3 min we called it 'late OH' (L-OH). We compared if OH in Parkinson's disease (PD) was more frequent after head-up tilt or on standing and if the period of postural challenge matters in detecting OH. Twenty-one (42%) patients had OH that occurred twice more often after tilting (n = 20) than on standing (n = 10). OH occurred within 3 min of tilting in 9 patients (18%) and appeared beyond the currently recommended 3 min in 11 patients (55%) (L-OH). Ten of the 20 patients developing OH on tilting were symptomatic. The 10 patients who had OH on standing were asymptomatic. Reporting of symptoms was independent of age or severity of BP fall. Most (90%) patients reporting orthostatic symptoms on standing had OH on tilting for 3 min. Orthostatic symptoms in PD have a high specificity but low sensitivity in predicting OH. In Parkinson's disease OH occurs often after tilting than on standing and is delayed (after 3 min). As OH in PD is often asymptomatic and delayed it could contribute to falls and increase morbidity. We suggest routine evaluation of OH in PD by tilting them longer than the recommended 3 minutes to detect delayed OH.

Obstructive sleep apnea syndrome and hypertension: ambulatory blood pressure

Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for hypertension and cardiovascular disease. OSAS is the frequent underlying disease of secondary hypertension and resistant hypertension. OSAS increases both daytime and night-time ambulatory blood pressures through the activation of various neurohumoral factors including the sympathetic nervous system and the renin-angiotensin-aldosterone system. In particular, OSAS predominantly increases ambulatory BP during sleep compared with the awake period, with the result that OSAS is likely to be associated with the non-dipping pattern (diminished nocturnal BP fall) or riser pattern (higher sleep BP than awake BP) of nocturnal BP. An additional characteristic of ABP in OSAS is increased BP variability. The newly developed non-invasive hypoxia-trigger BP-monitoring system detected marked midnight BP surges (ranging from around 10 to 100 mm Hg) during sleep in OSAS patients. The exaggerated BP surge may trigger OSAS-related cardiovascular events occurring during sleep. Clinically, as nocturnal hypoxia is the determinant of morning minus evening BP difference (ME difference), OSAS should be strongly suspected when morning BP cannot be controlled <135/85 mm Hg with increased ME difference even by the specific antihypertensive medications targeting morning hypertension such as bedtime dosing of antihypertensive drugs. Understanding the characteristics of OSAS-related hypertension is essentially important to achieve perfect BP control over a 24-h period, including the sleep period, for more effective prevention of cardiovascular disease.

Ambulatory blood pressure measurements are related to albumin excretion and are predictive for risk of microalbuminuria in young people with type 1 diabetes

The relationship between BP and microalbuminuria in young people with type 1 diabetes is not completely clear. As microalbuminuria is preceded by a gradual rise in albumin excretion within the normal range, we hypothesised that ambulatory BP (ABP) may be closely related to albumin excretion and progression to microalbuminuria. ABP monitoring (ABPM) was performed in 509 young people with type 1 diabetes (age median [range]: 15.7 [10.7-22.6] years) followed with annual assessments of three early morning urinary albumin:creatinine ratios (ACRs) and HbA(1c). Systolic BP (SBP) and diastolic BP (DBP) and the nocturnal fall in BP were analysed in relation to ACR. All ABPM variables were significantly related to baseline log(10) ACR (p < 0.001). After the ABPM evaluation, 287 patients were followed for a median of 2.2 (1.0-5.5) years. ABP at baseline was independently related to mean ACR during follow-up. Nineteen initially normoalbuminuric patients developed microalbuminuria after 2.0 (0.2-4.0) years and their baseline daytime DBP was higher than in normoalbuminuric patients (p < 0.001). After adjusting for baseline ACR and HbA(1c), there was an 11% increased risk of microalbuminuria for each 1 mmHg increase in daytime DBP. Forty-eight per cent of patients were non-dippers for SBP and 60% for DBP; however, ACR was not different between dippers and non-dippers and there were no differences in the nocturnal fall in BP between normoalbuminuric and future microalbuminuric patients. In this cohort of young people with type 1 diabetes, ABP was significantly related to ACR, and daytime DBP was independently associated with progression to microalbuminuria. Increasing albumin excretion, even in the normal range, may be associated with parallel rises in BP.

Hemodynamic Effects during Combined Spinal and Epidural Anesthesia: Role of Fluid Preloading and Prophylactic Vasoconstrictors

The most common complication encountered with combined spinal and epidural anaesthesia is hypotension. Several interventions can be planned for prevention of hypotension after combined spinal and epidural anaesthesia. We compare fluid preloading with prophylactic vasoconstrictors (Ephedrine) in reducing the hemodynamic side effects of combined spinal and epidural anaesthesia. The study was carried out randomly on 60 patients in age group of 20 –65 yrs. Patients classified under class 1-3 as per ASA classification. Patients were randomly allocated to the two groups. GROUP-1 patients had received crystalloid preloading (Ringer Lactate) 20 minute before procedure at a rate of 15ml /kg and GROUP-2 patients had received prophylactic ephedrine intravenously 5mg, 5mg at 1 and 2 minute and 1mg at every minute thereafter for 15 minutes after block. HR, BP were recorded immediately after placing patient in supine position and then at 5, 10, 15, 20, 25, 30, 45, 60, 90, 120 minutes. Minute to minute monitoring was done to assess any haemo-dynamic changes and early institution of corrective therapy. In both Group 1 and Group 2 sustained fall in systolic blood pressure was observed from baseline. In Group 1 the fall in BP was more and the difference was also statistically significant. There were comparable sequential rise in mean pulse rate in both the groups, although this was statistically non-significant. In Group 1 nine patients showed hypotension out of which four (44.5%) were managed with fluid challenge alone and rest five patients needed ephedrine. There were three hypotensive patients in Group 2; two out of them (66%) were managed by i.v. fluid boluses alone. Study showed that vasoconstrictor (ephedrine) is a more effective method in reducing the incidence and severity of fall in systolic blood pressure as compared to volume preloading.

Body mass index, nocturnal fall in blood pressure and organ damage in untreated essential hypertensive patients

We sought to investigate the relationship between body mass index (BMI) and parameters derived from 48-h ambulatory blood pressure monitoring (ABPM) as well as organ damage in human hypertension. A total of 658 consecutive outpatients with grade 1 and 2 hypertension, never treated with antihypertensive medications underwent the following procedures: (i) routine examination, (ii) 24-h urine collection for microalbuminuria, (iii) ABPM over two 24-h periods within 4 weeks, (iv) echocardiography and (v) carotid ultrasonography. Each patient was classified as lean (BMI<25 kg/m2) or overweight/obese (> or =25 kg/m2) and according to the consistency of the dipping or nondipping status in the first and second ABPM period, as dipper (DD), nondipper and variable dipper. Mean 48-h, daytime and nighttime systolic BP or diastolic BP were superimposable in the lean (n=314) and overweight (n=344) group. Overweight patients had a reduced nocturnal BP drop compared with their lean counterparts; the prevalence of DD pattern, indeed, was 15% lower in the overweight group as a whole, with a 17% difference in men and 13% in women. The prevalence of left ventricular hypertrophy was higher in overweight than in lean patients (31.8 vs. 15.9% in men and 48.7 vs. 15.6% in women, P<0.01); this more pronounced cardiac involvement was associated with structural carotid alterations. This study, the first to investigate the relationship between BMI and nocturnal BP patterns as assessed by two ABPM sessions, shows that overweight hypertensive patients are more likely to have a reduced nocturnal fall in BP and a greater cardiac and extracardiac organ damage as compared with their lean counterparts despite a similar overall BP load.

Very low frequency blood pressure fluctuations: not only myogenic responsiveness

Very low frequency blood pressure fluctuations: not only myogenic responsiveness

Impaired sodium excretion and increased blood pressure in mice with targeted deletion of renal epithelial insulin receptor

Renal tubule epithelial cells express the insulin receptor (IR); however, their value has not been firmly established. We generated mice with renal epithelial cell-specific knockout of the IR by Cre-recombinase-loxP recombination using a kidney-specific (Ksp) cadherin promoter. KO mice expressed significantly lower levels of IR mRNA and protein in kidney cortex (49-56% of the WT) and medulla (32-47%) homogenates. Immunofluorescence showed the greatest relative reduction in the thick ascending limb and collecting duct cell types. Body weight, kidney weight, and food and water intakes were not different from WT littermates. However, KO mice had significantly increased basal systolic blood pressure (BP, 15 mm Hg higher) as measured by radiotelemetry. In response to a volume load by gavage (20 ml/kg of body weight, 0.9% NaCl, 15% dextrose), KO mice had impaired natriuresis (37 +/- 10 versus 99 +/- 9 mmol of Na(+) per 2 h in WT). Furthermore, volume load led to a sustained increase in BP in KO mice only. In contrast, insulin administration i.p. (0.5 units/kg of body weight) resulted in a significant fall in BP in WT, but not in KO mice. To test the role of reduced renal nitric oxide (NO) production in these responses, basal urinary nitrates plus nitrites excretion (UNOx) was measured and found to be 61% lower in KO vs. WT mice. Furthermore, acute insulin increased UNOx by 202% in the WT, relative to a significantly blunted rise (67%) in KO animals. These results illuminate a previously uncharacterized role for renal IR to reduce BP and facilitate sodium and water excretion, possibly via NO production.

Cardiovascular control during sleep: “Sleep-dependent changes in the coupling between heart period and blood pressure in human subjects,” by Silvani et al.

it has become increasingly apparent that there is a bidirectional relationship between sleep and cardiovascular health ([5][1]). For example, hypertension in humans is often associated with a diminution or loss of the normal sleep-related fall in BP, a phenomenon referred to as a nondipping profile

Transdermal Therapeutic System of Enalapril Maleate Using Piperidine as Penetration Enhancer

The aim of this work was to formulate transdermal therapeutic system (TTS) of an antihypertensive drug, enalapril maleate (EM) using a new penetration enhancer, piperidine hydrochloride (PH), belonging to the class of Dihydropyridines. The TTS of EM was prepared by solvent evaporation technique using polymers Eudragit E100 and polyvinyl pyrrolidone K-30 in varying ratios, 5% w/w dibutylphthalate as plasticizer and 10% w/w PH as penetration enhancer. The TTS was evaluated for in-vitro drug release using paddle over disc method and ex-vivo skin permeation using modified Keshary and Chein diffusion cell. The interaction studies were carried out by comparing the results of assay, UV and TLC analysis for pure drug and medicated and TTS formulation. Skin irritation potential of TTS was assessed by visual examination of treated rat skin. Stability studies were conducted according to ICH guidelines at a temperature of 40+/-0.5 degrees C and 75+/-5% RH. The optimized formulation was evaluated for preclinical bioavailability and antihypertensive efficacy using albino rat model. The optimized formulation provided 87.3% drug release in-vitro and a flux of 380 microg/cm(2)/hr over a period of 48 hours. No chemical interaction was found between the drug and excipients and there were no signs of skin irritation on application of patch. The optimized formulation was stable with a tentative shelf life of two years. Significant fall in BP (p<0.001) was observed in experimental hypertensive rats which was maintained for 2 days. There was 3 fold improvement in bioavailability with TTS vis-à-vis marketed tablet (AUC(0 to t) : 1253.9 ng.h/ml vs. 422.88 ng.h/ml). These preclinicial studies indicate the feasibility of matrix-type TTS of EM for 2 day management of hypertension. Further studies on human beings are warranted to establish clinical utility of the above TTS.

The effect of intraduodenal glucose on muscle sympathetic nerve activity in healthy young and older subjects

The cardiovascular response to a meal is modulated by gastric distension and the interaction of nutrients, particularly carbohydrate, within the small intestine. We tested the hypothesis that the depressor effect of small intestinal glucose is greater in older than in young subjects, because the reflex increase in muscle sympathetic nerve activity (MSNA) is blunted by age. The effects of intraduodenal glucose infusion (IDGI) on blood pressure, heart rate and MSNA were evaluated in eight healthy young subjects (4 women; mean age +/- SEM: 28.8 +/- 3.4 years), eight healthy elderly (4 women; 75.3 +/- 1.6 years) and in two patients with symptomatic postprandial hypotension (PPH), one young (21 years), and one old (90 years). In both young and elderly healthy subjects, IDGI decreased blood pressure (P < 0.05), but the fall in systolic blood pressure was greater in the older subjects (-17.0 +/- 4.1 vs. -6.5 +/- 1.6 mmHg, P < 0.03). MSNA increased similarly, after infusion in both young (9.0 +/- 3.4 bursts/min) and elderly (7.8 +/- 1.0 bursts/min) subjects. Baroreflex sensitivity for number of sympathetic bursts was attenuated in the elderly (P < 0.03). The increase in burst area in the young patient with PPH was attenuated (18 vs. 63% in the healthy young group). The fall in BP induced by IDGI was greater in healthy elderly compared to healthy young subjects. The reason for this is unclear, as they have similar increases in MSNA.