Ambulatory blood pressure monitoring in dialysis patients and estimation of mean interdialytic blood pressure

To define blood pressure (BP) patterns and control in dialysis patients, 48-hour ambulatory BP monitoring was performed in 36 hemodialysis and 18 peritoneal dialysis patients. Monitoring began during a dialysis session for hemodialysis patients. Data revealed significantly lower diastolic BP (DBP) and lower diastolic load (percentage of diastolic values > 90 mm Hg) in hemodialysis patients compared with peritoneal dialysis patients (80.6 mm Hg v 88.8 mm Hg, respectively, [P < 0.03] and 26% v 45%, respectively [P < 0.03]) for the 48-hour period. When the 2 days were analyzed separately, the difference in diastolic pressures and loads was significant only for the first (dialysis) day. Similarly, trends toward lower systolic BP (SBP) and systolic load in hemodialysis patients existed throughout monitoring and were greater in magnitude during the first day. BP data were fit to a random-coefficient growth curve model to detect periodicity. This sensitive model did not detect diurnal variation of BP in either group. The incidence of hypotension did not differ between the two groups (2.0% v 1.0% of total observations, hemodialysis v peritoneal dialysis). In the hemodialysis group, the proportion of hypotensive observations was significantly greater during the 4 hours postdialysis compared with other periods (5.6% v 1.6%; P < 0.02), a finding that likely reflects the practice of holding antihypertensives until after hemodialysis. However, patient diaries did not reflect hypotensive symptoms during this time. In the hemodialysis group, mean BP and predialysis BP did not correlate with interdialytic sodium load or weight gain. Predialysis and postdialysis BP (recorded by dialysis nurses) correlated significantly with mean BP. Predialysis SBP overestimated mean SBP by an average of 10 mm Hg, while postdialysis SBP underestimated mean SBP by an average of 7 mm Hg. To create formulas to estimate mean SBP and DBP in hemodialysis patients, multiple linear regression was used to model these variables against age, sex, race, and average prehemodialysis/posthemodialysis BP. The model achieved a high degree of fit (r2 = 0.72 for SBP; r2 = 0.65 for DBP), demonstrating that prehemodialysis and posthemodialysis BP can be used to predict mean BP in hemodialysis patients. In summary, our data show the absence of a diurnal variation of BP in dialysis patients and lower BP in hemodialysis patients compared with peritoneal dialysis patients. Among hemodialysis patients, more hypotension occurred after dialysis compared with other periods, and predialysis and postdialysis BP can be used to model mean BP levels.     

Effects of hypervolemia on interdialytic hemodynamics and blood pressure control in hemodialysis patients

The influence of hypervolemia on hemodynamics and interdialytic blood pressure, as well as in relation to vascular compliance, was investigated in 10 hemodialysis patients who were not receiving vasoactive medication. All subjects were studied during a relative normovolemic interdialytic period (from 1 kg below dry weight postdialytic until dry weight predialytic) and a hypervolemic interdialytic period (from 1 kg above dry weight postdialytic until 3 kg above dry weight predialytic). Interdialytic blood pressure was measured with an ambulatory blood pressure monitor. Cardiac output was echographically measured and total peripheral resistance calculated postdialytic, mid-interdialytic, and predialytic. At the same time, a blood sample was drawn for analyzing vasoactive hormones, sodium, and hematocrit. In all patients, ideal dry weight was estimated by echography of the caval vein. Arterial and venous compliance were measured with an ultrasound vessel wall movement detector system and a strain-gauge plethysmograph. After fluid load, an increase in intravascular volume, an increase in caval vein diameter and cardiac output, and a decrease in peripheral resistance was observed. No significant influence of a 3-L fluid load was found on interdialytic blood pressure course (153+/-24 mm Hg/90+/-19 mm Hg in the hypervolemic period and 146+/-27 mm Hg/89+/-22 mm Hg in the normovolemic period). Sodium and osmolality were similar in the hypervolemic and normovolemic interdialytic periods. After fluid load, a decrease in arginine vasopressin and angiotensin II was observed, which probably contributed to the decreased systemic vascular resistance. Catecholamines were not influenced by fluid load, but increased during the interdialytic period, suggesting accumulation after dialysis. Three of the 10 patients had higher systolic but not diastolic blood pressures after fluid load (159+/-13 mm Hg/81+/-22 mm Hg in the hypervolemic period and 135+/-16 mm Hg/81+/-22 mm Hg in the normovolemic period). No correlation could be found between arterial or venous compliance and blood pressure changes. We concluded that a 3-L interdialytic fluid load does not result in higher blood pressure in most hemodialysis patients.     

A new method to analyze lung compliance when pressure-volume relationship is nonlinear

The aim of this multicenter, prospective, randomized cross-over study was to clarify whether on-line conductivity ultrafiltrate kinetic modeling (treatment B), as a substitute for sodium kinetic modeling, is capable of reducing intradialytic cardiovascular instability in comparison with standard treatment (treatment A), by reducing the sodium balance variability. Both treatments were performed by means of a modified hemodiafiltration technique. Treatment A was performed using fixed dialysate conductivity; treatment B made use of the dialysate conductivity derived from a conductivity kinetic model, in order to obtain an end-dialysis ultrafiltrate conductivity at each dialysis session that was equal to the mean value determined in the same patient during the four-week run-in period. Thus, during treatment B, the expected end-dialysis ultrafiltrate conductivity value of each patient should have been constant. The study was carried out according to a multicenter cross-over design of 16 weeks with two treatments (A or B), two sequences (1 = ABB and 2 = BAA), a run-in period of four weeks (period 1, treatment A), and three consecutive experimental periods of four weeks each. Analysis of variance for a cross-over design was used for the statistical analysis. Forty-nine hemodialysis patients prone to intradialytic hypotension (> 25% of sessions) were enrolled from 16 participating centers, and randomly assigned to either sequence 1 (26 patients) or sequence 2 (23 patients). Six patients dropped out and four were protocol violators, which left 39 patients selected for statistical analysis. There was no difference in the average dialysate conductivity, predialysis and end-dialysis plasma water ultrafiltrate conductivity or body weight between treatment A and treatment B. Thus, the observed mean sodium balance was not different and, as expected, only the intra-patient variability of end-dialysis ultrafiltrate conductivity (index of sodium balance variability) was reduced (21%). During treatment A, systolic blood pressure decreased by 23 mm Hg (95% confidence intervals 21 to 24 mm Hg) at the end of dialysis with respect to the pre-dialysis values. Treatment B reduced this intradialytic decrease (P = 0.001) with a maximum effect at the third hour of dialysis (4.4 mm Hg, 95% confidence intervals 1.9 to 6.9 mm Hg, 23% less than during treatment A, P 0.0005) without any period or carry-over effect (P = 0.53 and 0.08, respectively). There was no treatment effect on intradialytic diastolic blood pressure (P = 0.291). In conclusion, intradialytic cardiovascular stability was significantly improved by matching the interdialytic sodium load with intradialytic sodium removal using on-line conductivity ultrafiltrate kinetic modeling as an alternative to sodium kinetic modeling. Although highly significant, this effect was clinically not very large. By applying this conductivity kinetic model to patients with a more variable sodium intake from one session to another, a greater benefit can be expected.     

Changes in left ventricular structure and function in patients with white coat hypertension: cross sectional survey

OBJECTIVES: To assess the relation between white coat hypertension and alterations of left ventricular structure and function. DESIGN: Cross sectional survey. SETTING: Augsburg, Germany. SUBJECTS: 1677 subjects, aged 25 to 74 years, who participated in an echocardiographic substudy of the monitoring of trends and determinants in cardiovascular disease Augsburg study during 1994-5. OUTCOME MEASURES: Blood pressure measurements and M mode, two dimensional, and Doppler echocardiography. After at least 30 minutes' rest blood pressure was measured three times by a technician, and once by a physician after echocardiography. Subjects were classified as normotensive (technician <140/90 mm Hg, physician <160/95 mm Hg; n=849), white coat hypertensive (technician <140/90 mm Hg, physician >=160/95 mm Hg; n=160), mildly hypertensive (technician >=140/90 mm Hg, physician <160/95 mm Hg; n=129), and sustained hypertensive (taking antihypertensive drugs or blood pressure measured by a technician >=140/90 mm Hg, and physician >=160/95 mm Hg; n=538). RESULTS: White coat hypertension was more common in men than women (10.9% versus 8.2% respectively) and positively related to age and body mass index. After adjustment for these variables, white coat hypertension was associated with an increase in left ventricular mass and an increased prevalence of left ventricular hypertrophy (odds ratio 1.9, 95% confidence interval 1.2 to 3.2; P=0.009) compared with normotensive patients. The increase in left ventricular mass was secondary to significantly increased septal and posterior wall thicknesses whereas end diastolic diameters were similar in both groups with white coat hypertension or normotension. Additionally, the systolic white coat effect (difference between blood pressures recorded by a technician and physician) was associated with increased left ventricular mass and increased prevalence of left ventricular hypertrophy (P<0.05 each). Values for systolic left ventricular function (M mode fractional shortening) were above normal in subjects with white coat hypertension whereas diastolic filling and left atrial size were similar to those in normotension. CONCLUSION: About 10% of the general population show exaggerated inotropic and blood pressure responses when mildly stressed. This is associated with an increased risk of left ventricular hypertrophy.     

The hypertension of autonomic failure and its treatment

We studied the incidence and severity of supine hypertension in 117 patients with severe primary autonomic failure presenting to a referral center over a 9-year period. Patients were uniformly characterized by disabling orthostatic hypotension, lack of compensatory heart rate increase, abnormal autonomic function tests, and unresponsive plasma norepinephrine. Fifty-four patients had isolated autonomic impairment (pure autonomic failure). Sixty-three patients had central nervous system involvement in addition to autonomic impairment (multiple-system atrophy). Patients were studied off medications, in a metabolic ward, and on a controlled diet containing 150 mEq of sodium. Fifty-six percent of patients had supine diastolic blood pressure > or =90 mm Hg. The prevalence of hypertension was slightly greater in females (63%) than in males (52%). Potential mechanisms responsible for this hypertension were investigated. No correlation was found between blood volume and blood pressure. Similarly, plasma norepinephrine (92+/-15 pg/mL) and plasma renin activity (0.3+/-0.05 ng/mL per hour) were very low in the subset of patients with pure autonomic failure and supine hypertension (mean systolic/diastolic pressure, 177 +/- 6/108 +/- 2 mm Hg, range 167/97 to 219/121). Supine hypertension represents a challenge in the treatment of orthostatic hypotension. We found these patients to be particularly responsive to the hypotensive effects of transdermal nitroglycerin. Doses ranging from 0.025 to 0.1 mg/h decreased systolic blood pressure by 36+/-7 mm Hg and may effectively treat supine hypertension overnight, but the dose should be individualized and used with caution.     

Factors influencing reduction in blood pressure and left ventricular mass in hypertensive type-1 diabetic patients using captopril or doxazosin for 6 months

The effect of doxazosin versus captopril on blood pressure, albuminuria, and left ventricular mass was studied in 33 hypertensive type-1 diabetic patients randomized to 6 months treatment with captopril (17 patients, mean daily dose 100 mg) or doxazosin (16 patients, mean daily dose 9 mg). Casual and 24-h ambulatory blood pressure (24hBP) were reduced from 163/95 to 144/83 mm Hg and 152/86 to 145/81 mm Hg, respectively, in the captopril group, and from 160/93 to 145/86 mm Hg and 156/86 to 147/79 mm Hg in the doxazosin group (all P < .05). The achieved 24hBP on treatment was positively associated with pretreatment levels of glycosylated hemoglobin (HbA1c) and plasma atrial natriuretic peptide (r = 0.53 and 0.59, respectively, both P < .01). Albuminuria did not change significantly in either group. Left ventricular hypertrophy was present in 13 patients (7 in the captopril and 6 in the doxazosin group). Left ventricular mass was reduced by an average of 27% and 23%, respectively, in these patients (both P < .01), but did not change significantly in patients without left ventricular hypertrophy. The reduction in left ventricular mass was positively associated with the presence of baseline left ventricular hypertrophy and inversely with dietary sodium intake and achieved casual blood pressure on treatment (R2 = 0.59, P < .001). We conclude that doxazosin and captopril used for 6 months are equally effective in reducing blood pressure and left ventricular hypertrophy in hypertensive type-1 diabetic patients; the antihypertensive effect is closely related to glycemic control; and dietary sodium intake and achieved casual blood pressure after treatment are independent determinants of the reduction in left ventricular mass seen in these patients.     

Diurnal blood-pressure variations in haemodialysis and CAPD patients

The influence of variations in fluid state on diurnal blood pressure was studied by measuring day-time and night-time blood pressure during a 3-day interdialytic period in 10 normotensive and 10 hypertensive haemodialysis patients using Spacelab 90207 Monitors. Ambulatory blood pressure was also measured during 24 h in 11 normotensive and nine hypertensive CAPD patients, and in nine normotensive and 11 hypertensive control patients with a normal renal function. Antihypertensive drugs had been discontinued for at least 3 weeks before the study period. Optimal dry weight in the haemodialysis patients was estimated by echography of the inferior vena cava and in the CAPD patients on clinical grounds. Although in the dialysis patients and controls a significant nocturnal blood pressure reduction was found, day-night blood pressure difference in the dialysis patients was blunted when compared with the control patients. No significant differences in diurnal blood pressure variation was found between the normotensive and the hypertensive patients. Day-night blood pressure differences in the haemodialysis patients did not change during the 3-day interdialytic period. Also the more stable fluid state of the CAPD patients was not associated with significant different diurnal blood pressure variation compared to the haemodialysis patients. We conclude that factors other than changes in extracellular fluid volume are responsible for a blunted day-night difference in blood pressure in dialysis patients.     

Effect of reduced dietary sodium on blood pressure: a meta-analysis of randomized controlled trials

OBJECTIVE:- To ascertain whether restriction of dietary sodium lowers blood pressure in hypertensive and normotensive individuals. DATA SOURCES:- An English-language computerized literature search, restricted to human studies with Medical Subject Heading terms, "hypertension," "blood pressure," "vascular resistance," "sodium and dietary," "diet and sodium restricted," "sodium chloride," "clinical trial," "randomized controlled trial," and "prospective studies," was conducted. Bibliographies of review articles and personal files were also searched. TRIAL SELECTION:- Trials that had randomized allocation to control and dietary sodium intervention groups, monitored by timed sodium excretion, with outcome measures of both systolic and diastolic blood pressure were selected by blinded review of the methods section. DATA EXTRACTION:- Two observers extracted data independently, using purpose-designed forms, and discrepancies were resolved by discussion. DATA SYNTHESIS:- The 56 trials that met our inclusion criteria showed significant heterogeneity. Publication bias was also evident. The mean reduction (95% confidence interval) in daily urinary sodium excretion, a proxy measure of dietary sodium intake, was 95 mmol/d (71-119 mmol/d) in 28 trials with 1131 hypertensive subjects and 125 mmol/d (95-156 mmol/d) in 28 trials with 2374 normotensive subjects. After adjustment for measurement error of urinary sodium excretion, the decrease in blood pressure for a 100-mmol/d reduction in daily sodium excretion was 3.7 mm Hg (2.35-5.05 mm Hg) for systolic (P<.001) and 0.9 mm Hg (-0.13 to 1.85 mm Hg) for diastolic (P=.09) in the hypertensive trials, and 1.0 mm Hg (0.51-1.56 mm Hg) for systolic (P<.001) and 0.1 mm Hg (-0.32 to 0.51 mm Hg) for diastolic (P=.64) in the normotensive trials. Decreases in blood pressure were larger in trials of older hypertensive individuals and small and nonsignificant in trials of normotensive individuals whose meals were prepared and who lived outside the institutional setting. CONCLUSION:- Dietary sodium restriction for older hypertensive individuals might be considered, but the evidence in the normotensive population does not support current recommendations for universal dietary sodium restriction.     

Paradoxical hypertension after reversal of heart failure in patients treated with intensive vasodilator therapy

Hypertension is a major cause of heart failure, evolving from left ventricular hypertrophy to systolic and diastolic dysfunction. Although effective heart failure therapy has been associated with a lowering or no change in systemic arterial blood pressure in long-term follow-up, this study describes the symptomatic, clinical, and left ventricular functional response of a subgroup of heart failure patients with a prior history of hypertension who demonstrated a paradoxical hypertensive response despite high-dose vasodilator therapy. We prospectively identified 45 patients with a past history of hypertension who had become normotensive with symptomatic heart failure. Of these 45 heart failure patients, 12 became hypertensive while receiving therapy in follow-up, with systolic blood pressure > or = 140 mm Hg (Group A). The remaining 33 patients did not have a hypertensive response to therapy (Group B). In the 12 Group A patients, 60+/-10 years old, with symptomatic heart failure for 6.3+/-4.3 years, vasodilator therapy was intensified in the 2.0+/-0.5 years of follow-up, achieving final doses of enalapril 78+/-19 mg and isosorbide dinitrate 293 +/-106 mg per day. New York Heart Association classification improved from 2.9+/-0.8 to 1.3+/-0.5 (P < or = .0001), with a reduction in heart-failure-related hospitalizations. Left ventricular ejection fraction increased from 17+/-6% to 40+/-10% (P < .0001). Follow-up blood pressure at 1 to 3 months was unchanged. However, both systolic and diastolic blood pressure increased at final follow-up, rising from 116+/-14 to 154+/-13 mm Hg (P = .0001) and from 71+/-9 to 85+/-14 mm Hg (P = .004), respectively. Renal function remained unchanged. Although both groups had similar clinical responses, there were more blacks and women in the hypertensive Group A. Effectively, 12 of 45 (27%) heart failure patients with an antecedent history of hypertension demonstrated a paradoxical hypertensive response to vasodilator therapy. The recurrence of hypertension in a significant portion of patients successfully treated for heart failure has important clinical implications.     

Renin and aldosterone suppression in the antihypertensive action of clonidine

In 18 hypertensive patients receiving a constant (100 mEq/day) sodium diet, treatment with clonidine (0.3 mg/day for 5 days) decreased blood pressure in 11 patients with high and normal renin levels and 7 with low renin levels. The high and normal renin group had early and rapid reductions in blood pressure and plasma renin activity. In contrast, the low renin group had a more gradual hypotensive response and only a small absolute decrease in plasma renin. For all patients, pretreatment renin levels were related to the initial decrease in blood pressure but not to the reductions measured after 5 days. Thus, two mechanisms of action of clonidine are possible, one related to acute inhibition of the renin-angiotensin system in patients with high and normal renin levels and another that is independent of renin mechanisms and occurs in all hypertensive patients. In six additional patients with high renin levels induced by prior sodium depletion (10 mEq/day sodium diet), clonidine did not reduce blood pressure or renin, thus indicating that the suppressive action of this agent on renin pressor mechanisms occurs only in patients whose elevated renin levels are intrinsic to hypertension and unrelated to sodium depletion. Of the 18 patients receiving a normal sodium diet, 13 were classified as responding to treatment (decrease in both systolic and diastolic pressures of at least 10%). The five nonresponders had greater weight gain and higher values for aldosterone excretion. For all patients, there was a significant correlation between decrements in blood pressure and in aldosterone, suggesting that the countervailing effects of fluid accumulation on blood pressure in nonresponding patients resulted from a failure of aldosterone to be suppressed. Changes in aldosterone, in turn, correlated significantly with changes in renin. Thus, the antirenin effect of clonidine enhances its antihypertensive action not only by acutely ablating renin-angiotensin pressor mechanisms, but also by inhibiting aldosterone production and thereby minimizing longer-term reactive volume retention during treatment.     

Cardiovascular outcome in white-coat versus sustained mild hypertension: a 10-year follow-up study

BACKGROUND: The aim of this study was to compare the risk conferred by white-coat versus sustained mild hypertension for the development of cardiovascular disease. METHODS AND RESULTS: Patients (n=479) who underwent 24-hour intra-arterial ambulatory blood pressure monitoring on the basis of a persistently elevated clinic systolic blood pressure of 140 to 180 mm Hg were followed up for the development of subsequent cardiovascular events during a 9.1+/-4. 2-year period. White-coat hypertension, defined as a clinic systolic blood pressure of 140 to 180 mm Hg associated with a 24-hour ambulatory systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg, was present in 126 patients, and the remainder had sustained mild hypertension. A subgroup of patients without complications underwent follow-up echocardiography and carotid ultrasound. White-coat hypertensives were younger (44+/-12 versus 52+/-10 years, respectively; P<0.001) and had a significantly lower incidence of cardiovascular events (1.32 versus 2.56 events per 100 patient-years, respectively; P<0.001) than sustained hypertensives. Multivariate analysis revealed age (P=0.002), sex (P=0.007), race (P=0.001), smoking (P=0.005), and the presence of white-coat hypertension (hazard ratio, 0.29; 95% CI, 0.09 to 0.90; P=0.04) to be independent predictors of subsequent cardiovascular events. Subgroup analysis in patients without complications revealed a lower incidence of left ventricular hypertrophy and lesser degrees of carotid hypertrophy in the white-coat group. CONCLUSIONS: These findings indicate a relatively benign outcome in white-coat hypertension compared with sustained mild hypertension.     

Estimates of interdialytic sodium and water intake based on the balance principle: differences between nondiabetic and diabetic subjects on hemodialysis

Whether salt or water intake is the primary cause of interdialytic weight gain (deltaW) has important implication for the design of measures to prevent large deltaW. In 17 hemodialysis patients dialyzed against a bath containing 140 mmol/L of sodium, monthly predialysis serum sodium was compared with post dialysis serum sodium. A decrease in serum sodium in the interdialytic period would indicate that primary water consumption accounts for at least part of the deltaW. Interdialytic sodium intake, isotonic fluid gain (deltaW(isotonic)) and net pure water gain (deltaWH2O) were calculated by balance formulae. Serum sodium concentration was corrected in diabetic subjects to the value corresponding to euglycemia (100 mg/dl). Estimated interdialytic sodium intake was compared with the prescribed sodium intake and, in seven subjects, to sodium intake estimated from dietary records. Results for nondiabetic subjects (N = 9): [Na]post 139.3 +/- 1.9 mmol/L, [Na]pre 140.1 +/- 2.1 mmol/L (NS), deltaW 1.15 +/- 0.55 L/24 hr, deltaW(isotonic) 1.33 +/- 0.57 L/24 hr, deltaWH2O -0.20 +/- 0.58 L/24 hr, estimated sodium intake 206 +/- 75 mmol/24 hr, prescribed sodium intake 121 +/- 29 mmol/24 hr (p = 0.028). Results for diabetic subjects (N = 7): [Na]post 140.1 +/- 2.5 mmol/L, [Na]pre 137.7 +/- 3.1 mmol/L (p < 0.01), deltaW 1.26 +/- 0.38 L/24 hr, deltaW(isotonic) 0.59 +/- 0.63 L/24 hr, deltaWH2O 0.66 +/- 0.39 L/24 hr, estimated sodium intake 160 +/- 81 mmol/24 hr, prescribed sodium intake 124 +/- 30 mmol/24 hr (NS), glycosylated hemoglobin 9.7 +/- 2.8% (normal, 4.1-5.7%). In seven subjects, estimates of sodium intake from balance formulae (233 +/- 113 mmol/24 hr) were not different from estimates from dietary records (212 +/- 87 mmol/24 hr). Sodium intake accounted for all the interdialytic weight gain in nondiabetic subjects. In diabetic patients, only approximately half of the interdialytic weight gain was accounted for by sodium intake. The other half was due to pure water gain, probably caused by hyperglycemia.     

Effects of dipyridamole in spontaneously hypertensive rabbits with diffuse chronic cerebral ischemia

The effect of intravenous dipyridamole (0.7 mg/kg) on cerebral blood flow (CBF), mean arterial blood pressure (MABP), heart rate, respiration rate, cerebral electrical activity, arterial blood gases, pH, and glucose was investigated in 14 normotensive and 14 stroke-prone spontaneously hypertensive anesthetized rabbits. CBF was measured by hydrogen and heat clearance. In both groups, MABP decreased (normotensive: -24 mm Hg, hypertensive: -47 mm Hg; ANOVA: P < 0.0001) and CBF increased (normotensive: +59 ml/100 g/min, hypertensive: +72 ml/100 g/min; ANOVA: P < 0.0002). CBF returned to the initial level 21 min later in hypertensive than in normotensive rabbits. Changes in other parameters were insignificant. In additional experiments, 30 mg/kg theophylline entirely prevented the cerebral vasodilator and systemic hypotensive effects of dipyridamole in both normotensive and hypertensive rabbits. We conclude that, in stroke-prone spontaneously hypertensive rabbits, the longer-lasting and larger CBF increase in response to dipyridamole may be attributed to reversible functional changes in the cerebral vasculature resulting from hypertension.     

Indomethacin does not attenuate the hypotensive effect of trandolapril

This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.     

Effects of sodium restriction on blood pressure, renin, aldosterone, catecholamines, cholesterols, and triglyceride: a meta-analysis

CONTEXT: One of the controversies in preventive medicine is whether a general reduction in sodium intake can decrease the blood pressure of a population and thereby reduce the number of strokes and myocardial infarctions. In recent years the debate has been extended by studies indicating that reduced sodium intake has adverse effects. OBJECTIVE: To estimate the effects of reduced sodium intake on systolic and diastolic blood pressure (SBP and DBP), body weight, and plasma or serum levels of renin, aldosterone, catecholamines, cholesterols, and triglyceride, and to evaluate the stability of the blood pressure effect in relation to additional trials. DATA SOURCES: MEDLINE search from 1966 through December 1997 and reference lists of relevant articles. STUDY SELECTION: Studies randomizing persons to high-sodium and low-sodium diets were included if they evaluated at least one of the effect parameters. DATA EXTRACTION: Two authors independently recorded data. DATA SYNTHESIS: In 58 trials of hypertensive persons, the effect of reduced sodium intake as measured by urinary sodium excretion (mean, 118 mmol/24 h) on SBP was 3.9 mm Hg (95% confidence interval [CI], 3.0-4.8 mm Hg) (P<.001) and on DBP was 1.9 mm Hg (95% CI, 1.3-2.5 mm Hg) (P<.001). In 56 trials of normotensive persons, the effect of reduced sodium intake (mean, 160 mmol/24 h) on SBP was 1.2 mm Hg (95% CI, 0.6-1.8 mm Hg) (P<.001) and on DBP was 0.26 mm Hg (95% CI, -0.3-0.9 mm Hg) (P=.12). The cumulative analysis showed that this effect size has been stable since 1985. In plasma, the renin level increased 3.6-fold (P<.001), and the aldosterone level increased 3.2-fold (P<.001); the increases were proportional to the degree of sodium reduction for both renin (r=0.66; P<.001) and aldosterone (r=0.64; P<.001). Body weight decreased significantly, and noradrenaline, cholesterol, and low-density lipoprotein cholesterol levels increased. There was no effect on adrenaline, triglyceride, and high-density lipoprotein cholesterol. CONCLUSION: These results do not support a general recommendation to reduce sodium intake. Reduced sodium intake may be used as a supplementary treatment in hypertension. Further long-term studies of the effects of high reduction of sodium intake on blood pressure and metabolic variables may clarify the disagreements as to the role of reduced sodium intake, but ideally trials with hard end points such as morbidity and survival should end the controversy.     

Hemodynamic and renal excretory effects of human brain natriuretic peptide infusion in patients with congestive heart failure. A double-blind, placebo-controlled, randomized crossover trial

BACKGROUND: The pharmacological effects of infusion of human brain natriuretic peptide (hBNP) in patients with severe congestive heart failure have not been characterized previously. METHODS AND RESULTS: Twenty patients with severe congestive heart failure were randomized in a double-blind, placebo-controlled, crossover trial to receive incremental 90-minute infusions of hBNP (0.003, 0.01, 0.03, and 0.1 microgram/kg per minute) or placebo on 2 consecutive days. At the highest completed dose of the hBNP, mean pulmonary artery pressure decreased from 38.3 +/- 1.6 to 25.9 +/- 1.7 mm Hg; mean pulmonary capillary wedge pressure decreased from 25.1 +/- 1.1 to 13.2 +/- 1.3 mm Hg; mean right atrial pressure decreased from 10.9 +/- 1 to 4.8 +/- 1.0 mm Hg; mean arterial pressure decreased from 85.2 +/- 2.0 to 74.9 +/- 1.7 mm Hg; and cardiac index increased from 2.0 +/- 0.1 to 2.5 +/- 0.1 L/min per square meter (all P < .01 versus placebo). Urine volume and urine sodium excretion increased significantly during hBNP infusion when compared with placebo infusion (90 +/- 38 versus 67 +/- 27 mL/h and 2.6 +/- 2.4 versus 1.4 +/- 1.2 mEq/h, respectively, both P < .05 versus placebo), whereas creatinine clearance and urinary potassium excretion did not change. CONCLUSIONS: Infusion of incremental doses of hBNP is associated with favorable hemodynamic and natriuretic effects in patients with severe congestive heart failure.     

Globus sensation is associated with hypertensive upper esophageal sphincter but not with gastroesophageal reflux

Globus sensation (globus) is best described as a constant feeling of a lump or fullness in the throat. Although the etiology of globus remains unclear, it has been attributed to a hypertensive upper esophageal sphincter (UES) resting pressure and to gastroesophageal reflux (GER). The aim of this study was, therefore, to determine if significant associations existed among globus, UES resting pressure, and GER. We reviewed the records of all patients who had stationary esophageal manometry over a 21/2-year interval with specific attention to symptoms of globus, UES pressures, and ambulatory pH studies. Patients with hypotensive UES (<30 mm Hg) were excluded. Chi square (chi2) test was used to determine significant associations. Six hundred fifty patients had normal UES resting pressures and 101 patients had hypertensive UES (>118 mm Hg). Seventeen of the 650 (3%) (16 women/1 man; mean age: 48, range 32-81 years) with normal UES described globus. Conversely, 28 of the 101 (28%) (15 women/13 men; mean age: 43, range 23-61 years) patients with hypertensive UES described globus. There was a significant association between hypertonicity of the UES and globus (chi2=93.42, P < 0.0001). In patients with normal UES, globus occurred predominantly in females (chi2=6.33, P < 0.01). Twenty-three (16 women/7 men; mean age: 43, range 23-60 years) of the 45 patients with globus had prior ambulatory pH studies. Six of 23 (26%) had GER. Compared to an age-, sex-, and UES-pressure-matched group of 23 patients (16 women/7 men; mean age: 44, range 22-75 years) without globus, nine (39%) had GER, thus showing no significant association of globus with GER (P=0.35). There also was no significant association of GER with normal UES or with hypertensive UES in these patients. In conclusion, there is a significant association between hypertensive UES and globus. The data suggest two possible etiologies: female patients with normal UES pressure potentially having increased afferent sensation and a group with equal sex distribution but abnormally elevated UES resting pressure. This study does not support GER as an etiology of globus.     

Effects of antihypertensive therapy on left atrial function

OBJECTIVES: To investigate left atrial (LA) function as a reservoir, as a conduit and as a booster pump in essential hypertension (EH). LA volumes were echocardiographically measured in 28 untreated hypertensive patients and in 20 control subjects. BACKGROUND: LA makes a large contribution in left ventricular filling, especially in patients with impaired diastolic function. LA function is fundamental in left ventricular filling in hypertensive patients as hypertension results in left ventricular diastolic dysfunction. METHODS: Diagnosis of EH (blood pressure > 140/90 mm Hg) was based on three repeated readings of blood pressure (BP). Patients with myocardial infarction, cardiomyopathy, valvular or congenital heart disease were excluded. Doppler diastolic early (E) and late (A) velocity of mitral inflow were measured. The following indexes were calculated: left ventricular mass index (LVMI) using the Penn convention; left ventricular stroke volume (LVSV); LA reservoir volume (LARV = LA maximal volume at mitral valve opening minus minimal volume); LA conduit volume (LACV = LVSV-LARV). Atrial systolic function was assessed by calculating the active emptying fraction (volume at onset of atrial systole minus minimal volume/volume at onset of atrial systole, the E/A ratio and the LA ejection force (0.5 rho A2 MOA, where rho = the density of blood, MOA = mitral orifice area from the parasternal short axis view). Measurements were obtained in all hypertensive patients before and after 16 weeks administration of either enalapril (10 or 20 mg) or enalapril +/- chlorthalidone (20/25 mg) once a day. RESULTS: After 16 weeks of treatment, BP was reduced significantly (from 172/110 to 137/86 mm Hg, P < 0.001). LVMI decreased significantly as well (from 141 to 123 g/m2) although it was higher compared to controls (94 g/m2, P < 0.001). LARV decreased significantly (from 35.4 to 29.3 cm3, P < 0.05) while LACV increased significantly (from 43.8 to 51.3 cm3, P < 0.05), LA active emptying fraction and E/A ratio did not change. LA ejection force decreased significantly (from 20.9 to 18.1 kdynes, P < 0.05) but it was greater than controls (16.7 kdynes, P < 0.01). There was a positive relationship of LVMI to LARV (P < 0.01) in controls (r = 0.77) which held true in hypertensive patients, before (r = 0.72) and after treatment (r = 0.69). There was a negative relationship of LVMI to LACV (P < 0.01) in controls (r = -0.65), and in hypertensive patients untreated (r = -0.74) and after treatment (r = -0.72). CONCLUSIONS: Our results showed that in hypertensive patients, LA reservoir function increases and LA conduit function decreases, while LA ejection force increases. Antihypertensive treatment with enalapril and/or thiazide, induces normalisation of the LA function in parallel to left ventricular hypertrophy regression.     

Prevalence, knowledge, treatment and control of arterial hypertension in Oporto, Portugal

The aim of this study was to assess the prevalence, awareness, treatment and control of hypertension among subjects above the age of 39 years living in the urban area of Oporto, Portugal. One hundred and seventy seven individuals from the community were selected by random digit dialing. Each subject was asked about his/her personal history of hypertension, antihypertensive treatment and had his/her blood pressure measured. The prevalence of hypertension was 57.1%, defined by systolic blood pressure (SBP) > or = 140 mm Hg and/or diastolic blood pressure (DBP) > or = 90 mm Hg and/or administration of current the antihypertensive medication. If the values defining hypertension were SBP > or = 160 mm Hg, and DBP > or = 95 mm Hg the prevalence would be 37.9%. The overall prevalence of hypertension was higher in females, but a slightly higher non significant value was found in males in the fifth and sixth decades. Among hypertensives, 62.7% were aware of their condition, 56.7% were treated, 84.2% of hypertensives treated were controlled (SBP < 160 mm Hg and DBP < 95 mm Hg) and 44.7% were very well controlled (SBP < 140 mm Hg and DBP < 90 mm Hg). The question "Are you hypertensive?" had a sensitivity of 62.7%, a specificity of 83.6% and an accuracy of 75.7%. In the preliminary results of this study of an urban population with a high prevalence of hypertension, the awareness of hypertension is similar to that described in the United States of America twenty years ago, the percentage of hypertensives treated is similar to the American percentage fifteen years ago and the percentage of hypertensives treated and controlled is close to the current American percentage.     

Inter-examiner repeatability of heterophoria tests

To investigate how antihypertensive drugs with different pharmacological properties affect ambulatory blood pressure (BP) the JAPANESE Study Group developed a database of clinic and ambulatory BPs before and after antihypertensive treatment of patients throughout Japan. Drugs evaluated were nilvadipine (n = 195; b.i.d, 4-8 mg/day), amlodipine (n = 75; q.d., 2.5-10 mg/day), lisinopril (n = 80; q.d., 10-20 mg/day) and bisoprolol (n = 49; q.d., 5-10 mg/day). The relationship between basal ambulatory BP and the hypotensive effect on ambulatory BP during treatment was examined. All antihypertensive drugs significantly decreased both clinic BP and ambulatory BP. The hypotensive effect determined by measurement of clinic BP was significantly greater than that determined by ambulatory BP. The hypotensive effect was positively correlated with basal ambulatory BP. However, there was a quantitative difference in this characteristic among the drugs. The critical daytime systolic ambulatory BP below which a hypotensive effect was not observed was extrapolated to 128, 127 and 124 mm Hg with nilvadipine, amlodipine and bisoprolol, respectively, while that with lisinopril was 97 mm Hg. The slope of the correlation coefficient between basal daytime ambulatory systolic BP and hypotensive effect with lisinopril was significantly smaller than those with the other drugs (P < 0.0001). The slope for the relationship between night-time ambulatory systolic BP and the hypotensive effect with bisoprolol was the steepest (P < 0.0001). Antihypertensive drugs with different pharmacological properties exhibited differing hypotensive effects on the basal ambulatory BP. Such differences in efficacy of the drugs on the basal ambulatory BP may reflect adverse effects of the drugs and the prognosis of hypertension.