Evaluation and treatment of orthostatic hypotension

Orthostatic hypotension is defined as a decrease of at least 20 mm Hg in systolic blood pressure when an individual moves from a supine position to a standing position. Nonneurogenic causes of orthostatic hypotension are related to cardiac pump failure, reduced intravascular volume, venous pooling or a medication side effect. Neurogenic causes include both central and peripheral nervous system lesions. The diagnostic evaluation requires a systematic review of medications and coexisting medical conditions along with a neurologic examination to search for treatable factors that may be contributing to orthostatic hypotension. Specific testing of autonomic function is useful for detecting subclinical orthostatic hypotension or for monitoring autonomic function over a period of time. Treatment is directed at improving the patient's symptoms rather than achieving arbitrary blood pressure goals.     

Orthostatic hypotension predicts mortality in elderly men: the Honolulu Heart Program

BACKGROUND: Population-based data are unavailable concerning the predictive value of orthostatic hypotension on mortality in ambulatory elderly patients, particularly minority groups. METHODS AND RESULTS: With the use of data from the Honolulu Heart Program's fourth examination (1991 to 1993), orthostatic hypotension was assessed in relation to subsequent 4-year all-cause mortality among a cohort of 3522 Japanese American men 71 to 93 years old. Blood pressure was measured in the supine position and after 3 minutes of standing, with the use of standardized methods. Orthostatic hypotension was defined as a drop in systolic blood pressure (SBP) of >/=20 mm Hg or in diastolic blood pressure of >/=10 mm Hg. Overall prevalence of orthostatic hypotension was 6.9% and increased with age. There was a total of 473 deaths in the cohort over 4 years; of those who died, 52 had orthostatic hypotension. Four-year age-adjusted mortality rates in those with and without orthostatic hypotension were 56.6 and 38.6 per 1000 person-years, respectively. With the use of Cox proportional hazards models, after adjustment for age, smoking, diabetes mellitus, body mass index, physical activity, seated systolic blood pressure, antihypertensive medications, hematocrit, alcohol intake, and prevalent stroke, coronary heart disease and cancer, orthostatic hypotension was a significant independent predictor of 4-year all-cause mortality (relative risk 1.64, 95% CI 1.19 to 2.26). There was a significant linear association between change in systolic blood pressure from supine position to standing and 4-year mortality rates (test for linear trend, P<0.001), suggesting a dose-response relation. CONCLUSIONS: Orthostatic hypotension is relatively uncommon, may be a marker for physical frailty, and is a significant independent predictor of 4-year all-cause mortality in this cohort of elderly ambulatory men.     

Ambulatory blood pressure, nocturnal blood pressure reduction and plasma catecholamines

OBJECTIVE AND DESIGN: Controversial data have been reported on plasma catecholamines in hypertensives. Aims of this study were to find whether 24-hour ambulatory blood pressure was correlated with circulating catecholamines and to investigate whether nocturnal blood pressure reduction was associated with baseline plasma catecholamines. Samples for catecholamine determination were obtained in 34 consecutive male subjects after a 30-minute rest and before ambulatory blood pressure monitoring. RESULTS: Hypertensive patients (n = 22; 24-hour blood pressure: 145 +/- 14/94 +/- 6 mm Hg) showed similar norepinephrine and epinephrine levels when compared with normotensives (n = 12; 24-hour blood pressure: 124 +/- 6/81 +/- 6 mm Hg), and higher dopamine values (hypertensives: 64.6 +/- 58; normotensives: 26.2 +/- 31 pg/ml; p < 0.05). A positive correlation was observed between dopamine and diastolic nocturnal blood pressure (p < 0.05) while a negative correlation was found between dopamine and nocturnal diastolic blood pressure reduction (p < 0.025). No significant relationship was observed between both norepinephrine and epinephrine, and 24-hour blood pressures. CONCLUSIONS: Since previous reports have documented malfunctioning of dopaminergic system in hypertension, the higher levels of circulating plasma dopamine found in hypertensive patients in the present study may account for a peripheral compensatory increase. The correlation between dopamine and nocturnal blood pressure fall seems to indicate that the impairment of dopaminergic system may influence the 24-hour blood pressure profile, affecting the nocturnal blood pressure reduction.     

Antihypertensive effects of combined lisinopril and hydrochlorothiazide in elderly patients with systodiastolic or systolic hypertension: results of a multicenter trial

This study was aimed at evaluating the antihypertensive effect of lisinopril and hydrochlorothiazide administered in the fixed combination of 20 and 12.5 mg, respectively, on clinic and 24-h blood pressure in elderly patients (age, 68.8 +/- 5.8 years, mean +/- SD) with mild-to-moderate essential systodiastolic or isolated systolic hypertension. After a washout period of 4 weeks, patients received once daily lisinopril combined with hydrochlorothiazide for a 6-week period. At the end of the washout and treatment periods, clinic blood pressure was assessed 24 h after dosing, and 24-h ambulatory blood pressure was monitored, taking blood pressure readings every 15 min. Pretreatment clinic blood pressure was 171.3 +/- 14.0/103.7 +/- 5.1 mm Hg (systolic/diastolic) in the group with systodiastolic hypertension (n = 405) and 179.6 +/- 9.4/83.6 +/- 5.4 mm Hg in the group with isolated systolic hypertension (n = 165). The corresponding 24-h average blood pressures were 144.1 +/- 13.9/88.7 +/- 8.4 mm Hg (n = 114) and 150.7 +/- 15.5/80.8 +/- 9.4 mm Hg (n = 40). Clinic blood pressure was significantly reduced by treatment in both groups. This was the case also for ambulatory blood pressure, which was reduced by 9.6 +/- 0.9%/9.9 +/- 0.9% in systodiastolic and by 11.8 +/- 1.3%/8.5 +/- 1.5% in isolated patients with systolic hypertension (p < 0.05 at least for all differences). The antihypertensive effect was similar in patients older and younger than 70 years. In all groups, it was manifest both during the day and the nighttime and was still significant after 24 h. Thus single daily administration of combined lisinopril-hydrochlorothiazide effectively reduces blood pressure in elderly patients with hypertension.     

Effects of age and isolated systolic hypertension on cardiovascular reflexes

OBJECTIVES: Given the reported relationship between systolic hypertension and orthostatic hypotension in the elderly, to test the hypothesis that systolic hypertension causes impairment of the cardiovascular reflex function additional to the effects of age alone. DESIGN: Responses were compared in normotensive healthy young (n = 12) and elderly (n = 15) participants and elderly participants with disproportionate supine systolic hypertension (n = 11) using a baroreceptor-mediated stress (head-up tilt) and two non-baroreceptor-mediated stimuli (cold pressor test and isometric exercise). METHODS: Blood pressure and heart rate were measured by oscillometry before and during the three stress tests. Forearm blood flow was measured by venous occlusion plethysmography and pulse wave velocity (PWV) by Doppler ultrasound. RESULTS: Percentage changes in systolic/diastolic (SBP/DBP) blood pressure with head-up tilt were 0/+11, -3/0 and -6/+1 mmHg in the young and elderly normotensives and elderly systolic hypertensives, respectively. Both elderly groups had reduced DBP responses to tilt compared with the young (P < 0.01). All three groups had similar percentage changes in blood pressure responses to non-baroreflex-mediated stresses (cold pressor test: +10/+23, +11/+11, +10/+15; sustained isometric exercise: +18/+33, +22/+24, +13/+17 in the young and elderly normotensives and elderly systolic hypertensives, respectively). Aorto-iliac PWV adjusted for blood pressure was significantly higher in both elderly groups compared with the young (P < 0.01) but there was no difference between elderly normotensives and hypertensives. Unadjusted PWV was higher in elderly hypertensives than in elderly normotensives (P < 0.05). CONCLUSIONS: Compared with healthy young participants, both elderly groups had similarly attenuated blood pressure responses to tilt and reduced arterial compliance. Systolic hypertension is not associated with additional impairment of cardiovascular reflex function over and above the effects of age. The reported association between supine systolic hypertension and orthostatic hypotension does not appear to be a causative one.     

Cerebrovascular and cardiovascular responses to graded tilt in patients with autonomic failure

BACKGROUND AND PURPOSE: Patients with autonomic nervous system failure often experience symptoms of orthostatic intolerance while standing. It is not known whether these episodes are caused primarily by a reduced ability to regulate arterial blood pressure or whether changes in cerebral autoregulation may also be implicated. METHODS: Eleven patients and eight healthy age- and sex-matched control subjects were studied during a graded-tilt protocol. Changes in their steady state middle cerebral artery mean flow velocities (MFV), measured by transcranial Doppler, brain-level mean arterial blood pressures (MABPbrain), and the relationship between the two were assessed. RESULTS: Significant differences between patients and control subjects (P < .05) were found in both their MFV and MABPbrain responses to tilt. Patients' MFV dropped from 60 +/- 10.2 cm/s in the supine position to 44 +/- 14.0 cm/s at 60 degrees head-up tilt, whereas MABPbrain fell from 109 +/- 11.7 to 42 +/- 16.9 mm Hg. By comparison, controls' MFV dropped from 54 +/- 7.8 cm/s supine to 51 +/- 8.8 cm/s at 60 degrees, whereas MABPbrain went from 90 +/- 11.2 to 67 +/- 8.2 mm Hg. Linear regression showed no significant difference in the MFV-MABPbrain relationship between patients and control subjects, with slopes of 0.228 +/- 0.09 cm.s-1.mm Hg-1 for patients and 0.136 +/- 0.16 cm.s-1.mm Hg-1 for control subjects. CONCLUSIONS: The present study found significant differences between patients and control subjects in their MFV and MABPbrain responses to tilt but no difference in the autoregulatory MFV-MABPbrain relationship. These results suggest that patients' decreased orthostatic tolerance may primarily be the result of impaired blood pressure regulation rather than a deficiency in cerebral autoregulation.     

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.     

Cerebral hypoperfusion in orthostatic hypotension with globally denervated myocardium

A 57-yr-old woman had frequent syncope when rising from a seated position. Her blood pressure fell from 140/80 mmHg to 60-70/40 mmHg while changing positions. Iodine-123-metaiodobenzylguanidine ([123I]MIBG) did not accumulate in the heart, whereas 201Tl-Cl (201Tl) did. Raise-up 99mTc-hexamethyl-propyleneamine oxime (99mTc-HMPAO) brain SPECT revealed decreased activity in the bilateral frontal areas, and subsequent supine 99mTc-HMPAO brain SPECT revealed filling in these areas, indicating that the cerebral blood flow (CBF) was transiently decreased in the frontal areas more than others in a standing position. The plasma norepinephrine (NE) level of this patient was normal during supine rest, but when she stood up, failure to increase the plasma level of NE uncovered a sympathetic nervous dysfunction. The CBF abnormality in patients with orthostatic hypotension may be due to a "functional" hemodynamic mechanism that induces orthostatic stress. This patient had transient hypoperfusion in the frontal areas when standing, without organic cerebral arterial stenosis. Only CBF in the frontal areas revealed relative hypoperfusion. These regions might be highly susceptible to a change in blood flow. The causes of orthostatic hypotension of this patient were autonomic failure with a disturbance of the sympathetic nerve endings, which was revealed by 99mTc-HMPAO brain SPECT and cardiac [123l]MIBG imaging.     

Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension

The purpose of this study was to test the effect of vitamin B6 (pyridoxine-HCl, CAS 58-56-0) supplementation on arterial blood pressure in essential hypertension. The trial comprised 9 normotensive subjects (7 men and 2 women, aged between 32-58 years; mean +/- SD, 48 +/- 11) and 20 patients with essential hypertension (16 men and 4 women, aged between 32-69 years; mean +/- SD, 56 +/- 12). The patients were treated during 4 weeks with a single oral dose of pyridoxine (5 mg/kg body weight/day). After a 5-min rest, measurements were made in the supine position. When compared with the normotensive subjects, the hypertensive subject group had a significantly higher systolic and diastolic blood pressure (p < 0.001) and higher level of plasma norepinephrine (NE) (p < 0.01) before pyridoxine treatment. On the other hand, there were no significant differences in plasma epinephrine (E) and heart rates. Treatment of hypertensive patients with pyridoxine significantly reduced systolic (p < 0.01) and diastolic blood pressure (p < 0.005), plasma NE (p < 0.005) and E (p < 0.05) within 4 weeks. However, there was no significant difference in heart rate at the end of pyridoxine treatment. These results indicate a relationship between pyridoxine status and arterial blood pressure in the essential hypertensive patients.     

Application of USAF G-suit technology for clinical orthostatic hypotension: a case study

INTRODUCTION: The purpose of this study was to determine the effectiveness of a USAF anti-gravity suit (G-suit) on the stability of a patient with chronic orthostatic hypotension. METHODS: A 37-yr-old female with a history of insulin-dependent diabetes mellitus (IDDM) and symptomatic orthostasis was evaluated and the results were compared with those of non-diabetic controls, matched for age, height, and weight. Cardiac vagal tone was assessed by determination of standard deviation of 100 R-R intervals (R-R SD). We assessed the carotid-cardiac baroreflex response by plotting R-R intervals (ms) at each of eight neck pressure steps with their respective carotid distending pressures (mm Hg). Heart rate and blood pressure were recorded in response to the Valsalva maneuver (VM) performed at an expiratory pressure of 30 mmHg to assess integrated baroreflex responses. Blood pressures and heart rate were measured during three 5-min stand tests to assess orthostatic responses: a) without G-suit; b) with noninflated G-suit; and c) with inflated G-suit (50 mm Hg). RESULTS: The IDDM patient had minimal baseline cardiac vagal tone (R-R SD = 8.5 ms) compared with the average response of a control group of 24 subjects with orthostatic stability (R-R SD = 67.2 +/- 7.1 ms). Carotid-cardiac baroreflex response was virtually non-existent in the IDDM patient (Gain = 0.06 ms.mm Hg-1) compared to the control subjects (4.4 +/- 0.8 ms.mm Hg-1). VM responses corroborated the lack of cardiac baroreflex response in the IDDM patient, while blood pressure changes during the VM were similar to those of the controls. Upon standing, the IDDM patient demonstrated severe orthostatic hypotension (90 mm Hg SBP) and tachycardia without the G-suit. The G-suit, with and without pressure, reduced hypotension and tachycardia during standing. CONCLUSION: These results demonstrate successful application of Air Force technology as a useful alternative to pharmacologic intervention in the treatment of a patient with autonomic dysfunction leading to supine hypertension and orthostatic hypotension.     

Left atrial "stunning" following radiofrequency catheter ablation of chronic atrial flutter

Patients with autonomic neuropathy are more susceptible to insulin-induced hypotension than normal subjects, but the mechanisms are unclear. We quantitated the hemodynamic and metabolic effects of two doses of i.v. insulin (1 and 5 mU/kg.min, 120 min each) and several aspects of autonomic function in 28 patients with insulin-dependent diabetes mellitus (IDDM) and in 7 matched normal subjects under standardized normoglycemic conditions. The autonomic function tests included those predominantly assessing the integrity of vagal heart rate control (the expiration inspiration ratio during deep breathing and high frequency power of heart rate variability) and tests measuring sympathetic nervous function (reflex vasoconstriction to cold and blood pressure responses to standing and handgrip). During hyperinsulinemia, heart rate increased less (2 +/- 1 vs. 6 +/- 2 beats/min; P < 0.04) and diastolic blood pressure fell more (-3.1 +/- 1.2 vs. 0.9 +/- 2.1; P = NS) in the patients with IDDM than in the normal subjects. Forearm vascular resistance decreased significantly in the patients with IDDM [by -7.1 +/- 1.4 mm Hg/(mL/dL.min); P < 0.001 for high vs. low dose insulin], but not in the normal subjects (-0.1 +/- 2.5 mm Hg/(mL/dL.min; P = NS). Reflex vasoconstriction to cold was inversely correlated with the decreases in diastolic (r = -0.51; P < 0.005) and systolic (r = -0.59; P < 0.001) blood pressure and forearm vascular resistance (r = -0.53; P < 0.005), but not with the change in heart rate. The expiration inspiration ratio was, however, directly correlated with the insulin-induced change in heart rate (r = 0.63; P < 0.001), but not with diastolic or systolic blood pressure or forearm vascular resistance. Whole body (48 +/- 2 vs. 67 +/- 5 mumol/kg.min; P < 0.005) and forearm (44 +/- 4 vs. 67 +/- 8 mumol/kg.min; P < 0.05) glucose uptake were significantly lower in the IDDM patients than in the normal subjects. The latter could be attributed to a defect in the forearm glucose arterio-venous difference (1.5 +/- 0.1 vs. 2.2 +/- 0.2 mmol/L, respectively; P < 0.01), but not in blood flow. We conclude that both impaired vagal heart rate control and sympathetic nervous dysfunction exaggerate the hemodynamic effects of insulin in patients with IDDM and could contribute to insulin-induced hypotension.     

The effect of minoxidil on blood pressure and plasma renin activity in patients with essential and renal hypertension

The effect of the new vasodilator, minoxidil, on blood pressure and plasma renin activity was studied in 21 hypertensive patients: 12 patients with essential and 9 with renal hypertension. The average maximum dosage of minoxidil was 27.9 +/- 6.0 mg/day (M +/- SD). Average duration of treatment was 84.5 days. During the observation period the average systolic blood pressure fell from 195 +/- 18 to 159 +/- 7 mm Hg (M +/- SD), and the mean diastolic blood pressure fell from 120 +/- 8.3 to 92.5 +/- 8 mm Hg (p less than 0.01). These patients had been treated earlier with other antihypertensive agents, such as reserpine, saluretics, hydralazine, alpha-methyldopa, and clonidine, without any significant reduction in blood pressure. Before treatment, plasma renin activity after resting was 59 +/- 6.4 ng/ml/16 h (M +/- SE) and after saluretics and orthostasis 89 +/- 12.7 ng/ml/16 h. After treatment, the decline in renin value after resting was statistically significant: 42.7 +/- 3.3 ng/ml/16 h (p less than 0.05), and the stimulated renin had fallen to 70 +/- 3.4 ng/ml/16 h (p greater than 0.1). A comparison of the renin stimulation values of patients with renal hypertension also revealed a significant reduction (p less than 0.01). Side effects which appeared at a daily dose of 15 to 30 mg consisted mainly of tachycardia and fluid retention and could be controlled by the administration of propranolol and chlorthalidone. In 5 women and in 1 man was observed a cosmetically disturbing, reversible hypertrichosis. Orthostatic hypotension was observed in one patient. Minoxidil is an effective antihypertensive agent. However, because of its side effects, it generally must be administered with beta-receptor blocking agents and saluretics. It is possible that its blood pressure lowering effect is due, at least in part, to a suppression of the plasma renin activity.     

Hereditary macular dystrophies

BACKGROUND: Orthostatic hypotension is a common phenomenon in the elderly. Hormonal changes during orthostatic stress have been described in elderly normotensive people and in those with essential hypertension. However, the hormonal response in elderly people who have systolic hypertension during orthostasis has not yet been quantified. METHODS: In this study we investigated 14 non-diabetic men, aged 60 to 75 years, with untreated systolic hypertension who were subjected to 45 degrees passive head-up incline on a tilt table for 15 min. Their hormonal profile and hemodynamic changes were analyzed before and after the stress. RESULTS: In the supine position, plasma levels of norepinephrine, atrial natriuretic peptide and aldosterone were in the normal range, while the plasma renin activity was low. Immediately upon tilt the systolic blood pressure fell but it reverted to baseline values after 15 min of orthostasis. At that time the cardiac output decreased while the systemic vascular resistance and the plasma norepinephrine concentration rose. The atrial natriuretic peptide appeared to fall, and the renin-aldosterone level did not change. CONCLUSION: The physiologic response to orthostatic stress in elderly people with systolic hypertension is comparable to that of elderly normotensive people and those with essential hypertension, i.e. a decrease in cardiac output and an increase in plasma norepinephrine levels. The atrial natriuretic peptide appeared to fall appropriately. The response of the renin-aldosterone system mimicked that in elderly patients with low renin essential isolated hypertension. These observations may have a bearing on the management of elderly people with systolic hypertension who also have orthostatic symptoms; they may not require a different approach from that needed for others of the same age group.     

Role of nitrates in pharmacologic modulation of reflected waves and their significance in the treatment of arterial hypertension in the elderly

OBJECTIVE: To analyse the efficacy of a sustained release form of isosorbide mononitrate in the treatment of isolated systolic hypertension in the elderly. PATIENTS: 24 patients suffering from essential hypertension and with an average age of 68.5 +/- 1.1 years were studied: 20 male and four female patients, all with isolated systolic hypertension (systolic blood pressure (SBP) > 160 mmHg and diastolic blood pressure (DBP) < 90 mmHg). None of the patients had received pharmacological treatment for their hypertension. None were receiving other medication or displayed concomitant pathologies. METHODS: Assessment of all the patients was made with the measurement of their occasional blood pressure, ambulatory measurement of blood pressure and the measurement of pulse wave velocity in two arterial zones (carotid-femural) by mecanography before and after thirty days of monotherapy with a single 50 mg dose of a sustained release form of isosorbide mononitrate. Four patients were withdrawn from tests due to signs of intolerance to the drug. RESULTS: A fall in occasional blood pressure was recorded, with statistical significance in relation to SBP only: SBP-192 +/- 15.5-->164 +/- 10.2 mm Hg (p < 0.001); DBP-85 +/- 4.2-->83 +/- 5.4 mm Hg. Ambulatory blood pressure readings also showed a significant drop in average SBP readings over the 24 hours: SAP 152.6 +/- 13.6-->140.5 +/- 15.4 mm Hg (p < 0.03); DBP 77.2 +/- 8.7-->72.3 +/- 5.47 mm Hg. No significant changes in pulse wave velocity were recorded for the zones studied: carotid-femural -20.8 +/- 6.0-->21.7 +/- 5.1 m/sec; femural-foot -4.5 +/ -1.4-->4.4 +/- 2.6 m/sec; a marked alteration in the morphology of arterial pulse in the aortic zone was observed, however, with a clear levelling off and reduction of the systolic peak. CONCLUSION: Treatment with nitrates may be a new and effective alternative for the treatment of the age group in question. It acts specifically on the pathophysiological mechanisms of isolated systolic arterial hypertension in the elderly. Changes in reflected wave velocity (retrogrades) seem to cause the significant reduction in SBP, observed in this group of patients.     

Code Stroke: rapid transport, triage and treatment using rt-PA therapy. The NINDS rt-PA Stroke Study Group

In view of the concern regarding the potential risks and benefits of sodium restriction, the effect on biochemical and orthostatic responses from a moderate reduction in sodium intake in elderly persons that is sufficient to lower systolic blood pressure (SBP) was examined. Seventeen hypertensive subjects aged 65-79 years entered a double-blind randomized placebo controlled cross-over trial of a low sodium diet plus placebo tablets vs a low sodium diet plus sodium tablets (80 mmols/day) each for 5 weeks. At the end of high and low sodium periods, two 24-h urine collections and venous blood samples were undertaken and supine and standing BPs were recorded. On the low compared to the high sodium phase (urinary sodium excretion 95 +/- 36 vs 174 +/- 40 mmols/24-h, respectively), clinic supine SBP fell by 8 mm Hg (95% CI: 1-15 mm Hg, P< 0.05) and diastolic BP (DBP) by 1 mm Hg (CI: -3 to 5 mm Hg); there was no change in total LDL- and HDL-cholesterol and triglyceride levels, serum calcium, phosphate, parathyroid hormone, glucose, creatinine clearance or urinary albumin excretion rate. Serum urate was significantly higher during the low compared to high sodium intake (304 +/- 56 vs 277 +/- 44 micromols/l). Orthostatic BP responses during the high and low sodium intakes were unchanged. In summary, after 5 weeks of moderate sodium restriction no adverse effects other than an increase in serum urate was seen in elderly hypertensive persons.     

Strict dietary sodium reduction worsens insulin sensitivity by increasing sympathetic nervous activity in patients with primary hypertension

To assess the effects of sodium reduction on insulin sensitivity in hypertension, we examined the change of insulin sensitivity after two degrees of dietary sodium restriction by the euglycemic hyperinsulinemic glucose clamp method in 12 subjects with primary hypertension. A controlled period of 1 week, when the subjects were taking a normal sodium diet, was followed by a randomized crossover study in which the subjects were placed on either moderate or strict reduced sodium diets for 1 week. The result of the 1-week moderate dietary sodium reduction from 200 to 100 mmol/day showed significant decreases in systolic and diastolic blood pressure by 6.5 and 5.0 mm Hg, respectively. Strict dietary sodium reduction to 30 mmol/day for 1 week resulted in no further decrease in blood pressure, but it increased plasma insulin by 40.6% without changing plasma glucose. There were no changes in glucose infusion rate (GIR) or insulin sensitivity index (ISI), which is a measure of GIR divided by plasma insulin, after moderate dietary sodium reduction. However, strict dietary sodium reduction induced decreases in GIR by 19.8% (from 1318+/-189 to 1057+/-173 micromol/m2/ min; P < .01), and ISI by 20.5% (from 16.6+/-2.1 to 13.2+/-1.9 micromol/m2/min/microU/mL; P < .01) with a paralleled increase of plasma norepinephrine by 90.0% (from 150.5+/-61.6 to 287.3+/-114.9 pg/mL; P < .01). These results indicate that dietary sodium restriction leads to a deterioration of insulin sensitivity when plasma norepinephrine levels increase, and suggest that moderate dietary sodium reduction may lower blood pressure without a distinct adverse effect on glucose metabolism in subjects with primary hypertension.     

Improved orthostatic tolerance in familial amyloidotic polyneuropathy with unnatural noradrenaline precursor L-threo-3,4-dihydroxyphenylserine

Disabling orthostatic hypotension, due to insufficiency of the autonomic nervous system, is a common complication of type I familial amyloidotic polyneuropathy (FAP). We investigated whether oral treatment with L-threo-3,4-dihydroxyphenylserine (L-threo-Dops), a noradrenaline precursor, might be of therapeutical benefit. In twenty untreated FAP patients, aged 33 to 44 years, who, because of severe orthostatic hypotension, were bedridden or constrained to a sitting life, supine and erect blood pressure (BP), plasma noradrenaline and tilting time, defined as the interval (s) between the beginning of a 60 degrees head-up tilt and the occurrence of orthostatic symptoms (dizziness, blurred vision or near syncope) were determined before and at repeated intervals during oral treatment with L-threo-Dops, 100 mg bid, for 6 months. Before treatment supine mean BP was 80 (76-85) mmHg (mean and 95% CI), supine plasma noradrenaline was low, 59 (41-77) pg/ml and tilting time ranged from 38 to 118 s. In response to tilt, mean BP immediately fell by 36 (31-41) mmHg, whereas plasma noradrenaline increased by only 11 (0-21) pg/ml (p = 0.05). After 3 to 5 days of treatment with L-threo-Dops all patients experienced marked improvement of their orthostatic tolerance as reflected by their ability to walk freely around. This effect sustained throughout the six months of treatment. Plasma noradrenaline increased moderately by 37 (11-63) pg/ml (p = 0.02) and supine mean BP increased by 8.6 (5.8-12.4) mmHg (p < 0.001) during chronic treatment. Supine or nocturnal hypertension did not develop, the fall in mean BP in response to tilt diminished by 12.5 (6.5-17.3) mmHg (p < 0.001) and tilting time became longer than 600 s in all patients. Because of its efficacy, its sustained duration of action and the lack of side effects, L-threo-Dops is advocated to improve orthostatic tolerance in patients with autonomic insufficiency due to FAP.     

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.     

Management of severe childhood hypertension with minoxidil: a controlled clinical study

The therapeutic efficacy of four antihypertensive regimens (minoxidil, propranolol, and hydrochlorothiazide; propranolol and hydrochlorothiazide; methyldopa and hydroch-orothiazide; and hydrochlorothiazide alone) was evaluated in one child with systolic hypertension and in eight children with systolic and diastolic hypertension. The mean blood pressure of 148/98+/-8/4 mm Hg observed during the hydrochlorothiazide control period fell to 142/88+/-8/4 mm Hg following methyldopa and hydrochlorothiazide, 141/85+/-6/2 mm Hg following propranolol and hydrochlorothiazide, and 128/74+/-4/2 mm Hg following minoxidil, propranolol, and hydrochlorothiazide. The only side effect directly associated with administration of minoxidil was hypertrichosis. The effectiveness of minoxidil in the present study suggests that this drug offers an important adjunct to current antihypertensive therapy in children.     

An approach to the treatment of essential hypertension

The efficacy and side effects of the combined administration of propranolol and phenoxybenzamine were examined in 19 patients with moderate and moderately severe essential hypertension. By titrating the dosage of both drugs against pulse rate and blood pressure response, propranolol was given between 80 and 160 mg. and phenoxybenzamine between 20 and 50 mg. per day in divided doses. There was a substantial reduction in both systolic and diastolic blood pressure in both recumbent and upright positions without orthostatic hypotension. Normal blood pressure (140/90 mm. Hg or less) or near normal (150/100 mm. Hg or less) was attained in 14 of the patients in the recumbent and 17 in the upright position. Pulse rate also decreased significantly, whereas body weight increased but not significantly so. Except for a reduction of ejaculation in three out of six male subjects, no symptomatic side effects were detected, and no changes in the liver or renal function or in blood count were observed. Despite the short duration of therapy, 3 to 10 weeks, this study clearly demonstrates that propranolol and phenoxybenzamine given together in individualized doses are very effective in lowering arterial blood pressure with minimal side effects.