Effect of treadmill gait on bone markers and bone mineral density of quadriplegic subjects.

Quadriplegic subjects present extensive muscle mass paralysis which is responsible for the dramatic decrease in bone mass, increasing the risk of bone fractures. There has been much effort to find an efficient treatment to prevent or reverse this significant bone loss. We used 21 male subjects, mean age 31.95 +/- 8.01 years, with chronic quadriplegia, between C4 and C8, to evaluate the effect of treadmill gait training using neuromuscular electrical stimulation, with 30-50% weight relief, on bone mass, comparing individual dual-energy X-ray absorptiometry responses and biochemical markers of bone metabolism. Subjects were divided into gait (N = 11) and control (N = 10) groups. The gait group underwent gait training for 6 months, twice a week, for 20 min, while the control group did not perform gait. Bone mineral density (BMD) of lumbar spine, femoral neck, trochanteric area, and total femur, and biochemical markers (osteocalcin, bone alkaline phosphatase, pyridinoline, and deoxypyridinoline) were measured at the beginning of the study and 6 months later. In the gait group, 81.8% of the subjects presented a significant increase in bone formation and 66.7% also presented a significant decrease of bone resorption markers, whereas 30% of the controls did not present any change in markers and 20% presented an increase in bone formation. Marker results did not always agree with BMD data. Indeed, many individuals with increased bone formation presented a decrease in BMD. Most individuals in the gait group presented an increase in bone formation markers and a decrease in bone resorption markers, suggesting that gait training, even with 30-50% body weight support, was efficient in improving the bone mass of chronic quadriplegics.

Contribution of autonomic neuropathy to reduced plasma adrenaline responses to hypoglycemia in IDDM: evidence for a nonselective defect.

To determine the contribution of clinically overt diabetic autonomic neuropathy (DAN) to reduced plasma adrenaline responses to hypoglycemia in IDDM and to establish its selectivity for hypoglycemia, we studied 17 IDDM patients (7 without DAN [DAN-] and 10 with DAN [DAN+]), of whom 5 had and 5 did not have postural hypotension (DAN+PH+ and DAN+PH-, respectively), and 8 nondiabetic subjects on 2 different occasions, i.e., clamped hypoglycemia (steps from 5.0 to 2.2 mmol/l plasma glucose) and 30-min steady-state exercise at 55% V(O[2max]). Recent antecedent hypoglycemia was meticulously prevented before the studies to exclude hypoglycemia as a cause of reduced responses of adrenaline to hypoglycemia. In DAN- patients, maximal responses of adrenaline to hypoglycemia were reduced (2.44 +/- 0.58 nmol/l vs. 4.9 +/- 0.54 nmol/l in nondiabetic patients) (P < 0.05). In DAN+, adrenaline responses initiated at a lower plasma glucose and were lower than in DAN- (DAN+PH-, 1.06 +/- 0.38 nmol/l; DAN+PH+, 0.84 +/- 0.27 nmol/l; P < 0.001, but NS between PH- and PH+). In response to exercise, adrenaline increased less in DAN- (0.89 +/- 0.11 nmol/l) patients than in nondiabetic subjects (1.19 +/- 0.14 nmol/l; NS) and only to 0.36 +/- 0.07 nmol/l in DAN+PH- and 0.23 +/- 0.09 nmol/l in DAN+PH+ (P < 0.001 vs. DAN- and nondiabetic subjects). These results were confirmed when nondiabetic and DAN- subjects repeated the exercise at 60 watts (35 and 41% of V(O[2max]), respectively), i.e., at the same absolute workload of DAN+ patients. Thus, DAN (both PH+ and PH-) contributes to reduced responses of adrenaline to hypoglycemia independently of recent antecedent hypoglycemia. The adrenaline defect in DAN is not selective for hypoglycemia.

Long-term intensive therapy of IDDM patients with clinically overt autonomic neuropathy: effects on hypoglycemia awareness and counterregulation.

To test the hypothesis that hypoglycemia unawareness and impaired counterregulation are reversible after meticulous prevention of hypoglycemia in IDDM patients with diabetic autonomic neuropathy (DAN), 21 patients (8 without DAN [DAN-]; 13 with DAN [DAN+]; of the latter, 7 had orthostatic hypotension [DAN+PH+] and 6 did not [DAN+PH-]) and 15 nondiabetic subjects were studied during stepped hypoglycemia (plateau plasma glucose decrements from 5.0 to 2.2 mmol/l) before and 6 months after prevention of hypoglycemia (intensive therapy). After 6 months, frequency of mild hypoglycemia decreased from approximately 20 to approximately 2 episodes/patient-month while HbA1c increased from 6.2 +/- 0.3 to 6.9 +/- 0.2% (P < 0.05). Responses of adrenaline improved more in DAN- patients (from 1.17 +/- 0.12 to 2.4 +/- 0.22 nmol/l) than in DAN+PH- (from 0.75 +/- 0.25 to 1.56 +/- 0.23 nmol/l) and DAN+PH+ patients (from 0.80 +/- 0.24 to 1.15 +/- 0.27 nmol/l, P < 0.05) but remained lower than in nondiabetic subjects (4.9 +/- 0.37 nmol/l, P < 0.05), whereas glycemic thresholds normalized only in DAN-, not DAN+. Autonomic symptoms of hypoglycemia improved but remained lower in DAN- (6.2 +/- 0.6) than in nondiabetic subjects (8.1 +/- 1.1) and lower in DAN+PH+ (4 +/- 0.8) than in DAN+PH- subjects (5.1 +/- 0.8, P < 0.05), whereas neuroglycopenic symptoms normalized (NS). Cognitive function deteriorated less before than after prevention of hypoglycemia (P < 0.05). Thus, intensive therapy with emphasis on preventing hypoglycemia reverses hypoglycemia unawareness in DAN+ patients despite marginal improvement of adrenaline responses, results in low frequency of hypoglycemia despite impaired counterregulation, and maintains HbA1c in the range of intensive therapy. We conclude that DAN, long IDDM duration per se, and antecedent recent hypoglycemia contribute to different extents to impaired adrenaline responses and hypoglycemia unawareness.

Meticulous prevention of hypoglycemia normalizes the glycemic thresholds and magnitude of most of neuroendocrine responses to, symptoms of, and cognitive function during hypoglycemia in intensively treated patients with short-term IDDM.

To test the hypothesis that hypoglycemia unawareness is largely secondary to recurrent therapeutic hypoglycemia in IDDM, we assessed neuroendocrine and symptom responses and cognitive function in 8 patients with short-term IDDM (7 yr) and hypoglycemia unawareness. Patients were assessed during a stepped hypoglycemic clamp, before and after 2 wk and 3 mo of meticulous prevention of hypoglycemia, which resulted in a decreased frequency of hypoglycemia (0.49 +/- 0.05 to 0.045 +/- 0.03 episodes/patient-day) and an increase in HbA1c (5.8 +/- 0.3 to 6.9 +/- 0.2%) (P < 0.05). We also studied 12 nondiabetic volunteer subjects. At baseline, lower than normal symptom and neuroendocrine responses occurred at lower than normal plasma glucose, and cognitive function deteriorated only marginally during hypoglycemia. After 2 wk of hypoglycemia prevention, the magnitude of symptom and neuroendocrine responses (with the exception of glucagon and norepinephrine) nearly normalized, and cognitive function deteriorated at the same glycemic threshold and to the same extent as in nondiabetic volunteer subjects. At 3 mo, the glycemic thresholds of symptom and neuroendocrine responses normalized, and surprisingly, some of the responses of glucagon recovered. We concluded that hypoglycemia unawareness in IDDM is largely reversible and that intensive insulin therapy and a program of intensive education may substantially prevent hypoglycemia and at the same time maintain the glycemic targets of intensive insulin therapy, at least in patients with IDDM of short duration.

Mechanisms of arterial hypotension after therapeutic dose of subcutaneous insulin in diabetic autonomic neuropathy.

To assess whether a therapeutic, subcutaneous injection of insulin exerts hemodynamic effects in subjects with IDDM, 0.2 U/kg regular insulin was injected subcutaneously in 17 IDDM subjects: 6 without autonomic neuropathy, 7 with autonomic neuropathy and othostatic hypotension, and 4 with autonomic neuropathy but without orthostatic hypotension. Plasma glucose was maintained at approximately 8.5 mM throughout the studies. Mean blood pressure, plasma norepinephrine concentration, forearm vascular resistances, and calf venous volume were measured before and 120 min after subcutaneous insulin, in the supine position and 5 min after standing. Supine plasma volume ([125I]albumin and [131I]albumin) was measured before and after subcutaneous injection of insulin. In all three groups, subcutaneous insulin activated the sympathetic nervous system (approximately 30% increase in norepinephrine concentration). In subjects with IDDM but without autonomic neuropathy, standing forearm vascular resistance increased approximately 70% less after subcutaneous insulin, but supine or standing mean blood pressure did not decrease. In contrast, in subjects with IDDM with autonomic neuropathy and orthostatic hypotension, subcutaneous insulin decreased supine mean blood pressure (from 99 +/- 3 to 94 +/- 5 mmHg) and exaggerated the standing decrement in mean blood pressure (24 +/- 3 vs. 19 +/- 2 mmHg) (P < 0.05). This was associated with a decrease in forearm vascular resistance. Similarly, in subjects with IDDM with autonomic neuropathy without orthostatic hypotension, subcutaneously injected insulin decreased supine mean blood pressure (from 95 +/- 2 to 89 +/- 2 mmHg) and standing mean blood pressure by 8 +/- 1 mmHg (P < 0.05). Calf venous volume was not affected by subcutaneous insulin in any of the three groups. Plasma volume did not change after subcutaneous insulin in subjects with IDDM without autonomic neuropathy, whereas it decreased in those with autonomic neuropathy and orthostatic hypotension from 1.692 +/- 0.069 to 1.610 +/- 0.064 L/m2, without orthostatic hypotension from 1.631 +/- 0.027 to 1.593 +/- 0.024 L/m2, P < 0.05). No hemodynamic effects were observed when subjects with IDDM were restudied in a control experiment where placebo (distilled water), not insulin, was injected subcutaneously. In conclusion, therapeutic doses of subcutaneous insulin activate the sympathetic nervous system; decrease blood pressure in subjects with IDDM with autonomic neuropathy, but not in those without, primarily by decreasing arterial vascular resistances and plasma volume; and have no effects of capacitance vessels. Thus, in subjects with IDDM without autonomic neuropathy, greater activation of sympathetic nervous system after subcutaneous injection of insulin prevents orthostatic hypotension.(ABSTRACT TRUNCATED AT 400 WORDS)

Variability of indirect methods used to determine blood pressure. Office vs mean 24-hour automated blood pressures.

Blood pressure is a cardiovascular measurement with dynamic characteristics that can be influenced by a number of internal and external factors. The preferred blood pressure determination method would be one that reduces variability between measurements and that reflects the true blood pressure level. In this article, we present the variability of, and agreement between, the blood pressures collected by two indirect methods on the same patients during a hypertensive research project. Data obtained on patients in a typical clinical setting are also provided. Twenty-four-hour diastolic pressures obtained by the automated method demonstrated no regression to a lower mean, while blood pressures obtained casually in the office exhibited such regression. The 95% confidence interval of repeated measures for casual office blood pressure on a patient in a research setting (35/17 mm Hg) or in typical clinic practice (26/19 mm Hg) were similar, while the range of the mean 24-hour automated blood pressure monitoring (21/11 mm Hg) was smaller and demonstrated less variability. The magnitudes of the differences in blood pressures obtained on separate occasions in the same subjects were significantly lower with automated vs casual blood pressure determination methods (7.9/4.6 vs 13.7/7.4 mm Hg for both systolic and diastolic pressures). The agreement (95% confidence interval) between blood pressures obtained by the two methods (19/12 mm Hg) was found to be similar to the repeatability of automated blood pressure monitoring alone, and superior to that for data recorded casually in the office (35/17 mm Hg). Thus, the variability in mean 24-hour automated blood pressures is less than that for casual office blood pressures. The clinician should understand that the variability of blood pressures measured on an individual may be much greater than that reported for populations of hypertensive patients, and must be considered when applying epidemiologic group data to a specific patient. Moreover, any methodology of indirect blood pressure measurement that may reduce the variability and improve repeatability of casual office blood pressures deserves further consideration.

Nifedipine GITS (gastrointestinal therapeutic system) bezoar.

In a patient with a gastroplasty, gastric outlet obstruction developed after the dosage of nifedipine GITS (gastrointestinal therapeutic system) was increased from 30 to 60 mg/d. The hard, insoluble shell for this extended-release tablet appears causative.

Sexual dysfunction with antihypertensive drugs.

The relationship of antihypertensive drugs have a long history of association with sexual dysfunction; however, this relationship is poorly documented. There appears to be a higher rate of sexual dysfunction in untreated hypertensive men compared with normotensive men. Sexual dysfunction increases with age and is associated with physical and emotional symptoms. There are few studies assessing sexual dysfunction with female and African-American hypertensive patients. Sexual dysfunction is associated with impairment of quality of life and noncompliance. Since group data may hide individual drug effects, baseline data should be collected on all patients before initiating therapy with any antihypertensive agent. Although questionnaires may not provide objective information on sexual dysfunction, the response rate to direct questioning may be less than the response rate on a questionnaire and may be affected by the gender or race of the interviewer. Research protocols using a double-blind, placebo-controlled design should assess sexual dysfunction in men and women in a standardized fashion.

Effectiveness of once-daily monotherapy with a new nifedipine sustained release calcium antagonist.

Data from 2 separate multicenter, double-blind clinical studies following the same protocol, except for the selection of doses, were pooled to evaluate the efficacy and tolerability of fixed doses of a new sustained-release (SR) formulation of nifedipine compared with placebo in 388 patients with mild to moderate uncomplicated essential hypertension. After a 3-6 week placebo washout period, the patients were randomized to receive either placebo or nifedipine SR-20 mg (study I only), 50 mg, 100 mg, or 150 mg (study II only). Among the 278 patients who completed 6 weeks of active therapy, mean supine diastolic blood pressure reductions from pretreatment baseline were 5.9, 9.3, 9.2, 11.1, and 13.2 mm Hg in the placebo, 20-, 50-, 100-, and 150-mg groups, respectively. The reductions achieved in each of the nifedipine SR groups were statistically significant versus baseline values (p less than 0.001). All nifedipine-SR doses reduced supine systolic blood pressure significantly more than placebo (p less than 0.001). In addition, there was a significant linear relationship between the log of the dose and the blood pressure reduction (p less than 0.05). Automated ambulatory blood pressure recordings performed in 221 of the patients showed that the blood pressure was lowered evenly through the entire 24-hour dosing period. The doses that were effective and associated with the fewest adverse reactions were 20 mg and 50 mg once daily.

Influence of autonomic neuropathy of different severities on the hypercapnic drive to breathing in diabetic patients.

To investigate the effects of the autonomic nervous system on control of breathing, the neuromuscular (mouth occlusion pressure at 0.1 s after onset of inspiration [P0.1]) and ventilatory (minute ventilation [VE]) response to progressive hyperoxic hypercapnia was assessed in diabetic patients with autonomic dysfunction of different severity. Eighteen diabetics with autonomic neuropathy, nine with parasympathetic damage (DANp), and nine with parasympathetic and sympathetic damage (DANp+s), as indicated by marked postural hypotension, low increment of diastolic BP during sustained handgrip, and lowest resting catecholamine plasma levels, were studied together with a group of 10 diabetic patients without autonomic neuropathy (D) and a group of 10 normal subjects (C). All subjects had pulmonary function tests, including maximal voluntary ventilation and diffusion of carbon monoxide, measurements of respiratory muscle strength as maximal inspiratory mouth pressure (MIP) and maximal expiratory mouth pressure (MEP), and a CO2 rebreathing test (Read's method). Although in the normal range, lung volumes and FEV1 and forced expiratory flows were lower in the DANp and DANp+s groups than in the D and C groups, MIP and MEP were similar among C and diabetic groups, as well as resting P0.1, VE, tidal volume (VT), and respiratory rate (RR). The slope of the linear relationship between P0.1 and end-tidal PCO2 (PETCO2) was higher in DANp+s (0.63+/-0.07 cm H2O/mm Hg) than in C (0.45+/-0.06 cm H2O/mm Hg; p<0.05) and three times greater in DANp+s than in D (0.26+/-0.03 cm H2O/mm Hg; p<0.001) and DANp (0.24+/-0.03 cm H2O/mm Hg; p<0.001), who in turn showed a lower deltaP0.1/deltaPETCO2 than C. The VE increase with increasing PETCO2 was greater in DANp+s (3.70+/-0.85 L/min/mm Hg) than in DANp (2.13+/-0.20 L/min/mm Hg; p<0.05) and D (2.37+/-0.40 L/min/mm Hg; p=0.07), but not significantly higher from that of C (3.17+/-0.36 L/min/mm Hg). No differences were found for deltaVT/deltaPETCO2 among the groups, whereas the deltaRR/deltaPETCO2 relationship was steeper in DANp+s than in DANp (p<0.05) and D (p=0.055). These data reflect a depressed CO2 response both in D and DANp. The presumable decrease of the sympathetic nerve traffic in DANp+s appears to reverse this abnormality. DANp+s, however, exhibit an enhanced CO2 neuromuscular response even in respect to C, suggesting that the sympathetic nervous system might modulate the output of the respiratory centers to hypercapnic stimulus.

Assessment of echocardiographic left ventricular mass before and after acute volume depletion.

Left ventricular mass calculations are often performed to assess the need or effectiveness of antihypertensive drug therapy. However, there are multiple potential errors that may affect the accuracy of these calculations, which can possibly include acute changes in preload. Therefore, to assess the hypothesis that acute volume depletion might alter calculated left ventricular mass, 15 normotensive healthy male volunteers underwent standard M-mode echocardiographic evaluations (at the level of the chordae tendineae guided by two-dimensional echocardiography) before and 2 h after 40 mg of intravenous furosemide. One patient was eliminated due to hypotension prior to the final echocardiogram. The echocardiograms were blinded to patient identity and the time sequence and read separately by two investigators. Four to five cycles were read per echocardiogram by each investigator. All values measured were the mean of the two investigators. Echocardiographic measurements were derived by both the American Society of Echocardiography and Penn conventions. An average urine volume of 1728 mL was collected, and the mean weight change 2 h after furosemide administration was 1.78 kg (P = .001). Penn left ventricular diastolic diameter (1.8 mm, P = .015) and left ventricular mass index (10 g/m2, P = .04) were significantly decreased; however, there was no significant change in septal, posterior, or relative wall thicknesses. As it is unreasonable to believe that acute remodeling of the left ventricle resulted in a decline in left ventricular mass in 2 hours, it is concluded that acute volume changes resulted in a decrease in left ventricular mass measurement due to the influence of diastolic diameter on the calculation of cardiac mass.

Magnetic resonance imaging compared to echocardiography to assess left ventricular mass in the hypertensive patient.

Echocardiography (ECHO) is useful to document changes in left ventricular mass (LVM) in groups of patients, but may be too variable for use in the individual patient. Magnetic resonance imaging (MRI) may be a more precise and reliable method to quantify the mass of the left ventricule. This study reports the accuracy, precision, and reliability of LVM estimates by MRI as compared to data obtained by ECHO in hypertensive patients. Accuracy referred to the comparison of LVM by MRI to anatomical LVM determined by autopsy. Precision was examined using 34 duplicate MRI images and by blindly reading 24 duplicate M-mode strips. Reliability was assessed by MRI in four subjects over 2 months, and by ECHO in 22 hypertensive patients over 2 weeks. Agreement between MRI and ECHO estimates of LVM was determined in the same 17 hypertensive patients using linear regression. MRI LVM estimates were within 17.5 g (95% CI) of the true LVM. The linear agreement between MRI and ECHO estimates of LVM could be described by the equation MRI = 0.61 x ECHO + 49.57 (r = 0.63, P < .01). The precision of LVM by MRI (11 g) was over twice that observed with ECHO (26 g). The reliability of MRI LVM estimates was more consistent (+/- 8 g) than that for ECHO (+/- 49 g). MRI appears to be a more precise and reliable method for measuring LVM, and would be more suitable than ECHO for the clinical evaluation of the individual patient.

Accuracy of the urinary albumin to creatinine ratio as a predictor of albuminuria in adults with sickle cell disease.

AIM: To test the usefulness of a random urine specimen albumin to creatinine ratio (A/C) in predicting 12 hour urinary albumin excretion (12UA) in patients with sickle cell disease. METHODS: 12UA and A/C were measured in nocturnal urine collections and random morning urine samples, respectively, of 72 patients with sickle cell disease. RESULTS: The correlation of A/C values with 12UA values did not provide support for the use of random urine specimens for predicting urinary albumin excretion (UAE) in these patients. However, values of A/C >/= 0.45 and < 0.45 were indicative of raised and normal UAE, respectively. The sensitivity, specificity, and accuracy of the test were 100.0%, 87.2%, and 91.7%, respectively. CONCLUSIONS: This method cannot be recommended for predicting 12UA in patients with sickle cell disease, but it is useful for selecting patients who should collect 12 hour urine for the estimation of UAE.

Ventilatory response to exercise in diabetic subjects with autonomic neuropathy.

We have used diabetic autonomic neuropathy as a model of chronic pulmonary denervation to study the ventilatory response to incremental exercise in 20 diabetic subjects, 10 with (Dan+) and 10 without (Dan-) autonomic dysfunction, and in 10 normal control subjects. Although both Dan+ and Dan- subjects achieved lower O2 consumption and CO2 production (VCO2) than control subjects at peak of exercise, they attained similar values of either minute ventilation (VE) or adjusted ventilation (VE/maximal voluntary ventilation). The increment of respiratory rate with increasing adjusted ventilation was much higher in Dan+ than in Dan- and control subjects (P < 0.05). The slope of the linear VE/VCO2 relationship was 0.032 +/- 0.002, 0.027 +/- 0.001 (P < 0.05), and 0.025 +/- 0.001 (P < 0.001) ml/min in Dan+, Dan-, and control subjects, respectively. Both neuromuscular and ventilatory outputs in relation to increasing VCO2 were progressively higher in Dan+ than in Dan- and control subjects. At peak of exercise, end-tidal PCO2 was much lower in Dan+ (35.9 +/- 1.6 Torr) than in Dan- (42.1 +/- 1.7 Torr; P < 0.02) and control (42.1 +/- 0.9 Torr; P < 0.005) subjects. We conclude that pulmonary autonomic denervation affects ventilatory response to stressful exercise by excessively increasing respiratory rate and alveolar ventilation. Reduced neural inhibitory modulation from sympathetic pulmonary afferents and/or increased chemosensitivity may be responsible for the higher inspiratory output.

Cerebrovascular reactivity and hypercapnic respiratory drive in diabetic autonomic neuropathy.

Because abnormalities in cerebrovascular reactivity (CVR) in subjects with long-term diabetes could partly be ascribed to autonomic neuropathy and related to central chemosensitivity, CVR and the respiratory drive output during progressive hypercapnia were studied in 15 diabetic patients without (DAN-) and 30 with autonomic neuropathy (DAN+), of whom 15 had postural hypotension (PH) (DAN+PH+) and 15 did not (DAN+PH-), and in 15 control (C) subjects. During CO(2) rebreathing, changes in occlusion pressure and minute ventilation were assessed, and seven subjects in each group had simultaneous measurements of the middle cerebral artery mean blood velocity (MCAV) by transcranial Doppler. The respiratory output to CO(2) was greater in DAN+PH+ than in DAN+PH- and DAN- (P < 0.01), whereas a reduced chemosensitivity was found in DAN+PH- (P < 0.05 vs. C). MCAV increased linearly with the end-tidal PCO(2) (PET(CO(2))) in DAN+PH- but less than in C and DAN- (P < 0.01). In contrast, DAN+PH+ showed an exponential increment in MCAV with PET(CO(2)) mainly >55 Torr. Thus CVR was lower in DAN+ than in C at PET(CO(2)) <55 Torr (P < 0.01), whereas it was greater in DAN+PH+ than in DAN+PH- (P < 0.01) and DAN- (P < 0.05) at PET(CO(2)) >55 Torr. CVR and occlusion pressure during hypercapnia were correlated only in DAN+ (r = 0.91, P < 0.001). We conclude that, in diabetic patients with autonomic neuropathy, CVR to CO(2) is reduced or increased according to the severity of dysautonomy and intensity of stimulus and appears to modulate the hypercapnic respiratory drive.

Ambulatory blood pressure monitoring for evaluation and management of hypertensives: effect on outcome and cost effectiveness.

Blood pressure monitoring of hypertensives in the ambulatory state by automated portable devices (ABPM) as compared with casual office readings (COBPM) may predict outcome with greater precision and at an overall lower cost. Prospective trials that in random fashion require evaluation and management decisions on the basis of ABPM compared with COBPM are required to determine whether the above is true. End points such as death, stroke, or myocardial infarction occur at a low frequency rate. This would require thousands of patients to be followed 5 or more years to determine if evaluation and management by ABPM compared with COBPM results in a different outcome. A much smaller population can be used if end points are changes in left ventricular mass and left ventricular ischemia, arterial wall stiffness and thickness, endogenous creatinine clearance, renal albumin excretion, antihypertensive drug requirements, and adverse reactions. Until results from such a prospective trial are available, COBPM is the method of choice for evaluation and management of hypertensives. Automated blood pressure measurement can provide useful information in special circumstances and is of value for research purposes.

Clinical utility of ambulatory blood pressure monitoring in target organ complications and equipment choices.

Although population studies have demonstrated a relationship between casual office blood pressures and target organ events, the variability of these blood pressure measurements for individual patients has generated an interest in the role of ambulatory blood pressure monitoring for defining the presence of hypertension and assessing the response to therapy. Noninvasive devices provide fewer data than intra-arterial ambulatory blood pressure monitoring devices, but are safer. No current noninvasive device performs well during ambulation. Rigorous evaluation of these rapid proliferating electronic devices is important, as would be the case with any new antihypertensive agent. Although ambulatory blood pressure measurements correlate better with target organ damage for groups of patients than do casual office measurements, the predictability and limited data on reproducibility for individual patients does not support widespread application for routine testing for hypertensive patients. Ambulatory blood pressure monitoring should be viewed as a standard research tool for the evaluation of new cardiovascular drugs.

Variability and similarity of manual office and automated blood pressures.

The evaluation and management of hypertension is based on indirect blood pressures obtained in the office (COBPs) using the mercury sphygmomanometer. The usefulness of COBPs is limited by factors such as observer bias, which confound the ability to discern the true blood pressure value. Automated portable monitors have been marketed, which also measure blood pressure (ABP) indirectly throughout 24 hours, but without human intervention. Acceptance of a new device that indirectly records blood pressure depends largely on its the agreement with the established method of blood pressure measurement. This review compares the variability of blood pressures collected indirectly by standard mercury sphygmomanometer and by an auscultatory automated portable blood pressure monitor. The results indicate that blood pressure, when measured indirectly in a hypertensive patient, is quite variable. Automated blood pressures were lower and demonstrated less within-subject variability during repeated measures than COBPs. The agreement between ABPs and COBPs was better than the agreement between COBPs alone on successive visits. In addition, the mean hourly blood pressure profiles recorded throughout 24 hours by automated and manual methods from ten hypertensive patients were nearly identical. These data suggest that blood pressures measured by auscultatory automated methods are similar to and representative of those obtained manually.

Verapamil and nifedipine in combination for the treatment of hypertension.

The authors examined the efficacy and safety of the combination of verapamil and nifedipine in the control of hypertension. Retrospective analysis of blood pressures was obtained on 50 patients who had historically documented essential hypertension and were receiving verapamil and nifedipine. The patients had moderate to severe hypertension; 27 of 50 (54%) were uncontrolled on prescribed regimens of two or more separate classes of drugs. Control was defined by the ability to maintain a blood pressure of < or = 160/90 by providing doses of verapamil (max: 480 mg/day) and nifedipine (max: 180 mg/day). Twenty-nine (58%) were black and 21 (42%) were white. Ages ranged from 16 to 84 years. Mean duration of therapy was 1-2 years. Only 3 of 50 (6%) were control failures after providing verapamil and nifedipine. Three of 50 (6%) were discontinued because of side effects--reversible hepatitis (2) and rash (1). There were no serious adverse events, i.e., CHF or arrhythmias. Manageable ankle edema was seen in 14 of 50 (28%) patients. Verapamil and nifedipine, a combination of a dihydropyridine and a non-dihydropyridine calcium antagonist, was effective and safe in this group of patients with difficult-to-manage hypertension.

Once-daily verapamil in the treatment of mild-to-moderate hypertension: a double-blind placebo-controlled dose-ranging study.

Supine office blood pressures (SOBP) and 24-hour automated ambulatory blood pressure monitorings (AABPM) showed blood pressure reductions from a stable baseline to active treatment with 120-, 240-, and 480-mg doses of a new verapamil QD capsule (solid-spheroidal-oral once-daily drug-absorption system: (SODAS) in patients with mild-to-moderately severe (diastolic blood pressures 95-119 mm Hg) essential hypertension. Reductions were documented at 24 hours, hourly, and by the 24 hour average, using SOBP and AABPM, after the once-daily verapamil administration. Both SOBP and the 24-hour average by AABPM were significantly reduced from baseline by active verapamil treatment of 120-, 240-, and 480-mg doses. In comparison to verapamil QD (0 mg), blood pressure reductions from baseline to active treatment were significant at the 240- and 480-mg doses but not at the 120-mg dose. There was a significant linear dose response. This verapamil formulation (SODAS) was effective throughout the 24-hour period after once-daily dosing.