Failure of the community-based Vita-Stat automated blood pressure device to accurately measure blood pressure.

OBJECTIVE: To evaluate the Vita-Stat automated blood pressure computer (a patient-operated blood pressure measuring device available in the community) to determine its value as an instrument to monitor blood pressure in the ambulatory patient. DESIGN: Comparative study using the Vita-Stat vs a gold standard, the mercury sphygmomanometer. SETTING: Three local grocery stores. PARTICIPANTS: Sixty-three passersby who agreed to answer questions and to sit for several measurements of blood pressure. INTERVENTIONS: Simultaneous measurement of blood pressure with each subject wearing a Vita-Stat cuff on the left arm and a mercury sphygmomanometer cuff on the right arm. Two pressures were measured sequentially in the same manner. MAIN OUTCOME MEASURES: The reproducibility, accuracy, sensitivity, and specificity of the Vita-Stat computer compared with the gold standard. RESULTS: In sequential measurements, the Vita-Stat readings of both systolic and diastolic blood pressure correlated less well with each other than did the mercury readings (intramachine differences). The Vita-Stat readings also correlated poorly with the mercury readings of systolic and diastolic blood pressure (intermachine differences). The variability in readings recorded by the Vita-Stat were striking, with differences of up to 60 mm Hg from the mercury readings. More than half (63.2%) of the subjects had Vita-Stat readings that were more than 5 mm Hg different from the mercury readings. Vita-Stat systolic readings were usually lower than mercury readings and also varied by as much as 60 mm Hg below in one patient to 58 mm Hg above the mercury reading in another. The sensitivity of the Vita-Stat in correctly diagnosing hypertension was 0.26; the negative predictive value was 0.45. CONCLUSIONS: Our data suggest that the Vita-Stat is not only inconsistent but inaccurate in measuring blood pressure in the ambulatory patient and is, therefore, not appropriate to use as a monitoring device.

A prospective study of heparin-induced osteoporosis in pregnancy using bone densitometry.

OBJECTIVE: Our purpose was to evaluate the subclinical occurrence of heparin-induced osteoporosis in pregnancy, by means of bone densitometry. STUDY DESIGN: A prospective, consecutive cohort of 14 pregnant women requiring heparin therapy and 14 pregnant controls matched for age, race, and smoking status was identified by 20 weeks' gestation at a university medical center. Proximal femur bone density measurements were taken at baseline, immediately post partum, and 6 months post partum in the cases and controls. Vertebral measurements were also obtained on both groups immediately post partum and 6 months post partum. Bone density as a function of heparin dosing and duration was examined. Nonparametric statistical tests were used for all comparisons. RESULTS: Five of 14 cases (36%) had a > or = 10% decrease from the baseline proximal femur measurements to immediate postpartum values versus none of the 14 matched controls (p = 0.04). Mean proximal femur bone density measurements also decreased in the cases (p = 0.01); this difference continued to be statistically significant 6 months post partum (p = 0.03). No dose-response relationship could be demonstrated. CONCLUSION: Heparin adversely affected bone density in about one third of exposed patients.

The hypotensive action of captopril and enalapril is not prostacyclin dependent.

Angiotensin converting enzyme inhibitors have been proposed to have a prostaglandin-dependent component to their hypotensive action. The aim of this study was to assess whether the structurally dissimilar angiotensin converting enzyme inhibitors captopril and enalapril stimulate the synthesis of prostacyclin, whether their hypotensive action is blunted by indomethacin, and whether these biochemical or physiologic parameters differ for the two drugs, in white subjects with essential hypertension. Twelve patients were enrolled and 11 finished the study. The study consisted of a double blind, randomized, double-crossover design. All patients received either placebo or 50 mg indomethacin twice a day for 3 weeks; after 1 week of placebo or indomethacin either 50 mg captopril or 10 mg enalapril twice a day was added and continued for 2 weeks. Each patient received every possible combination. Neither captopril nor enalapril stimulated prostacyclin production as determined by measurement of the urinary excretion rate of its main enzymatic metabolite, 2,3-dinor-6-keto-prostaglandin-F1 alpha. Although indomethacin reduced the urinary excretion of the enzymatic metabolite of prostacyclin by more than 50%, it did not influence the hypotensive effect of captopril or enalapril. We conclude that neither captopril nor enalapril have a significant prostacyclin-dependent component to their hypotensive action.

Cytosolic calcium and insulin resistance in elderly patients with essential hypertension.

We evaluated insulin sensitivity in normotensive (blood pressure, BP, less than 135/85 mm Hg) and hypertensive (BP greater than 160/90 mm Hg) elderly subjects over 65 years old who were stratified as normal weight (body mass index, BMI, less than 27) and obese (BMI greater than 27). Obese hypertensive individuals demonstrated marked hyperinsulinemia (P less than .01) and significantly reduced (P less than .05) submaximally stimulated adipocyte 2-deoxyglucose (2-DOG) uptake (abdominal wall fat biopsy). Normal weight hypertensive subjects also demonstrated higher levels of insulinemia and lower insulin-stimulated 2-DOG uptake than nonobese controls. Adipocyte [Ca2+]i levels were elevated in all elderly subjects compared to young individuals (P less than .01). Basal and maximally stimulated 2-DOG uptake were similar in all groups. One month of therapy with a calcium channel blocker, 10 mg nitrendipine twice daily, reduced blood pressure in the hypertensive subjects, reduced plasma insulin to control values during an oral glucose tolerance test in obese hypertensive individuals (P less than .01), and restored adipocyte 2-DOG uptake at submaximally effective insulin concentration to control values in normal weight and obese hypertensive subjects. In summary, older hypertensive, and particularly older obese hypertensive, patients manifest significant insulin resistance accompanied by elevated levels of [Ca2+]i in their adipocytes.

The antihypertensive efficacy of hydrochlorothiazide is not prostacyclin dependent.

We tested the hypothesis that vascular prostacyclin synthesis is stimulated by hydrochlorothiazide and could account for some of the drug's antihypertensive effect. We studied 13 patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin on hydrochlorothiazide's ability to lower blood pressure, alter body weight, stimulate plasma renin activity, and modulate vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), measured by GC/MS. Administration of hydrochlorothiazide, 50 mg daily for 2 weeks, was associated with a significant decrease in both systolic and diastolic blood pressure in both supine (systolic, 148 +/- 3 to 136 +/- 3 mm Hg; diastolic, 97 +/- 2 to 94 +/- 3 mm Hg) and upright (systolic, 151 +/- 4 to 131 +/- 2 mm Hg; diastolic, 103 +/- 2 to 97 +/- 3 mm Hg) positions. Hydrochlorothiazide administration resulted in a 1 kg weight loss and stimulation of plasma renin activity from 1.7 +/- 0.4 to 5.3 +/- 1.1 ng angiotensin I/ml/hr. However, the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha was unchanged after administration of hydrochlorothiazide (86 +/- 13/ng/gm creatinine during placebo, 74 +/- 13 ng/gm during week 1 of hydrochlorothiazide, and 70 +/- 9 ng/gm during week 2 of the drug). Administration of indomethacin, 50 mg twice a day, resulted in greater than 60% inhibition of 2,3-dinor-6-keto-PGF1 alpha excretion but did not affect the antihypertensive response to hydrochlorothiazide. Indomethacin did not oppose the diuretic effect of hydrochlorothiazide as assessed by weight loss but did attenuate the rise in plasma renin activity. Our data demonstrate that the blood pressure-lowering effect of a thiazide diuretic does not require enhanced prostacyclin synthesis and the cyclooxygenase inhibitor indomethacin does not antagonize the antihypertensive efficacy of hydrochlorothiazide.

Lack of efficacy of hydergine in patients with Alzheimer's disease.

BACKGROUND: There is no effective pharmacologic treatment for Alzheimer's disease, the most common dementing illness in the United States. Hydergine, a combination of ergoloid mesylates, is the only approved medication for Alzheimer's disease, but despite widespread use its efficacy remains to be established. We conducted a clinical trial of Hydergine-LC, a newer preparation of ergoloid mesylates in the form of a liquid in a capsule (LC) that may have greater bioavailability, to determine its value in patients with Alzheimer's disease. METHODS AND RESULTS: Eighty older adults with probable Alzheimer's disease participated in this double-blind, placebo-controlled trial of Hydergine-LC for 24 weeks. The recommended dose of 1 mg orally three times daily was used. Cognition and behavior were evaluated before and after the trial, and the patients were monitored for adverse effects. The medication was safe and well tolerated. The Hydergine-LC group did not perform better after treatment than the placebo group on any test, and its performance was worse (P less than 0.01 and P less than 0.02, respectively) on one cognitive measure (Wechsler Adult Intelligence Scale Digit Symbol Substitution Task) and on one behavioral scale (the Geriatric Evaluation by Relatives Rating Instrument). CONCLUSIONS: Hydergine-LC appears to be ineffective as a treatment for Alzheimer's disease.

Hydralazine does not stimulate prostacyclin biosynthesis in hypertensive patients.

The hypothesis that vascular prostacyclin synthesis is stimulated by the oral administration of hydralazine and may account for part of its vascular effect was tested. Eight white patients with mild essential hypertension were studied in a randomized, double-blind design to assess the effects of indomethacin on hydralazine's ability to lower blood pressure, elevate pulse, and alter the vascular prostacyclin biosynthesis as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha) measured by gas chromatography-mass spectrometry. Administration of hydralazine at either 50 mg bid or 100 mg bid for a week, doses commonly administered in clinical settings, was not associated with a statistically significant fall in mean blood pressure, although there was a tendency towards a decrease but did result in an increase in heart rate. Administration of indomethacin had no effect on the hemodynamic parameters secondary to hydralazine. Administration of indomethacin resulted in a slight but significant weight gain compared to placebo, but the addition of hydralazine did not result in a further increase in weight. Neither dose of hydralazine resulted in an increase in the urinary excretion of 2,3-dinor-6-keto-PGF1 alpha. The excretion rate was 85 +/- 16 ng/g of creatinine during placebo, 88 +/- 16 ng/g of creatinine during hydralazine, 50 mg bid, and 65 +/- 8 ng/g of creatinine during hydralazine, 100 mg bid. Administration of indomethacin, 50 mg bid, resulted in a significant decrease in 2,3-dinor-6-keto-PGF1 alpha from 65 +/- 6 ng/g to 37 +/- 8 ng/g of creatinine.(ABSTRACT TRUNCATED AT 250 WORDS)

Research consent forms: continued unreadability and increasing length.

Consent forms are often long and incomprehensible. The authors studied 88 consecutive research consent forms generated at the Denver Veterans Administration Medical Center, evaluating the reading levels of the forms using the Fry Readability Scale and recording the numbers of lines of text. The mean grade reading level required for comprehension was 13.4 years of schooling. Twenty-two percent of all text passages scored were at the postgraduate level of readability. This difficult readability level has not improved since the forms were last tested in 1982. The mean length of the forms was 84.6 lines. Also found was a 58% increase in the length of forms since 1982, a factor known to impair comprehension. These factors, poor readability and increasing length, may make many consent forms incomprehensible. It is recommended that investigators be brief, use plain English, and write consent forms at appropriate reading levels, and receive training on how to obtain valid consent.

The natural history of medication compliance in a drug trial: limitations of pill counts.

To assess medication compliance over time, we prospectively performed pill counts among 121 ambulatory hypertensive subjects for less than or equal to 12 months. Prescribed regimens consisted of pinacidil or hydralazine administered four times a day and of secondary drugs administered up to twice daily. Surreptitious pill counts occurred every 1 to 12 weeks. Among a middle-aged subject group that had been selected for high rates of compliance, we observed mean compliance rates that approximated 100%. We noted marked intrasubject and intersubject variability for any one medication, between medications, and over time. From baseline blood pressures (+/- SE) of 155.5 +/- 1.9/97.3 +/- 1.0 mm Hg, subsequent mean blood pressures varied by compliance subgroup: "hypocompliers" (less than 80%), 151.3/91.0 mm Hg; "hypercompliers" (greater than or equal to 120%), 147.6/91.4 mm Hg; and "eucompliers" (80% to 119%), 143.3/88.5 mm Hg (systolic blood pressure: F1,52 = -220.9, NS; diastolic blood pressure: F1,52 = -121.4, NS). We concluded that weekly pill counts indicated marked intersubject and intrasubject variability, obscured by long-term averages; that compliance lapses appeared to be random; and that excessive medication-taking was the most consistent with "pill dumping."

Treatment of hypertension in the elderly with a new calcium channel blocking drug, nitrendipine.

PURPOSE: Treatment of hypertension in the elderly decreases cardiovascular morbidity and mortality. We hypothesized that nitrendipine would be efficacious in the treatment of hypertension in the elderly. We evaluated potential differences between nitrendipine and the commonly used drug hydrochlorothiazide (HCTZ). PATIENTS AND METHODS: The study was conducted as a double-blind randomized clinical trial of nitrendipine or HCTZ. Thirty hypertensive subjects over age 60 with a median sitting blood pressure greater than or equal to 95 mm of Hg were recruited into the study. A diastolic blood pressure with treatment of less than 95 mm Hg with a 5 mm Hg or greater decrease from baseline was considered a successful response. RESULTS: Nitrendipine decreased mean (+/- SEM) blood pressure from 163 +/- 3/102 +/- 1 to 142 +/- 2/89 +/- 2 mm Hg, and HCTZ decreased it from 164 +/- 4/102 +/- 1 to 143 +/- 5/91 +/- 2 mm Hg. A greater proportion of patients had a successful response with nitrendipine (81 percent) than with HCTZ (64 percent). The antihypertensive effect of nitrendipine twice daily appeared to be sustained for 24 hours. Blood pressure response to exercise was attenuated with both drugs. HCTZ caused gout, leg pains, muscle aches, hypokalemia, increased uric acid levels, and increased total cholesterol and triglyceride levels. Nitrendipine caused edema and tachycardia. CONCLUSION: Nitrendipine significantly reduces blood pressure with few side effects and no adverse metabolic effects, and offers a reasonable alternative for treating hypertension in the elderly.

Propranolol increases prostacyclin synthesis in patients with essential hypertension.

We tested the hypothesis that vascular prostacyclin synthesis is increased by propranolol and could account for some of the drug's antihypertensive effect. We studied 10 white patients with mild essential hypertension in a randomized, double-blind design to assess the effects of indomethacin with or without the addition of propranolol on blood pressure and vascular prostacyclin biosynthesis, as assessed by the urinary excretion of the major enzymatically produced metabolite of prostacyclin, 2,3-dinor-6-keto-prostaglandin F1 alpha (PGF1 alpha), F1 alpha (PGF1 alpha), measured by gas chromatography-mass spectrometry. Seven patients responded to propranolol with a lowering of mean arterial blood pressure in both supine and upright postures. The fall in mean arterial blood pressure (-14.1 +/- 2.1 mm Hg sitting; -17.4 +/- 1.7 mm Hg supine) with propranolol alone was significantly greater than that produced when propranolol was given to patients receiving indomethacin (-7.8 +/- 1.9 mm Hg sitting; -7.7 +/- 3.0 mm Hg supine). Our drug-responsive patients demonstrated a significantly lower excretion rate of 2,3-dinor-6-keto-PGF1 alpha than was found in an age and sex-matched group of normal volunteers. With propranolol treatment, drug-responsive patients showed a significant increase in the excretion of 2,3-dinor-6-keto-PGF1 alpha, such that the mean excretion was not significantly different from that in normal volunteers. Indomethacin caused a significant rise in mean arterial blood pressure and a significant fall in 2,3-dinor-6-keto-PGF1 alpha excretion, and it blocked the rise in urinary 2,3-dinor-6-keto-PGF1 alpha associated with propranolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of a simple method for measuring blood cholesterol levels using non-laboratory observers.

PURPOSE: Blood cholesterol is a good estimator of risk for coronary heart disease. Six criteria for a screening cholesterol measurement are: (1) high predictive value of elevated cholesterol compared with a "gold standard" cholesterol measurement; (2) high correlation with the national reference system for cholesterol; (3) acceptable results obtainable by volunteer observers; (4) results available quickly; (5) reproducible results; and (6) low cost. We hypothesized that cholesterol measurements performed on the Reflotron by volunteer nurses would meet these criteria. SUBJECTS AND METHODS: We recruited 345 subjects (160 men, 185 women, aged 20 to 84) and measured their blood cholesterol level by a method calibrated under the National Heart, Lung, and Blood Institute Lipid Standardization Program (Lab-chol) and on the Reflotron (R-chol method). RESULTS: Comparison of the results showed good agreement (slope = 0.937; intercept = 0.27 mmol/liter). Comparison of the risk assignments made by the R-chol method against those made by the Lab-chol method, using the 1987 Adult Treatment Panel classification criteria, showed that the R-chol method has a sensitivity of 0.79 and a specificity of 0.98. Assuming a national prevalence of hypercholesterolemia of 25 percent, the positive predictive value is 0.92 and the negative predictive value is 0.93. The cost per screen was $1.25. CONCLUSION: These data show that volunteer observers can obtain screening cholesterol results on the Reflotron that are accurate, reliable, quickly available at a low cost, and have high predictive value for hypercholesterolemia.

Pill count measures of compliance in a drug trial: variability and suitability.

To evaluate pill counts as a compliance measure for drug trials, we followed 121 ambulatory hypertensives selected for good compliance over less than or equal to 12 months. The medication regimens consisted of either pinacidil or hydralazine as monotherapy or with propranolol and/or hydrochlorothiazide. Pill counts for the two primary drugs were obtained at each of the 20 return visits. The population was characterized by chronic uncomplicated hypertension and sociodemographic diversity; mean age was 53 years. Despite excellent average weekly pill counts (overall mean compliance rate [+/- SD] = 96.0 +/- 13.2%), we observed large intersubject and intrasubject variance in weekly pill count assessment: individuals' mean standard deviation = 13.7% (range = 0%-86%) and mean coefficient of variation = 0.138 (range = 0.001-0.410). By pill count, 35% of individuals exhibited greater than 110% compliance on at least 1 visit. We conclude that (a) pill count variability is large, even among highly selected subjects, (b) traditional reports of overall pill counts are suboptimal, and (c) pill counts may unreliably measure medication-taking behavior because "supranormal" compliance by this method is improbable but common.

A double-blind, randomized, controlled trial comparing pinacidil to hydralazine in essential hypertension.

Pinacidil is a direct vasodilator with good absorption, a half-life of 2 to 4 hours, and side effects similar to those of other vasodilators. We hypothesized that controlled-release pinacidil would be comparable to or better than hydralazine for blood pressure control and side effects. A double-blind, randomized trial comparing pinacidil with hydralazine when combined with hydrochlorothiazide or propranolol to control side effects or the diastolic blood pressure was performed. Pinacidil decreased systolic and diastolic blood pressure from 156/100 mm Hg to 132/81 mm Hg. The increase in heart rate and weight with both drugs was controlled with the additional drugs. There was 1/17 successes on monotherapy with both drugs. When combined with other drugs there were 15/18 successes with hydralazine and 16/20 successes with pinacidil. Side effects were typical of vasodilators. Both drugs acutely increased plasma norepinephrine and epinephrine during chronic therapy.

Effect of a sustained-release formulation of trimazosin in mild to moderate hypertension.

A single-blind study was conducted to evaluate the blood pressure (BP) reduction and side effects of a sustained-release (SR) formulation of trimazosin in patients with mild to moderate hypertension. Eighteen individuals (age, 21-65 yr; mean diastolic BP, greater than 95 mm Hg) with essential hypertension were enrolled into the study. Each patient's dose was titrated to a range of 150-900 mg/d, with polythiazide added as necessary to achieve BP control. Four hours following the maximum titrated dose of trimazosin, mean standing and supine diastolic BPs were significantly lower than baseline readings. Supine systolic BP and supine and standing heart rate were not significantly lower than baseline. At 24 hours after administration of the maximum dose, there were no significant differences in heart rate of BP compared with baseline readings. Five of 16 patients responded to trimazosin therapy alone. Of the 11 treatment failures with trimazosin alone, five were therapeutic failures and six discontinued because of side effects. Only two of these 11 patients achieved satisfactory results with the combination therapy. Trimazosin SR acutely lowers BP three to six hours after administration. It appears to have a duration of action longer than six hours, but it is not sustained for 24 hours. The proportion of patients failing to respond in this sample was very high and suggests that for similar patients, the drug does not appear to be a very useful antihypertensive agent.