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Biomedical subjects

A A Carr

Publications and source records attributed to A A Carr.

At least 19 recordsLinked to original sources
PubMed1992

Novel drug-delivery systems for hypertension.

Although novel controlled-release drug-delivery systems have been used in other areas of medicine, their application in the treatment of hypertension has been relatively recent. Biotechnical use of chemical-dispensing systems has been applied to propranolol, clonidine (the transdermal therapeutic system), nifedipine (the gastrointestinal therapeutic system), verapamil (the sodium alginate and spheroidal oral-delivery absorption system), felodipine (the hydrophilic gel principle), metoprolol succinate (the multiple-unit pellet system), and diltiazem (one system comprising sustained-release beads and the other utilizing the patented Geomatrix extended-release system). Oral drug-delivery systems allow antihypertensive agents that previously had to be administered two to four times daily to be administered once each day. Potential disadvantages of the oral controlled-release products include delayed attainment of pharmacodynamic effect, unpredictable or reduced bioavailability, enhanced first-pass hepatic metabolism, dose dumping, sustained toxicity, dosing inflexibility, and increased cost. Potential advantages include reduced dosing frequency, enhanced compliance and convenience, reduced toxicity, stable drug levels, uniform drug effect, and decreased total dose. Although skin reactions are common, the transdermal drug delivery of clonidine provides another innovative approach to supplying transcutaneous, controlled, continuous delivery of drug for 7 days. It is possible that future research will prove that the agents that provide complete 24-hour control may reduce the cardiovascular events associated with the early-morning blood pressure surge. This evolution in antihypertensive therapy to achieve once-daily dosing may prove to be of great value to both physicians and patients in the 1990s.

Administration, Cutaneous↗
PubMed1992

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.

Adult↗
PubMed1992

Morphologic, hemodynamic and coronary perfusion characteristics in severe left ventricular hypertrophy secondary to systemic hypertension and evidence for nonatherosclerotic myocardial ischemia.

Patients with the clinical diagnosis of ischemic heart disease who were found to be free of significant coronary artery atherosclerotic disease (n = 150) underwent coronary vasodilator reserve testing, 2-dimensional echocardiography, and dipyridamole limited-stress thallium testing. After exclusions (predominantly for technically poor coronary artery Doppler signals or suboptimal echocardiography), 100 patients formed the study population. The purpose was to characterize typical cardiac and coronary artery findings in hypertensive patients with severe left ventricular (LV) hypertrophy (n = 15) and to investigate the evidence for myocardial ischemia unrelated to coronary atherosclerosis in early and advanced hypertensive heart disease. Normotensive and hypertensive control groups without LV hypertrophy (n = 12 and 34, respectively) were used for comparison. Severe LV hypertrophy was defined as LV mass index greater than or equal to 50% above established gender specific norms using 2-dimensional-directed M-mode echocardiography and the cube equation corrected to agree with necropsy estimates of mass. Clinical characteristics more often associated with severe LV hypertrophy were black race (67%), diabetes mellitus (33%), proteinuria (47%) and elevated creatinine (1.5 +/- 0.9 mg/dl). Baseline electrocardiograms and dipyridamole limited-stress thallium scans were highly likely to be abnormal (94 and 73%, respectively). Both eccentric and concentric cardiac hypertrophies were found in the severe group. Ejection fraction was significantly lower (0.51 vs 0.68, p = 0.002) and basal coronary flow velocity higher (12.0 vs 5.0 cm/s, p = 0.0004) among these patients when compared with normotensive control patients. Coronary flow reserve did not differ between control groups but was significantly depressed in patients with severe LV hypertrophy (2.5 vs 3.9, p = 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1992

Pharmacotherapy of unstable angina.

All patients with unstable angina should be admitted to a coronary or an intensive care unit. There should be an attempt to classify the patient according to the proposed Braunwald nomenclature. If the patient has a secondary cause for unstable angina (e.g., tachyarrhythmia, heart failure, fever, thyrotoxicosis, severe hypertension, hypoxia, unusual emotional stress, or anemia), this condition should be treated initially with therapy specific for that etiology. If the patient does not have a secondary etiology, therapy should be initiated with nitrates, preferably intravenous nitroglycerin. Heparin should be concomitantly administered. If the patient cannot receive heparin, aspirin should be initiated. All patients should receive beta-blockers. If the patient cannot take a beta-blocker, a calcium antagonist (probably diltiazem) should be initiated. However, if the patient is refractory to beta-blockers, the dihydropyridine nifedipine should be added. Failure to all pharmacologic interventions necessitates a progressive invasive approach dictated by the potential surgical risk of the patient. Long-term aspirin and beta-blockers should be strongly considered.

Angina, Unstable↗
PubMed1992

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.

Ambulatory Care↗
PubMed1992

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.

Blood Pressure↗
PubMed1992

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.

Ambulatory Care↗
PubMed1992

A negative thallium (+/- dipyridamole) stress test excludes significant obstructive epicardial coronary artery disease in hypertensive patients.

The operating characteristics of thallium stress testing for detection of significant epicardial coronary artery disease (CAD) in hypertensive subjects with chest pain or electrocardiographic (ECG) ischemia have not been previously defined. This becomes important because of the high prevalence of both hypertensive heart disease and CAD. Ninety-two hypertensives with a history of typical or atypical chest pain or ECG myocardial ischemia underwent coronary arteriography, 2D-guided echocardiography, and thallium-201 stress testing, combined with intravenous dipyridamole if the rate-pressure product was less than 20,000. Patients with myocardial infarction, prior revascularization procedure, valvular heart disease, and chronic ethanol abuse were excluded. The mean age was 54.8 +/- 9.9 years with 55% blacks and 46% women. Eighteen patients (19.6%) had significant (greater than or equal to 50% luminal diameter narrowing) epicardial CAD at catheterization, of whom 17 had positive thallium scans. Overall, there were 17 true positives, 47 true negatives, 27 false positives, and one false negative resulting in 94.4 +/- 5.4% sensitivity (95% confidence limits [95% CL] 71 to 100%), 63.5 +/- 5.6% specificity (95% CL 51 to 74%), 38.6 +/- 7.3% positive predictive value (95% CL 25 to 54%), 97.9 +/- 2.1% negative predictive value (95% CL 88 to 100%), and 69.6 +/- 4.8% overall accuracy (95% CL 59 to 79%). For hypertensive patients with chest pain or ECG myocardial ischemia, the high sensitivity and negative predictive value and low false negative rate support the role of thallium stress testing +/- dipyridamole as an exclusion test for significant CAD.

Adult↗
PubMed1992

Repeatability of automated ambulatory blood pressure measurements.

BACKGROUND: The repeatability of 24-hour automatic ambulatory blood pressure measurements recorded by noninvasive equipment (Del Mar Pressurometer IV) was assessed to determine the intrapatient variability of this test. METHODS: The usual antihypertensive medications of 73 patients with documented essential hypertension (supine diastolic blood pressure of 95 to 119 mm Hg) were withdrawn, and the patients were treated with placebo medication for 6 weeks. At the end of the placebo period, ambulatory blood pressure measurements of each patient were recorded every 15 minutes for 24 hours on two separate occasions 1 week apart. RESULTS: There was no significant difference in either the 24-hour systolic or diastolic blood pressure for the entire group between weeks. A mean difference for individual patients between the first and second recording within 5 mm Hg was observed in 49.3% and 52.1% of patients for 24-hour systolic and diastolic blood pressure, respectively. The correlation coefficient for 24-hour systolic blood pressure was greater than 24-hour diastolic blood pressure (r = .87 vs r = .67). A difference greater than 18.1/14.9 mm Hg for systolic/diastolic blood pressure would be required to assign a significant (P less than .05) change in blood pressure between two recordings in the same patient. CONCLUSIONS: These data quantify the usefulness of 24-hour ambulatory blood pressure measurements for a group of subjects. However, mean 24-hour ambulatory blood pressure varies significantly for individuals. Intrapatient variability may limit the usefulness of a single 24-hour ambulatory recording for an individual patient and suggests the need for more than one measurement to establish a level of blood pressure.

Adult↗
PubMed1992

Doppler echocardiographic assessment of filling and emptying parameters and ambulatory blood pressure measurements in normotensives and hypertensives.

To evaluate the relationship between office and ambulatory BP measurements and filling and emptying parameters, 15 hypertensive and 15 control subjects underwent both 24 hour ambulatory BP monitoring and Doppler echocardiography. No patient received antihypertensive medication for 3-4 weeks, had echocardiographic left ventricular hypertrophy (greater than or equal to 12 mm) or a diastolic BP greater than 100 mm Hg. The time from R wave on the electrocardiogram to onset of ejection was prolonged in hypertensives (P less than 0.05). There were no differences between the hypertensives and normotensives for diastolic filling abnormalities. Finally, neither office nor ambulatory BP correlated with either Doppler filling or emptying parameters.

Adult↗
PubMed1992

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.

Ambulatory Care↗
PubMed1991

Relationship between coronary blood flow and perfusion pressure during reactive hyperemia: a case report in an awake unanesthetized woman with normal coronary arteries.

The linear relationship between coronary blood flow and mean arterial pressure during reactive hyperemia is presented for the first time in an awake unanesthetized woman with normal coronary arteries during systemic hypotension induced by pharmacologic vasodilation. This case demonstrates the critical dependence of coronary flow reserve on simultaneous perfusion pressure.

Aged↗
PubMed1991

The effect of cardiac catheterization on fasting lipids.

Fasting lipid profiles were measured in 20 selected patients the day of and after cardiac catheterization in EDTA tubes. Samples were randomly labelled A or B, centrifuged, and stored at 3 degrees Centigrade. Lipid profiles were analyzed by a laboratory, which was participating in the Center for Disease Control Lipid Standardization Program, by using standard methods. The coefficients of variation for repeated measurements were: cholesterol = 1.9%, triglycerides = 3.6%, HDL cholesterol = 4.3%, and VLDL and LDL cholesterol = 2.6%. Data were evaluated by a two-tailed paired t-test and correlation coefficient. The total cholesterol was significantly lower (P less than .001) the day after cardiac catheterization as was the LDL cholesterol (P less than .002). Both VLDL and HDL cholesterol and triglycerides were lower, but these were not statistically significant. The mean dose of heparin was 3500 +/- 1469 units, and the mean dose of contrast was 181 +/- 30 cc. The total dose of heparin or contrast did not correlate with any change in lipid profiles. These results have implications on the number and timing of venous blood sampling for lipid measurements in regard to diagnosis and treatment of hyperlipidemia. Lipid profiles should not be drawn after cardiac catheterization but rather before and/or in the free-living state.

Adult↗
PubMed1991

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.

Blood Pressure↗
PubMed1991

Assessment of electrocardiographic ischemia in hypertensive patients treated with isradipine or placebo.

A total of 203 patients with hypertension (supine diastolic blood pressure of 100-119 mm Hg) from six centers entered into a 3-week placebo baseline followed by 5 weeks of active treatment (either placebo or isradipine 2.5, 5, 7.5, or 10 mg BID) to determine the effectiveness of isradipine on blood pressure control. Electrocardiographic criteria for left-ventricular ischemia were coded blindly using the Minnesota Codes 4-1 to 4-4 and 5-1 to 5-3 at the end of baseline and active treatment periods. One hundred seventy patients with hypertension and matching and complete electrocardiograms completed the study for analysis: 63 (37%) were white and 117 (69%) were men. They were 52.1 +/- 10.3 years old mean +/- SD; range: 22-77 years). No myocardial infarction occurred during the active phase. Fifty-eight of 170 (34%) at baseline and 54 of 116 (32%) at week 5 had left atrial enlargement. Romhilt-Estes left-ventricular hypertrophy was not significantly different at baseline versus active treatment: 14 of 170 (8.2%) versus 15 of 170 (8.8%). At baseline, the rate of active ischemia was 28.2% (48/170): 27.8% (10/36) were randomized to receive placebo during active treatment and 28.4% (38/134) were given isradipine (P = NS). For those without ischemia at baseline, the rate of change to electrocardiographic ischemia during active treatment was 0% (0/26) for those receiving placebo and 3.1% (3/96) for those taking isradipine (P = NS). For those with ischemia at baseline, the rate of change to no ischemia during active treatment was 20% (2/10) for those receiving placebo and 10.5% (4/38) for those taking isradipine (P = NS).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1991

Relationship of left ventricular mass to impairment of coronary vasodilator reserve in hypertensive heart disease.

An impaired coronary vasodilator reserve has been demonstrated in all stages of hypertensive heart disease but is most likely in the setting of hypertrophy. The decrease in coronary flow reserve has, however, not been predictable previously. We postulated that flow reserve depression might be related to a left ventricular mass threshold. Seventy-two patients (82% with hypertension) with suspected ischemic heart disease who were found to be free of significant coronary artery disease at cardiac catheterization were evaluated utilizing the intracoronary Doppler catheter and two-dimensional directed M-mode echocardiography for determination of coronary flow reserve and left ventricular mass. For left ventricular mass indexed (LVMI) by body surface area (BSA) greater than or equal to 50% above normal using established gender-specific norms, American Society of Echocardiography (ASE) and PENN methods (correction of LV mass by regression equation agreeing with necropsy estimates of mass) predicted impairment of flow reserve (p = 0.005 and 0.009, respectively). Unindexed left ventricular mass and LVMI by height were not helpful in this regard. Using the ASE method for LV mass determination, coronary flow reserve was moderately depressed (2.4 +/- 1.0) for those with LVMI greater than or equal to 50% above normal; in comparison, flow reserve was normal (3.5 +/- 1.3) for those with LVMI less than 50% above normal. A rare patient was able to maintain a normal flow reserve when ASE- and Penn-indexed mass estimates were greater than or equal to 50% above normal, but only in the setting of a markedly elevated mean arterial pressure.

Adult↗