Relations among impaired coronary flow reserve, left ventricular hypertrophy and thallium perfusion defects in hypertensive patients without obstructive coronary artery disease.

Invasive Doppler catheter-derived coronary flow reserve, echocardiographic measurements of left ventricular hypertrophy and intravenous dipyridamole-limited stress thallium-201 scintigraphy were compared in 48 patients (40 were hypertensive or diabetic) with clinical ischemic heart disease and no or minor coronary artery disease. Abnormal vasodilator reserve (ratio less than 3:1) occurred in 50% of the study group and markedly abnormal reserve (less than or equal to 2:1) occurred in 27%. Coronary vasodilator reserve was significantly lower (2.2 +/- 0.8 versus 3.5 +/- 1.3, p = 0.003) and indexed left ventricular mass significantly higher (152.6 +/- 42.2 versus 113.6 +/- 24.0 g, p = 0.0007) in patients with a positive (n = 11) versus a negative (n = 32) thallium perfusion scan. Coronary flow reserve was linearly related in coronary basal flow velocity as follows: y = -0.17x + 4.59; r = -0.57; p = 0.00002. The decrement in flow reserve was not linearly related to the degree of left ventricular hypertrophy. Abnormal vasodilator reserve subsets found in hypertensive patients were defined on the basis of basal flow velocity, indexed left ventricular mass and clinical factors. In this series, diabetes did not cause a detectable additional decrement in flow reserve above that found with hypertension alone. These findings demonstrate that thallium perfusion defects are associated with depressed coronary vasodilator reserve in hypertensive patients without obstructive coronary artery disease. Left ventricular hypertrophy by indexed mass criteria is predictive of which hypertensive patients are likely to have thallium defects.(ABSTRACT TRUNCATED AT 250 WORDS)

Racial differences in myocardial ischemia and coronary flow reserve in hypertension.

OBJECTIVES: Using invasive measurements of endothelium-independent coronary flow reserve and stress thallium testing with or without dipyridamole, this study investigated racial differences in ischemia and coronary reserve in hypertensive left ventricular hypertrophy. BACKGROUND: African Americans compared with Caucasian Americans appear to have a higher case fatality from coronary heart disease but lesser amounts of atherosclerotic coronary artery disease. This paradox may be explainable by intrinsic or acquired racial differences in coronary arteriolar autoregulation and vasoreactivity. METHODS: The study enrolled 91 African and 81 Caucasian Americans referred for cardiac catheterization because of suspected myocardial ischemia but found to have no significant coronary stenosis. Patients were stratified by degree of left ventricular hypertrophy for comparison purposes after calculation of indexed left ventricular mass by means of echocardiographic M-mode measurements. Coronary flow reserve measurements were made using the intracoronary Doppler catheter and hyperemic doses of intravenous dipyridamole in 100 patients and intracoronary papaverine and adenosine in 72 patients. Seventy-seven percent of patients underwent adequate stress thallium testing with or without dipyridamole. RESULTS: In African Americans, mean (+/- SD) coronary flow reserve decreased from 4.4 +/- 2.3 for 38 without mass hypertrophy to 3.2 +/- 1.3 for 53 with hypertrophy (p = 0.005) to 2.7 +/- 1.1 for 12 with severe hypertrophy (p = 0.02). Thallium testing was abnormal in 31% of those without mass hypertrophy and 59% of those with hypertrophy. In Caucasian Americans, coronary flow reserve decreased from 4.1 +/- 2 for 58 without hypertrophy to 3.6 +/- 1.5 for 23 with hypertrophy (p = NS) to 3 +/- 1.5 for 6 with severe hypertrophy (p = NS). Thallium testing was abnormal in 36% without mass hypertrophy and in 39% with hypertrophy. CONCLUSIONS: This study establishes that development of left ventricular hypertrophy in hypertension carries greater physiologic morbidity for African compared with Caucasian Americans, typified by marked reduction in endothelium-independent coronary flow reserve and increased frequency of abnormal thallium tests.

Heterogeneous vasomotor responses of coronary conduit and resistance vessels in hypertension.

OBJECTIVES: The purpose of our study was to investigate the relation between conductance and resistance coronary vasomotor responsiveness in hypertensive patients without atherosclerosis. BACKGROUND: Although similar in morphology, conduit and resistance coronary vessels differ importantly in size, function and local environment and appear to be differentially affected in certain disease processes, such as atherosclerosis and hypertension. However, little is known about the effect of hypertension on contiguous coronary conduit and resistance vessels in humans. METHODS: Changes in coronary blood flow (a measure of resistance vessel reactivity) and coronary artery diameter (a measure of conduit vessel reactivity) were investigated in response to graded infusion of the endothelium-dependent agonist acetylcholine (ACh) in 98 patients with normal coronary arteries. RESULTS: In 31 normotensive, euglycemic patients, conduit and resistance coronary artery responses to intracoronary infusion of ACh were significantly correlated (r = 0.73, p = 1 x 10[-6]), although eight patients (26%) had constriction of conduit but dilation of resistance arteries at peak effect. In 28 hypertensive patients without left ventricular hypertrophy (LVH), conduit and resistance artery responses to ACh remained significantly correlated (r = 0.5, p = 0.006), although 12 patients (43%) had discordant findings. Finally, in 39 hypertensive patients with LVH, conduit and resistance artery responses to ACh displayed the lowest correlation (r = 0.38, p = 0.02), with 22 patients (56%) demonstrating conduit artery constriction and resistance artery dilation. CONCLUSIONS: Despite angiographically normal coronary arteries, heterogeneous vasomotor responses (dilation and constriction) were demonstrated in contiguous conduit and resistance arteries in normotensive and hypertensive patients referred for cardiac catheterization because of chest pain. In addition to more severe endothelial dysfunction among conduit and resistance arteries, a greater frequency of discordant conduit and resistance artery responses and resistance vessel constriction was found with increasing severity of hypertension. Our study suggests differing mechanisms of endothelium responsiveness to ACh among conduit and resistance coronary arteries.

Metyrosine and pheochromocytoma.

BACKGROUND: Severe hemodynamic instability may occur during surgery for removal of pheochromocytoma, unless there is preoperative pharmacological treatment. OBJECTIVE: To evaluate the effects of metyrosine (alpha-methyl-p-tyrosine), a catecholamine synthesis inhibitor, and alpha-blockade with prazosin or phenoxybenzamine on cardiovascular morbidity during surgery for pheochromocytoma. METHODS: A retrospective analysis was made of patients followed up at the Medical College of Georgia, Augusta, during 28 years who received metyrosine and prazosin (n = 6), metyrosine and phenoxybenzamine alone (n = 14), phenoxybenzamine alone (n = 6), or no medication (n = 7) during 3 weeks before tumor removal. The percentage of patients not requiring pressors or phentolamine during the intraoperative period as well as the perioperative peak systolic pressures and peak heart rates were estimated in each group. RESULTS: There was a significant (P < .05) increase in intraoperative peak systolic pressures without preoperative treatment (mean +/- SD, 243 +/- 40 mm Hg) vs metyrosine (mean +/- SD, 168 +/- 27 mm Hg). Ninety-five percent of patients who received metyrosine did not require pressors intraoperatively vs 50% with phenoxybenzamine alone. Eighty-one percent of patients pretreated with metyrosine did not require intraoperative phentolamine vs 33% with phenoxybenzamine alone and 29% without medications. Two patients in the no medication group died as a results of hypertensive crisis. CONCLUSIONS: The combination of alpha-metyrosine and alpha-blockade results in better blood pressure control and less need for use of antihypertensive medication or pressors during surgery, compared with the classical method of single-agent adrenergic blockade. Preoperative treatment with metyrosine along with an alpha-blocker is a useful strategy for decreasing the surgical morbidity in patients with pheochromocytoma and assumes greater importance as long as the availability of phentolamine for intraoperative use is a problem.

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.

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.

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.

Isradipine vs propranolol in hydrochlorothiazide-treated hypertensives. A multicenter evaluation.

A randomized, parallel, controlled study was conducted to evaluate the safety and efficacy of isradipine, 2.5 to 10 mg orally twice a day, compared with propranolol hydrochloride, 60 to 240 mg orally twice a day, in 78 hypertensives whose supine diastolic blood pressure was greater than 95 mm Hg while receiving 50 mg/d or more of hydrochlorothiazide. Isradipine or propranolol was titrated during a 10-week double-blind phase to achieve a supine diastolic blood pressure below 90 mm Hg while a fixed dose of hydrochlorothiazide was maintained. Supine diastolic blood pressure was reduced by 10 mm Hg in 88% of the isradipine/hydrochlorothiazide-treated and 83% of the propranolol/hydrochlorothiazide-treated groups and to less than 90 mm Hg in 55% of the isradipine/hydrochlorothiazide-treated and 69% of the propranolol/hydrochlorothiazide-treated patients. There was no significant difference in supine blood pressure reduction between either group, but there was a 3-to 4-beats per minute increase in supine heart rate in isradipine-treated patients and an expected 15- to 20-beats per minute decrease in heart rate in propranolol-treated patients. Five of 7 patients in the isradipine-treated group and 8 of 9 patients in the propranolol-treated group discontinued the therapy because of adverse reactions or treatment failure. Using Fisher's Exact Test, we found no significant difference in the relative frequency of individual adverse reactions between groups, although the absolute adverse reaction frequency was significantly higher with isradipine. This study demonstrates the effectiveness and safety of supplemental isradipine in the treatment of hypertension not controlled by hydrochlorothiazide alone.

Carotid plaque associations among hypertensive patients.

OBJECTIVE: To assess the relationship between cardiovascular risk factors and carotid plaque. DESIGN: Hypertensive patients were screened for randomization into the Multicenter Isradipine Diuretic Atherosclerosis Study, a trial intended to determine if blood pressure control by isradipine as compared with hydrochlorothiazide will blunt the progression of carotid plaque (intima plus media thickness, 1.3 to 3.5 mm) in patients with serum cholesterol levels of less than 6.85 mmol/L (265 mg/dL) without insulin-dependent diabetes mellitus or estrogen therapy. Demographics of those who underwent B-mode ultrasound evaluations at common, bifurcation, and internal carotid artery sites to detect plaque were assessed from a southern and a northern site. SETTING: Participants were from ambulatory outpatient clinics associated with medical schools. PATIENTS: The initial screening included 1823 hypertensive volunteer patients who were between 40 and 83 years of age who had a diastolic pressure of 90 to 114 mm Hg (or < 90 mm Hg with treatment). OUTCOME MEASURES: Complete data were collected on the variables of age, cholesterol, cigarette smoking, race, gender, and the presence of carotid plaque in 1126 patients. RESULTS: All variables were significantly associated with carotid plaque (intima plus media thickness, > or = 1.3 mm). The adjusted percentage with plaque was 66.4% +/- 3.4% for blacks and 70.1% +/- 2.3% for whites at the southern site and 42.7% +/- 4.5% for blacks and 61.3% +/- 3.2% for whites at the northern site. The rate of plaque was 75.8% among cigarette smokers, despite a mildly elevated cholesterol level. CONCLUSIONS: Although these 1126 cases do not constitute a random sample of patients, these data suggest that there may be regional differences in racial tendencies toward plaque among blacks.

Direct effect of thyroid hormone on intracardiac conduction in acute and chronic hyperthyroid animals.

Studies of intracardiac conduction utilizing His bundle electrograms demonstrate direct thyroid hormone action on the conduction system in both acute and chronic hyperthyroid animals.

Detection of hypertensive left ventricular hypertrophy.

The risk of adverse cardiovascular events is higher in persons with electrocardiographic evidence of left ventricular hypertrophy, and the decision to treat patients with antihypertensive drugs is often determined by the presence of hypertrophy. In this study a number of electrocardiographic criteria for detection of left ventricular hypertrophy were applied to a population of 85 hypertensive subjects in an ongoing outpatient hypertension evaluation and treatment program. Included were one set of criteria in common use and three sets of criteria employed in prospective clinical trials. The results were compared with those obtained by M-mode echocardiography and left ventricular wall thickness of 12 mm or more, which was taken as an indicator of hypertrophy. By this criterion, 34 patients (40%) had left ventricular hypertrophy. The most sensitive of the electrocardiographic criteria allowed detection of only 13 (38%) of those hypertensive subjects with anatomical-echocardiographic left ventricular hypertrophy. Although the echocardiogram is more time-consuming to obtain and more expensive than the electrocardiogram, its superior sensitivity suggests that the echocardiogram should be used for evaluating patients with high blood pressure, especially those without electrocardiographic evidence of left ventricular hypertrophy, to detect anatomical left ventricular hypertrophy.

How can we diagnose coronary heart disease in hypertensive patients?

Chest pain is a common complaint among hypertensive patients. Hypertension and coronary heart disease each may present with symptoms and signs that are clinically indistinguishable. Noninvasive testing by routine exercise stress testing and stress radionuclide angiography are not reliably predictive of ischemia resulting from obstructive epicardial coronary artery disease and should be abandoned for that diagnostic purpose. Noninvasive thallium-201 myocardial perfusion imaging for this purpose may prove to be a valuable tool, avoiding the risk and expense of coronary arteriography. However, carefully performed prospective studies are not available. Because of the high prevalence of both diseases, a high priority must be given to obtaining these data and evaluating other noninvasive methods (especially positron emission tomography) if they appear promising.

Effect of African-American race and hypertensive left ventricular hypertrophy on coronary vascular reactivity and endothelial function.

Excess cardiovascular morbidity and mortality among African (black) Americans remains an important yet unexplained public health problem. One possible explanation proposes that intrinsic or acquired abnormalities in coronary vascular reactivity and endothelial function result in excess ischemia among black Americans. To examine this hypothesis, we subjected 80 individuals with normal coronary arteries to invasive testing of coronary artery and microvascular relaxation using intracoronary infusions of acetylcholine and adenosine, a Doppler tipped intracoronary guide wire, and quantitative coronary angiography. We measured the percent increase in coronary blood flow and epicardial diameter after graded infusion of intracoronary acetylcholine and in coronary blood flow after intracoronary adenosine in 31 normotensive subjects (10 black, 21 white) and 49 hypertensive subjects with left ventricular hypertrophy (25 black, 24 white). Categorical and multivariate analyses revealed that in response to intracoronary adenosine and acetylcholine, the depression in endothelium-independent and -dependent microvascular relaxation during peak agonist effect was largely related to the presence of chronic hypertension and left ventricular hypertrophy. Normotensive subjects demonstrated no intrinsic racial differences in conduit and resistance vessel vasoreactivity. In response to maximal infusion of acetylcholine, epicardial coronary arteries constricted similarly in black and white subjects with hypertensive left ventricular hypertrophy and dilated similarly in normotensive black and white subjects. Thus, our study shows that in a cohort of black and white subjects referred for coronary arteriography because of chest pain, African American race is not associated with excess intrinsic or acquired depression in coronary vascular relaxation during the peak effect of the endothelium-dependent and -independent agonists acetylcholine and adenosine, after adjustment for the presence of left ventricular hypertrophy.

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.

Coronary vasomotor reactivity among normotensive African and white American subjects with chest pain.

BACKGROUND AND OBJECTIVES: Excess cardiovascular morbidity and mortality among African (black) Americans is the subject of intensive investigation but the etiology remains speculative. One hypothesis proposes that inherent, or intrinsic, differences in coronary vascular reactivity and endothelial function predispose African Americans to enhanced vasoconstriction and/or depressed vasodilation, resulting in excess ischemia. The objective of this study was to establish whether coronary vasoreactivity differs among normotensive, nondiabetic African and white Americans with normal arteries referred for coronary arteriography because of chest pain. PATIENTS AND METHODS: Eleven African American (8 female, 3 male) and 28 white American (9 female, 19 male) normotensive, euglycemic patients with normal coronary arteries were prospectively recruited for invasive testing of coronary artery and microvascular relaxation using the endothelium-dependent and -independent agents, acetylcholine and adenosine; a Doppler tipped intracoronary guidewire; and quantitative coronary angiography. RESULTS: The study cohort consisted of 17 women (44%) and 22 men (56%) with a mean age of 46 +/- 10 yrs. Of 8 African American women, 6 were premenopausal and 2 were postmenopausal on estrogen replacement therapy. Of 9 white American women, 2 were premenopausal, 1 was 46-year old with a previous history of hysterectomy without ovariectomy, 2 were postmenopausal on estrogen replacement therapy, 2 were perimenopausal and 44- and 54-year old, and 2 were postmenopausal without estrogen replacement therapy. In response to maximal infusion of acetylcholine, epicardial coronary arteries and resistance vessels dilated similarly in black and white subjects. Dose-response curves revealed no significant racial differences during submaximal graded infusion of acetylcholine. In response to peak effect of adenosine, there were no racial differences in dilation of the microcirculation. CONCLUSIONS: In the absence of hypertension, diabetes mellitus, and angiographic evidence of coronary artery disease, African American women demonstrate no evidence of intrinsic predisposition to enhanced coronary conduit vasoconstriction or depressed microcirculatory dilation in response to the endothelium-dependent and -independent vasodilator agonists-acetylcholine and adenosine-when compared with responses of similar white men and women. Because of low enrollment of black males, definitive conclusions cannot be drawn regarding this group.

Conformation-activity relationship study of 5-HT3 receptor antagonists and a definition of a model for this receptor site.

A conformation-activity relationship study of 5-HT3 receptor antagonists was used to define a pharmacophore and receptor map to qualitatively account for their activity. The design and synthesis of specific keto-amino-indole derivatives that are potent 5-HT3 receptor antagonists gave some support to the model.

Bis-basic-substituted polycyclic aromatic compounds. A new class of antiviral agents. 7. Bisalkamine esters of 9-oxoxanthene-2,7-dicarboxylic acid, 3,6-bis-basic ethers of xanthen-9-one, and 2,7-bis(aminoacyl)xanthen-9-ones-xanthenes, and -thioxanthenes.

3,6-Bis[2-(dimethylamino)ethoxy]-9H-xanthen-9-one dihydrochloride (4, RMI 10874DA) and 1,1'-(9H-xanthene 2,7-diyl)bis[2-(dimethylamino)ethanone] dihydrochloride (16, RMI 11513DA) were found to prolong survival of mice infected with lethal challenges of encephalomyocarditis (EMC) virus. They were effective by oral as well as subcutaneous administration and showed broad-spectrum antiviral activity. They were selected for preclinical evaluation from the five series of compounds named in the title that were synthesized in analogy to tilorone and related fluorenone derivatives, described earlier. In addition to 4 and 16, compounds 11, 12, 17, and 18 showed high antiviral activity on oral as well as subcutaneous administration. High antiviral activity on subcutaneous admistration was found in the bisalkamine esters 1,2, and 14, the bis(aminoacyl)xanthenes 23 and 26, the bis(aminoalkylene)xanthene 31, the bis(aminoacyl)thioxanthenes 34-40, and the bis-basic ethers of 9-benzylide-nexanthenes 41 and 42. Structure-activity relationships showed a decrease of oral activity with increased length of side chains and increased molecular weight of dialkylamino substituents of 3,6-bis-basic ethers of xanthen-9-one and of 2,7-bis(aminoacyl)xanthenes and-xanthen-9-ones. At least one carbonyl or alkenyl function in conjugation to the xanthene nucleus either at the 9 position of the nucleus or in the side chains is required for high antiviral activity.

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)

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.

Coronary vasomotor function in a normotensive, nondiabetic referral population with normal coronary arteriograms.

In a referral normal cardiac population, endothelium-independent coronary relaxation is nearly always normal, but endothelium-dependent relaxation may be depressed in a significant proportion of patients. Further study of the natural history of referral subjects with endothelial dysfunction is necessary to assess the potential cardiovascular risk of this finding in a presumed low-risk population.