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Biomedical subjects

O S Randall

Publications and source records attributed to O S Randall.

At least 19 recordsLinked to original sources
PubMed2001

Effect of ramipril vs amlodipine on renal outcomes in hypertensive nephrosclerosis: a randomized controlled trial.

CONTEXT: Incidence of end-stage renal disease due to hypertension has increased in recent decades, but the optimal strategy for treatment of hypertension to prevent renal failure is unknown, especially among African Americans. OBJECTIVE: To compare the effects of an angiotensin-converting enzyme (ACE) inhibitor (ramipril), a dihydropyridine calcium channel blocker (amlodipine), and a beta-blocker (metoprolol) on hypertensive renal disease progression. DESIGN, SETTING, AND PARTICIPANTS: Interim analysis of a randomized, double-blind, 3 x 2 factorial trial conducted in 1094 African Americans aged 18 to 70 years with hypertensive renal disease (glomerular filtration rate [GFR] of 20-65 mL/min per 1.73 m(2)) enrolled between February 1995 and September 1998. This report compares the ramipril and amlodipine groups following discontinuation of the amlodipine intervention in September 2000. INTERVENTIONS: Participants were randomly assigned to receive amlodipine, 5 to 10 mg/d (n = 217), ramipril, 2.5 to 10 mg/d (n = 436), or metoprolol, 50 to 200 mg/d (n = 441), with other agents added to achieve 1 of 2 blood pressure goals. MAIN OUTCOME MEASURES: The primary outcome measure was the rate of change in GFR; the main secondary outcome was a composite index of the clinical end points of reduction in GFR of more than 50% or 25 mL/min per 1.73 m(2), end-stage renal disease, or death. RESULTS: Among participants with a urinary protein to creatinine ratio of >0.22 (corresponding approximately to proteinuria of more than 300 mg/d), the ramipril group had a 36% (2.02 [SE, 0.74] mL/min per 1.73 m(2)/y) slower mean decline in GFR over 3 years (P =.006) and a 48% reduced risk of the clinical end points vs the amlodipine group (95% confidence interval [CI], 20%-66%). In the entire cohort, there was no significant difference in mean GFR decline from baseline to 3 years between treatment groups (P =.38). However, compared with the amlodipine group, after adjustment for baseline covariates the ramipril group had a 38% reduced risk of clinical end points (95% CI, 13%-56%), a 36% slower mean decline in GFR after 3 months (P =.002), and less proteinuria (P<.001). CONCLUSION: Ramipril, compared with amlodipine, retards renal disease progression in patients with hypertensive renal disease and proteinuria and may offer benefit to patients without proteinuria.

Adrenergic beta-Antagonists↗
PubMed2001

Baseline characteristics of the diabetic participants in the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT).

OBJECTIVE: Hypertension (HTN) is a major risk factor for cardiovascular disease (CVD) in the setting of diabetes. There is no consensus on how best to treat hypertension among those with diabetes. Here we describe the characteristics of a cohort of hypertensive adults with diabetes who are part of a large prospective blood pressure study. This study will help clarify the treatment of HTN in the setting of diabetes. RESEARCH DESIGN AND METHODS: The Antihypertensive and Lipid-Lowering high-risk hypertensive participants, ages > or = 55 years, designed to determine whether the incidence of fatal and nonfatal coronary heart disease (CHD) and combined cardiovascular events (fatal and nonfatal CHD, revascularization surgery, angina pectoris, congestive heart failure, and stroke) differs between diuretic (chlorthalidone) treatment and three alternative antihypertensive therapies: a calcium channel blocker (amlodipine), an ACE inhibitor (lisinopril), and an alpha-adrenergic blocker (doxazosin). The planned follow-up is an average of 6 years, to be completed March 2002. RESULTS: There are 15,297 diabetic individuals in the ALLHAT study (36.0% of the entire cohort). Of these individuals, 50.2% are male, 39.4% are African-American, and 17.7% are Hispanic. Demographic and laboratory characteristics of the cohort are similar to those of other studies of the U.S. elderly population with HTN. The sample size has 42 and 93% confidence, treatments for the two study outcomes. CONCLUSIONS: The diabetic cohort in ALLHAT wil be able to provide valuable information about the treatment of hypertension in older diabetic patients at risk for incident CVD.

Adrenergic alpha-Antagonists↗
PubMed1997

Short-term effects of blood pressure control and antihypertensive drug regimen on glomerular filtration rate: the African-American Study of Kidney Disease and Hypertension Pilot Study.

The African-American Study of Kidney Disease and Hypertension pilot study randomized 94 nondiabetic black men and women (mean age, 53 years; 75% male) with presumed hypertensive nephrosclerosis and a baseline glomerular filtration rate (GFR) of 25 to 70 mL/min/1.73 m2 (mean, 52.3 mL/min/1.73 m2) to blood pressure control at either a low mean arterial pressure (MAP) goal of < or = 92 mm Hg or a usual MAP goal of 102 to 107 mm Hg and an antihypertensive drug regimen that included either a calcium antagonist (amlodipine), a beta-blocker (atenolol), or an angiotensin-converting enzyme (ACE) inhibitor (enalapril). After 3 months of follow-up (n = 90), the mean GFR was similar (53.0 mL/min/1.73 m2 v 53.7 mL/min/1.73 m2) to the baseline levels in participants randomized to the low MAP group (n = 44), whereas the mean GFR increased by 3.9 mL/min/1.73 m2 (P = 0.02) in participants randomized to the usual MAP group (n = 46). During the same period of time, the mean GFR increased significantly in participants randomized to the calcium channel blocker regimen (n = 28) (5.7 mL/min/ 1.73 m2; P = 0.01) but not in participants randomized to the beta-blocker regimen (n = 31) (1.7 mL/min/1.73 m2; P = 0.10) or the ACE inhibitor regimen (n = 31) (1.1 mL/min/1.73 m2; P = 0.52). Changes in GFR at 3 months were significantly different among the three treatment groups (P = 0.04). We conclude that the magnitude of short-term effects of blood pressure control and antihypertensive drug regimens on GFR should be considered when estimating sample size for clinical trials designed to evaluate the effects of these interventions on long-term changes in GFR slope.

Adolescent↗
PubMed1996

Design and baseline characteristics of participants in the African American Study of Kidney Disease and Hypertension (AASK) Pilot Study.

Hypertension and end-stage renal disease (ESRD) are major causes of morbidity and mortality in the United States, especially among African Americans. The African American Study of Kidney Disease and Hypertension (AASK) Pilot Study evaluated the feasibility of conducting a long-term clinical trial to compare the effects of two levels of blood pressure control and three different antihypertensive drug regimens on the rate of decline in glomerular filtration rate (GFR) in African Americans with clinically diagnosed hypertensive renal disease. African American men and women aged 18-70 years with a GFR of 25-70 ml/min/ 1.73m2 and hypertension were randomized in a 3 x 2 factorial design to initial treatment with either an angiotensin-converting enzyme inhibitor (enalapril), a calcium channel blocker (amlodipine), or a beta blocker (atenolol) and to a mean arterial blood pressure (goal MAP) of either 102-107 mm Hg or < or = 92 mm Hg. Furosemide, doxazosin, clonidine, hydralazine, and minoxidil were added sequentially until goal MAP was achieved. To compare the pathologic diagnosis with the clinical diagnosis of renal disease, study participants without contraindication were also asked to undergo a renal biopsy. The goals of the AASK Pilot Study were to evaluate recruitment techniques, adherence to prescribed antihypertensive drug regimens, ability of the antihypertensive regimens to achieve blood pressure goals, rates of participation in scheduled clinic visits and procedures, and variability of GFR measurements. A further goal was to obtain renal biopsy data in at least 75% of the randomized study participants. Compared to the ESRD patient population whose renal disease is caused by hypertension, women were underrepresented in the AASK Pilot Study. AASK Pilot Study participants had higher unemployment rates and lower income levels than African Americans in the general U.S. population.

Adult↗
PubMed1994

Uniformity of captopril benefit in the SAVE Study: subgroup analysis. Survival and Ventricular Enlargement Study.

The Survival and Ventricular Enlargement (SAVE) Study demonstrated that long-term administration of the angiotensin-converting enzyme inhibitor captopril to recent survivors of myocardial infarction with left ventricular dysfunction resulted in a reduction in cardiovascular mortality and morbidity. Analysis of multiple subgroups demonstrated that baseline demographics (older age) and clinical characteristics (such as prior MI, history of diabetes or hypertension), that have previously been associated with a higher risk of cardiovascular events, were associated with greater end point event rates in SAVE regardless of therapy assignment at the time of randomization. The effectiveness of captopril therapy in reducing cardiovascular mortality and morbidity was examined in multiple subgroups. Although not all subgroups provided adequate statistical power, the benefits of captopril therapy were relatively uniform in the SAVE study. This indicates that the benefits were not confined to one particular subgroup and conversely that targeting of captopril therapy should be to the broadest group, as defined by SAVE entry criteria, to result in a reduction in cardiovascular mortality and morbidity.

Captopril↗
PubMed1994

Dietary management of blood pressure.

Hypertension is a major cause of morbidity and mortality in the United States, particularly in the African-American population. Although there have been indications since the beginning of this century that blood pressure might be influenced by dietary factors, this has been generally ignored, and the mainstay of hypertension treatment has been the use of pharmacologic antihypertensives. Attention is now being focused, however, on dietary management of hypertension because of the high cost of drug therapy, the adverse reactions associated with some antihypertensives, and the fact that hypertensives treated only by pharmacologic means remain at risk for target-organ damage. The literature is replete with evidence that vegetarian and low-sodium dietary patterns are associated with lower blood pressure levels. This implies that if many people could adopt vegetarian and low-salt dietary habits, the prevalence of hypertension would be significantly reduced. However, most people find "unsalted" vegetarian diets tasteless and unacceptable. We therefore need to identify the macro- and micronutrients (other than sodium) that directly influence blood pressure. Several studies indicate that dietary patterns rich in fiber, calcium, potassium, and magnesium are favorable for blood pressure control. This review highlights some of these findings and emphasizes the need for large clinical trials to test blood-pressure-reducing dietary patterns by incorporating the aforementioned macro- and micronutrients into socioculturally acceptable and palatable menus, especially in the African-American population.

Adult↗
PubMed1993

Effect of cold stress on coronary sinus blood flow in patients with scleroderma.

The mechanism of cardiac involvement in scleroderma is not known. Histologic studies of the myocardium in patients who died of scleroderma revealed that half had myocardial damage. Characteristic involvement ranges from focal contraction-band necrosis to diffuse fibrosis despite the absence of obstructive coronary artery disease of the major epicardial vessels. These findings suggest that scleroderma heart disease might result from episodic reduction of coronary blood flow due to abnormalities of coronary vasomotor tone. Studies using cold pressor thallium 201 myocardial perfusion scans support this hypothesis. Our study measured coronary blood flow during hand immersion in ice water at cardiac catheterization to determine whether patients with scleroderma had an abnormal coronary blood flow response. Coronary sinus blood flow was measured using a thermodilution method. Five patients with scleroderma were compared with 5 control subjects. All patients and controls had normal coronary angiograms. The coronary blood flow at baseline in the scleroderma and the control group (130 +/- 33 mL/min and 86 +/- 27 mL/min, respectively) was not significantly different. During the cold pressor test, both groups had a small, insignificant increase in coronary blood flow from baseline to 60 seconds (130 to 144 mL/min, scleroderma patients; 86 to 89 mL/min, control subjects). Our findings suggest that the cold pressor test does not cause an abnormal increase in coronary vasomotor tone or an absolute reduction in coronary blood flow in patients with scleroderma, as previously suggested by thallium 201 cold pressor studies.

Adult↗
PubMed1992

Correlates of the estimated arterial compliance in the population of Tecumseh, Michigan.

An estimate of arterial compliance--the stroke volume/pulse pressure ratio (SV/PP)--was studied in 801 participants in the Tecumseh Blood Pressure Study, a population-based ongoing cardiovascular, epidemiological investigation. The subjects were normal young adults (mean age 30 +/- 5.6 years) and 373 were females. Cardiac anatomy and function were studied by echo-Doppler methods, blood pressure being measured at the same time by the indirect method. The distribution of the SV/PP ratio was skewed toward higher values in larger subjects. After statistical adjustments for body surface area, this estimate of arterial compliance was found to be higher in females (2.00 +/- 0.62) than in males (1.90 +/- 0.58) (p < 0.05). When subjects were divided into tertiles, the group with the lowest estimated arterial compliance was normotensive but had higher systolic pressure, lower diastolic pressure, a similar mean arterial pressure, higher heart rate and higher left ventricular wall thickness ratio compared to subjects with higher arterial compliance. Indices of systolic ejection decreased and diastolic function was altered in the low compliance subjects. In addition, low compliance subjects also had higher fasting insulin levels. These findings suggest that the low arterial compliance in an otherwise normal population has negative cardiovascular correlates. The early association of decreased arterial compliance with anatomic, functional and biochemical aberrations suggests that estimates of arterial compliance might prove useful for prediction of cardiovascular complications.

Adolescent↗
PubMed1992

Total arterial compliance: differences between spontaneously hypertensive rats and normotensive Wistar-Kyoto rats.

Invasive hemodynamic measurements were performed on 14 normotensive Wistar-Kyoto (WKY) rats and 15 spontaneously hypertensive rats (SHRs) to test the hypothesis that SHRs have lower total arterial compliance than WKY rats. Ascending aortic pressure was measured with a catheter-tip manometer, and aortic flow was measured with an electromagnetic flow probe. Prolonged diastoles were produced by an electrocardiographically timed aortic occluder. The aortic decay time constant (Tau) for each prolonged diastole was calculated by an exponential fit of the initial linear segment of the log (pressure)-time curve. Tau is the product of resistance (R) and compliance (C) in the Windkessel model for the arterial system. Total arterial compliance was therefore determined from the relation Tau/R. The total arterial compliance index was calculated by correcting for body weight. Compliance was also estimated by the stroke volume/pulse pressure ratio. Compared with WKY rats, SHRs have higher mean pressure (111 +/- 19 [SD] mm Hg vs 71 +/- 14, P less than .0001), higher mean flow (0.50 +/- 0.10 mL/sec vs 0.38 +/- 0.04, P less than .001), and a shorter decay time constant (365 +/- 54 msec vs 475 +/- 54, P less than .001).(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Physiology and pathophysiology of hypertension.

The exact cause of primary hypertension is unknown. Neurohumoral, renal, metabolic, race, genetic, and environmental factors have been shown to be related to the development of hypertension; thus, the multifactorial hypothesis of the pathophysiology of hypertension. The pathophysiologic hemodynamic mechanisms of hypertension are known. However, the pathogenic processes that result in the vascular abnormalities responsible for the hemodynamic expressions of hypertension are speculative. Available data suggest that during the early phases of hypertension, when several factors may act together or independently to turn neurohumoral systems on and off, transient exacerbated alterations in pressure-flow relation are produced in subjects with a hyperresponsive cardiovascular system due to altered vascular properties. Changes in arterioles, which increase total peripheral resistance, result in an increase in diastolic and a secondary increase in systolic blood pressures in response to pressor stimuli. Changes in arteries, which decrease vascular compliance, result in an increase in systolic and a decrease in diastolic blood pressures. Initially, this response is only slightly different from that seen in the nonstimulated state. However, if the stimulation is too frequent, changes occur in vascular properties that provide hemodynamic mechanisms for additional vascular alterations. This further amplifies the increase in pressure. The relative magnitude of arteriolar to arterial vascular alterations determines the relative changes in diastolic and systolic pressures and thereby contributes greatly to the shape of the oscillatory arterial pressure wave. The height of the mean blood pressure, a weighted average of the systolic and diastolic blood pressures, is the product of cardiac output and peripheral resistance.

Arteries↗
PubMed1989

Coronary artery disease in black Americans 1920-1960: the shaping of medical opinion.

Current opinions regarding the prevalence of coronary artery disease in black Americans are conflicting. Some physicians believe that the prevalence of coronary artery disease in black Americans is less than that in the general population; some find no difference; still others argue that the high prevalence of risk factors, such as hypertension, should result in a higher prevalence of coronary artery disease in black Americans. This article will not attempt to resolve these conflicts but instead will review some of the medical literature that may have influenced prevailing opinions.

Black People↗
PubMed1987

Tricuspid stenosis in prosthetic valve endocarditis. Diagnosis by Doppler echocardiography.

Valvular stenosis is an uncommon finding in bacterial endocarditis involving native cardiac valves. Prosthetic valve endocarditis, however, is more commonly associated with obstruction. Bioprosthetic cardiac valves may be particularly prone to this complication. A case of bioprosthetic tricuspid valve endocarditis with stenosis diagnosed by Doppler echocardiography and confirmed by operative findings is presented.

Adult↗
PubMed1986

Hemodynamic correlates of arterial compliance.

There is at present no good understanding of the exact clinical correlates of arterial compliance. The purpose of this study was to establish which hemodynamic variables are most strongly associated with compliance. Hemodynamic measurements were performed on 41 patients undergoing diagnostic cardiac catheterization. Cardiac outputs were determined by thermodilution, and pressures were measured in the ascending aorta with a catheter-tip manometer. Compliance was calculated from a mono-exponential fit of diastolic decay pressures. Pulse pressure(PP), stroke volume(SV), age, systolic blood pressure(SBP), and cardiac output(CO) were significantly related to compliance. The quotient SV/PP was a good estimate of compliance, as was a first-order function of both SV and PP. There appear to be specific clinical correlates of arterial compliance, as well as ways to estimate arterial compliance on the basis of conventional hemodynamic measurements when direct calculations are not possible.

Adult↗
PubMed1986

Reliability of stroke volume to pulse pressure ratio for estimating and detecting changes in arterial compliance.

Total arterial compliance is an important haemodynamic variable which is difficult to measure in vivo. Using a Windkessel model, it can be determined from the ratio of the diastolic-decay time constant (tau) of the arterial system and the peripheral resistance. Using this technique, paired estimates of arterial compliance were determined in control and in mechanically produced low-compliance steady states. Since determination of compliance based on the three-element Windkessel model is tedious the same data were retrospectively analysed to evaluate the reliability of the stroke volume to pulse pressure ratio (SV:PP) for estimating and predicting changes in compliance. The linear correlation coefficient for 148 paired values of compliance determined by the two methods was r = 0.85, P less than 0.001. Both methods indicated similar values (mean +/- s.e.m.) for compliance in the control steady state: 0.35 +/- 0.01 ml/mmHg (using tau/R) versus 0.36 +/- 0.01 ml/mmHg (using SV:PP), P was NS, and both methods detected a significant decrease in compliance, P less than 0.001, in the low-compliance steady state: 0.18 +/- 0.01 ml/mmHg (using tau/R) and 0.21 +/- 0.01 ml/mmHg (using SV:PP). Thus, SV:PP compared with (tau/R) was a good index of compliance and changes in compliance and may prove to be a useful index for estimating compliance clinically.

Animals↗
PubMed1986

Systolic, diastolic, and combined hypertension. Differences between groups.

We used a classification system of systolic, diastolic, and combined (both systolic and diastolic) hypertension to ascertain whether there were significant differences between the groups. The study involved 182 consecutive outpatients for whom no secondary cause of hypertension could be found. There were 96 male and 86 female patients, with a mean age of 45.8 years. There were significant differences in age, with the systolic group being the oldest and the diastolic group the youngest. There were also differences in the prevalence of complications among the categories. Peripheral vascular disease, retinopathy, and coronary artery disease were more prevalent in the systolic and combined groups, while diabetes was more prevalent in the systolic group. We conclude that there appear to be clinical differences between systolic, diastolic, and combined hypertension with respect to presenting characteristics and complications.

Adolescent↗
PubMed1984

Systemic compliance: does it play a role in the genesis of essential hypertension?

Arterial compliance is part of the load faced by the heart. Decreased compliance increases this load. We have studied the cardiovascular consequences of decreased systemic compliance in six closed chest anaesthetised dogs where ascending aortic flow transducers and left ventricular crystals had previously been implanted. A stiff tube was put into the abdominal aorta from the left flank and moved to the ascending aorta. Inflation of a cuff on the proximal end of the tube forced the heart to eject into a non-compliant outflow conduit. The distal end of the tube was connected to the distal aorta and, via a pump, to a carotid artery where mean pressure was kept above 80 mmHg. We measured systemic pressures (catheter-tip manometer), cardiac output (electromagnetic flowmeter) and either left ventricular end-diastolic pressure (fluid filled catheter, Statham P23Db) or left ventricular diameter (ultrasound transit time method). From these variables we calculated systemic compliance and input impedance. A 35% decrease in compliance caused a 12% increase in systolic, and a 12% decrease in diastolic pressure while mean pressure and cardiac output did not change significantly. With a decrease in compliance of 63% systolic pressure increased by 18%, while diastolic pressure decreased by 24%. Mean pressure did not change significantly but cardiac output fell by 21%. In both groups of altered compliance peripheral resistance rose slightly but this was not significant. Decreased compliance mainly caused changes in the low frequency range of the input impedance: moduli increased and phase angles became more negative.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗