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Biomedical subjects

R H McDonald

Publications and source records attributed to R H McDonald.

At least 19 recordsLinked to original sources

Comparison of ambulatory and clinic blood pressure and heart rate in older persons with isolated systolic hypertension.

We compared the blood pressure (BP) measurements obtained with a random-zero sphygmomanometer and an ambulatory BP monitor in older persons with isolated systolic hypertension at one site of the multicenter, randomized, double-blind clinical trial, the Systolic Hypertension in the Elderly Program (SHEP) randomized clinical trial. The subjects were community-dwelling elderly participants with isolated systolic hypertension enrolled in the SHEP study and already receiving stable doses of double-blind medication (n = 35 for active treatment group; n = 32 for placebo group). We measured seated (clinic) BP obtained with a random-zero sphygmomamanometer, pulse rate, and BP and heart rate measurements obtained with an ambulatory BP monitor (average 24 h, daytime, and nighttime BP and heart rate). Across treatment groups clinic and ambulatory systolic BPs were not significantly different, but the placebo group had higher ambulatory, but not clinic, diastolic BPs. Within each treatment group (active treatment and placebo) there were no significant differences between clinic and average 24 h, daytime, or nighttime ambulatory systolic BPs. There were also no significant differences between clinic diastolic BP and average 24 h, daytime, or nighttime ambulatory diastolic BPs in the active treatment group, but in the placebo group average 24 h diastolic BP obtained by the ambulatory monitor was 4.6 mm Hg higher than clinic diastolic BP (P = .001). The average 24 h heart rate was 6 to 7 beats/min higher as measured by the ambulatory monitor compared to clinic pulse (P < .01). In the placebo group of this study, average 24 h ambulatory diastolic BPs were consistently higher than clinic diastolic BPs.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged

Are race differences in the prevalence of hypertension explained by body mass and fat distribution? A survey in a biracial population.

Body mass and body fat distribution are important considerations in the study of hypertension. However, few studies have investigated the relationships with regards to race differences in elevated arterial pressure. A population-based sample of black and white adults was assessed by interview and physical measurement. The prevalence of hypertension (defined as 140/90 mmHg and/or medically treated) was disproportionately higher among blacks than whites. In addition, blacks had a higher prevalence of the more severe hypertension (160/95 mmHg) and hypertension with higher prevalence at earlier ages than whites. Black females had a significantly higher distribution of body mass index (BMI) than white females, while no difference was found in the distributions of males. White males had a higher distribution of waist to hip ratio (WHR) than black males, while black females had the higher values compared to white females. The prevalence of hypertension increased with BMI and WHR. Blacks maintained higher rates of hypertension after controlling for BMI and WHR, however, the margin of difference diminished when BMI and WHR was considered together. The black-white difference in hypertension was not completely explained by BMI and WHR. In addition, the strength of the association of hypertension and body size was different for blacks and whites which suggests possible differences in the mechanisms regulating blood pressure.

Adipose Tissue

Hypertension, creatinine, and plasma renin activity in heart transplant recipients.

Development of de novo hypertension in a large proportion of orthotopic heart transplant recipients receiving cyclosporine has previously been reported. This hypertension is characterized by a persistence of increased peripheral resistance, sodium retention, and loss of nocturnal decline in BP. Vascular nephropathy with plasma renin activity (PRA) elevation from cyclosporine (CsA) may also be major factor in the progress of hypertension. To investigate this hypothesis, observations of BP, creatinine (Cr), and PRA were made in 144 heart transplant recipients followed for up to four and a half years. Median Cr was 133 mumol/l. Average diastolic BP and mean PRA values were significantly higher in patients with Cr greater than or equal to the median. Cr and PRA were significantly correlated (r = 0.4; P less than 0.001) in recipients with Cr greater than or equal to 133 mumols/l but not in those with Cr less than 133 mumols/l. In a selected subsample of heart transplant recipients with repeated Cr and PRA values, Cr and PRA appeared to increase longitudinally after transplant. These data are derived from a case series of patients managed on a variety of antihypertensive agents (excluding ACE inhibitors) needed to control the persistent hypertension.

Antihypertensive Agents

A historical perspective of elevated systolic vs diastolic blood pressure from an epidemiological and clinical trial viewpoint.

The decision to use diastolic blood pressure as the basis for therapeutic intervention for hypertension was based primarily on clinical trials experience. The majority of observational studies shows as great or greater risk for elevated systolic blood pressure readings. Even many of the clinical trials in which a posteriori analyses have been performed confirm a greater effect of systolic rather than diastolic blood pressure as a predictor of coronary heart disease mortality. The current practice of using diastolic blood pressure readings as the sole treatment criterion should be reexamined in light of the observational studies and clinical trials reviewed here.

Adult

Premenopausal and postmenopausal women differ in their cardiovascular and neuroendocrine responses to behavioral stressors.

Middle-aged (45-51 years) women performed four tasks while their heart rate, blood pressure, and plasma catecholamines were measured. The tasks were serial subtraction, mirror image tracing, speech, and postural tilt. The speech task was considered to be particularly relevant to women because of its emphasis on social skills. Fifteen premenopausal women reported menstruating regularly and were tested in the early follicular phase. Sixteen postmenopausal women reported not menstruating for at least 12 months and their hormonal status was verified by serum levels of follicle-stimulating hormone. Results showed that postmenopausal women exhibited greater increases from baseline in heart rate during all tasks, relative to premenopausal women, with a particularly pronounced increase during the speech task. Postmenopausal women exhibited greater increases from baseline in systolic blood pressure and epinephrine, relative to premenopausal women, during the speech task only. Explanations for the stressor-specific effect of menopausal status were discussed. The results suggest that reproductive hormones may interact with stressor characteristics to determine middle-aged women's physiological responses to stress.

Arousal

Morbidity and mortality in the Systolic Hypertension in the Elderly Program (SHEP) pilot study.

The pilot study of the Systolic Hypertension in the Elderly Program was a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension. It followed 551 elderly participants with untreated blood pressures of greater than 160/less than 90 mm Hg for an average of 34 months. Mean age of the participants was 72 years; 63% were women, and 82% were white. Pretreatment blood pressures averaged 172/75 mm Hg. Participants were randomly assigned to treatment with chlorthalidone or placebo as Step I medication. Blood pressures at annual visits averaged 141/68 and 157/73 mm Hg for the drug-treated and placebo-treated groups, respectively, with 60% and 33% of the survivors on blinded medication having systolic blood pressures of less than 160 mm Hg at their last annual visit. All-cause mortality rates for the drug-treated and placebo-treated groups were 25.4 and 22.7 deaths per 1,000 participant-years of risk, and rates for definite "first stroke" were 8.3 and 12.8 per 1,000 years of risk. Differences between groups were significant for systolic and diastolic blood pressure but not for death or stroke rates. A full-scale study has begun to determine the effects of drug therapy for isolated systolic hypertension on stroke and mortality rates.

Antihypertensive Agents

The evolution of current hypertension therapy.

There has been a continuous evolution in hypertensive therapy during the last 30 years. Now, physicians have access to more than 40 agents for treating this widespread condition. Large-scale clinical trials have established that lowering blood pressure in patients with mild to moderate diastolic hypertension results in a decreased incidence of stroke and, to a lesser extent, a reduction in incidence of coronary heart disease [MacMahon SW, Cutler JA, Furberg CD, et al: Prog Cardiovasc Dis 1986; 29 (suppl 1): 99-118]. Even so, the decrease in overall mortality rate is not consistent. Although hypertension occurs with increasing frequency in those over 60 years of age, patients in this age group represent less than 12 percent of the subjects in large trials. Currently, stepped-care is the recommended approach for managing hypertension in patients of all ages. However, the availability of a variety of agents for initial therapy, all with approximately equal efficacy but differing side-effect profiles, calls such an approach into question.

Adult

Comparison of the antihypertensive effects of betaxolol to atenolol.

A randomized double-blind multicenter study compared a new oral beta 1-adrenergic antagonist, betaxolol 10 to 40 mg (n = 71), with atenolol 25 to 100 mg (n = 75). Each drug was administered once daily for 24 weeks in patients with mild to moderate hypertension. Blood pressure (BP) measurements were taken 24 hours after dosing. Each drug produced significant (p less than 0.01) reductions in mean supine diastolic BP. The mean decrease in supine diastolic BP with betaxolol was significantly greater at weeks 4, 6, 10 and 12 (p less than 0.05). Throughout the remainder of the trial (weeks 14 to 24), no significant differences in BP reduction were noted between treatment groups. Normotension (supine diastolic BP less than or equal to 90 mm Hg) was achieved in 72% of those given betaxolol compared with 52% of those given atenolol (p less than 0.05). The most common side effects noted were bradycardia, fatigue and headache. The incidence of these and of central nervous system side effects was similar between the betaxolol and atenolol groups. Both agents were well tolerated. At recommended doses, betaxolol once daily may be more effective than atenolol once daily in patients with mild to moderate hypertension.

Adrenergic beta-Antagonists

Patient characteristics and their influence on therapy and its outcome in hypertension of the elderly.

A retrospective study was undertaken to analyze the effects of various patient factors on therapy and its outcome in elderly hypertensive subjects. Two hundred and three male hypertensives with a mean age of 63.1 years at entry, were followed in a special hypertension clinic by nurse practitioners under physician supervision, for 2 years or more (mean 3.7 years). Good patient compliance (84%) and blood pressure (BP) reduction were achieved and these were enhanced by advancing age. Neither excessive weight, nor widespread atherosclerosis seemed to interfere with BP control. However, while diastolic BP was well controlled with antihypertensive therapy, systolic BP tended to remain higher than 160 mm Hg in many of the older and more atherosclerotic subjects. Pharmacological treatment did not prevent a gradual although modest deterioration of renal function, which was related to both age and hypertension, and represents a greater problem in black patients. Because of the limitations of such a retrospective study, its conclusions may not be extrapolated for treatment of hypertension in all the elderly.

Black or African American

Mortality associated with diastolic hypertension and isolated systolic hypertension among men screened for the Multiple Risk Factor Intervention Trial.

The large cohort of white men (317,871) 35 to 57 years old at initial screening for possible enrollment into the Multiple Risk Factor Intervention Trial (MRFIT) was examined with regard to initial blood pressure levels and subsequent coronary heart disease (CHD), stroke, and all-cause mortality. The overall prevalence of isolated systolic hypertension (ISH), defined as systolic blood pressure (SBP) greater than or equal to 160 mm Hg and diastolic blood pressure (DBP) less than 90 mm Hg, was 0.67% among white men screened for MRFIT and increased with age (0.31% among 35- to 39-year-olds to 1.7% among 55- to 57-year-olds). The 6 year CHD and all-cause mortality rates in men over 50 were highest in those with ISH compared with both subjects with diastolic hypertension and those with normal pressure. The relative risk of death from stroke in those with ISH, compared with that in those with SBP less than 160 mm Hg and those with DBP less than 90 mm Hg, was 3.0 (95% confidence interval 1.3 to 6.8). In addition, at any level of DBP, the level of SBP appeared to be the major determinant of all-cause and CHD mortality. The determinants of ISH in individuals under 60 years of age as well as the possible efficacy of its treatment should be evaluated further.

Adult

Background and design of the new U.S. trial on diet and drug treatment of "mild" hypertension (TOMHS).

A multicenter, randomized, controlled, double-blind U.S. trial is comparing the combined effects of diet treatment and 1 of 5 active drug regimens with diet treatment alone, for the long-term management of middle-aged adults with "mild" hypertension. Factors stimulating this trial are data documenting the high prevalence of mild hypertension in the adult population; mild hypertension's responsibility for a high proportion of morbidity and mortality attributable to hypertension overall; data from long-term hypertension intervention trials showing reduced morbidity and mortality of people with mild hypertension with use of either diuretics or beta blockers as step-1 therapy, and other trials that failed to demonstrate beneficial impact on morbidity and mortality, possibly due to residual questions concerning aspects of benefit to risk ratios with these medications; recent data from trials showing long-term control of mild hypertension and other risk factors by nutritional means; lack of data from long-term trials on benefit to risk ratios with newer drugs such as selective alpha 1 inhibitors, angiotensin converting enzyme inhibitors and calcium channel blockers; paucity of data from trials on long-term combined effects of diet and drug therapy, and of diet alone, for people with mild hypertension. During the next few years, phase 1 of the trial will study 6 groups of drugs. The step-1 drugs are angiotensin converting enzyme inhibitor (enalapril), alpha 1 inhibitor (doxazosin), beta blocker (acebutolol), calcium channel blocker (amlodipine), diuretic (chlorthalidone) and placebo. All participants are to receive vigorous sustained nutritional counseling to reduce obesity, moderate sodium intake and avoid heavy use of alcohol. Key endpoints for phase 1 of the study are the need for additional medication to control mild hypertension, side effects (i.e., clinical and biochemical) and consequent need to discontinue drug and quality of life. Phase-1 data are to be used to complete the phase-2 design, with the ultimate aim to assess effects on morbidity and mortality.

Adult

Relaxation therapy for hypertension. Comparison of effects with concomitant placebo, diuretic, and beta-blocker.

We compared the effects of relaxation therapy in hypertensive patients taking placebo, a beta-blocker (atenolol, 100 mg/d), or a diuretic (chlorthalidone, 50 mg/d), and we also compared the effects of relaxation therapy with the effects of the latter two drugs alone. Blood pressures were measured not only in the relaxation therapists' office and at a hypertension clinic, but also in the patient's environment by means of 24-hour ambulatory blood pressure recordings. The effect of relaxation therapy, while statistically significant, was modest. There was no generalization of effect to ambulatory blood pressure. Atenolol was significantly more effective than relaxation in reducing both systolic and diastolic pressure. Chlorthalidone was significantly more effective than relaxation in reducing systolic but not diastolic pressure in the hypertension clinic only. The long-term effects of relaxation were independent of concomitant drug use, but within the actual relaxation sessions blood pressure dropped further during chlorthalidone than during placebo or atenolol treatment.

Adrenergic beta-Antagonists

The contrasting effects of cyclosporin-A and azathioprine on arterial blood pressure and renal function following cardiac transplantation.

The effects of cyclosporin-A and azathioprine on the postoperative development of systemic hypertension and renal dysfunction in patients undergoing cardiac transplantation were compared retrospectively in 18 patients receiving cyclosporin-A and in 12 patients receiving azathioprine. Twelve months postoperatively, the average mean blood pressure was 116 +/- 13 mm Hg and 98 +/- 7.5 mm Hg; the average preoperative serum creatinine was 1.2 +/- 0.3 mg% and 1.5 +/- 0.3 mg%; and the postoperative serum creatinine was 2.2 +/- 0.8 mg% and 1.1 +/- 0.2 mg% (P less than 0.0001) in the cyclosporin-A-and azathioprine-treated groups respectively. Hemodynamic studies were done to characterize the de novo postoperative hypertension developing in the cyclosporin-A group. The pre- and postoperative cardiac output was 3.7 and 4.91/min, respectively (P less than 0.01). The pre- and postoperative systemic vascular resistance was 1707 and 1941 dynes sec X cm-5, respectively (P greater than 0.2). Peripheral renin activity and 24-hour urinary catecholamine excretion were not elevated. The mechanism of the hypertension developing in cyclosporin-A-treated patients is unknown, but is associated with normalization of cardiac output, an abnormally elevated systemic vascular resistance, and modest impairment of renal function. These findings are in marked contrast to azathioprine-treated patients, in whom postoperative hypertension and renal dysfunction do not occur. These observations implicate cyclosporin-A as the major contributing factor in the development of hypertension and renal dysfunction.

Adult

Systolic Hypertension in the Elderly Program, Pilot Study (SHEP-PS): morbidity and mortality experience.

SHEP-Pilot Study, a randomized, double-blind, placebo-controlled trial of drug therapy for isolated systolic hypertension, followed 551 participants aged 60 years or more with untreated blood pressures of greater than or equal to 160/less than 90 mmHg for an average of 34 months. Mean age was 72 years, 63% were female and 82% white. Pretreatment blood pressures averaged 172/75 mmHg. As their Step I drug, 443 participants were assigned chlorthalidone and 108 placebo. Of 512 surviving participants, 80% and 84% of the chlorthalidone and placebo groups, respectively, attended their last clinic visit; 71% and 60% were still taking blinded drug; and 60% and 33% had systolic blood pressures less than 160 mmHg. Final blood pressures averaged 140/67 and 154/72 mmHg for the chlorthalidone and placebo groups, respectively. All-cause mortality rates were 25 and 23 deaths per 1000 participant-years of risk, respectively; rates for 'definite' first strokes were 8.3 and 13 deaths. Differences between chlorthalidone and placebo groups were significant for blood pressure but not for event rates.

Aged

Once-a-day triple therapy with low-dose minoxidil for moderate hypertension.

Minoxidil was given to 16 men with hypertension of various degrees of severity, in conjunction with a diuretic and atenolol. Mean supine and standing blood pressures (BP) on diuretic + atenolol were 172/106 and 162/104 mm Hg, respectively. Minoxidil was added and the dose titrated to lower the diastolic pressure to less than 90 mm Hg. All drugs were taken together once daily. At the end of a maintenance period of 6 months on an average dose of minoxidil of 12 mg (range 2.5 to 20.0 mg), supine BP was 147/87 and standing BP 139/88 mm Hg. Similar BP had been measured throughout the maintenance period, and monitoring of the BP showed that the once daily regimen provided good control for 24 h. A strong correlation was found between the dose of minoxidil necessary to normalize the BP and the mean arterial pressure prior to minoxidil (r = 0.73, P less than 0.005). Serious adverse effects of the drug were observed only in patients receiving doses greater than 10 mg or those with widespread atherosclerosis, or both. We conclude that, when added to a diuretic and a beta-blocker in a once-a-day regimen, minoxidil in a daily dose of less than or equal to 10 mg is effective and well tolerated in mild to moderate hypertension, especially in patients who are free of atherosclerotic complications.

Adult

The excretion of rosaramicin in breast milk.

The excretion of rosaramicin, a macrolide antibiotic, was studied in the breast milk of ten lactating women. Breast milk and serum samples were collected for 48 hours after a single 250-mg oral dose of rosaramicin. Mean serum half-life, apparent volume of distribution, and oral clearance were 4.4 hours, 3.41 L/kg, and 6.34 mL/min/kg, respectively. Mean milk/serum ratio was 0.12 and the total amount of drug recovered over the first ten hours was 6.25 micrograms, approximately 0.0025% of the dose. A positive correlation between breast milk volume and breast milk clearance was found, suggesting that the amount of drug received by a nursing infant will depend on the volume of milk produced by the mother. Drug-induced toxicity from the parent drug is unlikely to occur in nursing infants since the amount of rosaramicin that a nursing infant could ingest is small.

Adult