Mary E. Heber

Carvedilol for systemic hypertension

Twenty-four hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new beta-blocker with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 +/- 3 mm Hg systolic and 19 +/- 3 mm Hg diastolic, and mean reduction in heart rate was 22 +/- 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first-line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional beta-blocking drugs.

Ambulatory intraarterial blood pressure in essential hypertension. Effects of age, sex, race, and body mass--the Northwick Park Hospital Database Study.

Twenty-four-hour recordings of intraarterial blood pressure (IABP) from 723 untreated hypertensive patients were analyzed for the effects of age, sex, race, and body mass index on the level of IABP and its circadian variation. Age had a highly significant positive relationship (P < .001) with the cuff systolic and diastolic blood pressures, with regression coefficients (SE) of +0.83 (0.07) and -0.24 (0.04) mm Hg/year, respectively. There was a similar (P < .001) positive relationship between age and 24-h mean systolic IABP, measuring +0.71 (0.07) mm Hg/year, but 24-h mean diastolic IABP did not increase significantly with age. There was a significant (P < .001) inverse relationship between age and 24-h mean heart rate (HR), at -0.17 (0.03) beats/min/year. Nocturnal fall in systolic and diastolic IABP, calculated as the difference between daytime and nighttime mean IABP, had a significant (P < .001) negative relationship with age. Nocturnal fall in HR, calculated similarly, also significantly (P < .001) decreased with age. Age did not affect long-term systolic and diastolic IABP variability but did decrease long-term HR variability significantly (P < .001). Hypertensive men and women of similar age, had comparable daytime mean systolic and diastolic IABP (P = .15 and P = .03 respectively), but women had significantly (P < .001) lower nighttime mean systolic and diastolic IABP than men. The nocturnal fall in systolic and diastolic IABP was significantly (P < .002) greater in women as compared to men. Women also had significantly (P < .01) greater long-term systolic and diastolic IABP variability than men. Women had significantly (P < .001) greater 24-h, daytime mean and nighttime mean HR than men. Twenty-four-hour, daytime and nighttime mean IABP were all significantly higher (P < .01) in Afro-Caribbeans as compared to whites and Asians. No significant differences were observed in the magnitude of nocturnal IABP fall or long-term IABP variability between the three races. Asians and Afro-Caribbeans had significantly (P < .001) lower nocturnal HR falls and long-term HR variability (P < .01) than whites. Body mass index (BMI) did not relate directly to the level of daytime blood pressure, clinic cuff, or daytime mean IABP, in either men or women. BMI did have a highly significant (P < .001) positive relationship with nighttime mean IABP in men, but not in women. The degree of nocturnal fall of IABP had a significant (P < .001) inverse relationship with BMI in hypertensive men.

24-hour blood pressure control with the once-daily calcium antagonist amlodipine.

The efficacy and toleration of once-daily amlodipine (5-10 mg) was studied in 11 patients with mild to moderate hypertension. Continuous intra-arterial blood pressure monitoring was used to study the effects of amlodipine over a 24-h period. Following a 2-week placebo run-in period, amlodipine was given initially as a single-blind 5-mg dose for 2 weeks and increased to 10 mg if required to control blood pressure for a further 4 weeks. Twenty-four-hour intra-arterial blood pressure recordings made after 6 weeks of treatment with amlodipine revealed that amlodipine effectively reduced blood pressure throughout the whole 24-h period without altering the normal circadian pattern. The mean daytime blood pressure was reduced from 165/103 to 147/89 mm Hg (p < 0.05) and the mean nighttime blood pressure was reduced from 137/79 to 121/69 mm Hg (p < 0.05). There was no significant change in heart rate. The mean supine blood pressure measured sphygmomanometrically was reduced from 169/103 mm Hg after placebo to 153/98 mm Hg after 2 weeks of treatment and to 145/92 mm Hg at the end of the study. The results of isometric and dynamic exercise testing showed that amlodipine decreased blood pressure, with no postural decrease on tilting and no change in the proportional increase in blood pressure at peak exercise. Amlodipine was well tolerated although one patient developed ankle edema that would have required discontinuation had she not already completed the study. This study has shown that amlodipine effectively reduced blood pressure for 24 h after once-daily dosing and was well tolerated.

Valvular tuberculous endocarditis: A case report and review of the literature

Tuberculous valvular endocarditis is exceptionally rare. It is usually manifest in the context of miliary tuberculosis, and in all but one case the diagnoses have been made at necropsy. Because of its rarity there is still uncertainty as to whether true tuberculous endocarditis exists as a clinical entity. This paper describes a case of miliary tuberculosis with aortic valvulitis that resolved on antituberculous therapy.

Effectiveness of the once-daily calcium antagonist, lacidipine, in controlling 24-hour ambulatory blood pressure

The efficacy of the new once-daily dihydropyridine calcium antagonist, lacidipine, in reducing ambulatory intraarterial blood pressure (BP) was examined in 12 untreated hypertensive patients. The intraarterial recording was commenced 24 hours before the first 4-mg dose and was continued for a further 24 hours thereafter. After dose titration and chronic therapy, a second 24-hour ambulatory BP recording was made. There was a steady onset of drug action, maximal at 2 hours, but with reflex tachycardia after the first dose. Chronic administration reduced BP throughout the 24-hour period, without tachycardia. Mean daytime reduction in BP was 20 mm Hg systolic (p less than 0.005) and 12 mm Hg diastolic (p less than 0.02). Mean nighttime reduction was 8-mm Hg systolic (p less than 0.05) and 6-mm Hg diastolic (difference not significant). There was no postural decrease in BP on 60 degrees head-up tilting and hypotensive action was maintained during isometric exercise (reduction at peak of 32/18 mm Hg, p less than 0.05) and throughout dynamic exercise (reduction at peak of 23/14 mm Hg, p less than 0.05). Lacidipine is an effective once-daily antihypertensive agent, with good control of stress response.

Assessment of 'once daily' verapamil for the treatment of hypertension using ambulatory, intra-arterial blood pressure recording.

SummaryA new, slow release formulation of verapamil, “verapamil o.d.” was administered to 12 patients with essential hypertension.Drug administration was started at a dose of 240 mg and increased to 480 mg after 2 weeks of treatment if the cuff blood pressure response was unsatisfactory.The drug reduced the daytime intra-arterial blood pressure significantly from 180.7/106.8 mm Hg to 157.3/89.4 mm Hg. The daytime heart rate fell from 88.1 to 71.8 beats/min. The nighttime blood pressure decreased from 155.7/87.2 mm Hg to 140.5/75.3 mm Hg. The nocturnal heart rate decreased from 62.8 to 57 beats/min. Hourly plots of mean systolic and diastolic pressure showed a significant reduction of systolic pressure for 21 of 24 h and of diastolic pressure for all 24 h following a single morning dose. The drug modified the absolute blood pressure and heart-rate response during both forms of exercise, but did not alter the magnitude or rate of blood pressure change. The tilt-test produced no evidence of postural hypotension.Only one patient experienced any side effects whilst taking the drug.These results indicate good 24-h blood pressure control and reduced exercise blood pressure levels during treatment with this new formulation of verapamil. The reduced frequency of drug administration should improve patient complicance with treatment of hypertension.

First dose response and 24-hour antihypertensive efficacy of the new once-daily angiotensin converting enzyme inhibitor, ramipril.

The reduction in blood pressure (BP) after the first dose and after 8 weeks of treatment with a new once-daily angiotensin converting enzyme (ACE) inhibitor, ramipril, was examined in 12 untreated hypertensive patients, using ambulatory intraarterial BP monitoring. The first period of monitoring began 24 hours before the first dose was given, and continued for 24 hours afterwards. A second 24-hour period of monitoring was carried out after 8 weeks of treatment, commencing immediately after the morning dose. Angiotensin II levels and serum drug levels were measured at 0, 2, 6 and 24 hours after the acute dose. BP decreased progressively from the first hour after the first dose, reached a maximum in the fifth hour (p less than 0.001) and then the effect diminished. The maximum reduction of systolic BP in any patient was 64 mm Hg, the minimum 4 mm Hg. Blood pressure was significantly (p less than 0.05) reduced throughout the 24 hours after dosing, with a mean daytime reduction of 13/12 mm Hg, and a mean nighttime reduction of 15/7 mm Hg. Angiotensin II levels were significantly (p less than 0.02) and maximally reduced by 2 hours after administration, but the reduction was no longer significant after 24 hours. Serum drug levels were also maximal 2 hours after administration. The trial population could be clearly divided into groups of good and poor responders on the basis of BP reduction. The angiotensin II levels were higher before treatment, and decreased further, in all patients with a good response than in those with a poor response.(ABSTRACT TRUNCATED AT 250 WORDS)

Carvedilol for systemic hypertension.

Summary: Twenty‐four hour profiles of intraarterial ambulatory blood pressure (BP) and heart rate were significantly reduced by administration of carvedilol, a new &bgr;‐blocker with vasodilating properties. Twelve patients were given carvedilol, 25 mg twice daily for 2 weeks; the dose was then increased to 50 mg twice daily if the target BP was not achieved. After 4 weeks of therapy, mean daytime reduction in BP was 25 ± 3 mm Hg systolic and 19 ± 3 mm Hg diastolic, and mean reduction in heart rate was 22 ± 3 beats/min. BP at the peak of isometric exercise and during dynamic exercise was also significantly reduced. Radionuclide measurements showed that left ventricular ejection fraction was not affected by treatment, but there was a significant reduction in systolic and diastolic volumes. The drug was well tolerated. This clinical trial suggests that carvedilol will be a useful first‐line drug for treatment of essential hypertension, and its vasodilating action may have a more favorable effect on left ventricular function than conventional &bgr;‐blocking drugs.

Twenty-four hour ambulatory blood pressure profile of a new, sustained-release preparation of nicardipine

SummaryThe 24-hour blood pressure (BP) profile of a new sustained-release preparation of nicardipine was assessed in 16 patients with essential hypertension (supine cuff diastolic BP>95 mmHg). Twenty-four hour ambulatory intraarterial BP monitoring (Oxford system) before treatment revealed a mean (SD) daytime BP of 174 (19) mmHg systolic and 105 (8) mmHg diastolic, and a mean nighttime BP of 142 (26) mmHg systolic and 83 (12) mmHg diastolic. Sustained release nicardipine (60 mg) was administered twice daily for 4–6 weeks and the ambulatory BP monitoring repeated. No significant change in heart rate occurred throughout the 24-hour period. However, there was a significant reduction (p<0.0001) in the mean daytime BP of 21 (13) mmHg systolic and 12 (9) mmHg diastolic and of mean nighttime BP of 21 (15) mmHg systolic and 13 (11) mmHg diastolic. A similar reduction in hourly mean BP occurred throughout the whole 24-hour period, including the steep early morning rise in BP. Although vasodilatory-type side effects occurred, they were generally mild to moderate and transient. This preparation produces a significant reduction in BP throughout the 24-hour period without reflex tachycardia.

Is there a relationship between ambulatory intra-arterial blood pressure and left ventricular function?

The relationship between ambulatory intra-arterial blood pressure and left ventricular ejection fraction was examined in a group of 23 untreated hypertensive subjects who underwent concurrent radionuclide ventriculography. All patients had a normal ejection fraction at rest (range, 50-80%), and no significant correlation was found between blood pressure and resting ejection fraction. Sixty-one percent of patients failed to increase their ejection fraction by 5% on exercise; the mean daytime systolic pressure (168 +/- 15 mm Hg) was lower in this group than in those who had a normal exercise response (188 +/- 17 mm Hg; p less than 0.005). Thirty percent of patients had left ventricular hypertrophy based on electrocardiographic criteria; this group had a higher mean blood pressure (189 +/- 20 mm Hg) than the remainder (170 +/- 15 mm Hg; p less than 0.05). A closer correlation was demonstrated between blood pressure and ejection fraction response to exercise in the group with left ventricular hypertrophy (r = 0.8) than in the group without hypertrophy (r = 0.3). These results failed to demonstrate a linear relationship between blood pressure and ejection fraction. However, a relationship between the height of blood pressure and the development of left ventricular hypertrophy was shown, and myocardial response to exercise was increased in patients with left ventricular hypertrophy.