White-coat hypertension as a cause of cardiovascular dysfunction.

BACKGROUND: The increasing use of 24 h ambulatory blood pressure monitoring has allowed diagnosis of white-coat hypertension, in which blood pressures are higher on clinic measurements than on ambulatory monitoring. Treatment is not generally thought to be necessary for this disorder. However, there is evidence that patients with white-coat hypertension develop renal impairment and left ventricular hypertrophy. We undertook this study to assess whether white-coat hypertension, in the absence of cardiovascular structural abnormalities, is associated with cardiovascular functional abnormalities. METHODS: Cardiovascular function was assessed by ultrasonography in three groups of patients classified as normotensive, persistently hypertensive, or white-coat hypertensive (23, 20, and 22 patients, respectively) on the basis of ambulatory blood pressure monitoring, carried out for 28 h with recordings taken every 15 min during the day and every 20 min during the night, and clinic measurements, made with a semi-automatic oscillometric device. RESULTS: Similar abnormalities of diastolic left ventricular function were identified in the patients with persistent hypertension and those with white-coat hypertension; both groups differed in these indices from the normotensive group (E/A ratios 0.94 [SD 0.23], 1.06 [0.21], and 1.24 [0.31] respectively; ANOVA p < 0.005). In addition, the white-coat and persistently hypertensive groups, when compared with the normotensive group, showed similar abnormalities of elasticity, compliance, and stiffness (stiffness index 4.32 [1.90], 4.53 [1.38], and 3.27 [0.95] respectively; ANOVA p < 0.05) of the large arteries. INTERPRETATION: Functional cardiovascular abnormalities were identified in white-coat hypertensive patients who had no identifiable structural abnormalities. Such functional abnormalities can be reversed by antihypertensive treatment. We propose that patients with white-coat hypertension might benefit from antihypertensive treatment as well as those with persistent hypertension. This hypothesis should be addressed in prospective clinical trials.

Haemodynamics, cardiac conduction and pharmacokinetics of mibefradil (Ro 40-5967), a novel calcium antagonist.

OBJECTIVES: Mibefradil (Ro40-5967) is a chemically novel non-dihydropyridine calcium antagonist. In this phase II study we compared its acute and chronic effects on blood pressure, heart rate and atrioventricular conduction (electrocardiographic PQ interval) with those of verapamil and diltiazem. PATIENTS AND METHODS: After a 4-week placebo run-in, 18 patients with mild to moderate essential hypertension were given single doses of mibefradil (150 mg), slow-release (SR) verapamil (240 mg), diltiazem (240 mg) and placebo at weekly intervals; pharmacokinetics and the effects on blood pressure, heart rate and PQ interval were studied on four 10-h study days. Seventeen of the same patients subsequently underwent 4 weeks of treatment with either mibefradil (100 mg daily; n = 10) or verapamil SR (240 mg daily; n = 7), and on the last day, they attended a further 10-h study day. Two studies were conducted: an acute, single-dose, double-blind, randomly allocated, placebo-controlled, crossover study and a chronic, open-label, randomly allocated, parallel-group study. RESULTS: Mibefradil was well tolerated. In the acute study, the antihypertensive effect (difference from placebo) of mibefradil 150 mg was of slower onset than that of verapamil or diltiazem, but comparable blood pressure reductions had been achieved by 6 h. The mean +/- SD maximal PQ prolongation (difference from placebo) was 15.6 +/- 16.1 ms, compared with 44.0 +/- 22.6 ms for verapamil and 56.0 +/- 48.9 ms for diltiazem (P<0.05 mibefradil versus verapamil; P<0.01 mibefradil versus diltiazem). In the chronic study there were no significant differences during steady-state conditions between mibefradil at 100 mg and verapamil SR at 240 mg in their effects on blood pressure, PQ and heart rate. The mean +/- SD elimination half-life (t1/2) of mibefradil under steady-state conditions was 26.8 +/- 5.5 h (versus an apparent t1/2 of 16.9 +/- 11.1 h for verapamil SR, P<0.05). CONCLUSIONS: Mibefradil is a well-tolerated and efficacious antihypertensive agent well suited to single daily dosing because of its intrinsic long plasma half-life. The effects on both blood pressure and PQ interval are of more gradual onset than those of unmodified verapamil and diltiazem after single doses.

Transcranial Doppler ultrasound in commercial air divers: a field study including cases with right-to-left shunting.

Many cases of decompression illness occur in divers using recommended decompression tables. Doppler ultrasound has been used for over 20 yr and has shown the presence of venous bubbles in asymptomatic divers working well within decompression limits. Previous studies have demonstrated an increased prevalence of patent foramen ovale in divers who have suffered neurologic decompression illness. It has been postulated that right-to-left shunting through a patent foramen ovale could allow arterialization of these bubbles, causing symptoms and signs of acute decompression illness and possibly chronic subclinical neurologic impairment. We set out to determine the incidence of bubbles in the cerebral circulation of commercial divers decompressing from air dives. Using transcranial Doppler ultrasound (TCD), the middle cerebral arteries of 17 divers were monitored after surfacing from depths ranging between 3 and 50 m. Peripheral contrast injection with simultaneous transthoracic echocardiography and TCD was used to screen for right-to-left shunting. Right-to-left shunting was detected in four divers by TCD (one at rest, two after a Valsalva maneuver, and one only after coughing); however, echocardiography was positive in only one of these subjects after a Valsalva maneuver (TCD was positive at rest in this subject). Seventy-three TCD recordings were performed in four settings: 41 after underwater decompression, 18 after surface decompression, 10 in the interval between surfacing and entering the decompression chamber, and 4 after a chamber dive. Twenty-three of these recordings were in four subjects with right-to-left shunting; no bubbles were detected in any of these recordings.(ABSTRACT TRUNCATED AT 250 WORDS)