Kizuku Kuramoto

Diminished nocturnal decline in blood pressure in elderly hypertensive patients with left ventricular hypertrophy

To assess the circadian blood pressure (BP) changes in elderly hypertensive patients with left ventricular hypertrophy (LVH), the ambulatory BP was measured noninvasively every 30 minutes for 24 hours in those patients with LVH (n = 15) and without LVH (n = 23), and in normotensive elderly subjects (n = 11). Although the daytime systolic BP (SBP) was comparable in the two hypertensive groups, the nighttime SBP in patients with LVH tended to be higher than in patients without LVH (149.0 +/- 15.1 versus 138.4 +/- 20.1 mm Hg, p less than 0.10). The LV mass index correlated significantly with the nighttime SBP (r = 0.43, p less than 0.01), but not with the daytime SBP (r = 0.24, ns), with clinic SBP (r = 0.14, p = ns) or the SBP after handgrip exercise (r = 0.31, p = ns). The difference in the systolic BP between daytime and nighttime (D-N SBP) in patients with LVH (2.8 +/- 9.4 mm Hg) was significantly less than that in patients without LVH (12.8 +/- 16.0 mm Hg) (p less than 0.02). In addition, the D-N SBP correlated inversely with the left ventricular mass index (r = -0.33, p less than 0.05). It was concluded that hypertension in the elderly with LVH was associated with a diminished nocturnal decline in blood pressure.

Cardiac implications of the morning surge in blood pressure in elderly hypertensive patients: Relation to arising time

Although morning surge in blood pressure has been shown to be associated with the occurrence of myocardial ischemic events and stroke, few studies have been done regarding its pathogenesis, probably because of a lack of method for the quantitative assessment of awakening time. We conducted an echocardiographic study and ambulatory blood pressure monitoring in 23 elderly hypertensive patients to evaluate the relationship between the hypertensive cardiac change and morning surge in blood pressure. Of note was that the time of arising from bed was assessed quantitatively by an activetracer equipped with an internal acceleration sensor to monitor the physical activity. The change in systolic blood pressure after arising from bed was correlated significantly with the left ventricular mass index (r = 0.51, P < .02) and the A/E ratio, which represents the diastolic function (r = 0.70, P < .01). In contrast, the change in systolic blood pressure before rising from bed was not correlated with any echocardiographic parameters. We conclude that the magnitude of morning surge in blood pressure after arising from bed was related with the severity of hypertensive target organ damage.

The cardiac functional reserve in elderly hypertensive patients with abnormal diurnal change in blood pressure

Objective: To evaluate the left ventricular function of hypertensive patients with abnormal diurnal change in blood pressure. Design: We compared left ventricular structural and functional characteristics between hypertensive patients with a normal diurnal change in blood pressure (H2 group) and those with a nocturnal blood pressure increment (H1 group) using echocardiography. Methods: The study group consisted of 36 hypertensives and 16 normotensives whose 24-h ambulatory blood pressure monitorings were measured non-invasively. The hypertensive group was subdivided into the H1 group, consisting of 11 patients (76 ± 7 years), and the H2 group with 25 patients (73 ±7 years). The normotensive control group had a mean age of 73 ± 6 years. Echocardiographic examinations were performed before and at the end of isometric exercise (handgrip for 3 min) and isoproterenol infusion (0.02 ug/kg per min for 5 min). Results: The left ventricular mass index in the H1 group was significantly greater than in the H2 or control group. Left ventricular fractional shortening (LVFS) at rest in the H1 group was also significantly greater than in the other two groups. However, the peak late: early diastolic filling ratio, which indicated diastolic function, significantly deteriorated in the H1 group compared with the H2 and control groups. Furthermore, changes in LVFS after isometric exercise in the H1 group were more supressed than in the H2 or control group. In addition, a significantly lower increment in LVFS after isoproterenol was observed in the H1 group compared with the H2 or control group. Conclusion: The H1 group had greater left ventricular mass and impaired left ventricular functional reserve than the H2 group.

A randomized, double-blind, four-arm parallel-group study of the efficacy and safety of azelnidipine and olmesartan medoxomil combination therapy compared with each monotherapy in Japanese patients with essential hypertension: the REZALT study

A 12-week randomized, double-blind, four-arm parallel-group, comparative study was conducted in patients with essential hypertension to evaluate the antihypertensive effect and safety of combination therapy with olmesartan medoxomil (OLM, an angiotensin-receptor blocker) 20 mg plus azelnidipine (AZL, a long-acting dihydropyridine calcium channel blocker) 16 mg, (O/A (20/16)), or OLM 10 mg/AZL 8 mg (O/A (10/8)) compared with those of monotherapy with OLM 20 mg (OLM (20)) or AZL 16 mg (AZL (16)). The change from baseline to week 12 in seated blood pressure (SeBP) was −23.6/−14.2 mm Hg (systolic/diastolic BP) in the O/A (20/16) group, and −20.3/−13.0 mm Hg in the O/A (10/8) group, which was a significantly greater reduction in SeBP than in the monotherapy groups (−15.7/−9.9 mm Hg in OLM (20); −15.0/−9.4 mm Hg in AZL (16)). The change from baseline in 24-h ambulatory BP was also significantly greater in the O/A (20/16) and O/A (10/8) combination groups (−22.1/−13.5 and −18.2/−10.6 mm Hg, respectively) than in the OLM (20) and AZL (16) monotherapy groups (−12.1/−6.9 and −12.0/−6.9 mm Hg). The proportion of patients achieving the SeBP goal (<130/85 mm Hg for normal BP or <140/90 mm Hg for high-normal BP) was significantly higher in the O/A (20/16) combination group than in the monotherapy groups. The incidence of adverse events was similar in the O/A combination groups and the monotherapy groups. These results showed that combination therapy with O/A was well tolerated and exerted a stronger antihypertensive effect compared with monotherapy with OLM or AZL in patients with essential hypertension.

Pseudohypertension in the elderly

Pseudohypertension is a condition in which indirect blood pressure measured by the cuff method overestimates the true intra-arterial blood pressure. Despite the clinical importance of pseudohypertension, reports regarding its prevalence are scarce. We compared direct measurements of brachial arterial blood pressure with those measured indirectly by the cuff method in 59 healthy volunteers aged greater than 65 years, with or without hypertension, in order to investigate the prevalence of pseudohypertension in the elderly. The average systolic blood pressure of 161.5 mmHg obtained by the indirect method was significantly lower than the 169.2 mmHg obtained by the direct method was not significantly different from the 76.9 mmHg obtained by the direct method. Only one volunteer was observed in whom the indirect cuff method overestimated the diastolic blood pressure by greater than 10 mmHg, which was defined as pseudohypertension. Thus, the prevalence of pseudohypertension was only 1.7%. The difference in systolic blood pressure between the two methods was 8.7 mmHg in Osler-positive cases and was not significantly different from the 6.9 mmHg observed in Osler-negative cases. Pulse wave velocity was significantly correlated with the systolic blood pressure (y = 11.4x + 66.1, r = 0.65, P less than 0.05). No correlation was observed between the pulse wave velocity and direct/indirect pressure differences for either systolic or diastolic measurements. These results show that the prevalence of pseudohypertension is very low in a non-selected elderly population and that Oslers maneuver was not related to the pressure difference between the direct and indirect methods.

Diagnostic value of electrocardiography and echocardiography for white coat hypertension in the elderly

Abstract Although white coat hypertension is common in clinical practice, 1–3 its pathogenesis and clinical prognosis remain unknown. In elderly patients with office hypertension, white coat hypertension should be differentiated from true hypertension, since the excessive reduction in blood pressure (BP) caused by antihypertensive medication may induce an ischemic event in a vital organ. The present study assesses the sensitivity and specificity of electrocardiography in detection of white coat hypertension and quantitatively measures left ventricular hypertrophy in such patients using echocardiography. Results are compared with those in normotensive control subjects and in patients with true persistent hypertension.

Hemodynamic effects of salbutamol, an oral long-acting beta-stimulant, in patients with congestive heart failure

As the efficacy of oral long-acting sympathomimetic drugs is not yet well established, we investigated the hemodynamic effects of orally administered salbutamol in eight heart failure patients. Cardiac index, heart rate, blood pressure, and left ventricular filling pressure were monitored for 6 hours after a single oral administration of 4 to 8 mg salbutamol and placebo. In patients who had received salbutamol, a 40% increase in the cardiac index (+0.75 L/min/m2, p less than 0.01) was noted 1 hour post administration; a 44% increase (peak effect) occurred at 2 hours (+0.84 L/min/m2, p less than 0.05); and a significant increase persisted for 6 hours. Changes in heart rate showed a similar time course; however, the increase was less pronounced (+27% at 2 hours). The changes in blood pressure were slight and none of the eight patients developed ventricular arrhythmia or other complications. After placebo administration, no consistent changes in the hemodynamic parameters were noted. The present study suggests that, due to its sustained positive action on cardiac output, the oral administration of salbutamol may be efficacious in ambulatory patients with low cardiac output due to heart failure.

Effects of combination olmesartan medoxomil plus azelnidipine versus monotherapy with either agent on 24-hour ambulatory blood pressure and pulse rate in japanese patients with essential hypertension: Additional results from the REZALT study

BACKGROUND In a previously reported randomized, double-blind, parallel-group study of the efficacy and tolerability of olmesartan medoxomil (OLM) and azelnidipine (AZL) combination therapy compared with monotherapy with each agent in Japanese patients with essential hypertension (the REZALT study), the use of a combination of OLM, an angiotensin II receptor blocker, plus AZL, a dihydropyridine calcium channel blocker, was associated with significantly greater reductions in office sitting blood pressure (BP) and 24-hour ambulatory BP compared with monotherapy with either agent, and was well tolerated. OBJECTIVE This article reports the results from an a priori planned analysis and post hoc analyses of the diurnal BP and pulse rate (PR) profiles of OLM/AZL versus monotherapy with either agent from the REZALT study. METHODS Male and female Japanese outpatients with essential hypertension were eligible if they met the following inclusion criteria: age > or = 20 years; systolic BP (SBP) > or = 140 to <180 mm Hg and diastolic BP (DBP) > or = 90 to <110 mm Hg; and 24-hour ambulatory SBP/DBP > or = 135/> or = 80 mm Hg. Patients were randomly assigned to receive OLM/AZL 10/8 mg, OLM/AZL 20/16 mg, OLM 20 mg, or AZL 16 mg, once daily for 12 weeks. The effectiveness of the treatments was assessed using 24-hour ambulatory BP monitoring (ABPM) and PR, analyzed by time period (BP and PR, 24 hours, daytime [7 AM-<10 PM], nighttime [10 PM-<7 AM], and early morning [6 AM-<9 AM]; PR, morning [6 AM -<11 AM]) and dipping status at baseline (dippers [(Daytime BP - Nighttime BP)/Daytime BP > or = 10%] or nondippers [(Daytime BP - Nighttime BP)/Daytime BP <10%]). RESULTS A total of 867 patients were enrolled, and 862 randomized patients were included in the full analysis set (590 men, 272 women; mean age, 56.6 years). A total of 839 patients had assessable ABPM data (213, 211, 206, and 209 patients in the OLM/AZL 10/8 mg, OLM/AZL 20/16 mg, OLM, and AZL groups, respectively). No clinically significant between-group differences were observed in baseline demographic and clinical characteristics. Combination therapy was associated with significantly greater antihypertensive effects on 24-hour ABPM compared with either monotherapy in all of the time periods, as follows: SBP/DBP reductions with OLM/AZL 20/16 mg in the daytime, nighttime, and early morning were -22.6/-14.1, -21.2/-12.5, and -20.6/-11.9 mm Hg, respectively (all, P < 0.05 vs the other 3 treatment groups). The SBP/DBP reductions with OLM/AZL 10/8 mg (daytime, -18.2/-11.0 mm Hg; nighttime, -18.1/-10.0 mm Hg; and early morning, -15.6/-9.3 mm Hg) were also significantly greater than with OLM 20 mg (-11.8/-6.7, -12.8/-7.2, and -11.0/ -6.9 mm Hg, respectively; all, P < 0.01) and AZL 16 mg (-13.1/-7.8, -10.2/-5.5, and -9.9/-6.1 mm Hg; all, P < 0.001) in all of the time periods. The antihypertensive effects associated with OLM/AZL 10/8 mg or 20/16 mg were significantly greater than those with monotherapies regardless of dipping pattern at baseline (all, P < 0.05) in all of the time periods, with the exception of nighttime reduction with OLM/AZL 10/8 mg versus OLM in dippers. The numbers of patients who had any increase in BP were 12/213 (5.6%) with OLM/AZL 10/8 mg, 13/211 (6.2%) with OLM/AZL 20/16 mg, 35/206 (17.0%) with OLM, and 36/209 (17.2%) with AZL. The AZL-containing regimens were associated with reduced morning PR (mean [95% CI] changes from baseline to week 12: -1.5 beats/min [-2.5 to -0.4] with OLM/AZL 10/8 mg, -2.1 beats/min [-3.0 to -1.1] with OLM/AZL 20/16 mg, 0.4 beat/min [-0.5 to 1.3] with OLM, and -1.9 beats/min [-2.8 to -1.0] with AZL). CONCLUSION In this study in Japanese patients with essential hypertension, the reductions in daytime, nighttime, and early-morning BP assessed using 24-hour ABPM were significantly greater with combination OLM/AZL than with either monotherapy, regardless of dipping pattern at baseline. Japan Pharmaceutical Information Center registration number: JapicCTI-060286.

Studies on the control of coronary circulation Part I. The effect of the stimulation of the nerves on the coronary circulation. Part II. The humoral effect on the coronary circulation

Abstract 1. 1. A study was made of the coronary vasodilatative effects of coronary venous blood samples obtained following the stimulation of the sympathetic and vagal nerves, and of norepinephrine, acetylcholine, and ATP. 2. 2. In the coronary venous blood samples, obtained either during or 15 seconds after the stimulation of the sympathetic nerves, some vasodilatative substances were demonstrated. They may play one of the important roles in sympathetic coronary vasodilatation. The exact nature of the vasodilatative substances are unknown, but they may be the metabolites released following the sympathetic stimulation. 3. 3. The coronary vasodilatative effect of norepinephrine differs in nature from that of acetylcholine, ATP, and effective coronary venous blood. It may result mainly from hemodynamic and metabolic action due to the modification of the heart. The action of norepinephrine on coronary vessels seems to be identical with that of the sympathetic nerves.

Clinical Evaluation of the Plasma Levels of Immunoreactive Atrial Natriuretic Peptide in Elderly Patients with Heart Diseases

Plasma levels of immunoreactive atrial natriuretic peptide (ANP) were estimated in 69 elderly patients over 60 years of age (mean 76.4 years) with or without heart diseases and in ten young, healthy volunteers (mean 33.0 years) to evaluate the clinical significance of ANP in the elderly. Plasma ANP levels in nine patients without heart diseases were significantly (P < .01) higher than in the ten young, healthy subjects (mean ± SD, 46.0 ± 22.0 vs 22.1 ± 6.3 pg/mL) and a significant positive correlation was observed between ANP level and age in these subjects (r = 0.60, P < 0.01). Plasma ANP levels in 60 patients with heart diseases (158.4 ± 158.5 pg/mL) were significantly (P < 0.05) greater than in nine patients without heart diseases. Plasma ANP levels in patients with congestive heart failure or atrial fibrillation were 285.8 ± 185.2 or 223.0 ± 185.9 pg/mL, respectively; each of these values was significantly (P < 0.01) higher than in patients without heart diseases. In three patients with paroxysmal atrial fibrillation, plasma ANP levels during atrial fibrillation were three times greater than when atrial fibrillation returned to normal sinus rhythm (377.3 ± 78.5 vs 101.1 ± 68.5 pg/mL).