Increased pulse pressure (PP) is recognized as a risk factor for cardiovascular disease, especially in elderly patients. However, blood pressure (BP) is known to have a circadian variation. Therefore, this study asked whether or not PP has a circadian variation and, if so, whether a circadian variation of PP has clinical importance. Ambulatory BP monitoring (every 30 min for 48 h) was performed in 255 patients with untreated essential hypertension (24 to 82 years old; mean: 52+/-12 years). Left ventricular mass index (LVMI) was estimated from M-mode echocardiography. PP was decreased during nighttime (10+/-11% reduction from daytime PP). Multivariate linear regression analysis showed that, among four variables-the degree of nighttime PP reduction, daytime PP, 48-h systolic BP, and nondipper hypertension-the degree of nighttime PP reduction had the strongest (inverse) correlation with LVMI in a subgroup of elderly patients (> or =60 years old, n =67) (standardized regression coefficient=-0.32, p =0.02), whereas this association was not significant in the whole patient population unclassified by age. Furthermore, a blunted reduction of nighttime PP in combination with nondipper hypertension was an incremental risk for increase in LVMI in the elderly patients. In conclusion, PP is reduced during nighttime, but the degree of reduction varies among patients. The blunted reduction of nighttime PP is a risk for left ventricular hypertrophy, an established predictor of hypertension-induced cardiovascular events, and it may thus play a role in cardiovascular complications, especially in elderly patients with nondipper hypertension.

Two patients with amiodarone-induced pulmonary toxicity (APT) showed abnormally increased serum SP-D concentrations, although their KL-6 level was within the normal range. In a 59-year-old man with ischemic heart disease, APT progressed rapidly and required steroid pulse therapy. During the clinical course, SP-D was as high as 375 ng/ml, although the KL-6 level was only 289 U/ml. In a 58-year-old man treated for dilated cardiomyopathy, SP-D increased to 289 ng/ml, while KL-6 remained at less than 500 U/ml. These cases indicate that SP-D is a useful and early diagnostic marker for APT even when KL-6 is not elevated.

A 25-year-old Japanese female complaining chest oppression and palpitation was admitted to hospital under the presumptive diagnosis of ischemic heart disease (IHD), although no obvious underlying disease associated with IHD was detected. Coronary angiography showed stenosis at the proximal site of left anterior descending artery (LAD), with dilatation and tortuosity at the bifurcation of the first and the second septal branches. Intravascular ultrasound imaging of the LAD showed intimal thickness without calcification at the site of stenosis. The stenosis was successfully and smoothly dilated by percutaneous transluminal angioplasty. Even with precise evaluation, the cause of the coronary artery disease in this young female patient was not clarified. Further careful follow-up is needed.

To evaluate the circadian variations and exercise response patterns of blood pressure (BP) and heart rate (HR) in white coat (WC-HT) and established hypertensives (E-HT), we performed 48-hr ambulatory BP monitoring (TM-2425, A&D, Japan) and symptom-limited treadmill exercise test (CASE-12, Marquette, USA; STBP-680,Colin, Japan) using a Bruce protocol at 15:00-17:00 in 109 untreated outpatients with mild to moderate essential hypertension. The mean values of HR, systolic (SBP) and diastolic BP (DBP) in daytime and nighttime were analyzed by reviewing the patients' diaries. These patients were then divided into two groups according to the mean daytime BP <135/85mmHg (WC-HT, n=34) or >135/85mmHg (E-HT, n=75). Values are expressed as mean±SD, *p<0.05 vs E-HT. (See Table) White coat hypertensives responded to dynamic exercise stress with exaggerated increases in HR and SBP compared with patients with established hypertension, and SBP during exercise was similar in two groups. In conclusion, these exaggerated responses in HR and SBP to exercise stress might lead to a white coat phenomenon in patients with white coat hypertension.

BACKGROUND:Angiocardiography is an important diagnostic modality for evaluation of heart disease. It is well known that the concentration of plasma atrial natriuretic peptide (ANP) increases after injection of contrast medium. On the other hand, some patients with hypertension, heart failure or cardiac hypertrophy have an increased plasma ANP concentration at baseline; however, whether ANP increases after angiography in these patients is unknown.OBJECTIVES:To investigate changes in plasma ANP concentrations after angiocardiography in patients with high ANP concentrations at baseline.PATIENTS AND METHODS:Plasma ANP concentrations of 32 patients with angina pectoris were measured before and after angiocardiography. They were then classified into two groups according to their ANP concentration before examination.RESULTS:ANP concentration after the injection of contrast medium increased significantly in patients with normal ANP concentrations before angiography but did not change in patients with high ANP concentrations at rest.CONCLUSIONS:These results suggest that the absence of an increase in ANP after angiography may in part be due to reduced sensitivity to the angiography stimulus or to an already maximal activation of ANP secretion at baseline.

The aim of this study was to evaluate the effects of nifedipine-coat core “adalat-CR” administered at different times of the day (morning vs evening) on circadian blood pressure (BP) profile in patients with essential hypertension. Nifedipine-coat core (40mg/day) was given at 07:00 or 19:00 for more than 4 weeks in a cross over fashion. Systolic (SBP) and diastolic BP (DBP) were monitored before and after morning and evening treatment every 30 minutes every 48 hours by ambulatory BP monitoring (TM-2425, A&D, Japan) in untreated 12 outpatients with essential hypertension. The daytime and nighttime mean, as well as the nighttime/daytime ratio (N/D ratio) of SBP and DBP were analyzed by reviewing the patients' diaries. (See Table) Values are expressed as mean±SD, *p<0.05, **p<0.01 as compared with before treatment. Morning treatment decreased only daytime BP. Evening treatment decreased BP throughout the day, and the N/D ratio of BP did not change before and after the evening treatment. In conclusion, evening treatment of nifedipine-coat core might be superior to morning treatment in reducing BP throuout 24 hours and preserving circadian BP profile.

To evaluate the behavior of cardiac arrhythmias in dipper and nondipper hypertensive patients, 48-h ambulatory blood pressure monitoring, 24-h Holter electrocardiogram recording and echocardiographic studies were performed in 56 untreated outpatients with essential hypertension. These patients were divided into 2 groups according to the presence (dipper, n=33) or absence (nondipper, n=23) of reduction of both systolic and diastolic blood pressure during nighttime by an average of more than 10% of daytime blood pressure. Mean 48-h systolic and diastolic blood pressures did not differ between the 2 groups. Nondipper patients had a significantly larger left atrial dimension (31.9+/-3.8 vs 35.6+/-3.7 mm; p<0.01), left ventricular mass index (114+/-26 vs 136+/-36 g/m2; p<0.05), as well as a larger number of total supraventricular (16+/-19 vs 89+/-197 beats; p<0.05) and ventricular ectopic beats (7+/-14 vs 47+/-96 beats; p<0.05) during daytime as compared with dippers. In conclusion, nondipper hypertensive patients are likely to experience supraventricular and ventricular arrhythmias more frequently than dippers. A blunted nocturnal blood pressure fall may be involved in the appearance of cardiac arrhythmias in patients with essential hypertension.

We used a Cardiopulmonary test to assess the physiological benefit of single lead VDD pacing in ten patients (six men, four women; aged 32–84 years, mean 69 years) with atrioventricular block. Maximal symptom‐limited treadmill exercise test using a ramp protocol was performed under VDD and VVIR or VVI pacing (VVI) in random sequence. The pacemaker was then programmed to the VDD mode, and Holter ECG was recorded in nine patients. Compared with findings during the VVI, the VDD mode had a greater chronotropic response (mean maximal heart rate, VDD 106 ± 17 beats/mm vs VVI 79 ± 19 beats/min, P = 0.03), and was associated with prolongation of exercise duration (VDD 11.2 ± 2.9 minute vs VVI 10.5 ± 3.1 minute; P = 0.01), and the onset of anaerobic threshold at a higher oxygen uptake (VDD 12.4 ± 3.4 mL/min per kilogram vs WI 10.0 ± 2.1 mL/min per kilogram; P < 0.01). Atriai sensing was recognized in almost all normal sinus P waves for all cases examined using Holter ECG. Thus, chronotropic response during exercise by VDD pacemaker improved exercise tolerance, indicating that a VDD pacemaker might be useful for patients requiring physical activity.

To evaluate the circadian variation of pulse pressure (PP) and left ventricular hypertrophy (LVH) in essential hypertension (HTN), we performed 48-hour ambulatory blood pressure (BP) monitoring (Colin, A&D, Japan) every 30 minutes and echocardiographic study (Hewlett Packard, USA) in 288 untreated patients with mild to moderate HTN. Mean 48-hour and the nocturnal reduction rate (NRR) of PP were calculated by reviewing the patients’ diaries. NRR (%) = (daytime mean − nighttime mean) / (daytime mean). LV mass index (LVMI=LVM/BSA, Penn Convention method) and relative wall thickness (RWT= 2 · LV posterior wall thickness / LV end diastolic dimension) were calculated. The NRR of PP, 48-hour mean systolic/diastolic BP, PP, and LVMI were 9±15%, 142±15/85±10mmHg, 57±9mmHg, 128±38g/m2, respectively. LVMI and RWT correlated with 48-hour mean PP (r = 0.36, 0.18; p<0.05), but not with the NRR of PP. LVMI in Group A (48-hour mean PP<50 mmHg: n=60), B (50≤ <55: n=71), C (55≤ <60: n=79) and D (602, respectively (* p<0.01 vs Group A, # p<0.01 vs B, \s p<0.05 vs C). In conclusion, hypertensive patients with increased 48-hour mean PP are likely to have more advanced LVH, and increased mean PP might be a risk factor for concentric LVH in patients with HTN.

The aim of this study was to assess the acute and chronic stresses on BP and HR rhythms at the specific time of the day, 2) to tune acute stress effect to the reference, 3) to tune circadian rhythm to the reference rhythm. The short term variabilities were monitored for 5 min. The cold pressure test was performed as the specific different time of the day. Circadian variables were monitored with ABPM (A/D Co.). The rhythms of essentially hypertensives were tuned to those rhythms obtained from the gender and age matched references (n=700). Effects of cold pressure test on circadian BP and HR in normotensives. Cold pressure test was performed twice at 11:00 and 23:00. The peak values of BP and HR attained by the test were significantly higher at 11:00 than at 23:00. The responses to the stress were function of the particular stage of circadian rhythm of BP and HR. Each individuals under the stress was asked to tune the rhythm to attain the reference resting level. The magnitude of the tuning was quantified nor only visually but also numerically. The age and gender matched reference circadian profile was established based on the reference individuals. The individuals who showed disturbed circadian profile were asked to tune their daily BP and HR to the circadian profile. This approaches were also successful to tune the circadian profile not only subjective visually but also numerically. In conclusion, the short and long term rhythm were distorted by the stress. In order to tune the rhythm the magnitude of the restoration could be assessed.

We assessed the relationship between blood pressure (BP) level and QT dispersion in patients with essential hypertension. 40 untreated essential hypertensive subjects were treated with antihypertensive drugs for 8 weeks. 21 were treated with ACE inhibitor (imidapril, 10 mg, s.i.d.; group I). 11 were treated with alpha 1 blocker (bunazosin, 3, 6 or 9 mg, s.i.d.; group B). 8 were treated with beta blocker (metoprolol, 120 mg, s.i.d.; group M). BP and heart rate were measured for 48 hours every 30 minutes by ambulatory BP monitoring device (TM-2425, A&D Co.) before and after treatment. Standard 12-lead electrocardiogram (ECG) and echocardiography (UCG) was performed before and after treatment. QT dispersion (the difference between the maximum and minimum QT interval in different leads) was measured. Left ventricular hypertrophy (LVH) was assessed by ECG and UCG. Diurnal and nocturnal BP were decreased, and maximum QT interval and QT dispersion were shortened in group I. Diurnal BP was decreased, but QT dispersion did not change in group B. Diurnal BP was decreased, and maximum and minimum QT interval and QT dispersion prolonged in group M. Antihypertensive therapy with imidapril reduced QT dispersion and left ventricular mass index. We conclude that long-term imidapril treatment of hypertensive patients with LVH improves LVH and reduces the dispersions of QT. This effect may be important in preventing sudden cardiac death in hypertensive subjects.

To evaluate the circadian variation of pulse pressure (PP) and heart rate variability (HRV) in essential hypertension (HTN), we performed 48-hr. ambulatory blood pressure (BP) monitoring (Colin, Japan) every 30 min. and Holter ECG recording (Del Mar Avionics, USA) in 56 untreated patients with mild to moderate HTN. Power spectral analysis of RR interval was performed from 24-hr. Holter ECG every 10 min. by the FFT method to obtain the low frequency band (LF:0.04–0.15Hz) and the high frequency band (UF: 0.15–0.40Hz). The nocturnal reduction rate (NRR) of PP was calculated according to the formula. NRR(%) = (daytime mean − nighttime mean) / (daytime mean). Mean BP and PP for 48 hrs. were 142±14 / 84±11, 65±9 mmHg, respectively. Both 24-hr. mean LF and HF correlated with 48-hr. mean PP (r = −0.30, −0.32; p<0.05), but not with the NRR of PP. Patients with 48-hr. mean PP≥60mmHg (n=43) had significantly smaller 24-hr. mean LF and HF than those (n=13) with <60mmHg (LF:4.8±0.6 vs. 5.3±0.7 msec/Hz2, HF:4.1±0.6 vs. 4.7±0.7 msec/Hz2, p<0.05). Mean LF/HF for 24-hrs. was similar in two groups. In conclusion, hypertensive patients with increased 48-hr. mean PP are likely to have more decreased HRV and parasympathetic activity, and increased mean PP might be a risk factor for autonomic dysfunction in patients with mild to moderate HTN.