Junichi Minami

Positive association of CYP11B2 gene polymorphism with genetic predisposition to essential hypertension

Predispositions to essential hypertension and cardiovascular diseases are possibly associated with gene polymorphisms of the renin–angiotensin system. Gene polymorphisms of angiotensinogen and angiotensin-converting enzyme genes have been suggested to be risk factors for hypertension and myocardial infarction. Concerning the polymorphism of aldosterone synthase (CYP11B2) gene, earlier studies have shown inconsistent results in terms of its relation to hypertension. In the present case–control study, we investigated the association of −344T/C polymorphism in the promoter region of human CYP11B2 gene with genetic predisposition to hypertension. The genotype of −344T/C polymorphism was determined in essential hypertension subjects (n=250) and normotensive subjects (n=221). The distributions of three genotypes (TT, TC, and CC) were significantly different between the hypertensive and the normotensive groups (χ2=9.61, P=0.008). Namely, the frequency of C allele was higher in the hypertensive patients than in the normotensive subjects (34.2 vs 26.5%, P=0.010). Our data suggest that the −344C allele of CYP11B2 gene polymorphism is associated with the genetic predisposition to develop essential hypertension.

Efonidipine reduces proteinuria and plasma aldosterone in patients with chronic glomerulonephritis.

Efonidipine, a dihydropirydine calcium channel blocker, has been shown to dilate the efferent glomerular arterioles as effectively as the afferent arterioles. The present study compared the chronic effects of efonidipine and amlodipine on proteinuria in patients with chronic glomerulonephritis. The study subjects were 21 chronic glomerulonephritis patients presenting with spot proteinuria greater than 30 mg/dL and serum creatinine concentrations of ≤1.3 mg/dL in men or ≤1.1 mg/dL in women. All patients were receiving antihypertensive medication or had a blood pressure ≥130/85 mmHg. Efonidipine 20–60 mg twice daily and amlodipine 2.5–7.5 mg once daily were given for 4 months each in a random crossover manner. In both periods, calcium channel blockers were titrated when the BP exceeded 130/85 mmHg. Blood sampling and urinalysis were performed at the end of each treatment period. The average blood pressure was comparable between the efonidipine and the amlodipine periods (133±10/86±5 vs. 132±8/86±5 mmHg). Urinary protein excretion was significantly less in the efonidipine period than in the amlodipine period (1.7±1.5 vs. 2.0±1.6 g/g creatinine, p=0.04). Serum albumin was significantly higher in the efonidipine period than the amlodipine period (4.0±0.5 vs. 3.8±0.5 mEq/L, p=0.03). Glomerular filtration rate was not significantly different between the two periods. Plasma aldosterone was lower in the efonidipine period than in the amlodipine period (52±46 vs. 72±48 pg/mL, p=0.009). It may be concluded that efonidipine results in a greater reduction of plasma aldosterone and proteinuria than amlodipine, and that these effects occur by a mechanism independent of blood pressure reduction. A further large-scale clinical trial will be needed in order to apply the findings of this study to the treatment of patients with renal disease.

Association of Smoking With Aortic Wave Reflection and Central Systolic Pressure and Metabolic Syndrome in Normotensive Japanese Men

BACKGROUNDnThe influences of smoking habits on blood pressure (BP) may have been underestimated substantially on the basis of conventional measurements. We compared the radial augmentation index (AI), brachial and central pressures, and prevalence of the metabolic syndrome (MetS) among never smokers, former smokers, and current smokers in a population of Japanese healthy men.nnnMETHODSnA total of 443 normotensive men who entered the health checkup program was divided into four groups according to smoking status; i.e., never smokers (n = 117), former smokers (n = 165), current mild to-moderate smokers (n = 105), and current heavy smokers (n = 56). Radial pulse waveforms were obtained using radial tonometry (HEM-9000AI), and the AI and late systolic pressure in the radial artery, an estimate of central systolic pressure, were measured.nnnRESULTSnThe AI was significantly higher in current smokers than both never and former smokers. Central systolic pressure was significantly higher in both current and former smokers than never smokers, although brachial systolic pressure was not significantly different among these groups. The MetS was more prevalent in current smokers than never smokers.nnnCONCLUSIONnSmoking habits have substantially different effects on the AI and central systolic pressure despite a similar level of brachial systolic pressure. Along with higher prevalence of the MetS, elevated AI and central systolic pressure may be potential mechanisms responsible for an increased risk of cardiovascular disease in smokers.

Relation between the angiotensin-converting enzyme insertion/deletion polymorphism and blood pressure in Japanese male subjects.

Inconsistent results have been reported regarding the association of the angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphism and hypertension. Recent studies of population-based samples of three different areas in Japan presented conflicting results regarding this association. We, thus, investigated the relation between the ACE I/D polymorphism and blood pressure (BP), or the frequency of hypertension, respectively, in 706 Japanese male subjects who participated in the health check-up programme of our hospital. The ACE I/D polymorphism was determined by the polymerase chain reaction technique. Of 706 subjects, 203 were found to have hypertension and the other 503 were found to be normotensive. In all subjects, the frequencies of the DD, ID, and II genotypes were 0.123, 0.432, and 0.445, respectively, and the allelic frequency of the D allele was 0.339. In the younger subjects aged <50 years (n=264), neither systolic nor diastolic BP differed significantly among the genotypes. Conversely, in the older subjects aged⩾50 years (n=442), the systolic BP was significantly higher by 5.9u2009mmHg in the subjects with the ID genotype than those with the II genotype (P<0.01), and the diastolic BP was significantly higher in the subjects with the DD and ID genotypes by 5.1 and 3.3u2009mmHg, respectively than those with the II genotype (P<0.05 for each), although age, BMI, percentage of smoking habits, drinking habits, or the use of antihypertensive drugs did not differ significantly among the genotypes. In addition, in the older subjects, the hypertensive subjects showed significantly higher frequencies of the DD and ID genotypes and the D allele than the normotensive subjects. These results demonstrated that there was no significant association of the ACE I/D polymorphism with BP or a prevalence of hypertension in younger Japanese men aged <50 years but there was in older Japanese men aged ⩾50 years.

Acute and chronic effects of a hypocaloric diet on 24-hour blood pressure, heart rate and heart-rate variability in mildly-to-moderately obese patients with essential hypertension.

We examined the acute and chronic effects of a nutritionally balanced, moderately hypocaloric diet on 24-hour ambulatory blood pressure, heart rate and heart-rate variability in mildly-to-moderately obese patients with essential hypertension. We enrolled 16 obese patients with essential hypertension [age: 51-76 years, body mass index (BMI): 26-32 kg/m2]. For the initial week, a standard diet of 2,000 kcal/day was given, followed by a 3-week of a hypocaloric diet of 850 kcal/day. In the last period of the standard diet and in the first and the last periods of the hypocaloric diet, each subjects 24-hour ambulatory blood pressure, heart rate and R-R intervals of the electrocardiogram were recorded, and electrolytes and catecholamines in 24-hour urine samples were also measured. A power spectral analysis of the heart-rate variability was performed over a 24-hour period based on the autoregressive method. The subjects lost 3.7+/-0.3 kg (mean +/- s.e.m.) of body weight during the 3-week hypocaloric diet period. The 24-hour blood pressure did not differ between the last period of the standard diet and the first period of the hypocaloric diet; however, it showed a significant reduction after 3 weeks of the hypocaloric diet. The decrease in the 24-hour blood pressure during the study period was 10.5+/-1.5 mm Hg systole and 4.3+/-1.8 mm Hg diastole. In contrast, the 24-hour heart rate was significantly reduced in the first period of the hypocaloric diet, although the body weight and blood pressure did not change, and the rate was maintained even in the last period of the hypocaloric diet. The decrease in the 24-hour heart rate during the study period was 2.8+/-0.9 beats per minute. The hypocaloric diet did not change any autonomic indices obtained from a power spectral analysis of the heart-rate variability. In conclusion, different responses to a hypocaloric diet were observed between the blood pressure and the heart rate in obese hypertensive patients. The changes in power spectral parameters of the heart-rate variability were less apparent than those found with the blood pressure or the heart rate.

Effects of landiolol on QT interval and QT dispersion during induction of anesthesia using computerized measurement

STUDY OBJECTIVEnTo examine the effects of landiolol on the QT interval, rate-corrected QT (QTc) interval, QT dispersion (QTD), and rate-corrected QTD (QTcD) during tracheal intubation using computerized measurement.nnnDESIGNnRandomized, double-blinded study.nnnSETTINGnDokkyo Medical University Hospital operating room.nnnPATIENTSn30 ASA physical status I patients scheduled for elective surgery.nnnINVENTIONSnPatients were randomized to receive either normal saline (saline group) or landiolol (landiolol group; one-min loading infusion of 0.125 mg/kg followed by 0.04 mg/kg/min infusion). Immediately after the start of administration of saline or landiolol, anesthesia was induced with intravenous (IV) fentanyl two microg/kg, propofol 1.5 mg/kg, and vecuronium 0.1 mg/kg. Six minutes after administration of saline or landiolol, tracheal intubation was performed within 20 seconds.nnnMEASUREMENTSnMean arterial pressure (MAP), RR interval, QT interval, QTc interval, QTD, and QTcD were consecutively recorded during the induction.nnnMAIN RESULTSnThere was no significant difference in MAP between groups during the study. RR interval in the landiolol group was significantly longer than in the saline group from two minutes after the start of the landiolol infusion to the end of the study. The QT interval in the landiolol group was significantly shorter than in the saline group from start of the infusion to 4 minutes after tracheal intubation. The QTc interval, QTD, and QTcD in the landiolol group were significantly shorter than those in the saline group from immediately after tracheal intubation to the end of study.nnnCONCLUSIONnA bolus of landiolol 0.125 mg/kg followed by an infusion of landiolol 0.04 mg/kg/min may reduce the risk of cardiac arrhythmias during induction of anesthesia.

Predictive Significance of Blood Pressure Values for the Incidence of Cardiovascular Events in Chronic Hemodialysis Patients

We conducted a prospective study investigating the relationship between blood pressure values and the risk of cardiovascular disease in patients with end-stage renal diseases. Five hundred fifty-three patients on chronic hemodialysis were followed for 5 years, and the relationship between systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP) and pulse pressure (PP) and the incidence of death and cardiovascular events were evaluated. There were 85 cardiovascular and 88 non-cardiovascular deaths during the 5 years. Fatal and nonfatal cardiovascular events occurred in 205 patients. Factors such as old age, diabetes and electrocardiographic findings of left ventricular hypertrophy and arrhythmia were associated with a high incidence of cardiovascular events as well as the incidence of death. With regard to blood pressure values, only PP was significantly associated with the risk of death (p=0.003). Both SBP and PP showed a significant association with the incidence of cardiovascular events (p=0.004 and p<0.001). In other words, an increase in PP by 10 mmHg corresponded to a 22% increase in cardiovascular events, and a 10 mmHg SBP increase corresponded to a 10% increase in cardiovascular events. In conclusion, PP is a better predictor of death and cardiovascular events than other blood pressure values in chronic hemodialysis patients.

Combination of Angiotensin II Receptor Antagonist with Calcium Channel Blocker or Diuretic as Antihypertensive Therapy for Patients with Chronic Kidney Disease

We compared treatment with an angiotensin II receptor antagonist (ARB) and a calcium channel blocker (CCB) combination and a fixed-dose ARB and thiazide diuretic in 18 chronic kidney disease (CKD) patients. A randomized crossover study was performed using a fixed-dose combination of losartan-hydrochlorothiazide or losartan combined with controlled-release nifedipine. Both systolic blood pressure (SBP) and diastolic blood pressures (DBPs) were lower during the nifedipine period than during the diuretic period. No significant difference was observed in urinary albumin excretion, but the estimated glomerular filtration rate was higher in the nifedipine than in the diuretic period. Serum uric acid and low-density lipoprotein cholesterol were higher in the diuretic than in the nifedipine period. A significantly low cardio-ankle vascular index, an index of arterial wall stiffness, was observed in the nifedipine period. A combination of ARB and a controlled-release nifedipine at 20–40 mg used showed a superior antihypertensive effect in CKD patients compared to a fixed-dose combination of losartan 50 mg-hydrochlorothiazide 12.5 mg in terms of blood control. The former combination is considered advantageous for maintaining renal function and artery wall elasticity without influencing uric acid or lipid metabolism.

Benazepril slows progression of renal dysfunction in patients with non-diabetic renal disease

Aim:u2003 The present study examined the effects of benazepril, an angiotensin‐converting enzyme inhibitor, on the progression of renal insufficiency in patients with non‐diabetic renal disease.

Pretreatment levels of plasma renin activity predict ambulatory blood pressure response to valsartan in essential hypertension.

Pretreatment levels of plasma renin activity predict ambulatory blood pressure response to valsartan in essential hypertension