The Bedtime Administration of Doxazosin Controls Morning Hypertension and Albuminuria in Patients with Type-2 Diabetes: Evaluation Using Home-Based Blood Pressure Measurements

The control of high blood pressure (BP) after awakening in the morning (morning hypertension) as determined by home BP (HBP), as well as BP control throughout the day, may prevent diabetic vascular complications. We examined the effect of an α-adrenergic blocker (doxazosin) on BP measurements taken by HBP after awakening and during clinic visits (CBP) in 50 patients with type-2 diabetes and morning hypertension. We evaluated the urinary albumin excretion rate as an indicator of nephropathy. Doxazosin was taken orally once at bedtime for 1 to 3 months. The mean (± SD) dose was 2.9 ± 2.1 mg/day (1 to 8 mg/day). The BP was measured monthly at the clinic during the day and at home after awakening in the morning. In this short-term trial (2.8 ± 0.4 months), the systolic HBP decreased significantly from 164 ± 17 mmHg before treatment to 146 ± 19 mmHg after treatment, and the diastolic HBP decreased significantly from 85 ± 14 mmHg before treatment to 80 ± 9 mmHg after treatment. The systolic, but not the diastolic CBP, decreased significantly after treatment. There was no significant difference in the systolic or diastolic values between the HBP and the CBP after treatment. The percentage change in the systolic HBP after treatment was three times greater than for the systolic CBP. The median (interquartile) urinary albumin excretion rate decreased significantly (P < 0.001) from 62 (25–203) mg/g creatinine before treatment to 19 (9–76) mg/g creatinine after treatment. On multiple regression analysis, the decrease in the systolic HBP with treatment positively correlated with the reduction in urinary excretion of albumin. The control of morning hypertension reduced the albuminuria found in both untreated and treated hypertensive patients with type-2 diabetes. Bedtime administration of doxazosin appears to be safe and effective in reducing morning hypertension as measured by HBP. This finding also demonstrates that HBP taken in the morning has a stronger predictive power for the albuminuria level than does CBP.     

An alpha-adrenergic blocker titrated by self-measured blood pressure recordings lowered blood pressure and microalbuminuria in patients with morning hypertension: the Japan Morning Surge-1 Study

BACKGROUND: The impact on microalbuminuria of strict treatment aimed at lowering of self-measured morning blood pressure using an adrenergic blockade is unclear. METHODS: We conducted an open-label multicenter trial, the Japan Morning Surge-1 Study, that enrolled 611 hypertensive patients, whose self-measured morning systolic blood pressure levels were more than 135 mmHg while taking antihypertensive drugs. These were randomly allocated to an experimental group, whose members received bedtime administration of 1-4 mg doxazosin (doxazosin group) or a control group whose members continued without any add-on medication (control group). The urinary albumin/creatinine ratio was investigated at the baseline and 6 months after the randomization. RESULTS: Both the morning and evening blood pressures and urinary albumin/creatinine ratio (-3.4 vs. 0.0 mg/gCr for urinary albumin/creatinine ratio; P < 0.001) were more markedly reduced in the doxazosin group than in the control group. This difference in the urinary albumin/creatinine ratio between the two groups was more marked in the patients with microalbuminuria (n = 238, -27.9 vs. -8.1 mg/gCr, P < 0.001). The reduction of urinary albumin/creatinine ratio was significantly associated with the use of doxazosin, and the change in all self-measured blood pressures (morning, evening, the average morning-evening), and these associations were independent of each other (P < 0.001). CONCLUSION: Adding a bedtime dose of an alpha-adrenergic blocker titrated by self-measured morning blood pressure in treated hypertensive patients with uncontrolled morning hypertension significantly reduced blood pressure and urinary albumin excretion rate, particularly in those with microalbuminuria.     

Accuracy of telemedical home blood pressure measurement in the diagnosis of hypertension

This study was conducted to compare the accuracy of clinic blood pressure (CBP) and telemedical home blood pressure (HBP) measurement in the diagnosis of hypertension in primary care. The study subjects were 411 patients with average CBP > or =140 mmHg systolic or > or =90 mmHg diastolic, who performed telemedical HBP measurement (5 days, four times daily) and ambulatory blood pressure (ABP) monitoring in random order. Main outcome measure was the agreement of CBP and HBP with daytime ABP. CBP was much higher than daytime ABP and average HBP (P<0.001) with no difference between the latter two. The correlation between CBP and ABP was weak (systolic: r=0.499, diastolic: r=0.543), whereas strong correlations existed between HBP and ABP (systolic: r=0.847, diastolic: r=0.812). A progressive improvement in the strength of the linear regression between average HBP of single days and ABP was obtained from day 1 to day 4, with no further benefit obtained on the fifth day. The HBP readings taken at noon and in the afternoon showed significantly stronger correlations with ABP than the blood pressures measured in the morning and in the evening. In conclusion, the accuracy of telemedical HBP measurement was substantially better than that of CBP in the diagnosis of hypertension in primary care. HBP most accurately reflected ABP on the fourth day of monitoring, and the readings at noon and in the afternoon seemed to be most accurate.     

Changes in home versus clinic blood pressure with antihypertensive treatments: a meta-analysis

Home blood pressure (HBP) monitoring is recommended for assessing the effects of antihypertensive treatment, but it is not clear how the treatment-induced changes in HBP compare with the changes in clinic blood pressure (CBP). We searched PubMed using the terms "home or self-measured blood pressure," and selected articles in which the changes in CBP and HBP (using the upper arm oscillometric method) induced by antihypertensive drugs were presented. We performed a systematic review of 30 articles published before March 2008 that included a total of 6794 subjects. As there was significant heterogeneity in most of the outcomes, a random effects model was used for the meta-analyses. The mean changes (+/-SE) in CBP and HBP (systolic/diastolic) were -15.2+/-0.03/-10.3+/-0.03 mm Hg and -12.2+/-0.04/-8.0+/-0.04 mm Hg respectively, although there were wide varieties of differences in the reduction between HBP and CBP. The reductions in CBP were correlated with those of HBP (systolic BP; r=0.66, B=0.48, diastolic BP; r=0.71, B=0.52, P<0.001). In 7 studies that also included 24-hour BP monitoring, the reduction of HBP was greater than that of 24-hour BP in systolic (HBP; -12.6+/-0.06 mm Hg, 24-hour BP; -11.9+/-0.04 mm Hg, P<0.001). In 5 studies that included daytime and nighttime systolic BP separately, HBP decreased 15% more than daytime ambulatory BP and 30% more than nighttime ambulatory BP. In conclusion, HBP falls approximately 20% less than CBP with antihypertensive treatments. Daytime systolic BP falls 15% less and nighttime systolic BP falls 30% less than home systolic BP.     

Morning blood pressure predicts hypertensive organ damage in patients with renal diseases: effect of intensive antihypertensive therapy in patients with diabetic nephropathy

Blood pressure (BP) measured at home early in the morning (HBP) has been recognized as a useful predictor for organ damage and has been viewed as an important therapeutic target in patients with hypertension. The present study was aimed to determine whether this notion holds true in patients with progressive renal disease.The study enrolled patients with mild to moderate renal impairment. They were all directed to record self-measured HBP to evaluate the adequacy of BP control. In addition to the conventional antihypertensive therapy, intensive treatment to more efficiently reduce elevated morning HBP was applied, especially in patients with diabetic nephropathy. The results were as follows: 1) The status of BP control assessed using HBP and office/clinic BP (OBP) shows predominance of morning hypertension. The prevalence of patients with well-controlled systolic HBP was 38%, those with poorly-controlled HBP 30%, masked hypertension 20% and white coat hypertension 12%. 2) Early morning systolic HBP in diabetics was significantly higher than that in non-diabetics. However, when evaluated on systolic OBP, both groups were comparable.3)Logistic regression analysis showed that the predictive variables to explain morning hypertension (more than 130 mmHg and increased systolic HBP) were age, amount of daily urinary protein excretion and left ventricular mass index (LVMI).4)Following conventional therapy, intensive antihypertensive therapy consisting of calcium channel blockers (CCB) and/or diuretics given in the morning, and angiotensin receptor blockers (ARB) given in the evening, together with alpha1-blockers given at bedtime, efficaciously reduced elevated HBP in the morning. This result was associated with significant reduction in daily urinary protein excretion and in serum plasminogen-activator inhibitor (PAI-1) concentration.The present study indicates that, regardless of ongoing conventional antihypertensive therapy, the majority of patients with renal disease had morning hypertension, suggesting that these patients are at a higher risk for cardiovascular disease. For the purpose of improving morning hypertension, intensive treatments with combined CCB, ARB and alpha1-blockers could have substantial benefit on the morbidity and prognosis in patients with diabetic nephropathy.     

Effect of doxazosin GITS on 24-hour blood pressure profile in patients with stage 1 to stage 2 primary hypertension

OBJECTIVE: To investigate the effect of the doxazosin gastrointestinal therapeutic system (GITS) on the 24 h blood pressure (BP) profile by ambulatory blood pressure measurements (ABPM) in patients with stage 1 to stage 2 primary hypertension. METHODS AND RESULTS: Seventeen hypertensive patients-either untreated or after a two-week run-in/washout period-underwent office and ABPM monitoring before and six weeks after an open-label once-daily morning dose of 4 mg of doxazosin GITS, an alpha(1)-adrenoceptor antagonist. Fourteen patients responded; three did not. Data analyses refers to the responders: linear analysis demonstrated statistically significant reductions from baseline in daytime, night-time, and total 24 h means for systolic BP (SBP) (7-10 mmHg) and diastolic BP (DBP) (5-10 mmHg) after treatment, with no statistically significant change in heart rate (HR). Rhythm analysis demonstrated statistically significant reductions from baseline in mean mesor (8 mmHg), maximum (6 mmHg) and minimum (10 mmHg) values in SBP, and in mean mesor (5 mmHg), maximum (7 mmHg) and minimum (5 mmHg) values in DBP. Circadian rhythm parameters in BP and HR were not significantly altered by treatment. Treatment with doxazosin GITS was well tolerated. CONCLUSIONS: A single morning dose of doxazosin GITS at 4 mg significantly reduced ambulatory SBP and DBP throughout a 24 h period while preserving a normal 24 h BP and HR rhythm profile in stage 1 to stage 2 hypertensives.     

Out-of-office blood pressure in children and adolescents: disparate findings by using home or ambulatory monitoring

BACKGROUND: The validity of home blood pressure (HBP) measurements in children has not been evaluated, although in clinical practice such measurements are being used. This study compares HBP, with clinic (CBP) and daytime ambulatory blood pressure (ABP) in children and adolescents. METHODS: Fifty-five children and adolescents aged 6 to 18 years were evaluated with CBP (three visits), HBP (6 days), and daytime ABP. Mean age was 12.3 +/- 2.9 (SD) years, 33 boys. According to the Task Force CBP criteria, 26 were hypertensives, 6 had high-normal BP (hypertensive group), and 23 were normotensives (normotensive group). RESULTS: In the hypertensive group, CBP was 130.8 +/- 7.6/72.5 +/- 8.1 mm Hg (systolic/diastolic), HBP 118.9 +/- 6.3/73.7 +/- 6.7, and ABP 130.8 +/- 8.1/75.5 +/- 8.3. In the normotensive group, CBP was 112.8 +/- 8/63.1 +/- 6.3, HBP 106.7 +/- 8.4/67.2 +/- 5.2, and ABP 123.9 +/- 7.2/72 +/- 4.3. Strong correlations (P < .001) were observed between CBP-HBP (r = 0.73/0.57, systolic/diastolic), CBP-ABP (r = 0.59/0.49), and HBP-ABP (r = 0.72/0.66). In normotensive subjects, ABP was higher than both CBP and HBP for systolic and diastolic BP (P < .001). Furthermore, systolic HBP was lower than CBP (P < .01), whereas the opposite was true for diastolic BP (P < .05). In hypertensive subjects systolic HBP was lower than both CBP and ABP (P < .001), whereas CBP did not differ from ABP. For diastolic BP no differences were found among measurement methods. CONCLUSIONS: These data suggest that, in contrast to adults in whom HBP is close to the levels of daytime ABP, in children and adolescents HBP appears to be significantly lower than daytime ABP. Until more data become available, caution is needed in the interpretation of HBP in children and adolescents.     

Effects of doxazosin on blood pressure, renin-angiotensin-aldosterone and urinary kallikrein.

Doxazosin, a new quinazoline-derivative postsynaptic alpha 1-adrenoceptor antagonist, was studied in this randomized, double-blind, placebo-controlled 12-week study. Its effects on blood pressure (BP), heart rate, metabolic functions and renal hormones were analyzed after administration of a single oral morning dose in a 3-phase fashion when administered to 17 patients (11 women, 6 men, 21 to 59 years) with mild to moderate uncomplicated essential hypertension. After titrating the antihypertensive effective dose biweekly from 1 to 8 mg/day and a mean end titration-point dose of 4.14 +/- 0.1 mg (mean +/- standard error of the mean) at week 8 of treatment, it was adjusted to maintain diastolic BP at levels less than or equal to 90 mm Hg for up to 12 weeks of treatment when, at a final mean dose of 4.35 +/- 0.2 mg/day, BP decreased in all patients by a mean 31 +/- 3/17 +/- 2 (supine) and 39 +/- 3/15 +/- 3 (standing) mm Hg (p less than 0.005) with no increase in heart rate and no "first-dose phenomenon." Neither the renin-aldosterone system nor electrolyte excretion was significantly affected. Renal function and metabolic parameters also remained unchanged. Urinary kallikrein excretion was augmented 2.47-fold (p less than 0.002). There was good tolerance; 1 patient discontinued the study because of dry nose. These results suggest that long-term monotherapy with doxazosin is an effective and safe antihypertensive agent for mild to moderate essential hypertension that stimulates urinary kallikrein excretion.     

A study of the white-coat phenomenon in patients with primary hypertension.

The objective of this study was to evaluate whether the discrepancy between clinic and home blood pressure (BP) in hypertensive subjects would disappear or diminish in magnitude if the BP measurement was taken under controlled conditions differing only with respect to location (clinic vs. home). Three hundred and sixty-seven patients aged 34-84 years with primary hypertension were enrolled. All of the patients or their spouses were taught to measure BP correctly with their own sphygmomanometer at home. The home BP value (HBP) was calculated as the average of 45 readings over 15 days. On days 6, 12, and 18 of the measurement period, rather than measuring their BP at home, patients and their spouses were asked to visit the hospital at the usual time of their BP measurement and to bring their own sphygmomanometer. The clinic BP value (CBP) was calculated as the average of the 9 readings taken on these visits by the patients or their spouses. The "white-coat phenomenon" (WCP) was considered to be present when the difference between the CBP and HBP was greater than 20/10 mmHg. The mean reading of home systolic/diastolic BP was 134.7/79.1 mmHg and the mean reading of clinic systolic/diastolic BP was 149.8/86.4 mmHg. In the total subject group, the prevalence rate of WCP was 31%-35% if the WCP was defined as DeltaBP (CBP - HBP) > or =20 mmHg/10 mmHg. In conclusion, ruling out the influence of different factors, including time of day, the sphygmomanometer, the individual taking the BP measurement, the climate, and the patients' health or mood, the WCP was still found to exist to a statistically significant degree. This study indicated that teaching patients to measure their own BP at home is an effective procedure to obtain a more accurate result of their BP level. It also helped to involve the patients more actively in controlling their hypertension.     

Effect of low-dose perindopril/indapamide on albuminuria in diabetes: preterax in albuminuria regression: PREMIER

Microalbuminuria in diabetes is a risk factor for early death and an indicator for aggressive blood pressure (BP) lowering. We compared a combination of 2 mg perindopril/0.625 mg indapamide with enalapril monotherapy on albumin excretion rate (AER) in patients with type 2 diabetes, albuminuria, and hypertension in a 12-month, randomized, double-blind, parallel-group international multicenter study. Four hundred eighty-one patients with type 2 diabetes and hypertension (systolic BP > or =140 mm Hg, <180 mm Hg, diastolic BP <110 mm Hg) were randomly assigned (age 59+/-9 years, 77% previously treated for hypertension). Results from 457 patients (intention-to-treat analysis) were available. After a 4-week placebo period, patients with albuminuria >20 and <500 microg/min were randomly assigned to a combination of 2 mg perindopril/0.625 mg indapamide or to 10 mg daily enalapril. After week 12, doses were adjusted on the basis of BP to a maximum of 8 mg perindopril/2.5 mg indapamide or 40 mg enalapril. The main outcome measures were overnight AER and supine BP. Both treatments reduced BP. Perindopril/indapamide treatment resulted in a statistically significant higher fall in both BP (-3.0 [95% CI -5.6, -0.4], P=0.012; systolic BP -1.5 [95% CI -3.0, -0.1] diastolic BP P=0.019) and AER -42% (95% CI -50%, -33%) versus -27% (95% CI -37%, -16%) with enalapril. The greater AER reduction remained significant after adjustment for mean BP. Adverse events were similar in the 2 groups. Thus, first-line treatment with low-dose combination perindopril/indapamide induces a greater decrease in albuminuria than enalapril, partially independent of BP reduction. A BP-independent effect of the combination may increase renal protection.     

Treatment of non-dipper hypertension with bedtime administration of valsartan

BACKGROUND: Previous results have indicated that valsartan administration at bedtime, as opposed to upon wakening, may improve the diurnal: nocturnal ratio of blood pressure without loss in 24-h coverage and efficacy. OBJECTIVES: To investigate the administration time-dependent antihypertensive efficacy of valsartan in non-dipper patients. METHODS: We studied 148 non-dipper patients with grade 1-2 essential hypertension, aged 53.0+/-12.6 years, who were randomly assigned to receive valsartan (160 mg/day) as a monotherapy either on awakening or at bedtime. Blood pressure was measured every 20 min during the day and every 30 min at night for 48 consecutive hours before and after 3 months of treatment. Physical activity was simultaneously monitored every minute by wrist actigraphy to accurately calculate the diurnal and nocturnal means of blood pressure on a per subject basis. RESULTS: The significant blood pressure reduction after 3 months of valsartan (P<0.001) was similar for both treatment times (13.1 and 8.5 mmHg reduction in the 24-h mean of systolic and diastolic blood pressure with morning administration; 14.7 and 10.3 mmHg with bedtime administration; P>0.126 for treatment-time effect). The diurnal: nocturnal ratio of blood pressure was significantly increased only when valsartan was administered before bedtime, which resulted in 75% of the patients in this group reverting to dippers, a significant increase in the percentage of patients with controlled blood pressure over 24 h, and a reduction in urinary albumin excretion. CONCLUSIONS: In non-dipper hypertensive patients, dosing time with valsartan should be chosen at bedtime, for improved efficacy during the nocturnal resting hours, as well as the potential associated reduction in cardiovascular risk.     

Tolerability and antihypertensive efficacy of Fosinopril on 24-hr ambulatory blood pressure in hypertensive elderly subjects

The tolerability and antihypertensive efficacy of Fosinopril were assessed in 34 elderly patients with mild to moderate hypertension. Twenty-four-hour ambulatory blood pressure (BP) was measured before and after 5 months of therapy. The patients' mean age was 67 years. At the end of the treatment the mean 24-hour systolic BP (SBP) fell from 153.4 +/- 14 to 137.7 +/- 13 mmHg and the mean 24-hour diastolic BP from 91 +/- 11 to 84.2 +/- 9 mmHg (p < 0.01). The mean decrease in SBP was 15.9 mmHg during the day and 10.3 during the night, and in diastolic BP (DBP) 8.3 mmHg during the day and 10.3 mmHg during the night (p < 0.05 between day and night). There was no significant percentage difference between the SBP and DBP decreases. The mean morning maximum of SBP decreased from 171 +/- 18 to 158 +/- 19 mmHg and there was a reduction in pressure increase between the night and day. The number of SBP peaks over 180 mmHg and 160 mmHg numerically decreased to 20.1% and 37.6% versus baseline, those of DBP over 105 mmHg and 95 mmHg to 41.6% and 58.3% versus baseline, respectively. There were no variations in the blood chemistry parameters and the drug had no adverse side effects. The authors conclude that Fosinopril is useful and well tolerated in the treatment of moderate hypertension in the elderly.     

Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension

Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.     

Effect of antihypertensive combinations on arterial pressure,albuminuria, and glycemic control in patients with type II diabetic nephropathy: a randomized study

Type II diabetic patients with albuminuria are at high risk for cardiovascular complications; the intense antihypertensive treatment required often involves using drug combinations. The aim of the present study was to compare the effect of two different, renin-angiotensin blocking combinations, on blood pressure (BP), albuminuria and glycemic control. Its design was prospective, randomised, controlled, of parallel branches, and performed in one Endocrinology Department, in Spain. 77 type-II diabetic patients, with stable albuminuria (30-1,000 mg/day) were included. After a pre-inclusion time of 2 weeks, patients were randomised to verapamil SR/trandolapril 180/2 (VT) or losartan/hydrochlorothiazide (LH) 20/12.5 mg/day. Duration of treatment was 1 year. The evaluated parameters were changes in blood pressure, urinary albumin excretion for 24 hours, glycated hemoglobin and plasmatic urea. Overall BP significantly decreased from 161.6 +/- 18.7/83.6 +/- 10.2 mmHg to 137.2 +/- 15.7/70.9 +/- 8.3 mmHg (p < 0.0005). Values, by treatment, were: For VT, 164.3 +/- 18.5/87.2 +/- 10.7 mmHg at baseline and 135.0 +/- 15.1/71.3 +/- 8.4 mmHg at conclusion. For LH, 158.8 +/- 17.4/80.1 +/- 8.4 mmHg at baseline and 139.3 +/- 16.1/70.5 +/- 8.2 mmHg at conclusion. Albuminuria significantly decreased from 308.2 +/- 544.7 mg/day to 198.0 +/- 285.3 mg/day. Both parameters showed no significant difference between treatments. Glycated hemoglobin decreased from 7.59 +/- 1.3% to 7.14 +/- 1.2% in the VT group, and from 7.96 +/- 1.29% to 7.84 +/- 1.62% in the LH group (ANOVA, p = 0.022). Changes adjusted from baseline values showed a trend to the difference between both treatments (p = 0.092). Plasmatic urea increased from 39.8 +/- 12.7 to 40.5 +/- 11.1 mg/dL in the TV group and from 43.4 +/- 12.0 mg/dL to 52.4 +/- 19.4 mg/dL in the LH group (ANOVA, p = 0.028). In conclusion, both treatments reduce blood pressure and albuminuria in a similar way in type II diabetic patients. The verapamil/trandolapril combination contributes to a better carbohydrate metabolism than losartan/hydroclorothiazide.     

Usefulness of the alpha1-blocker doxazosin as a third-line antihypertensive drug.

It has been reported that a substantial majority of hypertensives receive insufficient blood pressure (BP) control. As combination therapy for the treatment of hypertension, Ca channel blockers (CCBs), angiotensin II (AII) receptor blockers (ARBs), and/or AII-converting enzyme (ACE) inhibitors are mainly prescribed, while the efficacy of alpha(1)-blockers in such combination therapy remains unknown. The aim of this study was to investigate the efficacy of a low dose of an alpha(1)-blocker added to combination therapy with CCBs and either ARBs or ACE inhibitors for the treatment of hypertension. Subjects were 41 hypertensive patients (23 women and 18 men, mean age 66+/-12 years) who had been followed at the National Kyushu Medical Center. All patients showed poor BP control despite haven taken a combination of CCBs and ARBs or ACE inhibitors for more than 3 months. Doxazosin at a dose of 1 to 2 mg was added to each treatment regimen. The changes in various clinical parameters, including BP and blood chemistry, following the addition of doxazosin were then evaluated. The mean follow-up period was 170 days. BP decreased from 152+/-14/81+/-12 mmHg to 135+/-14/70+/-11 mmHg after the addition of doxazosin at a mean dose of 1.5 mg/day (p<0.001). When good systolic blood pressure (SBP) control was defined as <140 mmHg, the prevalence of patients with good SBP control increased from 24% to 61% (p<0.01). Similarly, the prevalence of patients with good diastolic blood pressure (DBP) control (<90 mmHg) increased from 78% to 98% (p<0.01). Patients whose SBP decreased more than 10 mmHg (n=25) showed significantly higher baseline SBP, serum total cholesterol and low-density lipoprotein (LDL) cholesterol levels compared to those who showed less SBP reduction (<10 mmHg) (n=16, p<0.01). Comparable BP reductions were obtained between obese (body mass index [BMI] > or =25, DeltaBP at 3 months: -15+/-15/-12+/-9 mmHg, n=18) and non-obese (BMI<25, DeltaBP: -14+/-19/-7+/-8 mmHg, n=23) patients. The results suggest that addition of a low dose of the alpha(1)-blocker doxazosin effectively reduces BP in patients taking CCBs and ARBs or ACE inhibitors. Thus, doxazosin seems to be useful as a third-line antihypertensive drug.     

Diurnal blood pressure pattern may predict the increase of urinary albumin excretion in normotensive normoalbuminuric type 1 diabetes mellitus patients

To characterise the relationship between diurnal blood pressure and the subsequent increase of urinary albumin excretion (UAE) in normotensive normoalbuminuric type 1 diabetic patients, ambulatory blood pressure monitoring (ABPM) was performed in 53 patients, who were then followed for 5 years. Albumin excretion rate changed from 12.4 (8.9-17.2) to 29.3 (15.2-47.0) mg/day. Macroalbuminuria developed in 2 (3.8%), microalbuminuria in 22 (41.5%) patients, 29 (54.7%) remained normoalbuminuric. Night-time diastolic blood pressure was significantly higher (64.3+/-6.5 vs. 60.9+/-5.5 mmHg, P<0.05), diastolic diurnal index significantly lower (15.5+/-9.7 vs. 22.3+/-6.2%, P<0.01) in patients who later progressed to micro- or macroalbuminuria. Diastolic diurnal index (r=-0.40; P<0.01) and nocturnal diastolic pressure (r=0.35; P<0.01) were correlated to the change in albumin excretion. In a multivariate analysis model with the change of albumin excretion as dependent, and means and diurnal indices of systolic and diastolic blood pressure, baseline UAE, cholesterol, triglycerides, HbA1c and retinopathy as independent parameters (r=0.68; P=0.001), diurnal index for diastolic blood pressure (beta=-0.30; r=0.013), baseline HbA1c (beta=0.32; P=0.010) and retinopathy (beta=0.44; P=0.001) were significant independent correlates. We conclude that the relative increase of nocturnal blood pressure is associated with the subsequent increase of albuminuria, which in turn is predictive of overt diabetic nephropathy.     

Continuous 24-hour registration of intra-arterial pressure in basal states and during therapy with a fixed slow-release oxprenolol-chlorthalidone combination, administered once a day

Intra-arterial 24 hour blood pressure (BP) recording (OXFORD MEDILOG) was carried out in 10 patients with essential hypertension, 6 males and 4 females, aged between 41 and 58 years, 3 at WHO stage 1 and 7 at stage 2, in basal conditions and after 6 weeks of treatment with a fixed combination of 160 mg of slow-release oxprenolol and 20 mg of chlorthalidone per tablet (tb). The fixed combination was given once daily, in the morning, at the dosage of 1 tb, which was increased to 2 tbs o.d. after the first 2 weeks in 6 patients. Computer calculated mean BP and heart rate (HR) values from each consecutive hour of the day were obtained in all patients. Hourly trend of BP and HR were plotted and circadian variations were thus determined. Treatment with fixed combination o.d. significantly reduced systolic and diastolic BP, compared to pretreatment values, throughout of the 24 hours (p less than 0.01; p less than 0.001), without altering the circadian rhythm. Before and after 6 weeks of treatment, a bicycle exercise test was performed in 8 patients, who reached 85% of the maximal predicted HR. Pretreatment resting mean BP (+/- SD) was 190 +/- 31/108 +/- 10 mmHg (HR: 68 +/- 9 b/min) and those during the last minute of exercise 242 +/- 29/125 +/- 5 mmHg (HR: 147 +/- 13 b/min); posttreatment resting BP was 161 +/- 20/88 +/- 7 mmHg (HR: 58 +/- 7 b/min) and at peak exercise, 212 +/- 16/106 +/- 7 mmHg (p less than 0.025 for the systolic pressure; p less than 0.001 for the diastolic pressure).(ABSTRACT TRUNCATED AT 250 WORDS)     

Masked Hypertension Assessed by Ambulatory Blood Pressure Versus Home Blood Pressure Monitoring: Is It the Same Phenomenon?

BACKGROUND: Masked hypertension is defined as normal clinic blood pressure (CBP) and elevated out-of-clinic blood pressure assessed using either self-monitoring of blood pressure (BP) by the patients at home (HBP) or ambulatory BP (ABP) monitoring. This study investigated the level of agreement between ABP and HBP in the diagnosis of masked hypertension. METHODS: Participants referred to an outpatient hypertension clinic had measurements of CBP (two visits), HBP (4 days), and ABP (24 h). The diagnosis of masked hypertension based on HBP (CBP <140/90 mm Hg and HBP > or =135/85) versus ABP (CBP <140/90 and awake ABP > or =135/85) was compared. RESULTS: A total of 438 subjects were included (mean age +/- SD, 51.5 +/- 11.6 years; 59% men and 41% women, 34% treated and 66% untreated). Similar proportions of subjects with masked hypertension were diagnosed by ABP (14.2%) and HBP (11.9%). In both treated and untreated subjects, the masked hypertension phenomenon was as common as the white coat phenomenon. Among 132 subjects with normal CBP, there was disagreement in the diagnosis of masked hypertension between the HBP and the ABP method in 23% of subjects for systolic and 30% for diastolic BP (kappa 0.56). When a 5-mm Hg gray zone for uncertain diagnosis was applied to the diagnostic threshold, the disagreement was reduced to 9% and 6% respectively. CONCLUSIONS: Similar proportions of subjects with masked hypertension are detected by ABP and HBP monitoring. Although disagreement in the diagnosis between the two methods is not uncommon, in the majority of these cases the deviation of the diagnostic BP above the threshold in not clinically important. Both ABP and HBP monitoring appear to be appropriate methods for the detection of masked hypertension.     

Bedtime administration of cilnidipine controls morning hypertension

Morning blood pressure (BP) level plays an important role in the incidence of cardiovascular disease. Recently, Kario, et al proposed the usefulness of ME difference (morning minus evening systolic BP) and ME average (average of morning and evening systolic BP) for the evaluation of antihypertensive treatment. Cilnidipine is a novel calcium channel blocker (CCB) that exerts inhibitory actions not only on L-type but also on N-type calcium channels. We investigated the effect of bedtime administration of cilnidipine (10 mg) in addition to the antihypertensive treatment for uncontrolled morning hypertension. Twenty-three hypertensive outpatients (13 males and 10 females; mean age, 66.9 years) with stable antihypertensive medication and uncontrolled morning BP were studied using self-measured BP monitoring in the morning and evening. Morning SBP (P < 0.001) and DBP (P < 0.001) decreased significantly from 150.2 +/- 8.7 and 87.8 +/- 9.3 to 132.7 +/- 7.4 and 77.5 +/- 8.5 mmHg, respectively, after the addition of cilnidipine. Morning heart rate did not change (63.3 +/- 7.0 to 64.1 +/- 9.4). The evening SBP, but not DBP, decreased significantly after treatment. Both the ME average (P < 0.001) and ME difference (P < 0.01) significantly decreased from 143.0 +/- 9.2 and 14.3 +/- 12.4 to 131.3 +/- 7.2 and 2.8 +/- 9.2 mmHg after treatment, respectively. The microalbuminuria decreased from 39.6 +/- 13.2 to 27.3 +/- 8.4 mg/g Cr. In conclusion, L-/N-type CCB cilnidipine may be useful for patients with uncontrollable morning hypertension by reducing both ME average and ME difference.     

Patients with uncontrolled hypertension or concomitant hypertension and benign prostatic hyperplasia

At optimal doses, individual antihypertensive agents lower blood pressure (BP) by an average of 10 mmHg. Many patients with hypertension, including those with stage 3 hypertension, target organ damage, or those at high risk for cardiovascular events and/or adverse effects of high-dose monotherapy, are likely to require combination antihypertensive drug treatment to achieve the recommended systolic/diastolic BP (< 140/90 mmHg). Two studies, a placebo-controlled, double-blind trial (n = 70) and a community-based, open-label trial (n = 491) investigated the antihypertensive efficacy of doxazosin, a long-acting selective alpha1-adrenoceptor blocker, as add-on therapy for uncontrolled hypertension with other antihypertensive medications and in patients with concomitant benign prostatic hyperplasia (BPH) and treated but inadequately controlled hypertension, respectively. The addition of doxazosin to baseline antihypertensive medication(s) significantly lowered BP and had a significantly positive effect on the serum lipid profile. In patients with concomitant BPH, doxazosin significantly improved all BPH symptom scores, regardless of initial symptom severity. Add-on doxazosin sufficiently reduced systolic/diastolic BP such that many patients whose hypertension was previously uncontrolled by other antihypertensive medications were able to reach goal BP (< 140/90 mmHg). Doxazosin as add-on therapy was well tolerated. In conclusion, doxazosin as add-on therapy improves BP control in hypertensive patients not at goal BP and improves lower urinary tract symptoms in patients with concomitant BPH.