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 alpha-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.     

Refractory hypertension and sleep apnoea: effect of CPAP on blood pressure and baroreflex.

This study was undertaken to determine whether abolition of obstructive sleep apnoea (OSA) by continuous positive airway pressure (CPAP) could reduce blood pressure (BP) in patients with refractory hypertension. In 11 refractory hypertensive patients with OSA, the acute effects of CPAP on nocturnal BP were studied during sleep and its longer term effects on 24-h ambulatory BP after 2 months. During a single night's application, CPAP abolished OSA and reduced systolic BP in stage 2 sleep from 138.3 +/- 6.8 to 126.0 +/- 6.3 mmHg. There was also a trend towards a reduction in average diastolic BP (from 77.7 +/- 4.5 to 72.9 +/- 4.5). CPAP usage for 2 months was accompanied by an 11.0 +/- 4.4 mmHg reduction in 24-h systolic BP. In addition, both the nocturnal and daytime components of systolic BP fell significantly by 14.4 +/- 4.4 and 9.3 +/- 3.9 mmHg, respectively. Diastolic BP was reduced significantly at night by 7.8 +/- 3.0 mmHg. In patients with refractory hypertension, acute abolition of obstructive sleep apnoea by continuous positive airway pressure reduces nocturnal blood pressure. These data also suggest that continuous positive airway pressure may reduce nocturnal and daytime systolic blood pressure chronically. Randomised trials are needed to confirm the latter results.     

Treatment of orthostatic hypotension with sleeping in the head-up tilt position, alone and in combination with fludrocortisone.

We studied the effect of sleeping in the head-up tilt (HUT) position, alone and in combination with fludrocortisone, on orthostatic tolerance and blood pressure (BP) in six patients with hypoadrenergic orthostatic hypotension. A high salt diet of 150-200 mmol Na+ d-1 was also administered. Combined treatment reduced orthostatic dizziness in all patients (P less than 0.001), and increased the maximal standing period to at least 10 min. HUT alone (n = 4) reduced the BP decrease after 1 min of standing from -64/-42/-25 +/- 29/21/17 mmHg to -53/-37/-23 +/- 31/24/20 mmHg (P less than 0.01 for systolic BP). Addition of fludrocortisone to HUT (HUT/fludro) (n = 5) further reduced the BP decrease after 1 min of standing from -63/-40/-24 +/- 20/12/11 mmHg to -21/-19/-8 +/- 12/10/5 mmHg (P less than 0.05 for systolic, mean and diastolic BP, respectively). BP at maximal standing time increased from 58/47/42 +/- 9/8/7 mmHg initially to 95/69/57 +/- 27/22/20 mmHg during combined treatment (P less than 0.05 for systolic and mean BP), and remained unchanged during the 14-month (range 8-70 month) follow-up period. Nocturnal sodium excretion decreased from 8.0 +/- 2.3 mmol h-1 to 5.9 +/- 1.9 mmol h-1 with combined treatment; body weight increased by 1.6 kg on average (range 0.5-2.4 kg) (P less than 0.01). We conclude that the combination of HUT and fludrocortisone effectively minimizes orthostatic symptoms and increases orthostatic BP in patients with hypo-adrenergic orthostatic hypotension.     

Ambulatory blood pressure is still elevated in treated hypertensive diabetic subjects compared with untreated diabetic subjects with the same office blood pressure.

Ambulatory blood pressure, ABP, was determined every 15 min for 24 h (Spacelabs 5200 system) in 16 hypertensive diabetic subjects treated for high blood pressure. Office blood pressure (OBP) in these subjects (systolic BP greater than 160 mmHg and diastolic BP greater than 95 mmHg before treatment) had been reduced by treatment to the borderline range (systolic less than or equal to 160 mmHg and/or diastolic less than or equal to 95 mmHg). Sixty-five diabetic subjects with normal or borderline OBP were included as controls. The two groups had the same age (58 +/- 10 yrs in both groups), duration of diabetes (15 +/- 9 yrs), 24 hr microalbumin, and included the same percentage of subjects with moderate neuropathy (36% and 29%, NS). The two groups had the same OBP (138 +/- 16 mmHg and 140 +/- 16 mmHg systolic, NS, 84 +/- 9 mmHg and 84 +/- 13 mmHg diastolic, NS). In contrast, ambulatory BP was significantly higher in the treated group, when compared with the controls (123 +/- 13 mmHg and 133 +/- 23 mmHg systolic, P less than 0.025, 77 +/- 7 mmHg and 84 +/- 16 mmHg diastolic, P less than 0.015). The difference was significant both in daytime and in nighttime, and was more significant in nighttime (11 mmHg systolic, P less than 0.02, 9 mmHg diastolic, P less than 0.004) than in daytime (9 mmHg systolic, P less than 0.05 and 5 mmHg diastolic, P less than 0.05). Ambulatory heart rate was also significantly higher in the treated group, but only in daytime (7 b/min difference, P less than 0.02). The study demonstrated the need to survey and investigate ABP in treated hypertensive diabetic subjects.     

Reproducibility of nocturnal blood pressure assessed by self-measurement of blood pressure at home.

To assess the reproducibility of nocturnal blood pressure (BP) during sleep as measured using a self-measurement device at home, we obtained repeated nocturnal home BP at 0200 h and quality of sleep assessment from a diary in 556 subjects (71% women, 62.4+/-11.1 years) in the general population. We used an Omron device (HEM-747IC-N, Omron Healthcare Co., Ltd., Kyoto, Japan), with which the time and frequency of monitoring can be preset and the readings stored. The mean+/-SD of the difference between test-retest BP measurements was 0.7+/-15.1 mmHg systolic and 0.2+/-9.7 mmHg diastolic with a mean interval of 5.9 days. The absolute differences were greater than 10 mmHg in 261 (46.9%) subjects for systolic and 145 (26.0%) subjects for diastolic. There was no evidence of regression to the mean in nocturnal measurements over at least three nights (n=390, p>0.22). The differences (the first minus the second measurement) were large in subjects who experienced sleep disturbance only in the first (n=64, 2.3+/-13.6 mmHg and 1.6+/-9.6 mmHg for systolic and diastolic, respectively) or second sessions (n=56, -4.1+/-16.4 mmHg and -2.5+/-11.4 mmHg) compared with the subjects without sleep disturbance (n=66, 1.5+/-17.8 mmHg and 0.8+/-10.3 mmHg) and those with sleep disturbance (n=370, 0.9+/-14.5 mmHg and 0.2+/-9.3 mmHg) in both sessions. In conclusion, the reproducibility of single nocturnal BP as assessed using a self-measurement device at home was not good, especially for subjects who experienced different quality of sleep in each session. To evaluate nocturnal BP using a self-measurement device, estimation of quality of sleep is indispensable.     

Ambulatory blood pressure reduction after rosiglitazone treatment in patients with type 2 diabetes and hypertension correlates with insulin sensitivity increase

BACKGROUND: Within the metabolic syndrome, insulin resistance and compensatory hyperinsulinemia are associated with blood pressure (BP) elevation through various potential mechanisms. Thiazolidinediones are antihyperglycemic agents that decrease insulin resistance. OBJECTIVE: To determine the effect of the thiazolidinedione rosiglitazone on BP and insulin resistance in patients with type 2 diabetes and hypertension. METHODS: In 20 subjects (nine men and 11 women) with type 2 diabetes but with a poor glycemic control, and with poorly controlled or newly diagnosed hypertension, rosiglitazone 4 mg daily was added-on therapy for 26 weeks. At baseline and at the end of the treatment period patients underwent ambulatory blood pressure monitoring, a hyperinsulinemic euglycemic clamp, and blood tests for glucose, insulin, HbA1c, lipids, and routine laboratory parameters. RESULTS: Insulin sensitivity estimated with the clamp significantly increased (Mbw/I index changed from 33.9 +/- 2.6 to 41.9 +/- 3.2 micromol/min per kg per nmol/l, P < 0.001) and the HOMA-IR index significantly decreased (6.34 +/- 0.39 versus 4.40 +/- 0.33, P < 0.001) during rosiglitazone treatment. Ambulatory BP presented small but significant reductions for the total 24-h period (135.3 +/- 1.8 versus 129.9 +/- 1.7 mmHg, P < 0.001 for systolic BP and 76.0 +/- 1.6 versus 71.9 +/- 1.6 mmHg, P < 0.001 for diastolic BP), daytime and night-time. The changes in systolic and diastolic BP correlated with the change in insulin sensitivity (r = -0.78, P < 0.01 and r = -0.68, P < 0.01, respectively). There were also significant reductions in fasting plasma glucose (9.39 +/- 0.41 versus 7.55 +/- 0.31 mmol/l, P < 0.001), insulin (94.0 +/- 0.41 versus 79.5 +/- 5.6 pmol/l, P < 0.01) and HbA1c (8.15 +/- 0.24 versus 7.24 +/- 0.19%, P < 0.001). CONCLUSIONS: Treatment of type 2 diabetic hypertensive patients with rosiglitazone significantly increased insulin sensitivity and lowered ambulatory BP. These changes were strongly correlated. Thiazolidinediones may thus possess a BP-lowering effect beyond their antihyperglycemic properties.     

The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial

BACKGROUND: There is growing evidence that oxidative stress contributes to the pathogenesis of hypertension and endothelial dysfunction. Thus, dietary antioxidants may beneficially influence blood pressure (BP) and endothelial function by reducing oxidative stress. OBJECTIVE: To determine if vitamin C and polyphenols, alone or in combination, can lower BP, improve endothelial function and reduce oxidative stress in hypertensive individuals. DESIGN: A total of 69 treated hypertensive individuals with a mean 24-h ambulatory systolic blood pressure > or = 125 mmHg participated in a randomized, double-blind, placebo-controlled, factorial trial. Following a 3-week washout, participants received 500 mg/day vitamin C, 1000 mg/day grape-seed polyphenols, both vitamin C and polyphenols, or neither for 6 weeks. At baseline and post-intervention, 24-h ambulatory BP, ultrasound-assessed endothelium-dependent and -independent vasodilation of the brachial artery, and markers of oxidative damage, (plasma and urinary F2-isoprostanes, oxidized low-density lipoproteins and plasma tocopherols), were measured. RESULTS: A significant interaction between grape-seed and vitamin C treatments for effects on BP was observed. Vitamin C alone reduced systolic BP versus placebo (-1.8 +/- 0.8 mmHg, P = 0.03), while polyphenols did not (-1.3 +/- 0.8 mmHg, P = 0.12). However, treatment with the combination of vitamin C and polyphenols increased systolic BP (4.8 +/- 0.9 mmHg versus placebo; 6.6 +/- 0.8 mmHg versus vitamin C; 6.1 +/- 0.9 mmHg versus polyphenols mmHg, each P < 0.0001) and diastolic BP (2.7 +/- 0.6 mmHg, P < 0.0001 versus placebo; 1.5 +/- 0.6 mmHg, P = 0.016 versus vitamin C; 3.2 +/- 0.7 mmHg, P < 0.0001 versus polyphenols). Endothelium-dependent and -independent vasodilation, and markers of oxidative damage were not significantly altered. CONCLUSION: Although the mechanism remains to be elucidated, these results suggest caution for hypertensive subjects taking supplements containing combinations of vitamin C and polyphenols.     

Safety and efficacy of the oral direct renin inhibitor aliskiren in elderly patients with hypertension

OBJECTIVES: To evaluate the efficacy, safety and tolerability of aliskiren in elderly patients (> or =65 years old) with essential hypertension. METHODS: In this double-blind, multicenter study, 355 elderly patients with hypertension [office mean sitting systolic blood pressure (msSBP) > or =145-<180 mmHg and mean 24-h ambulatory systolic BP (ASBP) > or =135 mmHg] were randomized to once-daily treatment for 8 weeks with aliskiren 75 mg (n = 91), 150 mg (n = 84), 300 mg (n = 94) or the comparator lisinopril 10 mg (n = 86). The primary efficacy variable was change in mean 24-h ASBP. RESULTS: At endpoint, aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg lowered mean 24-h ASBP (least-squares mean+/-SEM) by 8.4+/-0.8, 7.1+/-0.8, 8.7+/-0.8 and 10.2+/-0.9 mmHg, and mean 24-h ambulatory diastolic BP by 4.5+/-0.5, 3.6+/-0.5, 3.9+/-0.5 and 6.3+/-0.5 mmHg, respectively, with no significant difference between aliskiren doses. The trough-to-peak ratio for ASBP reduction with aliskiren 75 mg, 150 mg, 300 mg and lisinopril 10 mg was 0.77, 0.64, 0.79 and 0.87, respectively. All treatments lowered office msSBP and mean sitting diastolic BP (msDBP) compared with baseline. A significantly greater proportion of patients receiving aliskiren 300 mg achieved BP control (msSBP/msDBP <140/90 mmHg) compared with those receiving aliskiren 75 mg (36.2% vs 24.2%, p = 0.033). There was no evidence of dose-related increases in the rate of adverse events with aliskiren treatment. CONCLUSIONS: Aliskiren, a novel direct renin inhibitor, provides effective 24-h BP lowering with no evidence of dose-related increases in the incidence of adverse events in elderly patients with hypertension.     

Influence of autonomic neuropathy upon left ventricular dysfunction in insulin-dependent diabetic patients

BACKGROUND: Diabetic cardiomyopathy is a well-defined complication of diabetes that occurs in the absence of ischemic, vascular, and hypertensive disease. HYPOTHESIS: The study was undertaken to test the relationship among autonomic neuropathy (AN), 24-h blood pressure (BP) profile, and left ventricular function. METHODS: Nineteen type-1 diabetic patients underwent autonomic tests and echocardiographic examination. Patients were divided according to the presence (AN+) or absence (AN-) of AN. RESULTS: In the AN+ group (n = 8), the E/A ratio at echo was lower than in the AN- group (n = 11) (1.1 +/- 0.3 vs. 1.6 +/- 0.3; p < 0.005). Systolic and diastolic BP reductions during sleep were smaller in the AN+ than in the AN- group (6.6 +/- 6.6 vs. 13.0 +/- 4.3%; p < 0.03 for systolic and 12.8 +/- 6.8 vs. 20.0 +/- 4.0% for diastolic BP reduction; p < 0.03, respectively). Considering all patients, the E/A ratio correlated inversely with awake diastolic BP (r - 0.63; p = 0.005); sleep systolic BP (r - 0.48; p = 0.04), and sleep diastolic BP (r - 0.67; p = 0.002). The AN correlated with diastolic interventricular septum thickness (r 0.57; p = 0.01), sleep systolic BP (r 0.45; p = 0.05), sleep diastolic BP (r 0.54; p = 0.02), and correlated inversely with systolic and diastolic sleep BP reduction (r - 0.49; p = 0.03 and r - 0.67; p = 0.002, respectively). Finally, E/A ratio and AN score correlated between themselves (r - 0.6; p = 0.005). CONCLUSION: Our results suggest that left ventricular diastolic dysfunction may be detected very early in type-1 diabetic patients with AN. Parasympathetic lesion and nocturnal elevations in BP could be the link between AN and diastolic ventricular dysfunction.     

Therapeutic doses of phenylpropanolamine increase supine systolic blood pressure

The anorectic agent phenylpropanolamine (PPA) has a low therapeutic index and can cause severe hypertension at doses as low as 85 mg. To determine the effects of a therapeutic dose on blood pressure, PPA 37.5 mg (as a commercially available immediate release formulation) or placebo was administered orally to ten normotensive subjects using a randomized double-blinded crossover design. The mean increase in supine systolic blood pressure (BP) was greater after PPA (18.5 +/- 10.7 mmHg) than after placebo (5.1 +/- 5.4 mmHg, P = 0.005). Increases in systolic BP after PPA ranged from 8 to 43 mmHg. The BP increase due to PPA was postural, and there was no change in sitting or standing BP. Doses of PPA available in over-the-counter formulations can increase supine systolic BP. Recent use of products containing PPA should be considered when evaluating patients with hypertension.     

Control of blood pressure and prevention of end-organ damage in patients with accelerated hypertension by combination with arotinolol and extended release nifedipine.

In patients with accelerated (malignant) hypertension, end-organ damage is the determinant factor for prognosis. Although recent advances in antihypertensive therapy have improved the outcome of patients with accelerated hypertension, the effectiveness of antihypertensive therapy still remains less convinced. In this study, we followed 13 patients clinically diagnosed with accelerated hypertension (defined as diastolic blood pressure > 130 mmHg, retinopathy with K-W IV and accelerated renal impairment) for 3 yr. One patient died due to acute myocardial infarction arising from poor compliance with antihypertensive therapy. One patient was maintained on hemodialysis for 3 yr. One patient was introduced for continuous ambulatory peritoneal dialysis (CAPD) for a year and then lived without dialysis therapy. The remaining 10 patients were followed for 3 yr. All patients were initially treated with intravenous administration of calcium antagonist for reduction of blood pressure, followed by hemodialysis therapy if needed. After stabilization of blood pressure, combination therapy with extended release nifedipine (40 to 80 mg daily) and arotinolol (20 mg daily) was started. The targets for blood pressure control were a systolic pressure of 135 mmHg and a diastolic pressure of 80 mmHg. If blood pressure control was unsatisfactory, guanabenz (2 to 4 mg before bedtime), a central acting drug, was added. At presentation, the mean diastolic blood pressure (mDBP) among the 10 remaining patients was 134 +/- 2 mmHg, the mean serum creatinine (mScr) was 4.5 +/- 0.7 mg/dl and the left ventricular mass index (LVMi) as measured by echocardiography was 150 +/- 9 g/m2. At 1 yr, the mDBP was reduced to 90 +/- 3 mmHg, the mScr to 2.9 +/- 0.9 mg/dl and the LVMi to 140 +/- 9 g/m2. At 3 yr, the mDBP was stabilized at 79 +/- 3 mmHg, the mScr maintained at 2.2 +/- 0.4 mg/dl, and the LVMi reduced to 128 +/- 9 g/m2. These results indicate that appropriate blood pressure control is important for improvement of renal impairment and cardiac damage in patients with accelerated hypertension. Moreover, combination therapy with arotinolol and extended release nifedipine may be beneficial for this purpose.     

Evaluation of the overall system precision of the Welch-Allyn transtelephonic home blood pressure monitor in adults with Parkinson's disease

BACKGROUND: Non-invasive blood pressure (BP) devices should be independently evaluated before being used in special populations. The objective of this study was to assess the accuracy of the Welch-Allyn transtelephonic home blood pressure monitor in adults with Parkinson's disease to evaluate the device for use in a large clinical trial involving the safety and efficacy of a monoamine oxidase inhibitor. METHODS: BP measurements taken with the device were compared with the results obtained by two experienced observers using a mercury sphygmomanometer in patients with Parkinson's disease. The limits of agreement were then calculated for the device and compared with the results of the two observers. RESULTS: The agreement parameters between the two observers were -0.5 +/- 2.6 mmHg for systolic BP and 0.1 +/- 2.2 mmHg for diastolic BP. The agreement between the Welch-Allyn transtelephonic device and the observers was -2.6 +/- 4.5 mmHg and -1.9 +/- 3.2 mmHg for systolic and diastolic BP respectively. Nearly 90% of the readings were within 10 mmHg of the observers for both systolic and diastolic BP. Mild tremor had a moderate effect on the validity of the device. CONCLUSIONS: The Welch-Allyn transtelephonic device demonstrated acceptable precision in this cohort of patients with Parkinson's disease and is considered valid for use in a clinical trial involving these patients.     

Nurse-recorded and ambulatory blood pressure predicts treatment-induced reduction of left ventricular hypertrophy equally well in hypertension: results from the Swedish irbesartan left ventricular hypertrophy investigation versus atenolol (SILVHIA) study

OBJECTIVE : To compare the relationships of treatment-induced reductions of left ventricular hypertrophy to the changes in clinic and ambulatory blood pressure (BP). DESIGN : Double-blind and randomized treatment with irbesartan or atenolol for 48 weeks. PATIENTS : Patients with hypertension and left ventricular hypertrophy (n = 66) with a seated diastolic BP 90-115 mmHg (average of three measurements one minute apart by nurses). MAIN OUTCOME MEASURES : Registrations of echocardiographic left ventricular (LV) mass. Clinic and ambulatory BP. RESULTS : In the total material, nurse-measured BP was reduced by 23 +/- 15/16 +/- 7.7 mmHg and 24-h ambulatory BP fell 20 +/- 15/14 +/- 8.5 mmHg by treatment. The correlation between the change in nurse-measured BP and LV mass index (LVMI) induced by treatment was r = 0.35, P = 0.004 for systolic BP and r = 0.26, P = 0.03 for diastolic BP. Corresponding values for 24-h ambulatory BP were r = 0.29, P = 0.02 and r = 0.35, P = 0.004, respectively, with similar correlations for day- and night-time ambulatory BP. The nurse-recorded BP was slightly higher than ambulatory BP (systolic clinic - systolic 24-h ambulatory BP = 5 mmHg). Using 130/80 mmHg as a cut-off value for normal 24-h ambulatory BP, eight subjects had normal diastolic or systolic ambulatory BP, or both. Interestingly, these patients also experienced LVMI regression following treatment (low/normal ABP, -13 +/- 21 g/m2; remaining patients, -18 +/- 22 g/m2, P > 0.5). CONCLUSIONS : In patients with hypertension and left ventricular hypertrophy, ambulatory BP is not superior to carefully standardized nurse-recorded seated BP in terms of associations with treatment-induced changes in LV mass.     

Pulse wave velocity as endpoint in large-scale intervention trial. The Complior study. Scientific, Quality Control, Coordination and Investigation Committees of the Complior Study

OBJECTIVE: To evaluate the ability of an antihypertensive therapy to improve arterial stiffness as assessed by aortic pulse wave velocity (PWV) in a large population of hypertensive patients. SETTING: Sixty-nine healthcare centres, private and institutional (19 countries). PATIENTS: Subjects aged 18-79 years, with essential hypertension. A total of 2,187 patients were enrolled; 1,703 (52% male) completed the study: mean age = 50 +/- 12 years; mean baseline systolic/diastolic blood pressure (S/D BP) = 158 +/- 15/98 +/- 7 mmHg; mean baseline carotid-femoral PWV = 11.6 +/- 2.4 m/s. INTERVENTIONS: Patients were treated for 6 months, starting with perindopril (angiotensin converting enzyme (ACE) inhibitor) 4 mg once daily (OD), increased to 8 mg OD, and combined to diuretic (indapamide 2.5 mg OD) if BP was uncontrolled (> 140/90 mmHg). RESULTS: It was feasible to measure carotid-femoral PWV using the automatic device Complior at inclusion, 2 and 6 months, along with conventional BP assessments in a population of 1,703 patients. Significant decreases (P < 0.001) in BP (systolic: -23.7 +/- 16.8, diastolic: -14.6 +/- 10 mmHg), and carotid-femoral PWV (-1.1 +/- 1.4 m/s) were obtained at 2 and 6 months. CONCLUSIONS: The Complior Study is the first study to show the feasibility of a large-scale intervention trial using PWV as the endpoint in hypertensive patients. Adequate results may be obtained using an automatic device and rigorous criteria for assessment. A long-term controlled intervention study is needed to confirm the results of the present uncontrolled trial.     

ST-segment depression in hypertensive patients is linked to elevations in blood pressure,pulse pressure and double product by 24-h Cardiotens monitoring

BACKGROUND: Various statements are made concerning peaks of heart rate (HR), blood pressure (BP) and double product (product of HR and systolic BP) as triggers for ST-segment depression. The aim of the present study was to identify determinants of ST-segment depression with a new ambulatory device for simultaneous 24-h electrocardiogram (ECG) and BP monitoring. METHODS: A total of 63 treated patients (63 +/- 9 years, 33 women and 30 men) with arterial hypertension and ischemic heart disease were studied with a new ambulatory 24-h BP measurement (ABPM) device evaluated according to the BHS protocol (Cardiotens, Meditech, Hungary). This device allows simultaneous ST-segment analysis with extra BP recordings triggered by episodes of ST-segment depression. RESULTS: ST-segment (Holter ECG) depression (> 1 mm and > 60 s) was demonstrated in 26 patients with a mean duration of 4.95 +/- 2.6 min and a peak in the early morning hours. All ST-segment depressions were silent and occurred during a significant increase of BP (15 +/- 11 mmHg systolic and 10 +/- 5 mmHg diastolic, compared with the mean ABPM values) and a significant increase of the double product from 10 921 +/- 2 395 (24-h mean) to 14 515 +/- 2329 (during ST-depression). The recorded systolic and diastolic BP (SBP, DBP) values from the pre ST-event were significant higher compared with 24-h values (153 +/- 19 versus 145 +/- 22 mmHg systolic, 83 +/- 12 versus 78 +/- 14 diastolic). The mean pulse pressure (PP) value in the group with ST-depression was significantly higher than in the group without ST changes (69 +/- 16 versus 58 +/- 10 mmHg; P < 0.005). A total of 73% of patients with ST-events compared with 35% without ST-events showed a PP >or= 60 mmHg (P = 0.025). CONCLUSION: Simultaneous ABPM and ST-segment analysis identifies episodes of silent myocardial ischemia during increases of BP and HR. Hypertensive patients with ischemic heart disease and ST events show higher mean pulse pressure values than are observed in patients without events. A PP of >or= 60 mmHg is linked to an increased risk of silent myocardial ischemias.     

Effect of intensive blood pressure control with valsartan on urinary albumin excretion in normotensive patients with type 2 diabetes

BACKGROUND: Diabetes is the most common cause of renal failure in the United States, and data regarding the effects of aggressive blood pressure (BP) therapy in normotensive patients with type 2 diabetes are inadequate. METHODS: A total of 129 type 2 diabetic patients with a BP of <140/80 to 90 mm Hg without overt albuminuria were randomized to either intensive BP control (diastolic BP goal 75 mm Hg) using an angiotensin II receptor blocker, valsartan, versus moderate BP control (diastolic BP 80 to 90 mm Hg with placebo initially) to evaluate the effect on the change in urinary albumin excretion (UAE) from baseline. RESULTS: The mean entrance BP was 126 +/- 8.8/84 +/- 2.4 mm Hg. The mean follow-up period was 1.9 +/- 1.0 years. During the follow-up period, the mean BP was 118 +/- 10.9/75 +/- 5.7 for the intensive v 124 10.9/80 6.5 mm Hg for the moderate BP groups (P < .001). No difference was observed in change in creatinine clearance or serum creatinine from baseline between the two groups. An analysis of covariance model for change in log (UAE + 1), adjusting for age, HBA(1c), duration of diabetes, baseline log (UAE + 1), sex, and ethnicity resulted in a significant treatment difference at 2 years (P = .007) with intensive BP control reducing log (UAE+1) compared with moderate BP control. CONCLUSION: Intensive BP control with valsartan to <120/80 mm Hg in normotensive patients with type 2 diabetes and normo- or microalbuminuria significantly decreased the progression of UAE and in some cases caused regression of UAE.     

Predicting the blood pressure response to atenolol

The fall in blood pressure in response to atenolol 50 mg per day has been estimated using ambulatory BP and heart rate monitoring during the day in 35 mild to moderate hypertensive patients. The fall in pressure for the group averaged 18.2 +/- 11.3/11.5 +/- 8.3 mmHg. The 95% confidence internals were 14.5-22.0 mmHg systolic and 8.8-14.3 mmHg diastolic with the individual responses in diastolic pressure being related to the pretreatment variability of diastolic pressure (r = 0.65 P less than 0.001) and to the initial heart rate (r = 0.35 P less than 0.05). With atenolol treatment the BP fall is greater in patients with a more unstable BP. Blood pressure reduction is achieved by reducing the level of cardiac activity.     

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.     

Using different methods to evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension according to ambulatory blood pressure monitoring

OBJECTIVE: To evaluate the efficacy of olmesartan medoxomil in Chinese patients with mild to moderate essential hypertension using different methods according to ambulatory blood pressure monitoring. METHODS: Chinese patients 18-75 years of age with clinic diastolic blood pressure (BP) 90-109 mmHg and systolic BP less than 180 mmHg were treated with olmesartan medoxomil 20-40 mg once daily for 24 weeks to reach the goal BP (<140/90 and <130/80 mmHg in diabetes) in a multicenter study. The trough-to-peak ratio (T/P ratio) and the smoothness index (SI) for systolic/diastolic BP were calculated using different methods according to ambulatory blood pressure monitoring. RESULT: Olmesartan medoxomil 20-40 mg once daily reduced the systolic/diastolic ambulatory BP for 24-h, daytime, and night-time by 13.3±16.3/7.6±9.5, 13.9±17.4/8.0±10.4, and 12.3±18.1/6.8±10.2 mmHg in all eligible patients at week 24 from baseline (n=87, P<0.0001). The global and individual T/P ratios were 0.64/0.62 and 0.32/0.30 (n=87) for systolic/diastolic BP, whereas these were 0.71/0.70 and 0.31/0.39 in fair responders (n=71). Global and individual SI were 6.81/5.37 and 0.92/0.67 (n=87) for systolic/diastolic BP, whereas these were 7.04/5.44 and 1.03/1.03 in fair responders (n=71). Global and individual T/P ratios for systolic/diastolic BP were 0.75/0.82 and 0.45/0.46 in the 20 mg subgroup (n=41), whereas these were 0.44/0.59 and 0.30/0.29 in the 40 mg subgroup (n=30). Global and individual SI were 5.70/5.32 and 1.03/0.87 for systolic/diastolic BP in the 20 mg subgroup (n=41), but these were 3.64/2.46 and1.01/0.60 in the 40 mg subgroup (n=30). CONCLUSION: The duration of the antihypertensive action of olmesartan medoxomil with 20-40 mg once daily can be assessed by the global T/P ratio and SI rather than the individual values, even in different populations and dosages.     

Different circulatory response to melatonin in postmenopausal women without and with hormone replacement therapy

In young men and women, melatonin influences vascular reactivity and reduces blood pressure and norepinephrine levels. Herein, we investigated whether these effects are conserved in postmenopausal women without and with hormone replacement therapy (HRT). Oral melatonin (1 mg) or placebo was randomly and in double blind fashion administered to 18 untreated and 13 postmenopausal women who were treated continuously with transdermal estradiol (50 microg/day) plus cyclic medroxyprogesterone acetate (5 mg/day x 12 days every 28 days). Internal carotid artery pulsatility index (PI), an index of downstream resistance to blood flow, blood pressure and catecholamine levels were evaluated. In untreated postmenopausal women, melatonin was ineffective, while in HRT-treated women, studied during the only estrogenic phase, melatonin reduced, within 90 min, systolic (-8.1 +/- 9.9 mmHg; P = 0.054), diastolic (-5.0 +/- 7.0 mmHg; P = 0.049) and mean (- 6.0 +/- 6.6 mmHg; P = 0.037) blood pressure. Norepinephrine (-50.1 +/- 66.7 pg/mL; P = 0.019), but not epinephrine levels, were also significantly reduced. Similarly, resistance to blood flow in the internal carotid artery, as evaluated by the PI, decreased (-0.190 +/- 0.15; P = 0.0006) in a way that was linearly related to pre-existing PI values (r2 = 0.5; P = 0.0059). These data show that the circulatory response to melatonin is conserved in postmenopausal women on HRT but not in untreated postmenopausal women. Possible physiological and pharmacological implications of these data on the cardiovascular risk of postmenopausal women can be envisioned.