24-Hour ambulatory blood pressure control with triple-therapy amlodipine, valsartan and hydrochlorothiazide in patients with moderate to severe hypertension

To determine the effectiveness and safety of once-daily combination therapy with amlodipine, valsartan and hydrochlorothiazide for reducing ambulatory blood pressure (ABP) in patients with moderate to severe hypertension, a multicenter, double-blind study was performed (N=2271) that included ABP monitoring in a 283-patient subset. After a single-blind, placebo run-in period, patients were randomized to receive amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg), valsartan/hydrochlorothiazide (320/25?mg), amlodipine/valsartan (10/320?mg) or amlodipine/hydrochlorothiazide (10/25?mg) each morning for 8 weeks. Efficacy assessments included change from baseline in 24-h, daytime and night time mean ambulatory systolic BP (SBP) and diastolic BP (DBP). Statistically significant and clinically relevant reductions from baseline in all these parameters occurred in all treatment groups (P<0.0001, all comparisons versus baseline). At week 8, least squares mean reductions from baseline in 24-h, daytime and night time mean ambulatory SBP/DBP were 30.3/19.7, 31.2/20.5 and 28.0/17.8?mm?Hg, respectively, with amlodipine/valsartan/hydrochlorothiazide; corresponding reductions with dual therapies ranged from 18.8-24.1/11.7-15.5, 19.0-25.1/12.0-16.0 and 18.3-22.6/11.1-14.3?mm?Hg (P≤0.01, all comparisons of triple versus dual therapy). Treatment with amlodipine/valsartan/hydrochlorothiazide maintained full 24-h effectiveness, including during the morning hours; all hourly mean ambulatory SBP and mean ambulatory DBP measurements were ≤130/85?mm?Hg at end point. Amlodipine/valsartan/hydrochlorothiazide combination therapy was well tolerated. Once-daily treatment with amlodipine/valsartan/hydrochlorothiazide (10/320/25?mg) reduces ABP to a significantly greater extent than component-based dual therapy and maintains its effectiveness over the entire 24-h dosing period.     

A home blood pressure monitoring study comparing the antihypertensive efficacy of two angiotensin II receptor antagonist fixed combinations

BACKGROUND: The objective of this prospective, randomized, open-label, blinded-endpoint study was to compare the antihypertensive efficacy of valsartan 80 mg v irbesartan 150 mg when combined with hydrochlorothiazide (HCTZ) 12.5 mg. METHODS: Untreated or uncontrolled hypertensive adults (n = 800) were enrolled by primary care physicians. After a 5-week open-label lead-in phase in which all patients received 12.5 mg HCTZ once daily, subjects whose blood pressure (BP) remained uncontrolled were randomized (n = 464) to valsartan/HCTZ (80/12.5 mg) or irbesartan/HCTZ (150/12.5 mg) for 8 weeks. Home BP monitoring (HBPM) was performed in the morning and in the evening for 5 days, at baseline, and after 8 weeks. Office BP measurements were obtained at baseline and after 8 weeks. RESULTS: Irbesartan/HCTZ produced greater reductions in average systolic BP (SBP) and diastolic BP (DBP) measured by HBPM than valsartan/HCTZ (SBP: -13.0 v -10.6 mm Hg, P = .0094; DBP: -9.5 v -7.4 mm Hg, P = .0007). These differences were more pronounced in the morning (trough) than in the evening. Office BP measurements also showed greater reductions in trough seated SBP and DBP with irbesartan/HCTZ compared with valsartan/HCTZ. Normalization rates observed with HBPM (SBP <135 mm Hg and DBP <85 mm Hg) were significantly greater with irbesartan/HCTZ than with valsartan/HCTZ (50.2 v 33.2%; P = .0003). The overall safety was similar in the two groups. CONCLUSIONS: The superior BP-lowering potency of the fixed combination irbesartan/HCTZ (150/12.5 mg) over valsartan/HCTZ (80/12.5 mg), evidenced independently from the investigators by HBPM, supports the use of this technique in trials with prospective, randomized, open-label, blinded-endpoint designs.     

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.     

Weekly Variation of Home and Ambulatory Blood Pressure and Relation Between Arterial Stiffness and Blood Pressure Measurements in Community-Dwelling Hypertensives

Although blood pressure (BP) is a major determinant of pulse wave velocity (PWV), some treatments have independent effects on BP and arterial stiffness. Although both ambulatory BP (ABP) and self-measured BP at home (HBP) have become important measures for the diagnosis and management of hypertension, single day recordings may be insufficient for a proper diagnosis of hypertension or the evaluation of treatment efficacy. To evaluate weekly variations in BP using 7-day HBP and 7-day ABP monitoring and to determine the relation between arterial stiffness and BP measurements in community-dwelling patients with hypertension. We enrolled 68 community-dwelling hypertensive subjects in this study. Significant weekly variations in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found in the awake ABP data (p < .01, respectively), while no significant weekly variations in the asleep ABP or the morning and evening HBP data were observed. In untreated subjects, significant correlations were obtained between the brachial-ankle PWV and the average awake SBP, the average asleep SBP and the average SBP measured by HBP in the evening. In treated subjects, only the average SBP measured by HBP in the morning was significantly correlated with the baPWV. Differences in the weekly variations in BP were observed between HBP and ABP monitoring. In addition, the morning systolic HBP was not correlated with arterial stiffness in untreated subjectswith hypertension but was correlated in treated subjects. Relations between the morning HBP and arterial stiffness might be attributed to morning surges in BP and/or trough levels of antihypertensive drugs.     

Comparison of telmisartan versus losartan: meta-analysis of titration-to-response studies

OBJECTIVES: To compare the ability of telmisartan and losartan to reduce mean diastolic blood pressure (DBP) during the last 6 h of the 24-h dosing interval in a prospectively planned meta-analysis of ambulatory blood pressure monitoring (ABPM) data from two independent studies. METHODS: Data were from two independent randomized, double-blind, double-dummy, titration-to-response studies conducted in patients with mild-to-moderate hypertension (seated cuff DBP 95-109 mmHg, 24-h mean ambulatory DBP >or=85 mmHg). After a 4-week placebo run-in period, patients received once-daily telmisartan 40 mg or losartan 50 mg, with up-titration after 4 weeks to telmisartan 80 mg or losartan 100 mg, respectively, if seated trough cuff DBP >or=90 mmHg. Blood pressures were recorded using ABPM immediately before randomization and after 8 weeks of active treatment. In addition, seated trough cuff blood pressures were measured at baseline and after 4 and 8 weeks of active treatment. RESULTS: Titration to the higher dose was required in 60.1% of telmisartan patients and 69.5% of losartan patients (P=0.01). Reductions from baseline in the last 6 h mean ambulatory DBP with telmisartan and losartan were 6.6+/-0.4 and 5.1+/-0.4 mmHg, respectively (P<0.01, adjusted for baseline and study); the effects were homogeneous across the two studies. During the last 6 h of the 24-h dosing interval, telmisartan produced greater reductions in each of the observed hourly mean ambulatory DBP values. Telmisartan-induced reductions were also greater for the majority of the observed hourly mean ambulatory DBP values over the entire 24-h dosing interval. Reductions from baseline in the last 6 h adjusted mean ambulatory systolic blood pressure (SBP) for telmisartan and losartan were 9.9+/-0.6 and 7.8+/-0.6 mmHg, respectively (P=0.01). The 24-h profiles of ambulatory SBP hourly mean reductions were similar to those for DBP. Both telmisartan and losartan were found to be safe and well tolerated. CONCLUSIONS: Telmisartan 40/80 mg is superior to losartan 50/100 mg in controlling DBP and SBP during the last 6 h of the 24-h dosing interval.     

Weekly variation of home and ambulatory blood pressure and relation between arterial stiffness and blood pressure measurements in community-dwelling hypertensives

Although blood pressure (BP) is a major determinant of pulse wave velocity (PWV), some treatments have independent effects on BP and arterial stiffness. Although both ambulatory BP (ABP) and self-measured BP at home (HBP) have become important measures for the diagnosis and management of hypertension, single day recordings may be insufficient for a proper diagnosis of hypertension or the evaluation of treatment efficacy. To evaluate weekly variations in BP using 7-day HBP and 7-day ABP monitoring and to determine the relation between arterial stiffness and BP measurements in community-dwelling patients with hypertension. We enrolled 68 community-dwelling hypertensive subjects in this study. Significant weekly variations in systolic blood pressure (SBP) and diastolic blood pressure (DBP) were found in the awake ABP data (p < .01, respectively), while no significant weekly variations in the asleep ABP or the morning and evening HBP data were observed. In untreated subjects, significant correlations were obtained between the brachial-ankle PWV and the average awake SBP, the average asleep SBP and the average SBP measured by HBP in the evening. In treated subjects, only the average SBP measured by HBP in the morning was significantly correlated with the baPWV. Differences in the weekly variations in BP were observed between HBP and ABP monitoring. In addition, the morning systolic HBP was not correlated with arterial stiffness in untreated subjects with hypertension but was correlated in treated subjects. Relations between the morning HBP and arterial stiffness might be attributed to morning surges in BP and/or trough levels of antihypertensive drugs.     

Functional variants of the angiotensinogen gene determine antihypertensive responses to angiotensin-converting enzyme inhibitors in subjects of African origin

OBJECTIVE: To determine whether the response to angiotensin-converting enzyme inhibitor (ACEI) monotherapy in subjects of African origin is determined by genetic variants within the angiotensinogen (AGT) gene. METHODS: A total of 194 hypertensive patients of African ancestry were recruited from district clinics in Johannesburg, South Africa. Eighty patients received open-label ACEI (enalapril or lisinopril) monotherapy, and 114 open-label calcium antagonist (nifedipine) as a drug class comparator. Twenty-four hour ambulatory blood pressure (ABP) monitoring was performed at baseline (off medication) and after 2 months of therapy. DNA was analysed for functional variants (-217G-->A and -20A-->C) of the AGT gene. The impact of genotype on ABP responses to ACEI monotherapy or calcium antagonists; and on plasma aldosterone and renin levels after ACEI monotherapy was assessed. RESULTS: Adjusting for baseline ABP and type of ACEI in the ACEI-treated group, the -217G-->A variant predicted ABP responses to ACEI (n = 77; P < 0.01), but not to nifedipine (n = 108). ACEI in patients with the AA genotype of the -217G-->A variant failed to elicit an antihypertensive response [change in ABP, mmHg: systolic blood pressure (SBP) +0.84 +/- 2.89, P = 0.78; diastolic blood pressure (DBP) -0.47 +/- 1.74, P = 0.79]. In contrast, those patients with at least one copy of the -217G allele developed a 7.23 +/- 1.55 and 5.38 +/- 1.12 mmHg decrease (P < 0.0001) in SBP and DBP, respectively, after ACEI administration. Similarly, the -20A-->C variant predicted ABP responses to ACEI monotherapy (P < 0.01) but not to nifedipine. Moreover, patients who were AA genotype for both variants failed to develop an antihypertensive response to ACEI (change in ABP, mmHg: SBP +1.06 +/- 3.05, P = 0.73; DBP -0.39 +/- 1.83, P = 0.83); whereas patients with at least one copy of both the -217G and the -20C allele developed substantial decreases in ABP (change in ABP, mmHg: SBP -14.08 +/- 3.72, P < 0.0001; DBP -9.62 +/- 2.74, P < 0.0001). Patients with at least one copy of the -217G allele demonstrated a significant reduction in the aldosterone-to-renin ratio (-0.098 +/- 0.035, P < 0.01), whereas in those patients who were -217AA genotype the ratio was unchanged (-0.03 +/- 0.16, P = 0.85). CONCLUSION: Functional variants of the AGT gene contribute to the variability of antihypertensive responses to ACEI monotherapy in individuals of African ancestry, with genotype determining whether or not responses occur.     

Effect of telmisartan on blood pressure control and kidney function in hypertensive, proteinuric patients with chronic kidney disease

OBJECTIVES: To assess the antihypertensive and antiproteinuric efficacy and safety of the angiotensin II type 1 receptor blocker telmisartan in patients with hypertension and chronic kidney disease. METHODS: A multicenter, prospective trial was performed in adults with hypertension [systolic blood pressure (SBP)/diastolic blood pressure (DBP) >130/85 mmHg), chronic renal insufficiency (serum creatinine <4.0 mg/dl), and proteinuria (>1 g/24 h). In addition to existing antihypertensive therapy, the nature and doses of which remained unchanged throughout the study, patients received once-daily telmisartan 40 mg for the first 3 months followed by forced titration to telmisartan 80 mg for the subsequent 3 months to achieve a target SBP/DBP of <130/85 mmHg. The rationale for using telmisartan was its long half-life efficacy, greater antihypertensive effect compared with valsartan or losartan, and newly discovered potential antidiabetic effect. RESULTS: The study was conducted in 92 patients (45 men, 47 women), of whom 60 had diabetes mellitus (54 patients with type 2 disease). Five patients discontinued prematurely: two because of hyperkalemia, two because of protocol violation, and one because of lack of efficacy. After 6 months' telmisartan treatment, office trough seated SBP was reduced by 19.6 mmHg (P<0.001) from 154.9+/-14.6 mmHg and DBP by 11.8 mmHg (P<0.001) from 91.7+/-8.1 mmHg. Seated trough SBP/DBP of <130/85 mmHg was achieved at 6 months in 34.8% of patients. Ambulatory blood pressure monitoring also demonstrated significant reductions in mean daytime SBP of 10.9 mmHg (P=0.01), night-time SBP of 12.1 mmHg (P=0.05), daytime DBP of 3.1 mmHg (P=0.05), and night-time DBP of 6.5 mmHg (P=0.05). Proteinuria decreased significantly from 3.6+/-3.4 to 2.8+/-2.8 g/24 h (P=0.01). A decrease in proteinuria depended significantly on a decrease in SBP at the end of the study (P=0.044). Each decrease in SBP of about 10 mmHg led to a decrease in proteinuria of about 0.79 g/24 h (95% CI 0.02-1.56 g/24 h). Serum creatinine increased from 1.96+/-0.79 to 2.08+/-0.89 mg/dl (P=0.01), whereas creatinine clearance did not change significantly. CONCLUSIONS: Telmisartan effectively and safely reduced blood pressure and brought about regression of proteinuria in diabetic and nondiabetic, hypertensive, proteinuric patients with chronic kidney disease, even in those with mild-to-moderate chronic renal failure.     

Repeated automated versus daytime ambulatory blood pressure measurement in mild, moderate and severe untreated black hypertensive patients

OBJECTIVE: To examine the extent to which one session of repeated automated (30-45 min) blood pressure measurements in non-treated, hypertensive patients can be used to predict daytime ambulatory blood pressure (ABP). METHODS: Two hundred untreated black hypertensive patients (mean age 50.2+/-11.2) were retrospectively stratified on the basis of the daytime ambulatory diastolic blood pressure (DBP) into mild, moderate and severe hypertensives (90 mmHg 相似文献   

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.     

氯沙坦对高血压病人24小时血压的影响

目的观察氯沙坦对高血压病人24小时血压的影响,探讨其临床意义。 方法20例Ⅰ-Ⅱ级高血压病人,入院后停药2周,服氯沙坦50mg,qd,疗程12周,1个月后血压若未降至140/90mmHg以下,可加大剂量到100mg,qd,治疗前后复查24小时动态血压。以二次给药间距终末时血压下降数除以给药间距中最大血压下降数值作为药物降压的谷/峰比(T∶P),以夜间血压均值与白昼血压均值比较时下降10%或大于10mmHg者为夜间血压下降或"杓型者",反之为夜间血压不下降者或"非杓型者"。 结果　发现(1)氯沙坦能明显降低高血压病人的24小时平均血压(mmHg)(SBP134±14比113±8,DBP89±12比71±5,P<0.01);有效率为85.0%.(2)氯沙坦降压的SBP和DBPTP比率分别为78.6%(48%～93.9%)和76.2%(46.4%～89.6%).SBP,DBP和MBP的平滑曲线指数分别是1.23±0.32,1.36±0.41和1.32±0.38.(3)对夜间血压高于正常值(120/80mmHg)的高血压患者,氯沙坦明显降低夜间血压(mmHg)(SBP142.6±8.8降至116.3±11.4,DBP89.2±9.6降至74.3±6.8,P<0.01),对夜间血压已属正常者,氯沙坦无进一步降压作用(SBP120.3±3.7比116.3±6.8;DBP78.2±6.1比74.3±7.2,P>0.05).(3)24小时SBP,DBP下降幅度与治疗前SBP,DBP明显相关,r分别为0.803和0.797,P<0.01. 结论　氯沙坦是一种安全有效的降压药,其主要优点是24小时平稳降压,谷峰比满意,夜间无过度降压的危险,晨间血压上升受到明显抑制,基础血压越高,降压效果越好。     

Rosiglitazone reduces office and diastolic ambulatory blood pressure following 1-year treatment in non-diabetic subjects with insulin resistance

OBJECTIVE: Rosiglitazone (RSG) has been reported to reduce blood pressure (BP) in patients with type-2 diabetes, but similar effects in non-diabetic people with insulin resistance is less clear. Our aim was to test the long-term BP-lowering effects of RSG compared with placebo. METHODS: We recruited participants for BP evaluation of RSG treatment from a larger intervention trial. Office BP was recorded in 355 non-diabetic subjects with insulin resistance randomized to receive either RSG or placebo for 52 weeks. Ambulatory BP monitoring (ABPM; Spacelab 90207) was performed in a subgroup of 24 subjects (RSG: n = 11; placebo n = 13). RESULTS: After 1 year, the office BP decreased by -3.1 mmHg systolic (p<0.05) and -3.8 mmHg diastolic (p<0.001) in the RSG group versus placebo. In patients treated with RSG, at 1 year there was a trend for a reduction from baseline for mean 24-h diastolic BP (DBP), daytime DBP and night-time DBP (-4.39, -5.26 and -2.93 mmHg, respectively). However, only daytime DBP was significantly lower in the RSG group compared with control (adjusted mean difference: -4.41 mmHg, p = 0.007). There was also a non-significant trend for a reduction in mean 24-h systolic BP (SBP), daytime SBP and night-time SBP (-2.70, -2.51 and -3.35 mmHg, respectively). CONCLUSIONS: RSG treatment for 1 year was associated with a small but significant decrease in diastolic 24-h ambulatory diastolic BP, and both systolic and diastolic office BPs in non-diabetic people with insulin resistance.     

Significance of pulsatility of brachial artery pressure for blood pressure control

Few studies have examined predictors of poor blood pressure (BP) control. The aim of this study was to observe the relationship between the pulsatility of brachial artery pressure characterized as pulse pressure/diastolic pressure (PP/DP), suggesting aortic input impedance, and poor BP control. We obtained office BP measurements for 94 patients aged 40-75 years with either office systolic BP (SBP) >or= 140 mmHg or diastolic BP (DBP) >or= 90 mmHg. Patients were given a single antihypertensive agent or were untreated at baseline. The angiotensin II receptor blocker valsartan (80 mg) was administered to all patients. Patients were treated with 1 to 2 antihypertensive drugs (valsartan only or valsartan + Ca antagonist) for 6 months to achieve an office BP of less than 140/90 mmHg. At follow-up, 32 patients were taking a single drug (valsartan) with good BP control, 24 were receiving two drugs with good BP control, and 38 were on two drugs with poor BP control. SBP and DBP at baseline were similar in the 3 groups. PP/DP at baseline differed in the 3 groups (P<0.01). In multivariate analysis, only PP/DP at baseline correlated with lack of BP control. The pulsatility of brachial artery pressure is associated with achieving adequate BP control.     

24-hour ambulatory blood-pressure effects of valsartan and hydrochlorothiazide combinations compared with amlodipine in hypertensive patients at increased cardiovascular risk: a VAST sub-study

BACKGROUND: There is a lack of data on the effects of angiotensin-receptor blocker and diuretic combinations on ambulatory blood pressure (ABP) in hypertensive patients with additional cardiovascular risk factors. METHODS: In a randomized, double-blind trial, the effects on 24-h ABP of the combination valsartan 160 mg od and hydrochlorothiazide 25 or 12.5 mg during 24 weeks of therapy were compared with the effects of amlodipine 10 mg monotherapy (group A10) in 474 stage-II hypertensive patients with additional cardiovascular risk factors. After a two-week single-blind placebo run-in period, patients were randomized to receive valsartan 160 mg od or amlodipine 5 mg od. At week 4, HCTZ 12.5 mg (group V160/HCTZ12.5) and 25 mg (group V160/HCTZ25) were added to the valsartan groups and in the A10 patients the amlodipine dose was force-titrated to 10 mg od. RESULTS: All three treatments reduced 24-h BP as well as night-time and daytime BP levels from baseline. Twenty-four hour systolic blood pressure (SBP) was reduced by 15.9+/-1.0 mmHg (least-squares mean change+/-SE), 19.3+/-1.0 mmHg and 16.1+/-1.1 mmHg in the V160/HCTZ12.5, V160/HCTZ25 and A10 groups, respectively and 24-h diastolic blood pressure (DBP) was reduced by 9.3+/-0.6 mmHg, 11.4+/-0.6 mmHg and 9.6+/-0.7 mmHg in the three groups. The differences between the V160/HCTZ25 group and the A10 group were significant (p<0.05) for the changes in 24-h systolic BP as well as for changes in daytime systolic BP and night-time diastolic BP. Control rates defined as ABPM < or =130/80 mmHg were: 48.4%, 60.8% and 50.9% in the V160/HCTZ12.5, V160/25 and A10 groups, respectively. The differences in control rates between the V160/HCTZ25 group and the other two treatment groups were significant at p<0.05. CONCLUSIONS: The fixed-dose combination of valsartan 160 mg+HCTZ 25 mg od is an attractive therapeutic option measured on the effects on 24-h ABPM, night-time and daytime BP reduction and control rates in hypertensive patients at additional cardiovascular risk.     

Significance of mean blood pressure for blood pressure control

The significance of pulse pressure (PP) and mean blood pressure (MBP) for blood pressure (BP) control is unclear. The aim of this study was to examine the relationship between PP and MBP and BP control. We obtained home BP measurements for 117 patients aged 40-75 years with either office systolic BP (SBP) >or= 140 mmHg or office diastolic BP (DBP) >or= 90 mmHg. Patients were treated with 1 to 2 antihypertensive drugs for 6 months to achieve home SBP < 135 mmHg and home DBP < 85 mmHg. At follow-up, 72 patients were taking a single drug with good BP control, 23 were taking two drugs with good BP control, and 22 were taking two drugs without good BP control. Although office SBP and DBP at baseline were similar in the three groups, home SBP and DBP at baseline in the single drug group were lowest among the three groups (P < 0.01). Home MBP at baseline in the single drug group was lowest among the three groups (P < 0.01). Home PP at baseline was highest in the two-drug without good control group (P < 0.001). In multivariate logistic regression analysis, only home MBP at baseline was significantly correlated with a lack of BP control. Home MBP rather than home PP is associated with achieving adequate BP control.     

Effects of GH replacement on 24-h ambulatory blood pressure and its circadian rhythm in adult GH deficiency

OBJECTIVE: Increased prevalence of hypertension and cardiovascular mortality have been reported in hypopituitary patients who had been appropriately replaced with conventional pituitary hormones except GH. Growth hormone replacement (GHR) results in improvement of surrogate markers of cardiovascular function. Data on effects of GHR on blood pressure (BP) in adult growth hormone deficiency (AGHD), however, remain contradictory. There are as yet no reports on BP circadian rhythms in untreated or treated AGHD. Therefore, in a 12-month follow-up study, we evaluated the effects of GHR on ambulatory blood pressure (ABP) in AGHD patients. STUDY DESIGN: A prospective, open treatment design study to determine the effects of GHR on ABP and heart rate in AGHD patients. GH was commenced at a daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 4-weekly intervals to achieve and maintain IGF-I standard deviation score (IGF-I SD) between the median and upper end of the age-related reference range. PATIENTS: Twenty-two, post-pituitary surgery, severe AGHD patients (11 men), defined as peak GH response < 9 mU/l to provocative testing were recruited. The mean age +/- SEM was 48.8 +/- 2.5 years. Twenty-one patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment. MEASUREMENTS: Twenty-four-hour ABP and heart rate (HR), body mass index (BMI), waist hip ratio (WHR) and total body water (TBW) were measured before and after 12 months on GHR. Cosinor analysis was used to analyse BP and HR circadian rhythm parameter estimates. RESULTS: Target IGF-I SD was achieved within 3 months of commencement of GHR in all patients (-3.5 +/- 0.4 at baseline vs. 0.8 +/- 0.2 at 3 months, P < 0.001) and remained within range at 12 months (1.1 +/- 0.2, P < 0.001 compared to baseline). A significant increase in TBW (45.8 +/- 1.2 vs. 47.8 +/- 1.5 kg, P < 0.05) but no significant change in BMI (30.7 +/- 2.2 vs. 31.8 +/- 2.7, P = NS) or WHR (0.95 +/- 0.02 vs. 0.93 +/- 0.02, P = NS) was observed after 12 months on GHR. The 24-h mean systolic ABP (SBP; 126.2 +/- 2.8 vs. 120.1 +/- 2.7 mmHg, P < 0.001) and diastolic ABP (DBP; 78.2 +/- 1.6 vs. 71.4 +/- 1.8 mmHg, P < 0.001) significantly decreased following GHR with a parallel increase in 24-h mean HR (69.6 +/- 2.5 vs. 73.8 +/- 2.5 beats/min; P < 0.001). A significant nocturnal decrease in SBP and DBP was observed both before (SBP; daytime, 129.1 +/- 2.8 vs. night time, 115.9 +/- 3.0 mmHg, P < 0.001 and DBP; daytime, 80.7 +/- 1.6 vs. night time, 69.2 +/- 1.8 mmHg, P < 0.001) and following GHR (SBP; daytime, 122.8 +/- 2.6 vs. night time, 110.0 +/- 3.6 mmHg, P < 0.001 and DBP; daytime, 73.9 +/- 1.8 vs. night time, 62.0 +/- 2.3 mmHg, P < 0.001). Individual and population-mean cosinor analysis demonstrated significant circadian rhythms for SBP, DBP and HR before and after 12 months on GHR (P < 0.001), suggesting that SBP, DBP and HR circadian rhythms were not altered by GHR. There was, however, a significant reduction in SBP (124.2 +/- 2.8 vs. 118.4 +/- 2.8 mmHg, P < 0.001) and DBP (77.0 +/- 1.6 vs. 70.2 +/- 1.8 mmHg, P < 0.001) MESOR with an increase in HR MESOR (68.9 +/- 2.5 vs. 72.2 +/- 2.4 beats/min, P < 0.01) following GHR. CONCLUSIONS: Systolic and diastolic BP and HR circadian rhythms are preserved in AGHD following 12 months of GHR. However, there is a significant decrease in 24-h mean SBP and DBP and increase in 24-h mean HR after 12 months on GHR. We postulate that this decrease in 24-h mean SBP and DBP may result in a reduction of cardiovascular morbidity and mortality and may explain the beneficial effects of GHR on cardiovascular system previously reported in AGHD patients.     

A comparison of indapamide SR 1.5 mg with both amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients: a randomized double-blind controlled study

OBJECTIVE: To analyse the efficacy of indapamide sustained-release (SR) 1.5 mg in reducing blood pressure versus amlodipine 5 mg and hydrochlorothiazide 25 mg, in elderly hypertensive patients. DESIGN: Double-blind, randomized, 12 week study using three parallel groups. SETTING: European teaching hospitals and general practices. PATIENTS: Randomized patients, (n = 524) including 128 patients with isolated systolic hypertension (ISH); mean age: 72.4 years; mean systolic/diastolic blood pressures (SBP/DBP): 174.5/97.9 mmHg. MAIN OUTCOME MEASURES: Clinic systolic and diastolic blood pressure variations. RESULTS: Indapamide SR 1.5 mg demonstrates a similar efficacy to that of amlodipine 5 mg, as well as to that of hydrochlorothiazide 25 mg (equivalence P < 0.001); the mean decreases in SBP/DBP were -22.7/-11.8 mmHg, -22.2/-10.7 mmHg and -19.4/-10.8 mmHg, respectively. In the ISH subgroup, indapamide SR 1.5 mg tends to have greater efficacy than hydrochlorothiazide 25 mg in reducing the SBP (-24.7 versus -18.5 mmHg, respectively; equivalence P = 0.117), while similar results are obtained with amlodipine 5 mg (-23 mmHg, equivalence P < 0.001). The normalization rate was relatively high for indapamide SR 1.5 mg (75.3%), when compared with amlodipine (66.9%) and hydrochlorothiazide (67.3%), especially in the subgroup of isolated systolic hypertensive patients: 84.2 versus 80.0% for amlodipine, and versus 71.4% for hydrochlorothiazide. CONCLUSIONS: Indapamide SR 1.5 mg shows similar antihypertensive efficacy to amlodipine 5 mg and hydrochlorothiazide 25 mg in elderly hypertensive patients, while in patients with isolated systolic hypertension, indapamide SR 1.5 mg shows a similar efficacy to amlodipine 5 mg but a greater efficacy than hydrochlorothiazide 25 mg.     

A multicenter, 14-week study of telmisartan and ramipril in patients with mild-to-moderate hypertension using ambulatory blood pressure monitoring

BACKGROUND: Blood pressure (BP) has a circadian pattern with a morning surge that is associated with an increased risk of acute coronary and cerebrovascular events. In a prospective, randomized, open-label, blinded-endpoint, parallel-group, multicenter, forced-titration study of telmisartan and ramipril, the efficacy of both drugs on mean ambulatory diastolic BP (DBP) and systolic BP (SBP) during the last 6 h of a 24-h dosing interval was evaluated. METHODS: After screening and a single-blind run-in phase, 812 adults with mild-to-moderate hypertension (defined as a mean seated DBP > or =95 mm Hg and < or =109 mm Hg and a 24-h ABPM mean DBP 7 > or = 85 mm Hg) were randomized to the open-label, 14-week, forced-titration, active-treatment phase as follows: telmisartan 40 mg/80 mg/80 mg (n = 405) or ramipril 2.5 mg/5 mg/10 mg (n = 407), once daily in the morning. The primary efficacy variable was change from baseline in the last 6-h mean DBP and SBP at 8 and 14 weeks as assessed by ambulatory BP monitoring (ABPM). Secondary efficacy variables were changes from baseline in BP control during each of the 24-h periods and in-clinic trough cuff BP. RESULTS: Telmisartan 80 mg was superior to ramipril 5 mg and 10 mg in change from baseline in the last 6-h ABPM mean DBP and SBP at both 8 and 14 weeks (both P < .0001), respectively. At 14 weeks, the adjusted mean change from baseline in DBP for telmisartan 80 mg was -8.8 mm Hg compared with that for ramipril 10 mg of -5.4 mm Hg (P < .0001). For SBP, the adjusted mean change from baseline for telmisartan 80 mg was -12.7 mm Hg compared with that for ramipril 10 mg of -7.9 mm Hg (P < .0001). At 14 weeks, telmisartan 80 mg also yielded superior reductions from baseline in trough cuff BP compared with ramipril 10 mg (DBP: -11.0 mm Hg v -7.8 mm Hg, respectively; SBP: -14.3 mm Hg v -9.1 mm Hg, respectively; both P < .0001). Measures of 24-h BP control favored telmisartan 80 mg versus ramipril 10 mg (P < .0001), as did other secondary ABPM endpoints during the daytime, night-time, and morning periods. Treatment-related adverse events were uncommon; patients treated with ramipril had a higher incidence of cough than those treated with telmisartan (10.1% v 1.5%, respectively). CONCLUSIONS: Telmisartan 80 mg was consistently more effective than ramipril 10 mg in reducing both DBP and SBP during the last 6 h of the dosing interval, a measure of the early morning period when patients are at greatest risk of life-threatening cardiovascular and cerebrovascular events. Telmisartan 80 mg was also more effective than ramipril 10 mg in reducing BP throughout the entire 24-h dosing interval. Both drugs were well tolerated.     

Comparison of valsartan and amlodipine on ambulatory blood pressure variability in hypertensive patients

We tested the hypothesis that calcium channel blockers (CCBs: amlodipine group, n = 38)) are superior to angiotensin receptor blockers (ARBs: valsartan group, n = 38) against ambulatory blood pressure variability (BPV) in untreated Japanese hypertensive patients. Both drugs significantly reduced ambulatory systolic and diastolic BP values. With regard to BPV, standard deviation (SD) in SBP did not change with the administration of either drug, but the ARB significantly increased SD in awake DBP (12 ± 4–14 ± 4 mmHg). The ARB also significantly increased the coefficients of variation (CVs)in awake and 24-h SBP/DBP (all P < 0.05), but amlodipine did not change the CV. CCB significantly reduced the maximum values of awake SBP (193 ± 24–182 ± 27 mmHg, P = 0.02), sleep SBP (156 ± 18–139 ± 14 mmHg, P < 0 .001), and awake and sleep DBP (P < 0.01 in both cases), but the ARB did not change the maximum BP values. In conclusion, a once-daily morning dose of CCB amlodipine was more effective at controlling ambulatory BPV than ARB valsartan, especially in reducing maximum BP levels.     

Clinical prediction of normotension in borderline hypertensive men--a 10 year study

OBJECTIVE: To investigate 24-h ambulatory blood pressure measurements (ABPM) as a tool for long-term prediction of future blood pressure (BP) status in high normal and low stage 1 hypertensives. DESIGN, SETTING AND PARTICIPANTS: A total of 165 men from a population screening program with diastolic BP (DBP) 85-94 mmHg and a systolic BP (SBP) < 150 mmHg performed a 24-h ABPM. Ten years later, 120 participants (73%) returned for renewed measurements. MAIN OUTCOME MEASURES: Blood pressure status at 10 years. RESULTS: At the 10-year follow-up, 53% of the participants were classified as hypertensive (HT) (BP > or = 140/90 or taking anti-hypertensive medication) and 47% were classified as normotensive (NT) (BP < 140/90 mmHg). There was no significant baseline differences in office SBP levels between those who were normotensive or hypertensive at follow-up (136/91 versus 138/92 mmHg), whereas both SBP and DBP night-time levels were significantly lower in the future normotensives as compared to the future hypertensives (107/69 versus 112/74 mmHg, P < 0.01). Using recommended normalcy night-time ABP levels of < 120/75 mmHg in addition to office BP (140/90) at baseline, over 85% of the subjects were correctly classified provided they met both clinic and ambulatory night-time criteria for HT and NT classification at baseline. CONCLUSION: The use of ABPM in addition to office BP's in patients with borderline hypertension greatly increases the possibility of identifying those individuals who are at a very small risk of developing future hypertension. This could potentially lead to considerable savings in both patient anxiety, physician time and resource consumption.