Mean Ambulatory Diastolic Blood Pressure Research Articles

Effect of vitamin B2, vitamin C, vitamin D, vitamin E and folic acid in adults with essential hypertension: a systematic review and network meta-analysis

ObjectivesThe objective of the current study is to compare the treatment effects of different vitamins on essential hypertension to provide an initial basis for developing evidence-based practices.DesignSystematic review and network...

Ambulatory diastolic blood pressure: a marker of comorbidity in elderly fit hypertensive individuals?

BACKGROUNDMasked diastolic hypotension is a new blood pressure (BP) pattern detected by ambulatory blood pressure monitoring (ABPM) in elderly hypertensives. The aim of this study was to relate ABPM and comorbidity in a cohort of fit elderly subjects attending an outpatient hypertension clinic.METHODSComorbidity was assessed by Charlson comorbidity index (CCI) and CHA2DS2VASc score. All subjects evaluated with ABPM were aged ≥ 65 years. CCI and CHA2DS2VASc score were calculated. Diastolic hypotension was defined as mean ambulatory diastolic BP < 65 mmHg and logistic regression analysis was carried out in order to detect and independent relationship between comorbidity burden and night-time diastolic BP < 65 mmHg. RESULTSWe studied 174 hypertensive elderly patients aged 72.1 ± 5.2 years, men were 93 (53.4%). Mean CCI was 0.91 ± 1.14 and mean CHA2DS2VASc score of 2.68 ± 1.22. Subjects with night-time mean diastolic values < 65 mmHg were higher in females [54.7% vs. 45.3%, P = 0.048; odds ratio (OR) = 1.914, 95% CI: 1.047−3.500]. Logistic regression analysis showed that only CHA2DS2VASc score was independently associated with night-time mean diastolic values < 65 mmHg (OR = 1.518, 95% CI: 1.161−1.985; P = 0.002), but CCI was not. CONCLUSIONSABPM and comorbidity evaluation appear associated in elderly fit subjects with masked hypotension. Comorbid women appear to have higher risk for low ambulatory BP.

Long-term efficacy and safety of renal denervation in the presence of antihypertensive drugs (SPYRAL HTN-ON MED): a randomised, sham-controlled trial

Renal denervation has been shown to lower blood pressure in the presence of antihypertensive medications; however, long-term safety and efficacy data from randomised trials of renal denervation are lacking. In this pre-specified analysis of the SPYRAL HTN-ON MED study, we compared changes in blood pressure, antihypertensive drug use, and safety up to 36 months in renal denervation versus a sham control group. This randomised, single-blind, sham-controlled trial enrolled patients from 25 clinical centres in the USA, Germany, Japan, the UK, Australia, Austria, and Greece, with uncontrolled hypertension and office systolic blood pressure between 150 mm Hg and 180 mm Hg and diastolic blood pressure of 90 mm Hg or higher. Eligible patients had to have 24-h ambulatory systolic blood pressure between 140 mm Hg and less than 170 mm Hg, while taking one to three antihypertensive drugs with stable doses for at least 6 weeks. Patients underwent renal angiography and were randomly assigned (1:1) to radiofrequency renal denervation or a sham control procedure. Patients and physicians were unmasked after 12-month follow-up and sham control patients could cross over after 12-month follow-up completion. The primary endpoint was the treatment difference in mean 24-h systolic blood pressure at 6 months between the renal denervation group and the sham control group. Statistical analyses were done on the intention-to-treat population. Long-term efficacy was assessed using ambulatory and office blood pressure measurements up to 36 months. Drug surveillance was used to assess medication use. Safety events were assessed up to 36 months. This trial is registered with ClinicalTrials.gov, NCT02439775; prospectively, an additional 260 patients are currently being randomly assigned as part of the SPYRAL HTN-ON MED Expansion trial. Between July 22, 2015, and June 14, 2017, among 467 enrolled patients, 80 patients fulfilled the qualifying criteria and were randomly assigned to undergo renal denervation (n=38) or a sham control procedure (n=42). Mean ambulatory systolic and diastolic blood pressure were significantly reduced from baseline in the renal denervation group, and were significantly lower than the sham control group at 24 and 36 months, despite a similar treatment intensity of antihypertensive drugs. The medication burden at 36 months was 2·13 medications (SD 1·15) in the renal denervation group and 2·55 medications (2·19) in the sham control group (p=0·26). 24 (77%) of 31 patients in the renal denervation group and 25 (93%) of 27 patients in the sham control group adhered to medication at 36 months. At 36 months, the ambulatory systolic blood pressure reduction was -18·7 mm Hg (SD 12·4) for the renal denervation group (n=30) and -8·6 mm Hg (14·6) for the sham control group (n=32; adjusted treatment difference -10·0 mm Hg, 95% CI -16·6 to -3·3; p=0·0039). Treatment differences between the renal denervation group and sham control group at 36 months were -5·9 mm Hg (95% CI -10·1 to -1·8; p=0·0055) for mean ambulatory diastolic blood pressure, -11·0 mm Hg (-19·8 to -2·1; p=0·016) for morning systolic blood pressure, and -11·8 mm Hg (-19·0 to -4·7; p=0·0017) for night-time systolic blood pressure. There were no short-term or long-term safety issues associated with renal denervation. Radiofrequency renal denervation compared with sham control produced a clinically meaningful and lasting blood pressure reduction up to 36 months of follow-up, independent of concomitant antihypertensive medications and without major safety events. Renal denervation could provide an adjunctive treatment modality in the management of patients with hypertension. Medtronic.

The value of ambulatory blood pressure measurement to detect masked diastolic hypotension in older patients treated for hypertension.

assess how many patients with low ambulatory diastolic blood pressure (DBP) are not identified when relying on office DBP alone, and thus have 'masked diastolic hypotension'. cross-sectional, retrospective cohort study. academic hospital. 848 patients treated for hypertension who received ambulatory blood pressure monitoring (ABPM). cut-off value between on- and off-target systolic blood pressure (SBP): 140mmHg. Cut-off for low office and/or ambulatory DBP: DBP ≤ 70mmHg. 'Masked diastolic hypotension' was defined as office DBP > 70mmHg and mean ambulatory DBP ≤ 70mmHg. mean age of the sample was 60 ± 13years, 50% was female, 37% had diabetes, 42% preexisting cardiovascular disease (CVD), mean office blood pressure (BP) was 134/79mmHg. In all patients (n = 848), low office DBP was present in n = 84(10%), while n = 183(22%) had low ambulatory DBP. In all patients with normal-to-high office DBP (n = 764), n = 122(16%) had 'masked diastolic hypotension'. In this group, ambulatory DBP was 14-19mmHg lower than office DBP. Patients with low ambulatory DBP were older, had more (cardiovascular) comorbidities, and used more (antihypertensive) drugs. Antihypertensive drugs were lowered or discontinued in 30% of all patients with 'masked diastolic hypotension' due to side effects. 'masked diastolic hypotension' is common among patients treated for hypertension, particularly in older patients with CVD (e.g. coronary artery disease, diabetes), patient groups in which the European Society of Cardiology/Hypertension guideline advises to prevent low DBP. Although it remains to be examined at which BP levels the harms of low DBP outweigh the benefits of lowering SBP, our observations are aimed to increase awareness among physicians.

Efficacy and safety of sacubitril/valsartan in patients with essential hypertension uncontrolled by olmesartan: A randomized, double-blind, 8-week study.

A majority of patients with hypertension fail to achieve blood pressure (BP) control despite treatment with commonly prescribed drugs. This randomized, double-blind phase III trial assessed the superiority of sacubitril/valsartan 200mg (97/103mg) to continued olmesartan 20mg in reducing ambulatory systolic BP after 8-week treatment in patients with mild to moderate essential hypertension uncontrolled with olmesartan 20mg alone. A total of 376 patients were randomized to receive either sacubitril/valsartan (n=188) or olmesartan (n=188). Superior reductions in 24-hour mean ambulatory systolic BP were observed in the sacubitril/valsartan group vs the olmesartan group (-4.3mmHg vs -1.1mmHg, P<.001). Reductions in 24-hour mean ambulatory diastolic BP and pulse pressure and office systolic BP and diastolic BP were significantly greater with sacubitril/valsartan vs olmesartan (P<.014). A greater proportion of patients achieved BP control with sacubitril/valsartan vs olmesartan. The overall incidence of adverse events was comparable between the groups. Compared with continued olmesartan, sacubitril/valsartan was more effective and generally safe in patients with hypertension uncontrolled with olmesartan 20mg.

LCZ696, a promising novel agent in treating hypertension (a meta-analysis of randomized controlled trials).

BackgroundTo determine the effectiveness and safety of LCZ696 for the clinical treatment of hypertension, we performed a meta-analysis of the previous clinical trials.MethodsRelevant English articles and randomized controlled trials were searched in Pubmed, Embase, EBSCO, Cochrane base and ClinicalTrials.gov. The last search date was July 20th, 2017.ResultsCompared with 20mg olmesartan, 200mg and 400mg LCZ696 outperformed olmesartan in terms of reducing mean sitting systolic blood pressure, mean ambulatory systolic blood pressure, mean sitting diastolic blood pressure and mean ambulatory diastolic blood pressure. Compared with 20mg olmesartan, 200mg and 400mg LCZ696 was better than olmesartan in terms of reducing mean sitting pulse pressure. And these studies showed that 400mg LCZ696 was better than 20mg olmesartan in terms of reducing mean ambulatory pulse pressure, however, there was no significant difference between 200mg LCZ696 and 20mg olmesartan in terms of redducing mean ambulatory pulse pressure. In addition, 200mg and 400mg LCZ696 was better than placebo in terms of reducing blood pressure parameters mentioned above. Compared with placebo or 20 mg olmesartan, LCZ696 showed no superiority in terms of reducing adverse events or serious adverse events.ConclusionsLCZ696 at 200 mg or 400 mg was better at reducing most of blood pressure parameters than 20 mg olmesartan or placebo. Compared with placebo or 20 mg olmesartan, 200 mg or 400 mg LCZ696 do not result in more adverse events in treating hypertension.

Supported Telemonitoring and Glycemic Control in People with Type 2 Diabetes: The Telescot Diabetes Pragmatic Multicenter Randomized Controlled Trial.

BackgroundSelf-monitoring of blood glucose among people with type 2 diabetes not treated with insulin does not appear to be effective in improving glycemic control. We investigated whether health professional review of telemetrically transmitted self-monitored glucose results in improved glycemic control in people with poorly controlled type 2 diabetes.Methods and FindingsWe performed a randomized, parallel, investigator-blind controlled trial with centralized randomization in family practices in four regions of the United Kingdom among 321 people with type 2 diabetes and glycated hemoglobin (HbA1c) >58 mmol/mol. The supported telemonitoring intervention involved self-measurement and transmission to a secure website of twice-weekly morning and evening glucose for review by family practice clinicians who were not blinded to allocation group. The control group received usual care, with at least annual review and more frequent reviews for people with poor glycemic or blood pressure control. HbA1c assessed at 9 mo was the primary outcome. Intention-to-treat analyses were performed. 160 people were randomized to the intervention group and 161 to the usual care group between June 6, 2011, and July 19, 2013. HbA1c data at follow-up were available for 146 people in the intervention group and 139 people in the control group. The mean (SD) HbA1c at follow-up was 63.0 (15.5) mmol/mol in the intervention group and 67.8 (14.7) mmol/mol in the usual care group. For primary analysis, adjusted mean HbA1c was 5.60 mmol/mol / 0.51% lower (95% CI 2.38 to 8.81 mmol/mol/ 95% CI 0.22% to 0.81%, p = 0·0007). For secondary analyses, adjusted mean ambulatory systolic blood pressure was 3.06 mmHg lower (95% CI 0.56–5.56 mmHg, p = 0.017) and mean ambulatory diastolic blood pressure was 2.17 mmHg lower (95% CI 0.62–3.72, p = 0.006) among people in the intervention group when compared with usual care after adjustment for baseline differences and minimization strata. No significant differences were identified between groups in weight, treatment pattern, adherence to medication, or quality of life in secondary analyses. There were few adverse events and these were equally distributed between the intervention and control groups. In secondary analysis, there was a greater number of telephone calls between practice nurses and patients in the intervention compared with control group (rate ratio 7.50 (95% CI 4.45–12.65, p < 0.0001) but no other significant differences between groups in use of health services were identified between groups. Key limitations include potential lack of representativeness of trial participants, inability to blind participants and health professionals, and uncertainty about the mechanism, the duration of the effect, and the optimal length of the intervention.ConclusionsSupported telemonitoring resulted in clinically important improvements in control of glycaemia in patients with type 2 diabetes in family practice. Current Controlled Trials, registration number ISRCTN71674628.Trial RegistrationCurrent Controlled Trials ISRCTN 71674628

Associations between cystatin C-based eGFR, ambulatory blood pressure parameters, and in-clinic versus ambulatory blood pressure agreement in older community-living adults.

The objective of this study was to determine the relationship between chronic kidney disease [CKD; measured using cystatin C-based estimated glomerular filtration rate (eGFR)] and abnormal ambulatory blood pressure (including nocturnal dipping) in healthy older adults. Further, this study aimed to assess the agreement between clinic and ambulatory blood pressure monitoring. Serum cystatin C levels were measured to calculate eGFR. Participants underwent clinic and 24-h ambulatory blood pressure measurements. Multiple linear regression was performed to examine the association between reduced cystatin C-based eGFR (CKDcys) and blood pressure parameters. Bland-Altman analysis was carried out to evaluate the agreement between clinic and ambulatory measurements. The average age was 72 years. There were 60 individuals with CKDcys (eGFR<60 ml/min/1.73 m). Compared with those without CKDcys, individuals with CKDcys were older, more likely to have hypertension, and less likely to have normal dipping patterns. On multivariate analysis, the presence of CKDcys was found to be significantly associated with a lower mean ambulatory diastolic blood pressure (-2 mmHg, P=0.048), but not with nocturnal dipping or other blood pressure parameters. Clinic systolic blood pressure (SBP) significantly overestimated the mean wake-time ambulatory SBP; the mean difference was 11 mmHg for those without CKDcys (95% limits of agreement -14 to 35 mmHg) and 14 mmHg for those with CKDcys (95% limits of agreement -13 to 41 mmHg); there was no statistically significant effect modification by CKD status. In older, seemingly healthy adults, mild CKD was associated with lower ambulatory diastolic blood pressure. The presence of CKD did not affect interpretation of clinic versus ambulatory blood pressure monitoring, although the accuracy of clinic SBP was poor.

Comparative review of the blood pressure-lowering and cardiovascular benefits of telmisartan and perindopril

Hypertension is a major cardiovascular (CV) risk factor, and blood pressure (BP)-lowering treatment substantially reduces the risk. This review compares the available clinical evidence from the BP-lowering and CV-outcome studies of telmisartan and perindopril, which are among the most intensively studied members of their respective classes. The PubMed database was searched for telmisartan and perindopril publications meeting the following criteria: 1) head-to-head comparison trials for BP lowering; and 2) CV-outcome studies (ie, ones with a CV event, mortality, or hospitalization outcome) in patients with CV risk factors but without heart failure. In comparative trials, telmisartan treatment resulted in significantly higher reduction in trough BP and mean ambulatory diastolic BP for the last 8 hours of the dosing interval compared with perindopril. In mainly placebo-controlled CV-outcome studies in patients with hypertension, CV benefits with perindopril were associated with large reductions in BP. There were no CV outcome studies with telmisartan in patients with hypertension. The beyond-BP-lowering CV-protective benefits of telmisartan were demonstrated in the active-controlled ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) trial, which included patients with controlled BP at baseline. In general, the trials discussed in this review reinforce the fact that perindopril and telmisartan are two long-acting antihypertensive drugs that reduce BP over 24 hours, and are the best-evidenced drugs in their class with proven CV protection. It is also clear that the benefits are not a “class effect”, and vary between the different drugs within each class. Hence, the best approach for treatments tailored to individual patient needs should be evidence-based specific drugs, rather than a drug-class recommendation for achieving therapeutic targets.

Olmesartan medoxomil combined with hydrochlorothiazide improves 24-hour blood pressure control in moderate-to-severe hypertension

Background:Twenty-four-hour ambulatory blood pressure monitoring (ABPM) has been shown to be more reliable than conventional measurements for hypertension assessment and the associated increased risk of cardiovascular events. Olmesartan/hydrochlorothiazide combination therapy has demonstrated increased blood pressure lowering over 24 hours compared with the component monotherapies. This prespecified pooled analysis of data from two trials investigated the effects of olmesartan/hydrochlorothiazide combination therapy and olmesartan monotherapy on 24-hour blood pressure control in patients with moderate-to-severe hypertension.Methods:After 8 weeks’ open-label olmesartan 40 mg monotherapy, uncontrolled patients (mean trough seated blood pressure 90–115/140–180 mmHg and 24-hour mean ambulatory diastolic blood pressure ≥80 mmHg with ≥30% of daytime ambulatory diastolic blood pressure readings >85 mmHg) were randomised to 8 weeks’ double-blind treatment with olmesartan 40 mg or olmesartan/hydrochlorothiazide 20/12.5, 40/12.5 or 40/25 mg (Study 1) or olmesartan/hydrochlorothiazide 20/25 or 40/25 mg (Study 2). This prespecified analysis of ambulatory blood pressure was performed on patients from the full analysis set of pooled studies 1 and 2, restricted to patients who provided at least one valid ABPM measurement at baseline.Results:After 8 weeks’ double-blind treatment, reductions in 24-hour, daytime and night-time blood pressure from baseline were observed for all treatment groups. These reductions were dose-dependent, with olmesartan/hydrochlorothiazide 40/25 mg demonstrating the greatest reductions in 24-hour blood pressure from baseline to Week 16 versus olmesartan monotherapy: −14.0/−8.8 vs −2.7/−2.0 mmHg, respectively; p < 0.0001.Conclusions:Adding hydrochlorothiazide to olmesartan provides more effective 24-hour blood pressure control versus olmesartan monotherapy in patients with moderate-to-severe hypertension.Clinical trial registration:Trial registration: ClinicalTrials.gov identifier: NCT00430508.Trial registration: ClinicalTrials.gov identifier: NCT00430950.

24‐Hour Ambulatory Blood Pressure Response to Combination Valsartan/Hydrochlorothiazide and Amlodipine/Hydrochlorothiazide in Stage 2 Hypertension by Ethnicity: The EVALUATE Study

Several studies reported racial/ethnic differences in blood pressure (BP) response to antihypertensive monotherapy. In a 10-week study of stage 2 hypertension, 320/25 mg valsartan/hydrochlorothiazide (HCTZ) reduced ambulatory BP (ABP) significantly more effectively than 10/25 mg amlodipine/HCTZ. Results (post hoc analysis) are described in Caucasians (n=256), African Americans (n=79), and Hispanics (n=86). Compared with clinic-measured BP (no significant treatment-group differences in ethnic subgroups), least-squares mean reductions from baseline to week 10 in mean ambulatory systolic BP (MASBP) and mean ambulatory diastolic BP (MADBP) favored valsartan/HCTZ over amlodipine/HCTZ in Caucasians (-21.9/-12.7 mm Hg vs -17.6/-9.5 mm Hg; P=.0004/P<.0001). No treatment-group differences in MASBP/MADBP were observed in African Americans (-17.3/-10.6 vs -17.9/-9.5; P=.76/P=.40) or Hispanics (-17.9/-9.7 vs -14.2/-7.2; P=.20/P=.17). Based on ABP monitoring, valsartan/HCTZ is more effective than amlodipine/HCTZ in lowering ABP in Caucasians. In African Americans and Hispanics, both regimens are similarly effective.

COMBINATION THERAPY WITH ALISKIREN+HYDROCHLOROTHIAZIDE REDUCES 24-HOUR AMBULATORY BLOOD PRESSURE MORE EFFECTIVELY THAN RAMIPRIL IN OBESE PATIENTS WITH STAGE 2 HYPERTENSION: PP.5.191

Objective: Ambulatory blood pressure monitoring (ABPM) is a better predictor of cardiovascular events than clinic blood pressure (BP). Analysis of ABPM in a subset of patients in clinical trials is important to confirm observed changes in clinic BP. We previously showed in an 8-week, prospective, multicenter, randomized, double-blind study (N=380) that a single-pill combination of aliskiren (A) with hydrochlorothiazide (HCTZ) provided greater clinic BP reductions than ramipril (R) in obese patients (average body mass index = 35.3 ± 4.4 kg/m2) with hypertension (mean sitting systolic BP [SBP] >=160 mmHg and <200 mmHg). Here we present the efficacy and safety of A+HCTZ vs R on BP control in a subset of patients who underwent ABPM (n=89). Design and Methods: After a 1–4 week washout period, eligible patients received A+HCTZ 150/12.5 mg (n=45) or R 5 mg (n=44) for 1 week; force-titrated to A+HCTZ 300/25 mg or R 10 mg for 7 weeks. Results: Significantly greater reductions in both clinic BP and 24-hour ambulatory blood pressure (ABP) were observed at week 8 with A+HCTZ vs R (P < 0.05). Reductions in the hourly daytime (6AM-10PM) mean ambulatory systolic BP (maSBP), mean ambulatory diastolic BP (maDBP), and hourly nighttime (10PM-6AM) maDBP were also significantly greater for A+HCTZ vs R (Table). In the overall study, adverse event rates were similar in both groups (35.8%, A+HCTZ vs 37.3%, R), the most common being headache, nasopharyngitis, dizziness, and fatigue. Conclusion: The ABPM results suggest that A+HCTZ provides more effective and consistent 24-hour BP reductions than R in obese patients with stage 2 hypertension.

Maintenance of blood-pressure-lowering effect following a missed dose of aliskiren, irbesartan or ramipril: results of a randomized, double-blind study

Most patients inadvertently miss an occasional dose of antihypertensive therapy, and hence drugs that provide sustained blood-pressure (BP) reduction beyond the 24-h dosing interval are desirable. The primary objective of this study was to compare the 24-h mean ambulatory BP reductions from baseline after a simulated missed dose of the direct renin inhibitor aliskiren, irbesartan or ramipril. In this double-blind study, 654 hypertensive patients (24-h mean ambulatory diastolic BP (MADBP) >or=85 mm Hg) were randomized 1:1:1 to once-daily aliskiren 150 mg, irbesartan 150 mg or ramipril 5 mg. Doses were doubled after 2 weeks. At day 42, patients were again randomized equally within each group to receive 1 day of placebo ('missed dose') on either day 42 or day 49. Patients with a successful 24-h ambulatory BP measurement at baseline and on day 42/49 were included in the analyses. The 24-h mean ambulatory systolic BP (MASBP)/MADBP reductions from baseline after a missed dose of aliskiren 300 mg (9.3/7.0 mm Hg) were similar to irbesartan 300 mg (9.5/7.3 mm Hg) and significantly larger than ramipril 10 mg (7.1/5.0 mm Hg, P<or=0.008). Loss of BP-lowering effect with aliskiren in the 24 h after a missed dose (1.0/0.7 mm Hg for 24-48-h vs 0-24-h MASBP/MADBP) was significantly lower than with irbesartan (3.6/2.2 mm Hg, P<0.01) or ramipril (4.0/2.6, P<0.0001). This equates to maintenance of 91/91% of the MASBP/MADBP-lowering effect with aliskiren, greater than irbesartan (73/77%) or ramipril (64/65%). The incidence of adverse events was similar across treatments (32.9-36.0%), although ramipril treatment was associated with an increased incidence of cough (ramipril, 6.1%; aliskiren, 0.5%; irbesartan, 1.8%). Aliskiren 300 mg provided a sustained BP-lowering effect beyond the 24-h dosing interval, with a significantly smaller loss of BP-lowering effect in the 24-48 h period after dose than irbesartan 300 mg or ramipril 10 mg.

Comparison of fixed-dose combinations of telmisartan/hydrochlorothiazide 40/12.5 mg and 80/12.5 mg and a fixed-dose combination of losartan/hydrochlorothiazide 50/12.5 mg in mild to moderate essential hypertension: Pooled analysis of two multicenter, prospective, randomized, open-label, blinded-end point (PROBE) trials

Background: High incidences of cardiovascularevents coincide with a surge in blood pressure (BP) that occurs in the early morning hours at the time of arousal. Thus, control of BP at this time of day, using oral fixed-dose combinations (FDCs) as required, is important in reducing cardiovascular risk in hypertensive patients. Objective: The aim of this analysis was to compare the annhypertensive efficacy in the early morning hours and tolerability of oral FDCs of telmisartan/hydrochlorothiazide (HCTZ) (40/12.5 mg [T40/H12.5] and 80/12.5 mg [T80/H12.5]) versus a low-dose FDC of losartan 50 mg/HCTZ 12.5 mg (L50/H12.5). Methods: Data from 2 similarly designed prospective, randomized, open-label, blinded-end point (PROBE) studies were pooled and analyzed. The studies were conducted at 72 centers across the United States, and 70 centers in Canada, Europe (9 countries), and the Philippines. Adult male and female patients with mild to moderate essential hypertension (24-hour mean ambulatory diastolic BP [DBP], ≥85 mm Hg; seated cuff DBP, 90–109 mm Hg) were enrolled. Patients were randomly assigned to receive T40/H12.5, L50/H12.5, or T80/H12.5, QD (morning) for 6 weeks. Antihypertensive efficacy was assessed using 24-hour ambulatory BP monitoring (ABPM) and cuff sphygmomanometry at trough, performed at baseline and on completion of active treatment. The primary end point was the reduction from baseline in mean ambulatory DBP over the last 6 hours of the dosing interval. Secondary end points included other ABPM- and clinic-derived changes in DBP and systolic BP (SBP), and control and response rates ( SBP response defined as 24-hour mean SBP <130 mm Hg and/or reduction from baseline ≥10 mm Hg; DBP response defined as 24-hour mean DBP <85 mm Hg or reduction from baseline ≥10 mm Hg; DBP control defined as 24-hour mean DBP <85 mm Hg). Tolerability was assessed using patient interview, spontaneous reporting, and clinical evaluation. Results: A total of 1402 patients were enrolled(876 men, 525 women; mean [SD] age, 53.1 [9.9] years) (T40/H12.5, n = 517; L50/H12.5, n = 518; and T80/H12.5, n = 367). With T40/H12.5, the mean reduction in last-6-hour mean ambulatory DBP was 1.8 mm Hg greater compared with that achieved with L50/H12.5 (−11.3 [0.4] vs −9.4 [0.4] mm Hg; P < 0.001), and with T80/H12.5, the mean reduction was 2.6 mm Hg greater compared with that achieved with L50/H12.5 (−12.0 [0.4] vs -9.4 [0.4] mm Hg; P < 0.001). Analysis of secondary end points found that greater BP reduction occurred with T40/H12.5 and T80/H12.5 compared with L50/H12.5. ABPM SBP control and response rates were similar between the 3 groups, but the ABPM DBP control and response rates were significantly higher with T80/H12.5 compared with L50/H12.5 (46.6% vs 34.0% [ P < 0.002] and 69.4% vs 55.0% [ P < 0.001], respectively). Clinic SBP and DBP control and response rates were higher with T40/H12.5 and T80/H12.5 compared with L50/H12.5 (SBP response, 80.4% and 80.8% vs 68.5% [both, P < 0.001]; DBP response, 66.1% and 67.4% vs 54.4% [both, P < 0.001]; DBP control, 56.5% and 56.4% vs 44.1% [both, P < 0.001] ). The 2 most commonly recorded adverse events (AEs) were headache (T40/H12.5, 2.9%; L50/H12.5, 3.3%; and T80/H12.5, 3.0%) and dizziness (1.2%, 2.1%, and 3.0%, respectively). Most AEs were mild to moderate. Conclusions: The results of this pooled analysis of2 PROBE studies in adult patients with mild to moderate essential hypertension suggest that T40/H12.5 and T80/H12.5 conferred greater DBP and SBP control compared with low-dose L50/H12.5, including during the last 6 hours of the dosing interval. All 3 treatments were well tolerated.

The efficacy of telmisartan compared with perindopril in patients with mild-to-moderate hypertension

In this study, efficacy of the angiotensin II type 1 receptor blocker telmisartan given as monotherapy was compared with that of perindopril monotherapy in patients with mild-to-moderate hypertension. After a 2-week, single-blind, placebo run-in period, 60 patients were randomised to double-blind, once-daily treatment with telmisartan 80 mg or perindopril 4 mg for 6 weeks. Clinic and ambulatory blood pressure measurements and clinical laboratory evaluation were performed at the end of the placebo run-in and active treatment phases. Both telmisartan and perindopril significantly (p < 0.0001) reduced clinic systolic blood pressure (SBP) and diastolic blood pressure (DBP) compared with baseline values. Also, both drugs significantly (p < 0.0001) reduced 24-h mean ambulatory SBP and DBP compared with baseline. Comparison of the mean hourly antihypertensive activities showed that the reduction in mean ambulatory DBP for the last 8 h of the dosing interval was significantly greater (p < 0.05) in telmisartan-treated patients. A 24-h mean DBP of <85 mmHg was observed in 66.6% of the telmisartan-treated patients but in only 46.6% of the perindopril-treated patients (p < 0.05). It is concluded that telmisartan and perindopril both produce significant reductions in clinic SBP and DBP, but the mean reduction in ambulatory DBP during the last 8 h of the dosing interval is greater in patients treated with telmisartan.

EFFICACY AND TOLERABILITY OF FIXED‐DOSE COMBINATIONS OF TELMISARTAN PLUS HCTZ COMPARED WITH LOSARTAN PLUS HCTZ IN PATIENTS WITH ESSENTIAL HYPERTENSION

SUMMARYTelmisartan, an angiotensin II receptor blocker, is an effective once‐daily antihypertensive agent available either alone or in fixed‐dose combination with hydrochlorothiazide (HCTZ). This multicentre, prospective, randomised, open‐label, blinded‐endpoint (PROBE) study assessed the efficacy and safety of six weeks' treatment with telmisartan 40 mg/HCTZ 12.5 mg (n=199) and telmisartan 80 mg/HCTZ 12.5 mg (n=200) versus losartan 50 mg/HCTZ 12.5 mg (n=198) in patients with mild to moderate essential hypertension. During the last six hours of the dosing interval, telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg reduced mean ambulatory diastolic blood pressure (DBP) to a greater extent than losartan 50 mg/HCTZ 12.5 mg (treatment differences 1.8 mmHg [p&lt;0.05] and 2.5 mmHg [p&lt;0.001], respectively). Telmisartan 80 mg/HCTZ 12.5 mg also lowered mean 24‐hour DBP by 2.3 mmHg more than losartan 50 mg/HCTZ 12.5 mg (p&lt;0.001). Telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg produced greater reductions in ambulatory systolic blood pressure versus losartan 50 mg/HCTZ 12.5 mg of 2.5 mmHg and 3.4 mmHg, respectively, during the last six hours of the dosing interval (p&lt;0.05), and of 2.1 mmHg and 3.4 mmHg, respectively, over the entire 24‐hour dosing interval (p&lt;0.05). All treatments were well tolerated.

Birth weight and 24-hour ambulatory blood pressure in nonproteinuric hypertensive pregnancy

Objective: The aim of this study was to examine the relationship between maternal ambulatory blood pressure monitor measurements during pregnancy and birth weight in a population of women considered to have hypertension according to conventional antenatal clinic measurement. Study Design: A prospective observational study was carried out within the obstetric departments of Leicester Royal Infirmary and Queen Charlotte’s Hospital. A total of 237 women were found to have hypertension (blood pressure ≥140/90 mm Hg) without significant proteinuria during examination in the antenatal assessment area. Sequential-day unit blood pressure recordings and a 24-hour automated ambulatory blood pressure recording were performed, and the results were compared with the principal outcome measure of birth weight. Results: A significant inverse association (gradient, –13.5; 95% confidence interval –23.4 to –3.6) was found between daytime ambulatory diastolic blood pressure measurement and birth weight. An increase of 5 mm Hg in daytime mean diastolic blood pressure was associated with a fall in birth weight of 68.5 g. This association remained after adjustment for potential confounders that included maternal age, maternal weight, smoking status, ethnicity, and gestational age at delivery. No such association was found between obstetric day unit assessment of blood pressure and birth weight. Conclusion: There is a significant association between blood pressure and birth weight in nonproteinuric hypertensive pregnancies. The best predictor of this association is the daytime mean ambulatory diastolic blood pressure measurement. This is further evidence that maternal blood pressure may be an important confounding and potentially genetic variable in the association between birth weight and subsequent adult hypertension. (Am J Obstet Gynecol 2000;183:633-7.)

Efficacy and Safety of Nifedipine Coat-Core versus Amlodipine in Patients With Mild to Moderate Essential Hypertension: Comparison of 24-Hour Mean Ambulatory Diastolic Blood Pressure.

BACKGROUND: Calcium channel blockers have been successfully used for the treatment of hypertension. In this study, the antihypertensive efficacy and safety of the dihydropyridine calcium channel blockers nifedipine coat-core 30 mg and amlodipine 5 mg were evaluated. METHODS: This multicenter, double-blind, prospective, randomized, parallel-arm study compared once daily administration of nifedipine coat-core 30 mg with once daily amlodipine 5 mg in subjects with mild-to-moderate essential hypertension. A 4-week placebo run-in period was followed by an 8-week active treatment period. Blood pressure reduction was measured by ambulatory blood pressure monitoring and casual office blood pressure measured by mercury sphygmomanometer. RESULTS: Nifedipine coat-core and amlodipine produced equivalent reductions in mean diastolic blood pressure, as determined by 24-hour ambulatory blood pressure monitoring. Mean reduction in diastolic blood pressure was 5.4 mmHg and 5.8 mmHg for nifedipine coat-core and amlodipine, respectively. Both drugs were well tolerated and neither treatment resulted in a significant change in heart rate. CONCLUSIONS: Nifedipine coat-core 30 mg once-daily is comparable to amlodipine 5 mg once-daily for blood pressure reduction.

Influence of isolated diastolic hypertension identified by ambulatory blood pressure on target organ damage

Clinical decisions and controlled studies in regard to hypertension have long emphasized the casual diastolic blood pressure (DBP). The influence of superimposition of high systolic blood pressure (SBP) on the target organ damage has been less studied. To assess the role of isolated diastolic hypertension without interference of superimposition of systolic hypertension, 171 subjects with normal blood pressure, isolated diastolic hypertension (SBP < 140 and DBP ≥ 90 mmHg) isolated systolic hypertension (SBP ≥ 140 and DBP < 90 mmHg) or combined hypertension (SBP ≥ 140 and DBP ≥ 90 mmHg) determined by mean 24-h ambulatory blood pressure were compared in relation to target organ damage including ECG abnormality related to hypertension, cardiac enlargement by chest X-ray, proteinuria and retinopathy. The incidence of target organ damage was lower in subjects with normal BP than in the other three groups. The incidence of target organ damage was almost significantly higher in patients with isolated systolic hypertension than in those with isolated diastolic hypertension. No significant difference in the incidence of complications existed between patients with isolated systolic and combined hypertension. These findings demonstrate that the severity of hypertensive complications is more closely related to mean ambulatory SBP than mean ambulatory DBP. The level of systolic BP is important for predicting the severity of target organ damage in patients with high diastolic BP, because there is a significant difference in the incidence of target organ damage between isolated diastolic hypertension and combined hypertension.

Effects of cessation of caffeinated-coffee consumption on ambulatory and resting blood pressure in men

Coffee consumption has been weakly linked to high blood pressure (BP). The hypothesis that cessation of caffeinated-coffee consumption lowers ambulatory BP was tested in men in a randomized trial. One hundred eighty-six middle-aged, normotensive, male, habitual caffeinated-coffee consumers were recruited. Of these subjects, 150 had sufficiently complete, ambulatory BP measurements for analysis. After 2 months of standard caffeinated-coffee consumption, subjects were randomized to consume an equal amount of the same standard caffeinated coffee or a standard decaffeinated coffee, or to discontinue coffee consumption for 2 months. Diet composition, body weight and exercise did not change. Resting BP and heart rate were not different between the groups before and after intervention. In comparison with the continued caffeinated-coffeegroup (control), the decaffeinated-coffee group revealed significant reductions in mean ambulatory systolic BP during the morning (−4.0 ± 11 mm Hg; p =0.014), afternoon (−5.3 ± 10 mm Hg; p = 0.001) and evening (−3.2 ± 10 mm Hg; p = 0.003) hours, reductions in mean ambulatory diastolic BP during the afternoon (−1.8 ± 10 mm Hg; p =0.063) and evening (−1.8 ± 10 mm Hg; p = 0.059) hours and no change in ambulatory heart rate. The group randomized to no coffee revealed significant reductions in ambulatory systolic BP during the morning (−4.1 ± 9 mm Hg; p = 0.007), afternoon (−3.3 ± 10 mm Hg; p =0.023) and evening (−2.2 ± 11 mm Hg; p = 0.015) hours, significant reductions in ambulatory diastolic BP during the afternoon (−2.6 ± 6 mm Hg; p = 0.006) and evening (−2.1 ± 6 mm Hg; p = 0.016) hours, and no significant change in ambulatory heart rate. This suggests that cessation of caffeinated coffee results in significant reductions in ambulatory systolic and diastolic BP in normotensive men, which are not apparent from resting BP measurements.