Addition of spironolactone in patients with resistant arterial hypertension (ASPIRANT): a randomized, double-blind, placebo-controlled trial

There is currently limited data on which drug should be used to improve blood pressure (BP) control in patients with resistant hypertension. This study was designed to assess the effect of the addition of 25 mg of spironolactone on BP in patients with resistant arterial hypertension. Patients with office systolic BP >140 mm Hg or diastolic BP >90 mm Hg despite treatment with at least 3 antihypertensive drugs, including a diuretic, were enrolled in this double-blind, placebo-controlled, multicenter trial. One hundred seventeen patients were randomly assigned to receive spironolactone (n=59) or a placebo (n=58) as an add-on to their antihypertensive medication, by the method of simple randomization. Analyses were done with 111 patients (55 in the spironolactone and 56 in the placebo groups). At 8 weeks, the primary end points, a difference in mean fall of BP on daytime ambulatory BP monitoring (ABPM), between the groups was -5.4 mm Hg (95%CI -10.0; -0.8) for systolic BP (P=0.024) and -1.0 mm Hg (95% CI -4.0; 2.0) for diastolic BP (P=0.358). The APBM nighttime systolic, 24-hour ABPM systolic, and office systolic BP values were significantly decreased by spironolactone (difference of -8.6, -9.8, and -6.5 mm Hg; P=0.011, 0.004, and 0.011), whereas the fall of the respective diastolic BP values was not significant (-3.0, -1.0, and -2.5 mm Hg; P=0.079, 0.405, and 0.079). The adverse events in both groups were comparable. In conclusion, spironolactone is an effective drug for lowering systolic BP in patients with resistant arterial hypertension.     

Effects of the renin inhibitor MK-8141 (ACT-077825) in patients with hypertension

The renin inhibitor MK-8141 (ACT-077825) demonstrates substantial immunoreactive active renin (ir-AR) increase (sevenfold) without a persistent plasma renin activity (PRA) decrease. The present study assessed the antihypertensive efficacy of MK-8141 in hypertensive patients. In this double-blind, placebo- and active comparator-controlled study, 195 patients with hypertension (trough sitting diastolic blood pressure ≥92 to <105 mm Hg, trough sitting systolic blood pressure <170 mm Hg, and 24-hour mean diastolic blood pressure [DBP] ≥80 mm Hg) were randomized to one of four treatments (stratified by race, black versus others): MK-8141 250 mg, MK-8141 500 mg, enalapril 20 mg, or placebo. Blood pressure was measured at trough and as 24-hour ambulatory blood pressure monitoring. The primary end point was change from baseline in 24-hour mean ambulatory DBP measured after 4 weeks. At week 4, the change from baseline in 24-hour mean (95% CI) ambulatory DBP compared with placebo was ?1.6 mm Hg (?4.2, 1.1), ?1.1 mm Hg (?3.9, 1.6), and ?4.9 (?7.5, ?2.2) for MK-8141 250 mg, MK-8141 500 mg, and enalapril 20 mg, respectively. Only mean ambulatory DBP-lowering with enalapril 20 mg was statistically significant. Enalapril, but not MK-8141, also significantly lowered 24-hour mean ambulatory systolic blood pressure (SBP) compared with placebo (?6.7 mm Hg [?10.5, ?2.8]). Neither enalapril nor MK-8141 significantly lowered trough DBP and SBP compared with placebo. MK-8141 was generally well tolerated. In patients with hypertension, MK-8141 (ACT-077825) did not produce significant blood pressure–lowering efficacy despite a demonstrated effect of the drug on ir-AR, in the absence of durable PRA suppression.     

Effect of calcium and vitamin D supplementation on blood pressure: the Women's Health Initiative Randomized Trial

Experimental and epidemiological studies suggest that calcium and vitamin D supplements may lower blood pressure. We examined the effect of calcium plus vitamin D supplementation on blood pressure and the incidence of hypertension in postmenopausal women. The Women's Health Initiative Calcium/Vitamin D Trial randomly assigned 36 282 postmenopausal women to receive 1000 mg of elemental calcium plus 400 IU of vitamin D3 daily or placebo in a double-blind fashion. Change in blood pressure and the incidence of hypertension were ascertained. Over a median follow-up time of 7 years, there was no significant difference in the mean change over time in systolic blood pressure (0.22 mm Hg; 95% CI: -0.05 to 0.49 mm Hg) and diastolic blood pressure (0.11 mm Hg; 95% CI: -0.04 to 0.27 mm Hg) between the active and placebo treatment groups. This null result was robust in analyses accounting for nonadherence to study pills and in baseline subgroups of interest, including black subjects and women with hypertension or high levels of blood pressure, with low intakes of calcium and vitamin D or low serum levels of vitamin D. In 17 122 nonhypertensive participants at baseline, the hazard ratio for incident hypertension associated with calcium/vitamin D treatment was 1.01 (95% CI: 0.96 to 1.06.) In postmenopausal women, calcium plus vitamin D3 supplementation did not reduce either blood pressure or the risk of developing hypertension over 7 years of follow-up.     

Little Effect of Ordinary Antihypertensive Therapy on Nocturnal High Blood Pressure in Patients with Sleep Disordered Breathing

The antihypertensive effects of four different antihypertensive medications (β-blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release] 2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement (ABPM).Eighteen patients were randomized in a double-blind, crossover fashion to receive each of the four different medications for 8 weeks. ABPM was performed at baseline and after an 8-week treatment with these medications. A 2- to 3-week washout period occurred both at baseline and between each of the four medications. Three patients were omitted from statistical analysis because of technical problems of ABPM.Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased significantly after all four medications: 12 (SD ± 14) mm Hg with atenolol, 7 (SD ± 10) mm Hg with isradipine SRO, 3 mm Hg (SD ± 14) with HCTZ, and 6 (SD ± 15) mm Hg with spirapril (P < .01). During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly. According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar. Atenolol and spirapril lost their antihypertensive effect during the early morning hours. The antihypertensive effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no medication was >0.50.Negative correlation was observed between the apnea time and the mean systolic 24-h (r = −0.604, P = NS) and the mean systolic nocturnal blood pressure change (r = −0.590, P = NS).Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension. Instead none of the medications used decreased nocturnal high blood pressure markedly.     

Lack of agreement between office and ambulatory blood pressure responses to hydrochlorothiazide

BACKGROUND: Differences between the antihypertensive responses to drug therapy measured by office blood pressure (OBP) and ambulatory blood pressure monitoring (ABPM) techniques have been noted but rarely analyzed. We studied whether the OBP and 24-h ABPM responses to hydrochlorothiazide differ and, if so, the relevance of these differences. METHODS: The OBP and ABPM responses to hydrochlorothiazide (25 mg/d, for 4 weeks) were measured in 228 subjects with essential hypertension, and mean responses were compared between methods using the Student paired t test. To assess variation in the agreement between OBP and ABPM responses among subjects, the limits of agreement were calculated as the mean difference between OBP and ABPM responses +/-2 standard deviations. RESULTS: The mean systolic OBP response was 4.8 mm Hg greater than the response measured by ABPM (-14.3 v -9.5 mm Hg, P < .001), and the mean diastolic OBP response was 2.1 mm Hg greater than the response measured by ABPM (-7.5 v -5.5, P < .001). The limits of agreement between the OBP and ABPM responses ranged from -18.7 to +28.2 mm Hg for systolic response and from -12.9 to +17.1 mm Hg for diastolic response. The systolic and diastolic OBP and ABPM responses were in opposite directions in 22.8% and 23.7% of the subjects, respectively. CONCLUSIONS: Compared to ABPM, OBP overestimates the mean systolic and mean diastolic blood pressure responses to hydrochlorothiazide. Variation among subjects in the magnitude and direction of responses renders OBP an unreliable predictor of ABPM responses.     

Combination therapy with amlodipine and captopril for resistant systemic hypertension

This study was conducted to assess the therapeutic utility of combining amlodipine with captopril in patients with moderate-to-severe hypertension. Patients had hypertension of WHO grades I–III, with initial mean sitting and standing diastolic blood pressure of 100–119 mm Hg (phase V) after 2–4 weeks on placebo, and had remained uncontrolled (diastolic blood pressure > 95 mm Hg) despite a further 4 weeks on low-dose captopril. Twenty-nine patients entered the computer-randomized, double-blind, placebocontrolled, 2-way crossover comparison of either amlodipine 10 mg once daily or matching placebo added to continued therapy with captopril 25 mg twice daily for 4 weeks. Patients then acted as their own control and received the alternative amlodipine/placebo treatment plus their continued captopril therapy for another 4 weeks. Once-daily amlodipine was shown to be effective when combined with captopril. Mean baseline supine systolic blood pressure decreased from 167 to 149 mm Hg and standing systolic blood pressure from 167 to 144 mm Hg. Mean supine diastolic blood pressure decreased from 105 to 92 mm Hg, and standing diastolic blood pressure decreased from 110 to 96 mm Hg. The placebo-corrected amlodipine differences in mean changes from captopril baseline were −18/−12.2 mm Hg for supine and −20.1/−11.9 mm Hg for standing systolic and diastolic blood pressures, respectively (p < 0.001 for all 4 measurements). The most common side effects encountered with amlodipine were flushing and pedal edema. The combination of amlodipine and captopril was well tolerated, and no patient discontinued therapy. No significant treatment-related effects on biochemical and hematologic parameters were noted.     

Management of hypertension in patients with diabetes using an amlodipine-, olmesartan medoxomil-, and hydrochlorothiazide-based titration regimen

The safety and efficacy of an amlodipine/olmesartan medoxomil (OM)-based titration regimen was assessed in patients with type 2 diabetes mellitus and hypertension. After a 2- to 3-week placebo run-in period, 207 patients received amlodipine 5 mg and were uptitrated to amlodipine/OM 5/20, 5/40, and 10/40 mg and then amlodipine/OM 10/40 mg plus hydrochlorothiazide 12.5 and 25 mg in a step-wise manner at 3-week intervals if the seated blood pressure (BP) remained ≥120/70 mm Hg. The primary end point was the change from baseline in the mean 24-hour ambulatory systolic BP after 12 weeks of treatment. The baseline mean ± SD seated cuff systolic/diastolic BP was 158.8 ± 13.1/89.1 ± 10.1 mm Hg and the mean ± SD 24-hour ambulatory systolic/diastolic BP was 144.4 ± 11.7/81.6 ± 9.8 mm Hg. At week 12, the change from baseline in the mean ± SEM 24-hour ambulatory systolic/diastolic BP was -19.9 ± 0.8/-11.2 ± 0.5 mm Hg (p<0.0001 vs baseline), and 70% of patients had achieved a 24-hour ambulatory BP target of <130/80 mm Hg. At the end of 18 weeks of active treatment in patients uptitrated to amlodipine/OM 10/40 mg plus hydrochlorothiazide 25 mg, the change from baseline in the mean ± SEM seated BP was -28.0 ± 1.5/-13.7 ± 1.0 mm Hg (p<0.0001 vs baseline), with 62% of patients reaching the guideline-recommended seated BP goal of <130/80 mm Hg. Drug-related treatment-emergent adverse events occurred in 19.3% of patients. The most frequent events were peripheral edema (6%), dizziness (3%), and hypotension (2%). In conclusion, this amlodipine/OM-based titration regimen was well tolerated and effectively lowered BP throughout the 24-hour dosing interval in patients with hypertension and type 2 diabetes.     

Control of hypertension in adults with chronic kidney disease in the United States

Although improved control of hypertension is known to attenuate progression of chronic kidney disease (CKD), little is known about the adequacy of hypertension treatment in adults with CKD in the United States. Using data from the Fourth National Health and Nutrition Survey, we assessed adherence to national hypertension guideline targets for patients with CKD (blood pressure <130/80 mm Hg), we assessed control of systolic (<130 mm Hg) and diastolic (<80 mm Hg) blood pressure, and we evaluated determinants of adequate blood pressure control. Presence of CKD was defined as glomerular filtration rate <60 mL/min per 1.73 m2 or presence of albuminuria (albumin:creatinine ratio >30 microg/mg). Multivariable logistic regression with appropriate weights was used to determine predictors of inadequate hypertension control and related outcomes. Among 3213 participants with CKD, 37% had blood pressure <130/80 mm Hg (95% confidence interval [CI], 34.5% to 41.8%). Of those with inadequate blood pressure control, 59% (95% CI, 54% to 64%) had systolic >130 mm Hg, with diastolic < or =80 mm Hg, whereas only 7% (95% CI, 3.9 to 9.8%) had a diastolic pressure >80 mm Hg, with systolic blood pressure < or =130 mm Hg. Non-Hispanic black race (odds ratio [OR], 2.4; 95% CI, 1.5 to 3.9), age >75 years (OR, 4.7; 95% CI, 2.7 to 8.2), and albuminuria (OR, 2.4; 95% CI, 1.4 to 4.1) were independently associated with inadequate blood pressure control. We conclude that control of hypertension is poor in participants with CKD and that lack of control is primarily attributable to systolic hypertension. Future guidelines and antihypertensive therapies for patients with CKD should target isolated systolic hypertension.     

Long-term effect of continuous positive airway pressure on BP in patients with hypertension and sleep apnea

OBJECTIVE: To analyze the long-term effect of continuous positive airway pressure (CPAP) on ambulatory BP in patients with obstructive sleep apnea (OSA) and hypertension, and to identify subgroups of patients for whom CPAP could be more effective. METHODS: We conducted a prospective, long-term follow-up trial (24 months) in 55 patients with OSA and hypertension (mean CPAP use, 5.3 +/- 1.9 h/d [+/- SD]). Twenty-four-hour ambulatory BP monitoring (ABPM) was measured at baseline and after intervention with CPAP on an intention-to-treat basis. In addition, the correlation between the changes in 24-h mean arterial pressure (24hMAP) and CPAP compliance, OSA severity, and baseline ABPM was assessed. RESULTS: At the end of follow-up, a significant decrease was shown only in diastolic BP (- 2.2 mm Hg; 95% confidence interval [CI], - 4.2 to - 0.1; p = 0.03) but not in 24hMAP or other ABPM parameters. However, a correlation between changes in 24hMAP and baseline systolic BP (r = - 0.43, p = 0.001), diastolic BP (r = - 0.38, p = 0.004), and hours of use of CPAP (r = - 0.30, p = 0.02) was observed. A significant decrease in the 24hMAP was achieved in a subgroup of patients with incompletely controlled hypertension at entry (- 4.4 mm Hg; 95% CI, - 7.9 to - 0.9 mm Hg; p = 0.01), as well as in those with CPAP compliance > 5.3 h/d (- 5.3 mm Hg; 95% CI, - 9.5 to - 1.2 mm Hg; p = 0.01). Linear regression analysis showed that baseline systolic BP and hours of CPAP were independent predictors of reductions in BP with CPAP. CONCLUSION: Long-term CPAP reduced BP modestly in the whole sample. However, patients with higher BP at entry and good CPAP compliance achieved significant reductions in BP.     

Comparison of the efficacy and safety of azilsartan with that of candesartan cilexetil in Japanese patients with grade I-II essential hypertension: a randomized, double-blind clinical study

Azilsartan is a novel angiotensin receptor blocker being developed for hypertension treatment. This 16-week, multicenter, randomized, double-blind study compared the efficacy and safety of azilsartan (20-40 mg once daily by forced titration) and its ability to provide 24-h blood pressure (BP) control, with that of candesartan cilexetil (candesartan; 8-12 mg once daily by forced titration) in 622 Japanese patients with grade I-II essential hypertension. Efficacy was evaluated by clinic-measured sitting BP, and by ambulatory BP monitoring (ABPM) at week 14. Participants (mean age: 57 years, 61% males) had a mean baseline sitting BP of 159.8/100.4 mm Hg. The mean change from baseline in sitting diastolic BP at week 16 (primary endpoint) was -12.4 mm Hg in the azilsartan group and -9.8 mm Hg in the candesartan group, demonstrating a statistically significant greater reduction with azilsartan vs. candesartan (difference: -2.6 mm Hg, 95% confidence interval (CI): -4.08 to -1.22 mm Hg, P=0.0003). The week 16 (secondary endpoint) mean change from baseline in sitting systolic BP was -21.8 mm Hg and -17.5 mm Hg, respectively, a significant decrease with azilsartan vs. candesartan (difference: -4.4 mm Hg, 95% CI: -6.53 to -2.20 mm Hg, P<0.0001). On ABPM, the week 14 mean changes from baseline in diastolic and systolic BP were also significantly greater with azilsartan over a 24-h period, and during the daytime, night-time and early morning. Safety and tolerability were similar among the two groups. These data demonstrate that once-daily azilsartan provides a more potent 24-h sustained antihypertensive effect than that of candesartan but with equivalent safety.     

Isolated diastolic hypotension and incident heart failure in older adults

Aging is often associated with increased systolic blood pressure and decreased diastolic blood pressure. Isolated systolic hypertension or an elevated systolic blood pressure without an elevated diastolic blood pressure is a known risk factor for incident heart failure in older adults. In the current study, we examined whether isolated diastolic hypotension, defined as a diastolic blood pressure <60 mm Hg and a systolic blood pressure ≥100 mm Hg, is associated with incident heart failure. Of the 5795 Medicare-eligible community-dwelling adults age ≥65 years in the Cardiovascular Health Study, 5521 were free of prevalent heart failure at baseline. After excluding 145 individuals with baseline systolic blood pressure <100 mm Hg, the final sample included 5376 participants, of whom 751 (14%) had isolated diastolic hypotension. Propensity scores for isolated diastolic hypotension were calculated for each of the 5376 participants and used to match 545 and 2348 participants with and without isolated diastolic hypotension, respectively, who were balanced on 58 baseline characteristics. During >12 years of median follow-up, centrally adjudicated incident heart failure developed in 25% and 20% of matched participants with and without isolated diastolic hypotension, respectively (hazard ratio associated with isolated diastolic hypotension: 1.33 [95% CI: 1.10-1.61]; P=0.004). Among the 5376 prematch individuals, multivariable-adjusted hazard ratio for incident heart failure associated with isolated diastolic hypotension was 1.29 (95% CI: 1.09-1.53; P=0.003). As in isolated systolic hypertension, among community-dwelling older adults without prevalent heart failure, isolated diastolic hypotension is also a significant independent risk factor for incident heart failure.     

The comparative effects of azilsartan medoxomil and olmesartan on ambulatory and clinic blood pressure

The current study assesses the antihypertensive efficacy and safety of the investigational angiotensin receptor blocker (ARB), azilsartan medoxomil (AZL-M), compared with placebo and the ARB olmesartan medoxomil (OLM-M). This randomized, double-blind, placebo-controlled, multicenter study assessed change from baseline in mean 24-hour ambulatory systolic blood pressure (SBP) following 6 weeks of treatment. Patients with primary hypertension (n=1275) and baseline 24-hour mean ambulatory systolic pressure ≥ 130 mm Hg and ≤ 170 mm Hg were studied; 142 received placebo and the remainder received 20 mg, 40 mg, or 80 mg AZL-M or 40 mg OLM-M. Mean age of participants was 58 ± 11 years, baseline mean 24-hour SBP was 146 mm Hg. Dose-dependent reductions in 24-hour mean SBP at study end occurred in all AZL-M groups. Reduction in 24-hour mean SBP was greater with AZL-M 80 mg than OLM-M 40 mg by 2.1 mm Hg (95% confidence interval, -4.0 to -0.1; P=.038), while AZL-M 40 mg was noninferior to OLM-M 40 mg. The side effect profiles of both ARBs were similar to placebo. AZL-M is well tolerated and more efficacious at its maximal dose than the highest dose of OLM-M.     

Antihypertensive effect of valsartan 80 mg and hydrochlorothiazide 12.5 mg evaluated by ambulatory blood pressure monitoring

OBJECTIVE: The aim of the study was to evaluate by ambulatory blood pressure measurement (ABPM) the 24 hours antihypertensive efficacy of the fixed combination therapy, valsartan 80 mg + hydrochlorothiazide 12.5 mg (V + H), once daily, after 6 weeks of treatment, in patients with mild to moderate hypertension. STUDY DESIGN: It was a French, multicenter, double blind, randomized trial in parallel groups comparing V + H and placebo. After an initial two weeks placebo period, patients were assigned to receive either V + H or placebo for six weeks. Were eligible those with clinical arterial blood pressure, measured by sphygmomanometer, between 160/95 and 209/114 mmHg after monotherapy. A 26 hours ABPM, with Spacelabs 90,207, was done at J0 and J42 (one measurement every 15 minutes, in day time and at night). Responders were defined as a fall in day diastolic blood pressure > or = 5 mmHg and/or day diastolic blood pressure < 90 mmHg with ABPM. RESULTS: 123 of the 138 randomized patients had two interpretative measurements. Their average age was 59 + 10 years. 57% (78) of them were males and their average ABPM before treatment was 143 +/- 15/88 +/- 11 mmHg. With V + H, the reduction of the systolic and the diastolic blood pressure measured by ABPM, was significantly more important than with placebo (SBP: -15.4 +/- 10.9 mmHg versus -0.6 +/- 7.7 mmHg, p < 0.001; DBP: -9.1 +/- 7 mmHg versus -0.4 +/- 5.4 mmHg, p < 0.001). Pulse pressure (PP) was also significantly reduced with the combination therapy V + H, but it was not modified with placebo (-6.3 + 5.5 mmHg versus -0.2 + 4.1 mmHg, p < 0.001). ABPM responder rate was 73% with V + H versus 24% with placebo (p < 0.001). Trough/peak ratio was 80.3% for systolic blood pressure and 57.3% for diastolic blood pressure. The combination V + H was as well tolerated as placebo. CONCLUSION: The fixed combination V + H used for treatment of hypertension, after failure of monotherapy, is very effective in reducing pulse pressure, systolic and diastolic blood pressure, over 24 hours, homogeneously, and is as well tolerated as placebo.     

Prognostic importance of ambulatory arterial pressure monitoring in France. Initial results of the OCTAVE II study. OCTAVE II Research Group]

RATIONALE: Ambulatory blood pressure measurement (ABPM) is commonly used in clinical practice, whereas its added value to the management of hypertension is not definitely documented. OBJECTIVE: The OCTAVE II study was launched in 1991 to explore the prognostic value of ABPM, compared to that of the gold standard, the clinical blood pressure measurement. METHODS: Two hundred and six French cardiologists recruited 3569 participants over 18 years of age, provided they deemed ABPM was useful (mean age of 56 years, 52% of men, 65% already treated by antihypertensive drugs). The prognostic value of various blood pressure measurements, systolic or diastolic, clinical or ambulatory (diurnal, nocturnal or during 24 hours), has been assessed in multivariate models adjusted on the baseline characteristics associated with risk. The outcome was the occurrence of a major cardiovascular event, including stroke, myocardial infarction and cardiovascular death. RESULTS: After an average follow-up of five years, cardiovascular morbidity was known for 85% of the participants, and their vital status for 91%. On the whole population, the best prognostic indicators were systolic blood pressure compared with diastolic, ABPM compared with clinical blood pressure measurements, and nocturnal ABPM compared with diurnal ABPM. In the untreated participants at baseline, cardiovascular risk regularly increased among the four groups: normotensives, white-coat hypertensives, dippers, non-dippers. Between the extreme categories, the cardiovascular event rate was multiplied by 6.5. CONCLUSION: In this French population, ABPM and most of all its nocturnal component, was better correlated with cardiovascular prognosis. It remains to assess: 1) the general value of our findings, 2) the respective values of self blood pressure measurement versus ABPM, and 3) whether ABPM allows a better risk prevention.     

Coenzyme Q10 in the treatment of hypertension: a meta-analysis of the clinical trials

Our objective was to review all published trials of coenzyme Q10 for hypertension, assess overall efficacy and consistency of therapeutic action and side effect incidence. Meta-analysis was performed in 12 clinical trials (362 patients) comprising three randomized controlled trials, one crossover study and eight open label studies. In the randomized controlled trials (n=120), systolic blood pressure in the treatment group was 167.7 (95% confidence interval, CI: 163.7-171.1) mm Hg before, and 151.1 (147.1-155.1) mm Hg after treatment, a decrease of 16.6 (12.6-20.6, P<0.001) mm Hg, with no significant change in the placebo group. Diastolic blood pressure in the treatment group was 103 (101-105) mm Hg before, and 94.8 (92.8-96.8) mm Hg after treatment, a decrease of 8.2 (6.2-10.2, P<0.001) mm Hg, with no significant change in the placebo group. In the crossover study (n=18), systolic blood pressure decreased by 11 mm Hg and diastolic blood pressure by 8 mm Hg (P<0.001) with no significant change with placebo. In the open label studies (n=214), mean systolic blood pressure was 162 (158.4-165.7) mm Hg before, and 148.6 (145-152.2) mm Hg after treatment, a decrease of 13.5 (9.8-17.1, P<0.001) mm Hg. Mean diastolic blood pressure was 97.1 (95.2-99.1) mm Hg before, and 86.8 (84.9-88.8) mm Hg after treatment, a decrease of 10.3 (8.4-12.3, P<0.001) mm Hg. We conclude that coenzyme Q10 has the potential in hypertensive patients to lower systolic blood pressure by up to 17 mm Hg and diastolic blood pressure by up to 10 mm Hg without significant side effects.     

Azilsartan in Patients With Mild to Moderate Hypertension Using Clinic and Ambulatory Blood Pressure Measurements

This was a phase 2, multicenter, randomized, parallel-group, double-blind dose-ranging study. Hypertensive adults (n=555) received one of five doses of azilsartan (AZL; 2.5, 5, 10, 20, 40 mg), olmesartan medoxomil (OLM) 20 mg, or placebo once daily. The primary endpoint was change in trough clinic diastolic blood pressure (DBP) at week 8. Compared with placebo, all AZL doses (except 2.5 mg) provided statistically and clinically significant reductions in DBP and systolic blood pressure (SBP) based on both clinic blood pressure (BP) and 24-hour ambulatory BP monitoring (ABPM). AZL 40 mg was statistically superior vs OLM. Clinic BP was associated with a pronounced placebo effect (−6 mm Hg), whereas this was negligible with ABPM (±0.5 mm Hg). Adverse event frequency was similar in the AZL and placebo groups. Based on these and other findings, subsequent trials investigated the commercial AZL medoxomil tablet at doses 20 to 80 mg/d using 24-hour ABPM.     

Ambulatory Blood Pressure Monitoring to Assess the White‐Coat Effect in an Elderly East African Population

The authors hypothesized that published hypertension rates in Tanzania were influenced by the physiological response of individuals to blood pressure (BP) testing, known as the white‐coat effect (WCE). To test this, a representative sample of 79 participants from a baseline cohort of 2322 people aged 70 years and older were followed to assess BP using conventional BP measurement (CBPM) and ambulatory BP monitoring (ABPM). There was a significant difference between daytime ABPM and CBPM for both systolic BP (mean difference 29.7 mm Hg) and diastolic BP (mean difference 7.4 mm Hg). Rates of hypertension were significantly lower when measured by 24‐hour ABPM (55.7%) than by CBPM (78.4%). The WCE was observed in 54 participants (68.4%). The WCE was responsible for an increase in recorded BP. Accurate identification of individuals in need of antihypertensive medication is important if resources are to be used efficiently, especially in resource‐poor settings.     

比索洛尔/氢氯噻嗪复方片治疗中国轻中度原发性高血压的临床疗效和安全性研究

目的采用24小时动态血压监测观察比索洛尔／氢氯噻嗪复方片(Lodoz)治疗90例中国轻、中度高血压患者的降压效果和安全性。方法选择90例收缩压<180 mm Hg(1 mm Hg= 0．133 kPa),舒张压95-109 mm Hg的轻、中度高血压患者,口服Lodoz(2．5 mg/6．25 mg)共4周或Lodoz(5 mg／6．25 mg)8周,用24小时动态血压监测评价治疗4周、8周后动态血压变化及安全性。结果(1)4周和8周末诊室收缩压/舒张压分别降低(14．89±10．99)／(10．37±7．35)mm Hg和(19．40±10．55)／(13．31±7．77)mm Hg,全天、日间、夜间的24小时动态平均血压均明显降低,差异有统计学意义(P均<0．05)。4周和8周末的总有效率分别为59．3％和69．8％。(2)Lodoz(2．5 mg／6．25 mg)对收缩压和舒张压的谷／峰比值(T／P比值)分别为91．5％和94．4％,降压平滑指数(SI)为9．07／6．48;Lodoz(5 mg／6．25 mg)对收缩压和舒张压的T／P比值为79．9％和80．5％,SI为4．17／4．47。(3)Lodoz可能有使“非勺型”血压转变为“勺型”血压的趋势。(4)不良反应主要有血尿酸升高、头晕、头痛、腹泻、口干、肢端发凉、蚁行感,均为轻度。结论Lodoz能够持续、平稳、有效地降低24小时血压,且安全性良好。     

Retinal vessel diameters and risk of hypertension: the Rotterdam Study

Generalized retinal arteriolar narrowing is an important sign of systemic hypertension, and a lower arteriolar:venular diameter ratio predicts the risk of hypertension. We investigated whether this association was based on arteriolar or venular diameters or both. This study was based on the prospective population-based Rotterdam Study (1990-1993) and included 1900 participants (> or =55 years of age) of whom 739 persons had normal blood pressure (systolic <120 mm Hg and diastolic <80 mm Hg) and 1161 prehypertension (systolic 120 to 139 mm Hg or diastolic 80 to 89 mm Hg). For each participant, retinal arteriolar and venular diameters were measured on digitized images of 1 eye. After a mean follow-up of 6.6 years, 808 persons developed hypertension, defined as either systolic blood pressure > or =140 mm Hg or diastolic blood pressure > or =90 mm Hg or use of antihypertensive medication. Adjusted for age, gender, follow-up time, body mass index, smoking, diabetes mellitus, total and high-density lipoprotein cholesterol, C-reactive protein, and intima-media thickness, arteriolar narrowing was associated with an increased risk of hypertension (odds ratio per SD: 1.38; 95% CI, 1.23 to 1.55); for venular narrowing this was less striking (OR: 1.17; 95% CI, 1.04 to 1.32). Each SD decrease in the arteriolar:venular diameter ratio significantly increased the risk of hypertension by 24%. To examine the effect of baseline blood pressure, we stratified persons into those with "normal blood pressure" or "prehypertension." Within these strata, arteriolar narrowing was still related to incident hypertension. These data show that both retinal arteriolar and venular narrowing may precede the development of systemic hypertension.     

Hypertension, exercise, and beta-adrenergic blockade

STUDY OBJECTIVE: To determine whether beta-adrenergic blocking agents affect exercise tolerance, exercise conditioning response, and blood pressure response to conditioning in hypertensive patients. DESIGN: Randomized, double-blinded, placebo-controlled trial with a 10-week exercise period. SETTING: Outpatient, monitored exercise program at a community-based, university-sponsored cardiac rehabilitation facility. PATIENTS: Thirty adults with mean resting blood pressure of 145 mm Hg or greater (systolic), 95 mm Hg or greater (diastolic), or a combined systolic and diastolic pressure of 140/90 mm Hg or greater. Mean systolic pressure of 170 mm Hg or more or mean diastolic pressure of 105 mm Hg or more was exclusionary. Mean blood pressure was 145/95 mm Hg; mean age was 46.5 years. INTERVENTION: The beta-1-nonselective blocker was propranolol, 80 mg twice daily. The beta-1-selective blocker was metoprolol, 100 mg twice daily, compared with placebo. All patients did exercise conditioning consisting of 40 sessions of aerobic exercise with heart rate monitoring. MEASUREMENTS AND MAIN RESULTS: Resting systolic blood pressure measured without drug therapy was lowered markedly after exercise conditioning on placebo (146 to 135 mm Hg) and on metoprolol (144 to 133 mm Hg) (P less than 0.05), but not on propranolol (no change). Acutely, propranolol decreased both maximal oxygen consumption (VO2max) and exercise duration compared with metoprolol and placebo. Chronically, VO2max increased 24% (95% CI, 8 to 40) in response to training on placebo and 8% on metoprolol (95% CI, 3 to 14); it did not increase on propranolol (95% CI, -10 to 15). CONCLUSIONS: If an exercise program is to be recommended as an adjunct to pharmacologic beta-blockade for hypertension, blood-pressure-lowering effects are preserved and exercise capacity is less affected with a beta-1-selective agent than with a beta-1-nonselective agent. Antihypertensive medications may be avoided altogether for selected patients who sustain an aerobic exercise program.