Marked sympathetic activation and baroreflex dysfunction in true resistant hypertension.

BACKGROUND: An increase in sympathetic drive to the heart and the peripheral circulation characterizes mild and severe essential hypertension. However, it remains unsettled whether sympathetic cardiovascular influences are potentiated in true resistant hypertension (RHT). METHODS: In 32 RHT patients treated with 4.6 ± 0.3 drugs (mean ± SEM) and aged 58.6 ± 2.1 years, 35 non-resistant treated hypertensives (HT) and 19 normotensive controls (NT), all age-matched with RHT, we measured clinic, 24-hour ambulatory and beat-to-beat blood pressures (BP), heart rate (HR, EKG), muscle sympathetic nerve traffic (MSNA, microneurography) and spontaneous baroreflex MSNA-sensitivity. RESULTS: BP values were markedly greater in RHT patients than in NT and HT (172.2 ± 1.7/100.7 ± 1.2 vs 132.1 ± 1.3/82.1 ± 0.9 and 135.5 ± 1.2/83.6 ± 0.9 mmHg, P < 0.01). This was paralleled by a significant and marked increase in MSNA (87.8 ± 2.0 vs 46.8 ± 2.6 and 59.3 ± 1.7 and bursts/100 heartbeats, P < 0.01). In multiple regression analysis the MSNA increase observed in RHT was significantly related to hemodynamic, hormonal and metabolic variables. It was also significantly related to plasma aldosterone values as well as spontaneous baroreflex MSNA-sensitivity, which were the variables that at the multivariate analysis were more closely related to the adrenergic activation of RHT after adjustment for confounders, including antihypertensive treatment (r(2)partial=0.04405 and r(2)partial=0.00878, P<0.05 for both). CONCLUSIONS: These data represent the first evidence that RHT is a state of marked adrenergic overdrive, greater for magnitude than that detectable in HT. They also suggest that impaired baroreflex mechanisms, along with hemodynamic and neurohumoral factors, may be responsible for the phenomenon.

Effectiveness of barnidipine 10 or 20 mg plus losartan 50-mg combination versus losartan 100-mg monotherapy in patients with essential hypertension not controlled by losartan 50-mg monotherapy: A 12-week, multicenter, randomized, open-label, parallel-group study.

BACKGROUND: Increasing the dose or adding a second antihypertensive agent are 2 possible therapeutic choices when blood pressure (BP) is poorly controlled with monotherapy. OBJECTIVE: This study investigated the effectiveness and tolerability of barnidipine 10 or 20 mg added to losartan 50 mg versus losartan 100 mg alone in patients with mild to moderate essential hypertension whose BP was uncontrolled by losartan 50-mg monotherapy. METHODS: This was a 12-week, multicenter, randomized, open-label, parallel-group study. Eligible patients (aged 30-74 years) had uncontrolled hypertension, defined as office sitting diastolic BP (DBP) > or =90 mm Hg and/or systolic BP (SBP) > or =140 mm Hg, and mean daytime DBP > or =85 mm Hg and/or SBP > or =135 mm Hg. All were being treated with losartan 50 mg at enrollment. After a 1-week run-in period while taking losartan 50 mg, patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg or losartan 100-mg monotherapy. At the end of this period, patients with uncontrolled BP had barnidipine doubled to 20 mg and continued for an additional 6 weeks, whereas patients not achieving control on treatment with losartan 100 mg were discontinued. Office BP was measured at each visit, whereas 24-hour ambulatory BP monitoring (ABPM) was performed at randomization and at the final visit (ie, after 12 weeks of treatment, or at 6 weeks for patients not controlled on losartan 100 mg). The intent-to-treat population included all randomized patients who received at least one dose of study treatment and had valid ABPM recordings at baseline and the final visit. The primary end point was the change in daytime DBP between baseline and 12 weeks of treatment, compared between the combination treatment and monotherapy. Adverse events (AEs) were evaluated during each study visit. RESULTS: A total of 93 patients were enrolled (age range, 30-75 years; 60% [56/93] men). After the 1-week run-in period, 68 patients were randomly assigned to 6 weeks of treatment with open-label barnidipine 10 mg plus losartan 50 mg (n = 34) or losartan 100-mg monotherapy (n = 34). A total of 53 patients were evaluable (barnidipine plus losartan, n = 28; losartan, n = 25). After 6 weeks of treatment, 18 patients in the combination treatment group (64.3%) had their dose of barnidipine doubled from 10 to 20 mg because BP was not normalized by treatment, whereas 8 patients in the losartan group (32.0%) were discontinued for the same reason. The between-treatment difference (losartan alone - combination treatment) for changes from baseline in daytime DBP was -1.7 mm Hg (95% CI, -5.8 to 2.4 mm Hg; P = NS). A similar result was observed for daytime SBP (-3.2 mm Hg; 95% CI, -8.1 to 1.7 mm Hg; P = NS). Likewise, no significant differences were found for nighttime values (mean [95% CI] DBP, 0.5 mm Hg [-3.7 to 4.7 mm Hg]; SBP, 1.5 mm Hg [-4.1 to 7.1 mm Hg]) or 24-hour values (DBP, -0.9 mm Hg [-4.8 to 2.9 mm Hg]; SBP, -1.6 mm Hg [-5.9 to 2.7 mm Hg]). Combination treatment was associated with a significantly higher rate of SBP responder patients (ie, <140 mm Hg or a reduction of > or =20 mm Hg) compared with monotherapy (82.1% [23/28] vs 56.0% [14/25]; P = 0.044). Drug-related AEs were reported in 4 patients taking combination treatment (total of 7 AEs, including 2 cases of peripheral edema and 1 each of tachycardia, atrial flutter, tinnitus, confusion, and polyuria) and in 2 patients taking losartan alone (total of 2 AEs, both tachycardia). CONCLUSIONS: This open-label, parallel-group study found that there was no significant difference in the BP-lowering effect of barnidipine 10 or 20 mg in combination with losartan 50 mg compared with losartan 100-mg monotherapy in these patients with essential hypertension previously uncontrolled by losartan 50-mg monotherapy. However, the percentage of responders for SBP was significantly higher with the combination. Both treatments were generally well tolerated. European Union Drug Regulating Authorities Clinical Trials (EudraCT) no. 2006-001469-41.

PA.NET International Quality Certification Protocol for blood pressure monitors.

Although standard validation protocols provide assurance of the accuracy of blood pressure monitors (BPMs), there is no guidance for the consumer as to the overall quality of a device. The PA.NET International Quality Certification Protocol, developed by the Association for Research and Development of Biomedical Technologies and for Continuing Medical Education (ARSMED), a nonprofit organization, with the support of the Italian Society of Hypertension-Italian Hypertension League, and the dabl Educational Trust denotes additional criteria of quality for BPMs that fulfilled basic validation criteria, published in full in peer-reviewed medical journals. The certification is characterized by three phases: (i) to determine that the device fulfilled standard validation criteria; (ii) to determine the technical and functional characteristics of the device (e.g. operativity, display dimension, accessory functions, memory availability, etc.) and (iii) to determine the commercial characteristics (e.g. price-quality ratio, after-sale service, guarantee, etc.). At the end of the certification process, ARSMED attributes a quality index to the device, based on a scale ranging from 1 to 100, and a quality seal with four different grades (bronze, silver, gold and diamond) according to the achieved score. The seal is identified by a unique alphanumeric code. The quality seal may be used on the packaging of the appliance or in advertising. A quality certification is released to the manufacturer and published on www.pressionearteriosa.net and www.dableducational.org. The PA.NET International Quality Certification Protocol represents the first attempt to provide health care personnel and consumers with an independent and objective assessment of BPMs based on their quality.

The Hyper-Pract Study : a multicentre survey on the accuracy of the echocardiographic assessment of hypertensive left ventricular hypertrophy in clinical practice.

Left ventricular hypertrophy (LVH) assessed by echocardiography has a relevant impact in clinical decision making in hypertensive patients. We investigated the precision and accuracy of hypertensive LVH determination in current clinical practice by a regional-based survey. The study included 211 patients with essential hypertension consecutively attending six hospital outpatient hypertension clinics in the northern Italian region of Lombardy; all subjects had undergone an echocardiographic examination for hypertension-related problems in a non-academic or research ultrasound laboratory within 2 years. The original echocardiographic report was examined to ascertain whether the diagnosis of LVH was based on calculation of left ventricular (LV) mass according to validated formulae and indexed to body size (primary outcome) and whether LV geometrical patterns and indices of diastolic function were provided (secondary outcome). A total of 211 echocardiograms performed by 120 physicians operating in 73 different hospital and out-of-hospital ultrasound laboratories were collected. Absolute LV mass, LV mass index and relative wall thickness were calculated in 45.5%, 24.6% and 12.3% of the cases, respectively. Parameters of LV diastolic filling were measured in two-thirds of the cases and estimation of E/A ratio was provided by less than 20% of the examinations. This study shows that a large majority of echocardiographic examinations, routinely performed in hypertensive subjects in order to detect cardiac damage, do not report qualifying data on LV mass, LV geometry and diastolic function. These results indicate that a quantitative assessment of LVH and LV function is rarely provided in clinical practice.

Validation of the Artsana CS 410 automated blood pressure monitor in adults according to the International Protocol of the European Society of Hypertension.

BACKGROUND: Electronic blood pressure monitoring devices are widely used by patients for monitoring their blood pressure at home. Few of them, however, have been validated against recognized protocols and proved to be accurate. OBJECTIVE: This study aimed at verifying whether the automatic electronic oscillometric blood pressure measuring device, Artsana CS 410 (Artsana S.p.A., Grandate, Como, Italy), complied with the standard of accuracy indicated by the European Society of Hypertension (ESH) International Protocol. METHODS: Sequential measurements of systolic and diastolic blood pressure were obtained in 33 patients (13 males, 20 females, mean age+/-SD 49+/-12 years) using the mercury sphygmomanometer (two observers) and the test device (one supervisor). A standard adult cuff was always used during the study. According to the ESH validation protocol, 99 pairs of test device and reference blood pressure measurements were obtained during the two phases of the study (three pairs of measurements for each of the 33 patients). RESULTS: The Artsana CS 410 device successfully passed phase 1 of study validation with the number of absolute differences between test and reference device never <35 within 5 mmHg, never <40 within 10 mmHg and never <42 within 15 mmHg. The test device also passed phase 2 of the validation study with a mean (+/-SD) device-observer difference of -0.9+/-5.9 mmHg for systolic and -1.0+/-3.1 mmHg for diastolic blood pressure. CONCLUSION: According to the results of the validation study, based on the ESH International Protocol, the Artsana CS 410 may be recommended for clinical use in adults.

Validation of the Artsana CSI 610 automated blood pressure monitor in adults according to the International Protocol of the European Society of Hypertension.

BACKGROUND: There is evidence that blood pressure measurement outside the doctor's office can provide valuable information for the diagnostic evaluation of hypertensive patients and for monitoring their response to treatment. Home blood pressure monitoring devices have a major role in this setting, provided that their accuracy in measuring blood pressure is demonstrated by validation studies. OBJECTIVE: This study aimed at verifying whether the automatic electronic oscillometric blood pressure measuring device Artsana CSI 610 complied with the standard of accuracy indicated by the ESH International Protocol. METHODS: Sequential measurements of systolic and diastolic blood pressure were obtained in 33 participants using the mercury sphygmomanometer (two observers) and the test device (one supervisor). A standard adult cuff was always employed during the study. According to the ESH validation protocol, 99 couples of test device and reference blood pressure measurements were obtained during the two phases of the study (three pairs for each of the 33 participants). RESULTS: The Artsana CSI 610 device successfully passed phase 1 of study validation with the number of absolute differences between test and reference device never <35 within 5 mmHg and never <40 within 10 and 15 mmHg. The test device also passed phase 2 of the validation study with a mean (+/-SD) device-observer difference of -1.4+/-4.8 mmHg for systolic and -0.9+/-3.5 mmHg for diastolic blood pressure. CONCLUSIONS: According to the results of the validation study on the basis of the ESH International Protocol, the Artsana CSI 610 can be recommended for clinical use in adults.

Prevalence of home blood pressure measurement among selected hypertensive patients: results of a multicenter survey from six hospital outpatient hypertension clinics in Italy.

AIM: The purpose of this study was to evaluate the prevalence of home blood pressure (BP) measurement, the type of devices and accuracy in a large sample of hypertensive patients referred to hospital outpatient hypertension clinics. METHODS: Eight hundred and fifty-five consecutive treated hypertensive patients who attended six specialized centers during a period of 4 months were included. They underwent the following procedures: (i) detailed medical interview by a structured questionnaire; (ii) physical examination; (iii) standard 12-lead electrocardiogram; (iv) BP measurements taken by a validated mercury sphygmomanometer and patient's devices. RESULTS: A total of 640 (74.7%) of 855 patients were regularly performing home BP measurement. These patients were on average younger than those not practising it (58 vs 60 years, p<0.01); men were more numerous than women (58 vs 44%, p=0.03) and had higher educational level. Electronic arm-cuff instruments were the most frequently used devices (58%) followed by wrist devices (19%) and mercury or aneroid sphygmomanometers (23%). Significant correlations were found between BPs measured by validated mercury sphygmomanometers and patients' devices [r=0.85, p<0.0001 for systolic BP (SBP) and r=0.78, p<0.0001 for diastolic BP (DBP)]. Differences 5 mmHg in SBP or DBP were found in 50 and 60% of patients, respectively. CONCLUSIONS: Our findings indicate that: (i) home BP measurement is performed by a majority of treated hypertensives seen in specialized centers; (ii) male gender, age and educational level seem to influence the adoption of home BP monitoring; (iii) electronic arm-cuff devices are the most used instruments; (iv) a notable fraction of patient's devices do not meet the accuracy criteria recommended by US Association for the Advancement of Medical Instrumentation.