Antagonism of lipopolysaccharide-induced blood pressure attenuation and vascular contractility.

OBJECTIVE: Aim was to assess whether lipopolysaccharide (LPS)-induced decrease of total peripheral resistance depends on Toll-like receptor (TLR)4 signaling and whether it is sensitive to NO-synthase or TLR4 antagonists. METHODS AND RESULTS: C3H/HeN mice (control), expressing a functional, and C3H/HeJ mice, expressing a nonfunctional TLR4, were compared. LPS (20 mg/kg) was injected i.p. 6 hours before hemodynamic measurements. L-NAME and SMT, inhibitors of NO production, and Eritoran, a TLR4 antagonist, were tested for their impact on vascular contractility. Aortic rings were incubated for 6 hours with or without LPS (1 microg/mL), or with LPS+Eritoran (2 microg/mL) and their phenylephrine-induced contractility was measured using a myograph. The expression of cytokines in aortic tissue was examined by real-time polymerase chain reaction. In control mice LPS induced a significant decrease of blood pressure and an increase of heart rate, whereas C3H/HeJ remained unaffected. LPS induced an increase of cytokine expression and a depression of vascular contractility only in control mice but not in C3H/HeJ. L-NAME and SMT increased contractility in all rings and restored LPS-dependent depression of contractility. Eritoran prevented LPS-induced loss of contractility. CONCLUSIONS: LPS upregulates cytokine expression via TLR4 and induces attenuation of smooth muscle contractility which can be effectively antagonized.

Novel cellular activities for low density lipoprotein in vascular smooth muscle cells.

Hyperlipidemia and hypertension play important roles in the pathogenesis of atherosclerosis. To investigate the underlying intracellular mechanisms, we studied the effect of various concentrations of low density lipoprotein from normolipidemic subjects on concentrations of free intracellular calcium, intracellular pH, DNA synthesis, and vascular tone in vascular smooth muscle cells and rings from rat aortas. Low density lipoprotein in the range of 1-15 micrograms/ml induced a dose-dependent increase of concentration of free intracellular calcium and a biphasic change of the intracellular pH. Similar concentrations of low density lipoprotein led to an enhanced DNA synthesis. Furthermore, cumulative addition of 1-15 micrograms/ml low density lipoprotein produced a dose-dependent increase in contractile tension of thoracic aortic rings from rats. The maximal low density lipoprotein-induced contractile response was approximately 70% of that induced by 40 mM KCl. These findings indicate that low concentrations of low density lipoprotein occurring, for example, in the extravascular fluid might contribute to the pathogenesis of cardiovascular diseases by enhancing cell proliferation and vasoconstriction by changing intracellular calcium and intracellular pH.

The use of self-measured blood pressure determinations in assessing dynamics of drug compliance in a study with amlodipine once a day, morning versus evening.

OBJECTIVE: To test whether the time of administration influences the therapeutic response to a calcium antagonist taken once a day. Also, the dynamics of drug compliance and its impact on blood pressure control were investigated. DESIGN: Twenty outpatients with mild-to-moderate hypertension were included in a randomized, placebo-controlled open study. In a crossover design, all of the patients received 5 mg amlodipine, either in the morning or in the evening, during two consecutive 4-week treatment periods. METHODS: Blood pressure was taken by casual measurement, ambulatory 24-h monitoring (SpaceLabs 90202) and self-measurement at home, performed with a semi-automatic oscillometric device during the whole study period. Compliance was assessed using the Medication-Event-Monitoring System (MEMS). RESULTS: Neither casual nor ambulatory day- or night-time readings detected a significant difference between morning and evening administration. However, self-measurement documented significantly greater blood pressure reductions for morning than for evening administration. The MEMS showed different compliance on the days of ambulatory monitoring (100% with both drug regimens) compared with the whole treatment period. The number of days with missed medication was thus significantly higher for the evening dosing regimen. The difference in self-measured blood pressure between the two regimens was lost if the days with missed medication were removed from the statistical analysis. CONCLUSIONS: Time of once-a-day amlodipine administration does not influence its efficacy for 24-h blood pressure control. Furthermore, the use of self-measurement and the MEMS may provide useful additional information on the pharmacodynamic impact of different dosing patterns in hypertensive patients.

Cholesterol enhances contractile responses in isolated small mesenteric arteries of normotensive and spontaneously hypertensive rats.

OBJECTIVE: In order to examine possible mechanisms by which hypercholesterolemia may contribute to the development of cardiovascular disease, we investigated the effect of cholesterol enrichment on contractility in isolated small rat mesenteric arteries. DESIGN: Contractile responses of cholesterol-enriched isolated small mesenteric arteries of normotensive Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR) were compared with control groups. METHODS: First- to second-order mesenteric arteries (327-349 microm internal lumen diameter) were dissected from the mesenteric bed of 10-20-week-old male WKY rats and SHR, and incubated in cholesterol-free and cholesterol-rich (150 microg/ml) medium. Isolated arteries were mounted on a Mulvany-Halpern myograph for measurement of isometric tension. RESULTS: Cholesterol significantly increased active wall tension and active wall pressure in WKY rat arteries and active wall tension in SHR arteries in response to potassium chloride, norepinephrine and serotonin (P < 0.05). In addition, contractile responses to all agonists were significantly higher in cholesterol-enriched SHR arteries compared with cholesterol-enriched WKY rat vessels (P < 0.05). CONCLUSIONS: These findings suggest that elevated cholesterol content enhances agonist-stimulated contractility in small mesenteric resistance arteries, providing a possible mechanism by which hypercholesterolemia may contribute to the development of hypertension.

An evaluation of self-measured blood pressure in a study with a calcium-channel antagonist versus a beta-blocker.

In recent years self-measurement of blood pressure at home has gained increasing importance but there have been only a few studies comparing casual, ambulatory, and self-measured blood pressure determinations during a single clinical trial. We therefore compared treatment-induced blood pressure-reductions in a double-blind, placebo-controlled, parallel study design with a single morning dose of either 10 mg bisoprolol (n = 26) or 20 mg nitrendipine (n = 27) with casual blood pressure readings in the morning before the dose, ambulatory 24-h monitoring, and self-recorded measurements in the morning before the dose and in the evening. Mean reductions for systolic and diastolic blood pressure after 4 weeks of therapy were significantly greater for bisoprolol than for nitrendipine. The treatment-induced blood pressure reductions were most pronounced as assessed by casual readings but showed good agreement between casual, ambulatory, and self-measured blood pressure for group comparisons. In some patients, however, marked individual differences between the three methods were observed. Correlation coefficients between ambulatory and self-measured blood pressure were 0.4 for systolic blood pressure (P less than .05) and 0.6 for diastolic blood pressure (P less than .0005). Under the conditions of this parallel study design and the usual statistical risks, a difference of 5 mm Hg in diastolic blood pressure can be detected in 118 patients at the clinic, in 70 patients if ambulatory blood pressure is used, or in 56 patients if self-measured blood pressure is used. In conclusion, bisoprolol was more effective over 24 h than nitrendipine at the doses studied.(ABSTRACT TRUNCATED AT 250 WORDS)

What is the value of home (self) blood pressure monitoring in patients with hypertensive heart disease?

The acceptable maximal blood pressure values for patients monitoring their own blood pressure at home have not yet been determined. Risk of cardiovascular disease may be increased at lower blood pressure limits than those suggested by the World Health Organization (WHO) for clinic readings. We have investigated 25 patients with proven hypertensive small-vessel disease and compared self-monitored, ambulatory 24-h (ABPM) and clinic blood pressure measurements. The diagnosis of hypertensive small-vessel disease was based on clinical evidence of myocardial ischemia, angiographic exclusion of coronary heart disease, and abnormal single-photon emission computed tomography (SPECT) thallium-201 myocardial scintigraphy. Mean self-monitored values were 143.4 +/- 13.6/84.0 +/- 9.4 mm Hg (95% confidence intervals 137.6-149.0 mm Hg for systolic and 80.1-87.9 mm Hg for diastolic blood pressure). Both home and ambulatory daytime readings (141.2 +/- 11.8/83.9 +/- 10.2 mm Hg) were significantly lower than the clinic readings by the physicians (clinic systolic, 169.2 +/- 16.5 mg; clinic diastolic, 95.0 +/- 11.6 mm Hg; P < .0001 v home and ambulatory readings). There was no significant difference between home and ambulatory readings. Agreement between home and ambulatory values was much closer than for clinic v ABPM readings. The respective correlation coefficients for systolic values were r = 0.702 (home v ABPM; P < .0001) and r = 0.32 (clinic v ABPM; NS). For diastolic values correlation coefficients were r = 0.674 (home v ABPM; P < .0002) and r = 0.574 (clinic v ABPM; P < .003) respectively. In conclusion, the reported results suggest that the WHO suggested definition of hypertension (> or = 140/90 mm Hg) may be set too high when blood pressures are measured by the patient at home. A cutoff value of < 135/85 mm Hg, as in ABPM, may be a more realistic upper limit for self-monitoring.

Normal values of blood pressure self-measurement in view of the 1999 World Health Organization-International Society of Hypertension guidelines.

New guidelines for the management of hypertension have been published in 1999 by the World Health Organization (WHO) and the International Society of Hypertension (ISH). The WHO/ISH Committee has adopted in principle the definition and classification of hypertension provided by the JNC VI (1997). The new classification defines a blood pressure of 120/80 mm Hg as optimal and of 130/85 mm Hg as the limit between normal and high-normal blood pressure. It is unclear which self-measured home blood pressure values correspond to these office blood pressure limits. In this study we reevaluated data from our Dübendorf study to determine self-measured blood pressure values corresponding to optimal and normal office blood pressure using the percentiles of the (office and home) blood pressure distributions of 503 individuals (age, 20 to 90 years; mean age, 46.5 years; 265 men, 238 women). Self-measured blood pressure values corresponding to office values of 130/85 mm Hg and 120/80 mm Hg were 124.1/79.9 mm Hg and 114.3/75.1 mm Hg. Thus, we propose 125/80 mm Hg as a home blood pressure corresponding to an office blood pressure of 130/85 mm Hg (WHO 1999: normal) and 115/75 mm Hg corresponding to 120/80 mm Hg (optimal).

Reliability of reporting self-measured blood pressure values by hypertensive patients.

For self-measurement of blood pressure to be useful, patient reporting of test results must be reliable and accurate. Until now no study directly measured the accuracy and reliability of patients' reporting of self-measured blood pressure values. Thirty hypertensive patients (69 +/- 11 years) were instructed to measure blood pressure at home over 14 days with the highly accurate Omron IC monitor and to keep a record of all readings in a patient logbook. To assess the reliability of the records, patients were not informed about the memory capacity of the device. We compared automatically stored blood pressure readings with the respective logbook entries to analyze deletion (under-reporting), addition (over-reporting), and precision of reporting of test results. The prevalent pattern was under-reporting, averaging 36% +/- 24% (3% to 89%), which occurred significantly more than over-reporting (9% +/- 11%; 0% to 38%). The precision of reporting (identical values at corresponding times) was 76% +/- 34% (0% to 100%). This observer error did not affect group comparisons of automatically stored values and logbook entries, although the estimated limits of agreement were wide. Blood pressure control, duration of hypertension, age, or previous use of self-measurement and patterns of logbook entries were not found to be predictive of the patients' reliability. Our results demonstrate a substantial observer error in the reporting of self-measured blood pressure values. This bias may be reduced by memory-equipped blood pressure devices.

User procedure for self-measurement of blood pressure. First International Consensus Conference on Self Blood Pressure Measurement.

OBJECTIVE: To review the medical literature regarding the methodology of self-measurement of blood pressure and to provide some practical recommendations regarding protocol and procedure for measurement, documentation and analysis of data, choice and provision of devices and education of patients and physicians. PROCEDURE AND PROTOCOL FOR MEASUREMENTS: Technical recommendations regarding measurement of blood pressure do not differ from usual guidelines. Frequency of measurement remains a matter of discussion. At the beginning of the self-measurements of blood pressure and during the titration phase, there should be a 7-day measurement period with two measurement of blood pressure each morning and two measurements in the evening at pre-stipulated times. For long-term observation, a minimum measurement period of 1 week per quarter is required. The minimum number of measurements performed during each period should be a total of 12 readings recorded within seven working days. Depending on individual needs (e.g. poor compliance) or for pharmacologic studies, a higher frequency of readings could be used. DOCUMENTATION AND ANALYSIS OF DATA: Owing to the lack of reliability of patients' diaries, the use of printer-equipped or memory-equipped devices is advocated. All the recorded data, except those obtained on the first day, must be used for analysis. CHOICE AND PROVISION OF DEVICES: Self-measurement of blood pressure should be performed with validated fully automated devices using a brachial cuff. The preference should be given to apparatus offering the possibility of storing and transmitting measurements. Wrist apparatus should be used with caution due to the risk of measurement errors if it is used inappropriately. A manual device should be considered for patients suffering from irregular cardiac rhythms and patients with large or small arm circumferences, since automated devices have not been validated for use in these situations. Reimbursement of hypertensive patients using validated devices should be considered, so long as they are adequately trained and supervised. EDUCATION OF PATIENTS: In a therapeutic perspective, self-measurement of blood pressure should be performed by trained patients under the supervision of their practitioner. Teaching must be performed by skilled staff in hypertension centers and ultimately in general practice. Self-measurement of blood pressure is to be recommended for any hypertensive patient who is sufficiently motivated to participate in the treatment of his own hypertension. Patients with physical problems or mental disabilities that make them unable to perform or to understand the measuring technique represent the limits of the method. Education of patients must encompass information about hypertension and cardiovascular risk, blood-pressure-measurement procedures, advice on items of equipment and their proper use, protocols, and interpretation of data. A patient's proficiency must be checked before he or she should be considered competent at performing the procedure. Annual reevaluation is required.

Betablocking drugs in essential hypertension: transdermal bupranolol compared with oral metoprolol.

In the present study the antihypertensive efficacy and tolerability of transdermal bupranolol (30 mg once-daily) was compared with oral metoprolol (100 mg once-daily). Blood pressure measurements were performed in the office, at home, and with ambulatory 24-h blood pressure devices. Systemic and local side-effects, as well as compliance and acceptance, were evaluated every two weeks. The treatment period lasted eight weeks. The results showed a significant decrease in blood pressure under the bupranolol transdermal therapeutic system in the office, at home, and with 24-h blood pressure measurements day- (08h00-20h00) and night-time (20h00-08h00). Under oral metoprolol there was a significant blood pressure decrease in the office, at home, and in the mean daytime values of the 24-h blood pressure measurements. The night-time values, however, demonstrated only a slight decrease in blood pressure, being significant only for diastolic values. Systemic side-effects were comparable in both groups. 69% of the patients had local side-effects at the patch side (erythema, papulous exanthema, pruritus). Six patients dropped out because of localized urticarial exanthema (five patients treated with transdermal bupranolol, one patient treated with oral metoprolol). In comparison to the oral form, twice as many patients had admitted to have been non-compliant with the patches (13 versus 7 patients). At the end of the study, 24 out of 32 patients preferred to be treated with capsules.

[Peroneal weakness]. / Fussheberschwäche.

The 22 year old male patient was admitted because of right sided peroneal nerve palsy two months after transient foot drop on the left side. Both pareses developed under a strict dietary regime leading to a weight loss of about 30 kg within 3 months. Slimmers' paralysis of peroneal nerve was diagnosed after exclusion of polyneuropathy or trauma as possible causes. Complete remission followed after a less restrictive diet.

[How reliable is conventional blood pressure registration? Comparison with a semi-automatic device]. / Wie zuverlässig ist die konventionelle Blutdruckmessung? Vergleich mit einem halbautomatischen Messgerät.

The aim of the present study was to determine observer error in measuring blood pressure by the conventional auscultatory method. Casual blood pressure was measured in two age-matched groups of normo- and hypertensive patients with a conventional mercury sphygmomanometer (n = 181) or a semiautomatic device (n = 176) by ten doctors of the university hospital. Although there were no significant differences in mean systolic or diastolic blood pressure values between the groups, the conventionally determined values showed a distinctively different pattern of distribution in comparison to the semiautomatically taken readings. With conventional readings a highly significant preference for terminal digit "0" (44%) and fewer systolic and diastolic values in the lower blood pressure range were observed. Furthermore there was a higher frequency of conventional readings ending in "8" than in "2". Terminal digit preference in the whole group was mainly due to the doctors, who did not measure blood pressure to the nearest 2 mmHg mark. Our results thus stress the importance of better and regular training in the correct technique of measuring blood pressure in order to reduce sources of observer bias.

[Skin spots, skin nodules, gangrene of the toes]. / Hautflecken, Hautknoten, Zehengangrän.

A 42-year-old man with multiple cutaneous neurofibromacules, café-au-lait and gangrene of toes was diagnosed having neurofibromatosis in 1976. An aortography performed because of severe hypertension had shown a coarctation and bilateral renal artery stenosis in 1982. Conservative antihypertensive therapy with an ACE-inhibitor, a vasodilatating agent and a diuretic resulted in gradual normalisation of blood pressure values. A recent follow-up revealed minimal progression of neurofibromatosis and hypertensive lesions documenting a benign course for over 13 years.

[Combination therapy of cardiovascular risk factors]. / Kombinierte Therapie kardiovaskulärer Risikofaktoren.

Risk factors for cardiovascular diseases, which are the leading cause of mortality in the industrialized countries, are well investigated; however, the results of intervention studies on the therapy of single risk factors were disappointing in the past. Recently, there has been growing evidence that there might be a closer pathophysiological relation between arterial hypertension, hypercholesterolemia, obesity, impaired glucose tolerance and genetic disposition than previously thought. For the treatment of the individual patient, this concept requires a complete work-up and comprehensive therapy of all risk factors. The therapy of several mildly elevated risk factors may be more beneficial than a too vigorous reduction of the blood pressure alone. At the beginning of every therapeutic regimen, there has to be a nonpharmacological approach. Diet and weight reduction even in mild obesity are more efficient in influencing several risk factors at the same time than pharmacological therapy. Metabolic consequences of drug treatment have to be carefully monitored.

[Performing self-measurement of blood pressure: a patient survey]. / Umgang mit der Blutdruck-selbstmessung: eine Patientenumfrage.

In the present study the knowledge of 200 patients of our hypertension clinic about the technique of blood-pressure self-measurement was investigated using a questionnaire of 22 questions. 44-66% of the patients in different age groups measured their own blood-pressure, showing that self-measurement is commonly used, regardless of the age. 73% of the patients had bought a device on their own, but only 17% on the physician's advice. Possible causes for erroneous measurements were rarely known and underestimated by the patients. Due to lacking or insufficient instruction a relatively high percentage of the patients did not perform correct measurements. 45% did not measure the blood-pressure at the same time of day, 45% did not read systolic and diastolic pressures to the nearest 2 mmHg mark of the manometer scale, 59% did not count the pulse rate and 52% did not document the blood-pressure values. About half of the patients adjusted their medication on the ground of self-measured blood-pressure determinations. 45% of the elderly patients felt that their compliance had improved by self-measurement in contrast to 17% in the younger group. Given the increasing use of blood-pressure self-measurement we conclude that education of patients and physicians on possibilities and limitations of self-measurement as well as optimal training in the correct technique seem advisable.

[ Self measurement of blood pressure. Equipment and comparison of equipment]. / Blutdruckselbstmessung. Geräte und Gerätevergleich.

Precision is the primordial criterion for the evaluation of a blood pressure measuring device. While traditionally devices based on the auscultation technique have dominated semiautomatic devices have recently gained acceptance. The latter permit to reduce procedure-related errors. They are simpler to use and require less demanding instruction but are more expensive than stethoscopic devices.

[Self measurement of blood pressure: patient education]. / Blutdruckselbstmessung: Patienteninstruktion.

Many patients measure their blood pressure without any instruction due to the availability of modern measuring devices. Although the technique can be mastered by most of the patients, some sources of error have to be eliminated. The aim of such an instruction is to explain these sources of error to the patients and to give them opportunity to practise the self measurement under medical supervision. An instruction sheet is handed out as a pamphlet. The patients are also directed to keep a record of all measurements which is periodically controlled by the physician. It is also advisable to reexamine the measuring technique of the patient from time to time and to check the accuracy of the patients measuring device.

[Why are blood pressure values higher in the doctor's office than at home?]. / Weshalb liegen Blutdruckwerte in der Praxis höher als zu Hause?

Blood pressure values measured by the patients at home are lower than those measured during medical consultation. To test whether the person measuring the blood pressure is responsible for this difference, the blood pressure of 127 patients was measured first by the doctor and then by the patients themselves during the consultation. There was a good agreement and no significant difference between the two measurements. Values taken at home were however significantly lower. Our results indicate, that difference between clinic and home blood pressure values does not depend on the person performing the measurement.

[Diagnostic and prognostic aspects of home blood pressure measurement]. / Diagnostische und prognostische Aspekte der Heimblutdruckmessung.

Up to now the diagnosis of hypertension has been based on a few casual blood pressure measurements in the physician's office according to WHO guidelines. Blood pressure measurements at home in the recent years have gained increasing popularity as a supplementary diagnostic tool. The establishment of an everyday blood pressure profile and exclusion of "white coat" hypertension are the main diagnostic indications. In borderline hypertension those patients with elevated home blood pressures can be identified. However world-wide epidemiologic studies are urgently needed to develop definitions of normal and pathological values for self-recorded blood pressure readings. From our experience diastolic home-recorded values higher than 90 mm Hg should be regarded as pathological.

[The therapeutic significance of home blood pressure measurement]. / Therapeutische Bedeutung der Heimblutdruckmessung.

Optimization of antihypertensive therapy during the initial dose titration as well as the long term follow-up of chronic therapy constitute the main therapeutic indications of blood pressure measurement at home. Furthermore home blood pressure measurements may be of value in patients with unsatisfactory blood pressure response in whom poor compliance is suspected. Finally patients may adjust their antihypertensive therapy according to the level of self-recorded blood pressure measurements.