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Group-specific component is not only a vitamin-D-binding protein.

The vitamin-D-binding protein (DBP), also called group-specific component, is well known for two main reasons: its genetic polymorphism, and its binding affinities for actin and vitamin D compounds. In recent years, additional binding affinities have been described for this puzzling molecule, without any significant biological explanations being given for these observations. The molecular genetic data for DBP are analyzed in order to show that the affinities for vitamin D are supported by the genetic variability. The molecular evolution of the protein shows that the ancestral gene was present long before the development of related genes, such as those for albumin and alpha-fetoprotein. Other affinities for actin, C5a-desArg and for a B lymphocyte mitogen are also discussed. DBP is mainly present in the circulating blood as an apoprotein. The cytoplasmic presence of DBP has not been confirmed, and the major question today is to understand the biological role of this protein. In the last part of the review, the discussion focuses on relating the different binding affinities of DBP to its biological activities. Avenues for future research are also outlined: these include DBP metabolism, the differentiation of macrophages, and the activity of DBP during embryonic development.

Amino Acid Sequence↗

[Screening and characterization of dominant bacteria for the degradation of endocrine disruptor di-n-butyl phthalate].

OBJECTIVE: In order to screen the dominant bacteria for degrading endocrine disruptor di-n-butyl phthalate (DBP). METHODS: The activated sludge was acclimated by DBP as sole carbon source. DBP concentration was increased progressively. 5 strains were isolated from the sludge by the plane-table after 10 weeks, 1 strain of which grew and degraded DBP well. RESULTS: By orthogonal test, it was indicated that the appropriate degradation conditions of DBP for this best strain were degradation time 32 h, DBP concentration 200 mg/L, rate of shaking incubator 100 r/min, pH 7.0, temperature 30 degrees C. The degraded rate of DBP is more than 95% under above conditions. CONCLUSION: The bacterium was identified as Pseudomonas.

Bacteria↗

Kinetic radical scavenging activity and cytotoxicity of 2-methoxy- and 2-t-butyl-substituted phenols and their dimers.

The dimers bis-EUG, bis-MMP, bis-BHA, bis-BMP and bis-DBP were synthesized from the monomers 4-allyl-2-methoxyphenol (EUG), 2-methoxy-4-methylphenol (MMP), 2-t-butyl-4-methoxyphenol (BHA), 2-t-butyl-4-methylphenol (BMP) and 2,4-di-t-butylphenol (DBP), respectively. The stoichiometric factors (n; number of free radicals trapped by one mole of phenolic moiety) of these compounds were determined by induction period methods with a kinetic approach in the 2'2-azobisisobutyronitrile (AIBN) and benzoyl peroxide (BPO) systems at 70 degrees C. The n values for bis-EUG, bis-MMP and bis-BHA were approximately two-fold greater than those for their monomers in both the AIBN and BPO systems, whereas the n values for bis-BMP and bis-DBP were identical to those of their monomers. bis-EUG, bis-MMP and bis-BHA, containing methoxy groups, were potent antioxidants. The n values (1.3-1.6) for EUG and MMP were considerably less than 2, as is commonly observed for the stoichiometric factors of phenolic compounds. The antiradical efficiencies against DPPH (diphenylpicrylhydrazyl) of the monomers and their dimers were also investigated, likewise indicating that bis-EUG, bis-MMP and bis-BHA were potent antioxidants. DBP and bis-DBP were less effective radical scavengers because of the steric factor of their bulky t-butyl groups. On the basis of cytotoxic activity against a human submandibular gland carcinoma cell line (HSG) and human gingival fibroblasts (HGF), these compounds could be classified into a high-activity group (DBP, bis-DBP and bis-BMP, with butylated hydroxytoluene (BHT) as a positive control) and a low-activity group (MMP, EUG, BHA, BMP, bis-BHA and bis-EUG). The cytotoxicity of EUG and BHA was markedly reduced by dimerization, whereas that of MMP was enhanced. The sensitivity index (ratio of 50% cytotoxic concentration for HGF cells to that for HSG cells) of EUG, MMP, bis-MMP and bis-BHA was approximately 9, 5, 7 and 2, respectively, whereas that of the other compounds was approximately 1. Potential mechanisms of cytotoxicity were assessed by PM3 semiempirical molecular orbital (MO) calculations. Tumor cells were highly sensitive to 2-methoxy-4-alkylphenols such as EUG and MMP, possibly due to the formation of cytotoxic quinone methide intermediates. In contrast, the high sensitivity index of bis-MMP may be related to the production of a highly reactive substance, CH3+, via oxidation. Structure-activity relationship (SAR ) models using PM3 calculations may be useful to predict biological activity during the development of potential anticancer drugs.

Benzoyl Peroxide↗

[Prevalence of hypertension in an Indian community in the North of Argentina].

The prevalence of hypertension among adults of both sexes was assessed as part of a primary medical attention program in an Indian Wichi-Chorote community in Santa Victoria Este, province of Salta, Argentina. Arterial blood pressure was measured after a five minutes rest in a sitting position in adults (over 18 years old) of both sexes with a calibrated sphygmomanometer. A total of 522 adults (318 women and 204 men) were evaluated with median age of 43.5 +/- 16.3. The mean systolic blood pressure (SBP) was 125.2 +/- 22.7 mm Hg, and the mean dyastolic blood pressure (DBP) was 76.3 +/- 12.8 mm Hg. Thirty five percent of the people evaluated had normal pressure values (SBP<80 and DBP<120), 37% prehypertensive (SBP 120-139 or DBP 80-89) and 28% hypertensive (SBP > or = 140 or DBP > or = 90). Thirty one percent of the men (mean age: 43.93 +/- 17.11, mean SBP: 126.81 +/- 22.61 and mean DBP: 77.80 +/- 13.33) and 27% of the women studied (mean age: 42.93 +/- 16.3, mean SBP: 124.92 +/- 24.02 and mean DBP: 75.28 +/- 12.57) were hypertense. Fifty nine percent of the people over 65 years of age (n:58) (mean age: 73.15 +/- 6.36, mean SBP: 144.81 +/- 28.72 and mean DBP: 79.68 +/- 13.17) had blood pressure values in the hypertense range. The prevalence of hypertension in the evaluated rural population, suffering extreme demographic and sanitary conditions, is similar to that reported for urbanized societies in the USA but lower than the one reported for other rural areas of our country.

Adolescent↗

[Is masked hypertension an artefact due to the blood pressure measurement method and threshold effects?].

UNLABELLED: From results of office and home measurements of blood pressure (BP), patients can be classified as "hypertensive (HT)", "normotensive (NT)", "office hypertensive (OH)" or "masked hypertensive (MH)" by crossing the classifications obtained from each method. It seems that 9 to 20% of patients could be MH with a prognosis close to HT (SHEAF study). OBJECTIVES: To test the hypothesis that at least one part of the prevalence of MH would be an artefact due to the difference between the methods of measurements (shygmomanometer vs semi-automatic device) and/or due to different definitions of office hypertension (OHT). To determine the impact of different definitions of OHT on the prevalence of MH. METHODS: During the course of a phase IV study, BP was measured with the same semi-automatic device (OMRON 705CP) both at doctor's office (3 measurements at 1-minute intervals) and at home, by the patient himself (3 measurements in the morning and in the evening at 1-minute intervals over the 7 days before the visit). Following definitions were used: Office HT: SBP > or =140 mmHg, DBP > or =90 mmHg, SBP > or =140 mmHg or DBP > or =90 mmHg; Home HT: SBP > or =135 mmHg, DBP> or =85 mmHg, SBP > or =135 mmHg or DBP > or =85 mmHg. Another definition of office HT was used SBP > or =135 mmHg, DBP > or =85 mmHg SBP > or =135 mmHg or DBP > or =85 mmHg. RESULTS: 575 patients were analysed. Results from the two methods of measurements are closed but significantly different (difference for SBP: 3.2 +/- 16.5 mmHg; p < 0.0001; difference for DBP: 1.4 +/- 10.3 mmHg; p = 0.002)

Aged↗

Serial changes of pulse wave velocity and correlations with hemodynamic parameters during general anesthesia.

BACKGROUND: Increased pulse wave velocity (PWV) is a marker of increased arterial stiffness and is correlated with cardiovascular mortality and mortality of all causes in the elderly and in patients with essential hypertension and type 2 diabetes. There is also a positive correlation between PWV and arterial blood pressure. The changes of PWV in response to general anesthesia and surgical stimulation remain unclear. The aim of this study was to continuously monitor the PWV, blood pressure and heart rate, and to assess their correlations during general anesthesia in women receiving gynecologic surgery. METHODS: The values of PWV were obtained from calculation of the finger-to-toe distance divided by the transit time using dual-channel photoplethysmography system. The values of PWV, systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate were recorded before anesthesia induction, 5 min before incision, at incision, in continuation for at least 30 min thereafter, and 5 min after discontinuation of sevoflurane. The correlations between PWV and SBP, DBP and heart rate during the general anesthesia were analyzed using Pearson's correlation test. RESULTS: The serial records of PWV and hemodynamic parameters showed that PWV, SBP, DBP, and heart rate decreased after induction of anesthesia. SBP and DBP increased after surgical incision. There was a trend of progressively declining of PWV and DBP during the general anesthesia but SBP and heart rate remained stationary. All the values of PWV, SBP, DBP, and heart rate increased after discontinuation of anesthesia. There were significant correlations between PWV and SBP (r = 0.4558, P < 0.0001), between PWV and DBP (r = 0.2719, P < 0.0001), between PWV and pulse pressure (r = 0.2067, P < 0.0001), and between PWV and mean arterial pressure (r = 0.3969, P < 0.0001). CONCLUSIONS: We could evaluate the serial changes of PWV in response to general anesthesia and surgical stimulation using a simple and noninvasive dual-channel photoplethysmography system. The value of PWV, an index of arterial stiffness, has significant correlation with arterial blood pressure.

Adult↗

Ambulatory blood pressure monitoring: validation of the accuracy and reliability of the TM-2420 according to the AAMI recommendations.

The accuracy of the TM-2420 ambulatory blood pressure monitor (A&D Co, Japan) has been assessed by the indirect method according to the recommendations of the Association for the Advancement of Medical Instrumentation (AAMI). Ninety subjects (43 men and 47 women), aged 19-89 with a range of systolic blood pressures (SBP) of 81-211 mmHg and diastolic blood pressures (DBP) of 32-113 mmHg were studied. The monitor was compared with two observers using the Hawksley random zero sphygomomanometer. The standard deviation of the difference (SDD) between the observers was 3.0 mmHg for SBP and 2.3 mmHg for DBP. The mean differences between observers were -0.31 mmHg for SBP and 0.32 mmHg for DBP (both NS). The average of three readings for each subject recorded by the monitor was compared with the average of the simultaneous readings by the observers. The SDD was 7.2 mmHg for SBP and 5.5 mmHg for DBP (within the recommendations for accuracy). The differences between methods were -0.98 mmHg for SBP and 0.18 mmHg for DBP; these differences were not significant (NS). The monitor was also assessed against direct intra-brachial artery pressure in 12 subjects (36 readings). The mean difference between the monitor and simultaneous individual intra-arterial reading was -9.5 mmHg for SBP (P less than 0.001) and 3.7 mmHg for DBP (P less than 0.001). The SDD's between methods were 12 mmHg for SBP and 5.0 mmHg for DBP. Use of the monitor in general clinical practice in 100 patients was also assessed. The rate of errors was low (6.8%), and the device found to be acceptable.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Ultradian rhythmic models of blood pressure variation in normal human daily life.

To examine levels and variance structure of systolic blood pressure (SBP), diastolic blood pressure (DBP) and heart rate (HR), we measured those 3 variables every 7.5 min for 24 h (approximately 192 samples each subject) by ambulatory monitoring in 2 nominated groups of normal volunteers: younger (Y; 8 men, 5 women, 24-44 years) and older (O; 13 men, 12 women, 50-95 years). Y and O did not differ in either sleep or wake means for HR and DBP. Mean SBP in O was 17 mm Hg higher than in Y during wakefulness. Thirty-four subjects had significant low frequency variations (presumably the circadian rhythm) in SBP, DBP and HR, regardless of age. A periodic model fitting the time series required a 9 h feature (rhythm) for Y and O in DBP for best reduction of mean square error. In addition, O regularly showed 3 h features in both SBP and DBP, a 6 h feature in DBP and a 9 h feature in SBP, which were absent in Y. Our results suggest that low-power ultradian rhythms may appear in both SBP and DBP after age 50, and possibly serve as dynamic markers of normal cardiovascular aging.

Activity Cycles↗

Vitamin D and vitamin-D-binding protein kinetics in patients treated with continuous ambulatory peritoneal dialysis (CAPD).

Serum and dialysate levels of 25-hydroxycholecalciferol (25-OHD3), 1,25 dihydroxycholecalciferol (1,25-(OH)2D3), and vitamin-D-binding protein (DBP) were measured in 14 patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Serum levels of 25-OHD3 and DBP were within normal range (29.1 +/- 22.9 nmol/L and 5.9 +/- 1.1 mumol/L, respectively). Serum levels of 1,25-(OH)2D3 were subnormal in all (less than 16 pmol/L) but one. In 5 patients, dialysate concentrations of 25-OHD3 were 2.3 +/- 0.9 nmol/L, the rest had levels less than 1.0 nmol/L. Small quantities of 1,25-(OH)2D3 were found in the dialysate effluents. DBP could be detected in the dialysate in all patients (0.24 +/- 0.06 mumol/L). Mass transfer (MT) of 25-OHD3 and DBP were respectively -10.4 +/- 8.3 nmol/24 h and -1.46 +/- 0.46 0.46 mumol/24 h. Peritoneal clearances of 25-OHD3 and DBP were low (0.40 +/- 0.37 mL/min and 0.18 +/- 0.06 mL/min, respectively. We conclude that CAPD leads to losses of 25-OHD3 and DBP. However, the peritoneal loss of DBP is well compensated and does not result in serum deficiency. Serum 25-OHD3 levels did not correlate with time on CAPD.

Calcifediol↗

Biochemical analysis of adenovirus type 5 DNA-binding protein mutants.

We previously reported the isolation and functional characterization of seven adenovirus type 5 (Ad5) DNA-binding protein (DBP) point mutants (Quinn, C. O., and Kitchingman, G. R. (1986) J. Virol. 60, 653-661). Six of the seven mutants were defective in their ability to help adeno-associated virus replicate its DNA. To determine the level at which the mutations affect this function of the DBP, we analyzed several properties of the mutant proteins. All are transported to the nucleus and are post-translationally phosphorylated to the same extent. The half-lives of the proteins, measured by pulse-chase, were nearly identical to that of the wild-type DBP. The mutant DBPs were examined for their ability to bind to single-stranded DNA (ssDNA). Mutations in amino acids 322, 323, and 470 lowered the affinity of the DBP for ssDNA, while a mutation in amino acid 181 had no affect. Combinations of mutations in amino acid 470 with either 322 or 323 did not further lower the affinity of the protein for ssDNA. These data indicate that the functional defect for adeno-associated virus helper activity of the six mutants is due mainly, if not totally, to their reduced affinity for single-stranded DNA. These experiments have thus identified a functional domain of the adenovirus type 5 DBP potentially involved in DNA-protein interactions. Comparisons with temperature-sensitive DBP mutants indicate that the conserved region mutants are functionally distinct and represent a new class of DBP mutants.

Adenoviridae↗

Captopril versus perindopril: a double blind study in essential hypertension.

This was a double blind, parallel group, multicentre comparison of the therapeutic efficacy and acceptability of perindopril and captopril in essential hypertension. After one month of placebo, 165 patients with supine diastolic blood pressure (DBP) between 95 and 125 mmHg were randomised to perindopril 4 mg once daily or captopril 25 mg twice daily orally. The perindopril group (n = 82) had significantly higher pretreatment DBP (105.4 +/- 0.8 mmHg vs 102.3 +/- 0.6 mmHg) but other demographic variables were similar. Assessment was monthly for three months: 'uncontrolled' patients (DBP greater than 90 mmHg) had the dose doubled and then hydrochlorothiazide added. Two of the six withdrawals were attributed to drug side effects and were in the captopril group. There was no significant difference in the number of withdrawals or incidence of side effects between the drugs. The final titrated treatments were similar and monotherapy normalised DBP in 49% of each group. The final 'control' rate was higher with perindopril than captopril: 75% vs 57%, P = 0.016. The overall fall in DBP was greater in the perindopril group: 26.5 +/- 1.9 mmHg vs 18.9 +/- 1.9 mmHg, P = 0.005. The doses of diuretic were similar in the two groups. The DBP of patients who received only monotherapy for three months also fell more in the perindopril group (-17.5 +/- 1.4 mmHg vs -13.9 +/- 1.0 mmHg, P less than 0.01). At the doses studied, perindopril was more effective than captopril in lowering DBP, either as monotherapy or in combination with a diuretic.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin-Converting Enzyme Inhibitors↗

Blood pressure reactivity in the evaluation of resting blood pressure and mood responses to pindolol and propranolol in hypertensive patients.

OBJECTIVE: The purpose of this exploratory study was to evaluate the relationship of blood pressure reactivity during exercise to treatment responsiveness to two commonly used beta-adrenergic blocking agents, propranolol and pindolol. DESIGN: Prospective, placebo-controlled, balanced, cross-over clinical trial. SETTING: University-affiliated medical center. PATIENTS: A convenience sample of 19 white male subjects with mild to moderate essential hypertension were studied. The mean age was 63.4 years (SD = 5.2). The mean resting systolic blood pressure (SBP) was 158.6 mm Hg (SD = 12.3) and mean resting diastolic blood pressure (DBP) was 96.4 mm Hg (SD = 8.6). They had no clinical evidence of secondary hypertension, diabetes, heart, liver, pulmonary, or renal disease. OUTCOME MEASURES: Resting blood pressure; blood pressure reactivity to exercise; self-report measures of depressive symptoms, and mood disturbances. INTERVENTION: Antihypertensive medication was tapered off and subjects were free of all prescription drugs for 2 weeks. Subjects were randomly assigned to propranolol-pindolol or pindolol-propranolol group. Each 4- to 6-week treatment phase was preceded by a 2-week placebo phase. At the end of the initial placebo phase and each active drug treatment phase, subjects were assessed for depression and mood disturbances by use of standardized measures and were given a graded exercise test on a cycle ergometer. Resting blood pressure was assessed weekly and before each exercise test. RESULTS: Significant relationships between DBP reactivity to exercise during the placebo phase and the degree of blood pressure and mood responsiveness to pindolol and propranolol treatment were observed. Subjects demonstrating high DBP reactivity required high doses of beta-blocker for resting DBP reduction, and these subjects showed the least change in mood at high doses. Similar patterns were found for the relationship of SBP reactivity and blood pressure and mood responsiveness to drug treatment, but these relationships were not statistically significant. CONCLUSIONS: DBP reactivity to exercise during the placebo phase provides unique information about the essential hypertensive patient. DBP reactivity and drug dose were important determinants of resting blood pressure and mood responsiveness to both pindolol and propranolol. DBP reactivity and perhaps SBP reactivity may be useful measures in the study of central adrenergic and peripheral cardiovascular pathophysiology.

Affect↗

Comparative study of the efficacy and tolerability of hydroflumethiazide versus propranolol in Africans with mild to moderate hypertension.

Sixty patients with Diastolic Blood Pressure (DBP) of 100-110mmHg matched for age, sex and Bp levels were randomly assigned to propranolol 80mg daily or Hydroflumethiazide (HFM) 50mg daily. HFM causes a significant reduction in systolic blood pressure (SBP) and DBP within 4 weeks compared both with baseline and propranolol (SBP 143.7 +/- 12.3 vs 158.1 +/- 10.9mmHg, P < 0.05; DBP 92.0 +/- 4.5 vs 102.4 +/- 5.1mmHg, P < 0.05), (SBP 143.7 +/- 12.2 vs 152 +/- 11.0mmHg P < 0.05; DBP 92.0 +/- 4.5 vs 101.1 +/- 6.1mmHg, P < 0.05), respectively. Propranolol produced no significant difference from the baseline at 4 weeks (SBP 152.0 +/- H.0 vs 154.1 +/- 11.5mmHg NS; DBP 101.1 +/- 6.1 vs 102.2 +/- 5.6mmHg, NS). Reduction in BP by HFM was maintained after 8 and 12 weeks with further reduction but which did not achieve statistical significance. Increased dose of propranolol (160mg daily) after 4 weeks caused significant reduction in BP by 8 week (SBP 146.8 +/- 11.8 vs 152.0 +/- 11.0mmHg, P < 0.05; DBP 95.9 +/- 4.4 vs 101.1 +/- 6.1mmHg P < 0.05), which was maintained upto 12 weeks. The values however remained higher than in the HFM group. More patients in the HFM group achieved target BP (< 140/90), SBP 53.8% vs 29.6% P < 0.05, DBP 69.2% vs 14.8% P < 0.01. Incidence of side effects was similar and will be discussed. Thiazides are superior to B'blockers as initial monotherapy in black hypertensives.

Adult↗

Decreased cardiovascular responses to cisterna magna NaCl injection in hypertensive rats.

Albino rats were made hypertensive by 1% NaCl in the drinking water for 4-5 months, systolic (SBP) and distolic blood pressure (DBP) were 164.0 +/- 10.1 mm Hg and 118.7 +/- 4.6 mm Hg respectively, vs. control rats whose SBP and DBP were 119.0 +/- 4.4 mm Hg and 86.8 +/- 4.3 mm Hg respectively. Psychosocial stress (1 hour daily for 4-5 months) only raised SBP to 140.0 +/- 5.2 mm Hg; DBP remained unaltered. One percent NaCl intake combined with psychosocial stress, increased SBP and DBP but not significantly beyond the level observed with single 1% NaCl administration. Formerly described control and hypertensive rats were anesthetized with sodium pentobarbital (40 mg/kg) and stereotaxically injected into de cisterna magna (i.c.) with 20 microliters of 1.5 M NaCl solution. During i.c. injection, intraarterial SBP, DBP and heart rate (HR) were continuously recorded. After i.c., 1.5 M NaCl injection, mean arterial pressure (MAP) increased 21.0 +/- 4.0 mm Hg and HR 51.0 +/- 5.0 beats/min in control rats. Rats made hypertensive by 1% NaCl intake showed a significantly lower increase of MAP, 11.0 +/- 1.8 mm Hg; HR increased 37.0 +/- 4.3 beats/min. Rats submitted only to psychosocial stress displayed a response similar to the one described in control rats. Hypertensive rats submitted to both 1% NaCl intake and psychosocial stress had a more intense reduction of the hypertensive and tachycardic response, 8.0 +/- 2.2 mm Hg and 20.0 +/- 3.2 beats/min respectively. Control i.c. injection with the same volume of saline (0.15 M NaCl) did not change significantly SBP, DBP or HR in a separate group of rats. Left ventricle weight (0.754 +/- 0.0333 g) was augmented in the 1% NaCl treated group (0.795 +/- 0.038 g), and increased its protein content by 13.1% (changes not statistically significant). The highest increase of the left ventricle weight (23.7% above control) with no change in its protein content was observed in rats submitted to 1% NaCl intake plus psychosocial stress. In conclusion, chronic high NaCl intake increased blood pressure; psychosocial stress acted as a weak stimulus for SBP and DBP increase, and central nervous system sodium chloride sensitivity for delivering a peripheral sympathetic discharge was found decreased in rats made hypertensive by a high salt intake.

Animals↗

[Antihypertensive action and predictive factors of efficacy of benazepril in mild-to-moderate hypertension: clinical trial in general medical practice on 16,987 patients].

UNLABELLED: The aim of the study was to evaluate in general practice, in a large and unselected population of patients, the efficacy and safety of benazepril associated or not with hydrochlorothiazide (HCTZ) and to identify clinical and demographic predictive factors of antihypertensive efficacy. In this open uncontrolled study, 16,987 patients with mild to moderate hypertension were included by 5350 GPs. They received benazepril (BNZ) 10 mg once daily for 8 weeks. If sitting DBP remained > 90 mmHg after 4 weeks, HCTZ 12.5 mg once a day was then added for the last 4 weeks. RESULTS: In the intent to treat analysis, 54.5% of patients, after 4 weeks, and 80.6% of patients after 8 weeks, were controlled (DBP < 90 mmHg). Mean sitting DBP decreased from 100.5 +/- 5.5 mmHg (baseline) to 86.7 +/- 7.5 mmHg after 4 weeks and to 82.5 +/- 6.5 mmHg after 8 weeks. Mean SBP decreased from 169.5 +/- 13.1 mmHg to 150.5 +/- 12.5 mmHg after 4 weeks and to 145.0 +/- 10.9 mmHg after 8 weeks. Of the 16,900 patients included in the safety analysis, 853 (5.0%) dropped out of the study, 504 (3.0%) for adverse events (AE). The most frequent AE were: cough (3.5%), headache (0.9%), dizziness (0.8%), asthenia (0.6%) and nausea (0.5%). 13 deaths were observed during the study, mainly due to stroke or cancer. Six cases of raised serum creatinine level, 3 cases of angio-oedema and 2 cases of hepatitis were also reported. After 8 weeks of treatment, the main predictors of therapeutic response (DBP) were: recently discovered hypertension (86.3% of controlled DBP), regular exercise (85.5%) and age < 50 years (84.6%). Conversely: obesity, diabetes mellitus (77.9%), previously treated with several drugs (75.2%) and initial DBP > or = 105 mmHg (74.5%) were not predictive. Predictive factors emerging from logistic regression were : baseline DBP (< 105 mmHg), history of hypertension, body mass index, initial treatment of hypertension (no treatment--one drug--several drugs) and age. CONCLUSION: This large-scale study confirms, the antihypertensive efficacy and good tolerability of benazepril alone or associated with hydrochlorothiazide in general practice.

Aged↗

Systolic vs diastolic blood pressure control in the hypertensive patients of the PAMELA population. Pressioni Arteriose Monitorate E Loro Associazioni.

BACKGROUND: Previous studies have shown that in the treated fraction of the hypertensive population, blood pressure (BP) control is less common for systolic BP (SBP) than for diastolic BP (DBP) as measured in the physician's office. Whether this phenomenon is artifactually attributable to a temporary increase in BP owing to a "white-coat" effect or represents a true rarity of SBP control in daily life is unknown. METHODS: Data were obtained from the PAMELA (Pressioni Arteriose Monitorate E Loro Associazioni) study population, which involved individuals ranging in age from 25 to 74 years who were representative of the residents of Monza (a city near Milan, Italy) and who were stratified according to sex. Office (an average of 3 sphygmomanometric measurements), home (an average of morning and evening self-measurements using a semiautomatic device), and 24-hour ambulatory (average of measurements performed every 20 minutes during the day and at night) BP values were obtained in all study subjects. In the treated hypertensive patients, BP was regarded as controlled if office values were less than 140 (SBP) or 90 (DBP) mm Hg. Home and 24-hour average SBP and DBP were regarded as controlled if the values were lower than 132/83 and 125/79 mm Hg, respectively. RESULTS: In the study participants (n = 2051), the number of patients with hypertension who were receiving antihypertensive treatment was 398, or approximately 42% of all individuals with hypertension. In-office SBP control by treatment was less frequent than DBP control (29.9% vs 41.5%, P<.05). This was also the case when home and 24-hour SBP and DBP control was considered (38.3% vs 54.6% and 50.8 vs 64.9%, respectively, P<.05 for both). CONCLUSIONS: In the PAMELA population, SBP control by treatment was much less frequent than DBP control by treatment. This was the case not only for office BP values but also for home and 24-hour BP values, demonstrating that inadequate SBP control is not limited to artificial BP-measuring methods but occurs in daily life.

Adult↗

Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents.

CONTEXT: Renin profiling and age-race subgroup may help select single-drug therapy for stage 1 and stage 2 hypertension. OBJECTIVE: To compare the plasma renin profiling and age-race subgroup methods as predictors of response to single-drug therapy in men with stage 1 and 2 hypertension as defined by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. DESIGN: The Veterans Affairs Cooperative Study on Single-Drug Therapy of Hypertension, a randomized controlled trial. SETTING: Fifteen Veterans Affairs hypertension centers. PATIENTS: A total of 1105 ambulatory men with entry diastolic blood pressure (DBP) of 95 to 109 mm Hg, of whom 1031 had valid plasma and urine samples for renin profiling. INTERVENTIONS: Randomization to 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem (sustained release), or prazosin. MAIN OUTCOME MEASURE: Treatment response as assessed by percentage achieving goal DBP (<90 mm Hg) in response to a single drug that corresponded to patients' renin profile vs a single drug that corresponded to patients' age-race subgroup. RESULTS: Clonidine and diltiazem had consistent response rates regardless of renin profile (76%, 67%, and 80% for low, medium, and high renin, respectively, for clonidine and 83%, 82%, and 83%, respectively, for diltiazem for patients with baseline DBP of 95-99 mm Hg). Hydrochlorothiazide and prazosin were best in low- and medium-renin profiles; captopril was best in medium- and high-renin profiles (low-, medium-, and high-renin response rates were 82%, 78%, and 14%, respectively, for hydrochlorothiazide; 88%, 67%, and 40%, respectively, for prazosin; and 51%, 83%, and 100%, respectively, for captopril for patients with baseline DBP of 95-99 mm Hg). Response rates for patients with baseline DBP of 95 to 99 mm Hg by age-race subgroup ranged from 70% for clonidine to 90% for prazosin for younger black men, from 50% for captopril to 97% for diltiazem for older black men, from 70% for hydrochlorothiazide to 92% for atenolol for younger white men, and from 84% for hydrochlorothiazide to 95% for diltiazem for older white men. Patients with a correct treatment for their renin profile but incorrect for age-race subgroup had a response rate of 58.7%; patients with an incorrect treatment for their renin profile but correct for age-race subgroup had a response rate of 63.1% (P = .30). After controlling for DBP and interactions with treatment group, age-race subgroup (P<.001) significantly predicted response to single-drug therapy, whereas renin profile was of borderline significance (P= .05). CONCLUSIONS: In these men with stage 1 and stage 2 hypertension, therapeutic responses were consistent with baseline renin profile, but age-race subgroup was a better predictor of response.

Adult↗

Combined calcium, magnesium and potassium supplementation for the management of primary hypertension in adults.

BACKGROUND: Previous research suggests that increasing dietary intakes of calcium, potassium or magnesium separately may reduce BP to a small degree over the short term. It is unclear whether increasing intakes of a combination of these minerals produces a larger reduction in BP. OBJECTIVES: To evaluate the effects of combined mineral supplementation as a treatment for primary hypertension in adults. SEARCH STRATEGY: We searched the Cochrane Library, MEDLINE, EMBASE, Science Citation Index, ISI Proceedings, ClinicalTrials.gov, Current Controlled Trials, CAB abstracts, and reference lists of systematic reviews, meta-analyses and randomised controlled trials (RCTs) included in the review. The search was unrestricted by language or publication status. SELECTION CRITERIA: Inclusion criteria were: 1) RCTs of a parallel or crossover design comparing oral supplements comprising a combination of potassium, and/or calcium, and/or magnesium with placebo, no treatment, or usual care; 2) treatment and follow-up >=8 weeks; 3) participants over 18 years old, with raised systolic blood pressure (SBP) >=140 mmHg or diastolic blood pressure (DBP) >=85 mmHg with no known primary cause; 4) SBP and DBP reported at end of follow-up. We excluded trials where participants were pregnant, or received antihypertensive medication which changed during the study. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Disagreements were resolved by discussion or a third reviewer. Random effects meta-analyses and sensitivity analyses were conducted. MAIN RESULTS: We included three RCTs (n=277) with between 24 and 28 weeks follow-up. Three combinations of minerals were investigated: potassium & magnesium, calcium & magnesium, and calcium & potassium. One trial investigated combinations of calcium & magnesium and of calcium & potassium, and for each found a statistically non-significant increase in both SBP and DBP. All three trials investigated the combination of potassium & magnesium. None of the trials provided data on mortality or morbidity. The combination of potassium & magnesium compared to control resulted in statistically non-significant reductions in both SBP (mean difference = -4.6 mmHg, 95% CI: -9.9 to 0.7) and DBP (mean difference = -3.8 mmHg, 95% CI: -9.5 to 1.8), although the results were heterogeneous (I(2)=68% and 85% for SBP and DBP respectively).A sensitivity analysis using alternative reported values which accounted for missing data had very little effect on DBP but resulted in a larger, statistically significant reduction in SBP (mean difference = -5.8 mmHg, 95% CI: -10.5 to -1.0). The quality of the trials was not well reported. AUTHORS' CONCLUSIONS: We found no robust evidence that supplements of any combination of potassium, magnesium or calcium reduce mortality, morbidity or BP in adults. More trials are needed to investigate whether the combination of potassium & magnesium is effective.

Adult↗