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Disruption of microfilament organization in living nonmuscle cells by microinjection of plasma vitamin D-binding protein or DNase I.

Plasma vitamin D-binding protein (DBP), which binds to monomeric actin, causes the breakdown of stress fibers when it is microinjected into nonmuscle cells. Disruption of the stress fiber network is also accompanied by shape changes in the cell that resemble those seen after cytochalasin treatment. When DBP was coinjected with fluorescently labeled alpha-actinin, no fluorescent stress fibers or attachment plaques were visible 30 min after injection. Twelve hours later the cells regained their flattened shape and their stress fibers. Fluorescently labeled DBP causes the same reversible changes in cell shape as the unlabeled protein. Upon injection, the labeled DBP diffuses throughout the cytoplasm, becoming localized by 12 hr in a punctate pattern, presumably due to lysozomal sequestration. Similar injections of DBP into skeletal myotubes and cardiac myocytes did not lead to shape changes or breakdown of nascent and/or fully formed myofibrils, even though DBP has a 2-fold higher binding affinity for muscle actin over that of the nonmuscle isoactins. Similar differential effects in nonmuscle cells were also observed after the microinjection of DNase I, another protein capable of binding monomer actin. The effects of these microinjected monomer actin-binding proteins imply that an accessible pool of monomer actin is needed to maintain stress fiber integrity in nonmuscle cells but not the integrity of the nascent or fully formed myofibrils in muscle cells.

Actin Cytoskeleton↗

The formation of a flexible DNA-binding protein chain is required for efficient DNA unwinding and adenovirus DNA chain elongation.

The adenovirus DNA-binding protein (DBP) binds cooperatively to single-stranded DNA (ssDNA) and stimulates both initiation and elongation of DNA replication. DBP consists of a globular core domain and a C-terminal arm that hooks onto a neighboring DBP molecule to form a stable protein chain with the DNA bound to the internal surface of the chain. This multimerization is the driving force for ATP-independent DNA unwinding by DBP during elongation. As shown by x-ray diffraction of different crystal forms of the C-terminal domain, the C-terminal arm can adopt different conformations, leading to flexibility in the protein chain. This flexibility is a function of the hinge region, the part of the protein joining the C-terminal arm to the protein core. To investigate the function of the flexibility, proline residues were introduced in the hinge region, and the proteins were purified to homogeneity after baculovirus expression. The mutant proteins were still able to bind ss- and double-stranded DNA with approximately the same affinity as wild type, and the binding to ssDNA was found to be cooperative. All mutant proteins were able to stimulate the initiation of DNA replication to near wild type levels. However, the proline mutants could not support elongation of DNA replication efficiently. Even the elongation up to 26 nucleotides was severely impaired. This defect was also seen when DNA unwinding was studied. Binding studies of DBP to homo-oligonucleotides showed an inability of the proline mutants to bind to poly(dA)(40), indicating an inability to adapt to specific DNA conformations. Our data suggest that the flexibility of the protein chain formed by DBP is important in binding and unwinding of DNA during adenovirus DNA replication. A model explaining the need for flexibility of the C-terminal arm is proposed.

Adenoviridae↗

Changes with malnutrition in the concentration of plasma vitamin D binding protein in growing rats.

The work presented here examines the possible effects of nutritional deficiencies on the characteristics of the plasma transport protein for vitamin D and its metabolites (vitamin D binding protein, DBP) in the growing rat. Deficiencies in both dietary protein intake and dietary energy intake may decrease the concentration of DBP in the circulation, although plasma DBP was not affected by dietary Ca deficiency. None of the dietary factors examined appears to influence the affinity of DBP for its major ligand, 25-hydroxycholecalciferol (25(OH)D(3)). Protein-deficient rats seemed to have difficulty in maintaining adequate concentrations of 1,25-dihydroxycholecalciferol (1,25(OH)(2)D(3)) in the circulation. The sensitivity of DBP to dietary protein and energy intake may constitute a novel mechanism that may help to explain the observed associations between malnutrition and the development of metabolic bone disease, through alterations to the cellular availability of vitamin D ligands to DBP.

25-Hydroxyvitamin D 2↗

Evaluation of the efficacy and tolerability of nebivolol versus lisinopril in the treatment of essential arterial hypertension: a randomized, multicentre, double-blind study.

The main objective of this study was to compare the anti-hypertensive efficacy and safety of nebivolol (5 mg once daily) and lisinopril (20 mg once daily) given for 12 weeks in patients with mild to moderate essential hypertension. Fourteen centres participated in this randomized, double-blind parallel group study. Sixty-eight patients with uncomplicated mild-to-moderate hypertension were randomized, and sixty-five were eligible for the analysis of efficacy (intention-to-treat). Hypertensive patients were newly diagnosed, or previous antihypertensive therapy was withdrawn at least 1 month before active treatment, and were included in the study if their diastolic blood pressure (DBP) was > 95 and < 114 mmHg. The age range was 24-65 years. The primary endpoints of the study were: (i) response rate: patients were defined as "normalized" responders if their blood pressure values were < 140/90 mmHg, or as "non-normalized" responders if the reduction in blood pressure was 10 mmHg or more, compared with baseline; (ii) changes in sitting blood pressure at the end of the study. The secondary endpoints were: standing blood pressure and sitting or standing heart rate (HR). Results showed that baseline sitting DBP was significantly different between groups. Analysis of covariance of the raw data performed with baseline as covariate demonstrated that the DBP and HR values were significantly lower in the nebivolol group at the 8th week. However, when an analysis of variance for repeated measures was performed, a significant reduction in sitting systolic blood pressure (SBP) (p < 0.0001), DBP (p < 0.0001) and HR (p < 0.0001) was observed throughout the study in both groups. No difference was observed between treatments, although for DBP, a significant interaction between treatment-weeks was observed (p = 0.016). There was also a statistically significant difference in favour of the nebivolol group in the distribution of responders and non-responders at week 8. Lisinopril and nebivolol were equally well tolerated. In conclusion, nebivolol was slightly more effective, in comparison with lisinopril, in terms of reduction in DBP. This greater efficacy was obtained without any increase in adverse effects, since both treatments were equally well tolerated.

Adrenergic beta-Antagonists↗

DNA adduct formation and persistence in rat tissues following exposure to the mammary carcinogen dibenzo[a,l]pyrene.

Dibenzo[a,l]pyrene (DBP), an environmentally significant polycyclic aromatic hydrocarbon (PAH), is one of the most potent carcinogens with greater carcinogenicity in rodent mammary glands and skin than 7,12-dimethylbenz[a]anthracene or benzo[a]pyrene, respectively. In this study, we have examined the formation and persistence of stable DNA adducts in rats administered a carcinogenic intramammillary (i.m.) dose of DBP (0.25 micromol/gland). 32P-post-labeling analysis of mammary epithelial DNA 6 h, and 2, 5 and 14 days post-treatment produced one major (approximately 30%) and at least six minor adducts. Non-target tissue DNA (lung, heart, bladder and pancreas) also showed essentially the same adduct pattern as did mammary DNA, except liver which resulted in four additional adduct spots. The mammary DNA was most adducted (2640 +/- 532 adducts/10(9) nucleotides) on day 5 while the other tissue DNAs had 10- to 65-fold lower adduct levels (lung > liver > heart > bladder > pancreas). Adduct levels continued to increase at all time points examined for all tissues, except mammary tissue which showed a decline ( approximately 40%) on day 14. Chromatographic comparison with adducts formed in vitro by reaction of syn- and anti-DBP-11, 12-diol-13,14-epoxides (DBPDEs) with DNA and individual nucleotides indicated that the in vivo adducts were deoxyadenosine- and deoxyguanosine-derived, formed by interaction with both the anti- and syn-isomers; the adenine-derived adducts comprised 60-75% of the total adducts. However, the liver-specific DNA adducts (nos 8-11) were not derived from any of the DBPDE isomers. Our data show: (i) significantly higher DBP-DNA adduction in mammary tissue as compared with non-target tissues, which is consistent with its mammary carcinogenicity; (ii) adenine is highly reactive towards DBP metabolites as has been observed for many other PAHs; and (iii) the peak binding of DBP with DNA was shifted beyond 14 days for the non-target tissues by i.m. route of exposure.

Animals↗

Bisoprolol versus hydrochlorothiazide plus amiloride in essential hypertension, a randomized double-blind study.

Beta blocker monotherapy is often considered to be inadequate in essential hypertension. It was the aim of this study to compare the antihypertensive activity of the new betablocker bisoprolol with the diuretic combination: hydrochlorothiazide plus amiloride. Forty hypertensive patients (DBP 95-120 mmHg) were enrolled in the study, of which 34 were evaluable for efficacy. The patients were, under double-blind conditions, randomly allocated to receive 10 mg bisoprolol (B) or 50 mg hydrochlorothiazide plus 5 mg amiloride (HA) as single daily doses for 30 days. Patients whose DBP had been normalized (less than or equal to 90 mmHg) after 30 days (D 30) continued the monotherapy for another 30 days. Patients whose DBP remained over 90 mmHg were, under single-blind conditions, kept on their initial treatment but received in addition the alternative drug for another 30 days (D 60). Blood pressure measurements were performed 24 hours after drug intake. The two groups comprising 17 patients each were comparable with regard to the patients' characteristics and baseline blood pressure values. After 30 days of treatment supine SBP, DBP and HR were significantly more reduced with B than with HA. The mean reduction of DBP was 16.8 +/- 8.0 mmHg with B and 8.4 +/- 6.4 mmHg with HA (P less than 0.002). After 30 days of monotherapy, blood pressure was within the normal range in 15/17 (88.2%) patients treated with B but in only 4/17 (23.5%) patients treated with HA (B vs HA: P less than 0.001). In the B group, there was a further slight decrease in SBP, DBP and HR during the second 30 day period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗

Effects of phthalate esters on the developing reproductive tract of male rats.

Phthalate esters are a large group of chemical agents used predominantly as plasticizers and solvents. Certain members of this chemical class have been shown to cause reproductive and developmental toxicity. Recent attention has focused on the potential of these agents to interfere with male reproductive development through a postulated antiandrogenic mechanism. Observations have focused on di-n-butyl phthalate (DBP), di-(2-ethylhexyl) phthalate (DEHP) and butyl benzylphthalate, with most information relating to dose-response relationships obtained for DBP. Neither DBP, DEHP nor their major metabolites interacted with human or rodent androgen receptors (AR) in transcriptional activation assays. DBP was administered during the critical window of development of the male reproductive system, after which the resulting offspring were examined until adulthood. DBP elicited marked effects on the developing male reproductive tract, including malformations of the epididymis and vas deferens, and hypospadias. Retention of thoracic nipples/areolae and reductions in anogenital distance were also noted. Surprisingly, Leydig cell adenomas were induced in some male offspring at 100 days of age. All these events occurred in the absence of any toxicity in the pregnant dam. Examination of testes from fetal rats indicated markedly reduced testosterone levels and increased Leydig cell numbers after DBP administration to the dams. Leydig cells were positive for AR and 3-betahydroxysteroid dehydrogenase.

Aging↗

Adipose tissue fatty acids and blood pressure in middle-aged men from southern Italy.

Adipose tissue (AT) biopsies were performed in a random population sample of 74 clinically healthy middle-aged men (40-49 years) from southern Italy. The percentage of saturated fatty acids (FA) in AT was directly correlated with systolic (SBP) and diastolic (DBP) blood pressure (p less than 0.01). This relationship was independent of smoking habit and body weight. AT of men in the upper DBP quintile (range 90-102 mmHg) was significantly richer in palmitic acid (p less than 0.01) compared to that of men in the lowest DBP quintile. Dietary history demonstrated that the overall intake of saturated fat (% energy) was similar in the two extreme DBP quintiles. There was a relatively higher consumption of fish by those in the lowest DBP quintile (p less than 0.05). The amount of monounsaturated fat consumed (% energy) was also higher (p less than 0.05) in men with low blood pressure. Men in the upper quintile of DBP consumed more eggs (p less than 0.05).

Adipose Tissue↗

Dose-dependent alterations in androgen-regulated male reproductive development in rats exposed to Di(n-butyl) phthalate during late gestation.

Di(n-butyl) phthalate (DBP) is a commercially important plasticizer and ubiquitous environmental contaminant. Since previous, limited dose-response studies with DBP that reported alterations in male reproductive development and function failed to establish a NOAEL (no-observed-adverse-effect level), an extensive dose-response study was conducted. Pregnant CD rats were given DBP by gavage at 0, 0.5, 5, 50, or 100 mg/kg/day (n = 19-20) or 500 mg/kg/day (n = 11) from gestation day 12 to 21. In male offspring, anogenital distance was decreased at 500 mg DBP/kg/day. Retained areolas or nipples were present in 31 and 90% of male pups at 100 and 500 mg/kg/day, respectively. Preputial separation was not delayed by DBP treatment in males with normal external genitalia, but cleft penis (hypospadias) was observed in 5/58 rats (4/11 litters) at 500 mg/kg/day. Absent or partially developed epididymis (23/58 rats in 9/11 litters), vas deferens (16/58 animals in 9/11 litters), seminal vesicles (4/58 rats in 4/11 litters), and ventral prostate (1/58 animals) occurred at 500 mg/kg/day. In 110-day-old F(1) males, the weights of the testis, epididymis, dorsolateral and ventral prostates, seminal vesicles, and levator ani-bulbocavernosus muscle were decreased at 500 mg/kg/day. At 500 mg/kg/day, widespread seminiferous tubule degeneration was seen in 25/58 rats (in 9/11 litters), focal interstitial cell hyperplasia in 14/58 rats (in 5/11 litters), and interstitial cell adenoma in 1/58 rats (in 1/11 litters). For this 10-day prenatal (embryonic and fetal) exposure to DBP, the NOAEL and LOAEL (lowest-observed-adverse-effect level) were 50 and 100 mg/kg/day, respectively. This is currently the lowest NOAEL described for the toxicity of DBP.

Androgens↗

Quantitative changes in gene expression in fetal rat testes following exposure to di(n-butyl) phthalate.

Di(n-butyl) phthalate (DBP) alters male reproductive development by decreasing testicular testosterone (T) production when fetuses are exposed on gestation days (GD) 12-21. Previous studies have shown altered gene expression for enzymes in the T biosynthetic pathway following exposure to DBP. The objectives of this study were to develop a more detailed understanding of the effect of DBP on steroidogenesis, using a robust study design with increased numbers of dams and fetuses, compared with previous studies, and to explore messenger RNA (mRNA) expression for other critical genes involved in androgen biosynthesis and signaling. Additionally, immunohistochemical localization of protein expression for several key genes was performed to further confirm mRNA changes. Fetal Leydig cell lipid levels were also examined histochemically, using oil red O. Six to seven pregnant Crl:CD(SD)BR rats per group were gavaged with corn oil or DBP at 500 mg/kg/day on GD 12-19. Testicular RNA isolated from three randomly selected GD 19 fetuses per litter was used for real-time RT-PCR for the following genes: scavenger receptor class B-1 (SRB1), steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage enzyme (P450scc), 3beta-hydroxysteroid dehydrogenase (3beta-HSD), P450c17, 17beta-hydroxysteroid dehydrogenase (17beta-HSD), androgen receptor (AR), luteinizing hormone receptor (LHR), follicle-stimulating hormone receptor (FSHR), stem cell factor tyrosine kinase receptor (c-kit), stem cell factor (SCF), proliferating cell nuclear antigen (PCNA), and testosterone-repressed prostate message-2 (TRPM-2). mRNA expression was downregulated for SRB1, StAR, P450scc, 3beta-HSD, P450c17, and c-kit following DBP exposure, and TRPM-2 was upregulated. 17beta-HSD, AR, LHR, FSHR, and PCNA were not significantly changed. Immunohistochemical staining for c-kit was seen in fetal Leydig cells, which has not been previously reported. Downregulation of most of the genes in the T biosynthetic pathway confirms and extends previous findings. Diminished Leydig cell lipid content and alteration of cholesterol transport genes also support altered cholesterol metabolism and transport as a potential mechanism for decreased T synthesis following exposure to DBP.

Administration, Oral↗

Pharmacokinetics of dibutylphthalate in pregnant rats.

Dibutylphthalate (DBP) can cause adverse effects on the developing male reproductive tract when administered late in gestation to pregnant rats. The objectives of this study were to evaluate the metabolism of DBP in female rats, and the pharmacokinetics of DBP in pregnant rats on gestational day (g.d.) 20. The identities of DBP metabolites in urine and in maternal and fetal plasma were confirmed by LC-MS/MS, as monobutylphthalate (MBP) and its glucuronide, monohydroxybutylphthalate and its glucuronide, and butanoic acid phthalate and its glucuronide. An LC-MS/MS method was developed for the quantitation of MBP and its glucuronide. MBP and MBP glucuronide were quantitated in maternal and fetal plasma, and in amniotic fluid from pregnant rats administered a single dose of DBP (50, 100, or 250 mg/kg by gavage in corn oil) on g.d. 20. The pharmacokinetics of MBP and MBP glucuronide were determined. MBP was the major metabolite in maternal and fetal plasma. With increasing dose, there was a nonlinear increase in area under the curve (AUC) for MBP, with a ten-fold increase in maternal plasma, and an eight-fold increase in fetal plasma between 50 mg/kg and 250 mg/kg. In amniotic fluid, the major metabolite initially was MBP, but by 24 h after dosing, the major metabolite was MBP glucuronide. Isomers of the MBP glucuronide were detected in amniotic fluid, suggesting acyl group migration, known to occur with acyl glucuronides. This study indicated that MBP, thought to be the active metabolite of DBP, can cross the placenta in late gestation, and that the metabolism of MBP is saturable.

Algorithms↗

Long-term effects of a standardized complex mixture of urban dust particulate on the metabolic activation of carcinogenic polycyclic aromatic hydrocarbons in human cells in culture.

Humans are exposed to complex mixtures of polycyclic aromatic hydrocarbons in the atmosphere. We examined the long term effects of a standard reference material (SRM) 1649a over time on the metabolic activation and DNA adduct formation by two carcinogenic PAHs, benzo[a]pyrene (BP) and dibenzo[a,l]pyrene (DBP) in the human mammary carcinoma derived cell line MCF-7. PAH-DNA adduct analysis, cytochrome P450 (CYP) enzyme activity, CYP1A1 and CYP1B1 protein expression were determined in cells treated with SRM 1649a alone or SRM 1649a with either BP or DBP for 24 to 120 h. Averaging over time, significantly higher levels of DNA adducts were observed in cells treated with BP or DBP alone than in co-treatments with SRM 1649a and BP or DBP. Ethoxyresorufin O-deethylase assay indicated a significant increase in activity in cells treated with BP alone and co-treated with SRM1649a in comparison to other treatment groups. Induction of CYP1A1 and CYP1B1 protein expression was observed by immunoblots in cells treated with BP alone or in co-treatments of SRM 1649a and BP or DBP. These data demonstrate the influence of the components of SRM 1649a in inhibiting the activation of BP or DBP by CYP enzymes in the formation of DNA adducts. It also suggests that the carcinogenic activity of PAH within a complex mixture may vary with composition and activation of the components present in the complex mixture.

Aryl Hydrocarbon Hydroxylases↗

Cardiac regression and blood pressure control in the Dahl rat treated with either enalapril maleate (MK 421, an angiotensin converting enzyme inhibitor) or hydrochlorothiazide.

Enalapril maleate (MK 421), and hydrochlorothiazide were used to evaluate the control of hypertension and reversal of myocardial hypertrophy in Dahl sensitive (DS) and Dahl resistant (DR) rats given either a high (8% NaCl) or a low salt (0.4% NaCl) diet. Groups of six-week-old male DS and DR rats were treated with enalapril (15-100 mg/kg/day) in drinking water for eight weeks. Additional comparable groups of DS and DR were also treated with hydrochlorothiazide (60-400 mg/kg/day). Systolic blood pressure (SBP), diastolic blood pressure (DBP), heart rate (HR) and heart weight/body weight (Hwt/Bwt) ratio were determined. We observed significant reduction in Hwt/Bwt ratio (P less than 0.001) along with control of SBP and DBP in the DS given a high salt diet treated with either enalapril or hydrochlorothiazide. However, in the DR given a high salt diet, cardiac regression (Hwt/Bwt ratio, P less than 0.05), SBP and DBP (P less than 0.01) reduction were seen only with enalapril. Similarly, cardiac regression (Hwt/Bwt ratio, P less than 0.05) was observed along with reduction of SBP and DBP (P less than 0.001) in the DS given a low salt diet and DR given enalapril. These data indicate that enalapril reduced SBP and DBP in association with cardiac regression in hypertensive and normotensive rats. In contrast, hydrochlorothiazide only reduced SBP, DBP and caused cardiac reversal (Hwt/Bwt ratio) in DS placed on a high salt diet.

Animals↗

Can mean arterial pressure be estimated from measurements of systolic and diastolic blood pressure, and vice versa?

We investigated the reliability of calculating the mean blood pressure (MBP) in spontaneously hypertensive rats (SHR) from the systolic and diastolic blood pressures (SBP; DBP), using a form factor, calculated as: (MBP - DBP)/(SBP - DBP). The mean values of this form factor, as determined by blood pressure curve integration, were 0.459 and 0.450 in awake and anaesthetized SHR, respectively. There was no change in the form factor with pulse frequency. When direct femoral artery MBP measurements (x) were compared with MBP values (y) calculated from tail-cuff measurements of SBP and DBP using the form factor, the linear relationship between the two parameters was: y = 0.91x + 1.5 mmHg (r = 0.98). Actually, direct measurements confirmed that the tail artery MBP was 6-7% lower than the femoral artery MBP. In awake Wistar-Kyoto (WKY) rats, the form factor was 0.468. We therefore concluded that an approximate form factor value of 0.46 could be used in rats to estimate the MBP from known values of SBP and DBP. We further suggest that, because pulse pressure in any given rat remains relatively constant with time, SBP and DBP can be estimated in experiments by initially measuring the pulse pressure; thus, only the MBP need be recorded thereafter.

Animals↗

Inverse relationship between upright plasma renin activity and twenty-four hour blood pressure variability in borderline hypertension.

Office, i.e. measured by the physician at rest, and 24 h ambulatory systolic (SBP) and diastolic (DBP) blood pressures, heart rate, supine and upright plasma renin activities, supine and upright aldosterone concentrations and plasma and urine sodium and potassium were measured in 61 young male subjects aged 19-25 years, including 40 normotensive subjects (office DBP less than or equal to 90 mmHg and office SBP less than or equal to 140 mmHg) and 21 borderline hypertensive subjects (non-normal blood pressures with office DBP less than or equal to 95 mmHg and office SBP less than or equal to 160 mmHg). No significant differences were found in the plasma or urine K+ or Na+, upright or supine plasma renin activity or aldosterone concentration between normotensives and borderline hypertensive subjects. No correlation was detected between plasma and urine K+ or Na+, upright and supine aldosterone concentration or supine plasma renin activity and blood pressure. In contrast, significant inverse correlations were observed between upright plasma renin activity and blood pressure. The correlations were approaching statistical significance when upright plasma renin activity was related to office SBP and office DBP (r = -0.22, P = 0.097 and r = -0.25, P = 0.049, respectively), and were more significant when plasma renin activity was related to 24 h mean DBP (r = -0.32, P = 0.013) and to SBP and DBP standard deviations (r = -0.37, P = 0.004 and r = -0.26, P = 0.04, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Reproducibility of ambulatory and clinic blood pressure measurements in elderly hypertensive subjects.

OBJECTIVES: To compare the reproducibility of clinic and ambulatory blood pressure measurements in elderly hypertensive subjects. SUBJECTS: Twenty-two untreated elderly hypertensives, with a clinic systolic blood pressure (SBP) > 160 mmHg and/or diastolic blood pressure (DBP) > 95 mmHg, and a mean age of 76 years (range 66-86). METHODS: Following three supine clinic blood pressure readings the subjects underwent 24-h non-invasive ambulatory blood pressure monitoring, measurements being taken at 20-min intervals from 0700 to 2200 h and at 30-min intervals from 2200 to 0700 h. Measurements were repeated during a further visit at a median interval of 10 weeks (range 1-10 months). RESULTS: Daytime ambulatory SBP levels were 20 mmHg (95% confidence interval 14-27 mmHg, P < 0.001) lower than clinic SBP, although DBP values were similar. The mean 24-h ambulatory SBP and DBP reproducibility [assessed by the standard deviation of differences (SDD) between visits] was significantly better than that for mean clinic blood pressure (SBP 6.3 versus 17.4 mmHg, P < 0.001; DBP 4.8 versus 7.0 mmHg, respectively, P < 0.05). With daytime defined as 1000-1959 h, the SDD between visits was 12.4 mmHg for SBP and 8.3 mmHg for DBP, but with daytime defined as 0700-2159 h, the SDD fell to 6.0 mmHg for SBP and 4.8 mmHg for DBP, values almost identical to those obtained with full 24-h blood pressure monitoring. There was no difference in night-time blood pressure reproducibility, whether night-time was defined as 2400-0559 h or 2200-0659 h. CONCLUSIONS: Both 24-h and daytime ambulatory blood pressure monitoring significantly improve the reproducibility of blood pressure measurements compared with clinic blood pressure readings in elderly hypertensive subjects. Increasing the number of daytime blood pressure readings by 50% (from 30 to 45) reduced the variability of blood pressure measurement by 50%. Twenty-four-hour ambulatory blood pressure monitoring is of value in obtaining reproducible blood pressure measurements in elderly hypertensive subjects. However, more than 30 readings are needed during a daytime recording to significantly reduce variability compared with repeated clinic measurements, although night-time variability is not significantly affected if the number of readings is reduced to 12 over a 6-h period.

Age Factors↗

Risk of fatal stroke according to blood pressure level: an 18-year follow-up of the Oslo Study.

OBJECTIVE: To determine how blood pressure level predicts the incidence of fatal stroke. DESIGN: The Oslo Study is a prospective cohort study of preventive and epidemiological aspects of cardiovascular disorders in middle-aged men. Of 25,915 men invited, 16,209 aged 40-49 years attended the screening. A 7% random sample of men aged 20-39 years were also invited to attend. METHODS: The screening started in May 1972 and the analysis presented is an 18-year follow-up for fatal strokes. Men with a history of stroke were excluded from the analyses. RESULTS: Of 16,173 men with no history of stroke 85 died from stroke. Results from Cox proportional hazards regression analysis confirm diastolic (DBP) and systolic blood pressure (SBP) as strong independent risk factors of fatal stroke, with DBP being the stronger predictor. Analyses of risk of fatal stroke by quintile values show SBP to give significantly increased risk from the third quintile (136 mmHg), and DBP from the fifth quintile (95 mmHg) relative to the first quintile. No levelling off at highest levels can be seen when analysing decile values. No J-shape of the curve was evident. Men on drug treatment for hypertension with no stroke history (n = 440) had 4.7-fold (crude) and 2.8-fold (adjusted for age and DBP) the rate of stroke mortality of men not on drug treatment for hypertension. CONCLUSION: DBP was a stronger predictor than SBP, with increasing risk from the fifth quintile of DBP and the third quintile of SBP. Men on drug treatment for hypertension at screening were at increased risk during the follow-up period, indicating that their treatment did not sufficiently reduce their risk of stroke.

Adult↗

The importance of pulsatile components of hypertension in predicting carotid stenosis in older adults.

OBJECTIVE: To evaluate pulsatile components of the blood pressure as risk markers for carotid stenosis in isolated systolic hypertension. DESIGN: Duplex scans with Doppler measures of the blood flow velocity were used to diagnose carotid stenosis in 187 participants in the Systolic Hypertension in the Elderly Program and in 187 normotensive and mildly hypertensive control subjects. METHODS: The systolic blood pressure (SBP), diastolic blood pressure (DBP), pulse pressure, and mean arterial pressure (MAP) were selected as independent variables. A logistic regression model for carotid stenosis was used to adjust for potentially confounding risk factors. Serial models, each containing single or double blood pressure variables, were run to compare risk markers for carotid stenosis. Receiver operating characteristic curves were compared to assess the predictive value of each model. RESULTS: In the multivariate analysis, both the SBP (P = 0.005) and the pulse pressure (P < 0.001) were predictive of carotid stenosis, but the DBP and MAP were not. However, when either the SBP or the pulse pressure was included in the model, the DBP was associated negatively with carotid stenosis (P < 0.001 and P = 0.023, respectively). An increased pulse pressure and a decreased DBP were independent risk markers for carotid stenosis. Comparison of receiver operating characteristic curves indicated that the pulse pressure had superior predictive value to the SBP (P = 0.034). CONCLUSIONS: The pulse pressure is the single best predictor of carotid stenosis. There is a negative correlation between the DBP and carotid stenosis for subjects with isolated systolic hypertension, but this can be demonstrated only after one has stratified for the SBP or for the pulse pressure. Thus, the pulsatile components of the blood pressure, increased pulse pressure and decreased DBP, are the most sensitive risk markers for the diagnoses of carotid stenosis.

Adult↗