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PubMed1999

The long-term prognostic significance of repeated blood pressure measurements in the elderly: SPAA (Studio sulla Pressione Arteriosa nell'Anziano) 10-year follow-up.

BACKGROUND: In young and middle-aged people, both systolic (SBP) and diastolic (DBP) blood pressure have a continuous, strong, and independent relationship with subsequent cardiovascular morbidity and mortality. These relationships are not well documented in older people and, until now, studies in the elderly do not provide homogeneous results on the importance of DBP compared with SBP as a cardiovascular risk factor. OBJECTIVE: To determine whether SBP and DBP are independent indicators of mortality risk in the elderly. DESIGN: An observational prospective cohort study to analyze the long-term prognostic significance of repeated SBP and DBP measurements in the elderly. PATIENTS AND METHODS: A total of 3858 outpatients 65 years or older (mean age [SD], 72.9 [4.9] years, 43.5% men) were selected randomly by 444 Italian National Health Service general practitioners in 1983. The population was followed up for 10 years. Crude and adjusted incidence rates of total and cardiovascular mortality were analyzed for classes of SBP and DBP based on the values recorded at the 2 initial visits 1 week apart and those measured during the first 12 months of follow-up. RESULTS: During the 10-year follow-up, 74 patients (1.9%) were lost to follow-up and 1561 (41.3%) died, 709 (45.4% of all deaths) from cardiovascular causes. A positive continuous, graded, strong, and independent association was observed with both total (P<.001) and cardiovascular (P<.001) mortality for SBP but not for DBP. The pattern was similar in both sexes, in persons younger and older than 75 years, regardless of preexisting cardiovascular diseases, and whether they had been receiving antihypertensive treatment at baseline. There was no J-shaped mortality curve in the subjects with the lowest SBP and DBP. CONCLUSIONS: These findings suggest that SBP, but not DBP, is a strong, positive, continuous, independent indicator of mortality risk in the elderly and should be stressed much more than DBP in the diagnosis and treatment of hypertension in this age group.

Aged↗
PubMedDate not supplied

Pulse pressure and cardiovascular disease-related mortality: follow-up study of the Multiple Risk Factor Intervention Trial (MRFIT).

CONTEXT: The sixth Joint National Committee (JNC-VI) classification system of blood pressure emphasizes both systolic blood pressure (SBP) and diastolic blood pressure (DBP) for cardiovascular disease risk assessment. Pulse pressure may also be a valuable risk assessment tool. OBJECTIVE: To compare relationships of SBP, DBP, and pulse pressure, separately and jointly, with cardiovascular disease-related mortality in men. DESIGN AND SETTING: Data from the Multiple Risk Factor Intervention Trial (MRFIT), which screened men aged 35 to 57 years from 1973 through 1975 at 22 US centers, was used to assess cardiovascular disease-related mortality through 1996. PARTICIPANTS: A total of 342 815 men without diabetes or a history of myocardial infarction were divided into 2 groups based on their age at MRFIT screening (35- to 44-year-olds and 45- to 57-year olds). Participant blood pressure levels were classified into a JNC-VI blood pressure category based on SBP and DBP (optimal, normal but not optimal, high normal, stage 1 hypertension, stage 2-3 hypertension), and pulse pressure was calculated. MAIN OUTCOME MEASURE: Cardiovascular disease-related mortality. RESULTS: There were 25 721 cardiovascular disease-related deaths. Levels of SBP and DBP were more strongly related to cardiovascular disease than pulse pressure. Relationships of SBP, DBP, and pulse pressure to cardiovascular disease-related mortality varied within JNC-VI category. Concordant elevations of SBP and DBP were associated with a greater risk of cardiovascular disease-related mortality for both age groups of men. Among men aged 45 to 57 years, higher SBP and lower DBP (discordant elevations) also yielded a greater risk of cardiovascular disease-related mortality. CONCLUSION: In both age groups, cardiovascular disease risk assessment was improved by considering both SBP and DBP, not just SBP, DBP, or pulse pressure separately.

Adult↗
PubMedDate not supplied

Developmental effects of di-n-butyl phthalate after a single administration in rats.

The objective of this study was to determine the susceptible day for the developmental toxicity of di-n-butyl phthalate (DBP). Pregnant rats were given a single dose of DBP by gastric intubation at 1500 mg kg(-1) on one of days 6-16 of pregnancy. A significant increase in the incidence of postimplantation loss was found in pregnant rats given DBP on one of days 6-16, except for days 7 and 11. Significant increases in the incidences of fetuses with skeletal malformations, of fetuses with skeletal and internal malformations and of fetuses with external and skeletal malformations were noted after a single dosing of DBP on day 8, on day 9 and on day 15, respectively. Deformity of the cervical vertebrae was frequently observed after administration of DBP on day 8. Deformity of the cervical and thoracic vertebrae and ribs and dilatation of the renal pelvis were predominantly found in fetuses of dams treated with DBP on day 9. Cleft palate and fusion of the sternebrae were exclusively detected after administration of DBP on day 15. It could be concluded that the manifestation of deviant development induced by DBP varies with the developmental stage at the time of administration and that DBP induces two discrete responses from embryos to teratogenicity on days 8 and 9 and on day 15 of pregnancy.

Abnormalities, Drug-Induced↗
PubMed2005

Critical window of male reproductive tract development in rats following gestational exposure to di-n-butyl phthalate.

BACKGROUND: Gestational exposure to di-n-butyl phthalate (DBP), a ubiquitous environmental contaminant, has been shown to interfere with the development of the male reproductive tract by acting as an antiandrogen. This study was conducted to identify the critical days for the abnormal development of the male reproductive tract, specifically the testis and epididymis. METHODS: Timed-pregnant Sprague-Dawley rats were dosed with DBP at 500 mg/kg/day on gestation day (GD) 14 and 15, 15 and 16, 16 and 17, 17 and 18, 18 and 19, or 19 and 20 (GD 0=plug day). Anogenital distance (AGD) was measured on postnatal day (PND) 1 and 13, while areloa number was recorded on PND 13 only. After weaning, males were allowed to mature to PND 90 at which time they were necropsied. Areloa number and AGD were recorded and testes, epididymides, seminal vesicles, prostate gland, kidneys, and liver weighed. Blood serum was collected and assayed for total testosterone concentration. RESULTS: There were no observable effects on litter size, sex ratio, serum testosterone concentration, or mortality of pups. Statistically significant permanent reductions in AGD were seen in males exposed prenatally to DBP on GD 15 and 16 or GD 18 and 19. On PND 13, areola were present in males exposed to DBP on GD 15 and 16, 16 and 17, 17 and 18, and 19 and 20. However, permanent retention occurred only in males after DBP exposure on GD 16 and 17. Exposure to DBP on only GD 17 and 18 elicited a reduction in epididymal weights; while exposure on only GD 16 and 17 caused a significant increase in the weights of the testes due to edema. In this study, epididymal and testicular malformations were most prevalent after exposure to DBP on any gestational day. Epididymal malformations, characterized by agenesis of various regions and small or flaccid testes were significantly increased in DBP-exposed males only on GD 16 and 17. CONCLUSIONS: These findings suggest that 2-day DBP exposure is highly detrimental to the developing reproductive tract of the male fetus and the critical window for abnormal development is GD 16-18.

Abnormalities, Drug-Induced↗
PubMed1985

Two functions encoded by adenovirus early region 1A are responsible for the activation and repression of the DNA-binding protein gene.

Human adenovirus early region 1A (E1A) gene products differentially regulate the expression of early region 2A (E2A) encoding the DNA-binding protein (DBP). In a microinjection system, plasmids containing the DBP gene associated with both its early (map coordinate 75) and late (coordinate 72) promoters, or only with the early promoter, are inefficiently expressed, and the presence of E1A DNA is required for full expression. In contrast, the E2A plasmid in which the DBP gene is associated solely with its late promoter, efficiently produces DBP, the synthesis of which is significantly inhibited by an E1A gene product. To identify which of the E1A products is responsible for either activation or repression of DBP gene expression, two E1A mutants (Ad5hr1 and Ad2/5pm975) have been tested in the microinjection system in the presence of different DBP plasmids containing either one or both promoters. The results obtained indicate that the product encoded by the E1A 13S mRNA is responsible for the stimulation of DBP produced from the early promoter and that the 12S mRNA codes for the product which represses the synthesis of DBP from the late promoter. These results were confirmed using clones in which the E2A early or late promoter was associated to the chloramphenicol acetyltransferase (CAT) gene and assayed for CAT activity after cell transfection in the absence or in the presence of wild-type or mutant E1A plasmids, and we have also shown that this promoter-dependent regulation is reflected in the relative amount of specific DBP mRNA.

Acetyltransferases↗
PubMed1998

A possible new role for vitamin D-binding protein in osteoclast control: inhibition of extracellular Ca2+ sensing at low physiological concentrations.

Upon removal of its sialic acid or galactose residue, vitamin D-binding protein (DBP) becomes a potent macrophage-activating factor, DBP-MAF. Here we document a new function of DBP-MAF and its parent molecule, DBP, in osteoclast control. We show that all DBPs potently inhibit extracellular Ca2+ (cation) sensing at low nanomolar concentrations with the following rank order of potency: native DBP = sialidase-treated DBP > beta-galactosidase-treated DBP. This attenuation remains unaffected despite co-incubation either with the native DBP ligand, 1,25-dihydroxyvitamin D3, or with an asialoglycoprotein receptor modulator, asialoorosomucoid. Taken together, the results suggest that circulating DBP may play a role in the systemic control of osteoclastic bone resorption, a hitherto unrecognized action of the protein.

Animals↗
PubMed1995

Comparative developmental toxicity of n-butyl benzyl phthalate and di-n-butyl phthalate in rats.

n-Butyl benzyl phthalate (BBP) and di-n-butyl phthalate (DBP) were evaluated and compared for their developmental toxic potential. Pregnant rats were given either BBP or DBP by gastric intubation at a dose of 0.75, 1.0 and 1.25 g/kg on days 7-9, days 10-12 and days 13-15 of pregnancy. Regardless of the days of treatment, a significantly increased incidence of postimplantation loss was found at all doses of BBP and DBP. While treatment with BBP and DBP at doses of 0.75 g/kg and above on days 7-9 or days 13-15 resulted in a significant increase in the incidence of fetuses with malformations, no increase in the incidence of malformed fetuses was found after treatment with BBP and DBP on days 10-12. The incidences of postimplantation loss and malformed fetuses increased as the doses of BBP and DBP were increased. Deformity of the vertebral column and ribs commonly occurred after treatment with BBP and DBP on days 7-9. Cleft palate and fusion of the sternebrae were predominantly observed after treatment with BBP and DBP on days 13-15. The similarity in dependence of gestational days of treatment on the manifestation of developmental toxicity and on the spectrum of fetal malformations caused by BBP and DBP suggests that they may act by the same mechanism, possibly via a common metabolite of these two parent compounds.

Abnormalities, Drug-Induced↗
PubMed1978

Comparison of DNase, DNA-polymerase and RNA-polymerase activities present in the DNA-binding proteins of normal human dermis, epidermis, horny layer and psoriatic scales.

DNA-binding proteins (DBP) of normal human dermis, epidermis, horny layer and psoriatic scales represent a tissue-specific group of mostly nuclear nonhistone proteins. To analyse their function, the different DBP fractions were examined concerning the presence of DNase, DNA-polymerase and RNA-polymerase activities. DBP of normal epidermis and horny layer contain four different DNases. One DNase of both DBP fractions is active only at pH 5.0. Three DNases of epidermal DBP are active at a pH-range from 5.0--8.5, while the corresponding DNases of horny layer-DBP are most active at pH 7.4. Probably these DNases have changed their pH-optimum during keratinisation. DBP of psoriatic scales include no activity of these three DNases and the pH 5.0-DNases seem to have reduced DNA-affinity. Human dermis DBP contain quite another set of four DNases which hardly can be correlated to the DNases of epidermal DBP. DNA-polymerase activities are present in each fraction and derive from different DNA-polymerases. Two DNA-polymerases with pI-values of 4.5 and 9.3 may correspond to beta- and alpha-DNA-polymerase of eukaryotes, respectively. Further activity of proteins which are focussed at pH 6.5--7.2 and 8.2 could be detected. The proteins represent either tissue-specific DNA-polymerases or further thymidine monophosphate incorporating enzymes. Contrary, RNA-polymerase activity could not be enriched from correlating extracts by DNA-cellulose chromatography.

DNA-Directed DNA Polymerase↗
PubMed1992

The phosphonic acid analog of phosphatidylglycerol phosphate: influence on Escherichia coli growth and physiology.

At 20 microM, rac-3,4-dihydroxybutyl-1-phosphonate (DBP) has only a slight bacteriostatic effect on Escherichia coli. However, cells lose viability when the medium also contains either 20 mM magnesium or calcium ions. Magnesium ions stimulate the incorporation of DBP into (1,2-diacyl)-sn-glycerol-D-4'-phosphoryloxy-3'-hydroxybutyl-1'-pho sphonate, the phosphonate analog of phosphatidylglycerol phosphate. Much higher DBP concentrations are needed to block the growth of a pgsA3 mutant than to block the growth of an isogenic wild-type strain. The DBP-treated pgsA mutant also has a much higher survival rate when stored in the cold than does the DBP-treated wild-type strain. Furthermore, the pgsA3 mutant grows normally in the presence of DBP and magnesium ions. Treatment with DBP and magnesium ions does not appear to disrupt the cell's inner or outer membranes. However, it does block macromolecular and phosphoglyceride synthesis. A combination of 20 microM rac-DBP and 0.5 mM spermidine or 0.125 mM spermine is bacteriostatic. These studies indicate that the PGP analog contributes to DBP's bacteriostatic effect when the growth medium contains low concentrations of magnesium or calcium ions and is responsible for its bactericidal effect when the medium contains high concentrations of these ions.

Butylene Glycols↗
PubMed1983

Analysis of expression of adenovirus DNA (fragments) by microinjection in Xenopus oocytes. Independent synthesis of minor early region 2 proteins.

Injection of whole adenovirus DNA into Xenopus oocytes results in the synthesis of large amounts of the early region 2A DNA-binding protein (E2A-DBP) and smaller amounts of polypeptide IX. The lack of synthesis of any functional messenger RNAs transcribed from the major late promotor at 16.3 map units is remarkable. Cleavage of the adenovirus DNA outside the E2A gene proper by restriction enzymes decreases synthesis of the DBP to about 10% of the amount produced after injection of intact DNA. On the other hand, presence of the terminal (Bellett) protein on the injected template enhances DBP synthesis considerably. Experiments with injected DNA restriction fragments, as well as reconstructed genes cloned into pBR322, indicate that efficient synthesis of DBP in oocytes requires the presence of either or both of the two main promoters from which the E2A gene is transcribed plus an intact 3' end of the gene. In the absence of any known promotor, 100-fold lower amounts of otherwise normal DBP are produced. Unlike in a regular infection, synthesis of DBP in oocytes does not require the product of the E1A gene. The same series of experiments also demonstrates that the DBP, a phosphoprotein, is the substrate of a cellular rather than a virus-encoded protein kinase. Two minor E2A proteins, although colinear with the major DBP, are synthesized independently. Synthesis of a 44,000 Mr protein, probably corresponding to the carboxy-terminal 360 amino acid residues of the DBP, is not decreased after injection of "promotorless" E2A genes. Unlike the 44,000 Mr protein, production of a 67,000 Mr protein (carboxy-terminal 483 amino acid residues) by one DNA-construct is probably directed by a T-A-T-A-A-A-T-A sequence in the vector DNA.

Adenoviruses, Human↗
PubMed1990

Blood pressure, stroke, and coronary heart disease. Part 1, Prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias.

The associations of diastolic blood pressure (DBP) with stroke and with coronary heart disease (CHD) were investigated in nine major prospective observational studies: total 420,000 individuals, 843 strokes, and 4856 CHD events, 6-25 (mean 10) years of follow-up. The combined results demonstrate positive, continuous, and apparently independent associations, with no significant heterogeneity of effect among different studies. Within the range of DBP studied (about 70-110 mm Hg), there was no evidence of any "threshold" below which lower levels of DBP were not associated with lower risks of stroke and of CHD. Previous analyses have described the uncorrected associations of DBP measured just at "baseline" with subsequent disease rates. But, because of the diluting effects of random fluctuations in DBP, these substantially underestimate the true associations of the usual DBP (ie, an individual's long-term average DBP) with disease. After correction for this "regression dilution" bias, prolonged differences in usual DBP of 5, 7.5, and 10 mm Hg were respectively associated with at least 34%, 46%, and 56% less stroke and at least 21%, 29%, and 37% less CHD. These associations are about 60% greater than in previous uncorrected analyses. (This regression dilution bias is quite general, so analogous corrections to the relations of cholesterol to CHD or of various other risk factors to CHD or to other diseases would likewise increase their estimated strengths.) The DBP results suggest that for the large majority of individuals, whether conventionally "hypertensive" or "normotensive", a lower blood pressure should eventually confer a lower risk of vascular disease.

Adult↗
PubMed1994

Characterization of the developmental toxicity of di-n-butyl phthalate in rats.

The objective of this study was to determine the characterization of the developmental toxicity of di-n-butyl phthalate (DBP) in rats. Pregnant rats were given DBP by gastric intubation at a dose of 0.75, 1.0 or 1.5 g/kg on days 7-9, 10-12 or 13-15 of pregnancy. Postimplantation loss was 100% for each period of dosing at 1.5 g/kg. A significant increase in the postimplantation loss was found in dams given DBP at doses of 0.75 and 1.0 g/kg regardless of the days of treatment. No evidence of teratogenicity was detected when DBP was given on days 10-12. Treatment on days 7-9 with DBP at doses of 0.75 and 1.0 g/kg caused a significant increase in the number of skeletal malformations such as deformity of the vertebral column in the cervical and thoracic regions and of the ribs, but neither external nor internal malformations. Treatment with DBP on days 13-15 at doses of 0.75 and 1.0 g/kg resulted in a significant increase in the incidence of fetuses with external and skeletal malformations such as cleft palate and fusion of the sternebrae. The frequency of malformations increased as the dose of DBP was increased. The highest incidence of malformed fetuses occurred after treatment with DBP on days 13-15. It could be concluded that susceptibility to the teratogenicity of DBP varies with the developmental stage at the time of administration.

Abnormalities, Drug-Induced↗
PubMed2004

Tumor formation in the neonatal mouse bioassay indicates that the potent carcinogen dibenzo[def,p]chrysene (dibenzo[a,l]pyrene) is activated in vivo via its trans-11,12-dihydrodiol.

The hexacyclic aromatic hydrocarbon dibenzo[def,p]chrysene, better known as dibenzo[a,l]pyrene (DBP) in the field of chemical carcinogenesis, is present in the environment as a combustion product of organic matter. This compound is probably the strongest chemical carcinogen ever tested. As ultimate genotoxic metabolites of DBP two electrophilically reactive species are discussed: (i) radical cations generated by one-electron oxidation, and (ii) fjord region dihydrodiol epoxides formed via the trans-11,12-dihydroxy 11,12-dihydro derivative of DBP (11,12-dihydrodiol). In order to delineate the metabolic pathway(s) involved in tumor formation by DBP, newborn Crl:CD-1(ICR)BR mice were intraperitoneally treated with the parent compound, its 11,12-dihydrodiol, and the two diastereomeric fjord region dihydrodiol epoxides. Due to severe acute and chronic toxicity, the total dose of DBP and of the 11,12-dihydrodiol was limited to 40 nmol. For the same reason the dihydrodiol epoxides could only be applied in doses up to 0.4 nmol. The tumor incidence was determined 55 +/- 1 weeks after treatment. Under these conditions, DBP and its 11,12-dihydrodiol induced lung tumors (incidence: 86.5% versus 92.0%; yield: 2.88 versus 7.44 tumors per mouse), liver (incidence: 57.7% versus 60.0%; yield: 3.63 versus 5.28 tumors per mouse) and other organs (incidence: 36.5% versus 32.0%; yield: 0.56 versus 0.52 tumors per mouse). By contrast, only lung tumors at low incidence were detected in mice treated with solvent only (incidence: 28.8%; yield: 0.58 tumors per mouse). As with the parent hydrocarbon, mice treated with low doses of diastereomeric syn- and anti-dihydrodiol epoxides of DBP showed increased tumor incidences in liver (incidence: 19.0 and 46.7%; yield: 0.36 and 1.47 tumors per mouse, respectively), and in various other organs (incidence: 7.1 and 20.0%; yield: 0.07 and 0.20 tumors per mouse, respectively). In consideration of the 100-fold differences in the doses of compounds applied in this study, the tumor-inducing potency increases in the order DBP < 11,12-dihydrodiol < anti-dihydrodiol epoxide. This result provides strong evidence that the potent carcinogen DBP is activated in vivo in the mouse via its 11,12-dihydrodiol and not preferentially through alternative pathways.

Animals↗
PubMed2002

Pseudorabies virus DNA-binding protein stimulates the exonuclease activity and regulates the processivity of pseudorabies virus DNase.

The pseudorabies virus (PRV) DNase is an alkaline exonuclease and endonuclease, which exhibits an Escherichia coli RecBCD-like catalytic function. The PRV DNA-binding protein (DBP) promotes the renaturation of complementary single strands of DNA, which is an essential function for recombinase. To investigate the functional and physical interactions between PRV DBP and DNase, these proteins were purified to homogeneity. PRV DBP stimulated the DNase activity, especially the exonuclease activity, in a dose-dependent fashion. Acetylation of DBP by acetic anhydride resulted in a loss of DNA-binding ability and a 60% inhibition of the DNase activity, suggesting that DNA-binding ability of PRV DBP was required for stimulating the DNase activity. PRV DNase behaved in a processive mode; however, it was converted into a distributive mode in the presence of DBP, implying that PRV DBP stimulated the dissociation of DNase from DNA substrates. The physical interaction between DBP and DNase was further analyzed by enzyme-linked immunosorbent assay, and a significant interaction was observed. Thus, these results suggested that PRV DBP interacted with PRV DNase and regulated the DNase activity in vitro.

Acetic Anhydrides↗
PubMed2001

Application of matrix solid-phase dispersion in the determination of dibenzo[a,l]pyrene content of experimental animal diets used in a large-scale tumor study.

A method utilizing matrix solid-phase dispersion (MSPD) was developed for isolation and determination of dibenzo[a,l]pyrene (DBP) in experimental rainbow-trout diets used in a large-scale carcinogenesis study. A 0.5 g sample of moist ration containing 0-225 ppm DBP (dry basis) was mixed with 2 g C18 sorbent and benzo[a]pyrene internal standard was added to the mixture. Extraction and clean-up were accomplished in a single step by extracting the sample mixture with hexane-benzene 4:1 from a cartridge containing 2 g Florisil. DBP was quantified by HPLC on a C5 bonded phase column with fluorescence detection. Mean analytical recovery of DBP from control diet spiked at three concentration levels was 101 to 107% with relative standard deviations of 1 to 7%. The limit of detection of DBP was equivalent to 0.014 ppm in the ration. Application of the method to verification of DBP levels in trout rations from the carcinogenesis study is described. Control ration (0 ppm DBP) was screened for possible DBP contamination and none was found. This is the first report on analysis of DBP in experimental animal diets.

Animal Feed↗
PubMed2003

Is systolic blood pressure sufficient for classification of blood pressure and determination of hypertension based on JNC-VI in an Iranian adult population? Tehran lipid and glucose study (TLGS).

The purpose of this study was to determine if systolic blood pressure (SBP) by itself is sufficient for the JNC-VI (Sixth Report of the Joint National Committee on Detection, Evaluation, and Treatment of High Blood Pressure)-based classification of blood pressure of Tehranian adult population. Clinically, SBP and diastolic blood pressure (DBP) are sometimes at different stages in the same individual and the higher stage is considered to classify blood pressure level. The prevalence of disparate levels of SBP and DBP has only recently been noticed. Some researches have reported the importance of SBP level, and not DBP, in determining the appropriate classification of hypertension even in those undergoing treatment. Data were collected for 3823 men and 5159 women aged 20-69 years who were not using antihypertensive medication, in the Tehran Lipid and Glucose Study (TLGS), a cross-sectional phase of a large epidemiological study first established in 1999. The study used the mean of two separate blood pressure measurements in each individual. High blood pressure is defined according to the highest level of SBP or DBP. In 86.3% of the subjects, blood pressure stage was determined according to SBP and in 90.0% of them according to DBP. In 77.4% of the subjects (75.7% of men and 78.7% of women), SBP determined blood pressure in the same stage as DBP did. The role of SBP was the most prominent in age groups 20-29 and 60-69 years (91.4 and 90.8%, respectively) and the least in age group 40-49 years (80.4% of the subjects). DBP had a more prominent role in younger ages and the least significance in older ages. In conclusion, SBP has a more prominent role than DBP in determining blood pressure stage according to JNC-VI only in the 60-69-year-old group. The role of DBP is more prominent in other age groups.

Adult↗
PubMed2002

Effects of GH replacement on 24-h ambulatory blood pressure and its circadian rhythm in adult GH deficiency.

OBJECTIVE: Increased prevalence of hypertension and cardiovascular mortality have been reported in hypopituitary patients who had been appropriately replaced with conventional pituitary hormones except GH. Growth hormone replacement (GHR) results in improvement of surrogate markers of cardiovascular function. Data on effects of GHR on blood pressure (BP) in adult growth hormone deficiency (AGHD), however, remain contradictory. There are as yet no reports on BP circadian rhythms in untreated or treated AGHD. Therefore, in a 12-month follow-up study, we evaluated the effects of GHR on ambulatory blood pressure (ABP) in AGHD patients. STUDY DESIGN: A prospective, open treatment design study to determine the effects of GHR on ABP and heart rate in AGHD patients. GH was commenced at a daily dose of 0.5 IU, and titrated up by increments of 0.25 IU at 4-weekly intervals to achieve and maintain IGF-I standard deviation score (IGF-I SD) between the median and upper end of the age-related reference range. PATIENTS: Twenty-two, post-pituitary surgery, severe AGHD patients (11 men), defined as peak GH response < 9 mU/l to provocative testing were recruited. The mean age +/- SEM was 48.8 +/- 2.5 years. Twenty-one patients required additional pituitary replacement hormones following pituitary surgery and were on optimal doses at recruitment. MEASUREMENTS: Twenty-four-hour ABP and heart rate (HR), body mass index (BMI), waist hip ratio (WHR) and total body water (TBW) were measured before and after 12 months on GHR. Cosinor analysis was used to analyse BP and HR circadian rhythm parameter estimates. RESULTS: Target IGF-I SD was achieved within 3 months of commencement of GHR in all patients (-3.5 +/- 0.4 at baseline vs. 0.8 +/- 0.2 at 3 months, P < 0.001) and remained within range at 12 months (1.1 +/- 0.2, P < 0.001 compared to baseline). A significant increase in TBW (45.8 +/- 1.2 vs. 47.8 +/- 1.5 kg, P < 0.05) but no significant change in BMI (30.7 +/- 2.2 vs. 31.8 +/- 2.7, P = NS) or WHR (0.95 +/- 0.02 vs. 0.93 +/- 0.02, P = NS) was observed after 12 months on GHR. The 24-h mean systolic ABP (SBP; 126.2 +/- 2.8 vs. 120.1 +/- 2.7 mmHg, P < 0.001) and diastolic ABP (DBP; 78.2 +/- 1.6 vs. 71.4 +/- 1.8 mmHg, P < 0.001) significantly decreased following GHR with a parallel increase in 24-h mean HR (69.6 +/- 2.5 vs. 73.8 +/- 2.5 beats/min; P < 0.001). A significant nocturnal decrease in SBP and DBP was observed both before (SBP; daytime, 129.1 +/- 2.8 vs. night time, 115.9 +/- 3.0 mmHg, P < 0.001 and DBP; daytime, 80.7 +/- 1.6 vs. night time, 69.2 +/- 1.8 mmHg, P < 0.001) and following GHR (SBP; daytime, 122.8 +/- 2.6 vs. night time, 110.0 +/- 3.6 mmHg, P < 0.001 and DBP; daytime, 73.9 +/- 1.8 vs. night time, 62.0 +/- 2.3 mmHg, P < 0.001). Individual and population-mean cosinor analysis demonstrated significant circadian rhythms for SBP, DBP and HR before and after 12 months on GHR (P < 0.001), suggesting that SBP, DBP and HR circadian rhythms were not altered by GHR. There was, however, a significant reduction in SBP (124.2 +/- 2.8 vs. 118.4 +/- 2.8 mmHg, P < 0.001) and DBP (77.0 +/- 1.6 vs. 70.2 +/- 1.8 mmHg, P < 0.001) MESOR with an increase in HR MESOR (68.9 +/- 2.5 vs. 72.2 +/- 2.4 beats/min, P < 0.01) following GHR. CONCLUSIONS: Systolic and diastolic BP and HR circadian rhythms are preserved in AGHD following 12 months of GHR. However, there is a significant decrease in 24-h mean SBP and DBP and increase in 24-h mean HR after 12 months on GHR. We postulate that this decrease in 24-h mean SBP and DBP may result in a reduction of cardiovascular morbidity and mortality and may explain the beneficial effects of GHR on cardiovascular system previously reported in AGHD patients.

Adenoma↗
PubMed2002

Pulse pressure and risk of total mortality and cardiovascular events in patients on chronic hemodialysis.

BACKGROUND: Pulse pressure (PP) has been shown as a risk factor for mortality or cardiovascular events in several studies. However, the impact of PP on prognosis in a cohort of chronic hemodialysis patients has not been sufficiently studied. We examined the effect of PP on total mortality and cardiovascular events in chronic hemodialysis patients, and whether PP adds useful value to systolic blood pressure (SBP) or diastolic blood pressure (DBP) for predicting total mortality and cardiovascular events in chronic hemodialysis patients. METHODS: Chronic hemodialysis patients (N=1243, 720 men, 523 women) alive on January 1, 1991 at baseline were involved in this study. Cox regression, adjusted for age, sex, and other risk factors, was used to assess the relation between blood pressure components and risk of death and cardiovascular events over a nine-year follow-up. RESULTS: The association with the risk of total mortality was positive for PP (P=0.002) and SBP (P=0.04), but not significant for DBP (P=0.4), considering each pressure individually (single blood pressure component model, SPM); of the three measurements, PP yielded the highest chi2 value. When SBP and DBP were jointly entered into the Cox regression model (dual blood pressure component model, DPM), the association with the risk of total mortality was positive for SBP (HR, 1.083; 95% CI, 1.030 to 1.137) and negative for DBP (HR, 0.886; 0.808 to 0.970). After the addition of diabetes mellitus as an adjusted variable to the model, PP was not a significant predictor for total mortality; PP was a significant predictor for total mortality in non-diabetic patients, but not in diabetic patients. PP was positively associated with the risk of stroke, and stroke and AMI; however, predictive value of PP for each endpoint was not superior to SBP and DBP in SPM. In DPM with SBP and DBP, the association with the risk of stroke and acute myocardial infarction (AMI) was positive for SBP (P=0.02) but not significant for DBP (P=0.5). In DPM with SBP and PP, the association with the risk of stroke and AMI was positive for SBP (P=0.01) but not significant for PP (P=0.5). CONCLUSIONS: In non-diabetic patients on chronic hemodialysis, PP was an independent predictor of total mortality. PP was more potent predictor of total mortality than SBP or DBP. For predicting cardiovascular events, SBP was superior to PP or DBP.

Adult↗