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PubMed2002

Circadian pattern of blood pressure, heart rate, and double product in liver glycogen storage disease.

The objective of this study was to determine systolic, diastolic, and mean arterial blood pressure (SBP, DBP, and MAP), heart rate (HR), double-product (DP: SBP x HR), and activity levels and their 24h pattern in liver glycogen storage disease (LGSD) patients. A case series of 12 (11 pediatric and one adult) diurnally active LGSD (seven type I, three type III, and two type IX) subjects were simultaneously assessed by 24h ambulatory blood pressure monitoring and wrist actigraphy. Nine subjects were judged to be hypertensive based on the criterion of an elevated 24h mean SBP and/or DBP being elevated beyond reference standards or the SBP and/or DBP load (percentage of time BP exceeds normal values) being greater than 25%. Two of the three other subjects, not viewed as hypertensive based on their 24h average SBP or DBP, exhibited daytime or nighttime SBP and/or DBP load hypertension. Each study variables displayed statistically significant (p < 0.001) group circadian rhythmicity. The SBP, DBP, and MAP displayed comparable 24h patterns of appreciable amplitude (total peak-trough variation equal to 17.7, 23.6, and 19.6%, respectively, of the 24h mean) with highest values (orthophase) occurring approximately 11 h after the commencement of daytime activity. The sleep-time trough (bathyphase) occurred approximately 4.5 h before morning awakening. The statistically significant (p < 0.006) circadian rhythms of HR (amplitude equal to 33.2% of the 24h mean) and DP (amplitude equal to 49.4% of the 24h mean) peaked earlier, approximately 7.4 h into the daytime activity span. The sleep-time trough occurred approximately 3 h before morning awakening. The 24h pattern in the cardiovascular variables was correlated with the 24h pattern of activity, with r ranging from 0.50 for DBP to 0.39 for HR.

Adolescent↗
PubMed2004

A survey of Canadian practitioners regarding the management of the hypertensive disorders of pregnancy.

BACKGROUND: How Canadian practitioners are managing the hypertensive disorders of pregnancy (HDP) is not known, particularly in relation to the 1997 guidelines published by the Canadian Hypertension Society (CHS). METHODS: A survey, with French and English versions (and covering diagnosis, evaluation, and management of pregnancy hypertension), was mailed to all members of the Society of Obstetricians and Gynaecologists of Canada (SOGC) (N = 1757, including obstetricians, family doctors practicing obstetrics, and midwives). Additionally, internists [i.e., all nephrologists (N = 191) and a random sample of 25% of general internists (N = 450)] registered with the Royal College of Physicians and Surgeons of Canada were sampled. The survey was distributed in two mailings and one reminder card. Data were entered into Microsoft Access, and Graph Pad Prism used to summarize responses [N (%)]. Differences in practice between specialties were examined, with a Bonferroni correction used to calculate a significant p value based on the number of comparisons and alpha of 0.05. RESULTS: Respondents numbered 1187 (49.5%), with 466 not informative for the purpose of the study (due to retirement, or practices that do not include pregnant women with hypertension). The final analysis included 721 completed surveys. For all types of HDP, most internists, family doctors, and midwives initiate nonpharmacological therapy (most common advice to quit work) at dBP 80-89 mmHg (i.e., primary prevention). Only for preeclampsia do obstetricians most frequently use this threshold; otherwise, dBP 90-99 mmHg is usually chosen. For nonsevere hypertension, antihypertensive drug therapy (most commonly methyldopa or labetalol) is started by most practitioners at dBP 90-99 mmHg, although obstetricians are more likely to choose a higher threshold (p < 0.0001). There is little agreement about dBP treatment goal; most internists and family doctors normalize dBP, whereas obstetricians appear to be divided on dBP goals of 80-89 (46-51%) vs. 90-99 mmHg (41-44%) for all HDP (p = 0.66). Severe hypertension is commonly treated with parenteral hydralazine, labetalol, or magnesium sulphate. Short-acting or sustained release nifedipine is used rarely/never by most practitioners. Approximately one-third of obstetricians and family doctors use diazepam to treat eclampsia. The vast majority use MgSO4 prophylactically in women with preeclampsia. INTERPRETATION: This survey has clarified current stated management of women with HDP, and identified the need for both research into the dBP treatment goal that optimizes pregnancy outcomes among women with HDP, and translation of definitive studies into clinical practice.

Antihypertensive Agents↗
PubMed2001

Radical production and cytotoxic activity of tert-butyl-substituted phenols.

2,4,6-Tri-tert-butylphenol (TBP)-related compounds are used for stabilizing plastics by making them resistant to oxidation. However, the cytotoxic activity of these compounds has not yet been established. TBP produced phenoxyl radicals at pH >or= 9.0 and 2,4-di-t-butylphenol (DBP) at pH 12.5, but 3,3',5,5'-tetra-t-butyl-1,1'-biphenyl-2,2'-diol (bisDBP) did not, using ESR spectroscopy. Both superoxide anion radical (O(2)(-)) scavenging activity and reactive oxygen species (ROS) production activity declined in the order of TBP > DBP > bisDBP. The cytotoxic activity against human oral tumor cell lines (HSC-2, HSG) and human gingival fibroblast cells (HGF) declined in the order of DBP >> bisDBP = TBP = TBP-OOH (2,4,6-tri-t-butyl-4-hydroperoxy-2,5-cyclohexadiene-1-one). The cytotoxic activity of TBP, but not of DBP or bisDBP was significantly enhanced after visible light (VL)-irradiation for 10 min. The cytotoxicity of irradiated TBP was significantly higher than that of either original TBP or TBP-OOH, the oxidative metabolite of TBP, possibly due to the formation of TBP stable radical and ROS via oxidation. In contrast, the cytotoxic activity of DBP and bisDBP was independent of radical production, and therefore, may be intrinsic. A non-enzymatic oxidation decomposition of DBP or TBP was estimated from the formation of reaction enthalpy (DeltaH) using a modified neglect of diatomic overlap, parametric method 3 (MNDO-PM3) semi-empirical method, suggesting that O(2) is capable of activating DBP to a reactive quinone or dimer and that TBP phenoxyl radicals via oxidation directly affect extra- or intracellular bioactive materials, resulting in the induction of cytotoxicity.

Antioxidants↗
PubMed1992

Age and blood pressure measurement: experience with the TM2420 ambulatory blood pressure monitor and elderly people.

The accuracy of the TM-2420 ambulatory blood pressure monitor was assessed in elderly people. Ninety-four subjects (44 men and 50 women), aged 60-94 with systolic blood pressure (SBP) of 97-208 mmHg and diastolic blood pressure (DBP) of 45-109 mmHg, including 23 with isolated systolic hypertension, were studied in three centres. The monitor was compared simultaneously with pairs of observers using the Hawksley random zero sphygmomanometer. The standard deviation of the difference (SDD) between observers was 4.2 mmHg (SBP), 2.9 mmHg (DBP). The mean difference was 0.49 mmHg (SBP) and 0.27 mmHg (DBP). The SDD between the monitor and the average of the observers' readings was 6.7 mmHg (SBP), 5.5 mmHg (DBP); the mean differences were 4.4 mmHg (SBP) and 4.8 mmHg (DBP). There were no significant differences between the two versions of the monitor used (5 and 7) or between the three pairs of observers. The monitor was equally accurate in isolated systolic hypertension (SDD observers and monitor 6.2 mmHg for SBP, 3.9 mmHg for DBP, mean differences 4.3 mmHg for SBP, 4.5 mmHg for DBP). Twenty-four-hour ambulatory blood pressure monitoring was carried out in 129 subjects aged 60-79; 89% of the monitoring attempted were successful with error rates of < 10%. The mean error rate was 3.8%. The device was well tolerated with only 4.7% of the subjects not completing a monitoring.

Aged↗
PubMed1997

Relation of body mass and alcohol, nutrient, fiber, and caffeine intakes to blood pressure in the special intervention and usual care groups in the Multiple Risk Factor Intervention Trial.

This chapter presents analyses of relations of dietary variables to blood pressure, systolic (SBP) and diastolic (DBP), for men in the special intervention (SI) and usual care (UC) groups in the Multiple Risk Factor Intervention Trial. For each dietary factor, analyses were done at baseline, for trial years 1-6, and for change from baseline to years 1-6. Analyses were done for all participants and for men receiving or not receiving antihypertensive drug treatment and were controlled for age, race, education, serum cholesterol, smoking, special diet status, and (for specific nutrients) body mass index and alcohol intake. Nutrient data for trial years 1-6, which are based on four or five dietary recalls per man, are more reliable than the baseline or change data, which are based on only one recall. Therefore, this summary focuses on data for trial years 1-6, for SI and UC men pooled. Regression analyses confirmed direct independent relations of body mass index, alcohol intake, sodium, and ratio of sodium to potassium to SBP and DBP, and an inverse relation of potassium to SBP and DBP. Dietary starch was directly related to SBP and DBP; dietary saturated fatty acid and cholesterol and Keys score were directly related to DBP; dietary magnesium, fiber, and caffeine were inversely related to SBP and DBP; and dietary protein, polyunsaturated fatty acids, the ratio of polyunsaturated to saturated fatty acid, and other simple carbohydrates were inversely related to DBP. Method problems, all tending to produce underestimations, are also reviewed.

Alcohol Drinking↗
PubMed1994

Life style as a determinant of blood pressure in the general population.

This study investigated which life style factors were correlated with the level and the variability of systolic (SBP) and diastolic (DBP) pressure in a random population sample. Ten blood pressure readings were obtained at home in 405 men and 379 women (20 to 84 years). Each person's average pressure level was computed together with the standard deviation as index of variability. Sodium, potassium, and alcohol intake, smoking habits, social class, psychoemotional stress, and the calories spent at work and in sports were assessed from a questionnaire and from determinations on serum and on a 24-h urine sample. A P10 to P90 (10th and 90th percentile) increase of alcohol intake, as reflected by serum gamma-glutamyltransferase, was associated with a 3.2 +/- 0.9 mm Hg higher DBP in men and with a 3.1 +/- 1.6 mm Hg higher SBP and a 1.5 +/- 0.8 mm Hg higher DBP in women. A P10 to P90 increase in the calories spent in sports was accompanied by a decrease in pressure, averaging 1.5 +/- 0.8 mm Hg for DBP in men and 2.4 +/- 1.2 mm Hg and 1.8 +/- 0.8 mm Hg for SBP and DBP in women. A 2.2 +/- 0.7 mm Hg higher DBP was observed in women living in a working class area. After adjustment for age, the variability of DBP was inversely correlated with self-rated physical activity in men, whereas women living in a working class area showed a decreased SBP variability. In conclusion, in an affluent Western population, alcohol intake, participation in sports, and living in a working class area were identified as the life style factors of importance for the blood pressure level. By contrast, blood pressure variability, as measured in the present study, was only to a minor extent influenced by life style.

Adult↗
PubMed2006

A mixture model-based discriminate analysis for identifying ordered transcription factor binding site pairs in gene promoters directly regulated by estrogen receptor-alpha.

MOTIVATION: To detect and select patterns of transcription factor binding sites (TFBSs) which distinguish genes directly regulated by estrogen receptor-alpha (ERalpha), we developed an innovative mixture model-based discriminate analysis for identifying ordered TFBS pairs. RESULTS: Biologically, our proposed new algorithm clearly suggests that TFBSs are not randomly distributed within ERalpha target promoters (P-value < 0.001). The up-regulated targets significantly (P-value < 0.01) possess TFBS pairs, (DBP, MYC), (DBP, MYC/MAX heterodimer), (DBP, USF2) and (DBP, MYOGENIN); and down-regulated ERalpha target genes significantly (P-value < 0.01) possess TFBS pairs, such as (DBP, c-ETS1-68), (DBP, USF2) and (DBP, MYOGENIN). Statistically, our proposed mixture model-based discriminate analysis can simultaneously perform TFBS pattern recognition, TFBS pattern selection, and target class prediction; such integrative power cannot be achieved by current methods. AVAILABILITY: The software is available on request from the authors. CONTACT: lali@iupui.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Algorithms↗
PubMed1997

Microsome-mediated bioactivation of dibenzo[a,l]pyrene and identification of DNA adducts by 32P-postlabeling.

Dibenzo[a,l]pyrene (DBP) is one of the most potent bacterial mutagen and mammary carcinogens. When DBP (50 microM) was incubated with calf thymus DNA (300 microg/ml) in the presence of liver microsomes from beta-naphthoflavone (beta-NF)- or Aroclor 1254-treated rats, at least eight adduct spots were detected as analyzed by nuclease P1-enhanced 32P-postlabeling assay. DNA adduction was enhanced by nearly 20- and 60-fold with beta-NF- and Aroclor 1254-induced microsomes, respectively, as compared with uninduced microsomes, suggesting a possible involvement of CYP1A family in DBP activation. Inclusion of the selective P4501A1 inhibitor, alpha-naphthoflavone (50 microM) in the activation reaction almost completely (>98%) abolished adduct formation further supporting involvement of P4501A in DBP activation. Analysis of DNA and 2'-deoxynucleosides 3'-mononucleotide reacted with anti- and syn-DBP-11,12-diol-13,14-epoxides (DBPDEs) and co-chromatography analyses in multiple solvents showed that the microsomal DBP-DNA adducts were derived by interaction of both anti- and syn-DBPDEs with adenine and guanine in DNA in the following order: anti-DBPDE-dA approximately syn-DBPDE-dG >> anti-DBPDE-dG approximately syn-DBPDE-dA. It is concluded that (i) most or all DBP adducts were P4501A-mediated; (ii) both the anti- and syn-stereoisomers were involved in the DNA adduct formation; and (iii) both adenine and guanine in the DNA contributed equally to the formation of the major and minor adducts.

Animals↗
PubMed1998

Chemoprotection by natural chlorophylls in vivo: inhibition of dibenzo[a,l]pyrene-DNA adducts in rainbow trout liver.

Naturally occurring chlorophylls (Chl) have shown anti-mutagenic activity but little is known about their chemoprotective properties in vivo. This study examined the effect of Chl on formation in vivo of DNA adducts by the potent environmental carcinogen dibenzo[a,l]pyrene (DBP), using rainbow trout as the animal model. Fingerling trout were fed diets containing 200 p.p.m. DBP alone or with one of the following preparations incorporated at 3000 p.p.m. total chlorins: purified pheophytin a (Phe a) (94%); semi-purified Chl a (77%, 23% Phe a), commercial Chl a (88%, 12% other Chl a-related compounds); crude spinach extract (53% Chl a, 19% Chl b, 14% Phe a, 9% carotenoids); commercial Cu-chlorophyllin (55% chlorins, 45% neutral salts), as a known inhibitory control. After 2 weeks dietary treatment, the animals were killed and organs were collected. Stable DBP-DNA adducts from liver were quantified after 33P-post-labeling and separation by reversed-phase HPLC. Total DBP-DNA adducts in the DBP-only group were 2.46 +/- 0.32 adducts/10(6) nucleotides. All chlorophyll treatment groups showed significantly lower adduct levels (P < 0.001, Tukey's HSD test), as follows: crude spinach extract, 0.64 +/- 0.14; semi-pure Chl a, 0.5 +/- 0.11; commercial Chl a, 1.26 +/- 0.17; Phe a, 0.95 +/- 0.01; chlorophyllin, 0.78 +/- 0.09. The various treatments suppressed DBP-DNA adducts essentially uniformly across the HPLC profile, which is consistent with complex formation and reduced carcinogen uptake as the predominant protective mechanism. The chlorophyll-mediated reduction in DBP-DNA adducts in vivo is the first demonstration of anti-genotoxic activity of these common dietary phytochemicals in any vertebrate animal model.

Animals↗
PubMed2004

Meta-analysis of genome-wide scans for hypertension and blood pressure in Caucasians shows evidence of susceptibility regions on chromosomes 2 and 3.

Individual genome-wide scans of blood pressure (BP) and hypertension (HT) have shown inconsistent results. The aim of this study was to investigate whether there was any consistent evidence of linkage across multiple studies with similar ethnicity. We applied the genome-search meta-analysis method (GSMA) to nine published genome-wide scans of BP (n = 5) and HT (n = 4) from Caucasian populations. For each study, the genome was divided into 120 bins and ranked according to the maximum evidence of linkage within each bin. The ranks were summed and averaged across studies and significance levels were estimated, on the basis of a distribution function of summed ranks or permutation tests without (PU) or with (PW) a study sample size weighting factor. Chromosome 3p14.1-q12.3 showed consistent evidence of linkage to HT (PU = 0.0001 and PW = 0.0001), diastolic BP (DBP) (PU = 0.007 and PW = 0.02), HT and DBP pooled (PU = 0.00002 and PW = 0.0001) and HT and systolic BP (SBP) pooled (PU = 0.0003 and PW = 0.0005). Chromosome 2p12-q22.1 showed evidence of linkage to HT (PU = 0.003 and PW = 0.009), DBP (PU = 0.05 and PW = NS), HT and DBP pooled (PU = 0.001 and PW = 0.004) and HT and SBP pooled (PU = 0.001 and P W = 0.005). The summed ranks of the HT analysis correlated significantly with those of the DBP (r = 0.20, P = 0.03) but not with those of the SBP. Both loci showed clustering of significant bins in the analysis of HT and DBP. We conclude that modest or non-significant linkage on chromosomes 3p14.1-q12.3 and 2p12-q22.1 in each individual study translates into genome-wide significant or highly suggestive linkages to HT and DBP in our GSMA analysis.

Blood Pressure↗
PubMed1982

Nucleotide sequence of the gene encoding adenovirus type 2 DNA binding protein.

We have determined the nucleotide sequence of the gene encoding adenovirus type 2 (Ad2) DNA binding protein (DBP). From the nucleotide sequence the complete amino acid sequence of Ad2 DBP has been deduced. A comparison of the amino acid sequences of Ad2 and Ad5 DBP, both 529 residues long, reveals that the C-terminal 354 residues of both sequences are identical. Within the N-terminal 175 amino acid residues Ad2 and Ad5 show nine differences. The site of mutation in Ad2 ND1ts23, a mutant with a temperature-sensitive DNA replication, was mapped at the nucleotide level. A single nucleotide alteration in the DBP gene, resulting in a leucine leads to phenylalanine substitution at position 282 in the amino acid sequence is responsible for the temperature-sensitive character of this mutant. Previously, we localized the mutation of another DBP mutant with a temperature-sensitive DNA replication (H5ts125) at position 413 in the amino acid sequence of the DBP molecule (Nucleic Acids Res. 9 (1981) 4439-4457). These mapping data are discussed in relation to the structure and function of the DBP molecule.

Adenoviruses, Human↗
PubMed1993

The adenovirus DNA binding protein enhances intermolecular DNA renaturation but inhibits intramolecular DNA renaturation.

The Adenovirus DNA binding protein (DBP) imposes a regular, rigid and extended conformation on single stranded DNA (ssDNA) and removes secondary structure. Here we show that DBP promotes renaturation of complementary single DNA strands. Enhancement of intermolecular renaturation is sequence independent, can be observed over a broad range of ionic conditions and occurs only when the DNA strands are completely covered with DBP. When one strand of DNA is covered with DBP and its complementary strand with T4 gene 32 protein, renaturation is still enhanced compared to protein-free DNA, indicating that the structures of both protein-DNA complexes are compatible for renaturation. In contrast to promoting intermolecular renaturation, DBP strongly inhibits intramolecular renaturation required for the formation of a panhandle from an ssDNA molecule with an inverted terminal repeat. We explain this by the rigidity of an ssDNA-DBP complex. These results will be discussed in view of the crystal structure of DBP that has recently been determined.

Adenoviridae↗
PubMed1981

Structure and organization of the gene coding for the DNA binding protein of adenovirus type 5.

We have determined the nucleotide sequence of a region of adenovirus type 5 (Ad5) DNA located between map positions 61.7 and 71.4, which covers the gene form the 72 kD DNA binding protein (DBP) and the sequence encoding the amino-terminal part of the 100 kD protein. Sequence analysis of cDNA copies of DBP mRNA revealed the existence of two abundant species of spliced mRNA molecules. One species consists of two short leader sequences from positions 75.2 (67 and 68 nucleotides long) and 68.8 (77 nucleotides long), respectively, and the main body of the RNA molecules. The other species contains only the leader sequence from position 75.2 and the main body. The amino acid sequence of DBP is encoded entirely by a long open reading frame of 1587 nucleotides in the main body of DBP mRNA. From the nucleotide sequence of the DBP gene it can be derived that DBP contains 529 amino acid residues and has an actual molecular weight of 59,049 daltons. The sites of mutation in the mutants H5hr404 and H5ts125 were determined at the nucleotide level. Single nucleotide alterations were detected in H5hr404 and H5ts125 in the sequences corresponding to the amino-terminal part and the carboxy-terminal part of DBP, respectively. The implications of these mutations are discussed.

Adenoviruses, Human↗
PubMed1977

Effects of phthalate esters on the latent ATPase and swelling of mitochondria.

Phthalate esters have shown to stimulate the latent ATPase [EC 3.6.1.3] activity and induce mitochondrial swelling. Among the tested phthalate esters, di-n-butyl phthalate (DBP) exhibited the greatest activity, and the activity decreased progressively as the alkyl chain was lengthened or shortened. The DBP-stimulated ATPase was oligomycin-sensitive. The degree of stimulation of the ATPase was proportional to the extent of mitochondrial swelling induced by DBP in 0.1 M Tris-HCl (pH 7.2) containing 0.25 M sucrose. However, the swelling was dependent on the tonicity of the solution or the concentration of chloride ions, while the stimulation of ATPase was independent of these factors. Swelling was strongly induced by DBP at slightly acidic rather than neutral or alkaline pH. The pH-activity curve of DBP-stimulated ATPase was in inverse correlation with that of swelling, which showed a rather flat maximum at pH 8.0. When bovine serum albumin (BSA) was added to a solution containing mitochondria before addition of DBP, swelling was no longer caused by DBP, though the latent ATPase was stimulated to the same extent in the absence of added BSA.

Adenosine Triphosphatases↗
PubMed2004

Dose-dependent alterations in gene expression and testosterone synthesis in the fetal testes of male rats exposed to di (n-butyl) phthalate.

Exposure to di (n-butyl) phthalate (DBP) in utero impairs the development of the male rat reproductive tract. The adverse effects are due in part to a coordinated decrease in expression of genes involved in cholesterol transport and steroidogenesis with a resultant reduction in testosterone production in the fetal testis. To determine the dose-response relationship for the effect of DBP on steroidogenesis in fetal rat testes, pregnant Sprague-Dawley rats received corn oil (vehicle control) or DBP (0.1, 1.0, 10, 50, 100, or 500 mg/kg/day) by gavage daily from gestation day (GD) 12 to 19. Testes were isolated on GD 19, and changes in gene and protein expression were quantified by RT-PCR and Western analysis. Fetal testicular testosterone concentration was determined by radioimmunoassay. DBP exposure resulted in significant dose-dependent reductions in mRNA and protein concentration of scavenger receptor, steroidogenic acute regulatory protein (StAR), cytochrome P450 side-chain cleavage, 3beta-hydroxysteroid dehydrogenase, and cytochrome P450c17. Testicular testosterone was reduced at doses of 50 mg/kg/day and above. Whole-testis expression of peripheral benzodiazepine receptor (PBR) mRNA, which functions with StAR to transport cholesterol across the mitochondrial membrane, was upregulated following exposure to DBP at 500 mg/kg/day. By immunocytochemistry, however, PBR protein was reduced in interstitial cells and also expressed but not reduced in gonocytes. Our results demonstrate a coordinate, dose-dependent reduction in the expression of key genes and proteins involved in cholesterol transport and steroidogenesis and a corresponding reduction in testosterone in fetal testes following maternal exposure to DBP, at dose levels below which adverse effects are detected in the developing male reproductive tract. Alterations in gene and protein expression and testosterone synthesis may serve as sensitive indicators of testicular response to DBP.

3-Hydroxysteroid Dehydrogenases↗
PubMed2002

Blood pressure response after two-step exercise as a powerful predictor of hypertension: the Osaka Health Survey.

OBJECTIVE: To investigate the relationship between blood pressure at 4 min after exercise using a Master's two-step and the risk for hypertension. DESIGN: Prospective cohort study. SETTING: Work site in Osaka, Japan. PARTICIPANTS: A total of 6557 Japanese men, aged 35-63 years with systolic blood pressure (SBP) < 140 mmHg and diastolic blood pressure (DBP) < 90 mmHg, and no history of hypertension or diabetes at baseline. MAIN OUTCOME MEASURES: Blood pressure was measured by standard techniques, using 160/95 mmHg for diagnosis of hypertension. Normotension was defined as no history of hypertension, and SBP < 130 mmHg and DBP < 85 mmHg. High normal blood pressure was defined as no history of hypertension and SBP >or= 130 and < 140 mmHg or DBP >or= 85 and < 90 mmHg. RESULTS: During the 63 696 person-years follow-up period, we confirmed 660 cases of hypertension. SBP and DBP after exercise were associated with an increased risk for developing hypertension. The multiple-adjusted relative risk for SBP and DBP after exercise were 1.55 per 10 mmHg (confidence interval, 1.42-1.69) and 1.55 per 10 mmHg (confidence interval, 1.42-1.69), respectively. These associations were independent of resting SBP and DBP. Even after stratifying subjects according to blood pressure at rest, SBP or DBP at 4 min after exercise was associated with an increased risk for hypertension in subjects with normotension or high normal blood pressure at rest. CONCLUSIONS: The blood pressure response after exercise with a two-step was associated with an increased risk for hypertension, independently of resting blood pressures.

Adult↗
PubMed2003

Benefits and risks of more intensive blood pressure lowering in hypertensive patients of the HOT study with different risk profiles: does a J-shaped curve exist in smokers?

BACKGROUND: The Hypertension Optimal Treatment (HOT) Study investigated 18 790 hypertensives randomized to three diastolic blood pressure (DBP) targets (< or = 90, < or = 85, < or = 80 mmHg) for 3.8 years and found marked, significant reductions in cardiovascular events and mortality the lower the target DBP in the subset of diabetics. We investigated whether the benefits of intensive DBP lowering could be extended to other subgroups, and whether there are hypertensives in whom the risk of aggressive DBP lowering may outnumber the benefits. METHODS AND RESULTS: The 18 790 patients were stratified as: medium/high-very high global cardiovascular risk; men/women; older/younger; current smokers/non-smokers; higher/lower serum cholesterol; higher/lower serum creatinine; with/without diabetes; with/without ischaemic heart disease (IHD). Comparisons were made between the less aggressive target group (DBP < 90 mmHg) and the two more aggressive target groups together (< or = 85 and < or = 80 mmHg). A Cox proportional hazards model was used to calculate treatment-subgroup interactions and relative risks (RR) with 95% confidence intervals. Benefits were greatest in diabetics (RR 0.53 for cardiovascular events, and 0.67 for cardiovascular death), whereas in smokers more intensive DBP lowering was associated with increased risk of all types of cardiovascular event (RR 1.71-2.67; P = 0.01-0.001), except myocardial infarction. After excluding smokers, intensive DBP lowering was associated with significant reductions in cardiovascular events in diabetics (-49%), high-very high risk patients (-23%), IHD patients (-32%), patients with lower creatinine (-18%), women (-33%) and older patients (-23%). CONCLUSIONS: Although subanalyses have only a descriptive value, it appears reasonable to recommend intensive antihypertensive treatment to hypertensives with diabetes, IHD and high global cardiovascular risk. In smokers, treatment intensification should be associated with the greatest efforts to induce smoking cessation.

Aged↗
PubMed2004

Intervention at lower blood pressure levels to achieve target goals in type 2 diabetes: PRADID (PResión Arterial en DIabéticos tipo Dos) study.

BACKGROUND: Arterial hypertension greatly increases the risk of cardiovascular disease, renal insufficiency, and retinopathy in patients with type 2 diabetes. Epidemiological studies all document a reduced risk for the aforementioned consequences at a blood pressure (BP) lower than 130/80 mmHg. For this reason, lower target BPs are recommended by recent guidelines committees. A lower threshold BP for treatment, also proposed in guidelines, could facilitate the attainment of the recommended target BP. However, little data exist on the efficacy and safety of starting pharmacological therapy in type 2 diabetic patients exhibiting high-normal BP (HNBP) or the first stage of isolated systolic hypertension previously considered as borderline isolated systolic hypertension (BISH). OBJECTIVE: To determine the antihypertensive efficacy and safety of the fixed-dose combination of the non-dihydropiridine calcium channel blocker (CCB) and ACE inhibitor verapamil SR/trandolapril 180/2 mg (V + T), versus trandolapril 2 mg (T), versus placebo (P) in previously untreated type 2 diabetic patients diagnosed as having HNBP or BISH. METHODS: Multicentric, double-blind, placebo-controlled study with a 16-week follow-up in three groups totalling 438 participants. The primary end-point was to attain the recommended guideline goal of a systolic BP (SBP) value lower than 130 mmHg in all patients and a diastolic BP (DBP) value lower than 85 mmHg in HNBP. Participants were randomized (2:2:1) to verapamil V + T, T, or P. Doses were doubled at week 8 if BP was not controlled. RESULTS: Both active groups were more effective than placebo to decrease SBP and DBP. The mean difference in SBP from placebo was 7.1 mmHg (3.3-10.9, 95% confidence interval (CI); P < 0.001) for T and 7.8 mmHg (3.9-11.6, 95% CI; P < 0.001) for V + T, with no statistical difference between both active groups. Combined treatment (V + T) decreased DBP by 4.6 mmHg (2.3-6.9, 95% CI; P < 0.001) more than placebo and 2.1 mmHg (0.3-4.0, 95% CI; P = 0.021) more than T. At the end of the study, 36.5% in the T group, 37.8% in the V + T group, and 14.9% (P = 0.009, P versus V + T and T) had attained the primary end-point. No significant difference was found between T and V + T with regard to the percentage of good control for SBP, but the control rate on the DBP (DBP < 85 mmHg) was significantly higher in the V + T group (88.8%), when compared with T (79.1%) or P (63.5%) (P = 0.002). Withdrawal rates due to adverse effects did not differ among trandolapril alone (9.4%), the combination (11.7%) and placebo (8.1%). CONCLUSION: Antihypertensive treatment is more effective than placebo for controlling SBP and DBP in previously untreated participants with type 2 diabetes exhibiting low threshold BP values. Combination therapy with verapamil SR/trandolapril was more effective than trandolapril alone for controlling DBP.

Aged↗