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PubMed1987

Control of hypertension in elderly patients with felodipine and metoprolol: a double-blind, placebo-controlled clinical trial.

1. Forty-nine patients aged 65-80 years, whose Phase V diastolic blood pressure (dBP) was above 95 mmHg after 4 weeks open treatment with metoprolol 50 mg twice daily were randomized to receive, double-blind, the calcium antagonist felodipine (n = 32) 2.5 mg twice daily or placebo (n = 17) in addition to metoprolol for 2 weeks. If the dBP remained greater than 95 mmHg, the dose of felodipine or placebo was doubled for a further 2 weeks; if the dBP was still greater than 95 mmHg, the dose of felodipine was doubled again to 10 mg twice daily or the corresponding placebo dose given. The duration of the double-blind period was 6 weeks, all patients receiving metoprolol 50 mg twice daily throughout. 2. At the end of the double-blind period, the seated dBP was reduced from 103 +/- 5 (mean +/- s.d.) to 88 +/- 7 mmHg (P less than 0.001) by felodipine and from 105 +/- 100 +/- 11 mmHg (NS) by placebo. The differences between these reductions (P less than 0.01) and between the final dBPs (P less than 0.001) were significant. Eighty-nine per cent of patients receiving felodipine and 33% of those receiving placebo (P less than 0.001) had controlled (dBP less than or equal to 95 mmHg) BPs. Half (14/27 completing) of the patients receiving felodipine required 2.5 mg throughout; 9/27 needed 5 mg and 4/27 10 mg twice daily. Adverse events occurred with equal frequency in the two groups, but the profile was different.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed2005

Hypertension knowledge, awareness, and attitudes in a hypertensive population.

OBJECTIVE: Improved recognition of the importance of systolic blood pressure (SBP) has been identified as one of the major public health and medical challenges in the prevention and treatment of hypertension (HTN). SBP is a strong independent risk factor for cardiovascular disease but no information is available on whether patients understand the importance of their SBP level. The purpose of this study was to assess HTN knowledge, awareness, and attitudes, especially related to SBP in a hypertensive population. DESIGN/SETTING/PATIENTS: We identified patients with HTN (N=2,264) in the primary care setting of a large midwestern health system using automated claims data (International Classification of Diseases, Ninth Revision [ICD-9] codes 401.0-401.9). We randomly selected 1,250 patients and, after excluding ineligible patients, report the results on 826 completed patient telephone interviews (72% response rate [826/1,151]). MAIN RESULTS: Ninety percent of hypertensive patients knew that lowering blood pressure (BP) would improve health and 91% reported that a health care provider had told them that they have HTN or high BP. However, 41% of patients did not know their BP level. Eighty-two percent of all patients correctly identified the meaning of HTN as "high blood pressure." Thirty-four percent of patients correctly identified SBP as the "top" number of their reading; 32% correctly identified diastolic blood pressure (DBP) as the "bottom" number; and, overall, only 30% of patients were able to correctly identify both systolic and diastolic BP measures. Twenty-seven percent of patients with elevated SBP and DBP (as indicated by their medical records) perceived that their BP was high. Twenty-four percent of patients did not know the optimal level for either SBP or DBP. When asked whether the DBP or SBP level was more important in the control and prevention of disease, 41% reported DBP, 13% reported SBP, 30% reported that both were important, and 17% did not know. CONCLUSIONS: These results suggest that, although general knowledge and awareness of HTN is adequate, patients do not have a comprehensive understanding of this condition. For instance, patients do not recognize the importance of elevated SBP levels or the current status of their BP control. An opportunity exists to focus patient education programs and interventions on the cardiovascular risk associated with uncontrolled HTN, particularly elevated SBP levels.

Adult↗
PubMed1986

Phthalate esters: effects of orally administered dibutylphthalate on cytochrome P-450 mediated metabolism in rat liver and lung.

Dibutylphthalate (DBP) was administered to male Sprague Dawley rats in oral doses of 0.01, 0.1 and 1.0 mmol/kg for five days. The lower dose was considered relevant to human intake. Additional groups were given a recovery period of four weeks without DBP. DBP significantly increased the liver microsomal concentration of cytochrome P-450 (48%) at the lowest dose and NADPH-cytochrome-c-reductase activity (28-29%), at the two lower doses. The liver microsomal metabolism of n-hexane increased to about the same extent at all dosage levels. The main increase was found in the formation of the preneurotoxic metabolite 2-hexanol. The induction of cytochrome P-450 and NADPH-cytochrome-c-reductase in liver microsomes did not return to normal after the period of recovery, whereas the metabolism of n-hexane normalized during the same period of time, indicating that the majority of the induced forms of cytochrome P-450 were not related to n-hexane metabolism. No major changes were observed in the liver microsomal metabolism of B(a)P. The only effect found in cytochrome P-450 related metabolism in lung microsomes was a decrease of the B(a)P metabolism, especially in the formation of the 9,10- and 4,5-diol metabolites at lower dosage levels. It is suggested that DBP and its hydrolyzed products formed in the intestine after oral administration exert the same effect on some specific forms of cytochrome P-450 in liver and lung. It is concluded that DBP is a moderate to weak inducer of several minor forms of liver microsomal cytochrome P-450 enzymes in doses which may be relevant to human oral intake.

Administration, Oral↗
PubMed2004

Comparison of the efficacy and tolerability of telmisartan 40 mg vs. enalapril 10 mg in the treatment of mild-to-moderate hypertension: a multicentre, double-blind study in Taiwanese patients.

The purpose of this randomised, double-blind, double-dummy, parallel-group study was to evaluate the efficacy and tolerability of telmisartan 40 mg once daily vs. enalapril 10 mg once daily in 147 Taiwanese patients with mild-to-moderate essential hypertension (diastolic blood pressure [DBP] 90-109 mmHg). After 6 weeks' treatment, telmisartan produced a significantly greater reduction from baseline in the primary endpoint of trough seated DBP compared with enalapril 10 mg (11.7 vs. 8.7 mmHg, respectively; p = 0.02). Numerically greater reductions compared with baseline in seated systolic blood pressure (SBP), standing DBP, and standing SBP were achieved with telmisartan compared with enalapril. Also, numerically greater proportions of patients achieved blood pressure control (DBP/systolic blood pressure [SBP] <90/140 mmHg) and responded to treatment (reduction from baseline in trough seated DBP > or = 10 mmHg and/or post-treatment DBP <90 mmHg; reduction from baseline in trough seated SBP > or = 10 mmHg and/or post-treatment SBP <140 mmHg) with telmisartan 40 mg compared with enalapril 10 mg. Although both treatments were well tolerated, the incidence of cough was markedly lower with telmisartan 40 mg (8.5%) than with enalapril 10 mg (18.4%) in this population of Taiwanese hypertensive patients.

Adult↗
PubMed1982

Adeno-associated virus helper activity of adenovirus DNA binding protein.

The requirement for the adenovirus (Ad) single-stranded DNA binding protein (DBP) in the expression of adeno-associated virus (AAV) proteins was studied by specific immunofluorescent staining of infected cells and in vitro translation of RNA from infected cells. The Ad5 mutant ts125, which carries a mutation in the DBP gene, helped AAV as efficiently as the Ad5 wild type (WT) did at both the permissive (32 degrees C) and nonpermissive (40.5 degrees C) temperatures in HeLa and KB cells. Furthermore, at 40.5 degrees C ts125 was as efficient as Ad5WT was in inducing the expression of AAV proteins in a line of Detroit 6 cells which is latently infected with AAV. However, little if any AAV protein was synthesized when coinfections were carried out with Ad5WT in CV-C cells, a monkey cell line that is highly restrictive for human Ad replication unless the cells are also infected with simian virus 40. On the other hand, AAV protein was efficiently produced in CV-C cells in coinfections with the Ad5 mutant hr404, whose growth is unrestricted in CV-C cells and whose mutation also maps in the DBP gene. Finally, preparations of cytoplasmic RNA extracted from CV-C cells infected with AAV and Ad5WT or from CV-C cells infected with AAV, Ad5WT, and simian virus 40 were each capable of directing the in vitro synthesis of abundant amounts of AAV proteins in a rabbit reticulocyte lysate system. These results indicate that the abnormal DBP of ts125 still retains its helper function for AAV replication, but that the molecular feature of the DBP which relates to the monkey cell host range restriction of Ad's may also account for the observed block to AAV protein translation in CV-C cells.

Adenoviruses, Human↗
PubMed1992

Defective synthesis of early region 4 mRNAs during abortive adenovirus infections in monkey cells.

Human adenovirus 2 grows poorly in monkey cells, partly because of defects in late gene expression. Since deletions in early region 4 (E4) cause similar defects in late gene expression, we examined E4 mRNA expression in abortive infections. Processing of E4 mRNAs was defective during abortive infections, most likely at the level of splicing. At early times in productive infections in HeLa cells, the major E4 species produced is a 2-kb mRNA; at late times, a shift occurs so that smaller spliced E4 mRNAs are also produced. In CV-1 cells, a nonpermissive monkey cell line, this shift did not take place and only the 2-kb species was produced at late times, suggesting a defect in E4 mRNA splicing during abortive infections. The adenovirus DNA-binding protein (DBP) was required for normal processing of E4 mRNAs, since a host range mutant (hr602) containing an altered DBP gene showed a normal late E4 mRNA pattern in CV-1 cells; in addition, DBP was required during infections in HeLa cells for late E4 mRNA expression. DBP was not required for production of the late E4 pattern in transient expression assays in HeLa or 293 cells, suggesting that a second factor in addition to the DBP, present during infection but not transfection, modulates E4 mRNA processing.

Adenoviridae Infections↗
PubMed2000

The E1E4 protein of human papillomavirus type 16 associates with a putative RNA helicase through sequences in its C terminus.

Human papillomavirus type 16 (HPV16) infects cervical epithelium and is associated with the majority of cervical cancers. The E1E4 protein of HPV16 but not those of HPV1 or HPV6 was found to associate with a novel member of the DEAD box protein family of RNA helicases through sequences in its C terminus. This protein, termed E4-DBP (E4-DEAD box protein), has a molecular weight of 66,000 (66K) and can shuttle between the nucleus and the cytoplasm. It binds to RNA in vitro, including the major HPV16 late transcript (E1E4. L1), and has an RNA-independent ATPase activity which can be partially inhibited by E1E4. E4-DBP was detectable in the cytoplasm of cells expressing HPV16 E1E4 (in vivo and in vitro) and could be immunoprecipitated as an E1E4 complex from cervical epithelial cell lines. In cell lines lacking cytoplasmic intermediate filaments, loss of the leucine cluster-cytoplasmic anchor region of HPV16 E1wedgeE4 resulted in both proteins colocalizing exclusively to the nucleoli. Two additional HPV16 E1E4-binding proteins, of 80K and 50K, were identified in pull-down experiments but were not recognized by antibodies to E4-DBP or the conserved DEAD box motif. Sequence analysis of E4-DBP revealed homology in its E4-binding region with three Escherichia coli DEAD box proteins involved in the regulation of mRNA stability and degradation (RhlB, SrmB, and DeaD) and with the Rrp3 protein of Saccharomyces cerevisiae, which is involved in ribosome biogenesis. The synthesis of HPV16 coat proteins occurs after E1E4 expression and genome amplification and is regulated at the level of mRNA stability and translation. Identification of E4-DBP as an HPV16 E1E4-associated protein indicates a possible role for E1E4 in virus synthesis.

Cell Nucleus↗
PubMed2001

Characterization of adenovirus-induced inverted terminal repeat-independent amplification of integrated adeno-associated virus rep-cap sequences.

Stable packaging cell lines expressing the rep and cap genes for recombinant adeno-associated virus type 2 (rAAV-2) assembly constitute an attractive alternative to transient transfection protocols. We recently characterized a stable HeLa rep-cap cell clone (HeRC32) and demonstrated that upon vector transfection and adenovirus infection, efficient rAAV assembly correlated with a 100-fold amplification of the integrated rep-cap sequence with the inverted terminal repeats (ITRs) deleted. We now report a more detailed analysis of this phenomenon and highlight the key cellular and viral factors involved. Determination of the rep-cap copy number of HeRC32 cells indicated that maximum rep-cap amplification occurred between 24 and 48 h following adenovirus infection. Analysis by pulsed-field gel electrophoresis of adenovirus-infected HeRC32 cells indicated that amplified rep-cap sequences were found in an extrachromosomal form. Amplification of the rep-cap sequence with the ITRs deleted was not dependent on adenovirus replication and still occurred when the highly specific adenovirus polymerase was inactivated. In contrast, amplification was inhibited in the presence of aphidicolin, indicating that cellular polymerases were needed. Our study also documented that among the adenovirus gene products, the DNA-binding protein (DBP) was essential, since rep-cap amplification was severely abrogated when HeRC32 cells were infected at a nonpermissive temperature with an adenovirus mutant encoding a thermosensitive DBP. Furthermore, expression of DBP alone in HeRC32 cells was sufficient to induce a sustained level of rep-cap amplification. Finally, immunofluorescence analysis showed that HeRC32 cells expressing the DBP also simultaneously expressed the Rep proteins, suggesting a possible involvement of the latter in rep-cap amplification. Indeed, the lack of detectable amplification in an adenovirus-infected stable rep-cap HeLa cell clone unable to produce Rep proteins further supported that, among the viral gene products, both the DBP and Rep proteins are necessary to induce the targeted amplification of the integrated rep-cap sequences in the absence of the AAV ITRs.

Adenoviridae↗
PubMed1995

Seasonal changes in ambulatory blood pressure in employees under different indoor temperatures.

OBJECTIVE: The effect of indoor temperature control on summer and winter ambulatory blood pressure levels at work was studied. METHOD: Ambulatory systolic blood pressure (SBP) and diastolic blood pressure (DBP) were monitored once in summer and once in winter in 101 healthy normotensive subjects aged 28-63 years, engaged in similar physical work, from two plants with and three without air conditioning. Subjects were interviewed about health related habits, and measurements of environmental and occupational conditions were obtained. RESULTS: After controlling for possible confounders, mean SBP and DBP during work were significantly higher in winter than in summer (delta SBP = 3.4 mm Hg, P = 0.035; delta DBP = 3.3 mm Hg, P < 0.003). The seasonal change in SBP and DBP showed an independent association with the presence or absence of air conditioning of the industrial plants (SBP: beta = 0.194, P < 0.0001; DBP: beta = 0.054, P = 0.038). The percentage of subjects with increases of more than 10 mm Hg from summer to winter was higher in plants without than with air conditioning. CONCLUSIONS: (1) In normotensive subjects ambulatory working BP varies by season, with higher values in winter. If validated for hypertensive subjects, it may be necessary to tailor drug treatment to these variations. (2) The findings make it clear that drawing valid conclusions from comparisons of BPs between groups requires controlling for several factors, particularly season of the year. (3) Climatic conditions in the industrial plant influence the magnitude of seasonal variations in BP. Work in plants without air conditioning places a considerable added load on the employee's cardiovascular system.

Adult↗
PubMed1980

Localization of the dicarboxylate binding protein in the cell envelope of Escherichia coli K12.

Examination of the localization of the dicarboxylate binding protein (DBP) in the cell envelope of Escherichia coli K12 reveals that this protein is present on the cell surface, and also in the inner and outer regions of the periplasmic space. The cell surface DBP is release by treating the cells with EDTA. This protein can be surface labeled by lactoperoxidase radioiodination, and by diazo[125I]iodosulfanilic acid in whole cells. It also binds tightly, but not covalently, to lipopolysaccharide. The DBP located in the outer region of the periplasmic space is released when the outer membrane is dissociated by EDTA-osmotic shock treatment. The DBP located in the inner region of the periplasmic space is released only when the EDTA-osmotic shocked cells are subjected to lysozyme treatment. At the moment, it is not certain whether this protein is bound to or trapped by the peptidoglycan network. This protein cannot be surface labeled in whole cells or in EDTA-osmotic shock treated cells; and it is not associated with lipopolysaccharide. Analysis of transport mutants indicates that these DBP are coded by the same gene.

Alkaline Phosphatase↗
PubMed2001

Twenty-four-hour blood pressure changes in the course of lacunar disease.

BACKGROUND: Changes in blood pressure (BP) over time have not been considered in investigations on the relationship between BP and cerebrovascular disease (CVD). OBJECTIVE: To investigate BP changes throughout a 24-hour period in lacunar infarct patients with different outcomes. METHODS: Twelve control subjects (group 1) and 56 patients with symptomatic lacunar infarcts were studied. The infarct patients were divided into three groups: group 2, 25 patients with a fair outcome without any cerebrovascular attack or progressive dementia (mean follow-up period: 4.4 years); group 3, 14 patients with worsening of clinical dementia rating and silent lesions, which included lacunae and diffuse white matter lesions (4.5 years), and group 4, 17 patients who developed symptomatic infarcts (1.7 years). MRIs and ambulatory BP monitoring were performed for each patient on two separate occasions. No patient was treated with antihypertensive agents during the course of the study. RESULTS: In group 2, the second measurements were significantly higher than the first for 24-hour systolic BP (SBP), daytime SBP, 24-hour diastolic BP (DBP), daytime DBP (p < 0.01, for all) and nighttime DBP (p < 0.05). In group 3, the second measurements were significantly lower than the first for 24-hour SBP, daytime SBP, 24-hour DBP, and daytime DBP (p < 0.01, for all). In group 4, the second measurements were significantly lower than the first for 24-hour SBP and daytime SBP (p < 0.01). The correlation between BP and pulse rate became positive for group 2 in second measurements, but was not positive for groups 3 and 4. CONCLUSIONS: BP tended to elevate over time in patients with a fair outcome. In contrast, BP tended to decrease in those who developed dementia and symptomatic infarct. Autonomic functions including sympathetic activity might play a role in changes in BP in lacunar infarct patients during the course of disease.

Aged↗
PubMed2004

New chondrocyte genes discovered by representational difference analysis of chondroinduced human fibroblasts.

This report includes a review of the potential for gene expression analyses to provide new information for solving problems in skeletal repair and regeneration. It focuses on two approaches: high-throughput gene array methods and representational difference analysis (RDA). The principles underlying these methods are presented with experimental tutorials and some applications. Second, this report includes a review of results from applying both approaches to an in vitro model of postnatal chondroinduction by demineralized bone powder (DBP). Human dermal fibroblasts (hDFs) cultured with DBP acquire a chondroblast phenotype and express cartilage-specific matrix proteins after 7 days. We used cDNA macroarrays and RDA to identify the genes that were altered prior to expression of the chondroblast phenotype, i.e., after only 3 days' culture with DBP. Using a strategy of data management and reduction based upon biological functions, we reported several functional families of genes (cytoskeletal elements, protein synthesis/trafficking, and matrix molecules and their modifiers) that are upregulated during chondroinduction of hDFs. Together with histological and biochemical evidence of the chondroblast phenotype, the gene expression patterns indicate that there are specific stages of induced chondrocyte differentiation in this experimental system. Third, this report includes a new study, in which DBP-regulated genes were used as a data base to derive new information on the cell biology of chondrocytes. The objective was to determine whether a set of genes expressed during induction of chondrocyte differentiation is also expressed by mature articular chondrocytes. Our search of the literature for 59 of the DBP-regulated genes disclosed that expression of 20 of them (33%) had been documented in mature cartilage or chondrocytes. Of the 39 genes not previously documented in cartilage, 11 were tested by RT-PCR and all were found to be expressed in freshly isolated adult human chondrocytes. This review and these new data show how the strategy of high-throughput methods and functional data reduction can expand our knowledge of chondrocyte cell biology.

Animals↗
PubMed1985

Effects of clonidine on blood pressure, noradrenaline, cortisol, growth hormone, and prolactin plasma levels in high and low intestinal tone depressed patients.

Systolic blood pressure (SBP), diastolic blood pressure (DBP), norepinephrine (NE) plasma levels, cortisol (CRT), growth hormone (GH), and prolactin (PRL) plasma levels were investigated in 26 high intestinal tone (high-IT) and 24 low intestinal tone (low-IT) depressed patients, before and after the intramuscular injection of clonidine (2.5 micrograms/kg). A positive correlation was found between NE, DBP, and Hamilton Depression Rating Scale (HRS) values in low-IT depressed patients, while a negative correlation was found between HRS/IT and NE in high-IT depressed patients. Although clonidine induced significant reduction of SBP in both groups, the drug reduced DBP and NE in the low-IT group, only. CRT mean level was greater in the high-IT than in the low-IT depressed group. However, clonidine was unable to induce changes in CRT, GH, and PRL mean levels in any depressed group. Our results suggest that the clonidine-induced DBP reduction is a reliable index of sympathetic activity in depressed patients and that both parameters (DBP and IT) are useful physiological markers to differentiate two types of depressive syndromes.

Blood Pressure↗
PubMed1987

Comparison of enalapril and thiazide diuretics in the elderly hypertensive patient.

One hundred seventy-four patients, 65 years of age or older, entered a double-blind, seven-center, 16-week, controlled study to compare the effects of enalapril and hydrochlorothiazide (HCTZ) in an elderly hypertensive population. Sixty-eight percent of the patients were men, 32% were women. Thirty-two percent of the patients had isolated systolic hypertension. Approximately 80% of the patients were white. After a 4-week placebo run-in period, patients with sitting diastolic BP (DBP) of 90-120 mm Hg or systolic BP (SBP) greater than or equal to 160 mg Hg and DBP less than 90 mm Hg (isolated systolic hypertension) were randomized to receive 10 mg of enalapril or 12.5 mg of HCTZ once daily. If after 4 weeks their BPs were not controlled (i.e., DBP greater than 85 mm Hg or SBP greater than 140 mm Hg), the dose of the drug was doubled. If after successive 4-week intervals, their BPs were still not controlled, the other drug was added to their regimen and this was then doubled. The initial mean BPs were 167/94 mm Hg in both groups. By the end of the monotherapy phase at 8 weeks, the mean BPs had fallen significantly (p less than or equal to 0.01) to 148/85 mm Hg in both groups. By 16 weeks, the mean BPs had again fallen similarly: in the enalapril group to 144/83 mm Hg, and in the HCTZ group to 145/83 mm Hg. Seventy-nine percent of the enalapril group and 85% of the HCTZ group had controlled BPs at this time (DBP less than or equal to 85 or SBP less than or equal to 140 mm Hg). White and nonwhite patients in both drug groups had similar falls in SBP and DBP both at the end of the monotherapy period and the overall study. The white patients experienced more rapid falls in BP with enalapril, the nonwhite patients with HCTZ. Three serious adverse experiences occurred in the enalapril group, none of which were considered likely to be due to the drug therapy. Overall, 49% of the enalapril group and 61% of the HCTZ group reported an adverse effect during the study (not significant). Laboratory adverse effects occurred 10% more frequently in the HCTZ group: enalapril, 22%; HCTZ, 32% (not significant); none was serious. Both drugs therefore appeared to be equally efficacious antihypertensive agents in these elderly patients.

Aged↗
PubMed2005

Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients.

BACKGROUND: Stopping the detrimental effects of the renin-angiotensin system at the most upstream point of the cascade offers theoretical advantages for cardiovascular protection. This study compares the antihypertensive efficacy and safety of the novel oral renin inhibitor aliskiren with placebo and an active comparator. METHODS AND RESULTS: The study was a randomized, multicenter, double-blind, placebo-controlled, active-comparator 8-week trial in patients with mild-to-moderate hypertension (mean sitting diastolic blood pressure [DBP] > or =95 and <110 mm Hg). After a 2-week, single-blind placebo run-in, 652 patients were randomized to receive double-blind treatment with once-daily oral doses of aliskiren (150, 300, or 600 mg), irbesartan 150 mg, or placebo. Aliskiren 150, 300, and 600 mg effectively lowered both trough mean sitting DBP and systolic blood pressure (SBP) (P<0.001 versus placebo for both variables). The least-squares mean reductions in trough DBP were 9.3+/-0.8, 11.8+/-0.8, and 11.5+/-0.8 mm Hg, respectively, versus 6.3+/-0.8 mm Hg for placebo, and the least-squares mean reductions in trough SBP were 11.4+/-1.3, 15.8+/-1.2, and 15.7+/-1.2 mm Hg, respectively, versus 5.3+/-1.2 mm Hg for placebo. The antihypertensive effect of aliskiren 150 mg was comparable to that of irbesartan 150 mg (8.9+/-0.7 and 12.5+/-1.2 mm Hg, least-squares reduction in mean sitting DBP and SBP, respectively, for irbesartan). Aliskiren 300 and 600 mg lowered mean sitting DBP significantly more than irbesartan 150 mg (P<0.05). Aliskiren showed safety and tolerability comparable to those of placebo and irbesartan; the incidence of adverse events and number of patients discontinuing therapy were similar in all groups. CONCLUSIONS: Once-daily oral treatment with aliskiren lowers blood pressure effectively, with a safety and tolerability profile comparable to that of irbesartan and placebo, in patients with mild-to-moderate hypertension. Aliskiren 150 mg is as effective as irbesartan 150 mg in lowering blood pressure.

Administration, Oral↗
PubMed2000

Association of blood pressure with fibrinolytic potential in the Framingham offspring population.

BACKGROUND: Hypertension is an established risk factor for acute coronary events. Because fibrinolytic and hemostatic factors are also associated with cardiovascular disease, we examined the relations of systolic and diastolic blood pressures (SBP and DBP) to levels of plasminogen activator inhibitor antigen, tissue plasminogen activator antigen, fibrinogen, factor VII, von Willebrand factor, fibrinogen, and plasma viscosity in subjects of the Framingham Offspring Study. METHODS AND RESULTS: We studied 1193 men and 1459 women after the exclusion of subjects with known cardiovascular disease and those receiving anticoagulant or antihypertensive therapy. Linear regression models were used to evaluate SBP and DBP as predictors of fibrinolytic and hemostatic factor levels in separate sex models, with adjustment for age, body mass index, smoking, diabetes, total cholesterol, HDL, triglycerides, alcohol intake, and estrogen use (in women). In both sexes, levels of plasminogen activator inhibitor and tissue plasminogen activator antigen were positively related to SBP and DBP (P<0.001). Plasma viscosity was positively related to SBP (P=0.008) and DBP (P=0.001) in women only. There was no association between SBP or DBP and fibrinogen, factor VII, or von Willebrand factor in either sex. CONCLUSIONS: These data suggest that impaired fibrinolysis may play an important role in the pathogenesis of cardiovascular disease in hypertensive patients.

Adult↗
PubMed2000

Two-year changes in blood pressure and subsequent risk of cardiovascular disease in men.

BACKGROUND-It is unclear whether, given a current blood pressure level, the previous 2-year change in blood pressure adds important predictive information for cardiovascular disease (CVD). METHODS AND RESULTS-We conducted a prospective cohort study of 11 150 middle-aged and older men reporting blood pressure in the Physicians' Health Study. These men had no history of CVD or antihypertensive medication use through the time of the 2-year follow-up questionnaire; after this time, follow-up for the current study began. A total of 905 incident cases of CVD (705 cases of coronary heart disease and 200 cases of stroke) occurred during a median follow-up of 10.8 years. After controlling for current blood pressure and other coronary risk factors, we found that previous 2-year changes in systolic blood pressure were not associated with the risk of CVD. A similar lack of association was found for individual end points of coronary heart disease and stroke. However, previous 2-year changes in diastolic blood pressure (DBP) may be inversely associated with the risk of CVD (linear trend, P=0.049) independent of coronary risk factors and current DBP. In subgroup analyses, previous 2-year blood pressure changes only added information in leaner men (body mass index <24.39 kg/m(2)). CONCLUSIONS-In this normotensive population of men, the prior 2-year change in DBP, but not systolic blood pressure, may add information to current levels in relation to the risk of CVD. Clinicians may need to consider the previous pattern of DBP change when considering the risk associated with the current DBP level. These data require confirmation in other studies in which blood pressure is measured.

Adult↗
PubMed1984

Postural changes in diastolic blood pressure and the risk of myocardial infarction: the Normative Aging Study.

To assess the relationship of postural changes in blood pressure to risk of myocardial infarction, 1359 men were followed for an average of 8.7 years. The men were participants in the Normative Aging Study, a longitudinal study of aging initiated in 1963 at the Veterans Administration Outpatient Clinic in Boston. It was found that the relationship of sitting blood pressure to the subsequent incidence of myocardial infarction was modified by a variable formed by subtracting supine from standing diastolic blood pressure (delta DBP). The effect of sitting diastolic blood pressure on risk of myocardial infarction was confined primarily to men with a delta DBP of 10 mm Hg or more. The effect of sitting systolic blood pressure on risk of myocardial infarction was apparent in all categories of delta DBP (less than 1, 1 to 9, greater than or equal to 10 mm Hg), but the gradient of risk became stronger with increasing levels of delta DBP. The modifying influence of delta DBP remained even when standard coronary risk factors were included in multivariate analyses. These findings suggest a relationship of vascular responsiveness to risk of subsequent myocardial infarction and may have clinical utility.

Adult↗