摘要:

BackgroundArterial stiffness is an important determinant of pulse pressure, and of left ventricular load and coronary perfusion pressure.Assessments of stiffnessPrecise quantification is elusive, since stiffness is different in different arteries and even in the same artery at different pressures. Proximal elastic arteries and peripheral muscular arteries respond differently to aging change and to drugs. Various other terms are used to express stiffness, such as distensibility and compliance. Various indirect indices are also used, including pulse wave velocity, characteristic impedance and augmentation index.Increases in stiffnessWhile the literature is confusing, it is well established that stiffness of central arteries increases with aging and with elevated blood pressure. Effects of other diseases and of vasoactive agents are less clear-cut.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

Use of placebo controlsPlacebo controls can enhance the value of two types of hypertension trials: measurement of the blood pressure-lowering efficacy of antihypertensive treatment and determination of whether therapeutic interventions can affect clinical endpoints. However, the possibility of adverse outcomes in hpertensive patients allocated to placebo therapy raises ethical concerns.Efficacy studiesPlacebo controls in efficacy studies are particularly helpful in thoroughly quantifying the effect of treatment. The hazard to patients can be minimized by exposing them to placebo for the least possible amount of time and, assuming that blood pressure is itself the primary variable, reducing the probability of cardiovascular events by excluding subjects with severe hypertension or major concomitant risk factors.Endpoint studiesEndpoint studies present a more difficult challenge, for they are designed in anticipation of cardiovascular events and patients at high risk are often enrolled in order to more rapidly achieve the required number of endpoints for statistical analysis. In such circumstances, positive therapeutic controls, despite the complexities of analysis, must be preferred to placebo.Early-stage hypertensionImportant questions regarding the management of early-stage hypertension remain, and despite official treatment guidelines recommendations, currently based chiefly on extrapolation and judgement, many physicians routinely withhold therapy in mild hypertension, even when other risk factors are present. With appropriate safeguards, placebo-controlled trials may be necessary to examine potenial benefits of therapy in such patients. Indeed, resolving therapeutic uncertainty and creating well founded recommendations for the future management of the many patients with milder forms of hypertension can make placebo controls both ethical and appropriate.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveIn this meta-analysis, we attempted to derive pooled estimates for the putative associations between various cardiovascular–renal disorders and theM235Tpolymorphism of the angiotensinogen gene.MethodsCase–control studies were combined, using the Mantel and Haenszel approach. JointPvalues for continuous variables were calculated by Stouffer's method. Continuous measurements reported in different units were expressed on a percentage scale using the intrastudy mean of theMMgenotype as denominator.ResultsThe computerized database used for this analysis included 69 reports with an overall sample size of 27 906 subjects. Overall, possession of theTallele was associated with an increased risk of hypertension. In comparison with theMMreference group (number of studies,n= 32), the excess risk was 31% (P= 0.001) inTThomozygotes and 11% (P= 0.03) inTMheterozygotes. The sensitivity analysis showed that this association was present only in whites (Tallelic frequency,f= 42.2%), but not in blacks (f= 77.0%) or Asians (f= 78.0%). Atherosclerotic complications (n= 12), renal microvascular disorders (n= 13), cardiomyopathy (n= 2) or diabetic retinopathy (n= 3) were not correlated with theM235Tpolymorphism. Publication bias was observed for hypertension, but not for coronary heart disease, including myocardial infarction, and for microvascular nephropathy. Futhermore, in comparison with theMMcontrol group, the circulating angiotensinogen levels (n= 8) were raised by 11 and 7% (P= 0.01) inTTandTMsubjects, respectively. In contrast, plasma levels of the angiotensin I converting enzyme (n= 4) and body mass index (n= 15) were not associated with theTallele.ConclusionTheTallele encoding angiotensinogen is not associated with atherosclerotic or microvascular complications, but in Caucasians behaves as a marker for hypertension. This association, which may have been inflated by publication bias, does not necessarily imply causality.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo explore whether the inverse association between birth weight and mortality from circulatory diseases is mediated through blood pressure in men aged 50–75 years.DesignCohort study with retrospectively collected data on size at birth.Subjects and settingThe study included 1334 men born during 1920–1924, living in Uppsala, Sweden, who were examined at the ages of 50 and 60 years, and followedup to the end of 1995.Main outcome measuresMortality from circulatory diseases based on routine death registration.ResultsBirth weight showed a specific, inverse association with mortality from circulatory diseases: the rate ratio was 0.67 (95% confidence interval 0.50 to 0.89) per 1000 g increase in birth weight. This association was not appreciably affected by adjustment for sociodemographic characteristics or smoking, but was strengthened slightly by adjustment for body mass index at the ages of 50 and 60 years. Adjustment for systolic blood pressure at the age of 50 years only slightly reduced the strength of the inverse association between birth weight and mortality from ischaemic heart disease, and did not affect the inverse association between birth weight and mortality from stroke. Adjustments for systolic and diastolic blood pressure and hypertension treatment at the ages of 50 and 60 years did not reduce the strength of the association between birth weight and mortality from circulatory diseases at the age of 60–75 years.ConclusionsThe inverse association between birth weight and mortality from circulatory diseases in men aged 50–75 years is independent of adult sociodemographic characteristics, smoking and adult obesity and does not seem to be mediated through an increased blood pressure in those with low birth weight.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo examine the influence of genetic factors on plasma leptin levels.Subjects and methodsWe measured plasma leptin levels, body mass index and body fat distribution in healthy young female monozygotic (n= 19) and dizygotic (n= 14) twins. The twin zygosity was verified by determination of short tandem repeat and amplified fragment length polymorphism systems. The genetic analysis included analysis of variance-based and maximum likelihood-based methods.ResultsPlasma leptin levels were correlated significantly with body mass index (r= 0.59,P< 0.001), waist circumference (r = 0.54,P< 0.001) and hip circumference (r= 0.63,P< 0.001), but not with age (r = −0.17) or the waist: hip ratio (r= 0.02). The heritability estimates derived from intraclass correlations were significant for body mass index (P= 0.001), waist circumference (P= 0.004), hip circumference (P= 0.01) and plasma leptin levels (P= 0.005), but not for the waist : hip ratio (P= 0.22). In the maximum likelihood-based path analysis, heritability was estimated at 79% for body mass index and at 73% for plasma leptin levels. After adjustment for body mass index, the heritability estimate for leptin levels from the model-fitting approach was 55%.ConclusionsGenetic factors are major determinants of plasma leptin levels in humans and may account for as much as half of the variance in leptin levels.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo evaluate the possible association of three candidate gene polymorphisms with essential hypertension in the genetically homogeneous Sardinian population.Subjects and methodsWe studied 494 unrelated, nondiabetic subjects, 213 (43.2%) with essential hypertension. All subjects underwent a 75 g oral glucose tolerance test with determination of glycemia and insulinemia and serum lipids. The polymorphisms evaluated comprised Trp64Arg of the β3-adrenergic receptor, Gly40Ser of the glucagon receptor gene and the insertion/deletion polymorphism of the angiotensin converting enzyme (ACE) gene.ResultsAmong the overall population studied, 48 (9.7%) were heterozygous carriers of the Trp64Arg polymorphism. The frequency of the Trp64Arg variant was significantly higher in hypertensives (13.6%) than normotensives (6.8%; x25.73,P= 0.017). The 48 subjects with the Trp64Arg variant had significantly higher (P< 0.049) serum triglyceride levels than the 446 with the Trp64Trp variant, while no significant differences were observed, either fasting or during the 75 g oral glucose tolerance test, in glycemia and insulinemia. No differences were found between hypertensive and normotensive subjects forACEgene insertion/deletion polymorphism nor in the frequency of the Gly40Ser coding change in exon 2 of the glucagon receptor gene.ConclusionsOur results are consistent with the thesis that the Trp64Arg polymorphism of the β3-adrenergic receptor gene is associated more often with the condition of high blood pressure than with normal blood pressure.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveA previous study has shown significant linkage of five markers near the lipoprotein lipase locus to systolic blood pressure, but not to diastolic blood pressure, in nondiabetic members of 48 Taiwanese families selected for noninsulin-dependent diabetes. However, lipoprotein lipase markers did not appear strongly linked to systolic blood pressure in a study of Mexican–Americans using a variety of selection schemes. The objective of the current study was to test whether markers near the lipoprotein lipase gene were linked to hypertension in Caucasians.DesignTo test for linkage of genetic markers in or near the lipoprotein lipase gene to hypertension in Caucasians, two sets of Caucasian hypertensive sibships were genotyped. The samples included 261 sibships (431 effective sibpairs) from four field centers of the National Heart, Lung and Blood Institute Family Heart Study and 211 sibships (282 effective sibpairs) from the Health Family Tree database in Utah.ResultsTwo highly polymorphic markers in or near the lipoprotein lipase gene showed no evidence of excess allele sharing in either set of hypertensive sibships. Combining the two datasets resulted in 653 and 713 effective sibpairs for the two markers, sharing 0.495 ± 0.30 and 0.486 ± 0.28 alleles identical by descent compared to an expected sharing of 0.50. Multipoint analysis of the two loci also did not show linkage (P= 0.95).ConclusionsWe conclude that the lipoprotein lipase locus and nearby regions do not appear to be linked to hypertension in Caucasians.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe physiological and pathophysiological functions of endothelin-1 in modulating the regional blood flow of normal and spontaneously hypertensive rats (SHR) were studied in the perfused mesenteric vascular bed, a useful model for investigating resistance vessels.Design and methodsWe used 12-week-old SHR and Wistar–Kyoto (WKY) rats. Endothelin A (ETA) receptor responsiveness was evaluated by endothelin-1 (0.2–2 μmol/l) concentration–response curves, and repeated in the presence of indomethacin and the ETAand endothelin B (ETB) receptor antagonists BQ-485 and BQ-788, respectively. ETBreceptor responsiveness was tested by sarafotoxin S6c concentration–response curves, obtained in the noradrenaline-precontracted mesenteric vascular bed, and repeated after treatment with BQ-788 and after endothelial denudation.ResultsIn both groups, endothelin-1 induced concentration-dependent contraction; SHR exhibited a markedly increased maximal effect compared with WKY rats (P< 0.01). BQ-485 produced a shift to the right for endothelin-1 concentration–response curves in both groups, with a higher pA2(negative common logarithm of the antagonist that produces an agonist dose ratio of 2) value in SHR than in WKY rats (P< 0.01). The increase in the maximal effect produced by endothelin-1 in SHR was prevented by indomethacin, which also induced a significant increase in the endothelin-1 concentration producing the half-maximal response (EC50) in SHR (P< 0.05). Sarafotoxin S6c produced an ETB-dependent endothelium-mediated relaxant effect in WKY rats, which was not observed in SHR.ConclusionsThe higher vasoconstriction induced by endothelin-1 in SHR may be related to a greater number of available ETAreceptors, due to the presence of an ETAreceptor subtype. This mechanism may be linked to the production of prostanoids that add to the direct endothelin-1-evoked vasoconstriction. These results, together with the lack of relaxation in response to sarafotoxin S6c in SHR, suggest that an imbalance in the endothelin-1 ability to induce both contraction and relaxation is present in SHR with sustained hypertension, manifesting as a greater contractile effect evoked in this strain.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveThe aim of this study was to investigate the effects of calcium channel blockers on messenger RNA expression of endothelin-1 and endothelial-type nitric oxide synthase in the cardiovascular tissue of strokeprone spontaneously hypertensive rats (SHRSP).Materials and methodsThe calcium channel blocker nilvadipine (1.0 or 3.2 mg/kg per day) was subcutaneously administered to two groups of SHRSP, from 4 or 8 weeks of age, for 8 weeks and 4 weeks, respectively. For comparison, nifedipine (3.2mg/kg per day) was similarly administered to SHRSP from 4 weeks of age for 8 weeks. Kidney, heart, aorta and brain tissue samples were obtained when the rats were 12 weeks old. Messenger RNA expression of endothelin-1 and endothelial-type nitric oxide synthase was determined by reverse transcription-polymerase chain reaction followed by Southern blotting and a ribonuclease protection assay, respectively. Results were compared with those in untreated SHRSP and Wistar-Kyoto rats at 12 weeks of age.ResultsBoth nilvadipine and nifedipine significantly decreased blood pressure in SHRSP. Although there were no changes in the weights of the kidney and brain, there was a significant decrease in the weight of the left ventricle of the groups treated with nilvadipine (1.0 mg/kg per day: mean ± SEM 0.282 ± 0.003 g; 3.2 mg/kg per day: 0.269 ± 0.005 g) and nifedipine (1 mg/kg/day: 0.281 ± 0.012 g) for 8 weeks compared with untreated SHRSP (0.301 ± 0.004 g). Endothelin-1 messenger RNA expression, which was significantly increased by about twofold in the kidney, heart and brain of SHRSP compared with Wistar-Kyoto rats, was normalized by both calcium blockers. Endothelin-1 messenger RNA expression, which was decreased in the aorta of SHRSP, was further decreased by both calcium blockers. While there was no significant difference in endothelial-type nitric oxide synthase messenger RNA expression in the kidney, heart and aorta between the untreated SHRSP and Wistar-Kyoto rats, expression in the aorta was significantly increased in the group treated with these calcium blockers for 8 weeks from 4 weeks of age.ConclusionsThese results suggest that, in addition to their potent antihypertensive effects, calcium channel blockers may exhibit cardiovasculoprotective and renoprotective effects by modifying mRNA expression of endothelin-1 and endothelial-type nitric oxide synthase in tissue.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID

摘要:

ObjectiveTo evaluate blood pressure and humoral vasoconstrictor responses to recurrent episodes of obstructive sleep apnea and the effects of therapy by means of continuous positive airway pressure.Patients and methodsWe prospectively evaluated overnight changes in hemodynamics, oxygen saturation, the apnea–hypopnea index, circulating endothelin-1, norepinephrine and plasma renin activity in 22 patients with severe obstructive sleep apnea before and after successful therapy using continuous positive airway pressure therapy (three measurements). Measurements of endothelin-1 and blood pressure were also obtained on three occasions, at similar times, in 12 healthy control subjects without sleep disturbances.ResultsMean arterial pressure and endothelin-1 concentrations increased significantly after 4 h of untreated obstructive sleep apnea, and decreased after 5 h of continuous positive airway pressure. Changes in endothelin-1 levels were correlated with changes in mean arterial pressure (r= 0.44,P< 0.02) and with changes in oxygen saturation (r= 0.37,P< 0.05). Norepinephrine levels and plasma renin activity did not change significantly in patients with obstructive sleep apnea, and were not correlated with changes in blood pressure or oxygen saturation. In controls, blood pressure measurements at similar times during the night showed changes directionally opposite to that seen in obstructive sleep apnea, while endothelin-1 levels remained unchanged.ConclusionsSleep apnea elicits increases in blood pressure and endothelin-1, with reductions in both after treatment. Vasoconstrictor and mitogenic effects of endothelin-1 may be implicated in increased cardiovascular risk in patients with obstructive sleep apnea.

ISSN:0263-6352    

出版商:OVID    

年代:1999

数据来源: OVID