摘要:

ObjectiveThe Plaque Hypertension Lipid Lowering Italian Study (PHYLLIS), is the first study in patients with hypertension (diastolic blood pressure (DBP) 95–115 mmHg; systolic blood pressure (SBP) 150–210 mmHg), moderate hypercholesterolaemia (LDL-cholesterol 4.14–5.17 mmol/l (160–200 mg/dl) and initial carotid artery alterations (maximum intima–media thickness (IMT) Tmax⩾1.3 mm). The primary objective of PHYLLIS is investigating whether in these patients administration of an angiotensin converting enzyme inhibitor, fosinopril, and a statin, pravastatin, is more effective than administration of a diuretic and a lipid-lowering diet in retarding or regressing alterations in carotid IMT. While the study is in progress, baseline data are here reported to clarify the association of various risk factors with carotid IMT in these medium–high risk hypertensive patients.MethodsPatients numbering 508 have been randomized to PHYLLIS by 13 peripheral units, in Italy. Age was (mean±SD) 58.4±6.7 years, males were 40.2%, current smokers 16.5%, means±SD of serum total, low-density lipoprotein (LDL), high-density lipoprotein (HDL) cholesterol and triglycerides concentrations were 6.79±0.67, 4.69±0.51, 1.37±0.38, 1.59±0.64 mmol/l (262.4±25.8, 181.3±19.8, 53.0±14.6, 141.0±56.7 mg/dl). Means±SD of clinic sitting SBP/DBP were 159.8±9.0/98.3±4.2 mmHg. 483 of the 508 patients also had 24 h ambulatory BP monitoring, edited and read at a centralized unit (mean±SD 24 h SBP/DBP averages 136.3±14.1/84.0±10.0 mmHg). Quantitative B-mode ultrasound (Biosound 2000 II 5A, Biosound, Indianapolis, Indiana, USA) recordings of carotid arteries were taken by certified sonographers in the peripheral units and tracings were all read at a central unit. CBMmax(mean IMT of eight sites at common carotids and bifurcations) was 1.21±0.17; Mmax (mean of 12 sites also including internal carotids) 1.16±0.17, and Tmax(single maximum) 1.85±0.48 mm.ResultsAmbulatory SBP and pulse pressure (PP) (24 h, daytime, night-time averages) and their variability indices (24 h SD) were always significantly correlated with CBMmax and Mmax(P0.01–0.001), and the correlations remained significant after adjustment for age, gender and smoking. No measurement of DBP was ever associated with any IMT measurement. Likewise, no lipid variable was found associated with any IMT measurement.ConclusionsBaseline data from PHYLLIS indicate that in this population of hypertensive patients with moderate hypercholesterolaemia, SBP and PP are with age among the most significant factors associated with carotid artery alterations. However, the narrow range of inclusion LDL-cholesterol and DBP values may have obscured an additional role of these variables.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo assess changes in the activity of the brain renin–angiotensin system during (i) the development of salt-sensitive hypertension; and (ii) the prevention of salt-sensitive hypertension by blocking brain ‘ouabain'.MethodsIn protocol I, angiotensin converting enzyme (ACE) mRNA and activity and angiotensin I and II levels were assessed in the hypothalamus and pons of Dahl salt-sensitive (Dahl S) and salt-resistant (Dahl R) rats on regular (120 μmol Na+per g) or high (1370 μmol Na+per g) salt diet from 4–6 weeks or 4–9 weeks of age. In protocol II, ACE mRNA and activity were assessed in the hypothalamus and pons in Dahl S on regular or high salt treated with intracerebroventricular (i.c.v.) Fab fragments blocking brain ‘ouabain’ or γ-globulins, and in Dahl R on high or regular salt. ACE mRNA was assessed by quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) assay and angiotensin I and II by radioimmunoassay after high-performance liquid chromatography. In protocol III, effects of i.c.v. angiotensin I and i.c.v. bradykinin on renal sympathetic nerve activity (RSNA), heart rate and blood pressure before and after i.c.v. captopril were assessed in Dahl S and R rats on regular or high salt intake from 4–8 weeks of age.ResultsHigh salt diet caused a gradual, but marked increase in blood pressure in Dahl S but not Dahl R rats. Dahl S rats showed small but significant increases in ACE mRNA in the hypothalamus on regular salt diet. In Dahl S rats on high salt diet for 2 or 5 weeks ACE mRNA levels significantly increased in both hypothalamus and pons, compared with Dahl R rats on either diet or Dahl S rats on regular diet. After 5 weeks of high salt diet, ACE mRNA levels in the hypothalamus in Dahl S rats were almost three-fold higher and in the pons two-fold higher than in Dahl R rats on either diet or Dahl S on regular salt diet. High salt diet also increased ACE activity of the hypothalamus and pons in Dahl S but not Dahl R. Consistent with this increased ACE activity, central responses to angiotensin I were clearly enhanced and to bradykinin markedly diminished in Dahl S on high salt intake. Chronic blockade of brain ‘ouabain’ by i.c.v. Fab fragments prevented the increases in blood pressure, ACE mRNA and activity in the hypothalamus and pons by high salt intake in Dahl S rats. Angiotensin I levels in the hypothalamus and pons were similar in both groups of rats and there were no significant changes caused by high salt diet in Dahl S and R rats. On regular salt intake angiotensin II levels in the hypothalamus of Dahl S rats showed a significant decrease as compared with Dahl R rats on regular salt diet, and were similar in the pons of the two strains. High salt intake did not affect angiotensin II levels in either hypothalamus or pons in Dahl S and R rats.ConclusionsThese results indicate that high salt intake increases blood pressure, ACE expression and activity in the hypothalamus and pons of Dahl S rats without a parallel increase in angiotensin II levels. Effects of high salt intake on ACE mRNA and activity appear to be secondary to activation of brain ‘ouabain'.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveHomeostasis Model Assessment (HOMA index) is predictive of insulin sensitivity in normal and diabetic patients. This study was designed to see if insulin resistance in hypertensives, measured using the HOMA index, differs, based on salt sensitivity, renin status and sodium intake.MethodsFasting insulin and glucose were determined in subsets of 426 essential hypertensives, and normotensives. HOMA was calculated as fasting glucose (mmol) × fasting insulin (μU/ml)/22.5.ResultsFour hundred and twenty-six essential hypertensives and normotensives from four HERMES centers form the basis of this report. There was no difference in the HOMA index between hypertensives and normotensives (P= 0.291) or between hypertensives grouped according to blood pressure salt sensitivity (P= 0.153). However, when essential hypertensives were subgrouped by renin status, the low-renin group had significantly lower (P<0.01) HOMA index than the normal/high-renin group. When normal/high-renin group was divided into modulators and non-modulators, the non-modulators had significantly higher HOMA index (P<0.001) than other hypertensive subsets. The effect of sodium intake on the HOMA index was significant only for non-modulators (P<0.002), with salt restriction increasing insulin resistance.ConclusionInsulin sensitivity differs among subsets of essential hypertension, non-modulators being most insulin resistant and the low-renin subset insulin sensitive. Salt restriction might have an adverse effect on insulin sensitivity in non-modulators. The reduction in cardiovascular risk seen in low-renin hypertensives may be related to their increased insulin sensitivity; in contrast, the clustering of cardiovascular risk factors seen in non-modulators may be due to increased insulin resistance.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo measure the effects of hyperinsulinemia on serum electrolyte status and associated hormones, and on serum free fatty acid (FFA) concentrations, in patients with essential hypertension.Design and methodsThe serum electrolyte status (Na, K, Ca, ionized Ca, Mg, P, pH) and associated hormones [plasma renin activity (PRA), serum parathyroid hormone (PTH) and aldosterone concentrations], and FFA were measured during an euglycemic hyperinsulinemic clamp test in 49 patients with untreated essential hypertension.ResultsSerum potassium, phosphate, PTH, and FFA concentrations decreased during hyperinsulinemia, while serum ionized calcium concentration, pH, and PRA increased significantly (P<0.05). The changes in serum potassium and magnesium were both inversely related to the insulin-mediated glucose uptake (r= −0.62,P<0.0001;r= −0.31,P<0.05, respectively). Both body mass index (BMI) and insulin-mediated glucose disposal were significantly correlated to the changes in serum aldosterone concentration during hyperinsulinemia (r= 0.41,P<0.01;r= −0.40,P<0.01, respectively). The change in serum aldosterone during the clamp test was not significantly related to the change in PRA, but tended to correlate to the change in potassium concentration (r= 0.25,P= 0.10). A less pronounced reduction in FFA during induced hyperinsulinemia was associated with low insulin sensitivity (r= −0.35,P<0.05).ConclusionHypertensive patients with normal BMI and a more pronounced glucose uptake showed a larger serum potassium decline and lowered aldosterone concentrations during induced euglycemic hyperinsulinemia. Insulin-resistant patients showed a less pronounced reduction in FFA during hyperinsulinemia. The observations in the present study may indicate that alterations in aldosterone and FFA metabolism might be linked to the insulin resistance metabolic syndrome.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveInsulin-mediated vasodilation has been shown to be impaired with hypertension and aggravated by dietary sodium restriction. Whether vascular insulin resistance in this setting could be improved by antihypertensive therapy was unknown. Therefore, we determined the effect of therapy with an angiotensin-converting enzyme inhibitor, on vascular sensitivity to insulin in hypertensive subjects fed a sodium-restricted diet.Design and MethodsThe effects of 3 months of therapy with quinapril on vascular sensitivity to insulin was assessed in 11 hypertensive subjects using a randomized, placebo-controlled, double-blind design. Vascular sensitivity to insulin was assessed by determination of the insulin ED50 from dorsal hand vein linear variable differential transformer in phenylephrine-preconstricted vessels. Subjects were maintained on a 75 mmol/day sodium diet for 3 days prior to each study.ResultsQuinapril therapy significantly improved vascular sensitivity to insulin, as assessed by a decrease in the ED50for insulin (ED50 insulin: placebo = 501±189 μU/min; quinapril = 276±100 μU/min P<0.05). Isoproterenol-mediated relaxation was also enhanced by quinapril treatment (maximal isoproterenol-mediated relaxation: Placebo = 92±15% of baseline distension; Quinapril = 151±31% P<0.05).ConclusionsThe current study suggests the hypothesis that the ACE-inhibitor quinapril has beneficial effects on vascular function in general, and on insulin-mediated vascular responses, in particular.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo test whether inappropriate echocardiographic left ventricular (LV) mass (i.e. higher than predicted by individual body size, sex and cardiac load [Δ%LVM]) is associated with an increased rate of cardiovascular events, and whether values of LV mass lower than appropriate confer protection.DesignProspective, longitudinal.SettingInstitutional, hospital outpatient clinic.PatientsA total of 294 hypertensive patients, 84 with inappropriate and 21 with low LV mass (lower than appropriate).Main outcome measuresCardiovascular fatal and non-fatal events.ResultsBaselineΔ%LVM was higher in patients with follow-up total (n= 50) or fatal (n= 14) events than in event-free survivors (allP<0.0001) and predicted events independently of age and systolic pressure (allP<0.0001). Although the performance was not better than with use of more traditional definition of LV hypertrophy,Δ%LVM remained a predictor even in the subgroup of 126 patients (32 total events, 13 deaths) with clear-cut LV hypertrophy (P<0.009). Patients with low LV mass exhibited supranormal LV chamber and midwall function, slightly higher heart rate and higher cardiac index (allP<0.01). These patients had the same rate of events as those with appropriate LV mass.ConclusionsIn hypertensive patients, increase in LV mass beyond values required to compensate cardiac workload at a given body size and sex predicts cardiovascular risk independently of age and blood pressure, in the whole population as well as in the subset of patients with LV hypertrophy. Hypertensive patients with levels of LV mass lower than needed to compensate cardiac workload exhibit hyperdynamic circulatory status and the same risk pattern as patients with higher values of LV mass, possibly due to activation of the sympathetic system.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesTo clarify the relations of systemic hemodynamics to left ventricular (LV) geometric patterns in patients with moderate hypertension and target organ damage.BackgroundLV geometry stratifies risk in hypertension, but relations of LV geometry to systemic hemodynamic patterns in moderately severe hypertension have not been fully elucidated.DesignCross-sectional case–control study.SettingBaseline findings in the echocardiographic substudy of the Losartan Intervention For Endpoint Reduction in Hypertension Study (LIFE) and in a normotensive reference group.Patients/participantsNine hundred and sixty-four patients with Stage I–III hypertension and LV hypertrophy by Cornell voltage duration criteria ((SV3 + RaVL [+ 6 mm in women]) × QRS>2440 mm × ms) or modified Sokolow–Lyon voltage criteria (SV1 + RV5/RV6>38 mm), and 366 apparently normal adults.InterventionsNone.MethodsTwo-dimensional and Doppler echocardiograms were used to classify hypertensive patients into groups with normal geometry, concentric remodelling and concentric and eccentric hypertrophy, and to measure stroke volume (SV), cardiac output, peripheral resistance and pulse pressure/SV as a measure of arterial stiffness. Comparisons were adjusted for covariates by general linear model with the Sidak post-hoc test.ResultsMean SV was higher in patients with eccentric hypertrophy (83 ml/beat) and lower with concentric remodeling (68 ml/beat) than in normal adults (73 ml/beat). Cardiac output was highest in patients with eccentric LV hypertrophy and lower with concentric remodeling than eccentric hypertrophy; mean pressure and peripheral resistance were equally high in all hypertensive subgroups, whereas pulse pressure/SV was most elevated (by a mean of 47% versus reference subjects) with concentric remodeling and least so (mean + 15%) with eccentric hypertrophy. In multivariate analysis (MultipleR+ 0.68), LV mass was independently related to higher systolic pressure, older age, SV, male gender and body mass index (allP<0.001). Relative wall thickness was independently related (MultipleR+ 0.50) to older age, higher systolic pressure, lower SV (allP<0.001) and higher body mass index (P+ 0.007). SV and cardiac output were lower in patients with low stress-corrected midwall shortening.ConclusionIn patients with moderate hypertension and ECG LV hypertrophy, the levels of SV and pulse pressure/SV, are associated with, and may be stimuli to different LV geometric phenotypes.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

BackgroundIndexation to fat-free mass (FFM) seems to be the best option for adjusting left ventricular (LV) mass. However, measurements of FFM are frequently not available.ObjectivesTo define the relation of FFM with commonly available anthropometric measures in order to derive an approximation formula of FFM that can be used for valid indexation of LV mass.Subjects and methodsA total of 1371 subjects from a community survey were examined by echocardiography to measure LV mass and by bioelectrical impedance analyses (BIA) for the determination of FFM. An approximation of FFM was generated in a healthy subgroup of 213 men and 291 women by non-linear regression techniques.ConclusionsWe propose a novel approximation of FFM based on exponentials of body height and weight. It performed well in the indexation of LV mass in middle-aged men and women of this study. Evaluation of the equation in other populations should be awaited before its use is recommended in situations where direct determination of FFM is not possible.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectiveTo verify in a unitary view whether autonomic control of heart rate and cardiac structure and function are modified early in offspring of hypertensive families.Methods and resultsWe selected 87 age- and sex-matched young normotensive subjects with (n= 45) and without (n= 42) a family history of hypertension who underwent evaluations of arterial pressure, time-domain parameters of autonomic heart rate control (24-h ECG monitoring), spectral baroreflex sensitivity, left ventricular geometry and function (echo-Doppler) and plasma brain natriuretic peptide levels (BNP). The group with a family history of hypertension significantly differed from their counterparts for systolic pressure (119±11 versus 114±9 mmHg,P<0.05), heart rate (RR interval, 766±64 versus 810±93 ms,P<0.05), heart rate variability [the standard deviation of normal RR intervals (SDNN), 147±29 versus 171±33 ms,P<0.05], diastolic function (isovolumetric relaxation time, 65±9 versus 60±8 ms,P<0.05) and BNP (23±13 versus 37±10 pg/ml,P<0.05). Baroreflex sensitivity values did not differ between the two groups. When gender was considered, all the above-mentioned measures, as well as baroreflex sensitivity, were significantly different between males with and without a family history of hypertension but not between females, except for BNP, which was lower in males and females with a history of hypertension (males, 24±11 versus 38±8 pg/ml,P<0.01; females 21±14 versus 36±13 pg/ml,P<0.05).ConclusionsMale, but not female, hypertensive offspring have modified diastolic function and autonomic control of heart rate; BNP is the only parameter able to characterize hypertensive offspring independently from the influence of gender. This provides the hypothesis that the impaired production of this hormone could play a primary role in the pre-hypertensive state.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID

摘要:

ObjectivesHypertensive patients are a heterogeneous population that can be distributed in groups showing different cardiovascular risk and benefit from treatment. This study examines the cost-effectiveness of arterial hypertension treatment by age, sex, arterial hypertension stage, type of drug used and level of treatment compliance.DesignMarkov models combining absolute risks for stroke, coronary heart disease and all causes of death with relative risks from clinical trials and observational studies. Data on health costs were collected from hospitals and primary care settings in the Basque Country (Spain).ResultsCost-effectiveness ratios vary from 34 516 euros/quality adjusted life year (QALY) gained in 30-year-old women to 3307 euros/QALY in 80-year-old men. A treatment compliance of 50% increases these values to 45 270 and 4905 euros/QALY, respectively. Treatment of arterial hypertension stage II shows lower ratios (19 798 euros/QALY in 30-year-old women and 1918 euros/QALY in 80-year-old persons). Cost-effectiveness ratios for arterial hypertension stage I vary from 645 euros/QALY in 80-year-old men for diuretics to 47 325 euros/QALY in 30-year-old women for inhibitors of the angiotensin converting enzyme.ConclusionsThere are large variations in the cost-effectiveness of arterial hypertension treatment depending on age, sex, arterial hypertension stage, drug used and compliance. Improvement of treatment compliance yields the greatest gain both in effectiveness and efficiency.

ISSN:0263-6352    

出版商:OVID    

年代:2001

数据来源: OVID