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Showing papers in "Journal of Hypertension in 2000"


Journal ArticleDOI
TL;DR: The existing evidence support the view that oxidative stress may play a crucial role in cardiac and vascular abnormalities in different types of cardiovascular diseases and that the antioxidant therapy may prove beneficial in combating these problems.
Abstract: ObjectivesIn view of the critical role of intracellular Ca2+-overload in the genesis of myocyte dysfunction and the ability of reactive oxygen species (ROS) to induce the intracellular Ca2+-overload, this article is concerned with analysis of the existing literature with respect to the role of oxida

1,394 citations


Journal ArticleDOI
TL;DR: Both birth weight and head circumference at birth are inversely related to systolic blood pressure, and the relationship is present in adolescence but attenuated compared to both the pre- and post-adolescence periods.
Abstract: Objective To conduct a systematic review in order to (i) summarize the relationship between birthweight and blood pressure, following numerous publications in the last 3 years, (ii) assess whether other measures of size at birth are related to blood pressure, and (iii) study the role of postnatal catch-up growth in predicting blood pressure. Data identification All papers published between March 1996 and March 2000 that examined the relationship between birth weight and systolic blood pressure were identified and combined with the papers examined in a previous review. Subjects More than 444 000 male and female subjects aged 0-84 years of all ages and races. Results Eighty studies described the relationship of blood pressure with birth weight The majority of the studies in children, adolescents and adults reported that blood pressure fell with increasing birth weight, the size of the effect being approximately 2 mmHg/kg. Head circumference was the only other birth measurement to be most consistently associated with blood pressure, the magnitude of the association being a decrease in blood pressure by approximately 0.5 mmHg/cm. Skeletal and non-skeletal postnatal catch-up growth were positively associated with blood pressure, with the highest blood pressures occurring in individuals of low birth weight but high rates of growth subsequently. Conclusions Both birth weight and head circumference at birth are inversely related to systolic blood pressure. The relationship is present in adolescence but attenuated compared to both the pre- and post-adolescence periods. Accelerated postnatal growth is also associated with raised blood pressure.

1,069 citations


Journal ArticleDOI
TL;DR: A review of the methods most widely used to assess baroreflex function in humans, in the laboratory and in daily life finds that techniques based on computer analysis of spontaneous blood pressure and heart rate fluctuations allow spontaneous barore Flex sensitivity to be assessed in real life conditions.
Abstract: Arterial baroreflex function in humans is commonly assessed through a number of laboratory tests based on quantification of the reflex responses in heart rate or blood pressure to external stimuli applied to the cardiovascular system. Evidence is available that these laboratory estimates of baroreflex sensitivity have both pathophysiological and clinical relevance. Indeed, a number of studies have shown that the sensitivity of the baroreceptor-heart rate reflex may have a prognostic value in myocardial infarction, heart failure and diabetic patients, where mortality seems to be inversely related to the sensitivity of cardiac baroreflex modulation. A deeper insight into the features of daily-life baroreflex cardiovascular control has been offered more recently by techniques based on computer analysis of spontaneous blood pressure and heart rate fluctuations. This innovative approach allows spontaneous baroreflex sensitivity to be assessed in real life conditions, with no need for external stimulation of the patient as required by the older laboratory techniques. This review will briefly survey the methods most widely used to assess baroreflex function in humans, in the laboratory and in daily life.

491 citations


Journal ArticleDOI
TL;DR: A meta-analysis of randomised salt reduction trials shows that a modest reduction in salt intake for a duration of 4 or more weeks has a significant and, from a population viewpoint, important effect on blood pressure in both individuals with normal and elevated blood pressure.
Abstract: BACKGROUND Many randomised trials assessing the effect of salt reduction on blood pressure show reduction in blood pressure in individuals with high blood pressure. However, there is controversy about the magnitude and the clinical significance of the fall in blood pressure in individuals with normal blood pressure. Several meta-analyses of randomised salt reduction trials have been published in the last few years. However, most of these included trials of very short duration (e.g. 5 days) and included trials with salt loading followed by salt deprivation (e.g. from 20 to 1 g/day) over only a few days. These short-term experiments are not appropriate to inform public health policy which is for a modest reduction in salt intake over a prolonged period of time. A meta-analysis by Hooper et al is an important attempt to look at whether advice to achieve a long-term salt reduction (i.e. more than 6 months) in randomised trials causes a fall in blood pressure. However, most trials included in this meta-analysis achieved a small reduction in salt intake; on average, salt intake was reduced by 2 g/day. It is, therefore, not surprising that this analysis showed a small fall in blood pressure, and that a dose-response to salt reduction was not demonstrable. OBJECTIVES To assess the effect of the currently recommended modest reduction in salt intake (WHO 2003; SACN 2003; Whelton 2002), on blood pressure in individuals with normal and elevated blood pressure. To assess whether the magnitude of the reduction in blood pressure is dependent on the magnitude of the reduction in salt intake. SEARCH STRATEGY We searched MEDLINE, EMBASE, Cochrane library, CINAHL, and reference list of original and review articles. SELECTION CRITERIA We included randomised trials with a modest reduction in salt intake and a duration of 4 or more weeks. DATA COLLECTION AND ANALYSIS Data were extracted independently by two persons. Mean effect sizes were calculated using both fixed and random effect models using Review Manager 4.2.1 software. Weighted linear regression was used to examine the relationship between the change in urinary sodium and the change in blood pressure. We used funnel plots to detect publication and other biases in the meta-analysis. MAIN RESULTS Seventeen trials in individuals with elevated blood pressure (n=734) and 11 trials in individuals with normal blood pressure (n=2220) were included. In individuals with elevated blood pressure the median reduction in 24-h urinary sodium excretion was 78 mmol (4.6 g/day of salt), the mean reduction in systolic blood pressure was -4.97 mmHg (95%CI:-5.76 to -4.18), and the mean reduction in diastolic blood pressure was -2.74 mmHg (95% CI:-3.22 to -2.26). In individuals with normal blood pressure the median reduction in 24-h urinary sodium excretion was 74 mmol (4.4 g/day of salt), the mean reduction in systolic blood pressure was -2.03 mmHg (95% CI: -2.56 to -1.50) mmHg, and the mean reduction in diastolic blood pressure was -0.99 mmHg (-1.40 to -0.57). Weighted linear regression analyses showed a correlation between the reduction in urinary sodium and the reduction in blood pressure. REVIEWERS' CONCLUSIONS Our meta-analysis demonstrates that a modest reduction in salt intake for a duration of 4 or more weeks has a significant and, from a population viewpoint, important effect on blood pressure in both individuals with normal and elevated blood pressure. These results support other evidence suggesting that a modest and long-term reduction in population salt intake could reduce strokes, heart attacks, and heart failure. Furthermore, our meta-analysis demonstrates a correlation between the magnitude of salt reduction and the magnitude of blood pressure reduction. Within the daily intake range of 3 to 12 g/day, the lower the salt intake achieved, the lower the blood pressure.

416 citations


Journal ArticleDOI
TL;DR: Serum uric acid independently predicts cardiovascular events in older persons with isolated systolic hypertension and monitoring serum uric Acid change during diuretic treatment may help to identify patients who will most benefit from treatment.
Abstract: ObjectiveTo assess longitudinally the association of serum uric acid and its change due to diuretic treatment with cardiovascular events in hypertensive patients.DesignCohort study in a randomized trial.SettingCohort of hypertensive patients.ParticipantsA total of 4327 men and women, aged ≥ 60 years

298 citations


Journal ArticleDOI
TL;DR: PWV may be used as a relevant tool to assess the influence of cardiovascular risk factors on aortic stiffness in high-risk patients, and shows that the cumulative influence of risk factors, even treated, is an independent determinant of arterial stiffness.
Abstract: Objective To determine the relationships between pulse wave velocity (PWV), an estimate of arterial distensibility and cardiovascular risk factors. Design This cross-sectional population-based study was carried out from 1995 to 1997 to investigate these relationships. Population and methods Some 993 subjects, aged 35-64 years (52.7% men), living in the south-west of France, were randomly selected from electoral rolls and participated in a cross-sectional study. Medical examinations were performed by specially trained medical staff. Carotid-femoral PWV was measured using a semiautomatic device (Complior, Garges les Gonesse, France). The relationships between PWV and risk factors were assessed, first in subjects not treated with hypolipidaemic, antidiabetic and antihypertensive drugs and then in treated subjects. In subjects not treated for cardiovascular risk factors, age, gender, systolic blood pressure (SBP) and heart rate (P < 0.001) were the variables significantly associated with PWV. In treated patients, age (P < 0.01), SBP (P < 0.001), heart rate (P < 0.001), apolipoprotein B (P< 0.05) and the number of treated cardiovascular risk factors (P< 0.05) were positively correlated with PWV. Conclusion This study shows that, in a sample of subjects at high risk, the cumulative influence of risk factors, even treated, is an independent determinant of arterial stiffness. These results suggest that PWV may be used as a relevant tool to assess the influence of cardiovascular risk factors on aortic stiffness in high-risk patients.

258 citations


Journal ArticleDOI
TL;DR: There is a high prevalence of hypertension in rural and urban areas of Tanzania, with low levels of detection, treatment and control, which demonstrates the need for cost-effective strategies for primary prevention, detection and treatment of hypertension and the growing public health challenge of non-communicable diseases in Sub-Saharan Africa.
Abstract: ObjectiveTo describe the prevalence, detection, treatment and control of hypertension in an urban and rural area of Tanzania.DesignTwo linked cross-sectional population-based surveysSettingA middle-income urban district of Dar es Salaam (Ilala) and a village in the relatively prosperous rural area o

250 citations


Journal ArticleDOI
TL;DR: The studies that are required in hypertension should use two different approaches: novel titrations of conventional drugs to achieve a decrease in either SBP or pulse pressure, and development of new drugs acting selectively on the large artery wall, to facilitate the conduct of subsequent controlled trials.
Abstract: BACKGROUND Increased pulse pressure and arterial stiffness are identified as predictors of cardiovascular risk in older hypertensive populations, particularly that of myocardial infarction. Because increased pulse pressure involves an increase in systolic (SBP) and a decrease in diastolic blood pressure (DBP), and because the former promotes cardiac hypertrophy and the latter alters coronary perfusion, a drug regimen reducing pulse pressure and decreasing arterial stiffness might further reduce cardiovascular risk. Under conventional treatment, normalization of DBP (< or = 90 mmHg) is not consistently associated with normalization of SBP (< or = 140 mmHg). THERAPEUTIC DESIGNS In individuals older than 50 years, the goal of antihypertensive treatment should be, not only to decrease mean blood pressure (to less than 100 mmHg), but also to decrease pulse pressure (to less than 50 mmHg). Using appropriate pharmacological tools, trials should test whether an active decrease in arterial stiffness might produce an attenuation of the age-related increase in SBP and decrease in DBP, thus delaying the age-related increase in pulse pressure and decreasing further cardiovascular risk. This procedure requires concomitant non-invasive evaluations of aortic stiffness. CONCLUSION The studies that are required in hypertension should use two different approaches: novel titrations of conventional drugs to achieve a decrease in either SBP or pulse pressure, and development of new drugs acting selectively on the large artery wall, to facilitate the conduct of subsequent controlled trials.

236 citations


Journal ArticleDOI
TL;DR: The present study prospectively investigated the relation between ambulatory blood pressure and first symptomatic stroke risk in a general population demonstrated that 24-h, daytime and night-time ambulatoryBlood pressure values were linearly related to stroke risk.
Abstract: Objective To investigate the association between 24 h, daytime and night-time ambulatory blood pressures and first symptomatic stroke, to compare their predictive powers for stroke with that of casual (screening) blood pressure, and to compare the predictive power for stroke between daytime and night-time blood pressures, in a general population in Ohasama, Japan. Design A prospective cohort study. Subjects and methods We obtained ambulatory blood pressure on 1464 subjects aged ≥ 40 years without history of symptomatic stroke, then followed-up their stroke-free survival. There were 74 first symptomatic stroke during the follow-up period (mean = 6.4 years). The prognostic significance of blood pressure for stroke risk was examined by a Cox proportional hazards regression model adjusted for possible confounding factors. Results The non-parametric and parametric analysis indicated that 24-h, daytime and night-time ambulatory blood pressures were linearly related with stroke risk. The likelihood ratio analysis demonstrated that these ambulatory blood pressures were significantly better related to stroke risk than did screening blood pressure, and that daytime blood pressure better predicted stroke risk than did night-time blood pressure. Conclusions The present study which prospectively investigated the relation between ambulatory blood pressure and first symptomatic stroke risk in a general population demonstrated that (i) ambulatory blood pressure values were linearly related to stroke risk; (ii) ambulatory blood pressures had the stronger predictive power for stroke risk than did screening blood pressure; and (iii) daytime blood pressure better related to stroke risk than did night-time blood pressure.

230 citations


Journal ArticleDOI
TL;DR: In this paper, pharmacological interruption of angiotensin II type-1 (AT1) receptor-mediated effects in animals was found to have a significant effect on renal development.
Abstract: All components of the renin–angiotensin system (RAS) are highly expressed in the developing kidney in a pattern that suggests a role for angiotensin II in renal development. In support of this notion, pharmacological interruption of angiotensin II type-1 (AT1) receptor-mediated effects in animals wi

222 citations


Journal ArticleDOI
TL;DR: In patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniae antibodies level, which lends support to the hypothesis that inflammation plays a role in the pathogenesis of Atherosclerosis in these patients.
Abstract: OBJECTIVE To investigate the relationship between inflammatory processes and atherosclerosis in uraemic patients on chronic dialysis. DESIGN A cross-sectional study in 138 dialysis patients (92 on haemodialysis and 46 on continuous ambulatory peritoneal dialysis). METHODS Serum C-reactive protein (CRP), IgG anti-Chlamydia pneumoniae antibodies, lipoprotein (a), fibrinogen and plasma homocysteine as well as the intima-media thickness and the number of atherosclerotic plaques of the carotid arteries (by Echo-Colour-Doppler) were measured in each patient RESULTS One hundred and eight patients had at least one plaque and 26 had more than six plaques. Serum CRP was above the upper limit of the normal range (5 mg/I) in 85 of 138 patients (62%). IgG anti-Chlamydia pneumoniae antibodies were detectable in 64% of patients (high level in 24%, intermediate in 33% and low in 7%) and undetectable in the remaining 36% of patients. In a multiple regression model age (beta=0.35), serum CRP (beta=0.23), plasma homocysteine (beta=0.19), duration of dialysis (beta=0.19) and pulse pressure (beta=0.18) were independent predictors of intima-media thickness (R=0.54, P < 0.0001). Similarly, age (beta=0.33), serum CRP (beta=0.29), plasma homocysteine (beta=0.20) and serum albumin (beta=-0.18) were independent correlates of the number of atherosclerotic plaques (R = 0.55, P < 0.0001 ). Furthermore, in smokers, the interaction serum CRP-IgG anti-Chlamydia pneumoniae antibodies was the stronger independent predictor (beta=0.43, P=0.0001) of the number of atherosclerotic plaques while no such relationship (P=0.73) was found in non-smokers. CONCLUSIONS In patients on chronic dialysis treatment CRP is independently associated to carotid atherosclerosis and appears at least in part to be explained by IgG anti-Chlamydia pneumoniae antibodies level. These data lend support to the hypothesis that inflammation plays a role in the pathogenesis of atherosclerosis in these patients.

Journal ArticleDOI
TL;DR: The present guidelines highlight the need of a precise estimation of the global cardiovascular risk stratification in individuals and recommend the use of blood pressure measurements outside the doctor office (home or ambulatory monitoring) to overcome some of the limitations of the clinicBlood pressure measurements in specific situations.
Abstract: Introduction The present guidelines come at a critically important time for the management of hypertension and particularly for the use of the blood pressure measurement methods. In fact, the last international guidelines for the management of hypertension highlighted the need of a precise estimation of the global cardiovascular risk stratification in individuals [1,2]. This estimation has to be performed on the basis of accurate blood pressure assessment in the clinic. Concurrently, considering the variability of the blood pressure, they recommended the use of blood pressure measurements outside the doctor office (home or ambulatory monitoring) to overcome some of the limitations of the clinic blood pressure measurements in specific situations. Beside these general aspects and indications, no specific guidelines have been recommended for the use of these methods and especially the home or self-blood pressure monitoring (selfBPM).

Journal ArticleDOI
TL;DR: Investigation of the safety and tolerability of the combination of valsartan and benazepril indicates that short-term combination of an angiotensin-converting enzyme inhibitor and an angiotsin receptor blocker is safe and well tolerated in patients with moderate chronic renal failure.
Abstract: ObjectiveSeveral experimental and clinical studies indicate that the renin system may play a pivotal role in progressing renal disease. The combination of an angiotensin-converting enzyme inhibitor and an angiotensin receptor blocker could provide a higher degree of blockade of the renin-angiotensin

Journal ArticleDOI
TL;DR: Respiratory disturbance index (RDI) was significantly higher in patients with uncontrolled hypertension than in those with controlled hypertension and should be considered, in addition to traditional confounders, as a risk factor for poor blood pressure control in younger hypertensive patients.
Abstract: OBJECTIVE To test the hypothesis that sleep-related breathing disorder (SRBD) is associated with poor blood pressure control in hypertensive patients independent from confounding factors such as age, body mass index, alcohol, smoking and daytime blood gases. DESIGN AND METHODS This cross-sectional study of a sleep laboratory cohort was carried out at the University Hospital Sleep Disorders Centre, Marburg. The study comprised 599 patients referred for a sleep study, all of them with a documented history of systemic hypertension and/or previously initiated antihypertensive therapy. Data were obtained from a clinical interview, two unattended sleep studies and assessment of clinic blood pressure, cholesterol level, alcohol and nicotine consumption and daytime blood gases. The main outcome measure was a post hoc analysis of predictors for poor blood pressure control. RESULTS Respiratory disturbance index (RDI) was significantly higher in patients with uncontrolled hypertension (blood pressure > or = 160 and/or 95 mmHg, n = 463) than in those with controlled hypertension (n = 136) (34.0 +/- 26.8 versus 27.0 +/- 23.5, P < 0.01). The relative proportion of patients with uncontrolled hypertension increased significantly as SRBD activity increased (chi2, P< 0.05). Body mass index was the only independent predictor (P = 0.006) of uncontrolled hypertension in the whole study sample. However, in the subset of patients aged < or = 50 years, RDI (P= 0.006) and age (P = 0.016) were the only independent predictors. The probability of uncontrolled hypertension increased by approximately 2% (B = 0.019, P= 0.006) for each RDI unit. CONCLUSION SRBD should be considered, in addition to traditional confounders, as a risk factor for poor blood pressure control in younger hypertensive patients (< or = 50 years of age).

Journal ArticleDOI
TL;DR: In this article, the benefits of treating hypertension in elderly diabetic patients, in terms of achieving reductions in cardiovascular morbidity and mortality, have been documented in several recent prospective trials, however, there has been some controversy regarding the effect of different antihyperte
Abstract: BackgroundThe benefits of treating hypertension in elderly diabetic patients, in terms of achieving reductions in cardiovascular morbidity and mortality, have been documented in several recent prospective trials. There has, however, been some controversy regarding the effect of different antihyperte

Journal ArticleDOI
TL;DR: Although measurement of BNP cannot be recommended for the detection of marginally impaired LV function in the population, it may be helpful to suggest or exclude severe LV dysfunction with concomitant hypertrophy.
Abstract: OBJECTIVE To evaluate brain natriuretic peptide (BNP) as marker of left ventricular (LV) dysfunction and hypertrophy in a population-based sample of 610 middle-aged subjects (50-67 years) who were further characterized with respect to hemodynamic and anthropometric parameters and by echocardiography. RESULTS Left ventricular (LV) systolic function, LV mass-index, age, gender, heart rate, and medication with beta adrenergic receptor blockers were significant and independently correlated with BNP (multivariate analysis, P 110 g/m2 in women and > 134 g/m2 in men) were characterized by increased BNP. The increase in BNP associated with LV hypertrophy (n = 69, +101% versus control, P < 0.0001) was similar in magnitude to that associated with LV dysfunction (n = 39, +98% versus control, P < 0.03). These increases were markedly exceeded in subjects with severe LV dysfunction (n = 11, LV fractional shortening < 22%, BNP +197% versus control, P < 0.01), particularly in the presence of concomitant hypertrophy (n = 7, +227%, P < 0.01). The predictive values of BNP varied considerably with the degree of LV dysfunction and the presence or absence of concomitant LV hypertrophy. With 0.81, the highest area under the receiver operator characteristic curve was obtained for the detection of severe LV dysfunction and concomitant hypertrophy and sensitivity, specificity, positive and negative predictive value for this condition were 71, 86, 7 and 99.5%, respectively, for a cut-off of 34 pg/ml. CONCLUSIONS The current study provides new insight into regulation and diagnostic value of BNP in middle-aged subjects and demonstrates important independent effects of LV function and mass upon BNP plasma concentrations. Although measurement of BNP cannot be recommended for the detection of marginally impaired LV function in the population, it may be helpful to suggest or exclude severe LV dysfunction with concomitant hypertrophy.

Journal ArticleDOI
TL;DR: In this paper, the presence of autoantibodies against G-protein-coupled cardiovascular receptors was detected in 14, 33, 18 and 14% of patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases and control patients, respectively.
Abstract: Sera from patients with malignant essential hypertension (n = 14), malignant secondary hypertension mainly attributable to renovascular diseases (n = 12) and renovascular diseases without malignant hypertension (n = 11) and from normotensive healthy blood donors (n = 35) were studied for the presence of autoantibodies against G-protein-coupled cardiovascular receptors. Autoantibodies against the angiotensin II receptor (AT 1 ) were detected in 14, 33, 18 and 14% of patients with malignant essential hypertension, malignant secondary hypertension, renovascular diseases and control patients, respectively. Sensitivity of the enzyme immunoassay was assessed as 5 pg/ml IgG. Patients did not show antibodies against bradykinin (B 2 ) or angiotensin II subtype 2 (AT 2 ) receptors. Autoantibodies affinity-purified from positive patients localized AT receptors in Chinese hamster ovary transfected cells, and displayed a positive chronotropic effect on cultured neonatal rat cardiomyocytes. These results demonstrate the existence of autoantibodies against a functional extracellular domain of human AT1 receptors in patients with malignant hypertension, and suggest that these autoantibodies might be involved in the pathogenesis of malignant hypertension.

Journal ArticleDOI
TL;DR: The overall conclusion is that the bioavailability of nitric oxide is probably impaired not by a single defect, but by various mechanisms affecting nitric Oxide synthesis as well as nitricoxide breakdown.
Abstract: This review focuses on the role of impaired endothelial function for the developement of atherosclerosis in human arterial hypertension and hypercholesterolemia in vivo. Potential mechanisms underlying impaired endothelial function and decreased bioavailability of nitric oxide under these clinical conditions are discussed and potential differences in these mechanisms between arterial hypertension and hypercholesterolemia are outlined. It further addresses therapeutic strategies aiming to improve the bioavailability of nitric oxide in these patients. The overall conclusion is that the bioavailability of nitric oxide is probably impaired not by a single defect, but by various mechanisms affecting nitric oxide synthesis as well as nitric oxide breakdown. In both diseases, increased superoxide anion production and oxidative stress represents a major mechanism. However, potential differences in the underlying mechanisms of superoxide production or nitric oxide synthesis are evident between arterial hypertension and hypercholesterolemia. Decreased bioavailability of nitric oxide does not only impair endothelium-dependent vasodilation, but also activates other mechanisms that play an important role in the pathogenesis of atherosclerosis. Thus, therapeutic strategies should aim to restore bioavailability of nitric oxide, which has been demonstrated for lipid-lowering therapy in hypercholesterolemia. The mechanisms by which nitric oxide bioavailability can be improved by any drug therapy remain to be elucidated and may provide further insights into the mechanisms that are involved in impaired endothelial function and atherogenesis.

Journal ArticleDOI
TL;DR: The present review discusses the molecular, biochemical, physiological and pharmacological roles of magnesium in the regulation of vascular function and blood pressure and introduces novel concepts relating to magnesium as a second messenger in intracellular signaling in cardiovascular cells.
Abstract: Attention is growing for a potential role of magnesium in the pathoetiology of cardiovascular disease. Magnesium modulates mechanical, electrical and structural functions of cardiac and vascular cells, and small changes in extracellular magnesium levels and/or intracellular free magnesium concentration may have significant effects on cardiac excitability and on vascular tone, contractility and reactivity. Thus, magnesium may be important in the physiological regulation of blood pressure whereas alterations in cellular magnesium metabolism could contribute to the pathogenesis of blood pressure elevation. Although most epidemiological and experimental studies support a pathological role for magnesium in the etiology and development of hypertension, data from clinical studies have been less convincing. Furthermore, the therapeutic value of magnesium in the management of essential hypertension is unclear. The present review discusses the molecular, biochemical, physiological and pharmacological roles of magnesium in the regulation of vascular function and blood pressure and introduces novel concepts relating to magnesium as a second messenger in intracellular signaling in cardiovascular cells. In addition, alterations in magnesium regulation in experimental and clinical hypertension and the potential antihypertensive therapeutic effects of magnesium are addressed.

Journal ArticleDOI
TL;DR: The results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.
Abstract: Background and objective The European Lacidipine Study of Atherosclerosis (ELSA) is a prospective, randomized, double-blind, multi-national interventional trial to determine the effect of four-year treatment using the calcium antagonist lacidipine versus the beta-blocker atenolol on the progression of carotid atherosclerosis in 2259 asymptomatic hypertensive patients. B-mode ultrasound is used to measure the primary and secondary endpoints including the mean maximum intima-media thickness (IMT) of the carotid bifurcations and the common carotid arteries (CBM(max)), the mean maximum IMT of 12 standard carotid sites (M(max)) and the overall maximum IMT (T(max)). This paper reports the cross-sectional reproducibility of ultrasound measurements at baseline. Method To evaluate measurement reliability, each patient is scanned twice at baseline and again at four annual visits, with 80% of the replicate scans performed by the same sonographer and 20% by a different sonographer; 50% of the replicate scans are read by the same reader and the other 50% by different readers. Results The overall coefficient of reliability (R) was 0.859 for CBM(max), 0.872 for M(max) and 0.794 for T(max). The reliability for CBM(max) was stable during the 1 3/4-year baseline period (R = 0.848 to 0.953) and was uniform among the 23 field centres (R = 0.798 to 0.926). Intra- and inter-reader reliability were 0.915 and 0.872 respectively, and intra-sonographer reliability was 0.866. Conclusion The results demonstrate that by implementing standardized protocols and strict quality control procedures, highly reliable ultrasonic measurements of carotid artery IMT can be achieved in large multi-national trials.

Journal ArticleDOI
TL;DR: Two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolicheart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.
Abstract: Objective There are two phenotypes of heart failure, systolic failure and isolated diastolic heart failure with preserved left ventricular systolic function. Although isolated diastolic heart failure frequently occurs, there are only models for diastolic dysfunction unassociated with heart failure and models with overt diastolic heart failure have not been established. We attempted to develop two different models, i.e. diastolic and systolic failure models, based on hypertension. Materials and methods Dahl salt-sensitive rats were placed on 8% NaCl diet from 7 weeks old (7-week starting group) or 8 weeks old (8-week starting group). As an age-matched control, Dahl salt-sensitive rats were consistently placed on normal chow. In these rats, echocardiogram was serially recorded, followed by hemodynamic and histological studies. Results The 7-week starting rats showed a steep elevation in blood pressure and progressive left ventricular hypertrophy, and fell into overt heart failure at approximately 19 weeks. The development of heart failure was not associated with a decrease in left ventricular mid-wall fractional shortening or an increase in left ventricular end-diastolic dimension as compared with the age-matched control, which mimics the characteristics of clinically observed isolated diastolic heart failure. The 8-week starting rats showed a gradual rise in blood pressure and less progressive left ventricular hypertrophy, and fell into heart failure at approximately 26 weeks with a decrease in mid-wall fractional shortening and an increase in left ventricular end-diastolic dimension. Hemodynamic and histological studies at failing stage revealed comparable elevation of left ventricular end-diastolic pressure and comparable left ventricular fibrosis in both groups. Conclusion These two different models of overt heart failure may be useful as models of isolated diastolic heart failure and systolic heart failure based on the same hypertensive heart disease, respectively, and may contribute to discrimination of the mechanisms of the development of the two different phenotypes of heart failure.

Journal ArticleDOI
TL;DR: Differences in methodology between national surveys make international comparisons difficult, Nevertheless, low-cost hypertension control programmes in developing countries are needed, along with development of the primary prevention of hypertension.
Abstract: AIM Hypertension is an established major risk factor underlying the epidemic of coronary and cardiovascular diseases in most developed countries, and it has been shown to be a public health problem in many developing countries since the 1970s. This review was carried out to illustrate the current situation with regard to blood pressure levels and the prevalence and management of hypertension in developing countries. METHODS A search for papers published in medical journals from 1991 to 1998 was performed using the MEDLINE database. A total of 40 articles were selected according to previously defined criteria. RESULTS Hypertension is a public health problem for most of the developing countries reviewed, and it is frequently associated with low levels of awareness, treatment and control. A positive association between the gross national product per capita and the prevalence of hypertension in developing countries is also evident. CONCLUSIONS Differences in methodology between national surveys make international comparisons difficult. Nevertheless, low-cost hypertension control programmes in developing countries are needed, along with development of the primary prevention of hypertension.

Journal ArticleDOI
TL;DR: Indapamide SR 1.5 mg was significantly more effective than enalapril 20 mg at reducing LVMI in hypertensive patients with LVH, and progressively reduced wall thicknesses throughout the 1-year treatment period.
Abstract: ObjectiveTo compare the efficacy of indapamide sustained release (SR) 1.5 mg and enalapril 20 mg at reducing left ventricular mass index (LVMI) in hypertensive patients with left ventricular hypertrophy (LVH).DesignThe LIVE study (left ventricular hypertrophy regression, indapamide versus enalapril)

Journal Article
TL;DR: Increased blood pressure levels are directly responsible for the majority of stroke deaths and a substantial minority of deaths from coronary heart disease in Eastern Asia and both modest population-wide blood pressure reductions and more moderate targeted reductions in those with hypertension could be expected to produce large reductions in the burden of cardiovascular disease in these and other Asian regions.
Abstract: Objective To assist in prioritisation for strategies for the control of cardiovascular disease (CVD) worldwide, by estimating the size of the contribution of elevated blood pressure and, more importantly, the likely effects of its modification. Design We estimated the size of the disease burden attributable to increased blood pressure in Eastern Asia and describe a method for estimating the likely effects of blood pressure lowering strategies. Methods Attributable risk estimates were calculated to assess the likely contribution of increased blood pressure to death from CVD in Asia. Estimates were also made of the possible effects of population-wide (2% lower diastolic blood pressure [DBP] for all) and targeted (7% lower DBP for those with DBP > or =95 mm Hg) blood pressure lowering interventions. These estimates were based on data from several sources, including surveys of blood pressure values in Asian populations, estimates of the incidence of cardiovascular disease in Asia, studies of the associations of blood pressure with cardiovascular disease risks in Asia and elsewhere, and randomized trials of blood pressure lowering treatments. Results The results suggest that DBP values of 80 mm Hg or more account for about 57% of all stroke deaths and about 24% of all coronary heart disease deaths in Eastern Asian populations. The two intervention strategies proposed would each be expected to avert about 1 in 6 stroke deaths and about 1 in 20 coronary heart disease deaths. This would amount to about 1 million deaths per year throughout Asia by 2020, with about half of those deaths averted in the People's Republic of China. The benefits of the two different approaches would be approximately additive. Conclusions Increased blood pressure levels are directly responsible for the majority of stroke deaths (more than 50%) and a substantial minority of deaths from coronary heart disease (about 25%) in Eastern Asia. Both modest population-wide blood pressure reductions and more moderate targeted reductions in those with hypertension could be expected to produce large reductions in the burden of cardiovascular disease in these and other Asian regions.

Journal ArticleDOI
TL;DR: The results establish the role of the AT1 locus, on a genome-wide scale, as a major contributing locus to essential hypertension in this study sample.
Abstract: ObjectivesTo review, on a genome-wide scale, a linkage result obtained in an earlier candidate gene analysis in this same study sample, and to look for other possible contributing genetic loci predisposing to hypertension in this population.DesignAn affected sibpair linkage study with highly polymor

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TL;DR: It is believed that the judicious use of spectral methodology, in addition to other techniques, might provide unprecedented, useful insights into autonomic cardiovascular regulation, in both physiopathological and clinical circumstances.
Abstract: Computer analysis of spontaneous cardiovascular beat-by-beat variability has gained wide credibility as a means of inferring disturbances of autonomic cardiovascular regulation in a variety of cardiovascular conditions, including hypertension, myocardial infarction and heart failure. Recent applications of spectral analysis to muscle sympathetic nerve activity (MSNA) offer a new approach to a better understanding of the relationship between cardiovascular oscillations and autonomic regulation. However, areas of uncertainty and unresolved debates remain, mostly concerning different methodologies and interpretative models that we will consider in this article. Perusal of all available literature suggests that average sympathetic nerve activity and its oscillatory components, although correlated to some extent, are likely to provide different types of information. In addition, the specific experimental context is of paramount importance, as the rules that seem to govern the relationship between average and oscillatory properties of MSNA appear to be different in usual conditions and in conditions of extremes of activation or disease. In general, dynamic experiments, such as with graded tilt or with vasoactive drugs, are more suited to investigations of the complexity of autonomic regulation than are static comparisons. In addition, because the information is spread across variables and is affected by a potentially large error, it appears that several different techniques should be perceived as complementary rather than as mutually exclusive. Available evidence suggests that low-frequency and high-frequency oscillations in peripheral signals of variability might have a predominantly central, rather than a peripheral, origin and that this applies in particular to low-frequency oscillations. A crucial point in the assessment of the meaning of spectral components relates to consideration of the varying level of very-low-frequency noise, and the mathematical manipulation of derived indices, particularly using a normalization procedure. This appears easier to obtain with auto-regressive than with fast Fourier techniques. With this approach, discrepant interpretations seem to be resolved, provided adequate care is taken in separating direct physiological data from derived meaning, which relates to hidden information and neural codes; in the case of sympathetic discharge, the latter display greater complexity than simple average spike activity per unit time. Accordingly we believe, in conclusion, that the judicious use of spectral methodology, in addition to other techniques, might provide unprecedented, useful insights into autonomic cardiovascular regulation, in both physiopathological and clinical circumstances.

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TL;DR: In older adults high intakes of ascorbic acid have modest effects on lowering high systolic blood pressure, which could contribute to the reported association between higher vitamin C intake and lower risk of cardiovascular disease and stroke.
Abstract: ObjectivesTo determine the effect of oral vitamin C supplements on ambulatory blood pressure and plasma lipids.DesignA 6-month double-blind randomized placebo-controlled cross-over study with a 1-week washout between cross-over periods.MethodsVitamin C 500 mg daily or matching placebo was given to 4

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TL;DR: This research investigates whether measurement of blood pressure at home and by ambulatory monitoring (ABP) are reliable alternatives to the traditional strategy for the diagnosis of hypertension based on blood pressure measurement on repeated clinic visits.
Abstract: ObjectiveTo investigate whether measurement of blood pressure at home (HBP) and by ambulatory monitoring (ABP) are reliable alternatives to the traditional strategy for the diagnosis of hypertension based on blood pressure measurement on repeated clinic visits (CBP).DesignComparison of the diagnosis

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TL;DR: A low risk of hypertension two decades after childhood urinary tract infection is demonstrated and those with renal scarring had higher concentrations of atrial natriuretic protein which might indicate a counter-regulation mechanism.
Abstract: OBJECTIVE: To evaluate blood pressure in a population-based cohort with urographic renal scarring after childhood urinary tract infection. DESIGN: Follow-up investigation 16-26 years after the first recognized urinary tract infection. SETTING: University out-patient clinic for children with urinary infections serving the local area. PATIENTS: From the original cohort of 1221 consecutive children with first urinary tract infection diagnosed during 1970-1979, 57 of 68 with non-obstructive renal scarring participated as well as 51 matched subjects without scarring. MAIN OUTCOME MEASURE: 24 h ambulatory blood pressure. RESULTS: Acceptable blood pressure monitorings were obtained from 53 individuals with and 47 without scarring. There were no significant differences between the two groups even when only patients with the most extensive scarring (individual kidney clearance < 30 ml/min per 1.73 m2) or patients with bilateral scarring were compared with the non-scarring group. Mean systolic or diastolic blood pressure above +2 SD were found in 5/53 (9%) and 3/47 (6%) in the scarring and non-scarring group, respectively. Plasma renin activity, angiotensin II and aldosterone concentrations were not significantly different, but atrial natriuretic protein was significantly higher in the scarring group (P = 0.004). CONCLUSION: This study demonstrates a low risk of hypertension two decades after childhood urinary tract infection. It should be stressed that the patients with renal scarring were under close supervision throughout childhood. Those with scarring had higher concentrations of atrial natriuretic protein which might indicate a counter-regulation mechanism.

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TL;DR: Dietary α-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.
Abstract: Background and objectives: In spontaneously hypertensive rats (SHRs), excess endogenous aldehydes bind sulfhydryl groups of membrane proteins, altering membrane Ca2+ channels and increasing cytosolic free calcium and blood pressure. The thiol compound, N-acetyl cysteine, normalizes elevated blood pressure in SHRs by binding excess endogenous aldehydes and normalizing membrane Ca2+ channels and cytosolic free calcium. The aim of the present study was to investigate whether a dietary supplementation of an endogenous fatty acid, alpha-lipoic acid, another thiol compound that is known to increase tissue cysteine and glutathione, can lower blood pressure and normalize associated biochemical and histopathological changes in SHRs. Methods and results: Starting at 12 weeks of age, animals were divided into three groups of six animals each. Animals in the Wistar- Kyoto (WKY) rat control group and the SHR control group were given a normal diet, and the SHR-lipoic acid group was given a diet supplemented with lipoic acid (500 mg/kg feed) for the next 9 weeks. After 9 weeks, systolic blood pressure, platelet [Ca2+]i, plasma insulin and liver, kidney and aortic aldehyde conjugates were significantly higher in SHR controls as compared with WKY rat controls and the SHR lipoic acid group. SHR controls also showed smooth muscle cell hyperplasia in the small arteries and arterioles of the kidneys. Conclusions: Dietary alpha-lipoic acid supplementation in SHRs lowered the systolic blood pressure, cytosolic [Ca2+]i, blood glucose and insulin levels, and tissue aldehyde conjugates, and attenuated adverse renal vascular changes.