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Biomedical subjects

S Julius

Publications and source records attributed to S Julius.

At least 55 records · Page 3Linked to original sources
PubMed1998

The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial of cardiovascular events in hypertension. Rationale and design.

Essential hypertension is a major Public Health issue. Although the number of treated hypertensive patients has increased, only 25% of treated patients have their blood pressure levels under control. The benefit of treating hypertension has been proven, but cardiovascular morbidity and mortality rates remain high. The ideal antihypertensive drug should not only normalize blood pressure levels, but also reduce the associated cardiovascular morbidity and mortality rates. The role of angiotensin II in systemic hypertension and its complications has been recently redefined. The potent trophic effects of angiotensin II on blood vessels and on cardiac cells have been well demonstrated, especially the role of angiotensin II in left ventricular hypertrophy, vascular hypertrophy, endothelial dysfunction, and congestive heart failure. Of all ongoing mortality and morbidity trials in systemic hypertension, VALUE (Valsartan Antihypertensive Long-term Use Evaluation) is the only one comparing an angiotensin II antagonist (valsartan) with a third-generation calcium channel blocker (amlodipine). The main hypothesis of the VALUE trial is that, for an equivalent decrease in blood pressure, valsartan will be more effective than amlodipine in decreasing cardiac mortality and morbidity. VALUE is a prospective, multinational, multicentre, double-blind, randomized, active-controlled, 2-arm parallel group comparison with a response-dependent dose titration scheme. VALUE involves 14,400 patients in over 30 countries, who will be followed for 4 years or until 1450 patients experience a primary endpoint. The population to be included in VALUE consists of hypertensive men and women, aged 50 years or older, and at a relatively high risk of sustaining a cardiovascular event. The high risk profile is defined taking into account age, gender, and a list of cardiovascular risk factors and disease factors. Risk factors are cigarette smoking, hypercholesterolaemia, diabetes mellitus, uncomplicated left ventricular hypertrophy, proteinuria, and high serum creatinine. Disease factors include documented history of myocardial infarction, peripheral vascular disease, stroke or transient ischaemic attack, or the presence of left ventricular hypertrophy with strain on the ECG. A unique feature of VALUE is the assessment of the predictive power of this cardiovascular risk factor scale in a large population of treated hypertensive patients. The trial started on 10 September 1997.

Aged↗
PubMed1998

Consequences of the increased autonomic nervous drive in hypertension, heart failure and diabetes.

It is estimated that 40 million people in the USA have hypertension, 14 million are diabetic and 4 million suffer congestive heart failure. Since all three conditions are age-related, as the longevity in industrialized societies continues to improve, the overall burden of congestive heart failure, hypertension and diabetes will increase. These major diseases of civilization are characteristically associated with an increased autonomic cardiovascular drive. In our terminology the output that emanates from the central nervous system via sympathetic and parasympathetic efferents is referred to as "tone". The overall "drive" depends on the balance between inhibitory (parasympathetic) and excitatory (sympathetic) tone and the organ's responsiveness to that tone. The responsiveness, in turn, depends on the receptors' properties as well as on the intrinsic functional or anatomic properties of the responding organs. These components can change independently. For example, in the course of hypertension the alpha-adrenergic responsiveness increases whereas the beta-adrenergic responses are down-regulated. Another example is: plasma noradrenaline and sympathetic tone are increased in elderly subjects but their circulation does not show any tell-tale response of increased sympathetic tone, presumably because the responses to sympathetic tone decrease with aging. These complex interactions between the autonomic tone and organ responsiveness determine to a great extent the overall clinical impact of the autonomic abnormality in hypertension, non-insulin-dependent diabetes mellitus and in congestive heart failure. The major thesis of this review is that, whether primary or secondary, whether easily discerned or hidden, an enhanced autonomic drive, independent of the underlying condition, greatly increases the risk of poor cardiovascular outcomes. It follows that targeting the underlying autonomic imbalance in congestive heart failure, hypertension and diabetes may not only be pathophysiologically sound but such an approach may also lead to better outcomes.

Animals↗
PubMed1998

Anxiety and cardiovascular reactivity in the Tecumseh population.

OBJECTIVE: Increased cardiovascular reactivity has been proposed to be a critical mediator in the development of hypertension and cardiovascular disease. The personality factors associated with cardiovascular reactivity are still subject to debate. The studies reported here were undertaken to examine the relationship between trait anxiety and cardiovascular stress reactivity in a community-based sample (Tecumseh). DESIGN AND METHODS: All studies were carried out in an outpatient setting. Cardiovascular reactivity to isometric handgrip and mental arithmetic was assessed and recorded by automatic blood pressure monitoring in 832 subjects aged 19-41 years. Spielberger trait and state anxiety measures were collected immediately before the stressors were applied. RESULTS: No differences in baseline heart rate, systolic or diastolic blood pressure were observed across anxiety categories. There was a clear negative correlation between trait anxiety and cardiovascular reactivity to mental arithmetic. The pattern was less clear in response to isometric handgrip. CONCLUSIONS: These results suggest that individuals with high trait anxiety demonstrate reduced cardiovascular reactivity while those with low trait anxiety demonstrate increased reactivity, whereas the opposite might have been expected.

Adult↗
PubMed1998

Hypertension optimal treatment (HOT) study: home blood pressure in treated hypertensive subjects.

The Hypertension Optimal Treatment Study is a prospective trial conducted in 26 countries. The aims are to (1) evaluate the relationship between three levels of target office diastolic blood pressure (BP) (< or = 80, < or = 85, or < or = 90 mm Hg) and cardiovascular morbidity and mortality in hypertensive patients and (2) examine the effects on cardiovascular morbidity and mortality of 75 mg aspirin daily versus placebo. A total of 19,193 patients between 50 and 80 years of age had been randomized by the end of April 1994. Treatment was initiated with felodipine 5 mg daily, and additional therapy was given in accordance with a set protocol. The present substudy of 926 patients performed in nine countries aimed to (1) compare home with office BP in a representative subsample of the HOT population after the titration of treatment was completed and (2) clarify whether the separation into the target groups could be expanded into the out-of-office setting. The differences between office and home measurements in diastolic BP of 0.2 mm Hg (SD, 9; 95% confidence interval, -0.36 to 0.81; P=.40) and systolic BP of 0.5 mm Hg (SD, 15; 95% confidence interval, -0.53 to 1.46; P=.21) were not significant. The group differences in home BP were 1.9 mm Hg (< or = 80 versus < or = 85) and 1.2 mm Hg (< or = 85 versus < or = 90) for diastolic BP (F=11.69; ANOVA, P<.0001) and 2.6 and 2.1 mm Hg for systolic BP (F=8.44, P=.0002). Thus, office and home BPs measured with the same semiautomatic device are comparable in treated hypertensive subjects in the HOT Study, and the separation into the target groups based on office readings prevails at home.

Aged↗
PubMed1998

Characteristics of 9194 patients with left ventricular hypertrophy: the LIFE study. Losartan Intervention For Endpoint Reduction in Hypertension.

-Losartan was the first available orally administered selective antagonist of the angiotensin II type 1 receptor developed for the treatment of hypertension. The Losartan Intervention For Endpoint (LIFE) Reduction in Hypertension Study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality. Patients with essential hypertension, aged between 55 and 80 years, and ECG-documented left ventricular hypertrophy (LVH) were included. Altogether, 9223 patients in Scandinavia, the United Kingdom, and the United States were randomized from June 1995 through April 1997, and 9194 remain after exclusion of a study center at which irregularities were discovered. This population of hypertensives (mean systolic/diastolic blood pressure, 174.4/97.8 mm Hg) with LVH comprises women (54.1%) and men, mostly retired from active work (mean age, 66.9 years), with a high prevalence of overweight (mean body mass index, 28.0 kg/m2), diabetes mellitus (12.3%), lipid disorders (18.0%), and symptoms or signs of coronary heart disease (15.1%). There were fewer current smokers (<17%) than in the general population, and approximately 7% were nonwhite. Almost 30% of participants had been untreated for at least 6 months when screened for the study. Only 1557 persons who entered the placebo run-in period of 14 days were excluded, predominantly because of sitting blood pressures above or below the predetermined range of 160-200/95-115 mm Hg and ECG-LVH criteria not met. By application of simple 12-lead ECG criteria for LVH (Cornell voltage QRS duration product formula plus Sokolow-Lyon voltage read by a core laboratory), hypertensive patients with LVH with an average 5-year coronary heart disease risk of 22.3% according to the Framingham score were identified. This population is now being treated (goal, <140/90 mm Hg) in adherence with the protocol for at least 4 years after final enrollment (ie, through April 2001) and until at least 1040 patients suffer myocardial infarction, stroke, or cardiovascular death.

Aged↗
PubMed1998

Tachycardia: an important determinant of coronary risk in hypertension.

Heart rate and blood pressure are highly correlated and in large population studies, individuals with high blood pressure tend to have high heart rates. Fast heart rate precedes the development of high blood pressure and serves as an early indicator of coronary heart disease. Not only does the heart rate predict coronary mortality, but also the non-cardiovascular mortality and is, therefore, an overall predictor of longevity. In the Tecumseh Blood Pressure study, we have seen that 37% of all patients with borderline hypertension have the 'hyperkinetic hypertension state', which consists of elevated cardiac output, high heart rate, high sympathetic tone, and decreased parasympathetic tone. In this population, evidence of high heart rate exists in these individuals as children, and persists through early adulthood. This suggests that tachycardia is a reliable marker of high sympathetic tone. High sympathetic tone might be the mechanism whereby heart rate is associated with high insulin, insulin resistance, dyslipidemia, high hematocrit and excess weight. These mechanisms are discussed in details in this review. Tachycardia is a strong risk factor for sudden death and arrythmia. Heart rate, as one of the prime determinants of cardiac work, may contribute to greater cardiac strain. Animal studies have shown that a higher heart rate may be associated with a greater development of atherosclerotic plaque in coronary vasculature. Therefore, heart rate elevation is not merely a sign of underlying pathology, but it may also cause further damage that leads to increased mortality. In the treatment of hypertension, reducing heart rate by pharmacologic and non-pharmacologic measures may have a greater effect on coronary mortality than blood pressure reduction alone.

Autonomic Nervous System↗
PubMed1998

Clinical consequences of the autonomic imbalance in hypertension and congestive heart failure.

The reduction of coronary mortality is not as large as one would expect from the observed blood pressure lowering in trials of antihypertensive medications. This is not surprising; hypertension is a complex disease where the high blood pressure is only one of numerous coronary risk factors. Sympathetic overactivity in hypertension, independent of the blood pressure, may be conducive to premature atherosclerosis by inducing insulin resistance and dyslipidemia. Through its trophic effect on blood vessels, sympathetic overactivity potentiates vasoconstriction. This, in turn, accelerates hypertension and the metabolic syndrome. The hypertrophy of small coronary arterioles decreases the coronary reserve and enhances coronary spasms. Tachycardia, which is due to increased sympathetic tone and a decreased parasympathetic tone, favors arrhythmias and sudden death in congestive heart failure and hypertension. Increased hematocrit is frequently found in male patients with hypertension, and high hematocrit is a predictor of coronary heart disease/thrombosis. The increase of hematocrit is in part due to an alpha adrenergic postcapillary venoconstriction. Enhanced sympathetic drive, insulin resistance and dyslipidemia have been demonstrated also in congestive heart failure, but the clinical importance of these findings is not fully understood.

Animals↗
PubMed1998

Effect of sympathetic overactivity on cardiovascular prognosis in hypertension.

Increased sympathetic tone is found in about 30% of patients with hypertension. This abnormality is closely associated with the metabolic syndrome of dyslipidaemia and hyperinsulinaemia. In this short review we discuss the mechanisms by which sympathetic over-activity could cause the metabolic syndrome. Sympathetic stimulation enhances cardiac and vascular hypertrophy. Left ventricular hypertrophy is a strong predictor of poor cardiovascular outcomes. Hypertrophy of resistance vessels accelerates hypertension, whereas hypertrophy of smaller coronary vessels limits coronary reserve and increases tendency for coronary spasms. Epidemiologically, high haematocrit is associated with hypertension and is recognized as an independent coronary risk factor. Sympathetic stimulation increases haematocrit through an increase of post-capillary vascular resistance. Sympathetic over-activity is also associated with platelet activation which may further add to the risk of coronary thrombosis in neurogenic hypertension. Tachycardia, which is due to increased sympathetic and deceased parasympathetic tone, is a hallmark of neurogenic hypertension. Fast heart rate is a strong predictor of coronary events and sudden death. The mechanisms by which tachycardia increases the cardiovascular risk are outlined.

Arousal↗
PubMed1997

Optimizing the assessment of the elderly patient with borderline hypertension: the Hypertension and Ambulatory Recording in the OLD (HAROLD) study.

This article describes the objectives and protocol of the HAROLD study, a trial designed to assess whether home blood pressure (BP), 24-hour ambulatory BP, left ventricular structure and function, and albumin excretion rate are more accurate predictors of outcome than traditional sphygmomanometric BP in elderly subjects with borderline hypertension. Development of sustained hypertension (BP > or = 160/95 mmHg) and incidence of morbid events over a 5-year follow-up are considered soft and hard endpoints, respectively. Patients with blood pressure values between 140/90 and 159/94 mmHg after three months of observation and who have never been treated, are eligible for the study; these subjects must be 60 to 79 years old, and free from other important risk factors for atherosclerosis. Baseline exams, which include plasma renin and insulin, 24-hour urine collection for detection of microalbuminuria, and echo-doppler cardiac examination are repeated after three and five years follow-up, or when subjects develop sustained hypertension. To recruit a large enough number of subjects to allow a sufficient number of endpoints (over 1000 subjects), the study is conducted as a multicenter trial. Ninety Italian Hospital Centers have agreed to participate in the study.

Aged↗
PubMed1997

Home blood pressure as a predictor of future blood pressure stability in borderline hypertension. The Tecumseh Study.

We evaluated time-related blood pressure trends in the Tecumseh study participants, none of whom received antihypertensive treatment. At baseline the blood pressures were measured in the field clinic and by self measurement at home (twice daily for 7 days). After a mean of 3.2 +/- 0.42 years, the clinic and home pressure readings were repeated. Nine hundred forty-six subjects had clinic and home blood pressure readings at baseline. Of these 735 (380 men, 355 women; average age, 32 years) also completed the second examination. Blood pressure, morphometric data, and biochemical measures at the first examination were used as predictors of future clinic blood pressures. Five hundred ninety-six subjects were normotensive on both examinations (81%). Of 79 subjects (10.7%) with clinic hypertension (> 140 mg Hg systolic or 90 mm Hg diastolic) at baseline, 38 remained hypertensive ("sustained hypertension") and 41 became normotensive ("transient hypertension") after 3 years. Another 60 normotensives at baseline (10.4%) became hypertensive on second examination ("de novo hypertensives"; incidence; 8.1%). The home blood pressure readings on both examinations were reproducible. The three hypertensive groups had elevated home blood pressure, were overweight, had dyslipidemia, and higher insulin values. Only the home blood pressure proved predictive of subsequent blood pressure trends. A home blood pressure of 128 and 83 mm Hg or higher detected "sustained" hypertension with a 48% sensitivity and 93% specificity. Readings of 120 and 80 mm Hg or lower predicted future normotension with a 45% sensitivity and a 91% specificity. We conclude that self determination of the blood pressure at home is useful in the management of borderline hypertension. An algorithm for the management of these patients is proposed.

Adolescent↗
PubMed1997

Current trends in the treatment of hypertension: a mixed picture.

It has been calculated that hypertension ranks as the fourth largest mortality risk factor in the world, predicting 6% of all deaths. Mild hypertension accounts for the largest proportion of cardiovascular deaths in the United States because of its high prevalence. Thus, mild hypertension should be the focus of treatment efforts. In addition, to achieve better results in the next century, we will have to refocus the treatment from the global goal of blood pressure lowering to exploration of specific effects of drugs on the diverse pathophysiologic aspects of hypertension including the complex metabolic and hemodynamic aberrations associated with human hypertension, as well as trophic factors. Another disconcerting feature of current hypertension management is the inadequate lowering of the blood pressure in those patients treated for hypertension. The National Health and Nutrition Examination Study (NHANES) survey in United States shows that patients treated for hypertension have blood pressure values that are only slightly lower than in untreated hypertensives and remain higher than in normotensive subjects. Patient compliance with treatment is one major problem. The development of better tolerated drugs ought to bring improvement. Overall, an educational effort aimed at physicians, the general public, and health care providers is necessary to improve the treatment of hypertension and reverse the negative trends in cardiovascular mortality.

Blood Pressure↗
PubMed1997

Smoking is associated with higher cardiovascular risk in young women than in men: the Tecumseh Blood Pressure Study.

BACKGROUND: Tobacco smoking is associated with a higher prevalence of atherosclerosis and respiratory disease. OBJECTIVE: To investigate differences between hemodynamic and biochemical findings in smokers and nonsmokers in the two sexes separately in the Tecumseh population. METHODS: We studied 851 subjects. They were divided according to smoking habits into group 1, nonsmokers (258 men and 234 women); and group 2, smokers (185 men and 174 women). RESULTS: Unpaired Student's t-tests and nonparametric tests were performed to determine the between-group P-values. Only hematocrit differed significantly between smokers and nonsmokers in both sexes (43.9 +/- 0.2 and 44.6 +/- 9.3%, P < 0.05 in men; 39.2 +/- 0.3 and 40.3 +/- 0.3%, P = 0.007 in women, respectively in nonsmokers and smokers). Triglycerides (80.6 +/- 3.8 and 99.6 +/- 4.3 mg/dl, P < 0.001), left ventricular mass index (95.4 +/- 1.9 and 100.0 +/- 1.2 g/m2, P = 0.008), and posterior wall thickness (9.5 +/- 0.1 and 9.71 +/- 0.01 mm, P = 0.044) were elevated and high-density lipoproteins were decreased (48.7 +/- 0.8 and 44.5 +/- 0.9 mg/dl, P < 0.01) only in women smokers. After adjustment for home systolic blood pressure and body mass index the differences in women remained significant except for posterior wall thickness. CONCLUSION: Tobacco smoking is deleterious to both sexes but it appears to be particularly harmful to women. Our data can, in part, explain why the relative risk of myocardial infarction is higher in women than it is in men.

Adolescent↗
PubMed1997

Relationship of tachycardia with high blood pressure and metabolic abnormalities: a study with mixture analysis in three populations.

Faster resting heart rate has been shown to be associated with a higher risk of developing hypertension and a greater incidence of cardiovascular morbidity and mortality. The aim of this study was to investigate the distribution of heart rate and its relationship with blood pressure and other cardiovascular risk factors in three populations. One European general population (Belgian study), one North American general population (Tecumseh study), and one European hypertensive population (HARVEST trial) were studied. Within each population, mixture analysis was used to investigate whether a mixture of two normal distributions explained the variance in heart rate better than a single distribution. In the men of all populations, mixture analysis identified a larger subpopulation of subjects with normal heart rate and a smaller one with fast heart rate. The subgroups with tachycardia had higher blood pressure and lipid levels than those with normal heart rate. In the populations in which they were measured, fasting insulin and postload glucose were also higher in the men with faster heart rate. A subgroup with tachycardia could also be singled out among the women from Tecumseh, but no relation between heart rate and blood pressure could be found. These findings show that in Western societies, high heart rate pertains to a distinct subgroup of subjects, who are more frequently men and exhibit the characteristic features of the insulin resistance syndrome. Sympathetic overactivity is likely to be the mechanism underlying this clinical condition.

Adolescent↗
PubMed1997

Trends in left ventricular function over three years in the Tecumseh Study.

The relationship between blood pressure and left ventricular diastolic function was examined in participants of the Tecumseh Blood Pressure study. When subjects were divided into three blood pressure groups according to blood pressure levels 3 years apart, it was found that subjects who were had sustained "hypertension" at both time points (SH) had a decreased early/late diastolic filling rate (E/A ratio) compared to subjects who were hypertensive at only one of the timepoints (OH) and those who were consistently normotensive (NN) (1.71 +/- 0.02 NN vs 1.55 +/- 0.05 OH, (p < 0.0001) vs 1.56 +/- 0.07 SH, (p < 0.04)). This relative order was maintained when the second estimation of diastolic filling was performed 3 years later, but the E/A ratio had decreased significantly in all groups (1.54 +/- 0.01 NN vs 1.45 +/- 0.03 OH (p < 0.01) vs 1.37 +/- 0.06 SH (p < 0.006)), consistent with an age-related reduction in diastolic filling. Heart rates were significantly higher in the hypertensive groups initially (63.5 NN vs 66.2 OH (p < 0.03) vs SH 67.3 (p < 0.01)) and increased in all groups over time, with the largest increase in the SH group (64.9 +/- 0.04 NN vs 67.8 +/- 1.02 OH (p < 0.0001) vs 70.9 +/- 1.6 SH (p < 0.01)). Stroke volume index changed in all groups over time, with the increase greatest in the NN group and least in the SH groups the reverse of this pattern was seen for changes in heart rate. All subjects gained weight over the 3 years of the study so that these unexpected changes in stroke volume index and heart rate could be a consequence of a weight gain-related increase in the sympathetic tone, although we have no direct evidence that this is the case. Should this be so, the smaller increase in stroke volume in conjunction with the larger increase in the heart rate in the sustained hypertensive group may reflect the effects of mild blood pressure elevation in producing a reduction in left ventricular diastolic function associated with a decrease in the inotropic responsiveness of the heart to enhanced sympathetic tone.

Adolescent↗
PubMed1997

Coronary disease in hypertension: a new mosaic.

HYPERTENSION-ASSOCIATED ABNORMALITIES THAT PROMOTE CORONARY DISEASE: Although antihypertensive treatment has been effective in reducing premature cardiovascular mortality, the effect on various organ-specific morbid events has been unequal; the effect is much more impressive on stroke reduction than on reduction of coronary events. A student of pathophysiology would have anticipated such an outcome since blood pressure elevation is only one of multiple abnormalities in hypertension. Even in its mildest form hypertension is associated with the metabolic syndrome of dyslipidemia/insulin resistance which is conducive to early atherosclerosis. A large proportion of patients also have increased sympathetic and decreased parasympathetic tone, a constellation conducive to arrhythmias and, ultimately, to sudden death. An elevated hematocrit is also found in a substantial proportion of male patients and excessive platelet aggregability has also been described in hypertension. These hematologic abnormalities are conducive to coronary thrombosis. Angiotensin II and norepinephrine, two of the most potent trophic hormones, are frequently elevated in hypertension. The effect of these hormones on the cardiac and vascular structure further increases the predilection for negative outcomes. Left ventricular hypertrophy is a potent risk factor of coronary mortality, congestive heart failure and sudden death. Vascular hypertrophy reduces the coronary reserve and at the level of skeletal muscles contributes to the evolution of the metabolic syndrome. ORGAN-SPECIFIC HYPERTENSION TREATMENT: Because of these abnormalities we are entering a new era of treatment in hypertension. Whereas an effective fall in blood pressure remains the main goal of treatment, differential effects of various antihypertensive agents on organ-specific morbidity are being actively explored. If this research proves that certain drugs have a specific advantage in defined subgroups of patients, clinical practice will change. It is reasonable to expect that in the next century we will witness a further improvement in the impact of antihypertensive treatment on public health.

Coronary Disease↗
PubMed1997

The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group.

The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity, largely due to a decreased incidence of stroke, whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies. Furthermore, treated hypertensive patients still have a higher cardiovascular complication rate, compared with matched normotensives. This is particularly evident in patients with left ventricular hypertrophy (LVH), a major independent risk indicator for cardiovascular disease. In addition to elevating blood pressure, angiotensin II (A-II) exerts an important influence on cardiac structure and function, stimulating cell proliferation and growth. Thus, to further reduce morbidity and mortality when treating hypertensive patients, it may be important to effectively block the effects of A-II. This can be achieved directly at the A-II receptor level by losartan, the first of a new class of antihypertensive agents. It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy, and thus improves prognosis. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study is a double-blind, prospective, parallel group study designed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients (initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg) with electrocardiographically documented LVH. The study, which will continue for at least 4 years and until 1,040 patients experience one primary endpoint, has been designed with a statistical power that will detect a difference of at least 15% between groups in the incidence of combined cardiovascular morbidity and mortality. It is also the first prospective study with adequate power to link reversal of LVH to reduction in major cardiovascular events. The rationale of the study, which will involve more than 800 clinical centers in Scandinavia, the United Kingdom, and the United States, is discussed, and the major features of its design and general organization are described. On April 30, 1997, when inclusion was stopped, 9,218 patients had been randomized.

Adrenergic beta-Antagonists↗