bluuebunny/crossref_metadata_2025 huggingface dataset:
PROBLEMS OF PHASING: A RECONSIDERATION OF THE BLACK PATCH MIDDLE BRONZE AGE ‘NUCLEATED VILLAGE’
Authors: RUSSELL MILES
Published: May 2007

The Middle Bronze Age settlement complex of Black Patch, East Sussex, originally considered to represent the remains of a single phase ‘nucleated village’, is here reconsidered as representing the remains of two chronologically distinct settlement units. The dangers inherent in overlooking sequence and assuming contemporaneity for all archaeological features revealed within the course of a single excavation, are outlined.
PTOLEMAIC CAMEOS OF THE SECOND AND FIRST CENTURIES BC
Authors: PLANTZOS DIMITRIS
Published: May 2007

Cameos were devised some time in the Hellenistic period, and they were used in a decorative manner. In terms of style and subject matter they follow developments in the making of intaglios and other glyptic products as well as coinage. This paper examines two related series of cameos which seem to have been produced in Alexandria of the later Hellenistic period, and under direct Ptolemaic patronage. Their study is held in view of a reappraisal of the Tazza Farnese, and the presentation here of a further argument in support of this Grand Cameo's dating in the first century BC.
EARLY MEDIEVAL WEAPONS IN THE NORTH CAUCASUS – A PRELIMINARY REVIEW
Authors: KAMINSKY † V.N.
Published: May 2007

The early medieval weapons [of sixth to ninth centuries] which have been found in cemeteries in the northern Caucasus are given a preliminary classification. The implications for the contacts between peoples and for their changing mode of warfare are discussed.
COMMENTS ON F. BEGEMANN, E. PERNICKA, S. SCHMITT‐STRECKER, ‘THERMI ON LESBOS: A CASE STUDY OF CHANGING TRADE PATTERNS', OXFORD JOURNAL OF ARCHAEOLOGY, 14(2) (1995), 123–135.
Authors: GALE N.H.
Published: May 2007

Summary. A considerable part of the paper on which I comment is devoted to criticisms of the trace element analyses made in Oxford and the authors argue that analytical problems exist at Oxford for at least the elements Co, Pb and Zn. A close examination of ‘blind’ analyses made in the British Museum, in Heidelberg and in Oxford of a series of ancient copper based alloys circulated by V. Rychner, University of Neuchatel, shows that agreement is in fact excellent between these laboratories. Analyses in Oxford of a series of copper based alloys certified for their content of various trace elements by the U.S. National Institute for Standards and Technology shows excellent agreement with those certified values. There has been a problem with the analyses of very low contents of Co in copper alloys, less than about 10 ppm, which affects the published analyses of Co (at such low levels only) from both Oxford and Heidelberg prior to 1993; this problem has now been recognised and overcome independently by both laboratories.
EUBOIANS IN MACEDONIA? A CLOSER LOOK
Authors: PAPADOPOULOS JOHN K.
Published: May 2007

Summary. A number of recent studies, both archaeological and philological, have revived old arguments, in addition to presenting new evidence, for Euboian colonisation and pre‐colonisation in Macedonia, particularly the Chalkidike. As a result, a virtual consensus has arisen in current scholarship which views Euboia as an active early agent in the north Aegean Early Iron Age. A closer look at the evidence at hand, however, undermines rather than supports the arguments for Euboian pre‐eminence in the region and highlights the false and often hasty basis on which many arguments are founded. In addition to the archaeological, the philological evidence is reviewed and it is suggested that Chalkidike derives its name not from Euboian Chalkis but directly from chalkos and alludes to the rich metal deposits of the region.
THE PORT OF THOLOS IN EASTERN CRETE AND THE ROLE OF A ROMAN HORREUM ALONG THE EGYPTIAN ‘CORN ROUTE’
Authors: HAGGIS DONALD C.
Published: May 2007

Summary.Roman provincial warehouses and rural horrea in the Aegean and eastern Mediterranean remain largely undocumented and their functions are poorly understood. A recent intensive archaeological survey at the bay of Tholos in the Kavousi area of northeastern Crete has investigated one such horreum and has explored the regional archaeological context of the building and its hinterland. The present study discusses the architectural form and archaeological context of this warehouse and assesses its function within the broader political and economic sphere of eastern Mediterranean trade routes in the second century A.D. Patterns of coastal urbanization, settlement development, and land use in eastern Crete in the Classical and Hellenistic periods, are examined as background for discussion of Roman rule, and as factors that are crucial in understanding the economics of settlement and the role of Cretan cities and the port of Tholos in the first and second centuries A.D.
WATER, ANIMALS AND AGRICULTURAL TECHNOLOGY: A STUDY OF SETTLEMENT PATTERNS AND ECONOMIC CHANGE IN NEOLITHIC SOUTHERN GREECE
Authors: JOHNSON MATS
Published: May 2007

Summary.This study, based on evidence from archaeological surveys and excavations in southern Greece, demonstrates two major shifts in the subsistence economy during the Neolithic. In the EN and MN periods the presence of large villages in locations near reliable water‐sources and permanently moist or seasonally flooded soils of high and sustained productivity illustrates a village farming economy concentrating on arable agriculture. The first economic shift occurred in the late MN‐LN with occupation of highland caves and islands, indicating increased sheep/goat pastoralism, fishing, and perhaps hunting, with a reduced number of farming villages present in the plains. The second shift took place in the FN‐EBA, when a dispersal of agricultural settlements into dry upland regions indicates expanding plough agriculture and pastoralism, important factors contributing to the development of the flourishing EBA economy. The expansion of settlement was most marked in southeastern Greece, and it is suggested here that the extensive grazing areas provided by the open vegetation and mountainous terrain of this dry region, and its relative scarcity of well‐watered fertile lowlands, may have stimulated the LN‐FN expansion of pastoralism.
Illustrated by Children
Authors: JOHNSON PAUL
Published: May 2007

Art education has tended to omit illustration from any serious discussion in the curriculum. However, literacy educators now encourage the ‘reading’ of illustrations in picture books and scrutinise the relationship between word and image in child cognition. It is time art educators began to look at illustration seriously in the context of visual education.
Design Expertise Amongst Student Designers
Authors: CROSS NIGEL , CHRISTIAANS HENRI , DORST KEES
Published: May 2007

This report of a series of protocol studies of designers at varying levels of competence examines the pedagogical system of integrating developing skills with increasing project complexity as a definition of design expeitise. It comments on different kinds of problem‐solving strategies which are used to ensure the appropriateness of the aims of design education, and assesses the relative importance that novelty and creativity, uncertainty and information, imagination and constructive thought, and drawing and modelling play in the maturation of designers. The results show a lack of predictability, but that the abilities needed for design expertise can be articulated and developed as educational programmes.
Aesthetics as the Foundation of Human Experience
Authors: DAVEY NICHOLAS
Published: May 2007

The central argument of this paper is straightforward. Contrary to being peripheral to the study of art, aesthetics is not only central to unravelling art's evident meaningfulness but also paradigmatic in the understanding of human experience. Rather than being marginal within art education, aestheticsviaits elucidation of how art works ‘work’ should assume a key position in the understanding of art enabling the latter to unlock not only the workings of human experience but also that developmental, unfolding process of self‐formation and discovery which once went by the name of education. The argument is prescriptive and shamelessly so for it is inspired by a single ideological commitment:to remain truthful to nothing other than the intricacies and intensities of human experience itself.The argument makes the key assumption that ‘art speaks', and in that address translates us into realms not of our making. To accord aesthetics such power is to oppose these currents of a contemporary culture which seemingly seeks assurance in the domesticating certainties of technological reasoning. For the principal argument to take root, some of the strangulating preconceptions about philosophical aesthetics must first be cut down.
Microalbuminuria: What Is It? Why Is It Important? What Should Be Done about It?
Authors: Bakris George L.
Published: May 2007

Microalbuminuria (MA) is defined as persistent elevation of albumin in the urine, of 30–300 mg/day (20–200 μg/min). These values are less than the values detected by routine urine dipstick testing, which does not become positive until protein excretion exceeds 300–500 mg/day. Use of the albumin‐to‐creatinine ratio is recommended as the preferred screening strategy for all diabetic patients. MA is measured in spot morning urine obtained from the patient in the office and sent for measurement of both albumin and creatinine. A value above 0.03 mg/mg suggests that albumin excretion is above 30 mg/day and therefore MA is present. MA should be checked annually in everyone, and every 6 months within the first year of treatment to assess the impact in patients started on antihypertensive therapy. MA is an established risk factor for renal disease progression in type 1 diabetes and its presence is the earliest clinical sign of diabetic nephropathy. In addition, a number of studies suggest that MA is an important risk factor for cardiovascular disease and defines a group at high risk for early cardiovascular mortality in both type 2 diabetes and essential hypertension. MA also signifies abnormal vascular permeability and the presence of atherosclerosis. Among nondiabetic patients with essential hypertension, MA is associated with higher blood pressures, increased serum total cholesterol, and reduced serum high‐density lipoprotein cholesterol. Thus, taken together these data support the concept that the presence of MA is the kidney's notice to the physician/patient that there is a problem with the vasculature. MA can be reduced, and progression to overt proteinuria prevented, by aggressive blood pressure reduction. The National Kidney Foundation recommends that blood pressure levels be maintained at or below 130/80 mm Hg in anyone with diabetes or renal disease. This should be accomplished with antihypertensive agents that prevent the rise in MA and hence prevent development of proteinuria. Such agents are angiotensin‐converting enzyme inhibitors, angiotensin receptor blockers and, to a lesser extent, β blockers, non‐dihydropyridine calcium antagonists, and diuretics. In summary, the presence of MA is a marker of endothelial dysfunction and a harbinger of markedly enhanced cardiovascular risk. All patients with diabetes and/or hypertension should be screened for the presence of microalbuminuria with use of spot morning urine. To maximize prevention of MA development, the following goals should be instituted: 1) blood pressure should be maintained at <130/80 mm Hg and a low‐salt, moderate‐potassium diet instituted; 2) in diabetics, HbA1c should be kept at <7%; 3) in obese patients, a weight loss program should be implemented, with a goal BMI of <30; and 4) the physician and patient, working together, should maintain low‐density lipoprotein cholesterol at <120 mg/dL, and <100 mg/dL if diabetes is present.
The β Blockers: Are They as Protective in Hypertension as in other Cardiovascular Conditions?
Authors: Hanes Donna S. , Weir Matthew R.
Published: May 2007

Beta blockers are frequently used to treat hypertension because of their well established safety and efficacy. Large clinical trials yield a 12%–20% decline in cardiovascular end points in hypertensive patients treated with β blockers. However, β blockers account for only 11% of antihypertensive prescriptions, and their use appears to be declining as newer agents with fewer side effects become available. The metabolic side effects of β blockers have recently been examined. While they may raise triglycerides, lower high‐density lipoprotein cholesterol, induce glucose intolerance, and possibly unmask diabetes, these effects have not been shown to impact their clinical effectiveness. For hypertension, β blockers are still recommended as first‐line therapy in many patients, particularly those at high risk for cardiovascular disease. They are also indicated for other cardiovascular disorders, such as congestive heart failure and postmyocardial infarction, in which mortality reductions exceed that seen with hypertension treatment in patients without cardiovascular complications.
Prognostic Value of Direct, Continuous Ambulatory Blood Pressure Monitoring in Essential Hypertension
Authors: Khattar Rajdeep S. , Senior Roxy , Lahiri Avijit
Published: May 2007

This study assessed the prognostic value of ambulatory vs. clinic blood pressure measurement in 688 hypertensives who had undergone pretreatment 24‐hour intra‐arterial ambulatory blood pressure monitoring. A total of 157 first events were recorded over a follow‐up period of 9.2±4.4 years. Ambulatory systolic or diastolic blood pressure parameters (whether 24‐hour mean, daytime mean, or nighttime mean) or ambulatory pulse pressure provided independent prognostic information in conjunction with clinical variables. The most predictive models contained the ambulatory systolic blood pressure parameters. Age, male gender, South Asian origin, diabetes mellitus, and previous cardiovascular disease were additional independent predictors of events. In a subgroup of 295 uncomplicated patients, 24‐hour ambulatory pulse pressure was an independent predictor of left ventricular mass index and maximal carotid intima‐media thickness. Baseline clinic blood pressure parameters did not provide independent information for the prediction of events or target organ damage. Therefore, in this study, ambulatory blood pressure proved to be superior to clinic measurement for cardiovascular risk stratification. However, the routine use of ambulatory blood pressure monitoring is not currently recommended, mainly because of a lack of outcome trials based on the treatment of ambulatory blood pressure levels.
Treatment of Hypertension to Prevent Stroke: Translating Evidence into Clinical Practice
Authors: Kaplan Robert C.
Published: May 2007

Although programs such as the National High Blood Pressure Education Project emphasize that all patients with hypertension should be treated, it is perhaps natural for physicians to question the usefulness of aggressively treating those patients who have modestly elevated blood pressure levels but are otherwise healthy, asymptomatic individuals. Using the example of stroke, this review summarizes the clinical trial data demonstrating the efficacy of antihypertensive therapy in patients with severe and nonsevere forms of hypertension. Suggestions are made that will help practitioners to apply results from the published literature in clinical practice. The evidence suggests that treating patients with nonsevere hypertension would prevent a larger proportion of the population‐wide burden of stroke than treating only those with more severe hypertension. Helping physicians to understand and apply this evidence will bring us closer to the goal of population‐wide treatment and control of high blood pressure.
Working Group Report on High Blood Pressure in Pregnancy
Authors: Moser Marvin
Published: May 2007

This report updates the 1990 National High Blood Pressure Education Program Working Group Report on High Blood Pressure in Pregnancy and focuses on classification, pathophysiology, and management of the hypertensive disorders of pregnancy. Using evidence‐based medicine and consensus, this report updates contemporary approaches to hypertension control during pregnancy by expanding on recommendations made in the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC VI). The recommendations to use K5 for determining diastolic pressure and to eliminate edema as a criterion for diagnosing pre‐eclampsia are discussed. In addition, the use of blood pressure increases of 30 mm Hg systolic or 15 mm Hg diastolic as a diagnostic criterion has not been recommended, as available evidence shows that women in this group are not likely to suffer increased adverse outcomes. Management considerations are made between chronic hypertension that is present before pregnancy and those occurring as part of the pregnancy‐specific condition preeclampsia, as well as management considerations in women with comorbid conditions. A discussion of the pharmacologic treatment of hypertension in pregnancy includes recommendations for specific agents. The use of low‐dose aspirin, calcium, or other dietary supplements in the prevention of pre‐eclampsia is described, and expanded sections on counseling women for future pregnancies and recommendations for future research are included. Once again we thank Dr. Ray Gifford, Jr., and his committee for volunteering their time to produce this important report. We hope it helps the busy clinician prevent and manage a very important problem.—Claude Lenfant, MD, Director, National Heart, Lung, and Blood Institute, and Chair, National High Blood Pressure Education Program Coordinating Committee
The Challenge of Controlling Systolic Blood Pressure: Data from the National Health and Nutrition Examination Survey (NHANES III), 1988–1994
Authors: Whyte Joanna Louise , Lapuerta Pablo , L'Italien Gilbert J. , Franklin Stanley S.
Published: May 2007

Clinicians tend to focus on diastolic blood pressure (DBP), rather than systolic blood pressure (SBP), to identify and treat hypertension. The authors used data from the National Health and Nutrition Examination Survey (NHANES III, 1988–1994) Mobile Examination Center to examine the distributions of SBP and DBP in treated and untreated individuals with hypertension. We identified the percentage of the hypertensive population with SBP controlled to <140 mm Hg and the percentage with DBP controlled to <90 mm Hg, stratified by treatment status, gender, race, and ethnicity. Individuals were classified as having hypertension if they had SBP of >140 mm Hg or DBP of >90 mm Hg, or if they were taking medication for hypertension. A weighted analysis was performed to project the results to the entire U.S. population from 1988–1994; these totals were further estimated for the year 2000 by extrapolation. For men, women, whites, African Americans, and Hispanics, SBP control rates were uniformly poorer than DBP control rates. The difference persisted when subgroups were categorized according to treatment status. The disparity in SBP and DBP control rates was especially great for women: only 50% of treated white women with hypertension had SBP control, but 92% had DBP control. The prevalence of isolated systolic hypertension was greater than 50% among all individuals with hypertension in the 55–60‐year age group and increased with age thereafter. A greater emphasis on SBP is needed to improve population blood pressure control.
Roundtable Discussion: Blood Pressure Lowering by Any Means, or Do Specific Medications Make a Difference?
Authors: Moser Marvin , Pickering Thomas G. , Weber Michael A.
Published: May 2007

Following a symposium on hypertension sponsored by the National Heart, Lung, and Blood Institute in New York City on January 17, 2001, a panel of the speakers was convened to discuss the topic, “Is it blood pressure lowering alone that accounts for the reduction in morbidity and mortality, or do specific medications or functions make a difference?” Moderating the panel was Dr. Marvin Moser, Clinical Professor of Medicine at Yale University School of Medicine. Participants included Dr. Thomas G. Pickering, Professor of Medicine at the Mount Sinai School of Medicine in New York and Dr. Michael A. Weber, Professor of Medicine at the State University of New York Health Science Center in Brooklyn, New York. Subsequent to this discussion, several treatment trials were reported. The results of these have been added where appropriate.
Diagnosis and Treatment of Supine Hypertension in Autonomic Failure Patients With Orthostatic Hypotension
Authors: Jordan Jens , Biaggioni Italo
Published: May 2007

Orthostatic hypotension is seen in various medical conditions. It can be secondary to medications or volume depletion. It can also be due to autonomic neuropathy secondary to other diseases, such as diabetes mellitus, or to primary degenerative processes of the autonomic nervous system. Orthostatic hypotension dominates the clinical picture of patients suffering from autonomic failure. Paradoxically, about one half of these patients also suffer from supine hypertension, which induces pressure natriuresis, worsening orthostatic hypotension. It also complicates the treatment of orthostatic hypotension. Supine hypertension is mediated by an increase in peripheral vascular resistance. This is due to residual sympathetic tone in patients with multiple system atrophy (Shy‐Drager syndrome), but the cause is not known in patients with pure autonomic failure, who have increased vascular resistance despite very low levels or plasma norepinephrine and renin activity. The recent observation that patients with supine hypertension develop left ventricular hypertrophy suggests they should be treated. During the day, avoiding the supine position is often all that is required. Short‐acting vasodilators (e.g., transdermal nitroglycerin) can be used during the night.
Gender Differences in Vascular Compliance in Young, Healthy Subjects Assessed by Pulse Contour Analysis
Authors: Winer Nathaniel , Sowers James R. , Weber Michael A.
Published: May 2007

Objectives. Sex hormones exert important effects on the vasculature. Female sex hormones have been reported to enhance endothelial function, reduce oxidative stress, and protect against atherosclerosis. However, the effects of estrogen on vascular compliance have not been studied. Recently, noninvasive instrumentation that estimates vascular compliance by recording the radial artery pulse contour has been introduced. Reductions in the oscillatory or reflected component of the diastolic waveform have been observed in various clinical conditions, including hypertension, diabetes mellitus, and congestive heart failure, and may reflect endothelial dysfunction at the site of resistance vessels. In this study the authors examined gender‐related vascular compliance in a cohort of young, healthy, predominantly nonsmoking, medication‐free men and women to determine the influence of cardiovascular risk factors, including family and social history, serum lipids, plasma homocysteine, and insulin levels on vascular compliance.

Methods. The volunteers, consisting of 151 healthy men and women (mean age 24±4 years) completed a questionnaire detailing family and social history, medication use, and exercise habits. Large (C1) and small (C2) vessel compliance and various cardiovascular parameters were derived from arterial pulse wave contour analysis. Systolic, diastolic, and mean arterial blood pressure, pulse pressure, and pulse rate were determined simultaneously by oscillometry. Blood for fasting serum lipids, plasma homocysteine, and serum insulin were obtained in a subset of 135 subjects.

Results. The questionnaire revealed that 38% of parents had a history of hypertension, 31% had dyslipidemia, and 15% had coronary heart disease. C2 was lower in subjects with parental dyslipidemia. Compared to men, women had lower C2; lower systolic blood pressure, mean arterial pressure, and pulse pressure; higher serum high‐density lipoprotein cholesterol; lower serum triglycerides; and lower plasma homocysteine, but similar serum insulin levels. C1 correlated with height and pulse pressure, whereas C2 was proportional to height and weight and inversely related to systemic vascular resistance. Multivariate regression analysis showed that stroke volume, total vascular impedance, cardiac output, female gender, and systemic vascular resistance independently predicted changes in C2, but that height was not a significant factor. Conclusions. Women have reduced C2 despite lower systolic blood pressure and pulse pressure and more favorable lipid and homocysteine levels. C2 is independent of height and is lower in subjects with parental dyslipidemia. These data indicate that female sex hormones have unexpected negative effects on small vessel compliance. They may help to explain why premenopausal women hospitalized for myocardial infarction have higher mortality rates than men of the same age.
Transdermal Clonidine Skin Reactions
Authors: Prisant L. Michael
Published: May 2007

The clonidine transdermal therapeutic system is being used as a therapy for blood pressure treatment. Systemic side effects seem to be fewer than with oral clonidine. However, localized skin reactions occur frequently and the incidence increases with the dose and duration of use. Common signs include erythema, scaling, vesiculation, excoriation, and induration. Allergic contact dermatitis is less frequent but common. Hyperpigmentation and depigmentation also occur. Pretreatment with 0.5% hydrocortisone is associated with less skin irritation and higher blood levels. Although oral clonidine is no longer widely used in the management of hypertension, awareness of these reactions to the transdermal delivery of this agent is important.
Comparative Efficacy of Olmesartan, Losartan, Valsartan, and Irbesartan in the Control of Essential Hypertension
Authors: Oparil Suzanne , Williams David , Chrysant Steven G. , Marbury Thomas C. , Neutel Joel
Published: May 2007

In a multicenter, randomized, double‐blind trial, the authors compared the antihypertensive efficacy of once‐daily treatment with the new angiotensin II type 1 receptor blocker (ARB) olmesartan (20 mg) with recommended starting doses of losartan (50 mg), valsartan (80 mg), and irbesartan (150 mg) in 588 patients with a cuff diastolic blood pressure (DBP) of ≥100 and ≥115 mm Hg and a mean daytime DBP of ≥90 mm Hg and <120 mm Hg, as measured by ambulatory blood pressure monitoring. Cuff and ambulatory blood pressures were monitored at baseline and after 8 weeks of treatment. All groups were predominantly white and approximately 62% male, and their mean age was approximately 52 years. In all groups, mean baseline DBP and systolic blood pressure (SBP) were approximately 104 and 157 mm Hg, respectively. The reduction of sitting cuff DBP with olmesartan (11.5 mm Hg), the primary efficacy variable of this study, was significantly greater than with losartan, valsartan, and irbesartan (8.2, 7.9, and 9.9 mm Hg, respectively). Reductions of cuff SBP with the four ARBs ranged from 8.4–11.3 mm Hg and were not significantly different. The reduction in mean 24‐hour DBP with olmesartan (8.5 mm Hg) was significantly greater than reductions with losartan and valsartan (6.2 and 5.6 mm Hg, respectively) and showed a trend toward significance when compared to the reduction in DBP with irbesartan (7.4 mm Hg; p=0.087). The reduction in mean 24‐hour SBP with olmesartan (12.5 mm Hg) was significantly greater than the reductions with losartan and valsartan (9.0 and 8.1 mm Hg, respectively) and equivalent to the reduction with irbesartan (11.3 mm Hg). All drugs were well tolerated. The authors conclude that olmesartan, at its starting dose, is more effective than the starting doses of the other ARBs tested in reducing cuff DBP in patients with essential hypertension.
Choosing Initial Antihypertensive Drug Therapy for the Uncomplicated Hypertensive Patient
Authors: Moore Michael A.
Published: May 2007

Choosing the initial antihypertensive drug for the uncomplicated hypertensive patient is an important and frequent event for the primary care physician. Patients' first experience with antihypertensive drug therapy will likely affect their long‐term perception of hypertension treatment. The choice should be made on the basis of sound scientific data and from the patient's perspective and needs. The drug should be taken once a day, should have proven efficacy in hypertension control and cardiovascular morbidity and mortality reduction, and should have as few side effects as possible. Low‐dose thiazide diuretics meet this description, although the need to monitor electrolytes may make them less than ideal. The angiotensin II receptor antagonist class, with side‐effects similar to those of placebo in controlled trials, is the most attractive from the patient's perspective, although outcome trial data do not yet exist proving that hypertension treatment with angiotensin II receptor antagonists reduces cardiovascular events. The angiotensin‐converting enzyme inhibitors or angiotensin II receptor antagonists, with their low side‐effect profiles and unique effects on vascular remodeling, are attractive second choices to combine with a diuretic if needed, although low‐dose diuretic/β blocker combinations have also been shown to lower blood pressure with minimal side effects. At present, ensuring adequate long‐term hypertension control is the most important aspect of hypertensive care, and which antihypertensive drug(s) the physician chooses can greatly affect the hypertensive patient's ability to achieve and to maintain long‐term blood pressure control.
Factors Influencing the Systolic Blood Pressure Response to Drug Therapy
Authors: Campo Carlos , Segura Julián , Ruilope Luis M.
Published: May 2007

In the early stage of hypertension, diastolic blood pressure has greater prognostic importance, but in the elderly, systolic blood pressure is the most important marker of cardiovascular complications. Therefore, the need for more strict control of this component of blood pressure must be reconsidered. The benefit obtained in different studies in the elderly suggests that the treatment of isolated systolic hypertension is associated with a reduction in overall cardiovascular mortality of 22%, in coronary heart disease mortality of 26%, and in stroke mortality of 33%. However, a higher percentage of patients (73%) attain the diastolic goal of <90 mm Hg, while only 34% have systolic pressure reduced to <140 mm Hg. In a review of randomized trials comparing at least four different antihypertensive drugs, significant differences in systolic blood pressure reduction have not been demonstrated, except in black populations, in whom calcium channel blockers and diuretics seem to be more effective. In patients with isolated systolic hypertension, data are inconclusive, but calcium channel blockers and diuretics appear to lower blood pressure to a greater degree than do other antihypertensive drugs. Two main predictors of difficulty in controlling systolic blood pressure are the baseline blood pressure and the presence of diabetes. Other predictors are the duration of arterial hypertension, older age, the presence of target organ damage and associated clinical conditions (myocardial infarction, stroke, chronic renal failure), and an elevated serum uric acid level. It appears that the profile of patients with a poorer therapeutic response includes a greater severity of hypertension and/or the presence of cardiovascular disease.
Use of Lipid‐Lowering Drugs and Blood Pressure Control in Patients With Arterial Hypertension
Authors: Borghi Claudio , Dormi Ada , Veronesi Maddalena , Immordino Vincenzo , Ambrosioni Ettore
Published: May 2007

A large proportion of patients have both hypertension and hypercholesterolemia, two of the most important risk factors for cardiovascular diseases. Statins are the most widely used drugs for the treatment of plasma lipid abnormalities and have been reported to interact with elevated blood pressure. A reduction in blood pressure associated with the use of these agents has been reported in patients with untreated hypertension and in patients treated with antihypertensive drugs, particularly angiotensin‐converting enzyme inhibitors and calcium channel blockers. This effect on blood pressure control has also been observed in diabetic patients. The mechanism responsible for the hypotensive effect seems to be largely independent of the effect of statins on plasma cholesterol, and probably is related to the interaction of the medications with endothelial function or angiotensin II receptors. The capacity of statins to improve blood pressure control may represent a useful tool for improvement in the prevention of cardiovascular diseases.
Therapeutic Considerations in the Treatment of Obesity Hypertension
Authors: Wofford Marion R. , Miller Davis Margaret , Harkins Kimberly G. , King Deborah S. , Wyatt Sharon B. , Jones Daniel W.
Published: May 2007

Obesity, now recognized as an independent risk factor for cardiovascular disease, is closely associated with hypertension. Complex mechanisms link increasing body weight with increasing blood pressure. Treatment of the obese patient with hypertension requires consideration of physiologic changes related to obesity hypertension. Lifestyle modification, including weight reduction and increased physical activity, can directly influence blood pressure levels and improve blood pressure control in obese, hypertensive patients. Clinical trials are needed to determine the most effective antihypertensive drugs for the obese, hypertensive patient. Antiobesity drugs offer viable adjunctive pharmacotherapy for obesity hypertension, but additional long‐term studies are needed to support their safety and efficacy.
Salt Intake, Endothelial Dysfunction, and Salt‐Sensitive Hypertension
Authors: Bragulat Ernesto , Sierra Alejandro de la
Published: May 2007

Numerous epidemiologic and clinical studies have demonstrated a clear relationship between high salt intake and blood pressure. However, the mechanisms of a salt‐induced increase in blood pressure—a phenomenon known as salt sensitivity—and the heterogeneity of this effect are far from being completely understood. Endothelial dysfunction, and especially the nitric oxide system, is implicated in both experimental and clinical hypertension. Animal studies indicate that endogenous nitric oxide plays an important role in renal hemodynamics and sodium homeostasis, inducing renal vasodilation and natriuresis. Studies of essential hypertensive patients have also suggested that both high salt intake and salt sensitivity are associated with impaired endothelial function. Although there are many hypotheses concerning the nature of salt sensitivity, clinical data indicate that salt‐sensitive patients may be unable to up‐regulate the production of nitric oxide in response to salt intake. This endothelial dysfunction, which is more frequent in salt‐sensitive than in salt‐resistant essential hypertensive patients, may partially explain the blood pressure increase in response to salt intake and may underlie the more pronounced target organ damage and cardiovascular risk in salt‐sensitive patients.
Blood Pressure Changes in the Leg on Standing
Authors: Malhotra Arun , Cohen Debbie , Syms Charles , Townsend Raymond R.
Published: May 2007

Normotensive and hypertensive patients develop peripheral arterial disease. The authors hypothesized that significant changes in lower extremity blood pressures occur upon standing, which could play a role in the pathogenesis of peripheral arterial disease. Forty‐one subjects had blood pressure measurements performed in the arm and ankle in the supine and standing positions. The data show a marked increase in leg blood pressure on assuming the standing position, with mean increases of 65 mm Hg in systolic and 62 mm Hg in diastolic blood pressure in the lower extremities, compared with the arm on standing. In addition, the changes in diastolic pressure in the leg on standing were significantly correlated to height (r=0.47; p<0.002). These data reveal a previously unappreciated aspect of blood pressure, namely a large increase in lower extremity blood pressure values on standing, which may predispose to peripheral arterial disease
Salt Sensitivity Is Associated With an Increased Mortality in Both Normal and Hypertensive Humans
Authors: Weinberger Myron H
Published: May 2007

While a variety of studies have demonstrated the heterogeneity of the blood pressure response to salt loading and depletion, none has examined the relationship of these responses to mortality. We conducted a follow‐up study of 430 normal and 278 hypertensive subjects studied as long ago as 28 years by techniques to assess their blood pressure responses to salt and volume expansion and depletion (salt sensitivity). We found that 123 (21 %) of our study subjects had died in the interval since the initial study. The following measures were found to be significantly associated with the risk for death: blood pressure (systolic, diastolic, mean arterial, and pulse pressures), hypertension, age, salt sensitivity, baseline renin levels (inverse), and body mass index (but not body weight). Normotensive, saltsensitive subjects had a survival that was no different than that of hypertensive subjects. Only initially normotensive, salt‐resistant individuals had improved survival. Studies are continuing in order to elucidate the mechanisms by which salt sensitivity, even in normotensive subjects, may lead to reduced survival.
Essential Hypertension of Caribbean Hispanics: Sodium, Renin, and Response to Therapy
Authors: Laffer Cheryl L , Elijovich Fernando
Published: May 2007

Little is known about essential hypertension in Hispanic Americans, despite the fact that they are the fastest‐growing minority in the United States and have a disproportionate degree of hypertensive target organ damage. The authors studied 89 Caribbean Hispanic hypertensive patients who participated in six double‐blind, randomized trials of antihypertensive agents. Demographics, laboratory data, sodium excretion, plasma renin activity, and atrial natriuretic peptide were obtained after 3–4 weeks on placebo. Blood pressure responses to angiotensin‐converting enzyme (ACE) inhibitors, β blockers, calcium channel blockers, hydrochlorothiazide (HCTZ), and fixed combinations of ACE inhibitors and HCTZ, were compared to the placebo values after 8–12 weeks of treatment. Patients had a multiple risk factor profile (obesity and diabetes) and a wide spectrum of blood pressure elevation, left ventricular hypertrophy, and hypertensive renal damage. Urine sodium excretion rates indicated inability to comply with salt restriction in 65% of patients. Plasma renin activity was lower than that of Hispanic normotensive controls, and 62% of patients had low‐renin essential hypertension by renin profiling to sodium excretion. On analysis of variance, blood pressure reductions by calcium channel blockers, HCTZ, and ACE inhibitor/HCTZ combinations were significantly greater than that with placebo, while those of ACE inhibitors and β blockers as monotherapy were not. The authors conclude that essential hypertension of Caribbean Hispanics is associated with multiple risk factors and is largely of the low‐renin type. Responses to therapy are consistent with those observed in other populations with the low‐renin phenotype and suggest salt‐sensitivity of blood pressure in this population. Confirmation of the latter has implications for prevention and treatment of essential hypertension in Hispanics.
The Reliability of Patient Self‐Reported Blood Pressures
Authors: Cheng Cynthia , Studdiford James S. , Chambers Christopher V. , Diamond James J. , Paynter Nina
Published: May 2007

Self‐monitoring of blood pressure actively involves patients in hypertension management. However, the usefulness of self‐monitoring of blood pressure may be limited by inaccurate patient reporting. The study objective was to assess reliability of patient blood pressure reporting over 6 months. Forty‐nine subjects with Joint National Committee stage 1 or 2 hypertension were enrolled. Unaware that the monitors electronically store readings, the subjects were asked to check and record outpatient blood pressures twice weekly. Stored and written readings were compared. On average, patient‐recorded blood pressures were equivalent to stored monitor values 80% or more of the time. Reliability of patient self‐reporting was sustained over the 6‐month study period. Notably, patients did not selectively report lower blood pressure readings. The overall mean self‐reported and stored monitor blood pressures were nearly identical: blood pressure (±SD) 134±16.8/78±11.6 mm Hg and 135±19.6/80±13.3 mm Hg, respectively. The reliability of self‐reporting of blood pressures for many patients supports the potential usefulness of self‐monitoring of blood pressure in hypertension management.
Antihypertensive Efficacy of Olmesartan Medoxomil, a New Angiotensin II Receptor Antagonist, as Assessed by Ambulatory Blood Pressure Measurements
Authors: Neutel Joel M. , Elliott William J. , Izzo Joseph L. , Chen Chao L. , Masonson Harvey N.
Published: May 2007

Olmesartan medoxomil is a new angiotensin II receptor blocker. In this randomized, double‐blind, placebo‐controlled study, the efficacy and safety of olmesartan medoxomil was assessed in 334 patients with moderate to severe essential hypertension. Patients were randomized to receive placebo; 5, 20, or 80 mg olmesartan medoxomil q.d.; or 2.5, 10, or 40 mg olmesartan medoxomil b.i.d. Ambulatory and cuff blood pressure were measured prior to and after 8 weeks of treatment. Treatment with olmesartan medoxomil resulted in a significant placebo‐adjusted reduction of mean 24‐hour ambulatory diastolic blood pressure of 9.6 mm Hg, 12.2 mm Hg, and 10.6 mm Hg in the 5‐, 20‐, and 80‐mg q.d. groups, respectively. Corresponding reductions in mean ambulatory systolic blood pressure were 14.5 mm Hg, 16.5 mm Hg, and 15.4 mm Hg. Similar reductions of diastolic and systolic blood pressure were seen with b.i.d. dosing. The diastolic trough‐to‐peak ratios of the q.d. doses of olmesartan medoxomil ranged from 57%–70%, indicating 24‐hour effectiveness. The safety profile of olmesartan medoxomil was similar to that of placebo. Olmesartan medoxomil appears to be a safe and effective once‐a‐day treatment for hypertension.
The Losartan Intervention for Endpoint Reduction (LIFE) Trial—Have Angiotensin‐Receptor Blockers Come of Age?
Authors: Sica Domenic A. , Weber Michael
Published: May 2007

The Losartan Intervention for Endpoint Reduction trial is one of several end‐point trials that are now available with angiotensin‐receptor blockers. This trial compared two regimens—losartan‐based therapy to atenolol‐based therapy—in 9193 hypertensive patients with electrocardiographic evidence of left ventricular hypertrophy. In the instance of each of these therapeutic groups, hydrochlorothiazide add‐on therapy was permitted as per protocol. Although blood pressures were comparably reduced in both the losartan and the atenolol‐based treatment groups, stroke rate was notably less in the losartan‐treatment group. The 1195 patient diabetic cohort in this trial also experienced a substantial reduction in total and cardiovascular mortality favoring losartan. An additional finding in this trial was that new‐onset diabetes developed 25% less frequently in the losartan‐treated group. The results of this trial are both interesting and relevant to what is an expanding use of angiotensin‐receptor blockers in the hypertensive population.
The Association Between Hypertension and Other Cardiovascular Risk Factors in Young Adult African Americans
Authors: Borde‐Perry William C. , Campbell Kimberly L. , Murtaugh Kevin H. , Gidding Samuel , Falkner Bonita
Published: May 2007

Hypertension is a major cause of cardiovascular disease in African Americans. The excess morbidity and mortality due to cardiovascular disease in African Americans compared to Caucasians is not well explained. The purpose of this study was to examine the association between hypertension and other cardiovascular risk factors in young adult African Americans. A risk factor scoring system was developed, based on national guidelines for obesity, smoking, cholesterol levels, glucose tolerance, and blood pressure. Data from a previously studied cohort of 206 women and 117 men were analyzed for the association of hypertension with other risk factors. Among women, risk factor intensification is due to impaired glucose tolerance and obesity. Among men, intensification appears to be related to all major risk factor categories. These findings indicate that among hypertensive African Americans there is an amplification of other risk factors. The data also support the clinical management of multiple risk factors as well as the achievement of blood pressure control.
Clinical Impact of Renin‐Angiotensin System Blockade: Angiotensin‐Converting Enzyme Inhibitors vs. Angiotensin Receptor Antagonists
Authors: Izzo Joseph L. , Moser Marvin
Published: May 2007

Clinical trials have proved that blockade of the renin‐angiotensin‐aldosterone system (RAAS) offers primary and secondary protection of the cardiovascular system, brain, and kidneys. Drugs that interrupt the RAAS do so by several diverse mechanisms but it remains to be fully proved whether these mechanistic differences are associated with meaningful differences in clinical outcomes. This review summarizes current information about the basic mechanisms of action of three classes of anti‐RAAS drugs: angiotensin‐converting enzyme (ACE) inhibitors, combined ACE‐neutral endopeptidase inhibitors, and angiotensin receptor antagonists as well as results of major clinical outcome trials with these agents. Basic and clinical science information is then blended with insights from the clinical pharmacology of anti‐RAAS drugs to address four current controversies in clinical medicine: whether ACE inhibitors and angiotensin receptor antagonists are interchangeable, optimal dosing of available agents, potential justification of ACE inhibitor/angiotensin receptor antagonist combinations, and first‐line use of anti‐RAAS drugs in antihypertensive therapy.