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Background Multiple epidemiological studies from Europe and Asia have demonstrated increased cardiovascular risks associated with isolated elevation of home blood pressure (BP) or masked hypertension (MH). Previous studies have not addressed cardiovascular outcomes associated with MH and white-coat hypertension (WCH) in the general population in the United States. Objectives The goal of this study was to determine hypertensive target organ damage and adverse cardiovascular outcomes associated with WCH (high clinic BP, ≥140/90 mm Hg; normal home BP, Methods Associations among WCH, MH, sustained hypertension, and aortic pulsed wave velocity by magnetic resonance imaging; urinary albumin-to-creatinine ratio; and cystatin C were evaluated at study baseline. Then, associations between WCH and MH with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9 years were assessed. Results The study cohort comprised 3,027 subjects (50% African Americans). The sample-weighted prevalence rates of WCH and MH were 3.3% and 17.8%, respectively. Both WCH and MH were independently associated with increased aortic pulsed wave velocity, cystatin C, and urinary albumin-to-creatinine ratio. Both WCH (adjusted hazard ratio: 2.09; 95% confidence interval: 1.05 to 4.15) and MH (adjusted hazard ratio: 2.03; 95% confidence interval: 1.36 to 3.03) were independently associated with higher cardiovascular events compared with the normotensive group, even after adjustment for traditional cardiovascular risk factors. Conclusions In a multiethnic U.S. population, both WCH and MH were independently associated with increased aortic stiffness, renal injury, and incident cardiovascular events. Because MH is common and associated with an adverse cardiovascular profile, home BP monitoring should be routinely performed among U.S. adults.

Primary aldosteronism is widely held to be the most common cause of identifiable (secondary) hypertension, reported to be present in 6-10% of all hypertensive patients. This belief reflects the widespread use of the aldosterone-to-renin ratio (ARR) as a screening test. Unfortunately, the ARR is often wrong, leading to even more expensive testing that is also often misleading but that may then lead to potentially harmful additional measures. This review provides evidence that referral bias has markedly inflated the estimates of this condition and recommends a much less aggressive approach to the diagnosis of this condition based on more limited testing and the use of mineralocorticoid receptor antagonists in the treatment of most hypertensive patients.

This paper provides evidence that primary aldosteronism is likely much less common than is believed by the other authors of this collection. The basis for this contrarian view is simple: there is no way to know the true prevalence of PA because of the uncertain validity of all of the diagnostic procedures used to find and characterize this disease. Moreover, even if these uncertainties are overcome, the eventual treatment of most who have PA can be provided without the need for extensive testing and expensive treatment.

Although the term "prehypertension" has been challenged by some, its use to define people with systolic blood pressure (BP) between 120 and 139 mm Hg and/or diastolic pressures between 80 and 89 mm Hg has gained general acceptance. The category includes as many people as the number who have hypertension, defined as blood pressure of 140/90 or above. Such people are clearly at an increased risk of cardiovascular damage compared with people with BPs below 120/80 mm Hg. The major unresolved issue is the appropriate management of such patients. Two trials have attempted to document the value of short-term drug therapy to prevent the progression of BP to overt hypertension, but no outcome studies are currently available.

Objective Noninvasive blood pressure (BP) measurement often triggers a transient rise in BP, known as an alerting reaction. However, the prevalence and prognostic significance of the alerting reaction has never been assessed in the general population. Methods We evaluated the association between the alerting reaction and left ventricular mass by MRI and urinary albumin-to-creatinine ratio in the Dallas Heart Study, a large population sample of 3069 individuals. Participants were categorized into four groups based on levels of consecutive BP: first, normal first BP and average third to fifth (avg3-5) BP of less than 140/90 mmHg (control group); second, high first BP of at least 140/90 mmHg and normal (avg3-5) BP (alerting reaction group); third, normal first BP and high (avg3-5) BP; and fourth, high first to fifth BP. Then, associations between BP categories with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9.4 years were assessed. Results The sample-weighted prevalence of isolated hypertension during the first BP measurement was 9.6%. Presence of an alerting reaction was independently associated with increased left ventricular mass, urinary albumin-to-creatinine ratio, cardiovascular events after adjustment for traditional cardiovascular risk factors, and baseline BP (adjusted hazard ratio 1.24, 95% confidence interval 1.07-1.43). Conclusion Our study indicated that the alerting reaction is independently associated with increased cardiovascular and renal complications.

A panel was convened to discuss the question, “Is blood pressure lowering the sole determinant of outcome, or do specific drugs make a difference?” The panel was moderated by Marvin Moser, MD, Clinical Professor of Medicine at the Yale University School of Medicine, New Haven, CT. Panelists included Norman Kaplan, MD, Clinical Professor of Medicine at the University of Texas Southwestern Medical Center at Dallas, TX, and William Cushman, MD, Professor of Medicine at the University of Tennessee in Memphis, TN. The discussion was supported by Boehringer Ingelheim, and each author received an honorarium from Boehringer Ingelheim for time and effort spent participating in the discussion or reviewing the transcript for intellectual content before publication. The authors maintained full control of the discussion and the resulting content of this article.

My answer is “no.” Although primary aldosteronism (PA) is likely more common than most experts believed in the 1960–1990 interval, it is not nearly as common as Dr Calhoun and other investigators report from 1990 until now. As many younger clinicians may not remember, this same issue arose soon after Dr Jerome Conn characterized this disease in 1955.1 Reporting on the prevalence of PA in his highly referred population of likely suspects, Dr Conn and coworkers’ estimates were as high as 20%.2 Subsequently, studies on unreferred patients supported a prevalence of

Epidemiological studies have established a strong association between hypertension and coronary artery disease (CAD). Hypertension is a major independent risk factor for the development of CAD, stroke, and renal failure. The optimal choice of antihypertensive agents remains controversial, and there are only partial answers to important questions in the treatment of hypertension in the prevention and management of ischemic heart disease (IHD), such as: ● What are the appropriate systolic blood pressure (SBP) and diastolic blood pressure (DBP) targets in patients at high risk of developing CAD or in those with established CAD? ● Are the beneficial effects of treatment simply a function of blood pressure (BP) lowering, or do particular classes of drugs have uniquely protective actions in addition to lowering BP? ● Are there antihypertensive drugs that have shown particular efficacy in the primary and secondary prevention of IHD? ● Which antihypertensive drugs should be used in patients who have established CAD with stable or unstable angina pectoris, in those with non–ST-elevation myocardial infarction (NSTEMI), and in those with ST-elevation myocardial infarction (STEMI)?

Multiple epidemiological studies from Europe and Asia have demonstrated increased cardiovascular risks associated with isolated elevation of home blood pressure (BP) or masked hypertension (MH). Previous studies have not addressed cardiovascular outcomes associated with MH and white-coat hypertension (WCH) in the general population in the United States.The goal of this study was to determine hypertensive target organ damage and adverse cardiovascular outcomes associated with WCH (high clinic BP, ≥140/90 mm Hg; normal home BP, 135/85 mm Hg), MH (high home BP, ≥135/85 mm Hg; normal clinic BP, 140/90 mm Hg), and sustained hypertension (high home and clinic BP) in the DHS (Dallas Heart Study), a large, multiethnic, probability-based population cohort.Associations among WCH, MH, sustained hypertension, and aortic pulsed wave velocity by magnetic resonance imaging; urinary albumin-to-creatinine ratio; and cystatin C were evaluated at study baseline. Then, associations between WCH and MH with incident cardiovascular outcomes (coronary heart disease, stroke, atrial fibrillation, heart failure, and cardiovascular death) over a median follow-up period of 9 years were assessed.The study cohort comprised 3,027 subjects (50% African Americans). The sample-weighted prevalence rates of WCH and MH were 3.3% and 17.8%, respectively. Both WCH and MH were independently associated with increased aortic pulsed wave velocity, cystatin C, and urinary albumin-to-creatinine ratio. Both WCH (adjusted hazard ratio: 2.09; 95% confidence interval: 1.05 to 4.15) and MH (adjusted hazard ratio: 2.03; 95% confidence interval: 1.36 to 3.03) were independently associated with higher cardiovascular events compared with the normotensive group, even after adjustment for traditional cardiovascular risk factors.In a multiethnic U.S. population, both WCH and MH were independently associated with increased aortic stiffness, renal injury, and incident cardiovascular events. Because MH is common and associated with an adverse cardiovascular profile, home BP monitoring should be routinely performed among U.S. adults.

Following a hypertension symposium in Philadelphia in September 2005, a roundtable was convened to discuss the significance of out-of-office blood pressure. Dr. Marvin Moser of the Yale School of Medicine, New Haven, CT, moderated the panel discussion. Participants included Dr. Raymond Townsend of the University of Pennsylvania School of Medicine, Philadelphia, PA, and Dr. Norman Kaplan of the University of Texas Health Science Center in Dallas, Dallas, TX.

Although it is true that, in all previously published trials, an admixture of additional drugs with the initial agent being studied has been invariable, sometimes reaching 80% of the enrollers [2], ASCOT-BPLA is the first published study purposely designed to compare combinations of ‘older’ drugs (i.e. a b-blocker followed by a diuretic) versus ‘newer’ drugs [i.e. a calcium channel blocker (CCB) followed by an angiotensin-converting enzyme inhibitor (ACEI)]. The data show a significantly greater protection against various cardiovascular diseases by the CCB followed by ACEI regimen than by the b-blocker followed by diuretic regimen.

Hypertension remains the most common risk factor for cardiovascular morbidity and mortality. Its incidence is rising in both ageing and obese populations, but its control remains inadequate worldwide. We address several persisting controversies that may interfere with appropriate management of hypertension. They include: the reasons behind the increasing incidence of hypertension and the possible ways to slow the process, especially by lifestyle changes; the need for overall cardiovascular risk assessment; the major issues in the decision to institute drug therapy and the choice of drugs; and the importance of screening for various identifiable causes. We provide the background for these controversies, followed by some opinions on how to guide practitioners to offer more effective management of hypertension.

Hypertension that remains above 140/90 mmHg despite the use of three antihypertensive drugs in a rational combination at full doses and including a diuretic is known as 'resistant'. The percentage of hypertensives whose condition is resistant varies in large part upon the setting: those seen in general practice show a prevalence of perhaps 5%; those seen by nephrologists, probably 50%. This paper reviews the major causes of resistant hypertension and provides specific recommendations for the evaluation and management of patients with this threatening condition.

The management of solid organ cancers relies on accurate staging. Once distal metastasis has been excluded by conventional radiographic methods, local staging of the tumor and its nodal involvement is essential to determine the most optimal therapeutic approach. Many radiographic imaging modalities are unable to determine subtle tumor involvement. However, the emergence of endoscopic ultrasonography (EUS) has given promise to improved staging with its unique ability to examine tumors from within the gastrointestinal lumen with extremely close proximity. An additional advantage is the ability to perform fine-needle aspiration (FNA) biopsy to confirm or exclude tumor involvement. Many studies have shown superior accuracy in staging with EUS and EUS-FNA for tumors of the esophagus, stomach, pancreas, rectum, and mediastinum, including lung cancer. This review illustrates the principles of EUS and its role in staging of a variety of cancers and particularly its role alongside other imaging modalities.

Numerous epidemiological studies, numbering nearly 100, have documented an inverse association between alcohol consumption and vascular risk. The preponderance of evidence supports an independent beneficial effect of mild-to-moderate alcoholic beverage consumption on risk of coronary heart disease (CHD). However, it is important to remember that observational data cannot prove causation; unmeasured or incompletely controlled confounding factors cannot be excluded. That said, most authorities now attribute a causal role to the relationship: moderate alcohol consumption reduces the risk of CHD, and current research centers on the mechanistic underpinnings and whether patterns of drinking are important. Here, I review the association between alcohol use and CHD risk, explore putative mechanisms, and make recommendations.

Post-transplantation diabetes mellitus (PTDM) is defined as sustained hyperglycemia developing in any patient without history of diabetes before transplantation, that meets the current diagnostic criteria by the American Diabetes Association or the World Health Organization. Several risk factors have been identified: age, nonwhite ethnicity, and glucocorticoid therapy for rejection and chronic immunosuppression with cyclosporine and especially tacrolimus. The pathophysiology of this condition resembles that of type 2 diabetes mellitus: pretransplantation end-stage liver/renal and heart disease are insulin-resistant states, and after transplantation, glucocorticoids induce further peripheral insulin insensitivity. The "second hit" appears to be an acquired (yet reversible) insulin secretion defect resulting from the calcineurin inhibitors cyclosporine and tacrolimus. An international panel of experts has recently published the proceeding of a Consensus Conference proposing strategies for the screening, prevention and management of PTDM. Future directions include pre- and post-transplantation glucose load testing for high-risk individuals and pharmacological agents to decrease insulin resistance and to preserve beta-cell function.

Low-dose diuretics are recommended for the initial choice of antihypertensive therapy in the 7th US Joint National Committee report and are accepted as an appropriate choice among other classes of drugs in the 2003 European Society of Hypertension guidelines. The rationales for the use of low-dose diuretics include the following: Renal dysfunction interfering with normal natriuresis is likely a fundamental defect in the pathogenesis of hypertension. Subtle renal insufficiency that interferes with sodium excretion is a common consequence of uncontrolled hypertension. Diuretic-based therapy has been clearly documented in placebo-controlled, randomized trials to reduce cardiovascular morbidity and mortality, particularly in the treatment of elderly hypertensives.In multiple comparative trials, diuretic-based therapy has been shown to provide equal cardiovascular protection to that provided by newer agents. Diuretics enhance the antihypertensive efficacy of all other classes of agents. As lower blood pressure goals of therapy have been found to be needed, diuretic enhancement of other agents' efficacy has become even more essential. With such low doses, side effects are minimal in degree and infrequent in appearance.

Recent advances in understanding the mechanisms of disease have produced many new targets for gene therapy. However, it has been difficult to convert these new insights into clinically useful applications. In the field of cardiovascular medicine, most clinical studies of gene therapy have focused on angiogenesis as a treatment for ischemia. Initial enthusiasm was supported by small, uncontrolled, phase 1 trials. However, several large efficacy studies have recently been published that have not shown clinically significant improvement, and a few well-publicized complications of gene therapy have cast a pall over the entire field. In this review, we will summarize specific technical aspects of cardiovascular gene therapy, examine the recent series of clinical studies, and explore the direction of future work for the principal cardiovascular diseases.

New guidelines for the treatment of hypertension are being published, starting with the seventh report of the US Joint National Committee. These guidelines are certain to address the major developments that have been presented over the past few years. These include the risks of any level of increased blood pressure, either alone or in concert with other known risk factors; the value of out-of-office blood pressure measurements; the preventive potential of lifestyle changes; the results of multiple prospective comparative trials, which have largely negated the quest for the best initial choice of therapy; and the need to increase adherence to enough therapy to reach the appropriate goal for each patient.

Le Joint National Committee aux Etats-Unis a recemment publie son septieme rapport. Celui-ci comprend un certain nombre de modifications importantes en ce qui concerne la prise en charge de l’hypertension arterielle et notamment l’introduction du concept de « prehypertension », le choix du traitement medicamenteux initial, l’utilisation d’associations therapeutiques des la premiere intention et l’abaissement des cibles du traitement. Cet article presente et argumente ces nouvelles approches.

Cancer from an unknown primary site (CUP) is frequently encountered in clinical practice. This review is designed to help physicians identify those patients with CUP that benefit from specific therapeutic approaches. The utility of pathologic and diagnostic tests in patients with CUP will also be discussed, as will the prognosis and appropriate treatment of these patients.

There has been considerable interest and concern in recent years regarding the potential health effects of mycotoxins in the indoor environment. Although the existence of mycotoxins has been known for several decades, relatively little is known about their effects in humans. What is known comes almost exclusively from studies of ingestion as the route of exposure. This review summarizes what is known regarding health effects of mycotoxins in general and specifically examines the evidence for the role of indoor exposure to the fungi of the genus Stachybotrys as a cause of disease in humans. Much work remains to be done in the area of mycotoxin research. The risk of health effects from ingestion seems much more widespread than from indoor airborne exposure, although the latter has received considerably more media attention. Rigorously controlled studies are needed to clarify these issues.

Hepatitis C virus (HCV) affects 1.8% of the American population, and approximately 38% of patients with HCV will manifest symptoms of at least 1 extrahepatic manifestation during the illness. Renal disease, neuropathy, lymphoma, and Sjögren syndrome with or without mixed cryoglobulinemia are all strongly associated with HCV infection. Porphyria cutanea tarda and diabetes have also been linked to HCV. Most extrahepatic manifestations of chronic HCV infection are immunological, and the chronic infection seems to be necessary for their development. The molecular study of the unique way in which the HCV virus interacts with the human immune system is beginning to provide plausible explanations of the pathogenic role of HCV in some of these syndromes, but many pathogenetic links remain completely obscure.

The impressive anti-inflammatory effects of the tumor necrosis factor (TNF)alpha blockers etanercept and infliximab have led to their use in multiple inflammatory diseases besides their original indication, rheumatoid arthritis (RA). The well-studied clinical effects of both agents in RA are the reduction of signs and symptoms of joint inflammation as well as the arrest of bone destruction. Infliximab has also been Food and Drug Administration-approved in the treatment of Crohn disease; etanercept is now FDA-approved for juvenile chronic arthritis and psoriatic arthritis. Favorable initial clinical trials have been reported in other rheumatic diseases, including ankylosing spondylitis and adult Still disease. In addition, TNF alpha blockade is being studied in the treatment of uveitis, myelodysplastic syndromes, and graft-versus-host disease. Studies in sepsis and septic shock have identified small subsets of patients that may benefit from TNF alpha blockade, but broader use in septic patients has not improved survival. The TNF alpha blockers have had relatively infrequent serious side effects, especially compared with the immunosuppressive and cytotoxic agents otherwise employed to treat these diseases. Further studies of optimal dosing, combination with other therapies, and long-term benefits and side effects will emerge from future trials.

Delirium has been recognized for the last 3 millennia and is the most common complication found in hospitalized patients aged 65 and older in the United States. However, critical basic science and clinical research did not progress until the DSM III criteria clearly defined delirium 20 years ago. The term delirium then replaced many nonspecific entities, such as acute confusion state, acute brain syndrome, metabolic encephalopathy, and toxic psychosis. This review discusses the epidemiology, risk factors, interventions, causes, management, and outcomes of delirium. The pathophysiology of delirium has the potential to radically alter our management of delirium and is a controversial area of research.

The advent of symptomatic therapies for Alzheimer disease has placed increasing emphasis on early diagnosis of the dementia syndrome and its various types. This article reviews the definition and epidemiology of the condition that affects up to 50% of all Americans over the age of 80. Also discussed are the main causes of dementia, focusing on those that are not Alzheimer disease and a diagnostic approach that is based on guidelines recently published by the American Academy of Neurology.

The occurrence of additional cardiovascular events when the diastolic blood pressure is lowered below a critical level is referred to as “the diastolic J curve.” Although the critical level of diastolic blood pressure where the J curve begins is not certain, increasingly strong evidence from prospective, controlled studies has confirmed the existence of such a J curve. With the likely addition of more patients who will be treated more vigorously, in particular, elderly subjects with isolated systolic hypertension, the potential for an increase in the number of adverse cardiovascular events must be considered and caution used to avoid too low a diastolic blood pressure.

As more high-risk hypertensives are treated and the need for more intensive antihypertensive therapy is recognized, combination therapies are increasingly used. For initial therapy, particularly for relatively low-risk patients, low-dose combinations are often appropriate. For those who require additional therapy, higher doses of combinations may provide further efficacy while minimizing dose-dependent side effects of monotherapy, thereby improving adherence to therapy. Those combination agents should provide 24-h control with one daily dose, thereby ensuring protection in the early morning hours. Combining an angiotensin converting enzyme inhibitor and a calcium channel blocker is a rational approach to treating hypertension. Not only does it provide significantly better blood pressure control than individual components used as monotherapy, it also minimizes dose-dependent side effects. Also, combining agents from different classes results in complementary mechanisms of action that provide other cardiovascular protective benefits.

The rapidly growing number of patients with coexisting diabetes and hypertension must be intensively treated to protect them from their very high risk for premature cardiovascular morbidity and mortality. After careful ascertainment of their out-of-the-office blood pressure, and testing for postural hypotension, therapy should consist of both lifestyle modifications and antihypertensive drugs. Usually, two or more such drugs are needed to bring blood pressure below the 130/85 mm Hg level. In addition, control of hyperglycemia and dyslipidemia is usually required. Despite the costs and difficulties of achieving adequate control of these diseases, such patients can be protected from the debilities of diabetes and hypertension.

The use of vasodilator therapy in chronic AR and MR may be beneficial in selected patients and harmful in others. The hemodynamics of the two conditions are different and must be taken into account. In AR, vasodilators reduce afterload mismatch and can preserve LV function and delay the need for surgery. However, if the patient has severely reduced diastolic blood pressure, vasodilators could potentially impair coronary perfusion. In MR, vasodilators may reduce regurgitant volume and LV preload depending on the mechanism of MR. In patients with MR caused by dilated cardiomyopathy, vasodilators reduce symptoms, and improve functional class. However, in mitral valve prolapse or hypertrophic cardiomyopathy, vasodilators may worsen the MR and should be avoided. In other primary causes of MR, vasodilators could potentially mask the development of LV dysfunction and lead to unnecessary and harmful delays in surgery.

The current US dietary guideline for sodium is a limit of 2.4 g/d or 6 g NaCl/d. This amount of sodium is far in excess of any physiologic need and is likely an essential though not by itself sufficient primary cause of hypertension as well as a contributor to many other cardiovascular and renal abnormalities. The evidence incriminating the current excessive consumption of sodium derives from epidemiologic, experimental, and interventional data, most of which support a threshold of approximately 100 mmol/d for the harmful effects of sodium to be expressed. Although the current recommendation may not be low enough to go below that threshold, it is an appropriate and attainable goal for now.

(2000). Other Views (Commentary on “Antihypertensive Therapy: Beta-Blockers and Diuretics”) Baylor University Medical Center Proceedings: Vol. 13, No. 2, pp. 131-136.

Background: In March of 1998, The Advisory Commission on Consumer Protection and Quality in Health Industry released a report in response to the US Presidential Executive Order that recommended increasing funding for outcomes research. This report indicated that outcomes research was critical to assessing the effectiveness of treatment and the quality of care. Methods: A systematic review was conducted of the pertinent English literature that describes the development, methods, and limitations of outcomes research to identify methods for minimizing its limitations. Results: Current evidence indicates that approximately 80°/0 of commonly used medical treatments have not been shown to be efficacious, primarily because the necessary randomized controlled trials have not been conducted because of methodological problems, the time required for their execution, the expense, or ethical reasons. Therefore, physicians disagree on the value of many common clinical practices, which is reflected in the large variation in medical care prescribed for different populations. Outcomes research, which is conducted under actual clinical practice conditions using effectiveness studies, offers an efficient approach for investigating the link between medical care and outcomes. However, the major limitation of past outcomes research has been its limited ability to link medical care with outcomes, because of the lack of theory development to guide the research process, inadequate data sources, or both. Conclusions: The literature review suggests that the use of pertinent theoretical constructs to guide the outcomes research process will generate the results needed to assess the effectiveness of treatment and the quality of care.

In the past few years, angiotensin II-receptor blockers have become available and are being heavily marketed and increasingly used. In various ways they differ from angiotensin-converting enzyme inhibitors (ACEIs). Until outcome data are available, they should continue to be used primarily in patients who should receive an ACEI but cannot tolerate the drug because of cough.

Asthma responds to conventional therapy in the majority of patients. However, attention has recently focused on the 1 to 15% of asthmatics who are thought to manifest severe asthma, which responds poorly to commonly used regimens. In this review, current knowledge about the pathogenesis of severe asthma is reviewed and several distinct clinical syndromes of severe asthma are discussed.

Diuretics have been, except for during a few recent years, the most commonly used therapy for hypertension. Although use of these agents fell significantly in the early 1990s, since then it has begun to increase again. Their recent return to popularity reflects 3 major factors: (i) recognition of the effectiveness of much lower dosages than previously used, thereby providing good antihypertensive activity with fewer adverse effects; (ii) the excellent reductions in morbidity and mortality achieved by low dosage diuretic-based therapy in multiple randomised controlled trials in elderly patients with hypertension; and (iii) the increasing recognition that some diuretic-induced shrinkage of effective blood volume is essential for the adequate treatment of many, if not most, patients with hypertension. Therefore, diuretics will probably continue to be the basis for antihypertensive therapy, and the indapamide sustained release 1.5 mg formulation provides all the essential characteristics of diuretic therapy.