Eugene Braunwald

Bio: Eugene Braunwald is an academic researcher from Brigham and Women's Hospital. The author has contributed to research in topics: Myocardial infarction & TIMI. The author has an hindex of 230, co-authored 1711 publications receiving 264576 citations. Previous affiliations of Eugene Braunwald include Boston University & University of California, San Francisco.

Predictors of heart failure in patients with stable coronary artery disease: a PEACE study.

Abstract: Background— Heart failure (HF) is a disease commonly associated with coronary artery disease. Most risk models for HF development have focused on patients with acute myocardial infarction. The Prevention of Events with Angiotensin-Converting Enzyme Inhibition population enabled the development of a risk model to predict HF in patients with stable coronary artery disease and preserved ejection fraction. Methods and Results— In the 8290, Prevention of Events with Angiotensin-Converting Enzyme Inhibition patients without preexisting HF, new-onset HF hospitalizations, and fatal HF were assessed over a median follow-up of 4.8 years. Covariates were evaluated and maintained in the Cox regression multivariable model using backward selection if P<0.05. A risk score was developed and converted to an integer-based scoring system. Among the Prevention of Events with Angiotensin-Converting Enzyme Inhibition population (age, 64�8; female, 18%; prior myocardial infarction, 55%), there were 268 cases of fatal and nonfat...

Physiological Differences between the Effects of Neuronally Released and Bloodborne Norepinephrine on Beta Adrenergic Receptors in the Arterial Bed of the Dog

Abstract: This investigation was designed to define the role of the beta adrenergic receptors in the regulation of peripheral vascular resistance and to determine whether norepinephrine released from nerve terminals acts at the same receptor sites in the arterial bed as injected norepinephrine. In 34 anesthetized dogs the skinned hindlimb was perfused at a constant flow rate, and in 8 dogs a segment of the splanchnic vascular bed was similarly perfused through the aorta. The hemodynamic responses of the isolated perfused beds of control dogs were compared with those of dogs in which the alpha receptors had previously been blocked with phenoxybenzamine, thereby maximizing any contribution of the beta receptors. In the control animals, both carotid sinus hypotension and norepinephrine administered directly into the perfused segment increased vascular resistance. In those animals subjected to alpha-receptor blockade, carotid sinus hypotension still caused reflex vasoconstriction, though it was considerably attenuated, but intra-arterially injected norepinephrine produced vasodilation. Following subsequent beta-receptor blockade, no potentiation of reflex constriction occurred, although the response to injected norepinephrine reverted to constriction. These findings suggest that norepinephrine released from nerve terminals in the arterial tree does not produce physiologically significant beta-receptor stimulation; humorally transported norepinephrine, however, stimulates both alpha and beta receptors.

Reflex Control of the Systemic Venous Bed

Abstract: In a series of investigations on the control of venous tone, it was shown in anesthetized, open-chest dogs on cardiopulmonary bypass that venoconstriction occurs during the infusions of norepinephrine and epinephrine, while trimethaphan results in venodilatation. Lowering the pressure acting on the carotid baroreceptors and on the receptors within the left atrium and left ventricle results in reflex venoconstriction, while stimulation of these receptors relaxes the veins. Hypoxia produces venoconstriction as a result of stimulation of the carotid chemoreceptors, but the veno constriction which results from hypercapnia evidently is primarily central in origin. Reflex venoconstriction to carotid occlusion and central vagal stimulation can be blocked by the administration of guanethidine and reserpine. In intact, unanesthetized human subjects, to whom these drugs were administered orally in doses which are commonly utilized in clinical practice, reflex venoconstriction of the forearm veins was blocked. These investigations emphasize that the systemic venous bed reacts vigorously to neural and humoral stimuli, and that these reactions profoundly alter the cardiac output. In this manner, by exerting control of the rate at which the blood is delivered into the systemic arterial bed, the venous side of the circulation plays an important role in the control of the arterial pressure as well.

Reconsidering the Role for Digoxin in the Management of Acute Heart Failure Syndromes

Abstract: THE USE OF DIGITALIS PREPARATIONS FOR TREATMENT of cardiac maladies has been debated for centuries. Controversy regarding their effect on mortality has been the primary issue, given their relatively narrow toxic-therapeutic ratio. This led to the Digitalis Investigation Group trial, organized and conducted by the National Heart, Lung, and Blood Institute and the Department of Veterans Affairs. The trial, which involved patients with chronic heart failure and in sinus rhythm, demonstrated that, although digoxin did not affect survival, it was effective at reducing hospitalizations of patients receiving standard therapy—consisting of diuretics and angiotensinconverting enzyme (ACE) inhibitors—for heart failure. As a result, the US Food and Drug Administration granted regulatory approval to digoxin for the treatment of heart failure and atrial fibrillation in 1997. However, available data from registries and clinical trials of heart failure suggest that digoxin use has decreased considerably, from approximately 80% to 30% in the last 10 years. Several factors may have contributed to this decreased use of digoxin. Digoxin has received little attention at large cardiology meetings; has not been promoted by the pharmaceutical industry, given the very low cost of this generic drug; and has been supplanted by the introduction of life-saving therapies for heart failure including -blockers, angiotensin-receptor blocking agents, aldosterone-blocking agents, and cardiac resynchronization therapies. Moreover, retrospective studies of the Digitalis Investigation Group trial raised serious safety concerns, particularly for women, which may have further contributed to the decreased use of digoxin. Forgetting a drug is not necessarily a tragedy. In the last decade, however, registries and trials of acute heart failure syndromes resulting in hospitalization have shown mortality and rehospitalization rates as high as 15% and 30%, respectively, within 90 days of discharge. This high event rate occurred in patients already receiving evidence-based therapies, including loop diuretics, -blockers, ACE inhibitors, and angiotensin-receptor blockers. Although the main reason for heart failure–related admission and readmission results from hemodynamic instability due to a high left ventricular filling pressure, low cardiac output, or both, every new agent tested to date known to improve hemodynamics in acute heart failure syndromes has not been shown to be either efficacious or safe. In the last 15 years, only nesiritide has been approved by the Food and Drug Administration for acute heart failure syndromes, even though safety issues for nesiritide were raised after it was approved, including renal function impairment and, more importantly, mortality. The most recently evaluated agent, rolofylline, an adenosine-blocking agent, did not demonstrate clinical benefit and showed an increase in central nervous system events. With this background, the role of digoxin in acute heart failure syndromes should be reexamined. What would be an ideal agent for treatment of acute heart failure syndromes? Such a drug should (1) improve hemodynamics without adversely affecting heart rate or blood pressure or increasing myocardial oxygen demand and without reducing coronary perfusion; (2) prevent further neurohormonal activation, favorably modulate the existing neurohormonal milieu, or both; (3) be applicable in the context of known evidence-based therapies, such as ACE inhibitors and -blockers; (4) help control ventricular rate in atrial fibrillation; (5) have a formulation for intravenous use during the acute phase of heart failure and an oral formulation for long-term use; (6) importantly, improve symptoms and signs, decrease rehospitalization rate, improve survival, or all 3; and (7) be affordable for the millions of patients with heart failure throughout the world. This last point is particularly important because many patients with heart failure cannot afford newer, much more expensive drugs. Digoxin has many of these properties. It improves hemodynamics acutely, both at rest and with exercise. These hemodynamic effects are additive when digoxin is used with other vasoactive agents. Digoxin has beneficial neurohormonal actions, does not impair renal function, and has a neutral or beneficial effect on heart rate and blood pressure. The intravenous form can easily be switched to the oral form, which is taken once a day. Digoxin is inexpensive, and thera-

The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: the JNC 7 report.

Abstract: "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure" provides a new guideline for hypertension prevention and management. The following are the key messages(1) In persons older than 50 years, systolic blood pressure (BP) of more than 140 mm Hg is a much more important cardiovascular disease (CVD) risk factor than diastolic BP; (2) The risk of CVD, beginning at 115/75 mm Hg, doubles with each increment of 20/10 mm Hg; individuals who are normotensive at 55 years of age have a 90% lifetime risk for developing hypertension; (3) Individuals with a systolic BP of 120 to 139 mm Hg or a diastolic BP of 80 to 89 mm Hg should be considered as prehypertensive and require health-promoting lifestyle modifications to prevent CVD; (4) Thiazide-type diuretics should be used in drug treatment for most patients with uncomplicated hypertension, either alone or combined with drugs from other classes. Certain high-risk conditions are compelling indications for the initial use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, β-blockers, calcium channel blockers); (5) Most patients with hypertension will require 2 or more antihypertensive medications to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg for patients with diabetes or chronic kidney disease); (6) If BP is more than 20/10 mm Hg above goal BP, consideration should be given to initiating therapy with 2 agents, 1 of which usually should be a thiazide-type diuretic; and (7) The most effective therapy prescribed by the most careful clinician will control hypertension only if patients are motivated. Motivation improves when patients have positive experiences with and trust in the clinician. Empathy builds trust and is a potent motivator. Finally, in presenting these guidelines, the committee recognizes that the responsible physician's judgment remains paramount.

Cochrane Handbook for Systematic Reviews of Interventions

Abstract: The Cochrane Handbook for Systematic Reviews of Interventions is the official document that describes in detail the process of preparing and maintaining Cochrane systematic reviews on the effects of healthcare interventions.

Atherosclerosis — An Inflammatory Disease

Abstract: Atherosclerosis is an inflammatory disease. Because high plasma concentrations of cholesterol, in particular those of low-density lipoprotein (LDL) cholesterol, are one of the principal risk factors for atherosclerosis,1 the process of atherogenesis has been considered by many to consist largely of the accumulation of lipids within the artery wall; however, it is much more than that. Despite changes in lifestyle and the use of new pharmacologic approaches to lower plasma cholesterol concentrations,2,3 cardiovascular disease continues to be the principal cause of death in the United States, Europe, and much of Asia.4,5 In fact, the lesions of atherosclerosis represent . . .

Lifetime Prevalence and Age-of-Onset Distributions of DSM-IV Disorders in the National Comorbidity Survey Replication

Abstract: Context Little is known about lifetime prevalence or age of onset of DSM-IV disorders. Objective To estimate lifetime prevalence and age-of-onset distributions of DSM-IV disorders in the recently completed National Comorbidity Survey Replication. Design and Setting Nationally representative face-to-face household survey conducted between February 2001 and April 2003 using the fully structured World Health Organization World Mental Health Survey version of the Composite International Diagnostic Interview. Participants Nine thousand two hundred eighty-two English-speaking respondents aged 18 years and older. Main Outcome Measures Lifetime DSM-IV anxiety, mood, impulse-control, and substance use disorders. Results Lifetime prevalence estimates are as follows: anxiety disorders, 28.8%; mood disorders, 20.8%; impulse-control disorders, 24.8%; substance use disorders, 14.6%; any disorder, 46.4%. Median age of onset is much earlier for anxiety (11 years) and impulse-control (11 years) disorders than for substance use (20 years) and mood (30 years) disorders. Half of all lifetime cases start by age 14 years and three fourths by age 24 years. Later onsets are mostly of comorbid conditions, with estimated lifetime risk of any disorder at age 75 years (50.8%) only slightly higher than observed lifetime prevalence (46.4%). Lifetime prevalence estimates are higher in recent cohorts than in earlier cohorts and have fairly stable intercohort differences across the life course that vary in substantively plausible ways among sociodemographic subgroups. Conclusions About half of Americans will meet the criteria for a DSM-IV disorder sometime in their life, with first onset usually in childhood or adolescence. Interventions aimed at prevention or early treatment need to focus on youth.

Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure

Abstract: The National High Blood Pressure Education Program presents the complete Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure. Like its predecessors, the purpose is to provide an evidence-based approach to the prevention and management of hypertension. The key messages of this report are these: in those older than age 50, systolic blood pressure (BP) of greater than 140 mm Hg is a more important cardiovascular disease (CVD) risk factor than diastolic BP; beginning at 115/75 mm Hg, CVD risk doubles for each increment of 20/10 mm Hg; those who are normotensive at 55 years of age will have a 90% lifetime risk of developing hypertension; prehypertensive individuals (systolic BP 120-139 mm Hg or diastolic BP 80-89 mm Hg) require health-promoting lifestyle modifications to prevent the progressive rise in blood pressure and CVD; for uncomplicated hypertension, thiazide diuretic should be used in drug treatment for most, either alone or combined with drugs from other classes; this report delineates specific high-risk conditions that are compelling indications for the use of other antihypertensive drug classes (angiotensin-converting enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, calcium channel blockers); two or more antihypertensive medications will be required to achieve goal BP (<140/90 mm Hg, or <130/80 mm Hg) for patients with diabetes and chronic kidney disease; for patients whose BP is more than 20 mm Hg above the systolic BP goal or more than 10 mm Hg above the diastolic BP goal, initiation of therapy using two agents, one of which usually will be a thiazide diuretic, should be considered; regardless of therapy or care, hypertension will be controlled only if patients are motivated to stay on their treatment plan. Positive experiences, trust in the clinician, and empathy improve patient motivation and satisfaction. This report serves as a guide, and the committee continues to recognize that the responsible physician's judgment remains paramount.