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.

Effects of prior aspirin and anti-ischemic therapy on outcome of patients with unstable angina. TIMI 7 Investigators. Thrombin Inhibition in Myocardial Ischemia.

Abstract: Both aspirin and beta-adrenergic blocking drugs have been shown to reduce the risk of death or acute myocardial infarction (AMI) in patients with unstable angina, but their effect during chronic use on the presentation of acute coronary syndromes is less well defined Calcium antagonists and oral nitrates are also widely prescribed for patients with coronary disease, but their effect on presentation of acute myocardial ischemia is unknown We retrospectively examined the effects of prior aspirin and anti-ischemic medical therapy on clinical events in 410 patients hospitalized for unstable angina Ischemic pain occurred at rest for a duration of 5 to 60 minutes During hospitalization, 97% of patients received aspirin and all received the direct thrombin inhibitor bivalirudin for at least 72 hours Despite being older and more likely to have risk factors for coronary disease and poor outcome, patients receiving aspirin before admission were less likely to present with non-Q-wave AMI (5% vs 14% in patients not on aspirin, p = 0004) Prior beta blocker, calcium antagonist, or nitrate administration did not appear to modify presentation as unstable angina or non-Q-wave AMI In a multivariate model, the combined incidence of death, AMI not present at enrollment, or recurrent angina was best predicted by age (adjusted odds ratio [95% confidence interval] 238 [114 to 398]) and presence of electrocardiographic changes with pain on presentation (adjusted odds ratio 283 [150 to 535]) but was not related to prior or in-hospital medical therapy Thus, aspirin but not anti-ischemic therapy before hospitalization of patients with unstable angina was associated with a decreased incidence of non-Q-wave AMI on admission

Baseline characteristics of the patient population in the Saxagliptin Assessment of Vascular Outcomes Recorded in patients with diabetes mellitus (SAVOR)-TIMI 53 trial.

Abstract: Background and aims SAVOR-TIMI 53 was designed to study the effects of the DPP-4 inhibitor saxagliptin on cardiovascular outcomes in high risk type 2 diabetes patients with diverse levels of diabetes control and background anti-diabetic drugs. The goal of this article is to describe the baseline characteristics of this hypothesis driven study. Materials and methods A total of 16 496 diabetic patients from North America (31.9%), Western Europe (26.0%), Eastern Europe (17.3%), Latin America (16.4%) and Asia (8.3%), with either established cardiovascular disease (78.3%) or with ≥two additional cardiovascular risk factors (21.7%) were randomised to saxagliptin or placebo. Biomarkers of inflammation and insulin resistance were taken at baseline and 2 years later in order to correlate saxagliptin effect on cardiovascular outcome to its effect on inflammation and insulin resistance. Results Mean [+/−standard deviation (SD)] age was 65.0 (+/−8.6) years, 66.9% were male, body mass index was 31.2 kg/m2 (+/−5.6), mean diabetes duration was 11.9 years (+/−8.9) and the mean HbA1c 8.0% (+/−1.4%). HbA1c 9% was 30.7% in Latin America 27.0% in Asia and 15.1% in North America. Diabetic retinopathy was reported in 12.3% of patients, nephropathy in 17.7% and amputation in 2.5%. Diabetic treatments categories were as follows: no medication (5.4%), 1 oral anti-diabetic drug (OAD) (25.0%), ≥2 OAD (27.7%) and/or insulin (40.9%). The prevalence of micro-albuminuria was twice as high among insulin users compared with users of ≥2 OAD. Baseline statin use (78.3% overall) varied by region. Conclusion The SAVOR-TIMI 53 patient population, with differing background diabetes control and anti-diabetic treatment, provides global representation of diabetic patients with established cardiovascular disease or at high risk for cardiovascular disease and is well-positioned to determine the effect of saxagliptin on cardiovascular events. Copyright © 2013 John Wiley & Sons, Ltd.

Combined assessment of thrombolysis in myocardial infarction flow grade, myocardial perfusion grade, and ST-segment resolution to evaluate epicardial and myocardial reperfusion.

Abstract: The restoration of epicardial and myocardial flow remains the primary goal of reperfusion therapy in patients with ST-segment elevation myocardial infarction, but the optimal method to assess this goal has not been defined. Thrombolysis In Myocardial Infarction flow grade (TFG), myocardial perfusion grade (MPG), and ST-segment resolution (STRes) were combined to formulate a new measure of successful reperfusion in 649 patients who received pharmacologic reperfusion therapy in 3 recent phase II clinical trials of ST-segment elevation myocardial infarction. Coronary angiograms and electrocardiograms were analyzed at 60 minutes (before any intervention) after the initiation of reperfusion therapy. The complete restoration of perfusion, or the "trifecta," defined as the presence of TFG 3, MPG 3, and complete (> or =70%) STRes, occurred in 117 patients (18%). The achievement of this trifecta was associated with low rates of 30-day mortality (0% vs 3.9%, p = 0.02), congestive heart failure (CHF) (0.9% vs 7.1%, p = 0.01), and the combination of death or CHF (0.9% vs 10.7%, p = 0.001). When the results were stratified with respect to subsequent percutaneous coronary intervention (PCI) from 60 to 120 minutes, attainment of the trifecta at 60 minutes remained a strong predictor of better clinical outcomes, particularly in those patients who underwent early PCI. The achievement of TFG 3, MPG 3, and complete STRes at 60 minutes after fibrinolytic therapy and before PCI occurred in only 18% of patients but was associated with very low rates of death and CHF at 30 days. This new end point is proposed to evaluate the success of reperfusion therapy in patients who undergo early angiography.

Studies on the function of the adrenergic nerve endings in the heart.

Abstract: IT IS now clear from a iiumber of studies in experimental animals that the force of myocardial contraction can be profoundly augmented by an increase in the sympathetic influences acting upon the heart.'The effects on the myocardium of stimulating the cardiac sympathetic nerves closely resemble those resulting from the injection of the adrenergic neurotransmitter, norepinephrine,6 7 and it has been suggested that the cardiac sympathetic nerves play a fundamental role in regulating the activity of the heart.\" Accordingly, considerable effort is now being directed toward increasing our understanding of the detailed function of the sympathetic nerve endings in the heart and in other organs.9

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.