Eric J. Topol

Bio: Eric J. Topol is an academic researcher from Scripps Health. The author has contributed to research in topics: Myocardial infarction & Angioplasty. The author has an hindex of 193, co-authored 1373 publications receiving 151025 citations. Previous affiliations of Eric J. Topol include Loyola University Chicago & Cleveland Clinic.

Relation of Increased Arterial Blood Pressure to Mortality and Stroke in the Context of Contemporary Thrombolytic Therapy for Acute Myocardial Infarction: A Randomized Trial

Abstract: Background : Despite concern that hypertension increases the risk for intracranial hemorrhage during thrombolysis for acute myocardial infarction, the exact nature of the risk remains unclear. Objective : To assess the effects of previous hypertension and blood pressure at study entry on the outcomes of patients who had acute myocardial infarction and received thrombolysis. Design : Randomized trial. Setting : 1081 hospitals in 15 countries. Patients : 41 021 patients who had myocardial infarction accompanied by ST-segment elevation and who presented to hospitals within 6 hours of symptom onset. Intervention : One of four thrombolytic regimens. Main Outcome Measures : Mortality, stroke subtypes, and death plus disabling stroke in patients with previous hypertension and as functions of blood pressure at entry. Logistic regression analysis of relations among blood pressure at entry, baseline characteristics, and treatment effects. Results : The incidence of total stroke and intracranial hemorrhage increased as systolic blood pressure at entry increased and was particularly high for systolic pressures of about 175 mm Hg or more (incidence of total stroke, 3.4% compared with 1.17% for pressures between 100 and 124 mm Hg). Patients who had systolic blood pressure of 175 mm Hg or more at entry and who received accelerated alteplase therapy had a lower rate of death within 30 days (4.3% compared with 7.8% ; P = 0.044) and a lower rate of death plus disabling stroke (4.9% compared with 8.9% ; P = 0.031) than patients treated with streptokinase, despite having higher rates of total and hemorrhagic stroke (incidence of hemorrhagic stroke, 2.3% compared with 1.5%). Assumptions based on previous trials and rates of stroke from the GUSTO-I (Global Utilization of Streptokinase and t-PA for Occluded Coronary Arteries) trial suggest that in hypertensive patients with low risk for death from cardiac causes (no previous infarction, Killip class I), the risk-to-benefit ratio with thrombolysis is about unity, with about 13 lives saved per 1000 persons treated at the risk of about 13 intracranial hemorrhages. Conclusions : Patients with myocardial infarction and very elevated blood pressure who have thrombolysis and patients with myocardial infarction who do not have elevated blood pressure have a similar risk for death, but the risk for stroke is higher in the former group. Future studies should assess 1) the risk-to-benefit ratio of thrombolysis in these patients, especially those at low risk for death from cardiac causes, and 2) whether decreasing elevated blood pressure before thrombolysis reduces the incidence of stroke without increasing mortality rates.

Management and outcome of patients with atrial fibrillation during acute myocardial infarction: the GUSTO-III experience

Abstract: Objective: To investigate the use of antiarrhythmic agents and electrical cardioversion in the management of patients with atrial fibrillation complicating acute myocardial infarction, and their relation to 30 day and one year mortality. Design: Prospective study of 1138 patients with atrial fibrillation from the GUSTO-III trial. Interventions: Of the 1138 study patients, 317 (28%) received antiarrhythmic treatment, including class I antiarrhythmic agents (12%), sotalol (5%), and amiodarone (15%); electrical cardioversion was attempted in 116 (10%). Results: Sinus rhythm was restored in 72% of patients receiving class I antiarrhythmic agents, 67% of those receiving sotalol, 79% of those receiving amiodarone, and 64% of those having electrical cardioversion. After adjusting for baseline characteristics and complications occurring before the onset of atrial fibrillation, there was no difference among the treatment groups in the incidence of sinus rhythm at the time of discharge or before deterioration to hospital death. However, the use of class I antiarrhythmic drugs or sotalol was associated with a lower unadjusted 30 day and one year mortality. After adjustment for baseline factors and pre-atrial fibrillation complications, the odds ratios for 30 day and one year mortality were 0.42 (95% confidence interval (CI) 0.19 to 0.89) and 0.58 (95% CI 0.33 to 1.04) with class I agents, and 0.31 (95% CI 0.07 to 1.32) and 0.31 (95% CI 0.09 to 1.02) with sotalol. In contrast, there was no association between the use of amiodarone or electrical cardioversion and 30 day or one year mortality. Conclusions: There was a strong trend towards lower mortality associated with the use of class I antiarrhythmic agents or sotalol in managing patients with atrial fibrillation after acute myocardial infarction. Randomised trials are indicated.

The impact of anthropomorphic indices on clinical outcomes in patients with acute ST-elevation myocardial infarction.

Abstract: Aims Multiple studies have focused on the relationship of body anthropometric measures with clinical events in ST-elevation myocardial infarction (STEMI) patients, highlighting the ‘obesity paradox’. However, the relative prognostic importance of these measures over other baseline variables is less known. Method and results We performed a retrospective analysis of 94 108 STEMI patients from seven clinical trials evaluating various reperfusion strategies to study the relationship and prognostic importance of height, weight, body mass index (BMI), and body surface area (BSA) with 30-day death and in-hospital cardiogenic shock, major bleeding, and stroke. Main outcome measures of interest included 30-day death and in-hospital cardiogenic shock, major bleeding, and stroke. Weight, BMI, and BSA were inversely and independently related to all clinical events. Despite being statistically significant ( P < 0.0001), the prognostic information contributed by weight beyond that conferred by baseline clinical factors was minimal (<1% of total prognostic information) making it of limited clinical relevance for predicting 30-day death and cardiogenic shock. In contrast, weight accounted for 8.4% and 4.3% of the prognostic information in the logistic regression models for major bleeding and for stroke. BMI or BSA added little incremental value over simple measure of weight. Conclusion Although statistically significantly related to most outcomes in patients with STEMI including death and shock, body weight provided clinically relevant prognostic information only for the risk of major bleeding and of stroke. Furthermore, BMI or BSA contributed little incremental prognostic information beyond that provided by weight alone. Thus, the existing large body of information concerning the strong prognostic importance of anthropometric measures with outcomes after STEMI should be interpreted in the context of other more important risk factors.

Adjuncts to thrombolysis for myocardial reperfusion.

Abstract: ▪ Objective: To discuss adjunctive pharmacologic agents for acute myocardial infarction, to critique their initial effects in clinical trials, and to review their potential for improving the clinic...

The influence of body mass index on mortality and bleeding among patients with or at high-risk of atherothrombotic disease

Abstract: Aims We aimed to determine the relationship between body mass index (BMI) and cardiovascular events among individuals with or at-risk of atherothrombotic disease. Methods and results This was a prospective observational study of 15 532 patients enrolled in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial who were randomly assigned to clopidogrel or placebo, and followed-up for a median of 28 months for the occurrence of the primary endpoint (cardiovascular death, myocardial infarction, or stroke), all-cause mortality, and bleeding complications. Compared with the highest BMI quartile, the primary endpoint, cardiovascular, and all-cause mortality all occurred more frequently among patients in the lowest BMI quartile (about a third lower). The relationship between continuous BMI and adverse cardiovascular outcomes were presented as two linear spline terms with 29 kg/m2 as the cut-point for all-cause mortality. Lower BMI was associated with an increase in moderate and severe bleeding complications, largely accounted for by those receiving dual-antiplatelet agents with the highest tertile aspirin dose. Conclusion Adverse cardiovascular events and bleeding complications occurred more frequently among individuals with or at-risk for atherothrombotic disease and low BMI. Further studies should be directed to these patients to improve outcomes. The CHARISMA trial is registered with ClinicalTrials.gov, NCT00050817.

PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage Analyses

Abstract: Whole-genome association studies (WGAS) bring new computational, as well as analytic, challenges to researchers. Many existing genetic-analysis tools are not designed to handle such large data sets in a convenient manner and do not necessarily exploit the new opportunities that whole-genome data bring. To address these issues, we developed PLINK, an open-source C/C++ WGAS tool set. With PLINK, large data sets comprising hundreds of thousands of markers genotyped for thousands of individuals can be rapidly manipulated and analyzed in their entirety. As well as providing tools to make the basic analytic steps computationally efficient, PLINK also supports some novel approaches to whole-genome data that take advantage of whole-genome coverage. We introduce PLINK and describe the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation. In particular, we focus on the estimation and use of identity-by-state and identity-by-descent information in the context of population-based whole-genome studies. This information can be used to detect and correct for population stratification and to identify extended chromosomal segments that are shared identical by descent between very distantly related individuals. Analysis of the patterns of segmental sharing has the potential to map disease loci that contain multiple rare variants in a population-based linkage analysis.

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.

2013 ESH/ESC Guidelines for the management of arterial hypertension: The Task Force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC).

Abstract: ABCD : Appropriate Blood pressure Control in Diabetes ABI : ankle–brachial index ABPM : ambulatory blood pressure monitoring ACCESS : Acute Candesartan Cilexetil Therapy in Stroke Survival ACCOMPLISH : Avoiding Cardiovascular Events in Combination Therapy in Patients Living with Systolic Hypertension ACCORD : Action to Control Cardiovascular Risk in Diabetes ACE : angiotensin-converting enzyme ACTIVE I : Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events ADVANCE : Action in Diabetes and Vascular Disease: Preterax and Diamicron-MR Controlled Evaluation AHEAD : Action for HEAlth in Diabetes ALLHAT : Antihypertensive and Lipid-Lowering Treatment to Prevent Heart ATtack ALTITUDE : ALiskiren Trial In Type 2 Diabetes Using Cardio-renal Endpoints ANTIPAF : ANgioTensin II Antagonist In Paroxysmal Atrial Fibrillation APOLLO : A Randomized Controlled Trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly People ARB : angiotensin receptor blocker ARIC : Atherosclerosis Risk In Communities ARR : aldosterone renin ratio ASCOT : Anglo-Scandinavian Cardiac Outcomes Trial ASCOT-LLA : Anglo-Scandinavian Cardiac Outcomes Trial—Lipid Lowering Arm ASTRAL : Angioplasty and STenting for Renal Artery Lesions A-V : atrioventricular BB : beta-blocker BMI : body mass index BP : blood pressure BSA : body surface area CA : calcium antagonist CABG : coronary artery bypass graft CAPPP : CAPtopril Prevention Project CAPRAF : CAndesartan in the Prevention of Relapsing Atrial Fibrillation CHD : coronary heart disease CHHIPS : Controlling Hypertension and Hypertension Immediately Post-Stroke CKD : chronic kidney disease CKD-EPI : Chronic Kidney Disease—EPIdemiology collaboration CONVINCE : Controlled ONset Verapamil INvestigation of CV Endpoints CT : computed tomography CV : cardiovascular CVD : cardiovascular disease D : diuretic DASH : Dietary Approaches to Stop Hypertension DBP : diastolic blood pressure DCCT : Diabetes Control and Complications Study DIRECT : DIabetic REtinopathy Candesartan Trials DM : diabetes mellitus DPP-4 : dipeptidyl peptidase 4 EAS : European Atherosclerosis Society EASD : European Association for the Study of Diabetes ECG : electrocardiogram EF : ejection fraction eGFR : estimated glomerular filtration rate ELSA : European Lacidipine Study on Atherosclerosis ESC : European Society of Cardiology ESH : European Society of Hypertension ESRD : end-stage renal disease EXPLOR : Amlodipine–Valsartan Combination Decreases Central Systolic Blood Pressure more Effectively than the Amlodipine–Atenolol Combination FDA : U.S. Food and Drug Administration FEVER : Felodipine EVent Reduction study GISSI-AF : Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico-Atrial Fibrillation HbA1c : glycated haemoglobin HBPM : home blood pressure monitoring HOPE : Heart Outcomes Prevention Evaluation HOT : Hypertension Optimal Treatment HRT : hormone replacement therapy HT : hypertension HYVET : HYpertension in the Very Elderly Trial IMT : intima-media thickness I-PRESERVE : Irbesartan in Heart Failure with Preserved Systolic Function INTERHEART : Effect of Potentially Modifiable Risk Factors associated with Myocardial Infarction in 52 Countries INVEST : INternational VErapamil SR/T Trandolapril ISH : Isolated systolic hypertension JNC : Joint National Committee JUPITER : Justification for the Use of Statins in Primary Prevention: an Intervention Trial Evaluating Rosuvastatin LAVi : left atrial volume index LIFE : Losartan Intervention For Endpoint Reduction in Hypertensives LV : left ventricle/left ventricular LVH : left ventricular hypertrophy LVM : left ventricular mass MDRD : Modification of Diet in Renal Disease MRFIT : Multiple Risk Factor Intervention Trial MRI : magnetic resonance imaging NORDIL : The Nordic Diltiazem Intervention study OC : oral contraceptive OD : organ damage ONTARGET : ONgoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial PAD : peripheral artery disease PATHS : Prevention And Treatment of Hypertension Study PCI : percutaneous coronary intervention PPAR : peroxisome proliferator-activated receptor PREVEND : Prevention of REnal and Vascular ENdstage Disease PROFESS : Prevention Regimen for Effectively Avoiding Secondary Strokes PROGRESS : Perindopril Protection Against Recurrent Stroke Study PWV : pulse wave velocity QALY : Quality adjusted life years RAA : renin-angiotensin-aldosterone RAS : renin-angiotensin system RCT : randomized controlled trials RF : risk factor ROADMAP : Randomized Olmesartan And Diabetes MicroAlbuminuria Prevention SBP : systolic blood pressure SCAST : Angiotensin-Receptor Blocker Candesartan for Treatment of Acute STroke SCOPE : Study on COgnition and Prognosis in the Elderly SCORE : Systematic COronary Risk Evaluation SHEP : Systolic Hypertension in the Elderly Program STOP : Swedish Trials in Old Patients with Hypertension STOP-2 : The second Swedish Trial in Old Patients with Hypertension SYSTCHINA : SYSTolic Hypertension in the Elderly: Chinese trial SYSTEUR : SYSTolic Hypertension in Europe TIA : transient ischaemic attack TOHP : Trials Of Hypertension Prevention TRANSCEND : Telmisartan Randomised AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease UKPDS : United Kingdom Prospective Diabetes Study VADT : Veterans' Affairs Diabetes Trial VALUE : Valsartan Antihypertensive Long-term Use Evaluation WHO : World Health Organization ### 1.1 Principles The 2013 guidelines on hypertension of the European Society of Hypertension (ESH) and the European Society of Cardiology …

An integrated encyclopedia of DNA elements in the human genome

Abstract: The human genome encodes the blueprint of life, but the function of the vast majority of its nearly three billion bases is unknown. The Encyclopedia of DNA Elements (ENCODE) project has systematically mapped regions of transcription, transcription factor association, chromatin structure and histone modification. These data enabled us to assign biochemical functions for 80% of the genome, in particular outside of the well-studied protein-coding regions. Many discovered candidate regulatory elements are physically associated with one another and with expressed genes, providing new insights into the mechanisms of gene regulation. The newly identified elements also show a statistical correspondence to sequence variants linked to human disease, and can thereby guide interpretation of this variation. Overall, the project provides new insights into the organization and regulation of our genes and genome, and is an expansive resource of functional annotations for biomedical research.