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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.


Papers
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Journal ArticleDOI
01 Oct 2003-Heart
TL;DR: A raised pre-procedural WBC count in patients undergoing PCI is associated with an increased risk of long term death, suggesting a key role for inflammation in coronary artery disease.
Abstract: Background: Raised inflammatory markers are associated with worse outcome after percutaneous coronary interventions (PCI). An increase in the white blood cell (WBC) count is a non-specific response to inflammation. We hypothesised that a raised baseline WBC count would be a predictor of mortality in patients undergoing PCI. Methods: The association between preprocedural WBC count and long term mortality was studied in 7179 patients enrolled in the EPIC, EPILOG, and EPISTENT trials. The end points were the incidence of myocardial infarction at one year, and one and three year mortality. Results: There were 188 deaths and 582 myocardial infarctions at one year. While WBC count was a strong predictor of death at one year, with every increase of 1 k/μl (1×106/l) being associated with a hazard ratio (HR) of 1.109 (95% confidence interval (CI) 1.072 to 1.147, p < 0.001), there was no association with myocardial infarction at one year (HR 1.020, 95% CI 0.990 to 1.052, p = 0.195). There were a total of 406 deaths at three years with a strong association between WBC count and three year mortality (HR for every 1 k/μl increase 1.089, 95% CI 1.058 to 1.121, p < 0.001). WBC count remained a significant predictor of mortality after multivariable adjustment (HR for every 1 k/μl increase 1.100, 95% CI 1.069 to 1.131, p < 0.001). The association was significant across multiple subgroups, including diabetes, female sex, clinical presentation, and cigarette smoking. Conclusion: A raised pre-procedural WBC count in patients undergoing PCI is associated with an increased risk of long term death. These results suggest a key role for inflammation in coronary artery disease.

108 citations

Journal ArticleDOI
TL;DR: Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively and this association disappeared after adjustment for propensity for early PCI.
Abstract: BACKGROUND: Platelet glycoprotein (GP) IIb/IIIa antagonists prevent the composite end point of death or myocardial infarction (MI) in patients with acute coronary syndromes. There is uncertainty about whether this effect is confined to patients who have percutaneous coronary interventions (PCIs) and whether PCIs further prevent death or MI in patients already treated with GP IIb/IIIa antagonists. METHODS AND RESULTS: PURSUIT patients were treated with the GP IIb/IIIa antagonist eptifibatide or placebo; PCIs were performed according to physician practices. In 2253 of 9641 patients (23.4%), PCI was performed by 30 days. Early (<72 hours) PCI was performed in 1228 (12.7%). In 34 placebo patients (5.5%) and 10 treated with eptifibatide (1.7%) (P=0.001), MI preceded early PCI. In patients censored for PCI across the 30-day period, there was a significant reduction in the primary composite end point in eptifibatide patients (P=0.035). Eptifibatide reduced 30-day events in patients who had early PCI (11.6% versus 16.7%, P=0.01) and in patients who did not (14.6% versus 15.6%, P=0.23). After adjustment for PCI propensity, there was no evidence that eptifibatide treatment effect differed between patients with or without early PCI (P for interaction=0.634). PCI was not associated with a reduction of the primary composite end point but was associated with a reduced (nonspecified) composite of death or Q-wave MI. This association disappeared after adjustment for propensity for early PCI. CONCLUSIONS: Eptifibatide reduced the composite rates of death or MI in PCI patients and those managed conservatively.

108 citations

Journal ArticleDOI
TL;DR: Despite their proven benefits, coronary stents continue to be accompanied by several theoretical and practical limitations: they are costly, typically associated with a more marked degree of neointimal formation than balloon angioplasty, and difficult to use with some lesion subsets such as bifurcation stenoses.
Abstract: During the past 20 years, the equipment used to perform percutaneous coronary revascularization has undergone a dramatic transformation from simple balloon dilatation catheters to sophisticated mechanical devices and endoprostheses. The impetus for this evolution in technology was initially a byproduct of suboptimal immediate and long-term results obtained with standard balloon angioplasty. New techniques, including directional and rotational atherectomy, have resulted in improved procedural success rates, especially for more complex lesion subtypes, although their ability to curtail restenosis remains controversial.1 2 Intracoronary stents have had a dramatic impact on reduction of the incidence of acute complications after failed balloon angioplasty and represent the only currently available strategy shown to limit both clinical and angiographic restenosis.3 4 5 6 7 8 9 10 11 12 Based on these advantages, stent implantation is used in approximately half of all percutaneous interventions in the United States. However, despite their proven benefits, coronary stents continue to be accompanied by several theoretical and practical limitations: they are costly, typically associated with a more marked degree of neointimal formation than balloon angioplasty, and difficult to use with some lesion subsets such as bifurcation stenoses, and they have engendered the new and difficult-to-treat entity of in-stent restenosis. Although the major focus in the field of interventional cardiology over the past decade has been on the development of new devices and adjunctive pharmacological therapies, the short- and long-term success rates after standard balloon angioplasty have improved significantly. Part of the improvement is likely a manifestation of enhanced operator experience and better equipment, but the results of balloon angioplasty have also benefited greatly from the availability of coronary stents for both “bailout” (for actual or threatened abrupt closure) or “backup” (for suboptimal balloon results) indications, potentially allowing a strategy of more aggressive balloon dilatation than could be safely …

107 citations

Journal ArticleDOI
TL;DR: The results propose several new candidate genes for the metabolic syndrome and suggest that the genetic basis of this syndrome may be strongly modified by gender.
Abstract: Major genetic determinants of the metabolic syndrome — a clustering of abdominal obesity, high triglycerides, low HDL cholesterol, high blood pressure and high fasting glucose — remain elusive. We surveyed 207 single-nucleotide polymorphisms in 110 candidate genes among coronary artery disease patients, a population enriched for metabolic abnormalities. The number of abnormalities (0–5) was determined in the 214 male and 91 female patients, and the association with each polymorphism evaluated by means of ordinal regression analysis. Polymorphisms in eight genes, including LDLR, GBE1, IL1R1, TGFB1, IL6, COL5A2, SELE and LIPC, were associated with metabolic syndrome in the whole population (P values ranged from 0.047 to 0.008). Variants in seven additional genes showed significant gene by gender interaction. Among these, separate analyses in men and women revealed a strong association with a silent polymorphism in the low-density lipoprotein receptor-related protein gene, LRPAP1, among females (P=0.0003), but not males (P=0.292). Other genes associated only in females included THBS1, ACAT2, ITGB3, F2 and SELP (P values ranging from 0.032 to 0.002). Only one gene (PRCP) was significantly associated in men alone (P=0.039). Our results propose several new candidate genes for the metabolic syndrome and suggest that the genetic basis of this syndrome may be strongly modified by gender.

107 citations

Journal ArticleDOI
TL;DR: It is demonstrated that pseudothrombocytopenia is a benign laboratory condition that does not increase bleeding, stroke, transfusion requirements or the need for repeat revascularization.

106 citations


Cited by
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TL;DR: This work introduces PLINK, an open-source C/C++ WGAS tool set, and describes the five main domains of function: data management, summary statistics, population stratification, association analysis, and identity-by-descent estimation, which focuses on the estimation and use of identity- by-state and identity/descent information in the context of population-based whole-genome studies.
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.

26,280 citations

Journal ArticleDOI
TL;DR: Because of the increased complexity of analysis and interpretation of clinical genetic testing described in this report, the ACMG strongly recommends thatclinical molecular genetic testing should be performed in a Clinical Laboratory Improvement Amendments–approved laboratory, with results interpreted by a board-certified clinical molecular geneticist or molecular genetic pathologist or the equivalent.

17,834 citations

Journal ArticleDOI
TL;DR: 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.
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.

17,213 citations

Journal ArticleDOI
Giuseppe Mancia1, Robert Fagard, Krzysztof Narkiewicz, Josep Redon, Alberto Zanchetti, Michael Böhm, Thierry Christiaens, Renata Cifkova, Guy De Backer, Anna F. Dominiczak, Maurizio Galderisi, Diederick E. Grobbee, Tiny Jaarsma, Paulus Kirchhof, Sverre E. Kjeldsen, Stéphane Laurent, Athanasios J. Manolis, Peter M. Nilsson, Luis M. Ruilope, Roland E. Schmieder, Per Anton Sirnes, Peter Sleight, Margus Viigimaa, Bernard Waeber, Faiez Zannad, Michel Burnier, Ettore Ambrosioni, Mark Caufield, Antonio Coca, Michael H. Olsen, Costas Tsioufis, Philippe van de Borne, José Luis Zamorano, Stephan Achenbach, Helmut Baumgartner, Jeroen J. Bax, Héctor Bueno, Veronica Dean, Christi Deaton, Çetin Erol, Roberto Ferrari, David Hasdai, Arno W. Hoes, Juhani Knuuti, Philippe Kolh2, Patrizio Lancellotti, Aleš Linhart, Petros Nihoyannopoulos, Massimo F Piepoli, Piotr Ponikowski, Juan Tamargo, Michal Tendera, Adam Torbicki, William Wijns, Stephan Windecker, Denis Clement, Thierry C. Gillebert, Enrico Agabiti Rosei, Stefan D. Anker, Johann Bauersachs, Jana Brguljan Hitij, Mark J. Caulfield, Marc De Buyzere, Sabina De Geest, Geneviève Derumeaux, Serap Erdine, Csaba Farsang, Christian Funck-Brentano, Vjekoslav Gerc, Giuseppe Germanò, Stephan Gielen, Herman Haller, Jens Jordan, Thomas Kahan, Michel Komajda, Dragan Lovic, Heiko Mahrholdt, Jan Östergren, Gianfranco Parati, Joep Perk, Jorge Polónia, Bogdan A. Popescu, Zeljko Reiner, Lars Rydén, Yuriy Sirenko, Alice Stanton, Harry A.J. Struijker-Boudier, Charalambos Vlachopoulos, Massimo Volpe, David A. Wood 
TL;DR: In this article, a randomized controlled trial of Aliskiren in the Prevention of Major Cardiovascular Events in Elderly people was presented. But the authors did not discuss the effect of the combination therapy in patients living with systolic hypertension.
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 …

14,173 citations

Journal ArticleDOI
06 Sep 2012-Nature
TL;DR: The Encyclopedia of DNA Elements project provides new insights into the organization and regulation of the authors' genes and genome, and is an expansive resource of functional annotations for biomedical research.
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.

13,548 citations