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Supplementary Appendix This appendix has been provided by the authors to give readers additional information about their work. Supplement to: Nabel EG, Braunwald E. A tale of coronary artery disease and myocardial infarction. N Engl J Med 2012;366:54-63. (PDF updated March 8, 2012.)

Timeline of Events in Cardiology: 1628 Harvey describes the circulation and function of the heart. 1772 Heberden s describes angina. 1779 Parry speculates that angina is related to coronary-artery ossification (calcification). 1812 NEJM begins publication as the Boston Medical and Surgical Journal, in which the first paper by Warren amplifies the description of angina. 1844 Bernard catheterizes animals and measures cardiac and vessel pressures. 1867 Brunton describes use of amyl nitrite in treatment of angina. 1879 Hektoen speculates that myocardial infarction is caused by coronary thrombosis. 1879 Mahomed describes essential hypertension. 1895 Roentgen discovers X rays. 1896 Riva-Rocci develops the blood pressure cuff. 1898 Tigerstedt and Bergman describe renin. 1901 Einthoven describes the string galvanometer. 1905 Korotkoff describes the auscultatory measurement of blood pressure. 1908-1909 Publication of the first two cardiology journals: Archives des Maladies du Coeur in France (1908) and Zentralblatt fur Herzkrankheiten in Germany (1909). 1910 Windhaus describes the presence of cholesterol in human aortic plaques. 1910 Obraztsov and Strazhesko describe the clinical manifestations of acute myocardial infarction, which was confirmed at postmortem examination. 1912 Herrick describes coronary thrombosis as the cause of acute myocardial infarction, emphasizes total bed rest as its treatment, and uses electrocardiology to diagnose it.

1913 Anitschkow and Chalatow produce aortic atherosclerotic plaques by feeding cholesterol to rabbits. 1924 American Heart Association is established. 1929 Forssmann carries out a catheterization on his own heart. 1941 Cournand and Richards begin their systematic investigation of hemodynamics. 1948 The National Heart (now Heart, Lung, and Blood) Institute is established. 1948 First randomized clinical trial is reported by the British Medical Research Council. 1948 National Heart Institute establishes the Framingham Heart Study. 1952 Zoll develops the first external pacemaker. 1954 Gibbon describes the first successful open-heart operation. 1956 Forssmann, Cournand and Dickinson receive the Nobel Prize in Physiology or Medicine for their discoveries concerning heart catheterization and pathological changes in the circulatory system. 1957 Novello and Sprague develop thiazide diuretics. 1958 Sones develops coronary arteriography. 1961 Framingham investigators identify hypertension and hypercholesterolemia as risk factors for acute myocardial infarction and coronary artery disease. 1961 Julian develops the coronary care unit. 1962 Black develops the first beta-blocker. 1962 Schultz develops loop diuretics. 1964 Dotter and Judkins describe transluminal approaches to atherosclerotic obstructions. 1967 Fries shows improved survival in hypertensive patients with severe hypertension. 1969 Favaloro describes coronary-artery bypass grafting. 2

1972 The National Heart, Lung, and Blood Institute establishes the National High Blood Pressure Education Program. 1976 Chazov administers intracoronary streptokinase in treatment of acute myocardial infarction. 1976 Endo describes the first HMG-CoA inhibitor (mevastatin). 1979 Grüntzig develops coronary angioplasty. 1980 Mirowski develops the first implantable cardioverter-defibrillator. 1980 Furchgott describes role of endothelial relaxing factor (NO) in control of the coronary circulation. 1983 Coronary Artery Surgery Study defines role for medical versus surgical therapy in coronary artery disease. 1985 Brown and Goldstein receive the Nobel Prize in Physiology or Medicine for describing the receptor-mediated pathway for cholesterol homeostasis. 1985 National Heart, Lung, and Blood Institute establishes the National Cholesterol Education Program. 1985 Thrombolysis in Myocardial Infarction (TIMI) study group establishes the role for large, multi-center, randomized clinical trials in defining therapeutic guidelines. 1986 GISSI group shows reduction of deaths from myocardial infarction with intravenous streptokinase in first megatrial (>10,000 patients). 1988 Second International Study of Infarct Survival (ISIS-2) demonstrates that the addition of aspirin to thrombolysis further reduces mortality. 1992 Pfeffer and Braunwald show that angiotensin-converting enzyme inhibitors prevent ventricular remodeling and reduce mortality in acute myocardial infarction. 1993 Superiority of primary percutaneous coronary interventions (PCI) versus fibrinolysis in acute myocardial infarction (MI). 1994 4S group shows clinical benefit of cholesterol lowering in large trial of patients with hypercholesterolemia. 3

1998 Furchgott, Ignarro, and Murad receive the Nobel Prize in Physiology or Medicine for the discovery of nitric oxide as a physiological dilator of blood vessels. 2002 Moss demonstrates prolongation of life in heart failure patients with an implanted defibrillator. 2002 Efficacy of drug eluting stents versus bare metal stents established. 2007 Benefit of cardiac resynchronization therapy in heart failure demonstrated. 2007 Genotype and phenotype genome-wide association data from the Framingham Heart study made available by National Heart, Lung, and Blood Institute. 2009 Slaughter demonstrates life prolongation with a continuous flow left ventricular assist device. 2009 Myocardial Infarction Genetics Consortium describes genomewide association in early-onset myocardial infarction. 2009 National Heart, Lung, and Blood Institute begins whole-exome and wholegenome sequencing of Framingham Heart Study. 2009 Global Alliance for the Chronic Diseases established. 4