579. Nathan DM, Cleary PA, Backlund JY, et al. Intensive diabetes treatment and cardiovascular disease in patients with type 1 diabetes. N Engl J Med. 2005;353:2643 53. 580. Effect of intensive blood-glucose control with metformin on compli- cations in overweight patients with type 2 diabetes (UKPDS 34). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352: 854 65. 581. Dormandy JA, Charbonnel B, Eckland DJ, et al. Secondary prevention of macrovascular events in patients with type 2 diabetes in the PRO- active Study (PROspective pioglitAzone Clinical Trial In macro- Vascular Events): a randomised controlled trial. Lancet. 2005;366: 1279 89. 582. Skyler JS, Bergenstal R, Bonow RO, et al. Intensive glycemic control and the prevention of cardiovascular events: implications of the ACCORD, ADVANCE, and VA diabetes trials: a position statement of the American Diabetes Association and a scientific statement of the American College of Cardiology Foundation and the American Heart Association. Circulation. 2009;119:351 7. 583. Kelly TN, Bazzano LA, Fonseca VA, et al. Systematic review: glucose control and cardiovascular disease in type 2 diabetes. Ann Intern Med. 2009;151:394 403. 584. Selvin E, Bolen S, Yeh HC, et al. Cardiovascular outcomes in trials of oral diabetes medications: a systematic review. Arch Intern Med. 2008;168:2070 80. 585. Turnbull FM, Abraira C, Anderson RJ, et al. Intensive glucose control and macrovascular outcomes in type 2 diabetes. Diabetologia. 2009; 52:2288 98. 586. Ray KK, Seshasai SR, Wijesuriya S, et al. Effect of intensive control of glucose on cardiovascular outcomes and death in patients with diabetes mellitus: a meta-analysis of randomised controlled trials. Lancet. 2009;373:1765 72. 587. Currie CJ, Peters JR, Tynan A, et al. Survival as a function of HbA(1c) in people with type 2 diabetes: a retrospective cohort study. Lancet. 2010;375:481 9. 588. Holman RR, Paul SK, Bethel MA, et al. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med. 2008;359:1577 89. 589. Loke YK, Kwok CS, Singh S. Comparative cardiovascular effects of thiazolidinediones: systematic review and meta-analysis of observa- tional studies. BMJ. 2011;342:1309. 590. Woodcock J. Center for Drug Evaluation and Research. Decision on continued marketing of rosiglitazone (Avandia, Avandamet, Avandaryl) [Report NDA 021071]. 2010. Available at: http://www.fda. gov/downloads/Drugs/DrugSafety/PostmarketDrugSafetyInformation forPatientsandProviders/UCM226959.pdf. Accessed January 15, 2011. 591. Krolewski AS, Kosinski EJ, Warram JH, et al. Magnitude and deter- minants of coronary artery disease in juvenile-onset, insulindependent diabetes mellitus. Am J Cardiol. 1987;59:750 5. 592. Laing SP, Swerdlow AJ, Slater SD, et al. Mortality from heart disease in a cohort of 23 000 patients with insulin-treated diabetes. Diabe- tologia. 2003;46:760 5. 593. Gu K, Cowie CC, Harris MI. Diabetes and decline in heart disease mortality in US adults. JAMA. 1999;281:1291 7. 594. Kannel WB, McGee DL. Diabetes and cardiovascular disease. The Framingham study. JAMA. 1979;241:2035 8. 595. Manson JE, Colditz GA, Stampfer MJ, et al. A prospective study of maturity-onset diabetes mellitus and risk of coronary heart disease and stroke in women. Arch Intern Med. 1991;151:1141 7. 596. Getz GS. Report on the workshop on diabetes and mechanisms of atherogenesis. September 17th and 18th, 1992, Bethesda, Maryland. Arterioscler Thromb. 1993;13:459 64. 597. Alderman EL, Corley SD, Fisher LD, et al. Five-year angiographic follow-up of factors associated with progression of coronary artery disease in the Coronary Artery Surgery Study (CASS). CASS Partic- ipating Investigators and Staff. J Am Coll Cardiol. 1993;22:1141 54. 598. Reichard P, Nilsson BY, Rosenqvist U. The effect of long-term inten- sified insulin treatment on the development of microvascular compli- cations of diabetes mellitus. N Engl J Med. 1993;329:304 9. 599. McCormack J, Greenhalgh T. Seeing what you want to see in ran- domised controlled trials: versions and perversions of UKPDS data. United Kingdom prospective diabetes study. BMJ. 2000;320:1720 3. 600. Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545 59. 601. Gaede P, Vedel P, Larsen N, et al. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med. 2003;348:383 93. 602. Taylor RS, Brown A, Ebrahim S, et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta- analysis of randomized controlled trials. Am J Med. 2004;116:682 92. 603. Haskell WL, Lee IM, Pate RR, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007;116:1081 93. 604. US Department of Health and Human Services. 2008 Physical Activity Guidelines for Americans. Washington, DC: 2008. 605. Ken-Dror G, Lerman Y, Segev S, et al. [Development of a Hebrew questionnaire to be used in epidemiological studies to assess physical fitness validation against sub maximal stress test and predicted VO2max]. Harefuah. 2004;143:566 72, 623. 606. Cardinal BJ. Predicting cardiorespiratory fitness without exercise testing in epidemiologic studies: a concurrent validity study. J Epi- demiol. 1996;6:31 5. 607. Nowak Z, Plewa M, Skowron M, et al. Paffenbarger Physical Activity Questionnaire as an additional tool in clinical assessment of patients with coronary artery disease treated with angioplasty. Kardiol Pol. 2010;68:32 9. 608. Jurca R, Jackson AS, LaMonte MJ, et al. Assessing cardiorespiratory fitness without performing exercise testing. Am J Prev Med. 2005;29: 185 93. 609. Taylor RS, Dalal H, Jolly K, et al. Home-based versus centre-based cardiac rehabilitation. Cochrane Database of Systematic Reviews CD007130. 2010. Accessed January 6, 2012. 610. Clark AM, Haykowsky M, Kryworuchko J, et al. A meta-analysis of randomized control trials of home-based secondary prevention programs for coronary artery disease. Eur J Cardiovasc Prev Rehabil. 2010;17:261 70. 611. McCartney N, McKelvie RS, Haslam DR, et al. Usefulness of weight- lifting training in improving strength and maximal power output in coronary artery disease. Am J Cardiol. 1991;67:939 45. 612. Beniamini Y, Rubenstein JJ, Faigenbaum AD, et al. High-intensity strength training of patients enrolled in an outpatient cardiac rehabili- tation program. J Cardiopulm Rehabil. 1999;19:8 17. 613. Centers for Disease Control and Prevention. 2008 Physical Activity Guidelines. cdc.gov. 2008. Available at: http://www.cdc.gov/ physicalactivity/everyone/guidelines/. Accessed May 20, 2010. 614. Thomas RJ, King M, Lui K, et al. AACVPR/ACCF/AHA 2010 update: performance measures on cardiac rehabilitation for referral to cardiac rehabilitation/secondary prevention services: a report of the American Association of Cardiovascular and Pulmonary Rehabilitation and the American College of Cardiology Foundation/American Heart Asso- ciation Task Force on Performance Measures (Writing Committee to Develop Clinical Performance Measures for Cardiac Rehabilitation). Circulation. 2010;122:1342 50. 615. Froelicher V, Jensen D, Genter F, et al. A randomized trial of exercise training in patients with coronary heart disease. JAMA. 1984;252: 1291 7. 616. Hambrecht R, Niebauer J, Marburger C, et al. Various intensities of leisure time physical activity in patients with coronary artery disease: effects on cardiorespiratory fitness and progression of coronary ath- erosclerotic lesions. J Am Coll Cardiol. 1993;22:468 77. 617. May GA, Nagle FJ. Changes in rate-pressure product with physical training of individuals with coronary artery disease. Phys Ther. 1984; 64:1361 6. 618. Oldridge NB, McCartney N, Hicks A, et al. Improvement in maximal isokinetic cycle ergometry with cardiac rehabilitation. Med Sci Sports Exerc. 1989;21:308 12. 619. Ornish D, Scherwitz LW, Doody RS, et al. Effects of stress man- agement training and dietary changes in treating ischemic heart disease. JAMA. 1983;249:54 9. 620. Sebrechts CP, Klein JL, Ahnve S, et al. Myocardial perfusion changes following 1 year of exercise training assessed by thallium-201 circum- ferential count profiles. Am Heart J. 1986;112:1217 26. 621. Schuler G, Hambrecht R, Schlierf G, et al. Regular physical exercise and low-fat diet. Effects on progression of coronary artery disease. Circulation. 1992;86:1 11. 622. Todd IC, Ballantyne D. Effect of exercise training on the total ischaemic burden: an assessment by 24 hour ambulatory electrocardio- graphic monitoring. Br Heart J. 1992;68:560 6. 623. Rauramaa R, Li G, Vaisanen SB. Dose-response and coagulation and hemostatic factors. Med Sci Sports Exerc. 2001;33:S516 S520. 624. Milani RV, Lavie CJ, Mehra MR. Reduction in C-reactive protein through cardiac rehabilitation and exercise training. J Am Coll Cardiol. 2004;43:1056 61. 625. Blumenthal JA, Sherwood A, Babyak MA, et al. Effects of exercise and stress management training on markers of cardiovascular risk in patients with ischemic heart disease: a randomized controlled trial. JAMA. 2005;293:1626 34. 626. Hambrecht R, Adams V, Erbs S, et al. Regular physical activity improves endothelial function in patients with coronary artery disease by increasing phosphorylation of endothelial nitric oxide synthase. Circulation. 2003;107:3152 8. 627. Hosokawa S, Hiasa Y, Takahashi T, et al. Effect of regular exercise on coronary endothelial function in patients with recent myocardial infarction. Circ J. 2003;67:221 4. 628. Goldsmith RL, Bloomfield DM, Rosenwinkel ET. Exercise and autonomic function. Coron Artery Dis. 2000;11:129 35. 629. Malfatto G, Blengino S, Annoni L, et al. Original articles primary coronary angioplasty and subsequent cardiovascular rehabilitation are linked to a favorable sympathovagal balance after a first anterior myocardial infarction. Ital Heart J. 2005;6:21 7. 630. Digenio AG, Sim JG, Dowdeswell RJ, et al. Exercise-related cardiac arrest in cardiac rehabilitation. The Johannesburg experience. S Afr Med J. 1991;79:188 91. 631. Franklin BA, Bonzheim K, Gordon S, et al. Safety of medically supervised outpatient cardiac rehabilitation exercise therapy: a 16-year follow-up. Chest. 1998;114:902 6. 632. Van Camp SP, Peterson RA. Cardiovascular complications of out- patient cardiac rehabilitation programs. JAMA. 1986;256:1160 3. 633. Vongvanich P, Paul-Labrador MJ, Merz CN. Safety of medically supervised exercise in a cardiac rehabilitation center. Am J Cardiol. 1996;77:1383 5. 634. Rehabilitation after cardiovascular diseases, with special emphasis on developing countries. Report of a WHO Expert Committee. World Health Organ Tech Rep Ser. 1993;831:1 122. Fihn et al Stable Ischemic Heart Disease: Full Text e449 635. Bogers RP, Bemelmans WJ, Hoogenveen RT, et al. Association of overweight with increased risk of coronary heart disease partly inde- pendent of blood pressure and cholesterol levels: a meta-analysis of 21 cohort studies including more than 300 000 persons. Arch Intern Med. 2007;167:1720 8. 636. Klein S, Burke LE, Bray GA, et al. Clinical implications of obesity with specific focus on cardiovascular disease: a statement for profes- sionals from the American Heart Association Council on Nutrition, Physical Activity, and Metabolism. Circulation. 2004;110:2952 67. 637. Calle EE, Thun MJ, Petrelli JM, et al. Body-mass index and mortality in a prospective cohort of U.S. adults. N Engl J Med. 1999;341: 1097 105. 638. Jensen MK, Chiuve SE, Rimm EB, et al. Obesity, behavioral lifestyle factors, and risk of acute coronary events. Circulation. 2008;117: 3062 9. 639. Arnlov J, Ingelsson E, Sundstrom J, et al. Impact of body mass index and the metabolic syndrome on the risk of cardiovascular disease and death in middle-aged men. Circulation. 2010;121:230 6. 640. Lavie CJ, Milani RV, Ventura HO. Obesity and cardiovascular disease: risk factor, paradox, and impact of weight loss. J Am Coll Cardiol. 2009;53:1925 32. 641. Gruberg L, Weissman NJ, Waksman R, et al. The impact of obesity on the short-term and long-term outcomes after percutaneous coronary intervention: the obesity paradox? J Am Coll Cardiol. 2002;39: 578 84. 642. Jacobs EJ, Newton CC, Wang Y, et al. Waist circumference and all-cause mortality in a large US cohort. Arch Intern Med. 2010;170: 1293 301. 643. Hsieh SD, Yoshinaga H. Abdominal fat distribution and coronary heart disease risk factors in men-waist/height ratio as a simple and useful predictor. Int J Obes Relat Metab Disord. 1995;19:585 9. 644. Rimm EB, Stampfer MJ, Giovannucci E, et al. Body size and fat distribution as predictors of coronary heart disease among middleaged and older US men. Am J Epidemiol. 1995;141:1117 27. 645. McTigue K, Larson JC, Valoski A, et al. Mortality and cardiac and vascular outcomes in extremely obese women. JAMA. 2006;296: 79 86. 646. Pi-Sunyer FX. The obesity epidemic: pathophysiology and conse- quences of obesity. Obes Res. 2002;10 Suppl 2:97S 104S. 647. Romero-Corral A, Montori VM, Somers VK, et al. Association of bodyweight with total mortality and with cardiovascular events in coronary artery disease: a systematic review of cohort studies. Lancet. 2006;368:666 78. 648. Sjostrom L, Narbro K, Sjostrom CD, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357: 741 52. 649. Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, et al. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005;80:1157 62. 650. Critchley J, Capewell S. Smoking cessation for the secondary pre- vention of coronary heart disease. Cochrane Database Syst Rev. 2003; CD003041. 651. Rigotti NA. Helping smokers with cardiac disease to abstain from tobacco after a stay in hospital. CMAJ. 2009;180:1283 4. 652. Smith PM, Burgess E. Smoking cessation initiated during hospital stay for patients with coronary artery disease: a randomized controlled trial. CMAJ. 2009;180:1297 303. 653. Doll R, Peto R. Mortality in relation to smoking: 20 years observations on male British doctors. Br Med J. 1976;2:1525 36. 654. Willett WC, Green A, Stampfer MJ, et al. Relative and absolute excess risks of coronary heart disease among women who smoke cigarettes. N Engl J Med. 1987;317:1303 9. 655. Kannel WB, D Agostino RB, Belanger AJ. Fibrinogen, cigarette smoking, and risk of cardiovascular disease: insights from the Fra- mingham Study. Am Heart J. 1987;113:1006 10. 656. Davis JW, Hartman CR, Lewis HD Jr, et al. Cigarette smoking induced enhancement of platelet function: lack of prevention by aspirin in men with coronary artery disease. J Lab Clin Med. 1985;105: 479 83. 657. Zeiher AM, Schachinger V, Minners J. Long-term cigarette smoking impairs endothelium-dependent coronary arterial vasodilator function. Circulation. 1995;92:1094 100. 658. Taylor AE, Johnson DC, Kazemi H. Environmental tobacco smoke and cardiovascular disease. A position paper from the Council on Cardio- pulmonary and Critical Care, American Heart Association. Circulation. 1992;86:699 702. 659. Winniford MD, Jansen DE, Reynolds GA, et al. Cigarette smoking- induced coronary vasoconstriction in atherosclerotic coronary artery disease and prevention by calcium antagonists and nitroglycerin. Am J Cardiol. 1987;59:203 7. 660. Dobson AJ, Alexander HM, Heller RF, et al. How soon after quitting smoking does risk of heart attack decline? J Clin Epidemiol. 1991;44: 1247 53. 661. Gordon T, Kannel WB, McGee D, et al. Death and coronary attacks in men after giving up cigarette smoking. A report from the Framingham study. Lancet. 1974;2:1345 8. 662. Gorin SS, Heck JE. Meta-analysis of the efficacy of tobacco counseling by health care providers. Cancer Epidemiol Biomarkers Prev. 2004; 13:2012 22. 663. Hughes JR. Motivating and helping smokers to stop smoking. J Gen Intern Med. 2003;18:1053 7. 664. Lancaster T, Stead LF. Individual behavioural counselling for smoking cessation. Cochrane Database Syst Rev. 2005;CD001292. 665. Stead LF, Lancaster T. Group behaviour therapy programmes for smoking cessation. Cochrane Database Syst Rev. 2005;CD001007. 666. Stead LF, Lancaster T, Perera R. Telephone counselling for smoking cessation. Cochrane Database Syst Rev. 2003;CD002850. 667. Ussher M. Exercise interventions for smoking cessation. Cochrane Database Syst Rev. 2005;CD002295. 668. Silagy C, Lancaster T, Stead L, et al. Nicotine replacement therapy for smoking cessation. Cochrane Database Syst Rev. 2004;CD000146. 669. Hughes J, Stead L, Lancaster T. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2004;CD000031. 670. Gonzales D, Rennard SI, Nides M, et al. Varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs sustained-release bupropion and placebo for smoking cessation: a randomized controlled trial. JAMA. 2006;296:47 55. 671. Jorenby DE, Hays JT, Rigotti NA, et al. Efficacy of varenicline, an alpha4beta2 nicotinic acetylcholine receptor partial agonist, vs placebo or sustained-release bupropion for smoking cessation: a randomized controlled trial. JAMA. 2006;296:5 63. 672. US Food and Drug Administration. Information for Healthcare Profes- sionals. Varenicline (marketed as Chantix). Center for Drug Evaluation and Research. 2008. Available at: http://www.fda.gov/Drugs/Drug Safety/PostmarketDrugSafetyInformationforPatientsandProviders/ ucm124818.htm. Accessed October 9, 2008. 673. US Food and Drug Administration. Public Health Advisory. Important Information on Chantix (varenicline). Center for Drug Evaluation and Research. 2008. Available at: http://www.fda.gov/cder/drug/advisory/ varenicline.htm. Accessed October 9, 2008. 674. Honig A, Kuyper AM, Schene AH, et al. Treatment of postmyocardial infarction depressive disorder: a randomized, placebo-controlled trial with mirtazapine. Psychosom Med. 2007;69:606 13. 675. DiMatteo MR, Lepper HS, Croghan TW. Depression is a risk factor for noncompliance with medical treatment: meta-analysis of the effects of anxiety and depression on patient adherence. Arch Intern Med. 2000; 160:2101 7. 676. Taylor CB, Youngblood ME, Catellier D, et al. Effects of antide- pressant medication on morbidity and mortality in depressed patients after myocardial infarction. Arch Gen Psychiatry. 2005;62:792 8. 677. Murray CJ, Lopez AD. Global mortality, disability, and the contri- bution of risk factors: Global Burden of Disease Study. Lancet. 1997; 349:1436 42. 678. Moussavi S, Chatterji S, Verdes E, et al. Depression, chronic diseases, and decrements in health: results from the World Health Surveys. Lancet. 2007;370:851 8. 679. Carney RM, Rich MW, Tevelde A, et al. Major depressive disorder in coronary artery disease. Am J Cardiol. 1987;60:1273 5. 680. Frasure-Smith N, Lesperance F, Talajic M. Depression following myo- cardial infarction. Impact on month survival. JAMA. 1993;270: 1819 25. 681. Rudisch B, Nemeroff CB. Epidemiology of comorbid coronary artery disease and depression. Biol Psychiatry. 2003;54:227 40. 682. Schleifer SJ, ari-Hinson MM, Coyle DA, et al. The nature and course of depression following myocardial infarction. Arch Intern Med. 1989; 149:1785 9. 683. Spertus JA, McDonell M, Woodman CL, et al. Association between depression and worse disease-specific functional status in outpatients with coronary artery disease. Am Heart J. 2000;140:105 10. 684. Nicholson A, Kuper H, Hemingway H. Depression as an aetiologic and prognostic factor in coronary heart disease: a meta-analysis of 6362 events among 146 538 participants in 54 observational studies. Eur Heart J. 2006;27:2763 74. 685. Bonnet F, Irving K, Terra JL, et al. Anxiety and depression are associated with unhealthy lifestyle in patients at risk of cardiovascular disease. Atherosclerosis. 2005;178:339 44. 686. Caulin-Glaser T, Maciejewski PK, Snow R, et al. Depressive symptoms and sex affect completion rates and clinical outcomes in cardiac rehabilitation. Prev Cardiol. 2007;10:15 21. 687. Gehi A, Haas D, Pipkin S, et al. Depression and medication adherence in outpatients with coronary heart disease: findings from the Heart and Soul Study. Arch Intern Med. 2005;165:2508 13. 688. Kronish IM, Rieckmann N, Halm EA, et al. Persistent depression affects adherence to secondary prevention behaviors after acute coronary syndromes. J Gen Intern Med. 2006;21:1178 83. 689. McKellar JD, Humphreys K, Piette JD. Depression increases diabetes symptoms by complicating patients self-care adherence. Diabetes Educ. 2004;30:485 92. 690. Rieckmann N, Kronish IM, Haas D, et al. Persistent depressive symptoms lower aspirin adherence after acute coronary syndromes. Am Heart J. 2006;152:922 7. 691. Rieckmann N, Gerin W, Kronish IM, et al. Course of depressive symptoms and medication adherence after acute coronary syndromes: an electronic medication monitoring study. J Am Coll Cardiol. 2006; 48:2218 22. 692. Laghrissi-Thode F, Wagner WR, Pollock BG, et al. Elevated platelet factor 4 and beta-thromboglobulin plasma levels in depressed patients with ischemic heart disease. Biol Psychiatry. 1997;42:290 5. 693. Musselman DL, Tomer A, Manatunga AK, et al. Exaggerated platelet reactivity in major depression. Am J Psychiatry. 1996;153:1313 7. 694. Pollock BG, Laghrissi-Thode F, Wagner WR. Evaluation of platelet activation in depressed patients with ischemic heart disease after par- oxetine or nortriptyline treatment. J Clin Psychopharmacol. 2000;20: 137 40. 695. Shimbo D, Child J, Davidson K, et al. Exaggerated serotoninmediated platelet reactivity as a possible link in depression and acute coronary syndromes. Am J Cardiol. 2002;89:331 3. 696. Sherwood A, Hinderliter AL, Watkins LL, et al. Impaired endothelial function in coronary heart disease patients with depressive symptom- atology. J Am Coll Cardiol. 2005;46:656 9. 697. Agelink MW, Boz C, Ullrich H, et al. Relationship between major depression and heart rate variability. Clinical consequences and impli- cations for antidepressive treatment. Psychiatry Res. 2002;113: 139 49. 698. Carney RM, Blumenthal JA, Stein PK, et al. Depression, heart rate variability, and acute myocardial infarction. Circulation. 2001;104: 2024 8. 699. Gorman JM, Sloan RP. Heart rate variability in depressive and anxiety disorders. Am Heart J. 2000;140:77 83. 700. Kop WJ, Gottdiener JS, Tangen CM, et al. Inflammation and coagu- lation factors in persons .65 years of age with symptoms of depression but without evidence of myocardial ischemia. Am J Cardiol. 2002;89: 419 24. 701. Whooley MA, Avins AL, Miranda J, et al. Case-finding instruments for depression. Two questions are as good as many. J Gen Intern Med. 1997;12:439 45. 702. Kroenke K, Spitzer RL, Williams JB. The PHQ-9: validity of a brief depression severity measure. J Gen Intern Med. 2001;16:606 13. 703. Di Castelnuovo A., Rotondo S, Iacoviello L, et al. Meta-analysis of wine and beer consumption in relation to vascular risk. Circulation. 2002;105:2836 44. 704. Mukamal KJ, Maclure M, Muller JE, et al. Prior alcohol consumption and mortality following acute myocardial infarction. JAMA. 2001;285: 1965 70. 705. Muntwyler J, Hennekens CH, Buring JE, et al. Mortality and light to moderate alcohol consumption after myocardial infarction. Lancet. 1998;352:1882 5. 706. Greenfield JR, Samaras K, Hayward CS, et al. Beneficial postprandial effect of a small amount of alcohol on diabetes and cardiovascular risk factors: modification by insulin resistance. J Clin Endocrinol Metab. 2005;90:661 72. 707. Mukamal KJ, Mackey RH, Kuller LH, et al. Alcohol consumption and lipoprotein subclasses in older adults. J Clin Endocrinol Metab. 2007; 92:2559 66. 708. Davies MJ, Baer DJ, Judd JT, et al. Effects of moderate alcohol intake on fasting insulin and glucose concentrations and insulin sensitivity in postmenopausal women: a randomized controlled trial. JAMA. 2002; 287:2559 62. 709. Albert MA, Glynn RJ, Ridker PM. Alcohol consumption and plasma concentration of C-reactive protein. Circulation. 2003;107:443 7. 710. Sierksma A, van der Gaag MS, Kluft C, et al. Moderate alcohol consumption reduces plasma C-reactive protein and fibrinogen levels; a randomized, diet-controlled intervention study. Eur J Clin Nutr. 2002;56:1130 6. 711. Naimi TS, Brown DW, Brewer RD, et al. Cardiovascular risk factors and confounders among nondrinking and moderate-drinking U.S. adults. Am J Prev Med. 2005;28:369 73. 712. Pope CA III, Burnett RT, Thurston GD, et al. Cardiovascular mortality and long-term exposure to particulate air pollution: epidemiological evidence of general pathophysiological pathways of disease. Circu- lation. 2004;109:71 7. 713. Pope CA III, Muhlestein JB, May HT, et al. Ischemic heart disease events triggered by short-term exposure to fine particulate air pollution. Circulation. 2006;114:2443 8. 714. Pope CA III. Mortality effects of longer term exposures to fine par- ticulate air pollution: review of recent epidemiological evidence. Inhal Toxicol. 2007;19 Suppl 1:33 8. 715. Brook RD, Rajagopalan S, Pope CA, III, et al. Particulate matter air pollution and cardiovascular disease: An update to the scientific statement from the American Heart Association. Circulation. 2010; 121:2331 78. 716. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. BMJ. 2002;324:71 86. 717. Juul-Moller S, Edvardsson N, Jahnmatz B, et al. Double-blind trial of aspirin in primary prevention of myocardial infarction in patients with stable chronic angina pectoris. The Swedish Angina Pectoris Aspirin Trial (SAPAT) Group. Lancet. 1992;340:1421 5. 718. A randomised, blinded, trial of clopidogrel versus aspirin in patients at risk of ischaemic events (CAPRIE). CAPRIE Steering Committee. Lancet. 1996;348:1329 39. 719. Bhatt DL, Flather MD, Hacke W, et al. Patients with prior myocardial infarction, stroke, or symptomatic peripheral arterial disease in the CHARISMA trial. J Am Coll Cardiol. 2007;49:1982 8. 720. Hirsh J, Dalen JE, Fuster V, et al. Aspirin and other platelet-active drugs. The relationship among dose, effectiveness, and side effects. Chest. 1995;108:247S 57S. 721. Balsano F, Rizzon P, Violi F, et al. Antiplatelet treatment with ticlo- pidine in unstable angina. A controlled multicenter clinical trial. The Studio della Ticlopidina nell Angina Instabile Group. Circulation. 1990;82:17 26. 722. The Persantine-aspirin reinfarction study. The Persantine-aspirin Rein- farction Study (PARIS) research group. Circulation. 1980;62: V85 V88. 723. Peters RJ, Mehta SR, Fox KA, et al. Effects of aspirin dose when used alone or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) study. Circulation. 2003; 108:1682 7. 724. Yusuf S, Zhao F, Mehta SR, et al. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med. 2001;345:494 502. 725. Steinhubl SR, Berger PB, Mann JT, III, et al. Early and sustained dual oral antiplatelet therapy following percutaneous coronary intervention: a randomized controlled trial. JAMA. 2002;288:2411 20. 726. Helton TJ, Bavry AA, Kumbhani DJ, et al. Incremental effect of clopidogrel on important outcomes in patients with cardiovascular disease: a meta-analysis of randomized trials. Am J Cardiovasc Drugs. 2007;7:289 97. 727. Sirois C, Poirier P, Moisan J, et al. The benefit of aspirin therapy in type 2 diabetes: what is the evidence? Int J Cardiol. 2008;129:172 9. 728. Shuldiner AR, O Connell JR, Bliden KP, et al. Association of cyto- chrome P450 2C19 genotype with the antiplatelet effect and clinical efficacy of clopidogrel therapy. JAMA. 2009;302:849 57. 729. Collet JP, Hulot JS, Pena A, et al. Cytochrome P450 2C19 poly- morphism in young patients treated with clopidogrel after myocardial infarction: a cohort study. Lancet. 2009;373:309 17. Fihn et al Stable Ischemic Heart Disease: Full Text e451 730. Mega JL, Close SL, Wiviott SD, et al. Cytochrome p-450 poly- morphisms and response to clopidogrel. N Engl J Med. 2009;360: 354 62. 731. Simon T, Verstuyft C, Mary-Krause M, et al. Genetic determinants of response to clopidogrel and cardiovascular events. N Engl J Med. 2009;360:363 75. 732. Price MJ, Angiolillo DJ, Teirstein PS, et al. Platelet reactivity and cardiovascular outcomes after percutaneous coronary intervention: a time-dependent analysis of the Gauging Responsiveness with a VerifyNow P2Y12 assay: Impact on Thrombosis and Safety (GRAVITAS) trial. Circulation. 2011;124:1132 7. 733. Pare G, Mehta SR, Yusuf S, et al. Effects of CYP2C19 genotype on outcomes of clopidogrel treatment. N Engl J Med. 2010;363:1704 14. 734. Gilard M, Arnaud B, Le GG, et al. Influence of omeprazol on the antiplatelet action of clopidogrel associated to aspirin. J Thromb Haemost. 2006;4:2508 9. 735. Gilard M, Arnaud B, Cornily JC, et al. Influence of omeprazole on the antiplatelet action of clopidogrel associated with aspirin: the ran- domized, double-blind OCLA (Omeprazole CLopidogrel Aspirin) study. J Am Coll Cardiol. 2008;51:256 60. 736. Juurlink DN, Gomes T, Ko DT, et al. A population-based study of the drug interaction between proton pump inhibitors and clopidogrel. CMAJ. 2009;180:713 8. 737. Ho PM, Maddox TM, Wang L, et al. Risk of adverse outcomes associated with concomitant use of clopidogrel and proton pump in- hibitors following acute coronary syndrome. JAMA. 2009;301: 937 44. 738. O Donoghue ML, Braunwald E, Antman EM, et al. Pharmacodynamic effect and clinical efficacy of clopidogrel and prasugrel with or without a proton-pump inhibitor: an analysis of two randomised trials. Lancet. 2009;374:989 97. 739. Bhatt DL, Cryer BL, Contant CF, et al. Clopidogrel with or without omeprazole in coronary artery disease. N Engl J Med. 2010;363: 1909 17. 740. Li XQ, Andersson TB, Ahlstrom M, et al. Comparison of inhibitory effects of the proton pump-inhibiting drugs omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole on human cytochrome P450 activities. Drug Metab Dispos. 2004;32:821 7. 741. Siller-Matula JM, Spiel AO, Lang IM, et al. Effects of pantoprazole and esomeprazole on platelet inhibition by clopidogrel. Am Heart J. 2009;157:148 5. 742. Cuisset T, Frere C, Quilici J, et al. Comparison of omeprazole and pantoprazole influence on a high 15 mg clopidogrel maintenance dose the PACA (Proton Pump Inhibitors And Clopidogrel Association) prospective randomized study. J Am Coll Cardiol. 2009;54:1149 53. 743. Saw J, Brennan DM, Steinhubl SR, et al. Lack of evidence of a clopidogrel-statin interaction in the CHARISMA trial. J Am Coll Cardiol. 2007;50:291 5. 744. Hochholzer W, Trenk D, Frundi D, et al. Time dependence of platelet inhibition after a 60 mg loading dose of clopidogrel in a large, unse- lected cohort of candidates for percutaneous coronary intervention. Circulation. 2005;111:2560 4. 745. von Beckerath N., Taubert D, Pogatsa-Murray G, et al. Absorption, metabolization, and antiplatelet effects of 30 , 60 , and 90 mg loading doses of clopidogrel: results of the ISAR-CHOICE (Intra- coronary Stenting and Antithrombotic Regimen: Choose Between 3 High Oral Doses for Immediate Clopidogrel Effect) Trial. Circulation. 2005;112:2946 50. 746. Wiviott SD, Braunwald E, McCabe CH, et al. Prasugrel versus clopi- dogrel in patients with acute coronary syndromes. N Engl J Med. 2007;357:2001 15. 747. Wallentin L, Becker RC, Budaj A, et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med. 2009;361: 1045 57. 748. Jagathesan R, Rosen SD, Foale RA, et al. Effects of long-term oral dipyridamole treatment on coronary microcirculatory function in patients with chronic stable angina: A substudy of the persantine in stable angina (PISA) study. J Cardiovasc Pharmacol. 2006;48:110 6. 749. Tsuya T, Okada M, Horie H, et al. Effect of dipyridamole at the usual oral dose on exercise-induced myocardial ischemia in stable angina pectoris. Am J Cardiol. 1990;66:275 8. 750. Byzova TV, Plow EF. Networking in the hemostatic system. Integrin alphaiibbeta3 binds prothrombin and influences its activation. J Biol Chem. 1997;272:27183 8. 751. Dahlback B. Blood coagulation. Lancet. 2000;355:1627 32. 752. Held C, Hjemdahl P, Rehnqvist N, et al. Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm. Circulation. 1997;95:2380 6. 753. Anand SS, Yusuf S. Oral anticoagulants in patients with coronary artery disease. J Am Coll Cardiol. 2003;41:62S 9S. 754. Boekholdt SM, Bijsterveld NR, Moons AH, et al. Genetic variation in coagulation and fibrinolytic proteins and their relation with acute myocardial infarction: a systematic review. Circulation. 2001;104: 3063 8. 755. Martini CH, Doggen CJ, Cavallini C, et al. No effect of polymorphisms in prothrombotic genes on the risk of myocardial infarction in young adults without cardiovascular risk factors. J Thromb Haemost. 2005; 3:177 9. 756. No evidence of association between prothrombotic gene poly- morphisms and the development of acute myocardial infarction at a young age. Circulation. 2003;107:1117 22. 757. Kernis SJ, Harjai KJ, Stone GW, et al. Does beta-blocker therapy improve clinical outcomes of acute myocardial infarction after suc- cessful primary angioplasty? J Am Coll Cardiol. 2004;43:1773 9. 758. de Peuter OR, Lussana F, Peters RJ, et al. A systematic review of selective and non-selective beta blockers for prevention of vascular events in patients with acute coronary syndrome or heart failure. Neth J Med. 2009;67:284 94. 759. Freemantle N, Cleland J, Young P, et al. beta Blockade after myo- cardial infarction: systematic review and meta regression analysis. BMJ. 1999;318:1730 7. 760. Packer M, Bristow MR, Cohn JN, et al. The effect of carvedilol on morbidity and mortality in patients with chronic heart failure. U.S. Carvedilol Heart Failure Study Group. N Engl J Med. 1996;334: 1349 55. 761. Leizorovicz A, Lechat P, Cucherat M, et al. Bisoprolol for the treatment of chronic heart failure: a meta-analysis on individual data of two placebo-controlled studies CIBIS and CIBIS II. Cardiac Insuffi- ciency Bisoprolol Study. Am Heart J. 2002;143:301 7. 762. Poole-Wilson PA, Swedberg K, Cleland JG, et al. Comparison of carvedilol and metoprolol on clinical outcomes in patients with chronic heart failure in the Carvedilol Or Metoprolol European Trial (COMET): randomised controlled trial. Lancet. 2003;362:7 13. 763. Domanski MJ, Krause-Steinrauf H, Massie BM, et al. A comparative analysis of the results from 4 trials of beta-blocker therapy for heart failure: BEST, CIBIS-II, MERIT-HF, and COPERNICUS. J Card Fail. 2003;9:354 63. 764. Goldstein S. Beta-blocking drugs and coronary heart disease. Car- diovasc Drugs Ther. 1997;11 Suppl 1:219 25. 765. Frishman WH, Heiman M, Soberman J, et al. Comparison of celiprolol and propranolol in stable angina pectoris. Celiprolol International Angina Study Group. Am J Cardiol. 1991;67:665 70. 766. Narahara KA. Double-blind comparison of once daily betaxolol versus propranolol four times daily in stable angina pectoris. Betaxolol Inves- tigators Group. Am J Cardiol. 1990;65:577 82. 767. Kardas P. Compliance, clinical outcome, and quality of life of patients with stable angina pectoris receiving once-daily betaxolol versus twice daily metoprolol: a randomized controlled trial. Vasc Health Risk Manag. 2007;3:235 42. 768. Ryden L. Efficacy of epanolol versus metoprolol in angina pectoris: report from a Swedish multicentre study of exercise tolerance. J Intern Med. 1992;231:7 11. 769. Boberg J, Larsen FF, Pehrsson SK. The effects of beta blockade with (epanolol) and without (atenolol) intrinsic sympathomimetic activity in stable angina pectoris. The Visacor Study Group. Clin Cardiol. 1992; 15:591 5. 770. Hauf-Zachariou U, Blackwood RA, Gunawardena KA, et al. Carvedilol versus verapamil in chronic stable angina: a multicentre trial. Eur J Clin Pharmacol. 1997;52:95 100. 771. Raftery EB. The preventative effects of vasodilating beta-blockers in cardiovascular disease. Eur Heart J. 1996;17 Suppl B:30 8. 772. Jouven X, Empana JP, Schwartz PJ, et al. Heart-rate profile during exercise as a predictor of sudden death. N Engl J Med. 2005;352: 1951 8. 773. Diaz A, Bourassa MG, Guertin MC, et al. Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease. Eur Heart J. 2005;26:967 74. 774. Maqbool A, Hall AS, Ball SG, et al. Common polymorphisms of beta adrenoceptor: identification and rapid screening assay. Lancet. 1999;353:897. 775. Borjesson M, Magnusson Y, Hjalmarson A, et al. A novel poly- morphism in the gene coding for the beta(1)-adrenergic receptor asso- ciated with survival in patients with heart failure. Eur Heart J. 2000; 21:1853 8. 776. Mason DA, Moore JD, Green SA, et al. A gain-of-function poly- morphism in a G-protein coupling domain of the human beta a- drenergic receptor. J Biol Chem. 1999;274:12670 4. 777. Nieminen T, Lehtimaki T, Laiho J, et al. Effects of polymorphisms in beta adrenoceptor and alpha-subunit of G protein on heart rate and blood pressure during exercise test. The Finnish Cardiovascular Study. J Appl Physiol. 2006;100:507 11. 778. Xie HG, Dishy V, Sofowora G, et al. Arg389Gly beta adrenoceptor polymorphism varies in frequency among different ethnic groups but does not alter response in vivo. Pharmacogenetics. 2001;11:191 7. 779. Liu J, Liu ZQ, Tan ZR, et al. Gly389Arg polymorphism of beta a- drenergic receptor is associated with the cardiovascular response to metoprolol. Clin Pharmacol Ther. 2003;74:372 9. 780. Sofowora GG, Dishy V, Muszkat M, et al. A common beta adrenergic receptor polymorphism (Arg389Gly) affects blood pressure response to beta-blockade. Clin Pharmacol Ther. 2003;73:366 71. 781. Defoor J, Martens K, Zielinska D, et al. The CAREGENE study: polymorphisms of the beta adrenoceptor gene and aerobic power in coronary artery disease. Eur Heart J. 2006;27:808 16. 782. Johnson JA, Zineh I, Puckett BJ, et al. Beta adrenergic receptor poly- morphisms and antihypertensive response to metoprolol. Clin Pharmacol Ther. 2003;74:44 52. 783. Liu J, Liu ZQ, Yu BN, et al. beta Adrenergic receptor polymorphisms influence the response to metoprolol monotherapy in patients with essential hypertension. Clin Pharmacol Ther. 2006;80:23 32. 784. Karlsson J, Lind L, Hallberg P, et al. Beta adrenergic receptor gene polymorphisms and response to beta adrenergic receptor blockade in patients with essential hypertension. Clin Cardiol. 2004;27:347 50. 785. O Shaughnessy KM, Fu B, Dickerson C, et al. The gain-of-function G389R variant of the beta adrenoceptor does not influence blood pressure or heart rate response to beta-blockade in hypertensive subjects. Clin Sci (Lond). 2000;99:233 8. 786. Rehnqvist N, Hjemdahl P, Billing E, et al. Treatment of stable angina pectoris with calcium antagonists and beta-blockers. The APSIS study. Angina Prognosis Study in Stockholm. Cardiologia. 1995;40:301. 787. von Arnim T. Medical treatment to reduce total ischemic burden: total ischemic burden bisoprolol study (TIBBS), a multicenter trial com- paring bisoprolol and nifedipine. The TIBBS Investigators. J Am Coll Cardiol. 1995;25:231 8. 788. Savonitto S, Ardissiono D, Egstrup K, et al. Combination therapy with metoprolol and nifedipine versus monotherapy in patients with stable angina pectoris. Results of the International Multicenter Angina Exercise (IMAGE) Study. J Am Coll Cardiol. 1996;27:311 6. 789. Emanuelsson H, Egstrup K, Nikus K, et al. Antianginal efficacy of the combination of felodipine-metoprolol 10/100 mg compared with each drug alone in patients with stable effort-induced angina pectoris: a multicenter parallel group study. The TRAFFIC Study Group. Am Heart J. 1999;137:854 62. 790. Waysbort J, Meshulam N, Brunner D. Isosorbide mononitrate and atenolol in the treatment of stable exertional angina. Cardiology. 1991;79 Suppl 2:19 26. 791. Krepp HP. Evaluation of the antianginal and anti-ischemic efficacy of slow-release isosorbide mononitrate capsules, bupranolol and their combination, in patients with chronic stable angina pectoris. Car- diology. 1991;79 Suppl 2:14 8. 792. McMurray JJ, Ostergren J, Swedberg K, et al. Effects of candesartan in patients with chronic heart failure and reduced left-ventricular systolic function taking angiotensin-converting-enzyme inhibitors: the CHARM-Added trial. Lancet. 2003;362:767 71. 793. Nissen SE, Tuzcu EM, Libby P, et al. Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial. JAMA. 2004;292:2217 25. 794. Julius S, Weber MA, Kjeldsen SE, et al. The Valsartan Antihyper- tensive Long-Term Use Evaluation (VALUE) trial: outcomes in patients receiving monotherapy. Hypertension. 2006;48:385 91. 795. Danchin N, Cucherat M, Thuillez C, et al. Angiotensin-converting enzyme inhibitors in patients with coronary artery disease and absence of heart failure or left ventricular systolic dysfunction: an overview of long-term randomized controlled trials. Arch Intern Med. 2006;166: 787 96. 796. Al-Mallah MH, Tleyjeh IM, bdel-Latif AA, et al. Angioten- sinconverting enzyme inhibitors in coronary artery disease and pre- served left ventricular systolic function: a systematic review and meta- analysis of randomized controlled trials. J Am Coll Cardiol. 2006;47: 1576 83. 797. Pitt B, O Neill B, Feldman R, et al. The QUinapril Ischemic Event Trial (QUIET): evaluation of chronic ACE inhibitor therapy in patients with ischemic heart disease and preserved left ventricular function. Am J Cardiol. 2001;87:1058 63. 798. Lonn EM, Yusuf S, Jha P, et al. Emerging role of angioten- sinconverting enzyme inhibitors in cardiac and vascular protection. Circulation. 1994;90:2056 69. 799. Prasad A, Husain S, Quyyumi AA. Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin- converting enzyme inhibition: a potential role of bradykinin. J Am Coll Cardiol. 1999;33:796 804. 800. Tummala PE, Chen XL, Sundell CL, et al. Angiotensin II induces vascular cell adhesion molecule-1 expression in rat vasculature: A potential link between the renin-angiotensin system and atherosclero- sis. Circulation. 1999;100:1223 9. 801. Pfeffer MA, Braunwald E, Moye LA, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators. N Engl J Med. 1992;327: 669 77. 802. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators. Lancet. 2000;355:253 9. 803. Rouleau JL, Warnica WJ, Baillot R, et al. Effects of angioten- sinconverting enzyme inhibition in low-risk patients early after coronary artery bypass surgery. Circulation. 2008;117:24 31. 804. Turnbull F, Neal B, Pfeffer M, et al. Blood pressure-dependent and independent effects of agents that inhibit the renin-angiotensin system. J Hypertens. 2007;25:951 8. 805. Okin PM, Devereux RB, Jern S, et al. Regression of electrocardio- graphic left ventricular hypertrophy by losartan versus atenolol: The Losartan Intervention for Endpoint reduction in Hypertension (LIFE) Study. Circulation. 2003;108:684 90. 806. H5N1 avian influenza: first steps towards development of a human vaccine. Wkly Epidemiol Rec. 2005;80:277 8. 807. Davis MM, Taubert K, Benin AL, et al. Influenza vaccination as secondary prevention for cardiovascular disease: a science advisory from the American Heart Association/American College of Car- diology. J Am Coll Cardiol. 2006;48:1498 502. 808. de Diego C, Vila-Corcoles A, Ochoa O, et al. Effects of annual influenza vaccination on winter mortality in elderly people with chronic heart disease. Eur Heart J. 2008;30:209 16. 809. Couch RB, Winokur P, Brady R, et al. Safety and immunogenicity of a high dosage trivalent influenza vaccine among elderly subjects. Vaccine. 2007;25:7656 63. 810. Keitel WA, Atmar RL, Cate TR, et al. Safety of high doses of influenza vaccine and effect on antibody responses in elderly persons. Arch Intern Med. 2006;166:1121 7. 811. Hulley S, Grady D, Bush T, et al. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in post- menopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998;280:605 13. 812. Anderson GL, Limacher M, Assaf AR, et al. Effects of conjugated equine estrogen in postmenopausal women with hysterectomy: the Women s Health Initiative randomized controlled trial. JAMA. 2004; 291:1701 12. 813. Manson JE, Hsia J, Johnson KC, et al. Estrogen plus progestin and the risk of coronary heart disease. N Engl J Med. 2003;349:523 34. 814. Rossouw JE, Anderson GL, Prentice RL, et al. Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women s Health Initiative randomized controlled trial. JAMA. 2002;288:321 33. 815. de Gaetano G. Low-dose aspirin and vitamin E in people at cardiovas- cular risk: a randomised trial in general practice. Collaborative Group of the Primary Prevention Project. Lancet. 2001;357:89 95. Fihn et al Stable Ischemic Heart Disease: Full Text e453 816. Stephens NG, Parsons A, Schofield PM, et al. Randomised controlled trial of vitamin E in patients with coronary disease: Cambridge Heart Antioxidant Study (CHAOS). Lancet. 1996;347:781 6. 817. Yusuf S, Dagenais G, Pogue J, et al. Vitamin E supplementation and cardiovascular events in high-risk patients. The Heart Outcomes Pre- vention Evaluation Study Investigators. N Engl J Med. 2000;342: 154 60. 818. Bjelakovic G, Nikolova D, Gluud LL, et al. Mortality in randomized trials of antioxidant supplements for primary and secondary pre- vention: systematic review and meta-analysis. JAMA. 2007;297: 842 57. 819. Bazzano LA, Reynolds K, Holder KN, et al. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006;296:2720 6. 820. Bonaa KH, Njolstad I, Ueland PM, et al. Homocysteine lowering and cardiovascular events after acute myocardial infarction. N Engl J Med. 2006;354:1578 88. 821. Lonn E, Yusuf S, Arnold MJ, et al. Homocysteine lowering with folic acid and B vitamins in vascular disease. N Engl J Med. 2006;354: 1567 77. 822. Toole JF, Malinow MR, Chambless LE, et al. Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial. JAMA. 2004;291:565 75. 823. Guldager B, Jelnes R, Jorgensen SJ, et al. EDTA treatment of inter- mittent claudication a double-blind, placebo-controlled study. J Intern Med. 1992;231:261 7. 824. van Rij AM, Solomon C, Packer SG, et al. Chelation therapy for intermittent claudication. A double-blind, randomized, controlled trial. Circulation. 1994;90:1194 9. 825. Sloth-Nielsen J, Guldager B, Mouritzen C, et al. Arteriographic findings in EDTA chelation therapy on peripheral arteriosclerosis. Am J Surg. 1991;162:122 5. 826. Knudtson ML, Wyse DG, Galbraith PD, et al. Chelation therapy for ischemic heart disease: a randomized controlled trial. JAMA. 2002; 287:481 6. 827. Grady D, Rubin SM, Petitti DB, et al. Hormone therapy to prevent disease and prolong life in postmenopausal women. Ann Intern Med. 1992;117:1016 37. 828. Stampfer MJ, Colditz GA. Estrogen replacement therapy and coronary heart disease: a quantitative assessment of the epidemiologic evidence. Prev Med. 1991;20:47 63. 829. Stampfer MJ, Colditz GA, Willett WC, et al. Postmenopausal estrogen therapy and cardiovascular disease. Ten-year follow-up from the nurses health study. N Engl J Med. 1991;325:756 62. 830. Effects of estrogen or estrogen/progestin regimens on heart disease risk factors in postmenopausal women. The Postmenopausal Estrogen/ Pro- gestin Interventions (PEPI) Trial. The Writing Group for the PEPI Trial. JAMA. 1995;273:199 208. 831. Hong MK, Romm PA, Reagan K, et al. Effects of estrogen replacement therapy on serum lipid values and angiographically defined coronary artery disease in postmenopausal women. Am J Cardiol. 1992;69: 176 8. 832. Koh KK. Effects of estrogen on the vascular wall: vasomotor function and inflammation. Cardiovasc Res. 2002;55:714 26. 833. Manolio TA, Furberg CD, Shemanski L, et al. Associations of post- menopausal estrogen use with cardiovascular disease and its risk factors in older women. The CHS Collaborative Research Group. Circulation. 1993;88:2163 71. 834. Grady D, Herrington D, Bittner V, et al. Cardiovascular disease outcomes during 6.8 years of hormone therapy: Heart and Estrogen/ progestin Replacement Study follow-up (HERS II). JAMA. 2002;288: 49 57. 835. Waters DD, Alderman EL, Hsia J, et al. Effects of hormone replacement therapy and antioxidant vitamin supplements on coronary atherosclerosis in postmenopausal women: a randomized controlled trial. JAMA. 2002;288:2432 40. 836. Rimm EB, Stampfer MJ, Ascherio A, et al. Vitamin E consumption and the risk of coronary heart disease in men. N Engl J Med. 1993;328: 1450 6. 837. Stampfer MJ, Hennekens CH, Manson JE, et al. Vitamin E con- sumption and the risk of coronary disease in women. N Engl J Med. 1993;328:1444 9. 838. Vivekananthan DP, Penn MS, Sapp SK, et al. Use of antioxidant vitamins for the prevention of cardiovascular disease: meta-analysis of randomised trials. Lancet. 2003;361:2017 23. 839. Homocysteine and risk of ischemic heart disease and stroke: a meta- analysis. JAMA. 2002;288:2015 22. 840. Arnesen E, Refsum H, Bonaa KH, et al. Serum total homocysteine and coronary heart disease. Int J Epidemiol. 1995;24:704 9. 841. Nygard O, Nordrehaug JE, Refsum H, et al. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med. 1997;337:230 6. 842. Villarruz MV, Dans A, Tan F. Chelation therapy for atherosclerotic cardiovascular disease. Cochrane Database Syst Rev. 2002; CD002785. 843. Abrams J. Clinical practice. Chronic stable angina. N Engl J Med. 2005;352:2524 33. 844. Wight LJ, VandenBurg MJ, Potter CE, et al. A large scale comparative study in general practice with nitroglycerin spray and tablet formu- lations in elderly patients with angina pectoris. Eur J Clin Pharmacol. 1992;42:341 2. 845. VandenBurg MJ, Wight LJ, Griffiths GK, et al. Sublingual nitroglyc- erin or spray in the treatment of angina. Br J Clin Pract. 1986;40: 524 7. 846. Rousseau MF, Pouleur H, Cocco G, et al. Comparative efficacy of ranolazine versus atenolol for chronic angina pectoris. Am J Cardiol. 2005;95:311 6. 847. Chaitman BR, Pepine CJ, Parker JO, et al. Effects of ranolazine with atenolol, amlodipine, or diltiazem on exercise tolerance and angina frequency in patients with severe chronic angina: a randomized con- trolled trial. JAMA. 2004;291:309 16. 848. Stone PH, Gratsiansky NA, Blokhin A, et al. Antianginal efficacy of ranolazine when added to treatment with amlodipine: the ERICA (Efficacy of Ranolazine in Chronic Angina) trial. J Am Coll Cardiol. 2006;48:566 75. 849. Ishikawa K, Nakai S, Takenaka T, et al. Short-acting nifedipine and diltiazem do not reduce the incidence of cardiac events in patients with healed myocardial infarction. Secondary Prevention Group. Circu- lation. 1997;95:2368 73. 850. The effect of diltiazem on mortality and reinfarction after myocardial infarction. The Multicenter Diltiazem Postinfarction Trial Research Group. N Engl J Med. 1988;319:385 92. 851. Effect of verapamil on mortality and major events after acute myo- cardial infarction (the Danish Verapamil Infarction Trial II DAVIT II). Am J Cardiol. 1990;66:779 85. 852. Frishman WH, Sica DA. Calcium Channel Blockers. In: Frishman WH, Sonnenblick EH, Sica DA, editors. Cardiovascular Pharmacohera- peutics. New York: McGraw-Hill; 2003. 853. Abernethy DR, Schwartz JB. Calcium-antagonist drugs. N Engl J Med. 1999;341:1447 57. 854. Ezekowitz MD, Hossack K, Mehta JL, et al. Amlodipine in chronic stable angina: results of a multicenter double-blind crossover trial. Am Heart J. 1995;129:527 35. 855. Boman K, Saetre H, Karlsson LG, et al. Antianginal effect of conven- tional and controlled release diltiazem in stable angina pectoris. Eur J Clin Pharmacol. 1995;49:27 30. 856. Brogden RN, Benfield P. Verapamil: a review of its pharmacological properties and therapeutic use in coronary artery disease. Drugs. 1996; 51:792 819. 857. Antman E, Muller J, Goldberg S, et al. Nifedipine therapy for coronary-artery spasm. Experience in 127 patients. N Engl J Med. 1980;302:1269 73. 858. Pepine CJ, Feldman RL, Whittle J, et al. Effect of diltiazem in patients with variant angina: a randomized double-blind trial. Am Heart J. 1981;101:719 25. 859. Johnson SM, Mauritson DR, Willerson JT, et al. Verapamil adminis- tration in variant angina pectoris. Efficacy shown by ecg monitoring. JAMA. 1981;245:1849 51. 860. Alderman MH, Cohen H, Roque R, et al. Effect of long-acting and short-acting calcium antagonists on cardiovascular outcomes in hyper- tensive patients. Lancet. 1997;349:594 8. 861. Parmley WW, Nesto RW, Singh BN, et al. Attenuation of the circadian patterns of myocardial ischemia with nifedipine GITS in patients with chronic stable angina. N-CAP Study Group. J Am Coll Cardiol. 1992; 19:1380 9. 862. Tatti P, Pahor M, Byington RP, et al. Outcome results of the Fosinopril Versus Amlodipine Cardiovascular Events Randomized Trial (FACET) in patients with hypertension and NIDDM. Diabetes Care. 1998;21:597 603. 863. Gori T, Di Stolfo G, Sicuro S, et al. Nitroglycerin protects the endo- thelium from ischaemia and reperfusion: human mechanistic insight. Br J Clin Pharmacol. 2007;64:145 50. 864. Dawn B, Bolli R. Role of nitric oxide in myocardial preconditioning. Ann N Y Acad Sci. 2002;962:18 41. 865. Jneid H, Chandra M, Alshaher M, et al. Delayed preconditioning- mimetic actions of nitroglycerin in patients undergoing exercise tol- erance tests. Circulation. 2005;111:2565 71. 866. Parker JD, Parker JO. Nitrate therapy for stable angina pectoris. N Engl J Med. 1998;338:520 31. 867. Bottcher M, Madsen MM, Randsbaek F, et al. Effect of oral nitroglyc- erin and cold stress on myocardial perfusion in areas subtended by stenosed and nonstenosed coronary arteries. Am J Cardiol. 2002;89: 1019 24. 868. Munzel T, Mulsch A, Kleschyov A. Mechanisms underlying nitroglyc- erin-induced superoxide production in platelets: some insight, more questions. Circulation. 2002;106:170 2. 869. Lacoste LL, Theroux P, Lidon RM, et al. Antithrombotic properties of transdermal nitroglycerin in stable angina pectoris. Am J Cardiol. 1994;73:1058 62. 870. Munzel T, Daiber A, Mulsch A. Explaining the phenomenon of nitrate tolerance. Circ Res. 2005;97:618 28. 871. Gori T, Parker JD. The puzzle of nitrate tolerance: pieces smaller than we thought? Circulation. 2002;106:2404 8. 872. Azevedo ER, Schofield AM, Kelly S, et al. Nitroglycerin withdrawal increases endothelium-dependent vasomotor response to acetylcholine. J Am Coll Cardiol. 2001;37:505 9. 873. Heitzer T, Just H, Brockhoff C, et al. Long-term nitroglycerin treatment is associated with supersensitivity to vasoconstrictors in men with stable coronary artery disease: prevention by concomitant treatment with captopril. J Am Coll Cardiol. 1998;31:83 8. 874. Taylor AL, Ziesche S, Yancy C, et al. Combination of isosorbide dinitrate and hydralazine in blacks with heart failure. N Engl J Med. 2004;351:2049 57. 875. Gogia H, Mehra A, Parikh S, et al. Prevention of tolerance to hemo- dynamic effects of nitrates with concomitant use of hydralazine in patients with chronic heart failure. J Am Coll Cardiol. 1995;26: 1575 80. 876. DeMots H, Glasser SP. Intermittent transdermal nitroglycerin therapy in the treatment of chronic stable angina. J Am Coll Cardiol. 1989;13: 786 95. 877. Chrysant SG, Glasser SP, Bittar N, et al. Efficacy and safety of extended-release isosorbide mononitrate for stable effort angina pectoris. Am J Cardiol. 1993;72:1249 56. 878. Parker JO, Amies MH, Hawkinson RW, et al. Intermittent transdermal nitroglycerin therapy in angina pectoris. Clinically effective without tolerance or rebound. Minitran Efficacy Study Group. Circulation. 1995;91:1368 74. 879. Abrams J. Glyceryl trinitrate (nitroglycerin) and the organic nitrates. Choosing the method of administration. Drugs. 1987;34:391 403. 880. Iafrate RP Jr, Yost RL, Curry SH, et al. Effect of dose and ointment application technique on nitroglycerin plasma concentrations. Pharma- cotherapy. 1983;3:118 24. 881. Moe G, Armstrong PW. Influence of skin site on bioavailability of nitroglycerin ointment in congestive heart failure. Am J Med. 1986; 81:765 70. 882. Silber S. Nitrates: why and how should they be used today? Current status of the clinical usefulness of nitroglycerin, isosorbide dinitrate and isosorbide mononitrate. Eur J Clin Pharmacol. 1990;38 Suppl 1:S35 S51. 883. CV Therapeutics. Ranexa Package Insert. http://www.cvt.com/pdf/ RanexaPI.pdf. 2007. Available at: http://www.cvt.com/pdf/RanexaPI. pdf. Accessed July 15, 2008. 884. Chaitman BR, Skettino SL, Parker JO, et al. Anti-ischemic effects and long-term survival during ranolazine monotherapy in patients with chronic severe angina. J Am Coll Cardiol. 2004;43:1375 82. 885. Morrow DA, Scirica BM, Karwatowska-Prokopczuk E, et al. Effects of ranolazine on recurrent cardiovascular events in patients with non- STelevation acute coronary syndromes: the MERLIN-TIMI 36 ran- domized trial. JAMA. 2007;297:1775 83. 886. Vardeny O, Sweitzer NK, Detry MA, et al. Decreased immune responses to influenza vaccination in patients with heart failure. J Card Fail. 2009;15:368 73. 887. Arnold SV, Morrow DA, Wang K, et al. Effects of ranolazine on disease-specific health status and quality of life among patients with acute coronary syndromes: results from the MERLIN-TIMI 36 ran- domized trial. Circ Cardiovasc Qual Outcomes. 2008;1:107 15. 888. Morrow DA, Scirica BM, Chaitman BR, et al. Evaluation of the glycometabolic effects of ranolazine in patients with and without diabetes mellitus in the MERLIN-TIMI 36 randomized controlled trial. Circulation. 2009;119:2032 9. 889. Timmis AD, Chaitman BR, Crager M. Effects of ranolazine on exercise tolerance and HbA1c in patients with chronic angina and diabetes. Eur Heart J. 2006;27:42 8. 890. Scirica BM, Morrow DA, Hod H, et al. Effect of ranolazine, an antianginal agent with novel electrophysiological properties, on the incidence of arrhythmias in patients with non ST-segment elevation acute coronary syndrome: results from the Metabolic Efficiency With Ranolazine for Less Ischemia in Non ST-Elevation Acute Coronary Syndrome Thrombolysis in Myocardial Infarction 36 (MERLIN-TIMI 36) randomized controlled trial. Circulation. 2007;116:1647 52. 891. Mega JL, Hochman JS, Scirica BM, et al. Clinical features and outcomes of women with unstable ischemic heart disease: observations from metabolic efficiency with ranolazine for less ischemia in non-ST- elevation acute coronary syndromes-thrombolysis in myocardial infarction 36 (MERLIN-TIMI 36). Circulation. 2010;121:1809 17. 892. Jerling M, Abdallah H. Effect of renal impairment on multiple-dose pharmacokinetics of extended-release ranolazine. Clin Pharmacol Ther. 2005;78:288 97. 893. Markham A, Plosker GL, Goa KL. Nicorandil. An updated review of its use in ischaemic heart disease with emphasis on its cardioprotective effects. Drugs. 2000;60:955 74. 894. Nicorandil study ivestigators. Nicorandil for angina an update. Drug Ther Bull. 2003;41:86 8. 895. Treese N, Erbel R, Meyer J. Acute hemodynamic effects of nicorandil in coronary artery disease. J Cardiovasc Pharmacol. 1992;20 Suppl 3:S52 S56. 896. Doring G. Antianginal and anti-ischemic efficacy of nicorandil in comparison with isosorbide mononitrate and isosorbide dinitrate: results from two multicenter, double-blind, randomized studies with stable coronary heart disease patients. J Cardiovasc Pharmacol. 1992;20 Suppl 3:S74 S81. 897. Di Somma S, Liguori V, Petitto M, et al. A double-blind comparison of nicorandil and metoprolol in stable effort angina pectoris. Cardiovasc Drugs Ther. 1993;7:119 23. 898. Effect of nicorandil on coronary events in patients with stable angina: the Impact Of Nicorandil in Angina (IONA) randomised trial. Lancet. 2002;359:1269 75. 899. Rajaratnam R, Brieger DB, Hawkins R, et al. Attenuation of anti-is- chemic efficacy during chronic therapy with nicorandil in patients with stable angina pectoris. Am J Cardiol. 1999;83:1120 4, A9. 900. DiFrancesco D, Camm JA. Heart rate lowering by specific and selective I(f) current inhibition with ivabradine: a new therapeutic perspective in cardiovascular disease. Drugs. 2004;64:1757 65. 901. Joannides R, Moore N, Iacob M, et al. Comparative effects of ivabradine, a selective heart rate-lowering agent, and propranolol on systemic and cardiac haemodynamics at rest and during exercise. Br J Clin Pharmacol. 2006;61:127 37. 902. Manz M, Reuter M, Lauck G, et al. A single intravenous dose of ivabradine, a novel I(f) inhibitor, lowers heart rate but does not depress left ventricular function in patients with left ventricular dysfunction. Cardiology. 2003;100:149 55. 903. Camm AJ, Lau CP. Electrophysiological effects of a single intravenous administration of ivabradine (S 16257) in adult patients with normal baseline electrophysiology. Drugs R D. 2003;4:83 9. 904. Borer JS, Fox K, Jaillon P, et al. Antianginal and antiischemic effects of ivabradine, an I(f) inhibitor, in stable angina: a randomized, double- blind, multicentered, placebo-controlled trial. Circulation. 2003;107: 817 23. 905. Tardif JC, Ford I, Tendera M, et al. Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina. Eur Heart J. 2005;26:2529 36. 906. Fox K, Ford I, Steg PG, et al. Ivabradine for patients with stable coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:807 16. 907. Kantor PF, Lucien A, Kozak R, et al. The antianginal drug trimeta- zidine shifts cardiac energy metabolism from fatty acid oxidation to Fihn et al Stable Ischemic Heart Disease: Full Text e455 glucose oxidation by inhibiting mitochondrial longchain ketoacyl coenzyme A thiolase. Circ Res. 2000;86:580 8. 908. Marzilli M, Klein WW. Efficacy and tolerability of trimetazidine in stable angina: a meta-analysis of randomized, double-blind, controlled trials. Coron Artery Dis. 2003;14:171 9. 909. Ciapponi A, Pizarro R, Harrison J. Trimetazidine for stable angina. Cochrane Database Syst Rev. 2005;CD003614. 910. Arora RR, Chou TM, Jain D, et al. The multicenter study of enhanced external counterpulsation (MUST-EECP): effect of EECP on exercise- induced myocardial ischemia and anginal episodes. J Am Coll Cardiol. 1999;33:1833 40. 911. Mannheimer C, Eliasson T, Augustinsson LE, et al. Electrical stimu- lation versus coronary artery bypass surgery in severe angina pectoris: the ESBY study. Circulation. 1998;97:1157 63. 912. Hautvast RW, DeJongste MJ, Staal MJ, et al. Spinal cord stimulation in chronic intractable angina pectoris: a randomized, controlled efficacy study. Am Heart J. 1998;136:1114 20. 913. van der Sloot JA, Huikeshoven M, Tukkie R, et al. Transmyocardial revascularization using an XeCl excimer laser: results of a randomized trial. Ann Thorac Surg. 2004;78:875 81. 914. Guleserian KJ, Maniar HS, Camillo CJ, et al. Quality of life and survival after transmyocardial laser revascularization with the holmi- um: YAG laser. Ann Thorac Surg. 2003;75:1842 7. 915. Myers J, Oesterle SN, Jones J, et al. Do transmyocardial and percuta- neous laser revascularization induce silent ischemia? An assessment by exercise testing. Am Heart J. 2002;143:1052 7. 916. Ballegaard S, Pedersen F, Pietersen A, et al. Effects of acupuncture in moderate, stable angina pectoris: a controlled study. J Intern Med. 1990;227:25 30. 917. Ballegaard S, Jensen G, Pedersen F, et al. Acupuncture in severe, stable angina pectoris: a randomized trial. Acta Med Scand. 1986;220: 307 13. 918. Spertus JA, Jones PG, Coen M, et al. Transmyocardial CO(2) laser revascularization improves symptoms, function, and quality of life: 1 month results from a randomized controlled trial. Am J Med. 2001; 111:341 8. 919. Bridges CR, Horvath KA, Nugent WC, et al. The Society of Thoracic Surgeons practice guideline series: transmyocardial laser revascular- ization. Ann Thorac Surg. 2004;77:1494 502. 920. Vineberg AM. Development of an anastomosis between the coronary vessels and a transplanted internal mammary artery. Can Med Assoc J. 1946;55:117 9. 921. Stone GW, Teirstein PS, Rubenstein R, et al. A prospective, multi- center, randomized trial of percutaneous transmyocardial laser revas- cularization in patients with nonrecanalizable chronic total occlusions. J Am Coll Cardiol. 2002;39:1581 7. 922. Oesterle SN, Sanborn TA, Ali N, et al. Percutaneous transmyocardial laser revascularisation for severe angina: the PACIFIC randomised trial. Potential Class Improvement From Intramyocardial Channels. Lancet. 2000;356:1705 10. 923. Aaberge L, Nordstrand K, Dragsund M, et al. Transmyocardial revas- cularization with CO2 laser in patients with refractory angina pectoris. Clinical results from the Norwegian randomized trial. J Am Coll Cardiol. 2000;35:1170 7. 924. Frazier OH, March RJ, Horvath KA. Transmyocardial revasculariza- tion with a carbon dioxide laser in patients with end-stage coronary artery disease. N Engl J Med. 1999;341:1021 8. 925. Jones JW, Schmidt SE, Richman BW, et al. Holmium:YAG laser transmyocardial revascularization relieves angina and improves func- tional status. Ann Thorac Surg. 1999;67:1596 601. 926. Galinanes M, Loubani M, Sensky PR, et al. Efficacy of transmyo- cardial laser revascularization and thoracic sympathectomy for the treatment of refractory angina. Ann Thorac Surg. 2004;78:122 8. 927. Burkhoff D, Schmidt S, Schulman SP, et al. Transmyocardial laser revascularisation compared with continued medical therapy for treatment of refractory angina pectoris: a prospective randomised trial. ATLANTIC Investigators. Angina Treatments-Lasers and Normal Therapies in Comparison. Lancet. 1999;354:885 90. 928. Allen KB, Dowling RD, Fudge TL, et al. Comparison of transmyo- cardial revascularization with medical therapy in patients with refractory angina. N Engl J Med. 1999;341:1029 36. 929. Schofield PM, Sharples LD, Caine N, et al. Transmyocardial laser revascularisation in patients with refractory angina: a randomised con- trolled trial. Lancet. 1999;353:519 24. 930. Dowling RD, Petracek MR, Selinger SL, et al. Transmyocardial revas- cularization in patients with refractory, unstable angina. Circulation. 1998;98:II73 II75. 931. Allen KB, Dowling RD, Angell WW, et al. Transmyocardial revascu- larization: 5-year follow-up of a prospective, randomized multicenter trial. Ann Thorac Surg. 2004;77:1228 34. 932. Liao L, Sarria-Santamera A, Matchar DB, et al. Meta-analysis of survival and relief of angina pectoris after transmyocardial revascular- ization. Am J Cardiol. 2005;95:1243 5. 933. Mukherjee D, Bhatt DL, Roe MT, et al. 