Clinicians should work in partnership with patients to assess their readi- ness for sustained lifestyle improvements, identify po- tential barriers to change, and encourage them to try to achieve measurable goals and continue to monitor Finally, social determinants of ASCVD risk and their impact on the patient s ability to prevent or treat risk factors must be taken into account. Clini- cians need to consider patients health literacy and edu- cation levels and assess patients motivation to improve their lifestyle habits. The goal of the clinician is to match the intensity of preventive efforts with an individual s absolute risk of a future ASCVD event and with the individual s willing- ness and capacity to implement preventive strategies. Risk estimation is imperfect and based on group aver- ages that are then applied to individual patients. The clinician must balance an understanding of a patient s estimated ASCVD risk with potential benefits and ad- verse risk from pharmacological therapy in the context of a risk discussion. To determine the appropriateness of pharmacological therapy after quantitative risk estima- tion in cases that are unclear, risk-enhancing factors or selective use of a coronary artery calcium measurement can inform decision-making for cholesterol-lowering or antihypertensive medication use in intermediate-risk in- dividuals. This primary-prevention guideline strives to provide clinicians with the information they need to help their patients reduce their risk of ASCVD and encourage them to make healthier lifestyle changes when needed. ACC/AHA TASK FORCE MEMBERS Patrick T. O Gara, MD, MACC, FAHA, Chair; Joshua A. Beckman, MD, MS, FAHA, Chair-Elect; Glenn N. Levine, MD, FACC, FAHA, Immediate Past Chair*; Sana M. Al-Khatib, MD, MHS, FACC, FAHA; Kim K. Birtcher, PharmD, MS, AACC; Joaquin E. Cigarroa, MD, FACC; Anita Deswal, MD, MPH, FACC, FAHA; Lee A. Fleisher, MD, FACC, FAHA; Federico Gentile, MD, FACC; Zachary D. Goldberger, MD, MS, FACC, FAHA*; Mark A. Hlatky, MD, FACC, FAHA; John Iko- nomidis, MD, PhD, FAHA*; Jos A. Joglar, MD, FACC, FAHA; Laura Mauri, MD, MSc, FAHA*; Mariann R. Piano, RN, PhD, FAHA; Barbara Riegel, PhD, RN, FAHA*; Duminda N. Wijeysundera, MD, PhD PRESIDENTS AND STAFF American College of Cardiology C. Michael Valentine, MD, FACC, President Timothy W. Attebery, MBA, FACHE, Chief Executive Officer William J. Oetgen, MD, MBA, FACC, Executive Vice Presi- dent, Science, Education, Quality, and Publishing MaryAnne Elma, MPH, Senior Director, Science, Educa- tion, Quality, and Publishing Amelia Scholtz, PhD, Publications Manager, Science, Education, Quality, and Publishing American College of Cardiology/ American Heart Association Katherine A. Sheehan, PhD, Director, Guideline Strategy and Operations Abdul R. Abdullah, MD, Senior Manager, Guideline Science Thomas S.D. Getchius, Manager, Guideline Operations American Heart Association Ivor Benjamin, MD, FAHA, President Nancy Brown, Chief Executive Officer Rose Marie Robertson, MD, FAHA, Chief Science and Medicine Officer Gayle R. Whitman, PhD, RN, FAHA, FAAN, Senior Vice President, Office of Science Operations Cammie Marti, PhD, MPH, RN, Science and Medicine Advisor, Office of Science Operations Jody Hundley, Production and Operations Manager, Scientific Publications, Office of Science Operations ARTICLE INFORMATION This document was approved by the American College of Cardiology Clinical Policy Approval Committee, the American Heart Association Science Advisory and Coordinating Committee, and the American Heart Association Executive Committee in February 2019. Supplemental materials are available with this article at https://www. This article has been copublished in the Journal of the American College of Cardiology. Copies: This document is available on the websites of the American College of Cardiology (www.acc.org) and the American Heart Association (professional.heart.org/). A copy of the document is also available at https:// professional.heart.org/statements by selecting the Guidelines & Statements button. To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@ wolterskluwer.com. The expert peer review of AHA-commissioned documents (eg, scientific statements, clinical practice guidelines, systematic reviews) is conducted by the AHA Office of Science Operations. For more on AHA statements and guide- lines development, visit https://professional.heart.org/statements. Select the Guidelines & Statements drop-down menu near the top of the web page, then click Publication Development. Permissions: Multiple copies, modification, alteration, enhancement, and/ or distribution of this document are not permitted without the express permis- sion of the American Heart Association. Instructions for obtaining permission are are located at https://www.heart.org/permissions. A link to the Copyright Permissions Request Form appears in the second paragraph (https://www. heart.org/en/about-us/statements-and-policies/copyright-request-form). * Former Task Force member; current member during the writing effort. CLINICAL STATEMENTS AND GUIDELINES REFERENCES S1-1. Weir HK, Anderson RN, Coleman King SM, et al. Heart disease and cancer deaths trends and projections in the United States, 1969 2020. Prev Chronic Dis. 2016;13:E157. S1-2. Johnson NB, Hayes LD, Brown K, et al. CDC National Health Report: leading causes of morbidity and mortality and associated behavioral risk and protective factors United States, 2005 2013. MMWR Suppl. 2014;63:3 27. S1-3. Xu J, Murphy SL, Kochanek KD, et al. Mortality in the United States, 2015. NCHS Data Brief. 2016:1 8. S1-4. Greenland P, Knoll MD, Stamler J, et al. Major risk factors as ante- cedents of fatal and nonfatal coronary heart disease events. JAMA. 2003;290:891 7. S1-5. Lloyd-Jones DM, Hong Y, Labarthe D, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association s Strategic Impact Goal through 2020 and beyond. Circulation. 2010;121:586 613. S1-6. Turco JV, Inal-Veith A, Fuster V. Cardiovascular health promotion: an issue that can no longer wait. J Am Coll Cardiol. 2018;72:908 13. S1-7. Younus A, Aneni EC, Spatz ES, et al. A systematic review of the prevalence and outcomes of ideal cardiovascular health in US and non-US populations. Mayo Clin Proc. 2016;91:649 70. 1.1. Methodology and Evidence Review S1.1-1. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13 115. S1.1-2. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/ AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082 1143. 1.5. Class of Recommendation and Level of Evidence S1.5-1. Halperin JL, Levine GN, Al-Khatib SM, et al. Further evolution of the ACC/AHA clinical practice guideline recommendation classification system: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2016;133:1426 8. RECOMMENDATIONS FOR ASCVD PREVENTION EFFORTS 2.1. Patient-Centered Approaches for Providing Comprehensive ASCVD Prevention S2.1-1. Carter BL, Rogers M, Daly J, et al. The potency of team-based care interventions for hypertension: a meta-analysis. Arch Intern Med. 2009;169:1748 55. S2.1-2. Chisholm-Burns MA, Kim Lee J, Spivey CA, et al. US pharmacists effect as team members on patient care: systematic review and meta-analyses. Med Care. 2010;48:923 33. S2.1-3. Fazel MT, Bagalagel A, Lee JK, et al. Impact of diabetes care by pharmacists as part of health care team in ambulatory set- tings: a systematic review and meta-analysis. Ann Pharmacother. 2017;51:890 907. S2.1-4. Mills KT, Obst KM, Shen W, et al. Comparative effectiveness of implementation strategies for blood pressure control in hypertensive patients: a systematic review and meta-analysis. Ann Intern Med. 2018;168:110 20. S2.1-5. Proia KK, Thota AB, Njie GJ, et al. Team-based care and improved blood pressure control: a community guide systematic review. Am J Prev Med. 2014;47:86 99. S2.1-6. Chen Z, Ernst ME, Ardery G, et al. Physician-pharmacist co-man- agement and 24-hour blood pressure control. J Clin Hypertens (Greenwich). 2013;15:337 43. S2.1-7. Hirsch JD, Steers N, Adler DS, et al. Primary care-based, pharma- cist-physician collaborative medication-therapy management of hypertension: a randomized, pragmatic trial. Clin Ther. 2014;36: 1244 54. S2.1-8. Hunt JS, Siemienczuk J, Pape G, et al. A randomized controlled trial of team-based care: impact of physician-pharmacist collaboration on uncontrolled hypertension. J Gen Intern Med. 2008;23:1966 72. S2.1-9. Isetts BJ, Buffington DE, Carter BL, et al. Evaluation of pharmacists work in a physician-pharmacist collaborative model for the manage- ment of hypertension. Pharmacotherapy. 2016;36:374 84. S2.1-10. McLean DL, McAlister FA, Johnson JA, et al. A randomized trial of the effect of community pharmacist and nurse care on improving blood pressure management in patients with diabetes mellitus: study of cardiovascular risk intervention by pharmacists-hypertension (SCRIP-HTN). Arch Intern Med. 2008;168:2355 61. S2.1-11. Polgreen LA, Han J, Carter BL, et al. Cost-effectiveness of a physi- cian-pharmacist collaboration intervention to improve blood pres- sure control. Hypertension. 2015;66:1145 51. S2.1-12. Chen EH, Thom DH, Hessler DM, et al. Using the Teamlet Model to improve chronic care in an academic primary care practice. J Gen Intern Med 25 suppl 42010:S610 4. S2.1-13. Kravetz JD, Walsh RF. Team-based hypertension management to improve blood pressure control. J Prim Care Community Health. 2016;7:272 5. S2.1-14. Wan EYF, Fung CSC, Jiao27 FF, et al. Five-year effectiveness of the Multidisciplinary Risk Assessment and Management Programme- Diabetes Mellitus (RAMP-DM) on diabetes-related complications and health service uses a population-based and propensity-matched cohort study. Diabetes Care. 2018;41:49 59. S2.1-15. Buhse S, M ;hlhauser I, Heller T, et al. Informed shared decision- making programme on the prevention of myocardial infarc- tion in type 2 diabetes: a randomised controlled trial. BMJ Open. 2015;5:e009116. S2.1-16. Cooper LA, Roter DL, Carson KA, et al. A randomized trial to improve patient-centered care and hypertension control in underserved pri- mary care patients. J Gen Intern Med. 2011;26:1297 304. S2.1-17. Olomu A, Hart-Davidson W, Luo Z, et al. Implementing shared deci- sion making in federally qualified health centers, a quasi-exper- imental design study: the Office-Guidelines Applied to Practice (Office-GAP) program. BMC Health S24erv Res. 2016;16:334. S2.1-18. Parchman ML, Zeber JE, Palmer RF. Participatory decision making, patient activation, medication adherence, and intermediate clini- cal outcomes in type 2 diabetes: a STARNet study. Ann Fam Med. 2010;8:410 7. S2.1-19. Havranek EP, Mujahid MS, Barr DA, et al. Social determinants of risk and outcomes for cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2015;132:873 98. S2.1-20. Vilhelmsson A, stergren P-O. Reducing health inequalities with interventions targeting behavioral factors among individuals with low levels of education a rapid review. PLoS ONE. 2018;13: e0195774. S2.1-21. Schultz WM, Kelli HM, Lisko JC, et al. Socioeconomic status and cardiovascular outcomes: challenges and interventions. Circulation. 2018;137:2166 78. S2.1-22. Backholer K, Peters SAE, Bots SH, et al. Sex differences in the rela- tionship between socioeconomic status and cardiovascular disease: a systematic review and meta-analysis. J Epidemiol Community Health. 2017;71:550 7. S2.1-23. Beauchamp A, Peeters A, Tonkin A, et al. Best practice for prevention and treatment of cardiovascular disease through an equity lens: a review. Eur J Cardiovasc Prev Rehabil. 2010;17:599 606. S2.1-24. Khaing W, Vallibhakara SA, Attia J, et al. Effects of education and income on cardiovascular outcomes: a systematic review and meta- analysis. Eur J Prev Cardiol. 2017;24:1032 42. CLINICAL STATEMENTS AND GUIDELINES S2.1-25. Pollitt RA, Rose KM, Kaufman JS. Evaluating the evidence for models of life course socioeconomic factors and cardiovascular outcomes: a systematic review. BMC Public Health. 2005;5:7. S2.1-26. DeFilippis AP, Young R, McEvoy JW, et al. Risk score overestimation: the impact of individual cardiovascular risk factors and preventive therapies on the performance of the American Heart Association- American College of Cardiology-Atherosclerotic Cardiovascular Disease risk score in a modern multi-ethnic cohort. Eur Heart J. 2017;38:598 608. S2.1-27. Magnani JW, Mujahid MS, Aronow HD, et al. Health literacy and cardiovascular disease: fundamental relevance to primary and sec- ondary prevention: a scientific statement from the American Heart Association. Circulation. 2018;138:e48 74. S2.1-28. Powell TM, de Lemos JA, Banks K, et al. Body size misperception: a novel determinant in the obesity epidemic. Arch Intern Med. 2010;170:1695 7. S2.1-29. Padgett J, Biro FM. Different shapes in different cultures: body dis- satisfaction, overweight, and obesity in African-American and cau- casian females. J Pediatr Adolesc Gynecol. 2003;16:349 54. S2.1-30. US Department of Health and Human Services. Healthy People 2020. Washington, DC: 2010. Available at: https://www.healthypeople. gov. Accessed January 3, 2019. S2.1-31. Malambo P, Kengne AP, De Villiers A, et al. Built environment, selected risk factors and major cardiovascular disease outcomes: a systematic review. PLoS ONE. 2016;11:e0166846. S2.1-32. Bird EL, Ige JO, Pilkington P, et al. Built and natural environment planning principles for promoting health: an umbrella review. BMC Public Health. 2018;18:930. S2.1-33. Kaiser P, Diez Roux AV, Mujahid M, et al. Neighborhood environ- ments and incident hypertension in the Multi-Ethnic Study of Atherosclerosis. Am J Epidemiol. 2016;183:988 97. S2.1-34. Kumanyika SK, Gary TL, Lancaster KJ, et al. Achieving healthy weight in African-American communities: research perspectives and priori- ties. Obes Res. 2005;13:2037 47. S2.1-35. Grandner MA. Addressing sleep disturbances: an opportunity to pre- vent cardiometabolic disease? Int Rev Psychiatry. 2014;26:155 76. S2.1-36. Knutson KL. Sociodemographic and cultural determinants of sleep deficiency: implications for cardiometabolic disease risk. Soc Sci Med. 2013;79:7 15. S2.1-37. Ismail K, Winkley K, Rabe-Hesketh S. Systematic review and meta- analysis of randomised controlled trials of psychological interven- tions to improve glycaemic control in patients with type 2 diabetes. Lancet. 2004;363:1589 97. S2.1-38. Alam R, Sturt J, Lall R, et al. An updated meta-analysis to assess the effectiveness of psychological interventions delivered by psychologi- cal specialists and generalist clinicians on glycaemic control and on psychological status. Patient Educ Couns. 2009;75:25 36. S2.1-39. Bolen SD, Chandar A, Falck-Ytter C, et al. Effectiveness and safety of patient activation interventions for adults with type 2 diabetes: systematic review, meta-analysis, and meta-regression. J Gen Intern Med. 2014;29:1166 76. S2.1-40. Gonzalez JS, Tanenbaum ML, Commissariat PV. Psychosocial fac- tors in medication adherence and diabetes self-management: Implications for research and practice. Am Psychol. 2016;71: 539 51. S2.1-41. Javaheri S, Redline S. Insomnia and risk of cardiovascular disease. Chest. 2017;152:435 44. S2.1-42. Samuel LJ, Dennison Himmelfarb CR, Szklo M, et al. Social engage- ment and chronic disease risk behaviors: the Multi-Ethnic Study of Atherosclerosis. Prev Med. 2015;71:61 6. S2.1-43. Verbiest M, Brakema E, van der Kleij R, et al. National guidelines for smoking cessation in primary care: a literature review and evidence analysis. NPJ Prim Care Respir Med. 2017;27:2. 2.2. Assessment of Cardiovascular Risk S2.2-1. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S49 73. S2.2-2. American College of Cardiology, American Heart Association. ASCVD Risk Estimator. Available at: https://tools.acc.org/ldl/ascvd_ risk_estimator/index.html#!/calulate/estimator. Accessed September 21, 2018. S2.2-3. Ference BA, Graham I, Tokgozoglu L, et al. Impact of lipids on car- diovascular health: JACC Health Promotion Series. J Am Coll Cardiol. 2018;72:1141 56. S2.2-4. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/ AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082 1143. S2.2-5. Patel J, Al Rifai M, Scheuner MT, et al. Basic vs more complex definitions of family history in the prediction of coronary heart dis- ease: the Multi-Ethnic Study of Atherosclerosis. Mayo Clin Proc. 2018;93:1213 23. S2.2-6. del Rinc n ID, Williams K, Stern MP, et al. High incidence of car- diovascular events in a rheumatoid arthritis cohort not explained by traditional cardiac risk factors. Arthritis Rheum. 2001;44:2737 45. S2.2-7. Manzi S, Meilahn EN, Rairie JE, et al. Age-specific incidence rates of myocardial infarction and angina in women with systemic lupus erythematosus: comparison with the Framingham Study. Am J Epidemiol. 1997;145:408 15. S2.2-8. Wu P, Haththotuwa R, Kwok CS, et al. Preeclampsia and future cardiovascular health: a systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2017;10:e003497. S2.2-9. Tanz LJ, Stuart JJ, Williams PL, et al. Preterm delivery and mater- nal cardiovascular disease in young and middle-aged adult women. Circulation. 2017;135:578 89. S2.2-10. Wellons M, Ouyang P, Schreiner PJ, et al. Early menopause predicts future coronary heart disease and stroke: the Multi-Ethnic Study of Atherosclerosis. Menopause. 2012;19:1081 7. S2.2-11. Uddin SMI, Mirbolouk M, Dardari Z, et al. Erectile dysfunction as an independent predictor of future cardiovascular events. Circulation. 2018;138:540 2. S2.2-12. Triant VA, Perez J, Regan S, et al. Cardiovascular risk predic- tion functions underestimate risk in HIV infection. Circulation. 2018;137:2203 14. S2.2-13. Volgman AS, Palaniappan LS, Aggarwal NT, et al. Atherosclerotic cardiovascular disease in South Asians in the United States: epide- miology, risk factors, and treatments: a scientific statement from the American Heart Association. Circulation. 2018;138:e1 34. S2.2-14. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195 207. S2.2-15. DeFilippis AP, Young R, Carrubba CJ, et al. An analysis of calibra- tion and discrimination among multiple cardiovascular risk scores in a modern multiethnic cohort. Ann Intern Med. 2015;162:266 75. S2.2-16. Mahabadi AA, M hlenkamp S, Lehmann N, et al. CAC score improves coronary and CV risk assessment above statin indication by ESC and AHA/ACC primary prevention guidelines. JACC Cardiovasc Imaging. 2017;10:143 53. S2.2-17. Budoff MJ, Young R, Burke G, et al. Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the Multi-Ethnic Study of Atherosclerosis (MESA). Eur Heart J. 2018;39:2401 8. S2.2-18. McClelland RL, Jorgensen NW, Budoff M, et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors: derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) study and the DHS (Dallas Heart Study). J Am Coll Cardiol. 2015;66:1643 53. S2.2-19. Kavousi M, Desai CS, Ayers C, et al. Prevalence and prognostic impli- cations of coronary artery calcification in low-risk women: a meta- analysis. JAMA. 2016;316:2126 34. S2.2-20. Carr JJ, Jacobs DR Jr, Terry JG, et al. Association of coronary artery calcium in adults aged 32 to 46 years with incident coronary heart disease and death. JAMA Cardiol. 2017;2:391 9. S2.2-21. Mortensen MB, Fuster V, Muntendam P, et al. A simple disease- guided approach to personalize ACC/AHA-recommended statin allocation in elderly people: the BioImage Study. J Am Coll Cardiol. 2016;68:881 91. S2.2-22. Blaha MJ, Cainzos-Achirica M, Greenland P, et al. Role of coronary artery calcium score of zero and other negative risk markers for cardiovascular disease: The Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2016;133:849 58. S2.2-23. Patel J, Al Rifai M, Blaha MJ, et al. Coronary artery calcium improves risk assessment in adults with a family history of premature coronary CLINICAL STATEMENTS AND GUIDELINES heart disease: results from the Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Imaging. 2015;8:e003186. S2.2-24. Pursnani A, Massaro JM, D Agostino RB Sr, et al. Guideline-based statin eligibility, coronary artery calcification, and cardiovascular events. JAMA. 2015;314:134 41. S2.2-25. Valenti V, Hartaigh B, Heo R, et al. A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a pro- spective follow-up of 9 715 individuals. JACC Cardiovasc Imaging. 2015;8:900 9. S2.2-26. Yano Y, O Donnell CJ, Kuller L, et al. Association of coronary artery calcium score vs age with cardiovascular risk in older adults: an analysis of pooled population-based studies. JAMA Cardiol. 2017;2:986 94. S2.2-27. Yeboah J, Young R, McClelland RL, et al. Utility of nontraditional risk markers in atherosclerotic cardiovascular disease risk assessment. J Am Coll Cardiol. 2016;67:139 47. S2.2-28. Multi-Ethnic Study of Atherosclerosis. MESA 10-Year CHD Risk with Coronary Artery Calcification. Available at: https://www.mesa- nhlbi.org/MESACHDRisk/MesaRiskScore/RiskScore.aspx. Accessed September 21, 2018. S2.2-29. Astronaut Cardiovascular Health and Risk Modification (Astro- CHARM). 10-Year ASCVD Risk Calculator with Coronary Artery Calcium. Available at: http://astrocharm.org/calculator-working. Accessed September 21, 2018. S2.2-30. Gupta A, Lau E, Varshney R, et al. The identification of calcified coronary plaque is associated with initiation and continuation of pharmacological and lifestyle preventive therapies: a systematic review and meta-analysis. JACC Cardiovasc Imaging. 2017;10: 833 42. S2.2-31. Shah RV, Spahillari A, Mwasongwe S, et al. Subclinical atherosclero- sis, statin eligibility, and outcomes in African American individuals: the Jackson Heart Study. JAMA Cardiol. 2017;2:644 52. S2.2-32. Lloyd-Jones DM, Leip EP, Larson MG, et al. Prediction of lifetime risk for cardiovascular disease by risk factor burden at 50 years of age. Circulation. 2006;113:791 8. S2.2-33. Berry JD, Dyer A, Cai X, et al. Lifetime risks of cardiovascular disease. N Engl J Med. 2012;366:321 9. S2.2-34. Wilkins JT, Ning H, Berry J, et al. Lifetime risk and years lived free of total cardiovascular disease. JAMA. 2012;308:1795 801. S2.2-35. Pencina MJ, D Agostino RB Sr, Larson MG, et al. Predicting the 30-year risk of cardiovascular disease: the Framingham Heart Study. Circulation. 2009;119:3078 84. S2.2-36. Nasir K, Bittencourt MS, Blaha MJ, et al. Implications of coro- nary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association cho- lesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2015;66:1657 68. 3. LIFESTYLE FACTORS AFFECTING CARDIOVASCULAR RISK 3.1. Nutrition and Diet S3.1-1. Estruch R, Ros E, Salas-Salvad J, et al. Primary prevention of car- diovascular disease with a Mediterranean diet supplemented with extra-virgin olive oil or nuts. N Engl J Med. 2018;378:e34. S3.1-2. Kim H, Caulfield LE, Rebholz CM. Healthy plant-based diets are associated with lower risk of all-cause mortality in US adults. J Nutr. 2018;148:624 31. S3.1-3. Reedy J, Krebs-Smith SM, Miller PE, et al. Higher diet quality is asso- ciated with decreased risk of all-cause, cardiovascular disease, and cancer mortality among older adults. J Nutr. 2014;144:881 9. S3.1-4. Satija A, Bhupathiraju SN, Spiegelman D, et al. Healthful and unhealthful plant-based diets and the risk of coronary heart disease in US adults. J Am Coll Cardiol. 2017;70:411 22. S3.1-5. Sotos-Prieto M, Bhupathiraju SN, Mattei J, et al. Association of changes in diet quality with total and cause-specific mortality. N Engl J Med. 2017;377:143 53. S3.1-6. Whalen KA, Judd S, McCullough ML, et al. Paleolithic and Mediterranean diet pattern scores are inversely associated with all-cause and cause-specific mortality in adults. J Nutr. 2017;147:612 20. S3.1-7. Bao Y, Han J, Hu FB, et al. Association of nut consumption with total and cause-specific mortality. N Engl J Med. 2013;369:2001 11. S3.1-8. Bernstein AM, Sun Q, Hu FB, et al. Major dietary protein sources and risk of coronary heart disease in women. Circulation. 2010;122:876 83. S3.1-9. Song M, Fung TT, Hu FB, et al. Association of animal and plant pro- tein intake with all-cause and cause-specific mortality. JAMA Intern Med. 2016;176:1453 63. S3.1-10. Tharrey M, Mariotti F, Mashchak A, et al. Patterns of plant and animal protein intake are strongly associated with cardiovascular mortality: the Adventist Health Study-2 cohort. Int J Epidemiol. 2018;47:1603 12. S3.1-11. Mart nez-Gonz lez MA, S nchez-Tainta A, Corella D, et al. A pro- vegetarian food pattern and reduction in total mortality in the Prevenci n con Dieta Mediterr nea (PREDIMED) study. Am J Clin Nutr 100 suppl 12014:320S 8S. S3.1-12. Wang DD, Li Y, Chiuve SE, et al. Association of specific dietary fats with total and cause-specific mortality. JAMA Intern Med. 2016;176:1134 45. S3.1-13. Dehghan M, Mente A, Zhang X, et al. Associations of fats and carbo- hydrate intake with cardiovascular disease and mortality in 18 coun- tries from five continents (PURE): a prospective cohort study. Lancet. 2017;390:2050 62. S3.1-14. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pres- sure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3 10. S3.1-15. Cook NR, Cutler JA, Obarzanek E, et al. Long term effects of dietary sodium reduction on cardiovascular disease outcomes: observational follow-up of the trials of hypertension prevention (TOHP). BMJ. 2007;334:885 8. S3.1-16. Micha R, Pe alvo JL, Cudhea F, et al. Association between dietary factors and mortality from heart disease, stroke, and type 2 diabetes in the United States. JAMA. 2017;317:912 24. S3.1-17. Kiage JN, Merrill PD, Robinson CJ, et al. Intake of trans fat and all- cause mortality in the Reasons for Geographical and Racial Differences in Stroke (REGARDS) cohort. Am J Clin Nutr. 2013;97:1121 8. S3.1-18. L fvenborg JE, Andersson T, Carlsson P-O, et al. Sweetened bever- age intake and risk of latent autoimmune diabetes in adults (LADA) and type 2 diabetes. Eur J Endocrinol. 2016;175:605 14. S3.1-19. Yang Q, Zhang Z, Gregg EW, et al. Added sugar intake and car- diovascular diseases mortality among US adults. JAMA Intern Med. 2014;174:516 24. S3.1-20. Johnson RK, Lichtenstein AH, Anderson CAM, et al. Low- calorie sweetened beverages and cardiometabolic health: a sci- ence advisory from the American Heart Association. Circulation. 2018;138:e126 40. S3.1-21. Shikany JM, Safford MM, Newby PK, et al. Southern dietary pat- tern is associated with hazard of acute coronary heart disease in the Reasons for Geographic and Racial Differences in Stroke (REGARDS) study. Circulation. 2015;132:804 14. S3.1-22. Seidelmann SB, Claggett B, Cheng S, et al. Dietary carbohydrate intake and mortality: a prospective cohort study and meta-analysis. Lancet Public Health. 2018;3:e419 28. S3.1-23. Trichopoulou A, Psaltopoulou T, Orfanos P, et al. Low-carbohydrate- high-protein diet and long-term survival in a general population cohort. Eur J Clin Nutr. 2007;61:575 81. S3.1-24. Noto H, Goto A, Tsujimoto T, et al. Low-carbohydrate diets and all- cause mortality: a systematic review and meta-analysis of observa- tional studies. PLoS ONE. 2013;8:e55030. S3.1-25. Brandt EJ, Myerson R, Perraillon MC, et al. Hospital admissions for myocardial infarction and stroke before and after the trans-fatty acid restrictions in New York. JAMA Cardiol. 2017;2:627 34. S3.1-26. Micha R, Mozaffarian D. Trans fatty acids: effects on meta- bolic syndrome, heart disease and diabetes. Nat Rev Endocrinol. 2009;5:335 44. S3.1-27. Mozaffarian D. Dietary and policy priorities for cardiovascular dis- ease, diabetes, and obesity: a comprehensive review. Circulation. 2016;133:187 225. 3.2. Exercise and Physical Activity S3.2-1. Orrow G, Kinmonth A-L, Sanderson S, et al. Effectiveness of physical activity promotion based in primary care: systematic review and meta- analysis of randomised controlled trials. BMJ. 2012;344:e1389. CLINICAL STATEMENTS AND GUIDELINES S3.2-2. Sanchez A, Bully P, Martinez C, et al. Effectiveness of physical activity promotion interventions in primary care: a review of reviews. Prev Med 2015;76 suppl:S56 67. S3.2-3. Ekelund U, Steene-Johannessen J, Brown WJ, et al. Does physical activity attenuate, or even eliminate, the detrimental association of sitting time with mortality? A harmonised meta-analysis of data from more than 1 million men and women. Lancet. 2016;388: 1302 10. S3.2-4. Hamer M, Chida Y. Walking and primary prevention: a meta-analysis of prospective cohort studies. Br J Sports Med. 2008;42:238 43. S3.2-5. Kyu HH, Bachman VF, Alexander LT, et al. Physical activity and risk of breast cancer, colon cancer, diabetes, ischemic heart disease, and ischemic stroke events: systematic review and dose-response meta-analysis for the Global Burden of Disease Study 2013. BMJ. 2016;354:i3857. S3.2-6. Sattelmair J, Pertman J, Ding EL, et al. Dose response between physical activity and risk of coronary heart disease: a meta-analysis. Circulation. 2011;124:789 95. S3.2-7. Zheng H, Orsini N, Amin J, et al. Quantifying the dose-response of walking in reducing coronary heart disease risk: meta-analysis. Eur J Epidemiol. 2009;24:181 92. S3.2-8. Wahid A, Manek N, Nichols M, et al. Quantifying the association between physical activity and cardiovascular disease and diabe- tes: a systematic review and meta-analysis. J Am Heart Assoc. 2016;5:e002495. S3.2-9. Biswas A, Oh PI, Faulkner GE, et al. Sedentary time and its asso- ciation with risk for disease incidence, mortality, and hospitalization in adults: a systematic review and meta-analysis. Ann Intern Med. 2015;162:123 32. S3.2-10. Chomistek AK, Manson JE, Stefanick ML, et al. Relationship of sed- entary behavior and physical activity to incident cardiovascular dis- ease: results from the Women s Health Initiative. J Am Coll Cardiol. 2013;61:2346 54. S3.2-11. Patterson R, McNamara E, Tainio M, et al. Sedentary behaviour and risk of all-cause, cardiovascular and cancer mortality, and incident type 2 diabetes: a systematic review and dose response meta-analy- sis. Eur J Epidemiol. 2018;33:811 29. S3.2-12. Young DR, Hivert M-F, Alhassan S, et al. Sedentary behavior and cardiovascular morbidity and mortality: a science advisory from the American Heart Association. Circulation. 2016;134:e262 79. 4. OTHER FACTORS AFFECTING CARDIOVASCULAR RISK 4.1. Obesity and Being Overweight S4.1-1. LeBlanc EL, Patnode CD, Webber EM, et al. Draft evidence review for weight loss to prevent obesity-related morbidity and mortal- ity in adults: behavioral interventions. Kaiser Permanente Research Affiliates Evidence-based Practice Center, Kaiser Permanente Center for Health Research: Portland, OR; 2018. AHRQ Publication No. 18-05239-EF-1. Available at: https://www.uspreventiveservicestask- force.org/Page/Document/draft-evidence-review/obesity-in-adults- interventions1. Accessed January 5, 2019. S4.1-2. Ma C, Avenell A, Bolland M, et al. Effects of weight loss interventions for adults who are obese on mortality, cardiovascular disease, and cancer: systematic review and meta-analysis. BMJ. 2017;359:j4849. S4.1-3. Canoy D, Cairns BJ, Balkwill A, et al. Coronary heart disease inci- dence in women by waist circumference within categories of body mass index. Eur J Prev Cardiol. 2013;20:759 62. S4.1-4. Warren TY, Wilcox S, Dowda M, et al. Independent association of waist circumference with hypertension and diabetes in African American women, South Carolina, 2007 2009. Prev Chronic Dis. 2012;9:E105. S4.1-5. Czernichow S, Kengne A-P, Stamatakis E, et al. Body mass index, waist circumference and waist-hip ratio: which is the better discrimi- nator of cardiovascular disease mortality risk?: evidence from an individual-participant meta-analysis of 82 864 participants from nine cohort studies. Obes Rev. 2011;12:680 7. S4.1-6. Flint AJ, Rexrode KM, Hu FB, et al. Body mass index, waist circumfer- ence, and risk of coronary heart disease: a prospective study among men and women. Obes Res Clin Pract. 2010;4:e171 81. 4.2. Type 2 Diabetes Mellitus S4.2-1. Huo R, Du T, Xu Y, et al. Effects of Mediterranean-style diet on gly- cemic control, weight loss and cardiovascular risk factors among type 2 diabetes individuals: a meta-analysis. Eur J Clin Nutr. 2015;69:1200 8. S4.2-2. Azadbakht L, Fard NRP, Karimi M, et al. Effects of the Dietary Approaches to Stop Hypertension (DASH) eating plan on cardiovas- cular risks among type 2 diabetic patients: a randomized crossover clinical trial. Diabetes Care. 2011;34:55 7. S4.2-3. Snowling NJ, Hopkins WG. Effects of different modes of exercise training on glucose control and risk factors for complications in type 2 diabetic patients: a meta-analysis. Diabetes Care. 2006;29:2518 27. S4.2-4. Church TS, Blair SN, Cocreham S, et al. Effects of aerobic and resis- tance training on hemoglobin A1c levels in patients with type 2 dia- betes: a randomized controlled trial. JAMA. 2010;304:2253 62. S4.2-5. 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. S4.2-6. Maruthur NM, Tseng E, Hutfless S, et al. Diabetes medications as monotherapy or metformin-based combination therapy for type 2 diabetes: a systematic review and meta-analysis. Ann Intern Med. 2016;164:740 51. S4.2-7. Hong J, Zhang Y, Lai S, et al. Effects of metformin versus glipizide on cardiovascular outcomes in patients with type 2 diabetes and coronary artery disease. Diabetes Care. 2013;36:1304 11. S4.2-8. Griffin SJ, Leaver JK, Irving GJ. Impact of metformin on cardiovascu- lar disease: a meta-analysis of randomised trials among people with type 2 diabetes. Diabetologia. 2017;60:1620 9. S4.2-9. Zinman B, Wanner C, Lachin JM, et al. Empagliflozin, cardiovas- cular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117 28. S4.2-10. Neal B, Perkovic V, Mahaffey KW, et al. Canagliflozin and car- diovascular and renal events in type 2 diabetes. N Engl J Med. 2017;377:644 57. S4.2-11. Marso SP, Daniels GH, Brown-Frandsen K, et al. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:311 22. S4.2-12. Wiviott SD, Raz I, Bonaca MP, et al. Dapagliflozin and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2019;380:347 57. S4.2-13. Hernandez AF, Green JB, Janmohamed S, et al. Albiglutide and car- diovascular outcomes in patients with type 2 diabetes and cardio- vascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial. Lancet. 2018;392:1519 29. S4.2-14. Marso SP, Bain SC, Consoli A, et al. Semaglutide and cardiovas- cular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834 44. 4.3. High Blood Cholesterol S4.3-1. Grundy SM, Stone NJ, Bailey AL, et al. 2018 AHA/ACC/AACVPR/AAPA/ ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the man- agement of blood cholesterol: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019;139:e1082 1143. S4.3-2. Cholesterol Treatment Trialists (CTT) CollaborationBaigent C, Blackwell L, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170 000 participants in 26 randomised trials. Lancet. 2010;376:1670 81. S4.3-3. Baigent C, Landray MJ, Reith C, et al. The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): a randomised placebo-controlled trial. Lancet. 2011;377:2181 92. S4.3-4. Cholesterol Treatment Trialists (CTT) CollaborationHerrington W, Emberson J, et al. Impact of renal function on the effects of LDL cho- lesterol lowering with statin-based regimens: a meta-analysis of indi- vidual participant data from 28 randomised trials. Lancet Diabetes Endocrinol. 2016;4:829 39. S4.3-5. Chou R, Dana T, Blazina I, et al. Statin use for the prevention of cardiovascular disease in adults: a systematic review for the US Preventive Services Task Force. Report No. 14-05206-EF-2. Rockville, MD: U.S. Agency for Healthcare Research and Quality, 2016. Available at: http://www.ncbi.nlm.nih.gov/books/NBK396415. Accessed January 5, 2019. CLINICAL STATEMENTS AND GUIDELINES S4.3-6. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cho- lesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. JAMA. 1998;279:1615 22. S4.3-7. Ridker PM, Danielson E, Fonseca FAH, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359:2195 207. S4.3-8. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013:CD004816. S4.3-9. Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in inter- mediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374:2021 31. S4.3-10. Silverman MG, Ference BA, Im K, et al. Association between lower- ing LDL-C and cardiovascular risk reduction among different thera- peutic interventions: a systematic review and meta-analysis. JAMA. 2016;316:1289 97. S4.3-11. Colhoun HM, Betteridge DJ, Durrington PN, et al. Primary preven- tion of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004;364:685 96. S4.3-12. Collins R, Armitage J, Parish S, et al. MRC/BHF Heart Protection Study of cholesterol-lowering with simvastatin in 5963 people with diabetes: a randomised placebo-controlled trial. Lancet. 2003;361:2005 16. S4.3-13. de Vries FM, Denig P, Pouwels KB, et al. Primary prevention of major cardiovascular and cerebrovascular events with statins in diabetic patients: a meta-analysis. Drugs. 2012;72:2365 73. S4.3-14. Knopp RH, d Emden M, Smilde JG, et al. Efficacy and safety of atorvastatin in the prevention of cardiovascular end points in sub- jects with type 2 diabetes: the Atorvastatin Study for Prevention of Coronary Heart Disease Endpoints in non-insulin-dependent diabe- tes mellitus (ASPEN). Diabetes Care. 2006;29:1478 85. S4.3-15. Mulnier HE, Seaman HE, Raleigh VS, et al. Risk of myocardial infarc- tion in men and women with type 2 diabetes in the UK: a cohort study using the General Practice Research Database. Diabetologia. 2008;51:1639 45. S4.3-16. Rana JS, Liu JY, Moffet HH, et al. Diabetes and prior coronary heart disease are not necessarily risk equivalent for future coronary heart disease events. J Gen Intern Med. 2016;31:387 93. S4.3-17. Sever PS, Poulter NR, Dahl f B, et al. Reduction in cardiovascular events with atorvastatin in 2 532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial lipid-lowering arm (ASCOT-LLA). Diabetes Care. 2005;28:1151 7. S4.3-18. Soedamah-Muthu SS, Fuller JH, Mulnier HE, et al. High risk of cardio- vascular disease in patients with type 1 diabetes in the U.K.: a cohort study using the general practice research database. Diabetes Care. 2006;29:798 804. S4.3-19. Wong ND, Glovaci D, Wong K, et al. Global cardiovascular disease risk assessment in United States adults with diabetes. Diab Vasc Dis Res. 2012;9:146 52. S4.3-20. Besseling J, Hovingh GK, Huijgen R, et al. Statins in familial hyper- cholesterolemia: consequences for coronary artery disease and all- cause mortality. J Am Coll Cardiol. 2016;68:252 60. S4.3-21. Khera AV, Won H-H, Peloso GM, et al. Diagnostic yield and clini- cal utility of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578 89. S4.3-22. Nanchen D, Gencer B, Muller O, et al. Prognosis of patients with familial hypercholesterolemia after acute coronary syndromes. Circulation. 2016;134:698 709. S4.3-23. Perak AM, Ning H, de Ferranti SD, et al. Long-term risk of atheroscle- rotic cardiovascular disease in US adults with the familial hypercho- lesterolemia phenotype. Circulation. 2016;134:9 19. S4.3-24. Shepherd J, Cobbe SM, Ford I, et al. Prevention of coronary heart disease with pravastatin in men with hypercholesterolemia. West of Scotland Coronary Prevention Study Group. N Engl J Med. 1995;333:1301 7. S4.3-25. Versmissen J, Oosterveer DM, Yazdanpanah M, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008;337:a2423. S4.3-26. Mortensen MB, Fuster V, Muntendam P, et al. A simple disease- guided approach to personalize ACC/AHA-recommended statin allocation in elderly people: the BioImage Study. J Am Coll Cardiol. 2016;68:881 91. S4.3-27. Willeit P, Kiechl S, Kronenberg F, et al. Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospec- tive 15-year outcomes in the Bruneck Study. J Am Coll Cardiol. 2014;64:851 60. S4.3-28. Nasir K, Bittencourt MS, Blaha MJ, et al. Implications of coro- nary artery calcium testing among statin candidates according to American College of Cardiology/American Heart Association cho- lesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2015;66:1657 68. S4.3-29. Ridker PM, Mora S, Rose L, et al. Percent reduction in LDL choles- terol following high-intensity statin therapy: potential implications for guidelines and for the prescription of emerging lipid-lowering agents. Eur Heart J. 2016;37:1373 9. S4.3-30. Yano Y, O Donnell CJ, Kuller L, et al. Association of coronary artery calcium score vs age with cardiovascular risk in older adults: an analysis of pooled population-based studies. JAMA Cardiol. 2017;2:986 94. S4.3-31. Malik S, Zhao Y, Budoff M, et al. Coronary artery calcium score for long-term risk classification in individuals with type 2 diabetes and metabolic syndrome from the Multi-Ethnic Study of Atherosclerosis. JAMA Cardiol. 2017;2:1332 40. S4.3-32. Sniderman AD, Tsimikas S, Fazio S. The severe hypercholesterolemia phenotype: clinical diagnosis, management, and emerging thera- pies. J Am Coll Cardiol. 2014;63:1935 47. S4.3-33. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low- density lipoprotein cholesterol, non-high-density lipoprotein choles- terol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4:337 45. S4.3-34. Budoff MJ, Young R, Burke G, et al. Ten-year association of coronary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA). Eur Heart J. 2018;39:2401 8. S4.3-35. Cholesterol Treatment Trialists (CTT) CollaboratorsMihaylova B, Emberson J, et al. The effects of lowering LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 randomised trials. Lancet. 2012;380: 581 90. S4.3-36. Huo X, Gao L, Guo L, et al. Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross- sectional study. Lancet Diabetes Endocrinol. 2016;4:115 24. S4.3-37. Svensson MK, Cederholm J, Eliasson B, et al. Albuminuria and renal function as predictors of cardiovascular events and mortality in a general population of patients with type 2 diabetes: a nationwide observational study from the Swedish National Diabetes Register. Diab Vasc Dis Res. 2013;10:520 9. S4.3-38. Guo VY, Cao B, Wu X, et al. Prospective association between dia- betic retinopathy and cardiovascular disease a systematic review and meta-analysis of cohort studies. J Stroke Cerebrovasc Dis. 2016;25:1688 95. S4.3-39. Brownrigg JRW, de Lusignan S, McGovern A, et al. Peripheral neu- ropathy and the risk of cardiovascular events in type 2 diabetes mel- litus. Heart. 2014;100:1837 43. S4.3-40. Ogren M, Hedblad B, Engstr m G, et al. Prevalence and prognostic significance of asymptomatic peripheral arterial disease in 68-year- old men with diabetes. Results from the population study Men born in 1914 from Malm , Sweden. Eur J Vasc Endovasc Surg. 2005;29:182 9. S4.3-41. Pang X-H, Han J, Ye W-L, et al. Lower extremity peripheral arterial disease is an independent predictor of coronary heart disease and stroke risks in patients with type 2 diabetes mellitus in China. Int J Endocrinol. 2017;2017:9620513. S4.3-42. Waheed S, Pollack S, Roth M, et al. Collective impact of conventional cardiovascular risk factors and coronary calcium score on clinical out- comes with or without statin therapy: The St Francis Heart Study. Atherosclerosis. 2016;255:193 9. 4.4. High Blood Pressure or Hypertension S4.4-1. Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/ American Heart Association Task Force on Clinical Practice Guidelines. Hypertension. 2018;71:e13 115. CLINICAL STATEMENTS AND GUIDELINES S4.4-2. Neter JE, Stam BE, Kok FJ, et al. Influence of weight reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2003;42:878 84. S4.4-3. The effects of nonpharmacologic interventions on blood pressure of persons with high normal levels. Results of the Trials of Hypertension Prevention, Phase I. JAMA. 1992;267:1213 20. S4.4-4. Whelton PK, Kumanyika SK, Cook NR, et al. Efficacy of nonphar- macologic interventions in adults with high-normal blood pressure: results from phase 1 of the Trials of Hypertension Prevention. Trials of Hypertension Prevention Collaborative Research Group. Am J Clin Nutr. 1997;65:652S 60S. S4.4-5. Effects of weight loss and sodium reduction intervention on blood pressure and hypertension incidence in overweight people with high-normal blood pressure. The Trials of Hypertension Prevention, phase II. The Trials of Hypertension Prevention Collaborative Research Group. Arch Intern Med. 1997;157:657 67. S4.4-6. Sacks FM, Svetkey LP, Vollmer WM, et al. Effects on blood pres- sure of reduced dietary sodium and the Dietary Approaches to Stop Hypertension (DASH) diet. DASH-Sodium Collaborative Research Group. N Engl J Med. 2001;344:3 10. S4.4-7. Appel LJ, Moore TJ, Obarzanek E, et al. A clinical trial of the effects of dietary patterns on blood pressure. DASH Collaborative Research Group. N Engl J Med. 1997;336:1117 24. S4.4-8. Appel LJ, Champagne CM, Harsha DW, et al. Effects of comprehen- sive lifestyle modification on blood pressure control: main results of the PREMIER clinical trial. JAMA. 2003;289:2083 93. S4.4-9. Mozaffarian D, Fahimi S, Singh GM, et al. Global sodium con- sumption and death from cardiovascular causes. N Engl J Med. 2014;371:624 34. S4.4-10. He FJ, Li J, Macgregor GA. Effect of longer term modest salt reduc- tion on blood pressure: Cochrane systematic review and meta-anal- ysis of randomised trials. BMJ. 2013;346:f1325. S4.4-11. Whelton PK, Appel LJ, Espeland MA, et al. Sodium reduction and weight loss in the treatment of hypertension in older persons: a randomized controlled trial of nonpharmacologic interventions in the elderly (TONE). TONE Collaborative Research Group. JAMA. 1998;279:839 46. S4.4-12. Aburto NJ, Ziolkovska A, Hooper L, et al. Effect of lower sodium intake on health: systematic review and meta-analyses. BMJ. 2013;346:f1326. S4.4-13. Graudal NA, Hubeck-Graudal T, J rgens G. Effects of low-sodium diet vs. high-sodium diet on blood pressure, renin, aldosterone, cat- echolamines, cholesterol, and triglyceride (Cochrane Review). Am J Hypertens. 2012;25:1 15. S4.4-14. Whelton PK, He J, Cutler JA, et al. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA. 1997;277:1624 32. S4.4-15. Aburto NJ, Hanson S, Gutierrez H, et al. Effect of increased potas- sium intake on cardiovascular risk factors and disease: systematic review and meta-analyses. BMJ. 2013;346:f1378. S4.4-16. Geleijnse JM, Kok FJ, Grobbee DE. Blood pressure response to changes in sodium and potassium intake: a metaregression analysis of randomised trials. J Hum Hypertens. 2003;17:471 80. S4.4-17. World Health Association. Guideline: Potassium Intake for Adults and Children. Geneva, Switzerland: World Health Organization, Department of Nutrition for Health and Development; 2012. S4.4-18. Whelton PK, He J. Health effects of sodium and potassium in humans. Curr Opin Lipidol. 2014;25:75 9. S4.4-19. Cornelissen VA, Smart NA. Exercise training for blood pres- sure: a systematic review and meta-analysis. J Am Heart Assoc. 2013;2:e004473. S4.4-20. Whelton SP, Chin A, Xin X, et al. Effect of aerobic exercise on blood pressure: a meta-analysis of randomized, controlled trials. Ann Intern Med. 2002;136:493 503. S4.4-21. Carlson DJ, Dieberg G, Hess NC, et al. Isometric exercise training for blood pressure management: a systematic review and meta-analysis. Mayo Clin Proc. 2014;89:327 34. S4.4-22. Garc a-Hermoso A, Saavedra JM, Escalante Y. Effects of exercise on resting blood pressure in obese children: a meta-analysis of random- ized controlled trials. Obes Rev. 2013;14:919 28. S4.4-23. Rossi AM, Moullec G, Lavoie KL, et al. The evolution of a Canadian Hypertension Education Program recommendation: the impact of resistance training on resting blood pressure in adults as an example. Can J Cardiol. 2013;29:622 7. S4.4-24. Roerecke M, Kaczorowski J, Tobe SW, et al. The effect of a reduction in alcohol consumption on blood pressure: a systematic review and meta-analysis. Lancet Public Health. 2017;2:e108 20. S4.4-25. Xin X, He J, Frontini MG, et al. Effects of alcohol reduction on blood pressure: a meta-analysis of randomized controlled trials. Hypertension. 2001;38:1112 7. S4.4-26. Stewart SH, Latham PK, Miller PM, et al. Blood pressure reduc- tion during treatment for alcohol dependence: results from the Combining Medications and Behavioral Interventions for Alcoholism (COMBINE) study. Addiction. 2008;103:1622 8. S4.4-27. Dickinson HO, Mason JM, Nicolson DJ, et al. Lifestyle interventions to reduce raised blood pressure: a systematic review of randomized controlled trials. J Hypertens. 2006;24:215 33. S4.4-28. Wallace P, Cutler S, Haines A. Randomised controlled trial of general practitioner intervention in patients with excessive alcohol consump- tion. BMJ. 1988;297:663 8. S4.4-29. Lang T, Nicaud V, Darn B, et al. Improving hypertension control among excessive alcohol drinkers: a randomised controlled trial in France. The WALPA Group. J Epidemiol Community Health. 1995;49:610 6. S4.4-30. Law MR, Morris JK, Wald NJ. Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies. BMJ. 2009;338:b1665. S4.4-31. Ettehad D, Emdin CA, Kiran A, et al. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet. 2016;387:957 67. S4.4-32. Sundstr m J, Arima H, Jackson R, et al. Effects of blood pressure reduction in mild hypertension: a systematic review and meta-analy- sis. Ann Intern Med. 2015;162:184 91. S4.4-33. Xie X, Atkins E, Lv J, et al. Effects of intensive blood pressure low- ering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet. 2016;387:435 43. S4.4-34. SPRINT Research Group Wright JT Jr, Williamson JD, et al. A random- ized trial of intensive versus standard blood-pressure control. N Engl J Med. 2015;373:2103 16. S4.4-35. Czernichow S, Zanchetti A, Turnbull F, et al. The effects of blood pressure reduction and of different blood pressure-lowering regimens on major cardiovascular events according to baseline blood pressure: meta-analysis of randomized trials. J Hypertens. 2011;29:4 16. S4.4-36. Blood Pressure Lowering Treatment Trialists Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta- analysis of individual patient data. Lancet. 2014;384:591 8. S4.4-37. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure low- ering on outcome incidence in hypertension: 2. Effects at different baseline and achieved blood pressure levels overview and meta- analyses of randomized trials. J Hypertens. 2014;32:2296 304. S4.4-38. Thompson AM, Hu T, Eshelbrenner CL, et al. Antihypertensive treat- ment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis. JAMA. 2011;305:913 22. S4.4-39. Thomopoulos C, Parati G, Zanchetti A. Effects of blood pressure low- ering on outcome incidence in hypertension: 7. Effects of more vs. less intensive blood pressure lowering and different achieved blood pressure levels updated overview and meta-analyses of random- ized trials. J Hypertens. 2016;34:613 22. S4.4-40. Verdecchia P, Angeli F, Gentile G, et al. More versus less intensive blood pressure-lowering strategy: cumulative evidence and trial sequential analysis. Hypertension. 2016;68:642 53. S4.4-41. Bangalore S, Toklu B, Gianos E, et al. Optimal systolic blood pres- sure target after SPRINT: insights from a network meta-analysis of randomized trials. Am J Med. 2017;130:707 19.e8. S4.4-42. Bundy JD, Li C, Stuchlik P, et al. Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review and network meta-analysis. JAMA Cardiol. 2017;2:775 81. S4.4-43. Ruggenenti P, Perna A, Loriga G, et al. Blood-pressure control for renoprotection in patients with non-diabetic chronic renal dis- ease (REIN-2): multicentre, randomised controlled trial. Lancet. 2005;365:939 46. S4.4-44. Wright JT Jr, Bakris G, Greene T, et al. Effect of blood pres- sure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. JAMA. 2002;288:2421 31. CLINICAL STATEMENTS AND GUIDELINES S4.4-45. Upadhyay A, Earley A, Haynes SM, et al. Systematic review: blood pressure target in chronic kidney disease and proteinuria as an effect modifier. Ann Intern Med. 2011;154:541 8. S4.4-46. Jafar TH, Stark PC, Schmid CH, et al. Progression of chronic kidney disease: the role of blood pressure control, proteinuria, and angio- tensin-converting enzyme inhibition: a patient-level meta-analysis. Ann Intern Med. 2003;139:244 52. S4.4-47. Lv J, Ehteshami P, Sarnak MJ, et al. Effects of intensive blood pressure lowering on the progression of chronic kidney disease: a systematic review and meta-analysis. CMAJ. 2013;185:949 57. S4.4-48. Klahr S, Levey AS, Beck GJ, et al. The effects of dietary protein restriction and blood-pressure control on the progression of chronic renal disease. Modification of Diet in Renal Disease Study Group. N Engl J Med. 1994;330:877 84. S4.4-49. Emdin CA, Rahimi K, Neal B, et al. Blood pressure lowering in type 2 diabetes: a systematic review and meta-analysis. JAMA. 2015;313:603 15. S4.4-50. Arguedas JA, Leiva V, Wright JM. Blood pressure targets for hyper- tension in people with diabetes mellitus. Cochrane Database Syst Rev. 2013:CD008277. S4.4-51. Margolis KL, O Connor PJ, Morgan TM, et al. Outcomes of com- bined cardiovascular risk factor management strategies in type 2 diabetes: the ACCORD randomized trial. Diabetes Care. 2014;37: 1721 8. S4.4-52. Bress AP, Bellows BK, King JB, et al. Cost-effectiveness of inten- sive versus standard blood-pressure control. N Engl J Med. 2017;377:745 55. S4.4-53. Soliman EZ, Byington RP, Bigger JT, et al. Effect of intensive blood pressure lowering on left ventricular hypertrophy in patients with diabetes mellitus: Action to Control Cardiovascular Risk in Diabetes blood pressure trial. Hypertension. 2015;66:1123 9. S4.4-54. ACCORD Study Group Cushman WC, Evans GW, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010;362:1575 85. S4.4-55. Lewington S, Clarke R, Qizilbash N, et al. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of indi- vidual data for one million adults in 61 prospective studies. Lancet. 2002;360:1903 13. S4.4-56. Kassa B, Boissel J-P, Cucherat M, et al. Treatment of high blood pres- sure and gain in event-free life expectancy. Vasc Health Risk Manag. 2005;1:163 9. S4.4-57. van Dieren S, Kengne AP, Chalmers J, et al. Effects of blood pressure lowering on cardiovascular outcomes in different cardiovascular risk groups among participants with type 2 diabetes. Diabetes Res Clin Pract. 2012;98:83 90. S4.4-58. Montgomery AA, Fahey T, Ben-Shlomo Y, et al. The influence of absolute cardiovascular risk, patient utilities, and costs on the deci- sion to treat hypertension: a Markov decision analysis. J Hypertens. 2003;21:1753 9. S4.4-59. Lonn EM, Bosch J, L pez-Jaramillo P, et al. Blood-pressure lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374:2009 20. S4.4-60. Neaton JD, Grimm RH Jr, Prineas RJ, et al. Treatment of Mild Hypertension Study. Final results. Treatment of Mild Hypertension Study Research Group. JAMA. 1993;270:713 24. S4.4-61. Julius S, Nesbitt SD, Egan BM, et al. Feasibility of treating prehy- pertension with an angiotensin-receptor blocker. N Engl J Med. 2006;354:1685 97. S4.4-62. Lawes CMM, Bennett DA, Lewington S, et al. Blood pressure and coronary heart disease: a review of the evidence. Semin Vasc Med. 2002;2:355 68. S4.4-63. Inder JD, Carlson DJ, Dieberg G, et al. Isometric exercise training for blood pressure management: a systematic review and meta-analysis to optimize benefit. Hypertens Res. 2016;39:88 94. S4.4-64. National Institute on Alcohol Abuse and Alcoholism. What Is A Standard Drink? Available at: https://www.niaaa.nih.gov/alco- hol-health/overview-alcohol-consumption/what-standard-drink. Accessed August 16, 2017. S4.4-65. National Heart, Lung, and Blood Institute. Your Guide to Lowering Your Blood Pressure With DASH How Do I Make the DASH? Available at: https://health.gov/dietaryguidelines/dga2005/toolkit/ DASH/how_make_dash.htm. Accessed January 6, 2019. S4.4-66. Top 10 Dash Diet Tips. Available at: http://dashdiet.org/dash-diet- tips.html. Accessed January 6, 2019. 4.5. Tobacco Use S4.5-1. Carson KV, Verbiest MEA, Crone MR, et al. Training health pro- fessionals in smoking cessation. Cochrane Database Syst Rev. 2012:CD000214. S4.5-2. Patnode CD, Henderson JT, Thompson JH, et al. Behavioral coun- seling and pharmacotherapy interventions for tobacco cessation in adults, including pregnant women: a review of reviews for the US Preventive Services Task Force. Ann Intern Med. 2015;163:608 21. S4.5-3. Stead LF, Koilpillai P, Fanshawe TR1, et al. Combined pharmacother- apy and behavioural interventions for smoking cessation. Cochrane Database Syst Rev. 2016;3:CD008286. S4.5-4. Pan A, Wang Y, Talaei M, et al. Relation of smoking with total mortality and cardiovascular events among patients with diabe- tes mellitus: a meta-analysis and systematic review. Circulation. 2015;132:1795 804. S4.5-5. Mons U, M ezzinler A, Gellert C, et al. Impact of smoking and smok- ing cessation on cardiovascular events and mortality among older adults: meta-analysis of individual participant data from prospective cohort studies of the CHANCES consortium. BMJ. 2015;350:h1551. S4.5-6. Lv X, Sun J, Bi Y, et al. Risk of all-cause mortality and cardiovascular disease associated with secondhand smoke exposure: a systematic review and meta-analysis. Int J Cardiol. 2015;199:106 15. S4.5-7. Barua RS, Rigotti NA, Benowitz NL, et al. 2018 ACC Expert Consensus Decision Pathway on Tobacco Cessation Treatment: A Report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2018;72:3332 65. S4.5-8. Anthenelli RM, Benowitz NL, West R, et al. Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. Lancet. 2016;387:2507 20. S4.5-9. Prochaska JJ, Benowitz NL. The past, present, and future of nicotine addiction therapy. Annu Rev Med. 2016;67:467 86. 4.6. Aspirin Use S4.6-1. Guirguis-Blake JM, Evans CV, Senger CA, et al. Aspirin for the pri- mary prevention of cardiovascular events: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2016;164:804 13. S4.6-2. Whitlock EP, Burda BU, Williams SB, et al. Bleeding risks with aspirin use for primary prevention in adults: a systematic review for the US Preventive Services Task Force. Ann Intern Med. 2016;164:826 35. S4.6-3. Lotrionte M, Biasucci LM, Peruzzi M, et al. Which aspirin dose and preparation is best for the long-term prevention of cardiovascular disease and cancer? Evidence from a systematic review and network meta-analysis. Prog Cardiovasc Dis. 2016;58:495 504. S4.6-4. Raju N, Sobieraj-Teague M, Bosch J, et al. Updated meta-analysis of aspirin in primary prevention of cardiovascular disease. Am J Med. 2016;129:e35 6. S4.6-5. Ogawa H, Nakayama M, Morimoto T, et al. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type 2 diabetes: a randomized controlled trial. JAMA. 2008;300:2134 41. S4.6-6. Belch J, MacCuish A, Campbell I, et al. The prevention of progres- sion of arterial disease and diabetes (POPADAD) trial: factorial randomised placebo controlled trial of aspirin and antioxidants in patients with diabetes and asymptomatic peripheral arterial disease. BMJ. 2008;337:a1840. S4.6-7. Fowkes FGR, Price JF, Stewart MCW, et al. Aspirin for prevention of cardiovascular events in a general population screened for a low ankle brachial index: a randomized controlled trial. JAMA. 2010;303:841 8. S4.6-8. Ikeda Y, Shimada K, Teramoto T, et al. Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic risk factors: a randomized clinical trial. JAMA. 2014;312:2510 20. S4.6-9. McNeil JJ, Wolfe R, Woods RL, et al. Effect of aspirin on cardio- vascular events and bleeding in the healthy elderly. N Engl J Med. 2018;379:1509 18. S4.6-10. Garc a Rodr guez LA, Mart n-P rez M, Hennekens CH, et al. Bleeding risk with long-term low-dose aspirin: a systematic review of observa- tional studies. PLoS ONE. 2016;11:e0160046. CLINICAL STATEMENTS AND GUIDELINES 5. COST AND VALUE CONSIDERATIONS S5-1. Weintraub WS, Daniels SR, Burke LE, et al. Value of primordial and pri- mary prevention for cardiovascular disease: a policy statement from the American Heart Association. Circulation. 2011;124:967 90. S5-2. Anderson JL, Heidenreich PA, Barnett PG, et al. ACC/AHA state- ment on cost/value methodology in clinical practice guidelines and performance measures: a report of the American College of Cardiology/American Heart Association Task Force on Performance Measures and Task Force on Practice Guidelines. Circulation. 2014;129:2329 45. S5-3. Bress AP, Bellows BK, King JB, et al. Cost-effectiveness of inten- sive versus standard blood-pressure control. N Engl J Med. 2017;377:745 55. S5-4. Moran AE, Odden MC, Thanataveerat A, et al. Cost-effectiveness of hypertension therapy according to 2014 guidelines. N Engl J Med. 2015;372:447 55. S5-5. Park C, Wang G, Durthaler JM, et al. Cost-effectiveness analyses of antihypertensive medicines: a systematic review. Am J Prev Med. 2017;53:S131 42. S5-6. Richman IB, Fairley M, J rgensen ME, et al. Cost-effectiveness of intensive blood pressure management. JAMA Cardiol. 2016;1:872 9. S5-7. Heller DJ, Coxson PG, Penko J, et al. Evaluating the impact and cost- effectiveness of statin use guidelines for primary prevention of coro- nary heart disease and stroke. Circulation. 2017;136:1087 98. S5-8. Odden MC, Pletcher MJ, Coxson PG, et al. Cost-effectiveness and population impact of statins for primary prevention in adults aged 75 years or older in the United States. Ann Intern Med. 2015;162:533 41. S5-9. Heart Protection Study Collaborative Group. Statin cost-effective- ness in the United States for people at different vascular risk levels. Circ Cardiovasc Qual Outcomes. 2009;2:65 72. S6-1. Lehr AL, Driver SL, Stone NJ. The ABCDs of lifestyle counseling. JAMA Cardiol. 2016;1:505 6. APPENDIX 1. SEARCH CRITERIA 1. Patnode CD, Evans CV, Senger CA, et al. Behavioral counseling to pro- mote a healthful diet and physical activity for cardiovascular disease prevention in adults without known cardiovascular disease risk factors: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2017;318:175 93. 2. LeBlanc ES, Patnode CD, Webber EM, et al. Behavioral and pharmaco- therapy weight loss interventions to prevent obesity-related morbidity and mortality in adults: updated evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2018;320:1172 91. 3. Selph S, Dana T, Bougatsos C, et al. Screening for abnormal glucose and type 2 diabetes mellitus: a systematic review to update the 2008 US Preventive Services Task Force Recommendation. Report No. 13-05190- EF-1. 2015, US Agency for Healthcare Research and Quality:Rockville, MD. Available at: http://www.ncbi.nlm.nih.gov/books/NBK293871. Accessed January 5, 2019. 4. Patnode CD, Henderson JT, Thompson JH, et al. Behavioral counsel- ing and pharmacotherapy interventions for tobacco cessation in adults, including pregnant women: a review of reviews for the US Preventive Services Task Force. Ann Intern Med. 2015;163:608 21. 5. Guirguis-Blake JM, Evans CV, Senger CA, et al. Aspirin for the pri- mary prevention of cardiovascular events: a systematic evidence review for the US Preventive Services Task Force. Ann Intern Med. 2016;164:804 13. CLINICAL STATEMENTS AND GUIDELINES APPENDIX 1. SEARCH CRITERIA The rapid review conducted by the Evidence-based Practice Center to complete this literature search, in the limited timeframe provided, built on existing systematic reviews conducted on behalf of the USPSTF. Medical Subject Headings (MeSH) Terms Key Words Nutrition and Diet Search since the 2017 review1 exp Diet/ diet* exp Diet Therapy/ cardiovascular Healthy Diet coronary Primary Prevention/ heart myocardial infarction MI CVD CHD cerebrovascular stroke microvascular mortality prevent* Obesity and Weight Loss Search since the 2018 review2 exp Obesity/ obes* exp Weight Loss overweight Primary Prevention/ weight cardiovascular coronary heart myocardial infarction MI CVD CHD cerebrovascular stroke microvascular mortality prevent* Type 2 Diabetes Mellitus Search since the 2015 review3 exp Diabetes Mellitus, Type 2/ impaired fasting glucose Prediabetic State/ impaired glucose tolerance Glucose Intolerance/ Ifg Primary Prevention/ Igt prediabetes* type 2 diabet* DM cardiovascular coronary heart myocardial infarction MI CVD CHD cerebrovascular stroke microvascular mortality prevent* Tobacco Use Search since the 2015 review4 Smoking/ smoking exp "Tobacco Use Cessation"/ cigarette* "Tobacco Use Disorder"/ tobacco Electronic Cigarettes/ nicotine Primary Prevention/ vape vaping e-cigarette electronic cigarette electronic nicotine delivery system* ENDS cardiovascular coronary heart myocardial infarction MI CVD CHD cerebrovascular stroke microvascular mortality prevent* Aspirin Use Search since the 2016 review5 Aspirin aspirin exp Cerebrovascular Disorders/ acetylsalicylic acid exp Cardiovascular Diseases/ clopidogrel Primary Prevention/ cardiovascular coronary heart myocardial infarction Appendix 1. Continued Medical Subject Headings (MeSH) Terms Key Words (Continued) (Continued) CLINICAL STATEMENTS AND GUIDELINES Primary Prevention/ MI CVD CHD cerebrovascular stroke microvascular mortality prevent* Social Determinants of Health Search limited to English. 