Intensive versus mod- erate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004;350:1495 504. S3.2.1-14. LaRosa JC, Grundy SM, Waters DD, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005;352:1425 35. S3.2.1-15. Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of car- diovascular disease with pravastatin in Japan (MEGA Study): a pro- spective randomised controlled trial. Lancet. 2006;368:1155 63. S3.2.1-16. 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. S3.2.1-17. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials. Lancet. 2010;376:1670 81. S3.2.1-18. Naito R, Miyauchi K, Daida H. Racial differences in the cholesterol- lowering effect of statin. J Atheroscler Thromb. 2017;24:19 25. S3.2.1-19. Collins R, Reith C, Emberson J, et al. Interpretation of the evi- dence for the efficacy and safety of statin therapy. Lancet. 2016;388:2532 61. S3.2.1-20. American College of Cardiology. American College of Cardiology LDL-C Manager. Available at: http://tools.acc.org/ldl. Accessed January 8, 2018. 3.2.2. Nonstatin Therapies S3.2.2-1. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387 97. S3.2.2-2. Kashani A, Sallam T, Bheemreddy S, et al. Review of side-effect profile of combination ezetimibe and statin therapy in randomized clinical trials. Am J Cardiol. 2008;101:1606 13. S3.2.2-3. Khan AR, Bavishi C, Riaz H, et al. Increased risk of adverse neu- rocognitive outcomes with proprotein convertase subtilisin-kexin type 9 inhibitors. Circ Cardiovasc Qual Outcomes. 2017;10: e003153. S3.2.2-4. Robinson JG, Rosenson RS, Farnier M, et al. Safety of very low low- density lipoprotein cholesterol levels with alirocumab: pooled data from randomized trials. J Am Coll Cardiol. 2017;69:471 82. S3.2.2-5. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clini- cal outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713 22. S3.2.2-6. Giugliano RP, Mach F, Zavitz K, et al. Cognitive function in a ran- domized trial of evolocumab. N Engl J Med. 2017;377:633 43. 3.2.3. Nonstatin Add-on Drugs to Statin Therapy S3.2.3-1. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe Added to Statin Therapy after Acute Coronary Syndromes. N Engl J Med. 2015;372:2387 97. S3.2.3-2. Jacobson TA, Ito MK, Maki KC, et al. National lipid association rec- ommendations for patient-centered management of dyslipidemia: part 1 full report. J Clin Lipidol. 2015;9:129 69. S3.2.3-3. Cannon CP, Cariou B, Blom D, et al. Efficacy and safety of ali- rocumab in high cardiovascular risk patients with inadequately controlled hypercholesterolaemia on maximally tolerated doses of statins: the ODYSSEY COMBO II randomized controlled trial. Eur Heart J. 2015;36:1186 94. S3.2.3-4. Sabatine MS, Giugliano RP, Wiviott SD, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015;372:1500 9. 4. PATIENT MANAGEMENT GROUPS 4.1. Secondary ASCVD Prevention S4.1-1. Amarenco P, Bogousslavsky J, Callahan A 3rd, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006;355:549 59. S4.1-2. Athyros VG, Papageorgiou AA, Mercouris BR, et al. Treatment with atorvastatin to the National Cholesterol Educational Program goal versus usual care in secondary coronary heart disease prevention. The GREek Atorvastatin and Coronary-heart-disease Evaluation (GREACE) study. Curr Med Res Opin. 2002;18:220 8. S4.1-3. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials. Lancet. 2010;376:1670 81. S4.1-4. Collins R, Reith C, Emberson J, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet. 2016;388:2532 61. S4.1-5. Group HPSC. Randomized trial of the effects of cholesterol-lowering with simvastatin on peripheral vascular and other major vascular out- comes in 20536 people with peripheral arterial disease and other high-risk conditions. J Vasc Surg. 2007;45:645 54.; discussion 53 4. S4.1-6. Randomised trial of cholesterol lowering in 4444 patients with coro- nary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344:1383 9. S4.1-7. Sacks FM, Pfeffer MA, Moye LA, et al. The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investiga- tors. N Engl J Med. 1996;335:1001 9. S4.1-8. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998;339:1349 57. S4.1-9. Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med. 1997;336:153 62. S4.1-10. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of antioxidant vitamin supplementation in 20536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002;360:23 33. S4.1-11. 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. S4.1-12. Koren MJ, Hunninghake DB. Clinical outcomes in managed-care patients with coronary heart disease treated aggressively in lipid- lowering disease management clinics: the alliance study. J Am Coll Cardiol. 2004;44:1772 9. S4.1-13. Serruys PW, de Feyter P, Macaya C, et al. Fluvastatin for pre- vention of cardiac events following successful first percutane- ous coronary intervention: a randomized controlled trial. Jama. 2002;287:3215 22. CLINICAL STATEMENTS AND GUIDELINES S4.1-14. Bohula EA, Morrow DA, Giugliano RP, et al. Atherothrombotic risk stratification and ezetimibe for secondary prevention. J Am Coll Cardiol. 2017;69:911 21. S4.1-15. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387 97. S4.1-16. Giugliano RP, Mach F, Zavitz K, et al. Cognitive function in a ran- domized trial of evolocumab. N Engl J Med. 2017;377:633 43. S4.1-17. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clini- cal outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713 22. S4.1-18. Schwartz GG, Steg PG, Szarek M, et al. Alirocumab and cardiovas- cular outcomes after acute coronary syndrome. N Engl J Med. 2018. In press. S4.1-19. Wilson PWF, Polonsky TS, Miedema MD, et al. Systematic review for the 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:e1144 61. DOI: 10.1161/CIR.0000000000000626. S4.1-20. Hlatky MA, Kazi DS. PCSK9 inhibitors: economics and policy. J Am Coll Cardiol. 2017;70:2677 87. S4.1-21. Kazi DS, Moran AE, Coxson PG, et al. Cost-effectiveness of PCSK9 inhi bitor therapy in patients with heterozygous familial hypercholesterolemia or atherosclerotic cardiovascular disease. JAMA. 2016;316:743 53. S4.1-22. Gandra SR, Villa G, Fonarow GC, et al. Cost-effectiveness of LDL-C lowering with evolocumab in patients with high cardiovascular risk in the United States. Clin Cardiol. 2016;39:313 20. S4.1-23. Bellosta S, Corsini A. Statin drug interactions and related adverse reactions. Expert Opin Drug Saf. 2012;11:933 46. S4.1-24. Gnjidic D, Le Couteur DG, Blyth FM, et al. Statin use and clinical outcomes in older men: a prospective population-based study. BMJ Open 2013;3:e002333. S4.1-25. Gray SL, Boudreau RM, Newman AB, et al. Angiotensin-converting enzyme inhibitor and statin use and incident mobility limitation in community-dwelling older adults: the Health, Aging and Body Composition study. J Am Geriatr Soc. 2011;59:2226 32. S4.1-26. Ho CK, Walker SW. Statins and their interactions with other lipid- modifying medications: safety issues in the elderly. Ther Adv Drug Saf. 2012;3:35 46. S4.1-27. LaCroix AZ, Gray SL, Aragaki A, et al. Statin use and incident frailty in women aged 65 years or older: prospective findings from the Women s Health Initiative Observational Study. J Gerontol A Biol Sci Med Sci. 2008;63:369 75. S4.1-28. Pilotto A, Panza F, Copetti M, et al. Statin treatment and mortality in community-dwelling S4.1-frail older patients with diabetes mellitus: a retrospective observational study. PLoS One 2015:10;e0130946. S4.1-29. Qi K, Reeve E, Hilmer SN, et al. Older people s attitudes regard- ing polypharmacy, statin use and willingness to have statins depre- scribed in Australia. Int J Clin Pharm. 2015;37:949 57. S4.1-30. Scott D, Blizzard L, Fell J, et al. Statin therapy, muscle func- tion and falls risk in community-dwelling older adults. QJM. 2009;102:625 33. S4.1-31. Thai M, Reeve E, Hilmer SN, et al. Prevalence of statin-drug interac- tions in older people: a systematic review. Eur J Clin Pharmacol. 2016;72:513 21. S4.1-32. Feldman HH, Doody RS, Kivipelto M, et al. Randomized controlled trial of atorvastatin in mild to moderate Alzheimer disease: LEADe. Neurology. 2010;74:956 64. S4.1-33. Houx PJ, Shepherd J, Blauw GJ, et al. Testing cognitive function in elderly populations: the PROSPER study. PROspective Study of Pravastatin in the Elderly at Risk. J Neurol Neurosurg Psychiatry. 2002;73:385 9. S4.1-34. Rodriguez F, Maron DJ, Knowles JW, et al. Association between intensity of statin therapy and mortality in patients with atheroscle- rotic cardiovascular disease. JAMA Cardiol. 2017;2:47 54. S4.1-35. Sano M, Bell KL, Galasko D, et al. A randomized, double-blind, placebo-controlled trial of simvastatin to treat Alzheimer disease. Neurology. 2011;77:556 63. S4.1-36. Trompet S, van Vliet P, de Craen AJ, et al. Pravastatin and cogni- tive function in the elderly. Results of the PROSPER study. J Neurol. 2010;257:85 90. S4.1-37. Feinstein MJ, Jhund P, Kang J, et al. Do statins reduce the risk of myocardial infarction in patients with heart failure? A pooled individual-level reanalysis of CORONA and GISSI-HF. Eur J Heart Fail. 2015;17:434 41. S4.1-38. Kjekshus J, Apetrei E, Barrios V, et al. Rosuvastatin in older patients with systolic heart failure. N Engl J Med. 2007;357:2248 61. S4.1-39. Tavazzi L, Maggioni AP, Marchioli R, et al. Effect of rosuvastatin in patients with chronic heart failure (the GISSI-HF trial): a randomised, double-blind, placebo-controlled trial. Lancet. 2008;372:1231 9. S4.1-40. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group. Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. N Engl J Med. 1998; 339:1349 57. S4.1-41. Bonaca MP, Nault P, Giugliano RP, et al. Low-density lipoprotein cholesterol lowering with evolocumab and outcomes in patients with peripheral artery disease: insights from the FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk). Circulation. 2018;137:338 50. S4.1-42. Cannon CP, Khan I, Klimchak AC, et al. Simulation of lipid-lowering therapy intensification in a population with atherosclerotic cardio- vascular disease. JAMA Cardiol. 2017;2:959 66. S4.1-43. Virani SS, Akeroyd JM, Nambi V, et al. Estimation of eligibility for pro- protein convertase subtilisin/kexin type 9 inhibitors and associated costs based on the FOURIER Trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk): insights from the Department of Veterans Affairs. Circulation. 2017;135:2572 4. S4.1-44. Bohula EA, Bonaca MP, Braunwald E, et al. Atherothrombotic risk sStratification and the efficacy and safety of vorapaxar in patients with stable ischemic heart disease and previous myocardial infarc- tion. Circulation. 2016;134:304 13. S4.1-45. Tikkanen MJ, Holme I, Cater NB, et al. Comparison of efficacy and safety of atorvastatin (80 mg) to simvastatin (20 to 40 mg) in patients aged <65 versus >65 years with coronary heart disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] study) Am J Cardiol. 2009;103:577 82. S4.1-46. Rogers JK, Jhund PS, Perez AC, et al. Effect of rosuvastatin on repeat heart failure hospitalizations: the CORONA Trial (Controlled Rosuvastatin Multinational Trial in Heart Failure). JACC Heart Fail. 2014;2:289 97. S4.1-47. Cleland JG, McMurray JJ, Kjekshus J, et al. Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure). J Am Coll Cardiol. 2009;54:1850 9. 4.2. Severe Hypercholesterolemia (LDL-C 190 mg/dL [ 4.9 mmol/L]) S4.2-1. Besseling J, Hovingh GK, Huijgen R, et al. Statins in Familial Hypercholesterolemia: Consequences for Coronary Artery Disease and All-Cause Mortality. J Am Coll Cardiol. 2016;68:252 60. S4.2-2. Khera AV, Won HH, Peloso GM, et al. Diagnostic yield and clinical util- ity of sequencing familial hypercholesterolemia genes in patients with severe hypercholesterolemia. J Am Coll Cardiol. 2016;67:2578 89. S4.2-3. Nanchen D, Gencer B, Muller O, et al. Prognosis of patients with familial hypercholesterolemia after acute coronary syndromes. Circulation. 2016;134:698 709. S4.2-4. Perak AM, Ning H, de Ferranti SD, et al. Long-term risk of athero- sclerotic cardiovascular disease in US adults with the familial hyper- cholesterolemia phenotype. Circulation. 2016;134:9 19. S4.2-5. 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. S4.2-6. Versmissen J, Oosterveer DM, Yazdanpanah M, et al. Efficacy of statins in familial hypercholesterolaemia: a long term cohort study. BMJ. 2008;337:a2423. S4.2-7. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials. Lancet. 2010;376:1670 81. S4.2-8. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387 97. CLINICAL STATEMENTS AND GUIDELINES S4.2-9. 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. S4.2-10. Kastelein JJ, Akdim F, Stroes ES, et al. Simvastatin with or with- out ezetimibe in familial hypercholesterolemia. N Engl J Med. 2008;358:1431 43. S4.2-11. Huijgen R, Abbink EJ, Bruckert E, et al. Colesevelam added to com- bination therapy with a statin and ezetimibe in patients with familial hypercholesterolemia: a 12-week, multicenter, randomized, double- blind, controlled trial. Clin Ther. 2010;32:615 25. S4.2-12. Ross S, D Mello M, Anand SS, et al. Effect of bile acid sequestrants on the risk of cardiovascular events: a Mendelian randomization analysis. Circ Cardiovasc Genet. 2015;8:618 27. S4.2-13. Kastelein JJ, Ginsberg HN, Langslet G, et al. ODYSSEY FH I and FH II: 78 week results with alirocumab treatment in 735 patients with heterozygous familial hypercholesterolaemia. Eur Heart J. 2015;36:2996 3003. S4.2-14. Perez de Isla L, Alonso R, Mata N, et al. Predicting cardiovascular events in familial hypercholesterolemia: the SAFEHEART Registry (Spanish Familial Hypercholesterolemia Cohort Study). Circulation. 2017;135:2133 44. S4.2-15. Raal FJ, Stein EA, Dufour R, et al. PCSK9 inhibition with evo- locumab (AMG 145) in heterozygous familial hypercholesterolaemia (RUTHERFORD-2): a randomised, double-blind, placebo-controlled trial. Lancet. 2015;385:331 40. S4.2-16. Nicholls SJ, Brandrup-Wognsen G, Palmer M, et al. Meta-analysis of comparative efficacy of increasing dose of atorvastatin versus rosu- vastatin versus simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am J Cardiol. 2010;105:69 76. S4.2-17. Pedersen SB, Langsted A, Nordestgaard BG. Nonfasting mild-to- moderate hypertriglyceridemia and risk of acute pancreatitis. JAMA Intern Med. 2016;176:1834 42. S4.2-18. Robinson JG, Huijgen R, Ray K, et al. Determining when to add nonstatin therapy: a quantitative approach. J Am Coll Cardiol. 2016;68:2412 21. S4.2-19. Vallejo-Vaz AJ, Robertson M, Catapano AL, et al. Low-density lipo- protein cholesterol lowering for the primary prevention of cardio- vascular disease among men with primary elevations of low-density lipoprotein cholesterol levels of 190 mg/dL or above: analyses from the WOSCOPS (West of Scotland Coronary Prevention Study) 5-year randomized trial and 20-year observational follow-up. Circulation. 2017;136:1878 91. S4.2-20. Bohula EA, Morrow DA, Giugliano RP, et al. Atherothrombotic risk stratification and ezetimibe for secondary prevention. J Am Coll Cardiol. 2017;69:911 21. 4.3. Diabetes Mellitus in Adults S4.3-1. 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. S4.3-2. 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. S4.3-3. 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. S4.3-4. 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. S4.3-5. 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. S4.3-6. 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. S4.3-7. Sever PS, Poulter NR, Dahlof B, et al. Reduction in cardiovascular events with atorvastatin in 2532 patients with type 2 diabetes: Anglo-Scandinavian Cardiac Outcomes Trial lipid-lowering arm (ASCOT-LLA) Diabetes Ccare. 2005;28:1151 7. S4.3-8. Soedamah-Muthu SS, Fuller JH, Mulnier HE, et al. High risk of car- diovascular 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. S4.3-9. 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. S4.3-10. Karmali KN, Goff DC Jr, Ning H, et al. A systematic examination of the 2013 ACC/AHA pooled cohort risk assessment tool for athero- sclerotic cardiovascular disease. J Am Coll Cardiol. 2014;64:959 68. S4.3-11. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equations. JAMA. 2014;311:1406 15. S4.3-12. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials. Lancet. 2010;376:1670 81. S4.3-13. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive pro- tein. N Engl J Med. 2008;359:2195 207. S4.3-14. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387 97. S4.3-15. 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. S4.3-16. Brownrigg JR, 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. S4.3-17. Constantino MI, Molyneaux L, Limacher-Gisler F, et al. Long-term complications and mortality in young-onset diabetes: type 2 dia- betes is more hazardous and lethal than type 1 diabetes. Diabetes Care. 2013;36:3863 9. S4.3-18. Dabelea D, Stafford JM, Mayer-Davis EJ, et al. Association of type 1 diabetes vs type 2 diabetes diagnosed during childhood and ado- lescence with complications during teenage years and young adult- hood. JAMA. 2017;317:825 35. S4.3-19. 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. S4.3-20. 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. S4.3-21. Nezarat N, Budoff MJ, Luo Y, et al. Presence, characteristics, and volumes of coronary plaque determined by computed tomogra- phy angiography in young type 2 diabetes mellitus. Am J Cardiol. 2017;119:1566 71. S4.3-22. Ogren M, Hedblad B, Engstrom 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 Malmo, Sweden. Eur J Vasc Endovasc Surg. 2005;29:182 9. S4.3-23. Pambianco G, Costacou T, Ellis D, et al. The 30-year natural history of type 1 diabetes complications: the Pittsburgh Epidemiology of Diabetes Complications Study experience. Diabetes. 2006;55:1463 9. S4.3-24. Pang XH, Han J, Ye WL, 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. S4.3-25. 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. S4.3-26. Ridker PM, Lonn E, Paynter NP, et al. Primary prevention with statin therapy in the elderly: new meta-analyses from the con- temporary JUPITER and HOPE-3 randomized trials. Circulation. 2017;135:1979 81. S4.3-27. 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. CLINICAL STATEMENTS AND GUIDELINES S4.3-28. Cannon CP, Blazing MA, Giugliano RP, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015;372:2387 97. 4.4. Primary Prevention S4.4-1. 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. S4.4-2. Avorn J. The psychology of clinical decision making implications for medication use. N Engl J Med. 2018;378:689 91. S4.4-3. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Clinical Expert Consensus Documents. J Am Coll Cardiol. 2016;68:92 125. S4.4-4. Lloyd-Jones DM, Morris PB, Ballantyne CM, et al. 2017 focused update of the 2016 ACC expert consensus decision pathway on the role of non-statin therapies for LDL-cholesterol lowering in the man- agement of atherosclerotic cardiovascular disease risk: a report of the American College of Cardiology Task Force on Expert Consensus Decision Pathways. J Am Coll Cardiol. 2017;70:1785 822. S4.4-5. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease pooled cohort risk equations. JAMA. 2014;311:1406 15. S4.4-6. Eckel RH, Jakicic JM, Ard JD, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S76 99. S4.4-7. Jensen MD, Ryan DH, Apovian CM, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and The Obesity Society. Circulation. 2014;129:S102 38. S4.4-8. US Department of Health and Human Services. 2008 Physical Activity Guidelines for Americans. Available at: https://health.gov/ paguidelines/pdf/paguide.pdf. Accessed August 24, 2018. S4.4-9. Estruch R, Ros E, Salas-Salvado J, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368:1279 90. S4.4-10. Agriculture. 2015 2020 Dietary Guidelines for Americans. 8th ed. 2015. US Department of Health and Human Services and US Department of, 2015. Available at: http://health.gov/dietary guidelines/2015/guidelines/. Accessed August 24, 2018. S4.4-11. Lichtenstein AH, Appel LJ, Brands M, et al. Summary of American Heart Association diet and lifestyle recommendations revision 2006 Arterioscler Thromb Vasc Biol. 2006;26:2186 91. S4.4-12. Ginsberg HN, Kris-Etherton P, Dennis B, et al. Effects of reducing dietary saturated fatty acids on plasma lipids and lipoproteins in healthy subjects: the DELTA Study, protocol 1. Arterioscler Thromb Vasc Biol. 1998;18:441 9. S4.4-13. Dehghan M, Mente A, Zhang X, et al. Associations of fats and car- bohydrate intake with cardiovascular disease and mortality in 18 countries from five continents (PURE): a prospective cohort study. Lancet. 2017;390:2050 62. S4.4-14. Chen M, Li Y, Sun Q, et al. Dairy fat and risk of cardiovascular dis- ease in 3 cohorts of US adults. Am J Clin Nutr. 2016;104:1209 17. S4.4-15. Loria CM, Liu K, Lewis CE, et al. Early adult risk factor levels and subsequent coronary artery calcification: the CARDIA Study. J Am Coll Cardiol. 2007;49:2013 20. S4.4-16. 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. S4.4-17. Choosing interventions that are cost effective (WHO-CHOICE): cost-effectiveness thresholds. Geneva, Switzerland: World Health Organization. 2009. S4.4-18. Physical Activity Guidelines Advisory Committee report, 2008. To the Secretary of Health and Human Services. Part A: executive sum- mary. Nutr Rev. 2009;67:114 20. S4.4-19. Warburton DE, Charlesworth S, Ivey A, et al. A systematic review of the evidence for Canada s Physical Activity Guidelines for Adults. Int J Behav Nutr Phys Act. 2010;7:39. S4.4-20. Shiroma EJ, Lee IM. Physical activity and cardiovascular health: lessons learned from epidemiological studies across age, gender, and race/ethnicity. Circulation. 2010;122:743 52. S4.4-21. Sattelmair J, Pertman J, Ding EL, et al. Dose response between physical activity and risk of coronary heart disease: a meta-analy- sis. Circulation. 2011;124:789 95. 4.4.1. Evaluation and Risk Assessment 4.4.1.1. Essential Process of Risk Assessment S4.4.1.1-1. American College of Cardiology. ASCVD Risk Predictor Plus. Available at: http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/ calculate/estimate/. Accessed September 1, 2018. S4.4.1.1-2. American Heart Association. ASCVD-Risk-Calculator. Available at: https://professional.heart.org/professional/GuidelinesStatements/ ASCVDRiskCalculator/UCM_457698_ASCVD-Risk-Calculator.jsp. Accessed September 1, 2018. S4.4.1.1-3. Karp I, Abrahamowicz M, Bartlett G, et al. Updated risk factor values and the ability of the multivariable risk score to predict coronary heart disease. Am J Epidemiol. 2004;160:707 16. S4.4.1.1-4. 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. 4.4.1.2. Pooled Cohort Equations S4.4.1.2-1. 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. S4.4.1.2-2. Kavousi M, Leening MJ, Nanchen D, et al. Comparison of application of the ACC/AHA guidelines, Adult Treatment Panel III guidelines, and European Society of Cardiology guidelines for cardiovascular disease prevention in a European cohort. JAMA. 2014;311:1416 23. S4.4.1.2-3. Wolfson J, Vock DM, Bandyopadhyay S, et al. Use and custom- ization of risk scores for predicting cardiovascular events using electronic health record data. J Am Heart Assoc 2017;6;e003670. S4.4.1.2-4. 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. S4.4.1.2-5. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce ath- erosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1 45. S4.4.1.2-6. JBS3 Board. Joint British Societies consensus recommendations for the prevention of cardiovascular disease (JBS3) Heart 2014; 100 suppl 2. ii1 67. S4.4.1.2-7. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease Pooled Cohort risk equa- tions. JAMA. 2014;311:1406 15. S4.4.1.2-8. Andersson C, Enserro D, Larson MG, et al. Implications of the US cholesterol guidelines on eligibility for statin therapy in the commu- nity: comparison of observed and predicted risks in the Framingham Heart Study Offspring Cohort. J Am Heart Assoc. 2015;4:e001888. S4.4.1.2-9. Colantonio LD, Richman JS, Carson AP, et al. Performance of the atherosclerotic cardiovascular disease pooled cohort risk equations by social deprivation status. J Am Heart Assoc. 2017;6:e005676. S4.4.1.2-10. Cook NR, Ridker PM. Further insight into the cardiovascular risk calculator: the roles of statins, revascularizations, and underas- certainment in the Women s Health Study. JAMA Intern Med. 2014;174:1964 71. S4.4.1.2-11. Dalton JE, Perzynski AT, Zidar DA, et al. Accuracy of cardiovascular risk prediction varies by neighborhood socioeconomic position: a retrospective cohort study. Ann Intern Med. 2017;167:456 64. S4.4.1.2-12. Feinstein MJ, Nance RM, Drozd DR, et al. Assessing and refin- ing myocardial infarction risk estimation among patients with human immunodeficiency virus: a study by the Centers for AIDS Research Network of Integrated Clinical Systems. JAMA Cardiol. 2017;2:155 62. S4.4.1.2-13. Flueckiger P, Qureshi W, Michos ED, et al. Guideline-based statin/lipid- lowering therapy eligibility for primary prevention and accuracy of coronary artery calcium and clinical cardiovascular events: the Multi- Ethnic Study of Atherosclerosis (MESA). Clin Cardiol. 2017;40:163 9. CLINICAL STATEMENTS AND GUIDELINES S4.4.1.2-14. Loprinzi PD, Addoh O. Predictive validity of the American College of Cardiology/American Heart Association pooled cohort equa- tions in predicting all-cause and cardiovascular disease-specific mortality in a national prospective cohort study of adults in the United States. Mayo Clin Proc. 2016;91:763 9. S4.4.1.2-15. Mortensen MB, Afzal S, Nordestgaard BG, et al. Primary preven- tion with statins: ACC/AHA risk-based approach versus trial- based approaches to guide statin therapy. J Am Coll Cardiol. 2015;66:2699 709. S4.4.1.2-16. Mortensen MB, Nordestgaard BG, Afzal S, et al. ACC/AHA guide- lines superior to ESC/EAS guidelines for primary prevention with statins in non-diabetic Europeans: the Copenhagen General Population Study. Eur Heart J. 2017;38:586 94. S4.4.1.2-17. 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 cholesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis). J Am Coll Cardiol. 2015;66:1657 68. S4.4.1.2-18. Rana JS, Tabada GH, Solomon MD, et al. Accuracy of the ath- erosclerotic cardiovascular risk equation in a large contemporary, multiethnic population. J Am Coll Cardiol. 2016;67:2118 30. S4.4.1.2-19. Ungprasert P, Matteson EL, Crowson CS. Reliability of cardio- vascular risk calculators to estimate accurately the risk of car- diovascular disease in patients with sarcoidosis. Am J Cardiol. 2017;120:868 73. S4.4.1.2-20. 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. S4.4.1.2-21. 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. 4.4.1.3. Risk-Enhancing Factors S4.4.1.3-1. American College of Cardiology. ASCVD Risk Predictor Plus. Available at: http://tools.acc.org/ASCVD-Risk-Estimator-Plus/#!/ calculate/estimate/. Accessed September 1, 2018. S4.4.1.3-2. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce ath- erosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1 45. S4.4.1.3-3. Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374:2021 31. 4.4.1.4. Coronary Artery Calcium S4.4.1.4-1. 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 cholesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis) J Am Coll Cardiol. 2015;66:1657 68. S4.4.1.4-2. 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. S4.4.1.4-3. Han D, O Hartaigh B, Lee JH, et al. Assessment of coronary artery calcium scoring for statin treatment strategy according to ACC/ AHA guidelines in asymptomatic Korean adults. Yonsei Med J. 2017;58:82 9. S4.4.1.4-4. Hong JC, Blankstein R, Blaha M, et al. Cost-effectiveness of coro- nary artery calcium testing among statin candidates according to the American College of Cardiology and American Heart Association cholesterol guidelines. J Am Coll Cardiol 2017;69 11 suppl:1828. S4.4.1.4-5. Mahabadi AA, Mohlenkamp S, Lehmann N, et al. CAC score improves coronary and CV risk assessment above statin indication by ESC and AHA/ACC primary prevention guidelines. J Am Coll Cardiol Img. 2017;10:143 53. S4.4.1.4-6. 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. S4.4.1.4-7. 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. S4.4.1.4-8. Yeboah J, Polonsky TS, Young R, et al. Utility of nontraditional risk markers in individuals ineligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association cholesterol guidelines. Circulation. 2015;132:916 22. S4.4.1.4-9. Budoff MJ, McClelland RL, Nasir K, et al. Cardiovascular events with absent or minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA) Am Heart J. 2009;158:554 61. S4.4.1.4-10. McEvoy JW, Blaha MJ, Rivera JJ, et al. Mortality rates in smokers and nonsmokers in the presence or absence of coronary artery calcification. J Am Coll Cardiol Img. 2012;5:1037 45. S4.4.1.4-11. Cohen R, Budoff M, McClelland RL, et al. Significance of a posi- tive family history for coronary heart disease in patients with a zero coronary artery calcium score (from the Multi-Ethnic Study of Atherosclerosis) Am J Cardiol. 2014;114:1210 14. S4.4.1.4-12. Metkus TS, Brown T, Budoff M, et al. HIV infection is associated with an increased prevalence of coronary noncalcified plaque among participants with a coronary artery calcium score of zero: Multicenter AIDS Cohort Study (MACS) HIV Med. 2015;16:635 9. S4.4.1.4-13. Budoff MJ, Young R, Burke G, et al. Ten-year association of coro- nary artery calcium with atherosclerotic cardiovascular disease (ASCVD) events: the multi-ethnic study of atherosclerosis (MESA) Eur Heart J. 2018;39:2401 8. S4.4.1.4-14. Valenti V, B OH, Heo R, et al. A 15-year warranty period for asymptomatic individuals without coronary artery calcium: a pro- spective follow-Up of 9715 individuals. J Am Coll Cardiol Img. 2015;8:900 9. S4.4.1.4-15. Lehmann N, Erbel R, Mahabadi AA, et al. Value of progression of coronary artery calcification for risk prediction of coronary and cardiovascular events: result of the HNR Study (Heinz Nixdorf Recall) Circulation. 2018;137:665 79. S4.4.1.4-16. Alluri K, McEvoy JW, Dardari ZA, et al. Distribution and burden of newly detected coronary artery calcium: results from the Multi- Ethnic Study of Atherosclerosis. J Cardiovasc Comput Tomogr. 2015;9:337 344 e1. S4.4.1.4-17. Lee S-E, Chang H-J, Sung JM, et al. Effects of statins on coronary atherosclerotic plaques: the PARADIGM study. J Am Coll Cardiol Img. 2018;11:1475 84. S4.4.1.4-18. Rozanski A, Gransar H, Shaw LJ, et al. Impact of coronary artery calcium scanning on coronary risk factors and downstream test- ing the EISNER (Early Identification of Subclinical Atherosclerosis by Noninvasive Imaging Research) prospective randomized trial. J Am Coll Cardiol. 2011;57:1622 32. S4.4.1.4-19. Chevalier M, Moran P, Ten JI, et al. Patient dose in digital mam- mography. Med Phys. 2004;31:2471 9. 4.4.2. Primary Prevention Adults 40 to 75 Years of Age With LDL-C Levels 70 to 189 mg/dL S4.4.2-1. Baigent C, Blackwell L, Emberson J, et al. Efficacy and safety of more intensive lowering of LDL cholesterol: a meta-analysis of data from 170000 participants in 26 randomised trials. Lancet. 2010;376:1670 81. S4.4.2-2. 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. S4.4.2-3. Cholesterol Treatment Trialists (CTT) Collaboration, Herrington W, Emberson J, et al. Impact of renal function on the effects of LDL cholesterol lowering with statin-based regimens: a meta-analysis of individual participant data from 28 randomised trials. Lancet Diabetes Endocrinol. 2016;4:829 39. S4.4.2-4. 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. Rockville, MD: US Agency for Healthcare Research and Quality, 2016. Report No.: 14-05206-EF-2. S4.4.2-5. Downs JR, Clearfield M, Weis S, et al. Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study. Jama. 1998;279:1615 22. S4.4.2-6. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive pro- tein. N Engl J Med. 2008;359:2195 207. CLINICAL STATEMENTS AND GUIDELINES S4.4.2-7. Taylor F, Huffman MD, Macedo AF, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013:CD004816. S4.4.2-8. 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. S4.4.2-9. 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. S4.4.2-10. Karmali KN, Goff DC Jr, Ning H, et al. A systematic examination of the 2013 ACC/AHA pooled cohort risk assessment tool for athero- sclerotic cardiovascular disease. J Am Coll Cardiol. 2014;64:959 68. S4.4.2-11. Muntner P, Colantonio LD, Cushman M, et al. Validation of the atherosclerotic cardiovascular disease pooled cohort risk equations. JAMA. 2014;311:1406 15. S4.4.2-12. Krumholz HM. Treatment of cholesterol in 2017. JAMA. 2017;318:417 8. S4.4.2-13. Martin SS, Sperling LS, Blaha MJ, et al. Clinician-patient risk discus- sion for atherosclerotic cardiovascular disease prevention: impor- tance to implementation of the 2013 ACC/AHA Guidelines. J Am Coll Cardiol. 2015;65:1361 8. S4.4.2-14. Stacey D, Legare F, Lewis K, et al. Decision aids for people facing health treatment or screening decisions. Cochrane Database Syst Rev. 2017;4:CD001431. S4.4.2-15. 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. S4.4.2-16. 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. S4.4.2-17. 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 cholesterol management guidelines: MESA (Multi-Ethnic Study of Atherosclerosis) J Am Coll Cardiol. 2015;66:1657 68. S4.4.2-18. Ridker PM, Mora S, Rose L. Percent reduction in LDL cholesterol 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. S4.4.2-19. 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. S4.4.2-20. 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. S4.4.2-21. 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. S4.4.2-22. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4:337 45. S4.4.2-23. 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. S4.4.2-24. Mihaylova B, Emberson J, Blackwell L, 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. S4.4.2-25. Nakamura H, Arakawa K, Itakura H, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006;368: 1155 63. S4.4.2-26. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce ath- erosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1 45. S4.4.2-27. Navar AM, Stone NJ, Martin SS. What to say and how to say it: effective communication for cardiovascular disease prevention. Curr Opin Cardiol. 2016;31:537 44. S4.4.2-28. Laing ST. High-intensity statins: guideline expectations and clinical application. JAMA. 2017;317:2543 4. S4.4.2-29. Thanassoulis G, Pencina MJ, Sniderman AD. The benefit model for prevention of cardiovascular disease: an opportunity to harmonize guidelines. JAMA Cardiol. 2017;2:1175 6. S4.4.2-30. Soran H, Schofield JD, Durrington PN. Cholesterol, not just cardio- vascular risk, is important in deciding who should receive statin treatment. Eur Heart J. 2015;36:2975 83. S4.4.2-31. Samarasekera EJ, Neilson JM, Warren RB, et al. Incidence of cardio- vascular disease in individuals with psoriasis: a systematic review and meta-analysis. J Invest Dermatol. 2013;133:2340 6. S4.4.2-32. Feinstein MJ, Nance RM, Drozd DR, et al. Assessing and refin- ing myocardial infarction risk estimation among patients with human immunodeficiency virus: a study by the Centers for AIDS Research Network of Integrated Clinical Systems. JAMA Cardiol. 2017;2:155 62. S4.4.2-33. Goff DC Jr, Lloyd-Jones DM, Bennett G, et al. 2013 ACC/AHA guide- line 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(suppl 2):S49 73. S4.4.2-34. 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. S4.4.2-35. Cohen R, Budoff M, McClelland RL, et al. Significance of a posi- tive family history for coronary heart disease in patients with a zero coronary artery calcium score (from the Multi-Ethnic Study of Atherosclerosis) Am J Cardiol. 2014;114:1210 4. S4.4.2-36. 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. S4.4.2-37. Fudim M, Zalawadiya S, Patel DK, et al. Data on coronary artery calcium score performance and cardiovascular risk reclassification across gender and ethnicities. Data Brief. 2016;6:578 81. S4.4.2-38. 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. J Am Coll Cardiol Img. 2017;10:833 42. S4.4.2-39. Han D, O Hartaigh B, Lee JH, et al. Assessment of coronary artery calcium scoring for statin treatment strategy according to ACC/ AHA guidelines in asymptomatic Korean adults. Yonsei Med J. 2017;58:82 9. S4.4.2-40. Hong JC, Blankstein R, Blaha M, et al. Cost-effectiveness of coronary artery calcium testing among statin candidates according to the American College of Cardiology and American Heart Association cholesterol guidelines. J Am Coll Cardiol 2017;69 11 suppl:1828. S4.4.2-41. Kavousi M, Desai CS, Ayers C, et al. Prevalence and prognostic implications of coronary artery calcification in low-risk women: a meta-analysis. JAMA. 2016;316:2126 34. S4.4.2-42. Mahabadi AA, Mohlenkamp S, Lehmann N, et al. CAC score improves coronary and CV risk assessment above statin indication by ESC and AHA/ACC primary prevention guidelines. J Am Coll Cardiol Img. 2017;10:143 53. S4.4.2-43. 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. S4.4.2-44. 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. S4.4.2-45. Qureshi WT, Rana JS, Yeboah J, et al. Risk stratification for primary prevention of coronary artery disease: roles of C-reactive protein and coronary artery calcium. Curr Cardiol Rep. 2015;17:110. S4.4.2-46. 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. S4.4.2-47. Waheed S, Pollack S, Roth M, et al. Collective impact of conven- tional cardiovascular risk factors and coronary calcium score on clini- cal outcomes with or without statin therapy: the St Francis Heart Study. Atherosclerosis. 2016;255:193 9. CLINICAL STATEMENTS AND GUIDELINES S4.4.2-48. Yeboah J, Polonsky TS, Young R, et al. Utility of nontraditional risk markers in individuals ineligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association cholesterol guidelines. Circulation. 2015;132:916 22. S4.4.2-49. Yeboah J, Young R, McClelland RL, et al. Utility of nontraditional risk markers in atherosclerotic cardiovascular disease risk assess- ment. J Am Coll Cardiol. 2016;67:139 47. S4.4.2-50. Budoff MJ, McClelland RL, Nasir K, et al. Cardiovascular events with absent or minimal coronary calcification: the Multi-Ethnic Study of Atherosclerosis (MESA) Am Heart J. 2009;158:554 61. S4.4.2-51. Schulman-Marcus J, Valenti V, Hartaigh BO, et al. Prognostic util- ity of coronary artery calcium scoring in active smokers: a 15-year follow-up study. Int J Cardiol. 2014;177:581 3. S4.4.2 52. Valenti V, Hartaigh BO, Cho I, et al. Absence of coronary artery cal- cium identifies asymptomatic diabetic individuals at low near-term but not long-term risk of mortality: a 15-year follow-up study of 9715 patients. Circ Cardiovasc Imaging 2016;9:e003528. S4.4.2 53. Patel J, Al Rifai M, Blaha MJ, et al. Coronary artery calcium improves risk assessment in adults with a family history of pre- mature coronary heart disease: results from Multi-Ethnic Study of Atherosclerosis. Circ Cardiovasc Imaging. 2015:8;e003186. S4.4.2-54. Sharp Collaborative Group null. Study of Heart and Renal Protection (SHARP): randomized trial to assess the effects of lower- ing low-density lipoprotein cholesterol among 9438 patients with chronic kidney disease. Am Heart J. 2010;160:785 94; e10. S4.4.2-55. The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA. 1984;251:351 64. S4.4.2-56. Spence JD, Huff MW, Heidenheim P, et al. Combination therapy with colestipol and psyllium mucilloid in patients with hyperlipid- emia. Ann Intern Med. 1995;123:493 9. S4.4.2-57. Pandya A, Sy S, Cho S, et al. Cost-effectiveness of 10-year risk thresholds for initiation of statin therapy for primary prevention of cardiovascular disease. JAMA. 2015;314:142 50. S4.4.2-58. Singh A, Collins BL, Gupta A, et al. Cardiovascular risk and statin eligibility of young adults after an MI: Partners YOUNG-MI Registry. J Am Coll Cardiol. 2018;71:292 302. S4.4.2-59. Navar-Boggan AM, Peterson ED, D Agostino RB Sr, et al. Using age- and sex-specific risk thresholds to guide statin therapy: one size may not fit all. J Am Coll Cardiol. 2015;65:1633 9. S4.4.2-60. The Lipid Research Clinics Coronary Primary Prevention Trial results. II. The relationship of reduction in incidence of coronary heart dis- ease to cholesterol lowering. JAMA. 1984;251:365 74. 4.4.3. Monitoring in Response to LDL-C Lowering Therapy S4.4.3-1. Stone NJ, Robinson JG, Lichtenstein AH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce ath- erosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014;129:S1 45. S4.4.3-2. Benner JS, Tierce JC, Ballantyne CM, et al. Follow-up lipid tests and physician visits are associated with improved adherence to statin therapy. Pharmacoeconomics 2004:22 suppl 3:13 23. S4.4.3-3. Chiavaroli L, Nishi SK, Khan TA, et al. Portfolio dietary pattern and cardiovascular disease: a systematic review and meta-analysis of controlled trials. Prog Cardiovasc Dis. 2018;61:43 53. 4.4.4. Primary Prevention in Other Age Groups 4.4.4.1. Older Adults S4.4.4.1-1. Glynn RJ, Koenig W, Nordestgaard BG, et al. Rosuvastatin for primary prevention in older persons with elevated C-reactive pro- tein and low to average low-density lipoprotein cholesterol lev- els: exploratory analysis of a randomized trial. Ann Intern Med. 2010;152:488 96. w174. S4.4.4.1-2. Ridker PM, Danielson E, Fonseca FA, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive pro- tein. N Engl J Med. 2008;359:2195 207. S4.4.4.1-3. Ridker PM, Lonn E, Paynter NP, et al. Primary prevention with statin therapy in the elderly: new meta-analyses from the con- temporary JUPITER and HOPE-3 randomized trials. Circulation. 2017;135:1979 81. S4.4.4.1-4. Yusuf S, Bosch J, Dagenais G, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374:2021 31. S4.4.4.1-5. Orkaby AR, Gaziano JM, Djousse L, et al. Statins for primary pre- vention of cardiovascular events and mortality in older men. J Am Geriatr Soc. 2017;65:2362 8. S4.4.4.1-6. Mihaylova B, Emberson J, Blackwell L, et al. The effects of lower- ing LDL cholesterol with statin therapy in people at low risk of vascular disease: meta-analysis of individual data from 27 ran- domised trials. Lancet. 2012;380:581 90. S4.4.4.1-7. Savarese G, Gotto AM Jr, Paolillo S, et al. Benefits of statins in elderly subjects without established cardiovascular disease: a meta-analysis. J Am Coll Cardiol. 2013;62:2090 9. S4.4.4.1-8. Teng M, Lin L, Zhao YJ, et al. Statins for primary prevention of cardiovascular disease in elderly patients: systematic review and meta-analysis. Drugs Aging. 2015;32:649 61. S4.4.4.1-9. Kutner JS, Blatchford PJ, Taylor DH Jr, et al. Safety and benefit of discontinuing statin therapy in the setting of advanced, life- limiting illness: a randomized clinical trial. JAMA Intern Med. 2015;175:691 700. S4.4.4.1-10. Mahabadi AA, Mohlenkamp S, Lehmann N, et al. CAC score improves coronary and CV risk assessment above statin indication by ESC and AHA/ACC primary prevention guidelines. J Am Coll Cardiol Img. 2017;10:143 53. S4.4.4.1-11. 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. S4.4.4.1-12. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002;360:1623 30. S4.4.4.1-13. Mortensen MB, Falk E. Primary prevention with statins in the elderly. J Am Coll Cardiol. 2018;71:85 94. S4.4.4.1-14. Bell SP, Orr NM, Dodson JA, et al. What to expect from the evolving field of geriatric cardiology. J Am Coll Cardiol. 2015;66:1286 99. S4.4.4.1-15. Fleg JL, Forman DE, Berra K, et al. Secondary prevention of ath- erosclerotic cardiovascular disease in older adults: a scientific statement from the American Heart Association. Circulation. 2013;128:2422 46. S4.4.4.1-16. Garfinkel D, Ilhan B, Bahat G. Routine deprescribing of chronic medications to combat polypharmacy. Ther Adv Drug Saf. 2015;6:212 33. S4.4.4.1-17. Qi K, Reeve E, Hilmer SN, et al. Older peoples attitudes regarding polypharmacy, statin use and willingness to have statins depre- scribed in Australia. Int J Clin Pharm. 2015;37:949 57. S4.4.4.1-18. Rossello X, Pocock SJ, Julian DG. Long-term use of cardiovascu- lar drugs: challenges for research and for patient care. J Am Coll Cardiol. 2015;66:1273 85. S4.4.4.1-19. Han BH, Sutin D, Williamson JD, et al. Effect of statin treatment vs usual care on primary cardiovascular prevention among older adults: the ALLHAT-LLT randomized clinical trial. JAMA Intern Med. 2017;177:955 65. S4.4.4.1-20. Odden MC, Pletcher MJ, Coxson PG, et al. Cost-effectiveness and population impact of statins for primary prevention in adults aged 75 yearsorolderintheUnitedStates.AnnInternMed.2015;162:533 41. 4.4.4.2. Young Adults (20 to 39 Years of Age) S4.4.4.2-1. Strong JP, Malcom GT, Oalmann MC, et al. The PDAY Study: natural history, risk factors, and pathobiology. Pathobiological Determinants of Atherosclerosis in Youth. Ann N Y Acad Sci. 1997;811:226 35.; discussion 35 7. S4.4.4.2-2. McGill HC Jr, McMahan CA, Herderick EE, et al. Effects of coro- nary heart disease risk factors on atherosclerosis of selected regions of the aorta and right coronary artery. PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler Thromb Vasc Biol. 2000;20:836 45. S4.4.4.2-3. Williams RR, Hopkins PN, Hunt SC, et al. Population-based fre- quency of dyslipidemia syndromes in coronary-prone families in Utah. Arch Intern Med. 1990;150:582 8. S4.4.4.2-4. McGill HC Jr, McMahan CA, Malcom GT, et al. Effects of serum lipoproteins and smoking on atherosclerosis in young men and women. The PDAY Research Group. Pathobiological Determinants of Atherosclerosis in Youth. Arterioscler Thromb Vasc Biol. 1997;17:95 106. CLINICAL STATEMENTS AND GUIDELINES S4.4.4.2-5. Vodnala D, Rubenfire M, Brook RD. Secondary causes of dyslipid- emia. Am J Cardiol. 2012;110:823 5. S4.4.4.2-6. Lloyd-Jones DM, Wilson PW, Larson MG, et al. Lifetime risk of coronary heart disease by cholesterol levels at selected ages. Arch Intern Med. 2003;163:1966 72. S4.4.4.2-7. Domanski M, Lloyd-Jones D, Fuster V, et al. Can we dramatically reduce the incidence of coronary heart disease? Nat Rev Cardiol. 2011;8:721 5. S4.4.4.2-8. Durrington PN, Soran H. Cholesterol levels should play a more important role in identifying statin recipients. Circulation. 2017;135:627 9. S4.4.4.2-9. Thanassoulis G, Pencina MJ, Sniderman AD. The benefit model for prevention of cardiovascular disease: an opportunity to har- monize guidelines. JAMA Cardiol. 2017;2:1175 6. S4.4.4.2-10. Berry JD, Dyer A, Cai X, et al. Lifetime risks of cardiovascular dis- ease. N Engl J Med. 2012;366:321 9. S4.4.4.2-11. Lehr AL, Driver SL, Stone NJ. The ABCDs of lifestyle counseling. JAMA Cardiol. 2016;1:505 6. S4.4.4.2-12. Omura JD, Watson KB, Loustalot F, et al. Primary care providers awareness of physical activity-related intensive behavioral coun- seling services for cardiovascular disease prevention. Am J Health Promot. 2018. 890117118784226. S4.4.4.2-13. Domanski MJ, Fuster V, Diaz-Mitoma F, et al. Next steps in primary prevention of coronary heart disease: rationale for and design of the ECAD trial. J Am Coll Cardiol. 2015;66:1828 36. S4.4.4.2-14. 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. 4.4.4.3. Children and Adolescents S4.4.4.3-1. Iannuzzi A, Licenziati MR, Vacca M, et al. Comparison of two diets of varying glycemic index on carotid subclinical atherosclerosis in obese children. Heart Vessels. 2009;24:419 24. S4.4.4.3-2. Murphy EC, Carson L, Neal W, et al. Effects of an exercise inter- vention using Dance Dance Revolution on endothelial function and other risk factors in overweight children. Int J Pediatr Obes. 2009;4:205 14. S4.4.4.3-3. Pratt RE, Kavey RE, Quinzi D. Combined dyslipidemia in obese children: response to a focused lifestyle approach. J Clin Lipidol. 2014;8:181 6. S4.4.4.3-4. de Ferranti SD, Milliren CE, Denhoff ER, et al. Providing food to treat adolescents at risk for cardiovascular disease. Obesity (Silver Spring). 2015;23:2109 17. S4.4.4.3-5. Niinikoski H, Lagstrom H, Jokinen E, et al. Impact of repeated dietary counseling between infancy and 14 years of age on dietary intakes and serum lipids and lipoproteins: the STRIP study. Circulation. 2007;116:1032 40. S4.4.4.3-6. Obarzanek E, Kimm SY, Barton BA, et al. Long-term safety and efficacy of a cholesterol-lowering diet in children with elevated low-density lipoprotein cholesterol: seven-year results of the Dietary Intervention Study in Children (DISC) Pediatrics. 2001;107:256 64. S4.4.4.3-7. Dorgan JF, Liu L, Barton BA, et al. Adolescent diet and metabolic syndrome in young women: results of the Dietary Intervention Study in Children (DISC) follow-up study. J Clin Endocrinol Metab. 2011;96:E1999 2008. S4.4.4.3-8. Wong H, Chahal N, Manlhiot C, et al. Flaxseed in pediatric hyper- lipidemia: a placebo-controlled, blinded, randomized clinical trial of dietary flaxseed supplementation for children and adolescents with hypercholesterolemia. JAMA Pediatr. 2013;167:708 13. S4.4.4.3-9. Zachariah JP, Chan J, Mendelson MM, et al. Adolescent dyslipid- emia and standardized lifestyle modification: benchmarking real- world practice. J Am Coll Cardiol. 2016;68:2122 3. S4.4.4.3-10. Torvik K, Narverud I, Ottestad I, et al. Dietary counseling is associ- ated with an improved lipid profile in children with familial hyper- cholesterolemia. Atherosclerosis. 2016;252:21 7. S4.4.4.3-11. Koletzko B, Kupke I, Wendel U. Treatment of hypercholesterol- emia in children and adolescents. Acta Paediatr. 1992;81:682 5. S4.4.4.3-12. Tershakovec AM, Shannon BM, Achterberg CL, et al. One-year follow-up of nutrition education for hypercholesterolemic chil- dren. Am J Public Health. 1998;88:258 61. S4.4.4.3-13. Kusters DM, Caceres M, Coll M, et al. Efficacy and safety of ezetimibe monotherapy in children with heterozygous familial or nonfamilial hypercholesterolemia. J Pediatr. 2015;166:1377 84 e1-3. S4.4.4.3-14. Yeste D, Chacon P, Clemente M, et al. Ezetimibe as monotherapy in the treatment of hypercholesterolemia in children and adoles- cents. J Pediatr Endocrinol Metab. 2009;22:487 92. S4.4.4.3-15. Clauss S, Wai KM, Kavey RE, et al. Ezetimibe treatment of pediatric patients with hypercholesterolemia. J Pediatr. 2009;154:869 72. S4.4.4.3-16. Sonnett T, Robinson J, Milani P, et al. Role of colesevelam in man- aging heterozygous familial hypercholesterolemia in adolescents and children. Adolesc Health Med Ther. 2010;1:53 60. S4.4.4.3-17. Wald DS, Kasturiratne A, Godoy A, et al. Child-parent screening for familial hypercholesterolemia. J Pediatr. 2011;159:865 7. S4.4.4.3-18. Wald DS, Bestwick JP, Morris JK, et al. Child-parent familial hypercholesterolemia screening in primary care. N Engl J Med. 2016;375:1628 37. S4.4.4.3-19. Ritchie SK, Murphy EC, Ice C, et al. Universal versus targeted blood cholesterol screening among youth: the CARDIAC project. Pediatrics. 2010;126:260 5. S4.4.4.3-20. Skovby F, Micic S, Jepsen B, et al. Screening for familial hyper- cholesterolaemia by measurement of apolipoproteins in capillary blood. Arch Dis Child. 1991;66:844 7. S4.4.4.3-21. Garcia RE, Moodie DS. Routine cholesterol surveillance in child- hood. Pediatrics. 1989;84:751 5. S4.4.4.3-22. Ned RM, Sijbrands EJ. Cascade screening for familial hypercholes- terolemia (FH) PLoS Curr. 2011;3:RRN1238. S4.4.4.3-23. Bender R, Bell DA, Hooper AJ, et al. Screening for familial hyper- cholesterolaemia. Pathology. 2012;44:122 8. S4.4.4.3-24. National Institute for Health and Care Excellence (NICE) (UK). Familial hypercholesterolaemia: identification and management. Available at: http://www.nice.org.uk/guidance/CG71. Accessed August 24, 2018. S4.4.4.3-25. Kit BK, Kuklina E, Carroll MD, et al. Prevalence of and trends in dyslipidemia and blood pressure among US children and adoles- cents, 1999 2012 JAMA Pediatr. 2015;169:272 9. S4.4.4.3-26. May AL, Kuklina EV, Yoon PW. Prevalence of cardiovascular dis- ease risk factors among US adolescents, 1999 2008 Pediatrics. 2012;129:1035 41. S4.4.4.3-27. Lozano P, Henrikson NB, Morrison CC, et al. Lipid screening in childhood and adolescence for detection of multifactorial dys- lipidemia: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2016;316:634 44. S4.4.4.3-28. Gidding SS, Champagne MA, de Ferranti SD, et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation. 2015;132:2167 92. S4.4.4.3-29. Lozano P, Henrikson NB, Dunn J, et al. Lipid screening in child- hood and adolescence for detection of familial hypercholesterol- emia: evidence report and systematic review for the US Preventive Services Task Force. JAMA. 2016;316:645 55. S4.4.4.3-30. Vuorio A, Kuoppala J, Kovanen PT, et al. Statins for children with familial hypercholesterolemia. Cochrane Database Syst Rev. 2017;7:CD006401. S4.4.4.3-31. Schanberg LE, Sandborg C, Barnhart HX, et al. Use of atorvas- tatin in systemic lupus erythematosus in children and adolescents. Arthritis Rheum. 2012;64:285 96. S4.4.4.3-32. Ardoin SP, Schanberg LE, Sandborg CI, et al. Secondary analysis of APPLE study suggests atorvastatin may reduce atherosclerosis pro- gression in pubertal lupus patients with higher C reactive protein. Ann Rheum Dis. 2014;73:557 66. S4.4.4.3-33. Perak AM, Ning H, de Ferranti SD, et al. Long-term risk of ath- erosclerotic cardiovascular disease in US adults with the familial hypercholesterolemia phenotype. Circulation. 2016;134:9 19. S4.4.4.3-34. Neil HA, Hawkins MM, Durrington PN, et al. Non-coronary heart disease mortality and risk of fatal cancer in patients with treated heterozygous familial hypercholesterolaemia: a prospective regis- try study. Atherosclerosis. 2005;179:293 7. S4.4.4.3-35. Sniderman AD, Tsimikas S, Fazio S. The severe hypercholesterol- emia phenotype: clinical diagnosis, management, and emerging therapies. J Am Coll Cardiol. 2014;63:1935 47. S4.4.4.3-36. Smith AJ, Turner EL, Kinra S. Universal cholesterol screening in childhood: a systematic review. Acad Pediatr. 2016;16:716 25. S4.4.4.3-37. Kerr M, Pears R, Miedzybrodzka Z, et al. Cost effectiveness of cascade testing for familial hypercholesterolaemia, based on data from familial hypercholesterolaemia services in the UK. Eur Heart J. 2017;38:1832 9. CLINICAL STATEMENTS AND GUIDELINES S4.4.4.3-38. Berenson GS. Childhood risk factors predict adult risk associated with subclinical cardiovascular disease. The Bogalusa Heart Study. Am J Cardiol. 2002;90:3L 7L. S4.4.4.3-39. Juonala M, Magnussen CG, Venn A, et al. Influence of age on associations between childhood risk factors and carotid intima- media thickness in adulthood: the Cardiovascular Risk in Young Finns Study, the Childhood Determinants of Adult Health Study, the Bogalusa Heart Study, and the Muscatine Study for the International Childhood Cardiovascular Cohort (i3C) Consortium. Circulation. 2010;122:2514 20. S4.4.4.3-40. Juhola J, Magnussen CG, Viikari JS, et al. Tracking of serum lipid levels, blood pressure, and body mass index from childhood to adulthood: the Cardiovascular Risk in Young Finns Study. J Pediatr. 2011;159:584 90. S4.4.4.3-41. Expert Panel on Integrated Guidelines for Cardiovascular Health and Risk Reduction in Children and Adolescents, National Heart, Lung, and Blood Institute. Expert panel on integrated guide- lines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics 2011;128 suppl 5: S213 56. S4.4.4.3-42. Gidding SS, Daniels SR, Kavey RE, et al. Developing the 2011 integrated pediatric guidelines for cardiovascular risk reduction. Pediatrics. 2012;129:e1311 9. 4.5. Other Populations at Risk S4.5.1-1. Carnethon MR, Pu J, Howard G, et al. Cardiovascular health in African Americans: a scientific statement from the American Heart Association. Circulation. 2017;136:e393 423. abnormalities among normal-weight persons from five racial/eth- nic groups in the United States: a cross-sectional analysis of two cohort studies. Ann Intern Med. 2017;166:628 36. S4.5.1-3. Rao G, Powell-Wiley TM, Ancheta I, et al. Identification of obesity and cardiovascular risk in ethnically and racially diverse popula- tions: a scientific statement from the American Heart Association. Circulation. 2015;132:457 72. S4.5.1-4. Hata J, Kiyohara Y. Epidemiology of stroke and coronary artery disease in Asia. Circ J. 2013;77:1923 32. S4.5.1-5. Group H-TC. HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment. 