J Lipid Atheroscler.  2019 Sep;8(2):78-131. 10.12997/jla.2019.8.2.78.

2018 Guidelines for the Management of Dyslipidemia in Korea

• Rhee EJ
• Kim HC
• Kim JH
• Lee EY
• Kim BJ
• Kim EM
• Song Y
• Lim JH
• Kim HJ
• Choi S
• Moon MK
• Na JO
• Park KY
• Oh MS
• Han SY
• Noh J
• Yi KH
• Lee SH
• Hong SC
• Jeong IK
• On behalf of the Committee of Clinical Practice Guideline of Korean Society of Lipid and Atherosclerosis

• KMID: 2458377
• DOI: http://doi.org/10.12997/jla.2019.8.2.78

Abstract

No abstract available.

MeSH Terms

Dyslipidemias*
Korea*

Figure

• 

  Fig. 1 Trends of cardio-cerebrovascular mortality among Koreans, 1983 to 2016 (source: cause of death statistics). (A) Mortality rate (not age-adjusted). (B) Age-adjusted mortality rate (with reference to 2005 population).

• 

  Fig. 2 Trends of coronary artery disease mortality among Koreans, 1983 to 2016 (source: cause of death statistics). (A) Mortality rate (not age-adjusted). (B) Age-adjusted mortality rate (with reference to 2005 population).

• 

  Fig. 3 Trends of cerebrovascular disease mortality among Koreans, 1983 to 2016 (source: cause of death statistics). (A) Mortality rate (not age-adjusted). (B) Age-adjusted mortality rate (with reference to 2005 population).

• 

  Fig. 4 Serum lipid concentrations by age, sex, and menopause in Korean general population. (A) Total cholesterol, (B) low density lipoprotein cholesterol (LDL-C), (C) triglyceride, and (D) high density lipoprotein cholesterol (HDL-C) (data source: Korea National Health and Nutrition Examination Survey 2010 to 2016).20

• 

  Fig. 5 Trends in prevalence of hypercholesterolemia (A, source: National Health and Nutrition Examination Survey [KNHANES] 2005 to 2016) and sex and age-specific prevalence of dyslipidemia (B, source: KNHANES 2010 to 2012).2122

• 

  Fig. 6 Trends in hypercholesterolemia management (source: National Health and Nutrition Examination Survey).

• 

  Fig. 7 Dietary guideline for prevention and treatment dyslipidemia.

• 

  Fig. 8 Drug therapy strategy for hypercholesterolemia. LDL-C, low density lipoprotein cholesterol.

• 

  Fig. 9 Comparison of low density lipoprotein cholesterol (LDL-C) reduction effects of statins between foreigners and Koreans.75767778798081828384858687888990919293949596 Modified from Cholesterol Treatment Trialists' (CTT) Collaboration et al.27

• 

  Fig. 10 Korean data on the lipid-controlling efficacy of currently used statins.7576777879808182838485868788899091929394 LDL-C, low density lipoprotein cholesterol.

• 

  Fig. 11 Dyslipidemia treatment algorithm in children and adolescents. LDL-C, low density lipoprotein cholesterol; TG, triglyceride; CHILD, Cardiovascular Health Integrated Lifestyle Diet; CVD, cardiovascular disease; HDL-C, high density lipoprotein cholesterol.

Reference

1. World Health Organization. Global Health Observatory (GHO) data [Internet]. Geneva: World Health Organization;c2019. cited 2019 Jun 20. Available from: http://www.who.int/gho/ncd/mortality_morbidity/ncd_total/en/index.html.

2. World Health Organization. Preventing chronic diseases: a vital investment [Internet]. Geneva: World Health Organization;c2019. cited 2019 Jun 20. Available from: http://www.who.int/chp/chronic_disease_report/en.

3. Hong JS, Kang HC, Lee SH, Kim J. Long-term trend in the incidence of acute myocardial infarction in Korea: 1997-2007. Korean Circ J. 2009; 39:467–476.

4. Kim RB, Kim BG, Kim YM, Seo JW, Lim YS, Kim HS, et al. Trends in the incidence of hospitalized acute myocardial infarction and stroke in Korea, 2006-2010. J Korean Med Sci. 2013; 28:16–24.

5. Committee for the Korean Guidelines for the Management of Dyslipidemia. 2015 Korean guidelines for the management of dyslipidemia: executive summary (English Translation). Korean Circ J. 2016; 46:275–306.

6. Catapano AL, Graham I, De Backer G, Wiklund O, Chapman MJ, Drexel H, et al. 2016 ESC/EAS guidelines for the management of dyslipidaemias. Eur Heart J. 2016; 37:2999–3058.

7. Jellinger PS, Handelsman Y, Rosenblit PD, Bloomgarden ZT, Fonseca VA, Garber AJ, et al. American association of clinical endocrinologists and American college of endocrinology guidelines for management of dyslipidemia and prevention of cardiovascular disease. Endocr Pract. 2017; 23:Suppl 2. 1–87.

8. Dicembrini I, Giannini S, Ragghianti B, Mannucci E, Monami M. Effects of PCSK9 inhibitors on LDL cholesterol, cardiovascular morbidity and all-cause mortality: a systematic review and meta-analysis of randomized controlled trials. J Endocrinol Invest. 2019; 02. 14.

9. Yonsei University, Korea Centers for Disease Control and Prevention. 2012 Private Subsidized Project on the Computation of the Incidence of Myocardial Infarction. Seoul (KR): Yonsei University;2013.

10. The World Health Organization MONICA Project. Ecological analysis of the association between mortality and major risk factors of cardiovascular disease. Int J Epidemiol. 1994; 23:505–516.

11. Korea Centers for Disease Control and Prevention. 2017 Chronic Diseases and Issues: Chronic Disease Factbook. Cheongju (KR): Korea Centers for Disease Control and Prevention;2017.

12. Kim HC, Oh SM. Noncommunicable diseases: current status of major modifiable risk factors in Korea. J Prev Med Public Health. 2013; 46:165–172.

13. Jee SH, Jang Y, Oh DJ, Oh BH, Lee SH, Park SW, et al. A coronary heart disease prediction model: the Korean Heart Study. BMJ Open. 2014; 4:e005025.

14. Korean Society for Preventive Medicine. Clinical Preventive Medicine Based on Scientific Evidence. Seoul (KR): Gyechuk Munhwasa;2011. p. 183–221.

15. Wilson PW, D'Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998; 97:1837–1847.

16. D'Agostino RB Sr, Grundy S, Sullivan LM, Wilson P. CHD Risk Prediction Group. Validation of the Framingham coronary heart disease prediction scores: results of a multiple ethnic groups investigation. JAMA. 2001; 286:180–187.

17. Eichler K, Puhan MA, Steurer J, Bachmann LM. Prediction of first coronary events with the Framingham score: a systematic review. Am Heart J. 2007; 153:722–731.

18. Jee SH, Park JW, Lee SY, Nam BH, Ryu HG, Kim SY, et al. Stroke risk prediction model: a risk profile from the Korean study. Atherosclerosis. 2008; 197:318–325.

19. Park GM, Han S, Kim SH, Jo MW, Her SH, Lee JB, et al. Model for assessing cardiovascular risk in a Korean population. Circ Cardiovasc Qual Outcomes. 2014; 7:944–951.

20. Park JH, Lee MH, Shim JS, Choi DP, Song BM, Lee SW, et al. Effects of age, sex, and menopausal status on blood cholesterol profile in the Korean population. Korean Circ J. 2015; 45:141–148.

21. Ministry of Health and Welfare, Korea Centers for Disease Control and Prevention. 2016 National Health Statistics I, 7th National Health and Nutrition Examination Survey: First Year (2016). Cheongju (KR): Korea Centers for Disease Control and Prevention;2017.

22. Kim HC. Epidemiology of dyslipidemia in Korea. J Korean Med Assoc. 2016; 59:352–357.

23. Korean Society of Lipidology and Atherosclerosis. Dyslipidemia fact sheets in Korea, 2018 [Internet]. Seoul (KR): Korean Society of Lipidology and Atherosclerosis;2018. cited 2019 Jun 20. Available from: http://www.lipid.or.kr/file/Dyslipidemia%20Fact%20Sheets%20in%20Korea%202018.pdf.

24. Stone NJ, Robinson JG, Lichtenstein AH, Bairey Merz CN, Blum CB, Eckel RH, et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2014; 129:25 Suppl 2. S1–S45.

25. Vaucher J, Marques-Vidal P, Preisig M, Waeber G, Vollenweider P. Population and economic impact of the 2013 ACC/AHA guidelines compared with European guidelines to prevent cardiovascular disease. Eur Heart J. 2014; 35:958–959.

26. LaRosa JC, Grundy SM, Waters DD, Shear C, Barter P, Fruchart JC, et al. Intensive lipid lowering with atorvastatin in patients with stable coronary disease. N Engl J Med. 2005; 352:1425–1435.

27. Cholesterol Treatment Trialists' (CTT) Collaboration. Baigent 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; 376:1670–1681.

28. Garber AJ, Abrahamson MJ, Barzilay JI, Blonde L, Bloomgarden ZT, Bush MA, et al. Consensus statement by the American Association of Clinical Endocrinologists and American College of Endocrinology on the comprehensive type 2 diabetes management algorithm: 2018 executive summary. Endocr Pract. 2018; 24:91–120.

29. Cannon CP, Blazing MA, Giugliano RP, McCagg A, White JA, Theroux P, et al. Ezetimibe added to statin therapy after acute coronary syndromes. N Engl J Med. 2015; 372:2387–2397.

30. Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017; 376:1713–1722.

31. Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018; 379:2097–2107.

32. Amarenco P, Bogousslavsky J, Callahan A 3rd, Goldstein LB, Hennerici M, Rudolph AE, et al. High-dose atorvastatin after stroke or transient ischemic attack. N Engl J Med. 2006; 355:549–559.

33. NIPPON DATA80 Research Group. Risk assessment chart for death from cardiovascular disease based on a 19-year follow-up study of a Japanese representative population. Circ J. 2006; 70:1249–1255.

34. de Lemos JA, Blazing MA, Wiviott SD, Lewis EF, Fox KA, White HD, et al. Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial. JAMA. 2004; 292:1307–1316.

35. Lee KH, Jeong MH, Kim HM, Ahn Y, Kim JH, Chae SC, et al. Benefit of early statin therapy in patients with acute myocardial infarction who have extremely low low-density lipoprotein cholesterol. J Am Coll Cardiol. 2011; 58:1664–1671.

36. Heart Protection Study Collaborative Group. MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial. Lancet. 2002; 360:7–22.

37. Grundy SM, Cleeman JI, Merz CN, Brewer HB Jr, Clark LT, Hunninghake DB, et al. Implications of recent clinical trials for the National Cholesterol Education Program Adult Treatment Panel III Guidelines. J Am Coll Cardiol. 2004; 44:720–732.

38. Ferguson GG, Eliasziw M, Barr HW, Clagett GP, Barnes RW, Wallace MC, et al. The North American Symptomatic Carotid Endarterectomy Trial : surgical results in 1415 patients. Stroke. 1999; 30:1751–1758.

39. Randomised trial of endarterectomy for recently symptomatic carotid stenosis: final results of the MRC European Carotid Surgery Trial (ECST). Lancet. 1998; 351:1379–1387.

40. National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III). Third report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002; 106:3143–3421.

41. Furberg CD, Adams HP Jr, Applegate WB, Byington RP, Espeland MA, Hartwell T, et al. Effect of lovastatin on early carotid atherosclerosis and cardiovascular events. Asymptomatic Carotid Artery Progression Study (ACAPS) Research Group. Circulation. 1994; 90:1679–1687.

42. Teramoto T, Sasaki J, Ishibashi S, Birou S, Daida H, Dohi S, et al. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan: 2012 version. J Atheroscler Thromb. 2013; 20:517–523.

43. Toskes PP. Hyperlipidemic pancreatitis. Gastroenterol Clin North Am. 1990; 19:783–791.

44. Studer M, Briel M, Leimenstoll B, Glass TR, Bucher HC. Effect of different antilipidemic agents and diets on mortality: a systematic review. Arch Intern Med. 2005; 165:725–730.

45. Jun M, Foote C, Lv J, Neal B, Patel A, Nicholls SJ, et al. Effects of fibrates on cardiovascular outcomes: a systematic review and meta-analysis. Lancet. 2010; 375:1875–1884.

46. ACCORD Study Group. Ginsberg HN, Elam MB, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. N Engl J Med. 2010; 362:1563–1574.

47. Poobalan A, Aucott L, Smith WC, Avenell A, Jung R, Broom J, et al. Effects of weight loss in overweight/obese individuals and long-term lipid outcomes: a systematic review. Obes Rev. 2004; 5:43–50.

48. Korean Society for the Study of Obesity. Guideline for the Management of Obesity. Seoul (KR): Chungwoon;2018. p. 26–30.

49. Rees K, Dyakova M, Wilson N, Ward K, Thorogood M, Brunner E. Dietary advice for reducing cardiovascular risk. Cochrane Database Syst Rev. 2013; 12:CD002128.

50. Ministry of Health and Welfare, Korea Centers for Disease Control and Prevention. 2015 National Health Statistics: 6th National Health and Nutrition Examination Survey: Third Year (2015). Cheongju (KR): Korea Centers for Disease Control and Prevention;2015.

51. Ministry of Health and Welfare, Korean Nutrition Society. Dietary Reference Intake for Koreans 2015. Seoul (KR): Korean Nutrition Society;2015.

52. Mensink RP, Zock PL, Kester AD, Katan MB. Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials. Am J Clin Nutr. 2003; 77:1146–1155.

53. Eckel RH, Jakicic JM, Ard JD, de Jesus JM, Houston Miller N, Hubbard VS, 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; 129:25 Suppl 2. S76–S99.

54. Harris WS. n-3 fatty acids and serum lipoproteins: human studies. Am J Clin Nutr. 1997; 65:5 Suppl. 1645S–1654S.

55. Brown L, Rosner B, Willett WW, Sacks FM. Cholesterol-lowering effects of dietary fiber: a meta-analysis. Am J Clin Nutr. 1999; 69:30–42.

56. Anderson JW, Randles KM, Kendall CW, Jenkins DJ. Carbohydrate and fiber recommendations for individuals with diabetes: a quantitative assessment and meta-analysis of the evidence. J Am Coll Nutr. 2004; 23:5–17.

57. Chrysohoou C, Panagiotakos DB, Pitsavos C, Skoumas J, Toutouza M, Papaioannou I, et al. Effects of chronic alcohol consumption on lipid levels, inflammatory and haemostatic factors in the general population: the ‘ATTICA’ Study. Eur J Cardiovasc Prev Rehabil. 2003; 10:355–361.

58. Fletcher GF, Ades PA, Kligfield P, Arena R, Balady GJ, Bittner VA, et al. Exercise standards for testing and training: a scientific statement from the American Heart Association. Circulation. 2013; 128:873–934.

59. Taylor RS, Brown A, Ebrahim S, Jolliffe J, Noorani H, Rees K, et al. Exercise-based rehabilitation for patients with coronary heart disease: systematic review and meta-analysis of randomized controlled trials. Am J Med. 2004; 116:682–692.

60. Kraus WE, Houmard JA, Duscha BD, Knetzger KJ, Wharton MB, McCartney JS, et al. Effects of the amount and intensity of exercise on plasma lipoproteins. N Engl J Med. 2002; 347:1483–1492.

61. Haskell WL, Lee IM, Pate RR, Powell KE, Blair SN, Franklin BA, et al. Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association. Circulation. 2007; 116:1081–1093.

62. Kavazis AN. Exercise preconditioning of the myocardium. Sports Med. 2009; 39:923–935.

63. 2018 Physical Activity Guidelines Advisory Committee. 2018 Physical Activity Guidelines Advisory Committee Scientific Report. Washington, DC: U.S. Department of Health and Human Services;2018.

64. Kelley GA, Kelley KS. Impact of progressive resistance training on lipids and lipoproteins in adults: a meta-analysis of randomized controlled trials. Prev Med. 2009; 48:9–19.

65. Kelley GA, Kelley KS. Impact of progressive resistance training on lipids and lipoproteins in adults: another look at a meta-analysis using prediction intervals. Prev Med. 2009; 49:473–475.

66. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European Guidelines on cardiovascular disease prevention in clinical practice (version 2012). The Fifth Joint Task Force of the European Society of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012; 33:1635–1701.

67. Moriguchi EH, Fusegawa Y, Tamachi H, Goto Y. Effects of smoking on HDL subfractions in myocardial infarction patients: effects on lecithin-cholesterol acyltransferase and hepatic lipase. Clin Chim Acta. 1991; 195:139–143.

68. Hellerstein MK, Benowitz NL, Neese RA, Schwartz JM, Hoh R, Jacob P 3rd, et al. Effects of cigarette smoking and its cessation on lipid metabolism and energy expenditure in heavy smokers. J Clin Invest. 1994; 93:265–272.

69. McCall MR, van den Berg JJ, Kuypers FA, Tribble DL, Krauss RM, Knoff LJ, et al. Modification of LCAT activity and HDL structure. New links between cigarette smoke and coronary heart disease risk. Arterioscler Thromb. 1994; 14:248–253.

70. Craig WY, Palomaki GE, Haddow JE. Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. BMJ. 1989; 298:784–788.

71. Stubbe I, Eskilsson J, Nilsson-Ehle P. High-density lipoprotein concentrations increase after stopping smoking. Br Med J (Clin Res Ed). 1982; 284:1511–1513.

72. Gepner AD, Piper ME, Johnson HM, Fiore MC, Baker TB, Stein JH. Effects of smoking and smoking cessation on lipids and lipoproteins: outcomes from a randomized clinical trial. Am Heart J. 2011; 161:145–151.

73. Prescott E, Scharling H, Osler M, Schnohr P. Importance of light smoking and inhalation habits on risk of myocardial infarction and all cause mortality: a 22 year follow up of 12 149 men and women in the Copenhagen City Heart Study. J Epidemiol Community Health. 2002; 56:702–706.

74. National Institute for Health and Clinical Excellence. NICE Public Health Guidance 10. Smoking cessation services in primary care, pharmacies, local authorities and workplaces, particularly for manual working groups, pregnant women and hard to reach communities [Internet]. London: National Institute for Health and Clinical Excellence;c2019. cited 2019 Jun 20. Available from: http://www.nice.org.uk/nicemedia/pdf/PH010guidance.pdf.

75. Law MR, Morris JK, Wald NJ. Environmental tobacco smoke exposure and ischaemic heart disease: an evaluation of the evidence. BMJ. 1997; 315:973–980.

76. Mohiuddin SM, Mooss AN, Hunter CB, Grollmes TL, Cloutier DA, Hilleman DE. Intensive smoking cessation intervention reduces mortality in high-risk smokers with cardiovascular disease. Chest. 2007; 131:446–452.

77. Anthonisen NR, Skeans MA, Wise RA, Manfreda J, Kanner RE, Connett JE. Lung Health Study Research Group. The effects of a smoking cessation intervention on 14.5-year mortality: a randomized clinical trial. Ann Intern Med. 2005; 142:233–239.

78. Reiner Z. Combined therapy in the treatment of dyslipidemia. Fundam Clin Pharmacol. 2010; 24:19–28.

79. Khang AR, Song YS, Kim KM, Moon JH, Lim S, Park KS, et al. Comparison of different statin therapy to change low-density lipoprotein cholesterol and high-density lipoprotein cholesterol level in Korean patients with and without diabetes. J Clin Lipidol. 2016; 10:528–537.

80. American College of Cardiology. ODYSSEY Outcomes: results suggest use of PCSK9 inhibitor reduces CV events, LDL-C in ACS patients [Internet]. Washington, DC: American College of Cardiology;2018. cited 2019 Jun 20. Available from: https://www.acc.org/latest-in-cardiology/articles/2018/03/05/15/53/sat-9am-odyssey-outcomes-cv-outcomes-with-alirocumab-after-acs-acc-2018.

81. Keech A, Simes RJ, Barter P, Best J, Scott R, Taskinen MR, et al. Effects of long-term fenofibrate therapy on cardiovascular events in 9795 people with type 2 diabetes mellitus (the FIELD study): randomised controlled trial. Lancet. 2005; 366:1849–1861.

82. Balk EM, Lichtenstein AH, Chung M, Kupelnick B, Chew P, Lau J. Effects of omega-3 fatty acids on serum markers of cardiovascular disease risk: a systematic review. Atherosclerosis. 2006; 189:19–30.

83. Yokoyama M, Origasa H, Matsuzaki M, Matsuzawa Y, Saito Y, Ishikawa Y, et al. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007; 369:1090–1098.

84. Davidson MH, Stein EA, Bays HE, Maki KC, Doyle RT, Shalwitz RA, et al. Efficacy and tolerability of adding prescription omega-3 fatty acids 4 g/d to simvastatin 40 mg/d in hypertriglyceridemic patients: an 8-week, randomized, double-blind, placebo-controlled study. Clin Ther. 2007; 29:1354–1367.

85. Vaughan CJ, Gotto AM Jr. Update on statins: 2003. Circulation. 2004; 110:886–892.

86. Cholesterol Treatment Trialists' (CTT) Collaborators. Mihaylova 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; 380:581–590.

87. Tobert JA. Lovastatin and beyond: the history of the HMG-CoA reductase inhibitors. Nat Rev Drug Discov. 2003; 2:517–526.

88. Gotto AM Jr, Opie LH. Lipid-modifying and antiatherosclerotic drugs. In : Opie L, Gersh B, editors. Drugs for the Heart. 8th ed. Philadelphia (PA): Elsevier Saunders;2013. p. 398–435.

89. Jones PH, Davidson MH, Stein EA, Bays HE, McKenney JM, Miller E, et al. Comparison of the efficacy and safety of rosuvastatin versus atorvastatin, simvastatin, and pravastatin across doses (STELLAR* Trial). Am J Cardiol. 2003; 92:152–160.

90. Nicholls SJ, Brandrup-Wognsen G, Palmer M, Barter PJ. Meta-analysis of comparative efficacy of increasing dose of Atorvastatin versus Rosuvastatin versus Simvastatin on lowering levels of atherogenic lipids (from VOYAGER). Am J Cardiol. 2010; 105:69–76.

91. Smith MEB, Lee NJ, Haney E, Carson S. Drug class review: HMG-CoA reductase inhibitors (statins) and fixed-dose combination products containing a statin: final report update 5 [Internet]. Portland (OR): Oregon Health & Science University;2009. cited 2019 Jun 20. Available from: http://www.ncbi.nlm.nih.gov/books/NBK47273.

92. Lee HJ, Min CH, Choi KS, Ryu WS, Ryoo UH. Effects of lovastatin (Mevacor®) on lowering plasma lipids in patients with hyperlipidemia. Korean Circ J. 1991; 21:781–785.

93. Yoo WS, Lee SB, Ahn JH, Kim K, Lee DC, Rhee KJ, et al. Effect of lovastatin (Mevacor®) on serum lipids of patients with primary hyperlipidemia. Korean Circ J. 1989; 19:489–496.

94. Bae JH, Choue CW, Kim KS, Kim MS, Song JS. Hypolipidemic effects and safety of lovastatin in patients with primary hypercholesterolemia. Korean Circ J. 1991; 21:129–136.

95. Koh KK, Quon MJ, Sakuma I, Han SH, Choi H, Lee K, et al. Differential metabolic effects of rosuvastatin and pravastatin in hypercholesterolemic patients. Int J Cardiol. 2013; 166:509–515.

96. Koh KK, Lim S, Choi H, Lee Y, Han SH, Lee K, et al. Combination pravastatin and valsartan treatment has additive beneficial effects to simultaneously improve both metabolic and cardiovascular phenotypes beyond that of monotherapy with either drug in patients with primary hypercholesterolemia. Diabetes. 2013; 62:3547–3552.

97. Kim SH, Kim MK, Lee HY, Kang HJ, Kim YJ, Kim HS. Prospective randomized comparison between omega-3 fatty acid supplements plus simvastatin versus simvastatin alone in Korean patients with mixed dyslipidemia: lipoprotein profiles and heart rate variability. Eur J Clin Nutr. 2011; 65:110–116.

98. Kim SH, Kim MK, Seo HS, Hyun MS, Han KR, Cho SW, et al. Efficacy and safety of morning versus evening dose of controlled-release simvastatin tablets in patients with hyperlipidemia: a randomized, double-blind, multicenter phase III trial. Clin Ther. 2013; 35:1350–1360.

99. Park S, Kang HJ, Rim SJ, Ha JW, Oh BH, Chung N, et al. A randomized, open-label study to evaluate the efficacy and safety of pitavastatin compared with simvastatin in Korean patients with hypercholesterolemia. Clin Ther. 2005; 27:1074–1082.

100. Atorvastatin Study Group in Korea. Flexible initial dosing of atorvastatin based upon initial low-density lipoprotein cholesterol levels in type 2 diabetic patients. Korean J Intern Med. 2008; 23:22–29.

101. Koh KK, Quon MJ, Han SH, Lee Y, Kim SJ, Shin EK. Atorvastatin causes insulin resistance and increases ambient glycemia in hypercholesterolemic patients. J Am Coll Cardiol. 2010; 55:1209–1216.

102. Park JS, Kim YJ, Choi JY, Kim YN, Hong TJ, Kim DS, et al. Comparative study of low doses of rosuvastatin and atorvastatin on lipid and glycemic control in patients with metabolic syndrome and hypercholesterolemia. Korean J Intern Med. 2010; 25:27–35.

103. Her AY, Kim JY, Kang SM, Choi D, Jang Y, Chung N, et al. Effects of atorvastatin 20 mg, rosuvastatin 10 mg, and atorvastatin/ezetimibe 5 mg/5 mg on lipoproteins and glucose metabolism. J Cardiovasc Pharmacol Ther. 2010; 15:167–174.

104. Kim SH, Park K, Hong SJ, Cho YS, Sung JD, Moon GW, et al. Efficacy and tolerability of a generic and a branded formulation of atorvastatin 20 mg/d in hypercholesterolemic Korean adults at high risk for cardiovascular disease: a multicenter, prospective, randomized, double-blind, double-dummy clinical trial. Clin Ther. 2010; 32:1896–1905.

105. Kim SH, Seo MK, Yoon MH, Choi DH, Hong TJ, Kim HS. Assessment of the efficacy and tolerability of 2 formulations of atorvastatin in Korean adults with hypercholesterolemia: a multicenter, prospective, open-label, randomized trial. Clin Ther. 2013; 35:77–86.

106. Lee CW, Kang SJ, Ahn JM, Song HG, Lee JY, Kim WJ, et al. Comparison of effects of atorvastatin (20 mg) versus rosuvastatin (10 mg) therapy on mild coronary atherosclerotic plaques (from the ARTMAP trial). Am J Cardiol. 2012; 109:1700–1704.

107. Lee JH, Kang HJ, Kim HS, Sohn DW, Oh BH, Park YB. Effects of ezetimibe/simvastatin 10/20 mg vs. atorvastatin 20 mg on apolipoprotein B/apolipoprotein A1 in Korean patients with type 2 diabetes mellitus: results of a randomized controlled trial. Am J Cardiovasc Drugs. 2013; 13:343–351.

108. Lee SH, Kang SM, Park S, Jang Y, Chung N, Choi D. The effects of statin monotherapy and low-dose statin/ezetimibe on lipoprotein-associated phospholipase A₂. Clin Cardiol. 2011; 34:108–112.

109. Hong YJ, Jeong MH, Hachinohe D, Ahmed K, Choi YH, Cho SH, et al. Comparison of effects of rosuvastatin and atorvastatin on plaque regression in Korean patients with untreated intermediate coronary stenosis. Circ J. 2011; 75:398–406.

110. Lee SH, Cho KI, Kim JY, Ahn YK, Rha SW, Kim YJ, et al. Non-lipid effects of rosuvastatin-fenofibrate combination therapy in high-risk Asian patients with mixed hyperlipidemia. Atherosclerosis. 2012; 221:169–175.

111. Lee SH, Chung N, Kwan J, Kim DI, Kim WH, Kim CJ, et al. Comparison of the efficacy and tolerability of pitavastatin and atorvastatin: an 8-week, multicenter, randomized, open-label, dose-titration study in Korean patients with hypercholesterolemia. Clin Ther. 2007; 29:2365–2373.

112. Weng TC, Yang YH, Lin SJ, Tai SH. A systematic review and meta-analysis on the therapeutic equivalence of statins. J Clin Pharm Ther. 2010; 35:139–151.

113. Mukhtar RY, Reid J, Reckless JP. Pitavastatin. Int J Clin Pract. 2005; 59:239–252.

114. Baigent C, Keech A, Kearney PM, Blackwell L, Buck G, Pollicino C, et al. Efficacy and safety of cholesterol-lowering treatment: prospective meta-analysis of data from 90,056 participants in 14 randomised trials of statins. Lancet. 2005; 366:1267–1278.

115. Cannon CP, Braunwald E, McCabe CH, Rader DJ, Rouleau JL, Belder R, et al. Intensive versus moderate lipid lowering with statins after acute coronary syndromes. N Engl J Med. 2004; 350:1495–1504.

116. Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, et al. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002; 360:1623–1630.

117. Taylor F, Ward K, Moore TH, Burke M, Davey Smith G, Casas JP, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2011; 1:CD004816.

118. Mills EJ, Rachlis B, Wu P, Devereaux PJ, Arora P, Perri D. Primary prevention of cardiovascular mortality and events with statin treatments: a network meta-analysis involving more than 65,000 patients. J Am Coll Cardiol. 2008; 52:1769–1781.

119. Nakamura H, Arakawa K, Itakura H, Kitabatake A, Goto Y, Toyota T, et al. Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial. Lancet. 2006; 368:1155–1163.

120. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008; 359:2195–2207.

121. Eckel RH. Approach to the patient who is intolerant of statin therapy. J Clin Endocrinol Metab. 2010; 95:2015–2022.

122. Dale KM, White CM, Henyan NN, Kluger J, Coleman CI. Impact of statin dosing intensity on transaminase and creatine kinase. Am J Med. 2007; 120:706–712.

123. Berglund L, Brunzell JD, Goldberg AC, Goldberg IJ, Sacks F, Murad MH, et al. Evaluation and treatment of hypertriglyceridemia: an Endocrine Society clinical practice guideline. J Clin Endocrinol Metab. 2012; 97:2969–2989.

124. Harris WS, Ginsberg HN, Arunakul N, Shachter NS, Windsor SL, Adams M, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. J Cardiovasc Risk. 1997; 4:385–391.

125. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto miocardico. Dietary supplementation with n-3 polyunsaturated fatty acids and vitamin E after myocardial infarction: results of the GISSI-Prevenzione trial. Lancet. 1999; 354:447–455.

126. Glauber H, Wallace P, Griver K, Brechtel G. Adverse metabolic effect of omega-3 fatty acids in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1988; 108:663–668.

127. Annuzzi G, Rivellese A, Capaldo B, Di Marino L, Iovine C, Marotta G, et al. A controlled study on the effects of n-3 fatty acids on lipid and glucose metabolism in non-insulin-dependent diabetic patients. Atherosclerosis. 1991; 87:65–73.

128. Kaushik M, Mozaffarian D, Spiegelman D, Manson JE, Willett WC, Hu FB. Long-chain omega-3 fatty acids, fish intake, and the risk of type 2 diabetes mellitus. Am J Clin Nutr. 2009; 90:613–620.

129. Wu JH, Micha R, Imamura F, Pan A, Biggs ML, Ajaz O, et al. Omega-3 fatty acids and incident type 2 diabetes: a systematic review and meta-analysis. Br J Nutr. 2012; 107:Suppl 2. S214–S227.

130. Pedersen HS, Mulvad G, Seidelin KN, Malcom GT, Boudreau DA. N-3 fatty acids as a risk factor for haemorrhagic stroke. Lancet. 1999; 353:812–813.

131. Gajos G, Zalewski J, Rostoff P, Nessler J, Piwowarska W, Undas A. Reduced thrombin formation and altered fibrin clot properties induced by polyunsaturated omega-3 fatty acids on top of dual antiplatelet therapy in patients undergoing percutaneous coronary intervention (OMEGA-PCI clot). Arterioscler Thromb Vasc Biol. 2011; 31:1696–1702.

132. Wu D, Meydani SN. n-3 polyunsaturated fatty acids and immune function. Proc Nutr Soc. 1998; 57:503–509.

133. AIM-HIGH Investigators. Boden WE, Probstfield JL, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011; 365:2255–2267.

134. Rossebø AB, Pedersen TR, Boman K, Brudi P, Chambers JB, Egstrup K, et al. Intensive lipid lowering with simvastatin and ezetimibe in aortic stenosis. N Engl J Med. 2008; 359:1343–1356.

135. Baigent C, Landray MJ, Reith C, Emberson J, Wheeler DC, Tomson 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; 377:2181–2192.

136. Cannon CP, Giugliano RP, Blazing MA, Harrington RA, Peterson JL, Sisk CM, et al. Rationale and design of IMPROVE-IT (IMProved Reduction of Outcomes: Vytorin Efficacy International Trial): comparison of ezetimbe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes in patients with acute coronary syndromes. Am Heart J. 2008; 156:826–832.

137. Sabatine MS, Giugliano RP, Wiviott SD, Raal FJ, Blom DJ, Robinson J, et al. Efficacy and safety of evolocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015; 372:1500–1509.

138. Robinson JG, Farnier M, Krempf M, Bergeron J, Luc G, Averna M, et al. Efficacy and safety of alirocumab in reducing lipids and cardiovascular events. N Engl J Med. 2015; 372:1489–1499.

139. Athyros VG, Papageorgiou AA, Athyrou VV, Demitriadis DS, Pehlivanidis AN, Kontopoulos AG. Atorvastatin versus four statin-fibrate combinations in patients with familial combined hyperlipidaemia. J Cardiovasc Risk. 2002; 9:33–39.

140. Farnier M, Steinmetz A, Retterstøl K, Császár A. Fixed-dose combination fenofibrate/pravastatin 160/40 mg versus simvastatin 20 mg monotherapy in adults with type 2 diabetes and mixed hyperlipidemia uncontrolled with simvastatin 20 mg: a double-blind, randomized comparative study. Clin Ther. 2011; 33:1–12.

141. Zhao XQ, Krasuski RA, Baer J, Whitney EJ, Neradilek B, Chait A, et al. Effects of combination lipid therapy on coronary stenosis progression and clinical cardiovascular events in coronary disease patients with metabolic syndrome: a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), the HDL-Atherosclerosis Treatment Study (HATS), and the Armed Forces Regression Study (AFREGS). Am J Cardiol. 2009; 104:1457–1464.

142. Galan P, Kesse-Guyot E, Czernichow S, Briancon S, Blacher J, Hercberg S. SU.FOL.OM3 Collaborative Group. Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial. BMJ. 2010; 341:c6273.

143. HPS2-THRIVE Collaborative Group. Landray MJ, Haynes R. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014; 371:203–212.

144. Amarenco P, Labreuche J, Lavallée P, Touboul PJ. Statins in stroke prevention and carotid atherosclerosis: systematic review and up-to-date meta-analysis. Stroke. 2004; 35:2902–2909.

145. Hosomi N, Nagai Y, Kohriyama T, Ohtsuki T, Aoki S, Nezu T, et al. The Japan Statin Treatment Against Recurrent Stroke (J-STARS): a multicenter, randomized, open-label, parallel-group study. EBioMedicine. 2015; 2:1071–1078.

146. Goldstein LB, Amarenco P, Szarek M, Callahan A 3rd, Hennerici M, Sillesen H, et al. Hemorrhagic stroke in the stroke prevention by aggressive reduction in cholesterol levels study. Neurology. 2008; 70:24 Pt 2. 2364–2370.

147. Tonelli M, Wanner C. Kidney Disease: Improving Global Outcomes Lipid Guideline Development Work Group Members. Lipid management in chronic kidney disease: synopsis of the Kidney Disease: Improving Global Outcomes 2013 clinical practice guideline. Ann Intern Med. 2014; 160:182.

148. Holdaas H, Fellström B, Jardine AG, Holme I, Nyberg G, Fauchald P, et al. Effect of fluvastatin on cardiac outcomes in renal transplant recipients: a multicentre, randomised, placebo-controlled trial. Lancet. 2003; 361:2024–2031.

149. Wanner C, Krane V, März W, Olschewski M, Mann JF, Ruf G, et al. Atorvastatin in patients with type 2 diabetes mellitus undergoing hemodialysis. N Engl J Med. 2005; 353:238–248.

150. Fellström BC, Jardine AG, Schmieder RE, Holdaas H, Bannister K, Beutler J, et al. Rosuvastatin and cardiovascular events in patients undergoing hemodialysis. N Engl J Med. 2009; 360:1395–1407.

151. European Association for Cardiovascular Prevention & Rehabilitation. Reiner Z, Catapano AL, et al. ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011; 32:1769–1818.

152. Zhao YY, Weir MA, Manno M, Cordy P, Gomes T, Hackam DG, et al. New fibrate use and acute renal outcomes in elderly adults: a population-based study. Ann Intern Med. 2012; 156:560–569.

153. Harper CR, Jacobson TA. Managing dyslipidemia in chronic kidney disease. J Am Coll Cardiol. 2008; 51:2375–2384.

154. Kidney Disease Outcomes Quality Initiative (K/DOQI) Group. K/DOQI clinical practice guidelines for management of dyslipidemias in patients with kidney disease. Am J Kidney Dis. 2003; 41:4 Suppl 3. S1–S91.

155. Davidson MH, Armani A, McKenney JM, Jacobson TA. Safety considerations with fibrate therapy. Am J Cardiol. 2007; 99:6A. 3C–18C.

156. Mottillo S, Filion KB, Genest J, Joseph L, Pilote L, Poirier P, et al. The metabolic syndrome and cardiovascular risk a systematic review and meta-analysis. J Am Coll Cardiol. 2010; 56:1113–1132.

157. Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart disease in subjects with type 2 diabetes and in nondiabetic subjects with and without prior myocardial infarction. N Engl J Med. 1998; 339:229–234.

158. Boekholdt SM, Arsenault BJ, Mora S, Pedersen TR, LaRosa JC, Nestel PJ, et al. Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis. JAMA. 2012; 307:1302–1309.

159. Ilanne-Parikka P, Eriksson JG, Lindström J, Peltonen M, Aunola S, Hämäläinen H, et al. Effect of lifestyle intervention on the occurrence of metabolic syndrome and its components in the Finnish Diabetes Prevention Study. Diabetes Care. 2008; 31:805–807.

160. Colhoun HM, Betteridge DJ, Durrington PN, Hitman GA, Neil HA, Livingstone SJ, et al. Primary prevention of cardiovascular disease with atorvastatin in type 2 diabetes in the Collaborative Atorvastatin Diabetes Study (CARDS): multicentre randomised placebo-controlled trial. Lancet. 2004; 364:685–696.

161. Shepherd J, Barter P, Carmena R, Deedwania P, Fruchart JC, Haffner S, et al. Effect of lowering LDL cholesterol substantially below currently recommended levels in patients with coronary heart disease and diabetes: the Treating to New Targets (TNT) study. Diabetes Care. 2006; 29:1220–1226.

162. Lee SH, Kwon HS, Park YM, Ko SH, Choi YH, Yoon KH, et al. Statin discontinuation after achieving a target low density lipoprotein cholesterol level in type 2 diabetic patients without cardiovascular disease: a randomized controlled study. Diabetes Metab J. 2014; 38:64–73.

163. Sacks FM, Carey VJ, Fruchart JC. Combination lipid therapy in type 2 diabetes. N Engl J Med. 2010; 363:692–694.

164. Moriarty PM, Jacobson TA, Bruckert E, Thompson PD, Guyton JR, Baccara-Dinet MT, et al. Efficacy and safety of alirocumab, a monoclonal antibody to PCSK9, in statin-intolerant patients: design and rationale of ODYSSEY ALTERNATIVE, a randomized phase 3 trial. J Clin Lipidol. 2014; 8:554–561.

165. Zhang XL, Zhu QQ, Zhu L, Chen JZ, Chen QH, Li GN, et al. Safety and efficacy of anti-PCSK9 antibodies: a meta-analysis of 25 randomized, controlled trials. BMC Med. 2015; 13:123.

166. Statistics Korea. Statistical report of population and housing census in 2017 [Internet]. Daejeon (KR): Statistics Korea;c1996. cited 2019 Jun 20. Available from: http://kostat.go.kr/portal/eng/index.action.

167. Glynn RJ, Koenig W, Nordestgaard BG, Shepherd J, Ridker PM. Rosuvastatin for primary prevention in older persons with elevated C-reactive protein and low to average low-density lipoprotein cholesterol levels: exploratory analysis of a randomized trial. Ann Intern Med. 2010; 152:488–496.

168. Neil HA, DeMicco DA, Luo D, Betteridge DJ, Colhoun HM, Durrington PN, et al. Analysis of efficacy and safety in patients aged 65-75 years at randomization: Collaborative Atorvastatin Diabetes Study (CARDS). Diabetes Care. 2006; 29:2378–2384.

169. Wenger NK, Lewis SJ, Herrington DM, Bittner V, Welty FK. Treating to New Targets Study Steering Committee and Investigators. Outcomes of using high- or low-dose atorvastatin in patients 65 years of age or older with stable coronary heart disease. Ann Intern Med. 2007; 147:1–9.

170. Lewis SJ, Moye LA, Sacks FM, Johnstone DE, Timmis G, Mitchell J, et al. Effect of pravastatin on cardiovascular events in older patients with myocardial infarction and cholesterol levels in the average range. Results of the Cholesterol and Recurrent Events (CARE) trial. Ann Intern Med. 1998; 129:681–689.

171. 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 guidelines for cardiovascular health and risk reduction in children and adolescents: summary report. Pediatrics. 2011; 128:Suppl 5. S213–S256.

172. Yang S, Hwang JS, Park HK, Lee HS, Kim HS, Kim EY, et al. Serum lipid concentrations, prevalence of dyslipidemia, and percentage eligible for pharmacological treatment of Korean children and adolescents; data from the Korea National Health and Nutrition Examination Survey IV (2007-2009). PLoS One. 2012; 7:e49253.

173. Srinivasan SR, Frontini MG, Xu J, Berenson GS. Utility of childhood non-high-density lipoprotein cholesterol levels in predicting adult dyslipidemia and other cardiovascular risks: the Bogalusa Heart Study. Pediatrics. 2006; 118:201–206.

174. Cui Y, Blumenthal RS, Flaws JA, Whiteman MK, Langenberg P, Bachorik PS, et al. Non-high-density lipoprotein cholesterol level as a predictor of cardiovascular disease mortality. Arch Intern Med. 2001; 161:1413–1419.

175. Frontini MG, Srinivasan SR, Xu JH, Tang R, Bond MG, Berenson G. Utility of non-high-density lipoprotein cholesterol versus other lipoprotein measures in detecting subclinical atherosclerosis in young adults (The Bogalusa Heart Study). Am J Cardiol. 2007; 100:64–68.

176. Daniels SR. Pediatric guidelines for dyslipidemia. J Clin Lipidol. 2015; 9:5 Suppl. S5–S10.

177. McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents: a scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, with the Council on Cardiovascular Nursing. Circulation. 2007; 115:1948–1967.

178. National Cholesterol Education Program (NCEP): highlights of the report of the Expert Panel on Blood Cholesterol Levels in Children and Adolescents. Pediatrics. 1992; 89:495–501.

179. Manlhiot C, Larsson P, Gurofsky RC, Smith RW, Fillingham C, Clarizia NA, et al. Spectrum and management of hypertriglyceridemia among children in clinical practice. Pediatrics. 2009; 123:458–465.

180. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Genetic causes of monogenic heterozygous familial hypercholesterolemia: a HuGE prevalence review. Am J Epidemiol. 2004; 160:407–420.

181. Marks D, Thorogood M, Neil HA, Humphries SE. A review on the diagnosis, natural history, and treatment of familial hypercholesterolaemia. Atherosclerosis. 2003; 168:1–14.

182. Hovingh GK, Davidson MH, Kastelein JJ, O'Connor AM. Diagnosis and treatment of familial hypercholesterolaemia. Eur Heart J. 2013; 34:962–971.

183. Gidding SS, Champagne MA, de Ferranti SD, Defesche J, Ito MK, Knowles JW, et al. The agenda for familial hypercholesterolemia: a scientific statement from the American Heart Association. Circulation. 2015; 132:2167–2192.

184. Landmesser U, Chapman MJ, Stock JK, Amarenco P, Belch JJF, Borén J, et al. 2017 Update of ESC/EAS task force on practical clinical guidance for proprotein convertase subtilisin/kexin type 9 inhibition in patients with atherosclerotic cardiovascular disease or in familial hypercholesterolaemia. Eur Heart J. 2018; 39:1131–1143.

185. Butte NF. Carbohydrate and lipid metabolism in pregnancy: normal compared with gestational diabetes mellitus. Am J Clin Nutr. 2000; 71:5 Suppl. 1256S–1261S.

186. Herrera E, Lasunción MA, Gomez-Coronado D, Aranda P, López-Luna P, Maier I. Role of lipoprotein lipase activity on lipoprotein metabolism and the fate of circulating triglycerides in pregnancy. Am J Obstet Gynecol. 1988; 158:6 Pt 2. 1575–1583.

187. Jovanovic L, Metzger BE, Knopp RH, conley MR, Park E, Lee YJ, et al. The Diabetes in Early Pregnancy Study: beta-hydroxybutyrate levels in type 1 diabetic pregnancy compared with normal pregnancy. NICHD-Diabetes in Early Pregnancy Study Group (DIEP). National Institute of Child Health and Development. Diabetes Care. 1998; 21:1978–1984.

188. Jellinger PS, Smith DA, Mehta AE, Ganda O, Handelsman Y, Rodbard HW, et al. American association of clinical endocrinologists' guidelines for management of dyslipidemia and prevention of atherosclerosis. Endocr Pract. 2012; 18:Suppl 1. 1–78.

189. Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis. 2012; 34:290–296.

190. French Study of Aortic Plaques in Stroke Group. Amarenco P, Cohen A, et al. Atherosclerotic disease of the aortic arch as a risk factor for recurrent ischemic stroke. N Engl J Med. 1996; 334:1216–1221.

191. Task Force Members, Montalescot G, Sechtem U, et al. 2013 ESC guidelines on the management of stable coronary artery disease: the task force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013; 34:2949–3003.

192. Bedi US, Singh M, Singh PP, Bhuriya R, Bahekar A, Molnar J, et al. Effects of statins on progression of carotid atherosclerosis as measured by carotid intimal: medial thickness: a meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol Ther. 2010; 15:268–273.

193. Meschia JF, Bushnell C, Boden-Albala B, Braun LT, Bravata DM, Chaturvedi S, et al. Guidelines for the primary prevention of stroke: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2014; 45:3754–3832.

194. McClelland RL, Chung H, Detrano R, Post W, Kronmal RA. Distribution of coronary artery calcium by race, gender, and age: results from the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2006; 113:30–37.

195. Allison MA, Criqui MH, Wright CM. Patterns and risk factors for systemic calcified atherosclerosis. Arterioscler Thromb Vasc Biol. 2004; 24:331–336.

196. Jensky NE, Criqui MH, Wright MC, Wassel CL, Brody SA, Allison MA. Blood pressure and vascular calcification. Hypertension. 2010; 55:990–997.

197. Rennenberg RJ, Kessels AG, Schurgers LJ, van Engelshoven JM, de Leeuw PW, Kroon AA. Vascular calcifications as a marker of increased cardiovascular risk: a meta-analysis. Vasc Health Risk Manag. 2009; 5:185–197.

198. Park KY, Kim YB, Moon HS, Suh BC, Chung PW. Association between cerebral arterial calcification and brachial-ankle pulse wave velocity in patients with acute ischemic stroke. Eur Neurol. 2009; 61:364–370.

199. Tsuchiya M, Suzuki E, Egawa K, Nishio Y, Maegawa H, Inoue S, et al. Stiffness and impaired blood flow in lower-leg arteries are associated with severity of coronary artery calcification among asymptomatic type 2 diabetic patients. Diabetes Care. 2004; 27:2409–2415.

200. Chung PW, Park KY, Moon HS, Kim YB, Youn YC, Byun JS, et al. Intracranial internal carotid artery calcification: a representative for cerebral artery calcification and association with white matter hyperintensities. Cerebrovasc Dis. 2010; 30:65–71.

201. Chung PW, Park KY, Kim JM, Shin DW, Ha SY. Carotid artery calcification is associated with deep cerebral microbleeds. Eur Neurol. 2014; 72:60–63.

202. Tinana A, Mintz GS, Weissman NJ. Volumetric intravascular ultrasound quantification of the amount of atherosclerosis and calcium in nonstenotic arterial segments. Am J Cardiol. 2002; 89:757–760.

203. O'Rourke RA, Brundage BH, Froelicher VF, Greenland P, Grundy SM, Hachamovitch R, et al. American College of Cardiology/American Heart Association Expert Consensus Document on electron-beam computed tomography for the diagnosis and prognosis of coronary artery disease. J Am Coll Cardiol. 2000; 36:326–340.

204. Sangiorgi G, Rumberger JA, Severson A, Edwards WD, Gregoire J, Fitzpatrick LA, et al. Arterial calcification and not lumen stenosis is highly correlated with atherosclerotic plaque burden in humans: a histologic study of 723 coronary artery segments using nondecalcifying methodology. J Am Coll Cardiol. 1998; 31:126–133.

205. Detrano R, Guerci AD, Carr JJ, Bild DE, Burke G, Folsom AR, et al. Coronary calcium as a predictor of coronary events in four racial or ethnic groups. N Engl J Med. 2008; 358:1336–1345.

206. American Diabetes Association. 9. Cardiovascular disease and risk management: standards of medical care in diabetes: 2018. Diabetes Care. 2018; 41:Suppl 1. S86–S104.

207. Marwan M, Ropers D, Pflederer T, Daniel WG, Achenbach S. Clinical characteristics of patients with obstructive coronary lesions in the absence of coronary calcification: an evaluation by coronary CT angiography. Heart. 2009; 95:1056–1060.

208. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D'Agostino RB, Gibbons R, 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; 129:25 Suppl 2. S49–S73.

209. Conroy RM, Pyörälä K, Fitzgerald AP, Sans S, Menotti A, De Backer G, et al. Estimation of ten-year risk of fatal cardiovascular disease in Europe: the SCORE project. Eur Heart J. 2003; 24:987–1003.

210. Hajifathalian K, Ueda P, Lu Y, Woodward M, Ahmadvand A, Aguilar-Salinas CA, et al. A novel risk score to predict cardiovascular disease risk in national populations (Globorisk): a pooled analysis of prospective cohorts and health examination surveys. Lancet Diabetes Endocrinol. 2015; 3:339–355.