Skip to main content

Advertisement

SpringerLink
Log in

Optimizing Dyslipidemia Management for the Prevention of Cardiovascular Disease: a Focus on Risk Assessment and Therapeutic Options

  • Lipid Abnormalities and Cardiovascular Prevention (G De Backer, Section Editor)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Primary prevention of incident atherosclerotic cardiovascular disease (ASCVD) as well as decreasing the risk of future events in those with established atherosclerosis is critical from a public health perspective. Management of dyslipidemias constitutes a key target in decreasing the risk of developing ASCVD events. While there have been great strides in the treatment of dyslipidemia over the last three decades, there are important recent developments and ongoing research that will expand the available therapeutic options and enable further cardiovascular risk reduction.

Purpose of Review

The purpose of this paper is to review new developments relating to the primary prevention and management of ASCVD with a specific focus on optimizing the treatment of dyslipidemias.

Recent Findings

In the realm of ASCVD risk prediction, mounting evidence over the last decade has demonstrated that coronary artery calcium testing is superior to any serum biomarker in the prediction of future ASCVD events and in discriminating future cardiovascular risk. As such, it has been incorporated into the most recent ACC/AHA primary prevention guideline to help guide management decisions in select patients. In terms of the management of dyslipidemias, PCSK9 inhibitors lower LDL-C by 50–70% and provide an additional 15% reduction in key cardiovascular events in high-risk patients with known ASCVD, as demonstrated in the ODYSSEY and FOURIER trials. Cholesteryl ester transfer protein (CETP) inhibitors, which significantly increase HDL-C levels, demonstrated mixed results in large clinical trials and have helped reframe HDL-C as a risk marker rather than a modifiable risk factor. In regard to the management of triglycerides, the REDUCE-IT trial demonstrated a nearly 5% absolute reduction in key cardiovascular events with a highly purified fish-oil derivative named icosapent ethyl in high-risk patients already on statin therapy. Finally, in regard to lipoprotein(a)—which is a strong risk factor for ASCVD—there are exciting developments in the therapeutic pipeline which reduce circulating lipoprotein(a) levels by nearly 90%.

Summary

The management of dyslipidemias continues to be an exciting field with several ongoing cardiovascular outcomes trials, improvement in risk prediction models, and new therapeutic agents in the pipeline that will further mitigate residual cardiovascular risk in both primary and secondary prevention patients.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance

  1. GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392(10159):1736–88.

    Article  Google Scholar 

  2. Murphy SL, Xu J, Kochanek KD, Arias E. Mortality in the United States, 2017. NCHS Data Brief. 2018(328):1–8.

  3. Weir HK, Anderson RN, Coleman King SM, Soman A, Thompson TD, Hong Y, et al. Heart disease and cancer deaths - trends and projections in the United States, 1969-2020. Prev Chronic Dis. 2016;13:E157.

    PubMed  PubMed Central  Google Scholar 

  4. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol. Circulation. 2018;0(0):CIR0000000000000625.

    Google Scholar 

  5. Benjamin EJ, Muntner P, Alonso A, Bittencourt MS, Callaway CW, Carson AP, et al. Heart disease and stroke statistics-2019 update: a report from the American Heart Association. Circulation. 2019;139(10):e56–e528.

    Article  PubMed  Google Scholar 

  6. Lloyd-Jones DM, Hong Y, Labarthe D, Mozaffarian D, Appel LJ, Van Horn L, et al. Defining and setting national goals for cardiovascular health promotion and disease reduction: the American Heart Association’s strategic impact goal through 2020 and beyond. Circulation. 2010;121(4):586–613.

    Article  PubMed  Google Scholar 

  7. D’Agostino RB Sr, Vasan RS, Pencina MJ, Wolf PA, Cobain M, Massaro JM, et al. General cardiovascular risk profile for use in primary care: the Framingham Heart Study. Circulation. 2008;117(6):743–53.

    Article  PubMed  Google Scholar 

  8. Conroy RM, Pyorala 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(11):987–1003.

    Article  CAS  PubMed  Google Scholar 

  9. Goff DC Jr, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB Sr, 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. J Am Coll Cardiol. 2014;63(25 Pt B):2935–59.

    Article  PubMed  Google Scholar 

  10. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, et al. 2019 ACC/AHA guideline on the primary prevention of cardiovascular disease. Circulation. 2019;0(0):CIR0000000000000678.

    Google Scholar 

  11. 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(39):2999–3058.

    Article  PubMed  Google Scholar 

  12. Lloyd-Jones DM, Braun LT, Ndumele CE, Smith SC Jr, Sperling LS, Virani SS, et al. Use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease. Circulation. 2018;0(0):CIR0000000000000638.

    Google Scholar 

  13. Karmali KN, Goff DC Jr, Ning H, Lloyd-Jones DM. A systematic examination of the 2013 ACC/AHA pooled cohort risk assessment tool for atherosclerotic cardiovascular disease. J Am Coll Cardiol. 2014;64(10):959–68.

    Article  PubMed  Google Scholar 

  14. DeFilippis AP, Young R, McEvoy JW, Michos ED, Sandfort V, Kronmal RA, et al. Risk score overestimation: the impact of individual cardiovascular risk factors and preventive therapies on the performance of the American Heart Association-American College of Cardiology-Atherosclerotic Cardiovascular Disease risk score in a modern multi-ethnic cohort. Eur Heart J. 2017;38(8):598–608.

    CAS  PubMed  Google Scholar 

  15. Singh A, Collins BL, Gupta A, Fatima A, Qamar A, Biery D, et al. Cardiovascular risk and statin eligibility of young adults after an MI: Partners YOUNG-MI Registry. J Am Coll Cardiol. 2018;71(3):292–302.

    Article  PubMed  Google Scholar 

  16. •• Nasir K, Bittencourt MS, Blaha MJ, Blankstein R, Agatson AS, Rivera JJ, et al. Implications of coronary 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(15):1657–68 This important analysis underscores the utility of coronary artery calcium testing in accurately classifying ASCVD risk.

    Article  CAS  PubMed  Google Scholar 

  17. Hong JC, Blankstein R, Shaw LJ, Padula WV, Arrieta A, Fialkow JA, et al. Implications of coronary artery calcium testing for treatment decisions among statin candidates according to the ACC/AHA cholesterol management guidelines: a cost-effectiveness analysis. JACC Cardiovasc Imaging. 2017;10(8):938–52.

    Article  PubMed  Google Scholar 

  18. Pletcher MJ, Pignone M, Earnshaw S, McDade C, Phillips KA, Auer R, et al. Using the coronary artery calcium score to guide statin therapy: a cost-effectiveness analysis. Circ Cardiovasc Qual Outcomes. 2014;7(2):276–84.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Roberts ET, Horne A, Martin SS, Blaha MJ, Blankstein R, Budoff MJ, et al. Cost-effectiveness of coronary artery calcium testing for coronary heart and cardiovascular disease risk prediction to guide statin allocation: the Multi-Ethnic Study of Atherosclerosis (MESA). PLoS One. 2015;10(3):e0116377.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Blanco Mejia S, Messina M, Li SS, Viguiliouk E, Chiavaroli L, Khan TA, et al. A meta-analysis of 46 studies identified by the FDA demonstrates that soy protein decreases circulating LDL and total cholesterol concentrations in adults. J Nutr. 2019;149:968–81.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Martinez-Gonzalez MA, Sanchez-Tainta A, Corella D, Salas-Salvado J, Ros E, Aros F, et al. A provegetarian food pattern and reduction in total mortality in the Prevencion con Dieta Mediterranea (PREDIMED) study. Am J Clin Nutr. 2014;100(Suppl 1):320S–8S.

    Article  CAS  PubMed  Google Scholar 

  22. Najjar RS, Moore CE, Montgomery BD. A defined, plant-based diet utilized in an outpatient cardiovascular clinic effectively treats hypercholesterolemia and hypertension and reduces medications. Clin Cardiol. 2018;41(3):307–13.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Shah B, Newman JD, Woolf K, Ganguzza L, Guo Y, Allen N, et al. Anti-inflammatory effects of a vegan diet versus the American Heart Association-Recommended Diet in Coronary Artery Disease Trial. J Am Heart Assoc. 2018;7(23):e011367.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  24. Yokoyama Y, Levin SM, Barnard ND. Association between plant-based diets and plasma lipids: a systematic review and meta-analysis. Nutr Rev. 2017;75(9):683–98.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Emerging Risk Factors C, Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000.

    Article  Google Scholar 

  26. • Trialists CT. 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(9753):1670–81 This large meta-analysis demonstrated the safety and efficacy of further LDL-C lowering, without evidence of a threshold effect.

    Article  CAS  Google Scholar 

  27. Ference BA, Yoo W, Alesh I, Mahajan N, Mirowska KK, Mewada A, et al. Effect of long-term exposure to lower low-density lipoprotein cholesterol beginning early in life on the risk of coronary heart disease: a Mendelian randomization analysis. J Am Coll Cardiol. 2012;60(25):2631–9.

    Article  CAS  PubMed  Google Scholar 

  28. Austin MA, Hutter CM, Zimmern RL, Humphries SE. Familial hypercholesterolemia and coronary heart disease: a HuGE association review. Am J Epidemiol. 2004;160(5):421–9.

    Article  PubMed  Google Scholar 

  29. Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Mutations causative of familial hypercholesterolaemia: screening of 98 098 individuals from the Copenhagen General Population Study estimated a prevalence of 1 in 217. Eur Heart J. 2016;37(17):1384–94.

    Article  CAS  PubMed  Google Scholar 

  30. Ridker PM. LDL cholesterol: controversies and future therapeutic directions. Lancet. 2014;384(9943):607–17.

    Article  CAS  PubMed  Google Scholar 

  31. •• Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72 This wide-ranging analysis demonstrated the nearly incontrovertible causal relationship between LDL-C and ASCVD.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Libby P. Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368(21):2004–13.

    Article  CAS  PubMed  Google Scholar 

  33. Shepherd J, Cobbe SM, Ford I, Isles CG, Lorimer AR, MacFarlane PW, 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(20):1301–7.

    Article  CAS  PubMed  Google Scholar 

  34. Downs JR, Clearfield M, Weis S, Whitney E, Shapiro DR, Beere PA, 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(20):1615–22.

    Article  CAS  PubMed  Google Scholar 

  35. Yusuf S, Bosch J, Dagenais G, Zhu J, Xavier D, Liu L, et al. Cholesterol lowering in intermediate-risk persons without cardiovascular disease. N Engl J Med. 2016;374(21):2021–31.

    Article  CAS  PubMed  Google Scholar 

  36. Scandinavian Simvastatin Survival Study G. Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S). Lancet. 1994;344(8934):1383–9.

    Google Scholar 

  37. Silverman MG, Ference BA, Im K, Wiviott SD, Giugliano RP, Grundy SM, et al. Association between lowering LDL-C and cardiovascular risk reduction among different therapeutic interventions: a systematic review and meta-analysis. JAMA. 2016;316(12):1289–97.

    Article  CAS  PubMed  Google Scholar 

  38. Lloyd-Jones DM, Morris PB, Ballantyne CM, Birtcher KK, Daly DD Jr, DePalma SM, 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 Management 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(14):1785–822.

    Article  PubMed  Google Scholar 

  39. 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(9784):2181–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. • 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(25):2387–97 The IMPROVE-IT trial demonstrated the ability of a non-statin agent to both reduce LDL-C and recurrent ASCVD events in secondary prevention.

    Article  CAS  PubMed  Google Scholar 

  41. • 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(18):1713–22 The FOURIER trial with the PCSK9 inhibitor evolocumab demonstrated the therapeutic role of these agents in secondary prevention.

    Article  CAS  PubMed  Google Scholar 

  42. • 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(22):2097–107 The ODYSSEY trial with the PCSK9 inhibitor alirocumab demonstrated the therapeutic role of these agents in secondary prevention.

    Article  CAS  PubMed  Google Scholar 

  43. • Ray KK, Landmesser U, Leiter LA, Kallend D, Dufour R, Karakas M, et al. Inclisiran in patients at high cardiovascular risk with elevated LDL cholesterol. N Engl J Med. 2017;376(15):1430–40 This large phase II trial of the siRNA molecule inclisiran demonstrated the tolerability and efficacy of this unique molecule in reducing LDL-C via the PCSK9 receptor.

    Article  CAS  PubMed  Google Scholar 

  44. Ray KK, Bays HE, Catapano AL, Lalwani ND, Bloedon LT, Sterling LR, et al. Safety and efficacy of bempedoic acid to reduce LDL cholesterol. N Engl J Med. 2019;380(11):1022–32.

    Article  CAS  PubMed  Google Scholar 

  45. Gordon T, Castelli WP, Hjortland MC, Kannel WB, Dawber TR. High density lipoprotein as a protective factor against coronary heart disease. Am J Med. 1977;62(5):707–14.

    Article  CAS  PubMed  Google Scholar 

  46. Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD, Castelli WP, Knoke JD, et al. High-density lipoprotein cholesterol and cardiovascular disease. Four prospective American studies. Circulation. 1989;79(1):8–15.

    Article  CAS  PubMed  Google Scholar 

  47. Rader DJ, Hovingh GK. HDL and cardiovascular disease. Lancet. 2014;384(9943):618–25.

    Article  CAS  PubMed  Google Scholar 

  48. Frikke-Schmidt R, Nordestgaard BG, Stene MC, Sethi AA, Remaley AT, Schnohr P, et al. Association of loss-of-function mutations in the ABCA1 gene with high-density lipoprotein cholesterol levels and risk of ischemic heart disease. JAMA. 2008;299(21):2524–32.

    Article  CAS  PubMed  Google Scholar 

  49. Holmes MV, Asselbergs FW, Palmer TM, Drenos F, Lanktree MB, Nelson CP, et al. Mendelian randomization of blood lipids for coronary heart disease. Eur Heart J. 2015;36(9):539–50.

    Article  CAS  PubMed  Google Scholar 

  50. Voight BF, Peloso GM, Orho-Melander M, Frikke-Schmidt R, Barbalic M, Jensen MK, et al. Plasma HDL cholesterol and risk of myocardial infarction: a Mendelian randomisation study. Lancet. 2012;380(9841):572–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Group HTC, Landray MJ, Haynes R, Hopewell JC, Parish S, Aung T, et al. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371(3):203–12.

    Article  CAS  Google Scholar 

  52. Investigators A-H, Boden WE, Probstfield JL, Anderson T, Chaitman BR, Desvignes-Nickens P, et al. Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy. N Engl J Med. 2011;365(24):2255–67.

    Article  CAS  Google Scholar 

  53. Lincoff AM, Nicholls SJ, Riesmeyer JS, Barter PJ, Brewer HB, Fox KAA, et al. Evacetrapib and cardiovascular outcomes in high-risk vascular disease. N Engl J Med. 2017;376(20):1933–42.

    Article  PubMed  Google Scholar 

  54. Schwartz GG, Olsson AG, Abt M, Ballantyne CM, Barter PJ, Brumm J, et al. Effects of dalcetrapib in patients with a recent acute coronary syndrome. N Engl J Med. 2012;367(22):2089–99.

    Article  CAS  PubMed  Google Scholar 

  55. Barter PJ, Caulfield M, Eriksson M, Grundy SM, Kastelein JJ, Komajda M, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357(21):2109–22.

    Article  CAS  PubMed  Google Scholar 

  56. Group HTRC, Bowman L, Hopewell JC, Chen F, Wallendszus K, Stevens W, et al. Effects of anacetrapib in patients with atherosclerotic vascular disease. N Engl J Med. 2017;377(13):1217–27.

    Article  Google Scholar 

  57. Mody P, Joshi PH, Khera A, Ayers CR, Rohatgi A. Beyond coronary calcification, family history, and C-reactive protein: cholesterol efflux capacity and cardiovascular risk prediction. J Am Coll Cardiol. 2016;67(21):2480–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  58. Rohatgi A, Khera A, Berry JD, Givens EG, Ayers CR, Wedin KE, et al. HDL cholesterol efflux capacity and incident cardiovascular events. N Engl J Med. 2014;371(25):2383–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Bhatt A, Rohatgi A. HDL cholesterol efflux capacity: cardiovascular risk factor and potential therapeutic target. Curr Atheroscler Rep. 2016;18(1):2.

    Article  PubMed  CAS  Google Scholar 

  60. Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007;298(3):299–308.

    Article  CAS  PubMed  Google Scholar 

  61. Bansal S, Buring JE, Rifai N, Mora S, Sacks FM, Ridker PM. Fasting compared with nonfasting triglycerides and risk of cardiovascular events in women. JAMA. 2007;298(3):309–16.

    Article  CAS  PubMed  Google Scholar 

  62. Madsen CM, Varbo A, Nordestgaard BG. Unmet need for primary prevention in individuals with hypertriglyceridaemia not eligible for statin therapy according to European Society of Cardiology/European Atherosclerosis Society guidelines: a contemporary population-based study. Eur Heart J. 2018;39(7):610–9.

    Article  CAS  PubMed  Google Scholar 

  63. Do R, Willer CJ, Schmidt EM, Sengupta S, Gao C, Peloso GM, et al. Common variants associated with plasma triglycerides and risk for coronary artery disease. Nat Genet. 2013;45:1345–52.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  64. Jorgensen AB, Frikke-Schmidt R, West AS, Grande P, Nordestgaard BG, Tybjaerg-Hansen A. Genetically elevated non-fasting triglycerides and calculated remnant cholesterol as causal risk factors for myocardial infarction. Eur Heart J. 2013;34(24):1826–33.

    Article  CAS  PubMed  Google Scholar 

  65. Nichols GA, Philip S, Reynolds K, Granowitz CB, Fazio S. Increased cardiovascular risk in hypertriglyceridemic patients with statin-controlled LDL cholesterol. J Clin Endocrinol Metab. 2018;103(8):3019–27.

    Article  PubMed  Google Scholar 

  66. Nordestgaard BG, Varbo A. Triglycerides and cardiovascular disease. Lancet. 2014;384(9943):626–35.

    Article  CAS  PubMed  Google Scholar 

  67. Ginsberg HN. New perspectives on atherogenesis: role of abnormal triglyceride-rich lipoprotein metabolism. Circulation. 2002;106(16):2137–42.

    Article  PubMed  Google Scholar 

  68. Chapman MJ, Ginsberg HN, Amarenco P, Andreotti F, Boren J, Catapano AL, et al. Triglyceride-rich lipoproteins and high-density lipoprotein cholesterol in patients at high risk of cardiovascular disease: evidence and guidance for management. Eur Heart J. 2011;32(11):1345–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Libby P. Triglycerides on the rise: should we swap seats on the seesaw? Eur Heart J. 2015;36(13):774–6.

    Article  PubMed  Google Scholar 

  70. Dattilo AM, Kris-Etherton PM. Effects of weight reduction on blood lipids and lipoproteins: a meta-analysis. Am J Clin Nutr. 1992;56(2):320–8.

    Article  CAS  PubMed  Google Scholar 

  71. Brunzell JD. Clinical practice. Hypertriglyceridemia. N Engl J Med. 2007;357(10):1009–17.

    Article  CAS  PubMed  Google Scholar 

  72. Bakker-Arkema RG, Davidson MH, Goldstein RJ, Davignon J, Isaacsohn JL, Weiss SR, et al. Efficacy and safety of a new HMG-CoA reductase inhibitor, atorvastatin, in patients with hypertriglyceridemia. JAMA. 1996;275(2):128–33.

    Article  CAS  PubMed  Google Scholar 

  73. • Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. N Engl J Med. 2019;380(1):11–22 The REDUCE-IT trial demonstrated the added cardiovascular benefit of targeted triglyceride lowering with a highly purified fish-oil derivative named icosapent ethyl.

    Article  CAS  PubMed  Google Scholar 

  74. Graham MJ, Lee RG, Bell TA 3rd, Fu W, Mullick AE, Alexander VJ, et al. Antisense oligonucleotide inhibition of apolipoprotein C-III reduces plasma triglycerides in rodents, nonhuman primates, and humans. Circ Res. 2013;112(11):1479–90.

    Article  CAS  PubMed  Google Scholar 

  75. Tsimikas S. RNA-targeted therapeutics for lipid disorders. Curr Opin Lipidol. 2018;29(6):459–66.

    Article  CAS  PubMed  Google Scholar 

  76. Schmitz J, Gouni-Berthold I. APOC-III antisense oligonucleotides: a new option for the treatment of hypertriglyceridemia. Curr Med Chem. 2018;25(13):1567–76.

    Article  CAS  PubMed  Google Scholar 

  77. Emerging Risk Factors C, Erqou S, Kaptoge S, Perry PL, Di Angelantonio E, Thompson A, et al. Lipoprotein(a) concentration and the risk of coronary heart disease, stroke, and nonvascular mortality. JAMA. 2009;302(4):412–23.

    Article  Google Scholar 

  78. Kamstrup PR, Benn M, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and risk of myocardial infarction in the general population: the Copenhagen City Heart Study. Circulation. 2008;117(2):176–84.

    Article  CAS  PubMed  Google Scholar 

  79. Kamstrup PR, Tybjaerg-Hansen A, Steffensen R, Nordestgaard BG. Genetically elevated lipoprotein(a) and increased risk of myocardial infarction. JAMA. 2009;301(22):2331–9.

    Article  CAS  PubMed  Google Scholar 

  80. Thanassoulis G, Campbell CY, Owens DS, Smith JG, Smith AV, Peloso GM, et al. Genetic associations with valvular calcification and aortic stenosis. N Engl J Med. 2013;368(6):503–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Elevated lipoprotein(a) and risk of aortic valve stenosis in the general population. J Am Coll Cardiol. 2014;63(5):470–7.

    Article  CAS  PubMed  Google Scholar 

  82. Willeit P, Ridker PM, Nestel PJ, Simes J, Tonkin AM, Pedersen TR, et al. Baseline and on-statin treatment lipoprotein(a) levels for prediction of cardiovascular events: individual patient-data meta-analysis of statin outcome trials. Lancet. 2018;392(10155):1311–20.

    Article  CAS  PubMed  Google Scholar 

  83. Koschinsky ML, Marcovina SM. Structure-function relationships in apolipoprotein(a): insights into lipoprotein(a) assembly and pathogenicity. Curr Opin Lipidol. 2004;15(2):167–74.

    Article  CAS  PubMed  Google Scholar 

  84. Berg K. A new serum type system in man—the Lp system. 1963;59(3):369–82.

  85. Ballantyne CM. Clinical lipidology: a companion to Braunwald’s heart disease. Philadelphia: 2nd edition; 2015.

    Google Scholar 

  86. Boerwinkle E, Leffert CC, Lin J, Lackner C, Chiesa G, Hobbs HH. Apolipoprotein(a) gene accounts for greater than 90% of the variation in plasma lipoprotein(a) concentrations. J Clin Invest. 1992;90(1):52–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Rader DJ, Cain W, Ikewaki K, Talley G, Zech LA, Usher D, et al. The inverse association of plasma lipoprotein(a) concentrations with apolipoprotein(a) isoform size is not due to differences in Lp(a) catabolism but to differences in production rate. J Clin Invest. 1994;93(6):2758–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. N Engl J Med. 2009;361(26):2518–28.

    Article  CAS  PubMed  Google Scholar 

  89. Wei W-Q, Li X, Feng Q, Kubo M, Kullo IJ, Peissig PL, et al. LPA variants are associated with residual cardiovascular risk in patients receiving statins. Circulation. 2018;138(17):1839–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Cook NR, Mora S, Ridker PM. Lipoprotein(a) and cardiovascular risk prediction among women. J Am Coll Cardiol. 2018;72(3):287–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Paré G, Çaku A, McQueen M, Anand Sonia S, Enas E, Clarke R, et al. Lipoprotein(a) levels and the risk of myocardial infarction among 7 ethnic groups. Circulation. 2019;139(12):1472–82.

    Article  PubMed  CAS  Google Scholar 

  92. Cao J, Steffen BT, Budoff M, Post WS, Thanassoulis G, Kestenbaum B, et al. Lipoprotein(a) levels are associated with subclinical calcific aortic valve disease in White and Black individuals: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2016;36(5):1003–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Virani SS, Brautbar A, Davis BC, Nambi V, Hoogeveen RC, Sharrett AR, et al. Associations between lipoprotein(a) levels and cardiovascular outcomes in Black and White subjects: the Atherosclerosis Risk in Communities (ARIC) Study. Circulation. 2012;125(2):241–9.

    Article  CAS  PubMed  Google Scholar 

  94. Guan W, Cao J, Steffen BT, Post WS, Stein JH, Tattersall MC, et al. Race is a key variable in assigning lipoprotein(a) cutoff values for coronary heart disease risk assessment: the Multi-Ethnic Study of Atherosclerosis. Arterioscler Thromb Vasc Biol. 2015;35(4):996–1001.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. Nordestgaard BG, Chapman MJ, Ray K, Boren J, Andreotti F, Watts GF, et al. Lipoprotein(a) as a cardiovascular risk factor: current status. Eur Heart J. 2010;31(23):2844–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Thanassoulis G. Screening for high lipoprotein(a). Circulation. 2019;139(12):1493–6.

    Article  PubMed  PubMed Central  Google Scholar 

  97. Willeit P, Kiechl S, Kronenberg F, Witztum JL, Santer P, Mayr M, et al. Discrimination and net reclassification of cardiovascular risk with lipoprotein(a): prospective 15-year outcomes in the Bruneck Study. J Am Coll Cardiol. 2014;64(9):851–60.

    Article  PubMed  Google Scholar 

  98. •• Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69(6):692–711 This comprehensive review of lipoprotein(a) and cardiovascular disease synthesizes important insights into the lipoprotein(a) and its future as a therapeutic target.

    Article  CAS  PubMed  Google Scholar 

  99. • O’Donoghue ML, Fazio S, Giugliano RP, Stroes ESG, Kanevsky E, Gouni-Berthold I, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation. 2019;139(12):1483–92 This analysis of the FOURIER trial demonstrated that the PCSK9 inhibitor evolocumab reduced the risk of major cardiovascular events by a greater degree in patients with an elevated Lp(a) as compared with those with Lp(a) levels below the median. This analysis supported Lp(a) as a modifiable risk factor and provides insight into which patients may benefit the most from PCSK9 inhibition.

    Article  PubMed  CAS  Google Scholar 

  100. Levin AA. Treating disease at the RNA level with oligonucleotides. N Engl J Med. 2019;380(1):57–70.

    Article  PubMed  Google Scholar 

  101. Viney NJ, van Capelleveen JC, Geary RS, Xia S, Tami JA, Yu RZ, et al. Antisense oligonucleotides targeting apolipoprotein(a) in people with raised lipoprotein(a): two randomised, double-blind, placebo-controlled, dose-ranging trials. Lancet. 2016;388(10057):2239–53.

    Article  CAS  PubMed  Google Scholar 

  102. Tsimikas S, Viney NJ, Hughes SG, Singleton W, Graham MJ, Baker BF, et al. Antisense therapy targeting apolipoprotein(a): a randomised, double-blind, placebo-controlled phase 1 study. Lancet. 2015;386(10002):1472–83.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Departments of Medicine (Cardiovascular Division) and Radiology, Brigham and Women’s Hospital, Harvard Medical School, 75 Francis Street, Boston, MA, 02115, USA

    Adam N. Berman & Ron Blankstein

Authors
  1. Adam N. Berman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ron Blankstein
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Ron Blankstein.

Ethics declarations

Conflict of Interest

Adam Berman declares that he has no conflict of interest.

Ron Blankstein reports grants from Astellas Inc. and Amgen Inc.

Human and Animal Rights and Informed Consent

This article does not contain any studies with human or animal subjects performed by any of the authors.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This article is part of the Topical Collection on Lipid Abnormalities and Cardiovascular Prevention

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Berman, A.N., Blankstein, R. Optimizing Dyslipidemia Management for the Prevention of Cardiovascular Disease: a Focus on Risk Assessment and Therapeutic Options. Curr Cardiol Rep 21, 110 (2019). https://doi.org/10.1007/s11886-019-1175-z

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-019-1175-z

Keywords

Search

Navigation