Skip to main content
SpringerLink
Log in

Dyslipidemias and Cardiovascular Prevention: Tailoring Treatment According to Lipid Phenotype

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

Abstract

Purpose of Review

This study aimed to present the current information on the genetic background of dyslipidemias and provide insights into the complex pathophysiological role of several plasma lipids/lipoproteins in the pathogenesis of atherosclerotic cardiovascular disease. Furthermore, we aim to summarize established therapies and describe the scientific rationale for the development of novel therapeutic strategies.

Recent Findings

Evidence from genetic studies suggests that besides lowering low-density lipoprotein cholesterol, pharmacological reduction of triglyceride-rich lipoproteins, or lipoprotein(a) will reduce risk for coronary heart disease.

Summary

Dyslipidemia, in particular hypercholesterolemia, is a common clinical condition and represents an important determinant of atherosclerotic vascular disease. Treatment decisions are currently guided by the causative lipid phenotype and the presence of other risk factors suggesting a very high cardiovascular risk. Therefore, the identification of lipid disorders and the optimal combination of therapeutic strategies provide an outstanding opportunity for reducing the onset and burden of cardiovascular disease.

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
Fig 3
Fig 4

Similar content being viewed by others

Abbreviations

ACC:

American College of Cardiology

ACS:

Acute coronary syndrome

AHA:

American Heart Association

ANGPTL4:

Angiopoietin-like protein 4

ApoA:

Apolipoprotein(a)

ApoB-100:

Apolipoprotein B-100

ApoC-III:

Apolipoprotein C-III

appr.:

Approximately

ASCVD:

Atherosclerotic cardiovascular disease

CETP:

Cholesterylester transfer protein

CHD:

Coronary heart disease

CTT:

Cholesterol Treatment Trialists

CV:

Cardiovascular

CVD:

Cardiovascular disease

DLCN:

Dutch lipid clinic network

EMA:

European Medicines Agency

FDA:

US Food and Drug Administration

FH:

Familial Hypercholesterolemia

HDL-C:

High-density lipoprotein cholesterol

HeFH:

Heterozygous FH

HMG-CoA:

Inhibitors of 3-Hydrxy-3-Methylglutaryl-Coenzyme A

HoFH:

Homozygous FH

HOPE:

Heart Outcomes Prevention Evaluation

HTG:

Hypertriglyceridemia

IDL:

Intermediate-Density Lipoprotein

IHD:

Ischemic heart disease

IMPROVE-IT:

Improved Reduction of Outcomes: Vytorin Efficacy International Trial

LDL-C:

Low-density lipoprotein cholesterol

LDLR:

LDL receptor

Lp(a):

Lipoprotein(a)

LPL:

Lipoprotein lipase

MTP:

Microsomal triglyceride transfer protein

NPC1L1:

Niemann–Pick C1–like 1

OM3-FAs:

Omega-3 fatty acids

PCSK9:

Proprotein convertase subtilisin/kexin Type 9

PPAR-α:

Peroxisome proliferator-activated receptor-α

SPPARM:

Selective peroxisome proliferator activator receptor modulator

TG:

Triglyceride

TRLs:

TG-rich lipoproteins

VLDL:

Very-low density Lipoprotein

References

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

  1. Ramasamy I. Update on the molecular biology of dyslipidemias. Clin Chim Acta; Int J Clin Chem. 2016;454:143–85. doi:10.1016/j.cca.2015.10.033.

    Article  CAS  Google Scholar 

  2. 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. doi:10.1093/eurheartj/eht571.

    Article  CAS  PubMed  Google Scholar 

  3. 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. doi:10.1093/eurheartj/ehq386.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Goldstein JL, Brown MS. A century of cholesterol and coronaries: from plaques to genes to statins. Cell. 2015;161(1):161–72. doi:10.1016/j.cell.2015.01.036.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

  6. Luscher TF. Dyslipidaemias: new mechanistic insights and the 2016 ESC guidelines. Eur Heart J. 2016;37(39):2963–5. doi:10.1093/eurheartj/ehw504.

    Article  PubMed  Google Scholar 

  7. Goldstein JL, Brown MS. Molecular medicine. The cholesterol quartet. Science (New York, NY). 2001;292(5520):1310–2.

    Article  CAS  Google Scholar 

  8. Rader DJ, Cohen J, Hobbs HH. Monogenic hypercholesterolemia: new insights in pathogenesis and treatment. J Clin Invest. 2003;111(12):1795–803. doi:10.1172/jci18925.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Sniderman AD, Tsimikas S, Fazio S. The severe hypercholesterolemia phenotype: clinical diagnosis, management, and emerging therapies. J Am Coll Cardiol. 2014;63(19):1935–47. doi:10.1016/j.jacc.2014.01.060.

    Article  CAS  PubMed  Google Scholar 

  10. Raal FJ, Santos RD. Homozygous familial hypercholesterolemia: current perspectives on diagnosis and treatment. Atherosclerosis. 2012;223(2):262–8. doi:10.1016/j.atherosclerosis.2012.02.019.

    Article  CAS  PubMed  Google Scholar 

  11. Maxfield FR, van Meer G. Cholesterol, the central lipid of mammalian cells. Curr Opin Cell Biol. 2010;22(4):422–9. doi:10.1016/j.ceb.2010.05.004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Marais AD. Familial hypercholesterolaemia. Clin Biochem Rev. 2004;25(1):49–68.

    PubMed  PubMed Central  Google Scholar 

  13. Nordestgaard BG, Chapman MJ, Humphries SE, Ginsberg HN, Masana L, Descamps OS, et al. Familial hypercholesterolaemia is underdiagnosed and undertreated in the general population: guidance for clinicians to prevent coronary heart disease: consensus statement of the European Atherosclerosis Society. Eur Heart J. 2013;34(45):3478–90a. doi:10.1093/eurheartj/eht273.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Civeira F. Guidelines for the diagnosis and management of heterozygous familial hypercholesterolemia. Atherosclerosis. 2004;173(1):55–68. doi:10.1016/j.atherosclerosis.2003.11.010.

    Article  CAS  PubMed  Google Scholar 

  15. Horton JD, Cohen JC, Hobbs HH. PCSK9: a convertase that coordinates LDL catabolism. J Lipid Res. 2009;50(Suppl):S172–7. doi:10.1194/jlr.R800091-JLR200.

    PubMed  PubMed Central  Google Scholar 

  16. Benn M, Watts GF, Tybjaerg-Hansen A, Nordestgaard BG. Familial hypercholesterolemia in the Danish general population: prevalence, coronary artery disease, and cholesterol-lowering medication. J Clin Endocrinol Metab. 2012;97(11):3956–64. doi:10.1210/jc.2012-1563.

    Article  CAS  PubMed  Google Scholar 

  17. •• 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. doi:10.1093/eurheartj/ehw272. Most recent European Dyslipidemia Guidelines

    Article  PubMed  Google Scholar 

  18. 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. doi:10.1016/j.jacc.2013.11.005.

    Article  PubMed  Google Scholar 

  19. Catapano AL., Graham IM. ‘Ten Commandments’ from the 2016 ESC/EAS Guidelines for the management of dyslipidaemias. Eur Heart J. 2016;37(39):2966. doi:10.1093/eurheartj/ehw415.

  20. McGorrian C, Yusuf S, Islam S, Jung H, Rangarajan S, Avezum A, et al. Estimating modifiable coronary heart disease risk in multiple regions of the world: the INTERHEART modifiable risk score. Eur Heart J. 2011;32(5):581–9. doi:10.1093/eurheartj/ehq448.

    Article  PubMed  Google Scholar 

  21. 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. doi:10.1056/NEJMoa1600176.

    Article  CAS  PubMed  Google Scholar 

  22. • 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):S1–45. doi:10.1161/01.cir.0000437738.63853.7a. Most recent US Prevention Guidelines

    Article  PubMed  Google Scholar 

  23. Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, Bhala N, 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(9753):1670–81. doi:10.1016/S0140-6736(10)61350-5.

    Article  CAS  PubMed  Google Scholar 

  24. Fulcher J, O’Connell R, Voysey M, Emberson J, Blackwell L, Mihaylova B, et al. Efficacy and safety of LDL-lowering therapy among men and women: meta-analysis of individual data from 174,000 participants in 27 randomised trials. Lancet (London, England). 2015;385(9976):1397–405. doi:10.1016/s0140-6736(14)61368-4.

    Article  CAS  Google Scholar 

  25. •• Ridker PM, Mora S, Rose L, Group JTS. 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(17):1373–9. doi:10.1093/eurheartj/ehw046. This study provides interesting data on the variability of response to statin treatment.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Rosenson RS, Brewer HB Jr, Ansell BJ, Barter P, Chapman MJ, Heinecke JW, et al. Dysfunctional HDL and atherosclerotic cardiovascular disease. Nat Rev Cardiol. 2016;13(1):48–60. doi:10.1038/nrcardio.2015.124.

    Article  CAS  PubMed  Google Scholar 

  27. Di Angelantonio E, Sarwar N, Perry P, Kaptoge S, Ray KK, Thompson A, et al. Major lipids, apolipoproteins, and risk of vascular disease. JAMA. 2009;302(18):1993–2000. doi:10.1001/jama.2009.1619.

    Article  CAS  PubMed  Google Scholar 

  28. Musunuru K, Kathiresan S. Surprises from genetic analyses of lipid risk factors for atherosclerosis. Circ Res. 2016;118(4):579–85. doi:10.1161/circresaha.115.306398.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. 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 (London, England). 2012;380(9841):572–80. doi:10.1016/s0140-6736(12)60312-2.

    Article  CAS  Google Scholar 

  30. 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. doi:10.1056/NEJMoa0706628.

    Article  CAS  PubMed  Google Scholar 

  31. 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. doi:10.1056/NEJMoa1206797.

    Article  CAS  PubMed  Google Scholar 

  32. Nicholls SJ, Lincoff AM, Barter PJ, Brewer HB, Fox KA, Gibson CM, et al. Assessment of the clinical effects of cholesteryl ester transfer protein inhibition with evacetrapib in patients at high-risk for vascular outcomes: rationale and design of the ACCELERATE trial. Am Heart J. 2015;170(6):1061–9. doi:10.1016/j.ahj.2015.09.007.

    Article  CAS  PubMed  Google Scholar 

  33. Rosenson RS, Brewer HB, Rader DJ. Lipoproteins as biomarkers and therapeutic targets in the setting of acute coronary syndrome. Circ Res. 2014;114(12):1880–9. doi:10.1161/circresaha.114.302805.

    Article  CAS  PubMed  Google Scholar 

  34. Besler C, Heinrich K, Rohrer L, Doerries C, Riwanto M, Shih DM, et al. Mechanisms underlying adverse effects of HDL on eNOS-activating pathways in patients with coronary artery disease. J Clin Invest. 2011;121(7):2693–708. doi:10.1172/jci42946.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Hafiane A, Jabor B, Ruel I, Ling J, Genest J. High-density lipoprotein mediated cellular cholesterol efflux in acute coronary syndromes. Am J Cardiol. 2014;113(2):249–55. doi:10.1016/j.amjcard.2013.09.006.

    Article  CAS  PubMed  Google Scholar 

  36. 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. doi:10.1056/NEJMoa0902604.

    Article  CAS  PubMed  Google Scholar 

  37. 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. doi:10.1001/jama.2009.801.

    Article  CAS  PubMed  Google Scholar 

  38. 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. doi:10.1016/S0140-6736(15)61252-1.

    Article  CAS  PubMed  Google Scholar 

  39. Tsimikas S, Hall JL. Lipoprotein(a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies. J Am Coll Cardiol. 2012;60(8):716–21. doi:10.1016/j.jacc.2012.04.038.

    Article  CAS  PubMed  Google Scholar 

  40. Raal FJ, Giugliano RP, Sabatine MS, Koren MJ, Langslet G, Bays H, et al. Reduction in lipoprotein(a) with PCSK9 monoclonal antibody evolocumab (AMG 145): a pooled analysis of more than 1,300 patients in 4 phase II trials. J Am Coll Cardiol. 2014;63(13):1278–88. doi:10.1016/j.jacc.2014.01.006.

    Article  CAS  PubMed  Google Scholar 

  41. Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG, Tybjaerg-Hansen A. Loss-of-function mutations in APOC3 and risk of ischemic vascular disease. N Engl J Med. 2014;371(1):32–41. doi:10.1056/NEJMoa1308027.

    Article  PubMed  CAS  Google Scholar 

  42. Triglyceride Coronary Disease Genetics C, Emerging Risk Factors C, Sarwar N, Sandhu MS, Ricketts SL, Butterworth AS, et al. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010;375(9726):1634–9. doi:10.1016/S0140-6736(10)60545-4.

    Article  CAS  Google Scholar 

  43. Miller M, Stone NJ, Ballantyne C, Bittner V, Criqui MH, Ginsberg HN, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292–333. doi:10.1161/CIR.0b013e3182160726.

    Article  PubMed  Google Scholar 

  44. Kotseva K, Wood D, De Backer G, De Bacquer D, Pyorala K, Keil U, et al. EUROASPIRE III: a survey on the lifestyle, risk factors and use of cardioprotective drug therapies in coronary patients from 22 European countries. Eur J Cardiovasc Prev Rehabil. 2009;16(2):121–37. doi:10.1097/HJR.0b013e3283294b1d.

    Article  PubMed  Google Scholar 

  45. 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. doi:10.1093/eurheartj/ehs431.

    Article  CAS  PubMed  Google Scholar 

  46. 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(11):1345–52. doi:10.1038/ng.2795.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. Varbo A, Benn M, Tybjaerg-Hansen A, Jorgensen AB, Frikke-Schmidt R, Nordestgaard BG. Remnant cholesterol as a causal risk factor for ischemic heart disease. J Am Coll Cardiol. 2013;61(4):427–36. doi:10.1016/j.jacc.2012.08.1026.

    Article  CAS  PubMed  Google Scholar 

  48. Nordestgaard BG, Abildgaard S, Wittrup HH, Steffensen R, Jensen G, Tybjaerg-Hansen A. Heterozygous lipoprotein lipase deficiency: frequency in the general population, effect on plasma lipid levels, and risk of ischemic heart disease. Circulation. 1997;96(6):1737–44.

    Article  CAS  PubMed  Google Scholar 

  49. Kersten S. The genetics of dyslipidemia—when less is more. N Engl J Med. 2016;374(12):1192–3. doi:10.1056/NEJMe1601117.

    Article  PubMed  Google Scholar 

  50. Myocardial Infarction G, Investigators CAEC, Stitziel NO, Stirrups KE, Masca NG, Erdmann J, et al. Coding variation in ANGPTL4, LPL, and SVEP1 and the risk of coronary disease. N Engl J Med. 2016;374(12):1134–44. doi:10.1056/NEJMoa1507652.

    Article  CAS  Google Scholar 

  51. 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. doi:10.1001/jama.298.3.299.

    Article  CAS  PubMed  Google Scholar 

  52. Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease: new insights from epidemiology, genetics, and biology. Circ Res. 2016;118(4):547–63.

    Article  CAS  PubMed  Google Scholar 

  53. Sofi F, Abbate R, Gensini GF, Casini A. Accruing evidence on benefits of adherence to the Mediterranean diet on health: an updated systematic review and meta-analysis. Am J Clin Nutr. 2010;92(5):1189–96. doi:10.3945/ajcn.2010.29673.

    Article  CAS  PubMed  Google Scholar 

  54. Estruch R, Ros E, Salas-Salvado J, Covas MI, Corella D, Aros F, et al. Primary prevention of cardiovascular disease with a Mediterranean diet. N Engl J Med. 2013;368(14):1279–90. doi:10.1056/NEJMoa1200303.

    Article  CAS  PubMed  Google Scholar 

  55. Kris-Etherton P, Eckel RH, Howard BV, St Jeor S, Bazzarre TL. AHA Science advisory: Lyon diet heart study. Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association step I dietary pattern on cardiovascular disease. Circulation. 2001;103(13):1823–5.

    Article  CAS  PubMed  Google Scholar 

  56. Estruch R, Ros E, Martinez-Gonzalez MA. Mediterranean diet for primary prevention of cardiovascular disease. N Engl J Med. 2013;369(7):676–7. doi:10.1056/NEJMc1306659.

    CAS  PubMed  Google Scholar 

  57. de Lorgeril M, Salen P, Martin JL, Monjaud I, Delaye J, Mamelle N. Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction: final report of the Lyon diet heart study. Circulation. 1999;99(6):779–85.

    Article  PubMed  Google Scholar 

  58. Rivellese AA, Giacco R, Annuzzi G, De Natale C, Patti L, Di Marino L, et al. Effects of monounsaturated vs. saturated fat on postprandial lipemia and adipose tissue lipases in type 2 diabetes. Clin Nutr (Edinburgh, Scotland). 2008;27(1):133–41. doi:10.1016/j.clnu.2007.07.005.

    Article  CAS  Google Scholar 

  59. 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.

    CAS  PubMed  Google Scholar 

  60. Stein EA, Raal FJ. Polygenic familial hypercholesterolaemia: does it matter? Lancet. 2013;381(9874):1255–7. doi:10.1016/S0140-6736(13)60187-7.

    Article  PubMed  Google Scholar 

  61. Collins R, Reith C, Emberson J, Armitage J, Baigent C, Blackwell L, et al. Interpretation of the evidence for the efficacy and safety of statin therapy. Lancet (London, England). 2016;388(10059):2532–61. doi:10.1016/s0140-6736(16)31357-5.

    Article  CAS  Google Scholar 

  62. Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, Barnes EH, 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 (London, England). 2012;380(9841):581–90. doi:10.1016/s0140-6736(12)60367-5.

    Article  CAS  Google Scholar 

  63. Taylor F, Huffman MD, Macedo AF, Moore TH, Burke M, Davey Smith G, et al. Statins for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2013;(1):Cd004816. doi:10.1002/14651858.CD004816.pub5.

  64. 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(2):139–51. doi:10.1111/j.1365-2710.2009.01085.x.

    Article  CAS  PubMed  Google Scholar 

  65. Mukhtar RY, Reid J, Reckless JP. Pitavastatin. Int J Clin Pract. 2005;59(2):239–52. doi:10.1111/j.1742-1241.2005.00461.x.

    Article  CAS  PubMed  Google Scholar 

  66. Davignon J. Beneficial cardiovascular pleiotropic effects of statins. Circulation. 2004;109(23 Suppl 1):III39–43. doi:10.1161/01.CIR.0000131517.20177.5a.

    PubMed  Google Scholar 

  67. Zhou Q, Liao JK. Pleiotropic effects of statins—basic research and clinical perspectives. Circ J: Off J Jpn Circ Soc. 2010;74(5):818–26.

    Article  CAS  Google Scholar 

  68. Sudhop T, Lutjohann D, Kodal A, Igel M, Tribble DL, Shah S, et al. Inhibition of intestinal cholesterol absorption by ezetimibe in humans. Circulation. 2002;106(15):1943–8.

    Article  CAS  PubMed  Google Scholar 

  69. Kosoglou T, Meyer I, Veltri EP, Statkevich P, Yang B, Zhu Y, et al. Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin. Br J Clin Pharmacol. 2002;54(3):309–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  70. Stitziel NO, Won HH, Morrison AC, Peloso GM, Do R, Lange LA, et al. Inactivating mutations in NPC1L1 and protection from coronary heart disease. N Engl J Med. 2014;371(22):2072–82. doi:10.1056/NEJMoa1405386.

    Article  PubMed  CAS  Google Scholar 

  71. 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. doi:10.1056/NEJMoa1410489.

    Article  CAS  PubMed  Google Scholar 

  72. The lipid research clinics coronary primary prevention trial results. II. The relationship of reduction in incidence of coronary heart disease to cholesterol lowering. JAMA. 1984;251(3):365–74.

  73. The Lipid Research Clinics Program. Pre-entry characteristics of participants in the Lipid Research Clinics’ Coronary Primary Prevention Trial. J Chronic Dis. 1983;36(6):467–79.

  74. The lipid research clinics coronary primary prevention trial. Results of 6 years of post-trial follow-up. The Lipid Research Clinics Investigators. Arch Intern Med. 1992;152(7):1399–410.

  75. Hennuyer N, Duplan I, Paquet C, Vanhoutte J, Woitrain E, Touche V, et al. The novel selective PPARalpha modulator (SPPARMalpha) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis. Atherosclerosis. 2016;249:200–8. doi:10.1016/j.atherosclerosis.2016.03.003.

    Article  CAS  PubMed  Google Scholar 

  76. 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(9729):1875–84. doi:10.1016/S0140-6736(10)60656-3.

    Article  CAS  PubMed  Google Scholar 

  77. Lee M, Saver JL, Towfighi A, Chow J, Ovbiagele B. Efficacy of fibrates for cardiovascular risk reduction in persons with atherogenic dyslipidemia: a meta-analysis. Atherosclerosis. 2011;217(2):492–8. doi:10.1016/j.atherosclerosis.2011.04.020.

    Article  CAS  PubMed  Google Scholar 

  78. Bruckert E, Labreuche J, Deplanque D, Touboul PJ, Amarenco P. Fibrates effect on cardiovascular risk is greater in patients with high triglyceride levels or atherogenic dyslipidemia profile: a systematic review and meta-analysis. J Cardiovasc Pharmacol. 2011;57(2):267–72. doi:10.1097/FJC.0b013e318202709f.

    Article  CAS  PubMed  Google Scholar 

  79. Kamanna VS, Kashyap ML. Mechanism of action of niacin. Am J Cardiol. 2008;101(8A):20B–6B. doi:10.1016/j.amjcard.2008.02.029.

    Article  CAS  PubMed  Google Scholar 

  80. Canner PL, Berge KG, Wenger NK, Stamler J, Friedman L, Prineas RJ, et al. Fifteen year mortality in coronary drug project patients: long-term benefit with niacin. J Am Coll Cardiol. 1986;8(6):1245–55.

    Article  CAS  PubMed  Google Scholar 

  81. Bruckert E, Labreuche J, Amarenco P. Meta-analysis of the effect of nicotinic acid alone or in combination on cardiovascular events and atherosclerosis. Atherosclerosis. 2010;210(2):353–61. doi:10.1016/j.atherosclerosis.2009.12.023.

    Article  CAS  PubMed  Google Scholar 

  82. 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. doi:10.1056/NEJMoa1107579.

    Article  CAS  Google Scholar 

  83. 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. doi:10.1056/NEJMoa1300955.

    Article  CAS  Google Scholar 

  84. Benes LB, Bassi NS, Davidson MH. Omega-3 carboxylic acids monotherapy and combination with statins in the management of dyslipidemia. Vasc Health Risk Manag. 2016;12:481–90. doi:10.2147/vhrm.s58149.

    Article  PubMed  PubMed Central  Google Scholar 

  85. Ballantyne CM, Bays HE, Kastelein JJ, Stein E, Isaacsohn JL, Braeckman RA, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110(7):984–92. doi:10.1016/j.amjcard.2012.05.031.

    Article  CAS  PubMed  Google Scholar 

  86. Kotwal S, Jun M, Sullivan D, Perkovic V, Neal B. Omega 3 fatty acids and cardiovascular outcomes: systematic review and meta-analysis. Circ Cardiovasc Qual Outcomes. 2012;5(6):808–18. doi:10.1161/CIRCOUTCOMES.112.966168.

    Article  PubMed  Google Scholar 

  87. Abifadel M, Varret M, Rabes JP, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34(2):154–6. doi:10.1038/ng1161.

    Article  CAS  PubMed  Google Scholar 

  88. 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(16):1489–99. doi:10.1056/NEJMoa1501031.

    Article  CAS  PubMed  Google Scholar 

  89. 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(16):1500–9. doi:10.1056/NEJMoa1500858.

    Article  CAS  PubMed  Google Scholar 

  90. Navarese EP, Kolodziejczak M, Schulze V, Gurbel PA, Tantry U, Lin Y, et al. Effects of proprotein convertase subtilisin/kexin type 9 antibodies in adults with hypercholesterolemia: a systematic review and meta-analysis. Ann Intern Med. 2015;163(1):40–51. doi:10.7326/M14-2957.

    Article  PubMed  Google Scholar 

  91. Navarese EP, Kolodziejczak M, Dimitroulis D, Wolff G, Busch HL, Devito F, et al. From proprotein convertase subtilisin/kexin type 9 to its inhibition: state-of-the-art and clinical implications. Eur Heart J Cardiovasc Pharmacother. 2016;2(1):44–53. doi:10.1093/ehjcvp/pvv045.

    Article  PubMed  Google Scholar 

  92. Gupta N, Fisker N, Asselin MC, Lindholm M, Rosenbohm C, Orum H, et al. A locked nucleic acid antisense oligonucleotide (LNA) silences PCSK9 and enhances LDLR expression in vitro and in vivo. PLoS One. 2010;5(5):e10682. doi:10.1371/journal.pone.0010682.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  93. Lindholm MW, Elmen J, Fisker N, Hansen HF, Persson R, Moller MR, et al. PCSK9 LNA antisense oligonucleotides induce sustained reduction of LDL cholesterol in nonhuman primates. Mol Ther: J Am Soc Gene Ther. 2012;20(2):376–81. doi:10.1038/mt.2011.260.

    Article  CAS  Google Scholar 

  94. Fitzgerald K, White S, Borodovsky A, Bettencourt BR, Strahs A, Clausen V, et al. A highly durable RNAi therapeutic inhibitor of PCSK9. N Engl J Med. 2017;376(1):41–51. doi:10.1056/NEJMoa1609243.

    Article  PubMed  Google Scholar 

  95. Fitzgerald K, Frank-Kamenetsky M, Shulga-Morskaya S, Liebow A, Bettencourt BR, Sutherland JE, et al. Effect of an RNA interference drug on the synthesis of proprotein convertase subtilisin/kexin type 9 (PCSK9) and the concentration of serum LDL cholesterol in healthy volunteers: a randomised, single-blind, placebo-controlled, phase 1 trial. Lancet (London, England). 2014;383(9911):60–8. doi:10.1016/s0140-6736(13)61914-5.

    Article  CAS  Google Scholar 

  96. Strat AL, Ghiciuc CM, Lupusoru CE, Mitu F. New class of drugs: therapeutic RNAi inhibition of PCSK9 as a specific LDL-c lowering therapy. Rev Med Chir Soc Med Nat Iasi. 2016;120(2):228–32.

    CAS  PubMed  Google Scholar 

  97. Ahmad Z, Khera A. The role of microsomal triglyceride transfer protein inhibitors in the treatment of patients with familial hypercholesterolemia: risks, benefits, and management. Curr Atheroscler Rep. 2015;17(1):469. doi:10.1007/s11883-014-0469-2.

    Article  PubMed  CAS  Google Scholar 

  98. Cuchel M, Meagher EA, du Toit TH, Blom DJ, Marais AD, Hegele RA, et al. Efficacy and safety of a microsomal triglyceride transfer protein inhibitor in patients with homozygous familial hypercholesterolaemia: a single-arm, open-label, phase 3 study. Lancet (London, England). 2013;381(9860):40–6. doi:10.1016/s0140-6736(12)61731-0.

    Article  CAS  Google Scholar 

  99. Kastelein JJ, Wedel MK, Baker BF, Su J, Bradley JD, Yu RZ, et al. Potent reduction of apolipoprotein B and low-density lipoprotein cholesterol by short-term administration of an antisense inhibitor of apolipoprotein B. Circulation. 2006;114(16):1729–35. doi:10.1161/circulationaha.105.606442.

    Article  CAS  PubMed  Google Scholar 

  100. Rader DJ, Kastelein JJ. Lomitapide and mipomersen: two first-in-class drugs for reducing low-density lipoprotein cholesterol in patients with homozygous familial hypercholesterolemia. Circulation. 2014;129(9):1022–32. doi:10.1161/circulationaha.113.001292.

    Article  PubMed  Google Scholar 

  101. Akdim F, Visser ME, Tribble DL, Baker BF, Stroes ES, Yu R, et al. Effect of mipomersen, an apolipoprotein B synthesis inhibitor, on low-density lipoprotein cholesterol in patients with familial hypercholesterolemia. Am J Cardiol. 2010;105(10):1413–9. doi:10.1016/j.amjcard.2010.01.003.

    Article  CAS  PubMed  Google Scholar 

  102. Tg, Hdl Working Group of the Exome Sequencing Project NHL, Blood I, Crosby J, Peloso GM, Auer PL, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. N Engl J Med. 2014;371(1):22–31. doi:10.1056/NEJMoa1307095.

    Article  CAS  Google Scholar 

  103. Onat A, Hergenc G, Sansoy V, Fobker M, Ceyhan K, Toprak S, et al. Apolipoprotein C-III, a strong discriminant of coronary risk in men and a determinant of the metabolic syndrome in both genders. Atherosclerosis. 2003;168(1):81–9.

    Article  CAS  PubMed  Google Scholar 

  104. Khetarpal SA, Qamar A, Millar JS, Rader DJ. Targeting ApoC-III to reduce coronary disease risk. Curr Atheroscler Rep. 2016;18(9):54. doi:10.1007/s11883-016-0609-y.

    Article  PubMed  CAS  Google Scholar 

  105. Pollin TI, Damcott CM, Shen H, Ott SH, Shelton J, Horenstein RB, et al. A null mutation in human APOC3 confers a favorable plasma lipid profile and apparent cardioprotection. Science. 2008;322(5908):1702–5. doi:10.1126/science.1161524.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Khera AV, Cuchel M, de la Llera-Moya M, Rodrigues A, Burke MF, Jafri K, et al. Cholesterol efflux capacity, high-density lipoprotein function, and atherosclerosis. N Engl J Med. 2011;364(2):127–35. doi:10.1056/NEJMoa1001689.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  107. Li XM, Tang WH, Mosior MK, Huang Y, Wu Y, Matter W, et al. Paradoxical association of enhanced cholesterol efflux with increased incident cardiovascular risks. Arterioscler Thromb Vasc Biol. 2013;33(7):1696–705. doi:10.1161/ATVBAHA.113.301373.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  108. 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. doi:10.1056/NEJMoa1409065.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Heller DA, de Faire U, Pedersen NL, Dahlen G, McClearn GE. Genetic and environmental influences on serum lipid levels in twins. N Engl J Med. 1993;328(16):1150–6. doi:10.1056/nejm199304223281603.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Deutsches Herzzentrum München, Technische Universität München, Lazarettstr. 36, 80636, Munich, Germany

    Veronika Sanin, Vanessa Pfetsch & Wolfgang Koenig

  2. DZHK (German Centre for Cardiovascular Research), Partner Site Munich Heart Alliance, Munich, Germany

    Wolfgang Koenig

Authors
  1. Veronika Sanin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vanessa Pfetsch
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wolfgang Koenig
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wolfgang Koenig.

Ethics declarations

Conflict of Interest

Veronika Sanin and Vanessa Pfetsch declare that they have no conflict of interest.

Wolfgang Koenig reports receiving research support from Abbott, Roche Diagnostics, Beckmann, and Singulex. He has received honoraria for lectures or been a consultant for Novartis, AstraZeneca, Amgen, Pfizer, Sanofi, Berlin-Chemie, The Medicines Company, GSK, DalCor, and Kowa.

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

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

Sanin, V., Pfetsch, V. & Koenig, W. Dyslipidemias and Cardiovascular Prevention: Tailoring Treatment According to Lipid Phenotype. Curr Cardiol Rep 19, 61 (2017). https://doi.org/10.1007/s11886-017-0869-3

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11886-017-0869-3

Keywords

Search

Navigation