Genetic Risk Prediction for Primary and Secondary Prevention of Atherosclerotic Cardiovascular Disease: an Update

Cardiovascular Genomics (TL Assimes, Section Editor)
First Online:
Part of the following topical collections:
  1. Topical Collection on Cardiovascular Genomics

Abstract

Purpose of Review

This review aims to summarize the research on genetic risk scores and their ability to improve risk prediction in both a primary and a secondary prevention population.

Recent Findings

Several groups have examined the role of genetic scores in different patient populations. Recent studies have capitalized on the growing number of identified genetic variants to construct polygenic risk scores that include hundreds and sometimes thousands of SNPs. Also, recent studies have demonstrated that individuals with high genetic risk scores can attenuate their risk with lifestyle modifications and with statins, for which the benefit of treatment may be greater in those at highest genetic risk.

Summary

Genetic risk scores when added to existing clinical models appear to improve risk prediction, particularly in the setting of incident cardiovascular disease and may provide actionable information to optimize prevention early in life. Future research will need to establish how to best use this genetic risk information either as a means to further individualize treatment decisions or to better identify high-risk populations.

Keywords

Genetic risk score Single nucleotide polymorphism Risk prediction Prevention 
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Notes

Compliance with Ethical Standards

Conflict of Interest

Christopher Labos declares that he has no conflict of interest.

Dr. Thanassoulis reports grants and personal fees from Ionis; and personal fees from Amgen, Sanofi, and Servier.

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.

References

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

  1. 1.
    Ridker PM, Buring JE, Rifai N, Cook NR. Development and validation of improved algorithms for the assessment of global cardiovascular risk in women: the Reynolds Risk Score. JAMA Am Med Assoc. 2007;297:611–9.CrossRefGoogle Scholar
  2. 2.
    Ridker PM, Paynter NP, Rifai N, Gaziano JM, Cook NR. C-reactive protein and parental history improve global cardiovascular risk prediction: the Reynolds Risk Score for men. Circulation. 2008;118:2243–51. 4p following 2251CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    D’Agostino RB, 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. Lippincott Williams & Wilkins. 2008;117:743–53.CrossRefPubMedGoogle Scholar
  4. 4.
    Dawber TR, Kannel WB, Revotskie N, Stokes J, Kagan A, Gordon T. Some factors associated with the development of coronary heart disease: six years' follow-up experience in the Framingham study. Am J Public Health Nations Health. American Public Health Association. 1959;49:1349–56.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Kannel WB, Dawber TR, Kagan A, Revotskie N, Stokes J. Factors of risk in the development of coronary heart disease—six year follow-up experience. The Framingham Study. Ann Intern Med. 1961;55:33–50.CrossRefPubMedGoogle Scholar
  6. 6.
    Canto JG, Kiefe CI, Rogers WJ, Peterson ED, Frederick PD, French WJ, et al. Number of coronary heart disease risk factors and mortality in patients with first myocardial infarction. JAMA Am Med Assoc. 2011;306:2120–7.Google Scholar
  7. 7.
    Greenland P, Knoll MD, Stamler J, Neaton JD, Dyer AR, Garside DB, et al. Major risk factors as antecedents of fatal and nonfatal coronary heart disease events. JAMA Am Med Assoc. 2003;290:891–7.CrossRefGoogle Scholar
  8. 8.
    Khot UN, Khot MB, Bajzer CT, Sapp SK, Ohman EM, Brener SJ, et al. Prevalence of conventional risk factors in patients with coronary heart disease. JAMA Am Med Assoc. 2003;290:898–904.CrossRefGoogle Scholar
  9. 9.
    Yusuf S, Hawken S, Ounpuu S, Dans T, Avezum A, Lanas F, et al. Effect of potentially modifiable risk factors associated with myocardial infarction in 52 countries (the INTERHEART study): case-control study. Lancet. 2004;364:937–52.CrossRefPubMedGoogle Scholar
  10. 10.
    Friedlander Y. Familial clustering of coronary heart disease: a review of its significance and role as a risk factor for the disease. Genetic factors in coronary heart disease. Dordrecht: Springer; 1994. p. 37–53.Google Scholar
  11. 11.
    Chow CK, Islam S, Bautista L, Rumboldt Z, Yusufali A, Xie C, et al. Parental history and myocardial infarction risk across the world: the INTERHEART Study. J Am Coll Cardiol. 2011;57:619–27.CrossRefPubMedGoogle Scholar
  12. 12.
    Nielsen M, Andersson C, Gerds TA, Andersen PK, Jensen TB, Køber L, et al. Familial clustering of myocardial infarction in first-degree relatives: a nationwide study. Eur Heart J. 2013;34:1198–203.CrossRefPubMedGoogle Scholar
  13. 13.
    Andresdottir MB, Sigurdsson G, Sigvaldason H, Gudnason V, Reykjavik Cohort Study. Fifteen percent of myocardial infarctions and coronary revascularizations explained by family history unrelated to conventional risk factors. The Reykjavik Cohort Study. Eur Heart J. 2002;23:1655–63.CrossRefPubMedGoogle Scholar
  14. 14.
    Lloyd-Jones DM, Nam B-H, D'Agostino RB, Levy D, Murabito JM, Wang TJ, et al. Parental cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults: a prospective study of parents and offspring. JAMA Am Med Assoc. 2004;291:2204–11.CrossRefGoogle Scholar
  15. 15.
    Murabito JM, Pencina MJ, Nam B-H, D'Agostino RB, Wang TJ, Lloyd-Jones D, et al. Sibling cardiovascular disease as a risk factor for cardiovascular disease in middle-aged adults. JAMA Am Med Assoc. 2005;294:3117–23.CrossRefGoogle Scholar
  16. 16.
    Otaki Y, Gransar H, Berman DS, Cheng VY, Dey D, Lin FY, et al. Impact of family history of coronary artery disease in young individuals (from the CONFIRM registry). Am J Cardiol. 2013;111:1081–6.CrossRefPubMedGoogle Scholar
  17. 17.
    Roncaglioni MC, Santoro L, D’Avanzo B, Negri E, Nobili A, Ledda A, et al. Role of family history in patients with myocardial infarction. An Italian case-control study. GISSI-EFRIM Investigators. Circulation. 1992;85:2065–72.CrossRefPubMedGoogle Scholar
  18. 18.
    Sesso HD, Lee IM, Gaziano JM, Rexrode KM, Glynn RJ, Buring JE. Maternal and paternal history of myocardial infarction and risk of cardiovascular disease in men and women. Circulation. 2001;104:393–8.CrossRefPubMedGoogle Scholar
  19. 19.
    Sivapalaratnam S, Boekholdt SM, Trip MD, Sandhu MS, Luben R, Kastelein JJP, et al. Family history of premature coronary heart disease and risk prediction in the EPIC-Norfolk prospective population study. Heart. BMJ Publishing Group Ltd. 2010;96:1985–9.CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    Mulders TA, Meyer Z, van der Donk C, Kroon AA, Ferreira I, Stehouwer CDA, et al. Patients with premature cardiovascular disease and a positive family history for cardiovascular disease are prone to recurrent events. Int J Cardiol. 2011;153:64–7.CrossRefPubMedGoogle Scholar
  21. 21.
    de Faire U, Pedersen N. Studies of twins and adoptees in coronary heart disease. Genetic factors in coronary heart disease. Dordrecht: Springer; 1994. p. 55–68.CrossRefGoogle Scholar
  22. 22.
    Zdravkovic S, Wienke A, Pedersen NL, Marenberg ME, Yashin AI, de Faire U. Heritability of death from coronary heart disease: a 36-year follow-up of 20 966 Swedish twins. J Intern Med. 2002;252:247–54.CrossRefPubMedGoogle Scholar
  23. 23.
    Wienke A, Holm NV, Skytthe A, Yashin AI. The heritability of mortality due to heart diseases: a correlated frailty model applied to Danish twins. Twin Res. 2001;4:266–74.CrossRefPubMedGoogle Scholar
  24. 24.
    Marenberg ME, Risch N, Berkman LF, Floderus B, de Faire U. Genetic susceptibility to death from coronary heart disease in a study of twins. N Engl J Med. Massachusetts Medical Society. 1994;330:1041–6.CrossRefPubMedGoogle Scholar
  25. 25.
    Wellcome Trust Case Control Consortium. Genome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nat Nat Publ Group. 2007;447:661–78.Google Scholar
  26. 26.
    Erdmann J, Grosshennig A, Braund PS, König IR, Hengstenberg C, Hall AS, et al. New susceptibility locus for coronary artery disease on chromosome 3q22.3. Nat Genet. 2009;41:280–2.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Gudbjartsson DF, Bjornsdottir US, Halapi E, Helgadottir A, Sulem P, Jonsdottir GM, et al. Sequence variants affecting eosinophil numbers associate with asthma and myocardial infarction. Nat Genet. 2009;41:342–7.CrossRefPubMedGoogle Scholar
  28. 28.
    Helgadottir A, Thorleifsson G, Manolescu A, Gretarsdottir S, Blondal T, Jonasdottir A, et al. A common variant on chromosome 9p21 affects the risk of myocardial infarction. Science. American Association for the Advancement of Science. 2007;316:1491–3.CrossRefPubMedGoogle Scholar
  29. 29.
    Myocardial Infarction Genetics Consortium, Voight BF, Purcell S, Engert JC, Erdmann J, Reilly MP, et al. Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants. Nat Genet. 2009;41:334–41.CrossRefPubMedCentralGoogle Scholar
  30. 30.
    McPherson R, Pertsemlidis A, Kavaslar N, Stewart A, Roberts R, Cox DR, et al. A common allele on chromosome 9 associated with coronary heart disease. Science. American Association for the Advancement of Science. 2007;316:1488–91.CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Samani NJ, Erdmann J, Hall AS, Hengstenberg C, Mangino M, Mayer B, et al. Genomewide association analysis of coronary artery disease. N Engl J Med. Massachusetts Medical Society. 2007;357:443–53.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Trégouët D-A, König IR, Erdmann J, Munteanu A, Braund PS, Hall AS, et al. Genome-wide haplotype association study identifies the SLC22A3-LPAL2-LPA gene cluster as a risk locus for coronary artery disease. Nat Genet. 2009;41:283–5.CrossRefPubMedGoogle Scholar
  33. 33.
    Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Collier JM, Hébert S, et al. A PYY Q62P variant linked to human obesity. Hum Mol Genet. 2006;15:387–91.CrossRefPubMedGoogle Scholar
  34. 34.
    Ahituv N, Kavaslar N, Schackwitz W, Ustaszewska A, Martin J, Hébert S, et al. Medical sequencing at the extremes of human body mass. Am J Hum Genet. 2007;80:779–91.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Speliotes EK, Willer CJ, Berndt SI, Monda KL, Thorleifsson G, Jackson AU, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet Nat Res. 2010;42:937–48.CrossRefGoogle Scholar
  36. 36.
    International Consortium for Blood Pressure Genome-Wide Association Studies, Ehret GB, Munroe PB, Rice KM, Bochud M, Johnson AD, et al. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nat Nat Res. 2011;478:103–9.Google Scholar
  37. 37.
    Schunkert H, König IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43:333–8.CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M, et al. Biological, clinical and population relevance of 95 loci for blood lipids. Nat Nat Res. 2010;466:707–13.Google Scholar
  39. 39.
    Willer CJ, Sanna S, Jackson AU, Scuteri A, Bonnycastle LL, Clarke R, et al. Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet Nat Publ Group. 2008;40:161–9.CrossRefGoogle Scholar
  40. 40.
    Kathiresan S, Melander O, Anevski D, Guiducci C, Burtt NP, Roos C, et al. Polymorphisms associated with cholesterol and risk of cardiovascular events. N Engl J Med. Massachusetts Medical Society. 2008;358:1240–9.CrossRefPubMedGoogle Scholar
  41. 41.
    Visel A, Zhu Y, May D, Afzal V, Gong E, Attanasio C, et al. Targeted deletion of the 9p21 non-coding coronary artery disease risk interval in mice. Nat Nat Publ Group. 2010;464:409–12.Google Scholar
  42. 42.
    Klarin D, Zhu QM, Emdin CA, Chaffin M, Horner S, McMillan BJ, et al. Genetic analysis in UK Biobank links insulin resistance and transendothelial migration pathways to coronary artery disease. Nat Genet Nat Res. 2017;49:1392–7.CrossRefGoogle Scholar
  43. 43.
    Howson JMM, Zhao W, Barnes DR, Ho W-K, Young R, Paul DS, et al. Fifteen new risk loci for coronary artery disease highlight arterial-wall-specific mechanisms. Nat Genet. 2017;49:1113–9.CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Nelson CP, Goel A, Butterworth AS, Kanoni S, Webb TR, Marouli E, et al. Association analyses based on false discovery rate implicate new loci for coronary artery disease. Nat Genet Nat Res. 2017;49:1385–91.CrossRefGoogle Scholar
  45. 45.
    CARDIoGRAMplusC4D Consortium, Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet Nat Res. 2013;45:25–33.CrossRefGoogle Scholar
  46. 46.
    Webb TR, Erdmann J, Stirrups KE, Stitziel NO, Masca NGD, Jansen H, et al. Systematic evaluation of pleiotropy identifies 6 further loci associated with coronary artery disease. J Am Coll Cardiol. 2017;69:823–36.CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Goldstein BA, Knowles JW, Salfati E, Ioannidis JPA, Assimes TL. Simple, standardized incorporation of genetic risk into non-genetic risk prediction tools for complex traits: coronary heart disease as an example. Front Genet Front. 2014;5:254.Google Scholar
  48. 48.
    Salfati EL, Herrington DM, Assimes TL. Associations between a genetic risk score for clinical CAD and early stage lesions in the coronary artery and the aorta. Dubé M-P, editor. PLoS ONE. Public Libr Sci; 2016;11:e0166994.Google Scholar
  49. 49.
    Thanassoulis G, Peloso GM, Pencina MJ, Hoffmann U, Fox CS, Cupples LA, et al. A genetic risk score is associated with incident cardiovascular disease and coronary artery calcium: the Framingham Heart Study. Circ Cardiovasc Genet. American Heart Association, Inc. 2012;5:113–21.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Labos C, Wang RHL, Pilote L, Bogaty P, Brophy JM, Engert JC, et al. Traditional risk factors and a Genetic Risk Score are associated with age of first acute coronary syndrome. Heart. BMJ Publishing Group Ltd and British Cardiovascular Society. 2014;100:1620–4.CrossRefPubMedGoogle Scholar
  51. 51.
    Hindieh W, Pilote L, Cheema A, Al-Lawati H, Labos C, Dufresne L, et al. Association between family history, a genetic risk score, and severity of coronary artery disease in patients with premature acute coronary syndromes. Arterioscler Thromb Vasc Biol. American Heart Association, Inc. 2016;36:1286–92.CrossRefPubMedGoogle Scholar
  52. 52.
    Bjornsson E, Gudbjartsson DF, Helgadottir A, Gudnason T, Gudbjartsson T, Eyjolfsson K, et al. Common sequence variants associated with coronary artery disease correlate with the extent of coronary atherosclerosis. Arterioscler. Thromb. Vasc. Biol. American Heart Association, Inc. 2015;35:1526–31.CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Tikkanen E, Havulinna AS, Palotie A, Salomaa V, Ripatti S. Genetic risk prediction and a 2-stage risk screening strategy for coronary heart disease. Arterioscler Thromb Vasc Biol. American Heart Association, Inc. 2013;33:2261–6.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
    Talmud PJ, Cooper JA, Palmen J, Lovering R, Drenos F, Hingorani AD, et al. Chromosome 9p21.3 coronary heart disease locus genotype and prospective risk of CHD in healthy middle-aged men. Clin Chem. 2008;54:467–74.CrossRefPubMedGoogle Scholar
  55. 55.
    Horne BD, Carlquist JF, Muhlestein JB, Bair TL, Anderson JL. Association of variation in the chromosome 9p21 locus with myocardial infarction versus chronic coronary artery disease. Circ Cardiovasc Genet. American Heart Association, Inc. 2008;1:85–92.CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Paynter NP, Chasman DI, Buring JE, Shiffman D, Cook NR, Ridker PM. Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3. Ann Intern Med. NIH Public Access. 2009;150:65–72.CrossRefPubMedPubMedCentralGoogle Scholar
  57. 57.
    Paynter NP, Chasman DI, Paré G, Buring JE, Cook NR, Miletich JP, et al. Association between a literature-based genetic risk score and cardiovascular events in women. JAMA. American Medical Association. 2010;303:631–7.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Ripatti S, Tikkanen E, Orho-Melander M, Havulinna AS, Silander K, Sharma A, et al. A multilocus genetic risk score for coronary heart disease: case-control and prospective cohort analyses. Lancet. 2010;376:1393–400.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Davies RW, Dandona S, Stewart AFR, Chen L, Ellis SG, Tang WHW, et al. Improved prediction of cardiovascular disease based on a panel of single nucleotide polymorphisms identified through genome-wide association studies. Circ Cardiovasc Genet. American Heart Association, Inc. 2010;3:468–74.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Bolton JL, Stewart MCW, Wilson JF, Anderson N, Price JF. Improvement in prediction of coronary heart disease risk over conventional risk factors using SNPs identified in genome-wide association studies. Xiong M, editor. PLoS ONE. Public Libr Sci; 2013;8:e57310.Google Scholar
  61. 61.
    Krarup NT, Borglykke A, Allin KH, Sandholt CH, Justesen JM, Andersson EA, et al. A genetic risk score of 45 coronary artery disease risk variants associates with increased risk of myocardial infarction in 6041 Danish individuals. Atherosclerosis. 2015;240:305–10.CrossRefPubMedGoogle Scholar
  62. 62.
    • Abraham G, Havulinna AS, Bhalala OG, Byars SG, De Livera AM, Yetukuri L, et al. Genomic prediction of coronary heart disease. European Heart Journal. 2016;37:3267–78. This study developed a genetic risk score using the greatest number of SNPs used thus far. It demonstrated an association with cardiovascular events and an improvement in risk prediction metrics.CrossRefPubMedPubMedCentralGoogle Scholar
  63. 63.
    Ganna A, Magnusson PKE, Pedersen NL, de Faire U, Reilly M, Arnlöv J, et al. Multilocus genetic risk scores for coronary heart disease prediction. Arterioscler Thromb Vasc Biol. American Heart Association, Inc. 2013;33:2267–72.CrossRefPubMedGoogle Scholar
  64. 64.
    Buysschaert I, Carruthers KF, Dunbar DR, Peuteman G, Rietzschel E, Belmans A, et al. A variant at chromosome 9p21 is associated with recurrent myocardial infarction and cardiac death after acute coronary syndrome: the GRACE Genetics Study. Eur Heart J. 2010;31:1132–41.CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    Patel RS, Su S, Neeland IJ, Ahuja A, Veledar E, Zhao J, et al. The chromosome 9p21 risk locus is associated with angiographic severity and progression of coronary artery disease. Eur Heart J. 2010;31:3017–23.CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Ardissino D, Berzuini C, Merlini PA, Mannuccio Mannucci P, Surti A, Burtt N, et al. Influence of 9p21.3 genetic variants on clinical and angiographic outcomes in early-onset myocardial infarction. J Am Coll Cardiol. 2011;58:426–34.CrossRefPubMedGoogle Scholar
  67. 67.
    Schunkert H, Götz A, Braund P, McGinnis R, Trégouët D-A, Mangino M, et al. Repeated replication and a prospective meta-analysis of the association between chromosome 9p21.3 and coronary artery disease. Circulation. American Heart Association, Inc. 2008;117:1675–84.CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    Wauters E, Carruthers KF, Buysschaert I, Dunbar DR, Peuteman G, Belmans A, et al. Influence of 23 coronary artery disease variants on recurrent myocardial infarction or cardiac death: the GRACE Genetics Study. Eur Heart J. 2013;34:993–1001.CrossRefPubMedGoogle Scholar
  69. 69.
    Tragante V, Doevendans PAFM, Nathoe HM, van der Graaf Y, Spiering W, Algra A, et al. The impact of susceptibility loci for coronary artery disease on other vascular domains and recurrence risk. Eur Heart J. 2013;34:2896–904.CrossRefPubMedGoogle Scholar
  70. 70.
    Patel RS, Sun YV, Hartiala J, Veledar E, Su S, Sher S, et al. Association of a genetic risk score with prevalent and incident myocardial infarction in subjects undergoing coronary angiography. Circ Cardiovasc Genet. American Heart Association, Inc. 2012;5:441–9.CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Weijmans M, de Bakker PIW, van der Graaf Y, Asselbergs FW, Algra A, Jan de Borst G, et al. Incremental value of a genetic risk score for the prediction of new vascular events in patients with clinically manifest vascular disease. Atherosclerosis. 2015;239:451–8.CrossRefPubMedGoogle Scholar
  72. 72.
    Assimes TL, Roberts R. Genetics: implications for prevention and management of coronary artery disease. J Am Coll Cardiol. 2016 Dec 27;68(25):2797–818.CrossRefPubMedGoogle Scholar
  73. 73.
    Labos C, Martinez SC, Leo Wang RH, Lenzini PA, Pilote L, Bogaty P, et al. Utility of a genetic risk score to predict recurrent cardiovascular events 1 year after an acute coronary syndrome: a pooled analysis of the RISCA, PRAXY, and TRIUMPH cohorts. Atherosclerosis. 2015;242:261–7.CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    • Mega JL, Stitziel NO, Smith JG, Chasman DI, Caulfield MJ, Devlin JJ, et al. Genetic risk, coronary heart disease events, and the clinical benefit of statin therapy: an analysis of primary and secondary prevention trials. Lancet. 2015;385:2264–71. This study examines the predictive capacity of a genetic risk score and also evaluates the relative benefit drawn from statin therapy based on genetic risk.CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Vaara S, Tikkanen E, Parkkonen O, Lokki M-L, Ripatti S, Perola M, et al. Genetic risk scores predict recurrence of acute coronary syndrome. Circ Cardiovasc Genet. American Heart Association, Inc. 2016;9:172–8.CrossRefPubMedGoogle Scholar
  76. 76.
    Christiansen MK, Nyegaard M, Larsen SB, Grove EL, Würtz M, Neergaard-Petersen S, et al. A genetic risk score predicts cardiovascular events in patients with stable coronary artery disease. Int J Cardiol. 2017;241:411–6.CrossRefPubMedGoogle Scholar
  77. 77.
    Wirtwein M, Melander O, Sjogren M, Hoffmann M, Narkiewicz K, Gruchala M, et al. Relationship between selected DNA polymorphisms and coronary artery disease complications. Int J Cardiol. 2017;228:814–20.CrossRefPubMedGoogle Scholar
  78. 78.
    Pereira A, Mendonca MI, Sousa AC, Borges S, Freitas S, Henriques E, et al. Genetic risk score and cardiovascular mortality in a southern european population with coronary artery disease. Int J Clin. Pract 3rd ed 2017;71:e12956.Google Scholar
  79. 79.
    Patel RS, Asselbergs FW. The GENIUS-CHD consortium. Eur Heart J. 2015;36(40):2674–6.PubMedGoogle Scholar
  80. 80.
    Amsterdam EA, Wenger NK, Brindis RG, Casey DE, Ganiats TG, Holmes DR, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. American Heart Association, Inc; 2014. pp. 2354–94.Google Scholar
  81. 81.
    Natarajan P, Young R, Stitziel NO, Padmanabhan S, Baber U, Mehran R, et al. Polygenic risk score identifies subgroup with higher burden of atherosclerosis and greater relative benefit from statin therapy in the primary prevention setting. Circulation. American Heart Association, Inc. 2017;135:2091–101.CrossRefPubMedGoogle Scholar
  82. 82.
    Thanassoulis G, Williams K, Altobelli KK, Pencina MJ, Cannon CP, Sniderman AD. Individualized statin benefit for determining statin eligibility in the primary prevention of cardiovascular disease. Circulation. Lippincott Williams & Wilkins. 2016;133:1574–81.CrossRefPubMedGoogle Scholar
  83. 83.
    Thanassoulis G, Pencina MJ, Sniderman AD. The benefit model for prevention of cardiovascular disease: an opportunity to harmonize guidelines. JAMA Cardiol. 2017;2:1175–6.CrossRefPubMedGoogle Scholar
  84. 84.
    • Khera AV, Emdin CA, Drake I, Natarajan P, Bick AG, Cook NR, et al. Genetic risk, adherence to a healthy lifestyle, and coronary disease. N Engl J Med. Massachusetts Medical Society; 2016;375:2349–58. This study demonstrates that standard lifestyle interventions can attenuate high cardiovascular risk mediated through genetic factors.Google Scholar
  85. 85.
    Hollands GJ, French DP, Griffin SJ, Prevost AT, Sutton S, King S, et al. The impact of communicating genetic risks of disease on risk-reducing health behaviour: systematic review with meta-analysis. BMJ. BMJ Publishing Group. 2016;i1102:352.Google Scholar
  86. 86.
    Kullo IJ, Jouni H, Austin EE, Brown S-A, Kruisselbrink TM, Isseh IN, et al. Incorporating a genetic risk score into coronary heart disease risk estimates: effect on low-density lipoprotein cholesterol levels (the MI-GENES clinical trial). Circulation. American Heart Association, Inc. 2016;133:1181–8.CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Knowles JW, Zarafshar S, Pavlovic A, Goldstein BA, Tsai S, Li J, et al. Impact of a genetic risk score for coronary artery disease on reducing cardiovascular risk: a pilot randomized controlled study. Front Cardiovasc Med Front. 2017;4:53.CrossRefGoogle Scholar

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Authors and Affiliations

  1. 1.Division of Cardiology, Preventive and Genomic CardiologyMcGill University Health CenterMontrealCanada

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