Advertisement

Genetic Risk, Adherence to a Healthy Lifestyle, and Ischemic Heart Disease

  • Thomas F. WhayneJrEmail author
  • Sibu P. Saha
Ischemic Heart Disease (D Mukherjee, Section Editor)
  • 74 Downloads
Part of the following topical collections:
  1. Topical Collection on Ischemic Heart Disease

Abstract

Purpose of Review

The purpose of this review is to investigate and discuss two aspects of coronary artery disease (CAD)—genetic risk and therapeutic lifestyle change (TLC)—both of which have key importance for patients and their care but which actually receive inadequate attention.

Recent Findings

Genetic risk has generally been relegated to a broad association with the presence of one or more inherited cardiovascular (CV) risk factors such as hypercholesterolemia, family history of atherosclerosis, hypertension, and diabetes mellitus. However, the future of genetic risk is an understanding of specific genes, a genetic risk score, specific genetic loci known as selective nucleotide polymorphisms (SNPs), specific alleles, and microribonucleic acids (miRNAs). Healthy lifestyle is fashionably referred to as TLC and encompasses physical fitness, exercise, behavioral modification, diet, and stress reduction.

Summary

In the past decade, aggressive treatment of cholesterol with statins has received the major emphasis for CV risk reduction. Genetics, of course, can only be modified by factors that influence epigenetics, and TLC could have an effect on genetics by this mechanism. On the other hand, each individual component of TLC has been shown to contribute to a reduction of CV risk. Although aggressive pharmaceutical approaches are now in vogue, whatever TLC can contribute, depending on the degree of individual patient adherence, should never be forgotten.

Keywords

Atherosclerosis Coronary artery disease Genetics Hyperlipoproteinemias Lipoprotein (a) Low-density lipoprotein cholesterol Therapeutic lifestyle change 

Abbreviations

AF

Atrial fibrillation

CAD

Coronary artery disease

CIMT

Carotid intima-media thickness

CSF1

Colony-stimulating factor 1

CTA

Computed tomography angiography

CV

Cardiovascular

CXCL12

Cell-derived factor 1

DM

Diabetes mellitus

GRS

Genetic risk score

HHS

Health Heart Score

hsCRP

High sensitivity C-reactive protein

LDL

Low-density lipoprotein

LDL-C

Low-density lipoprotein cholesterol

Lp(a)

Lipoprotein (a)

MedDiet

Mediterranean diet

MetS

Metabolic syndrome

MI

Myocardial infarction

MiRNAs

Microribonucleic acids

MPO

Myeloperoxidase

PAD

Peripheral arterial disease

PCI

Percutaneous coronary intervention

PCSK9

Proprotein convertase subtilisin/kexin type 9

SCD

Sudden cardiac death

SNPs

Selective nucleotide polymorphisms

TLC

Therapeutic lifestyle change

UK

United Kingdom

Notes

Acknowledgments

The authors thank Colleen McMullen, MA, MBA, for her excellent editorial critique.

Compliance with Ethical Standards

Conflict of Interest

Thomas F. Whayne, Jr. and Sibu P. Saha confirm that there are no conflicts of interest involving any pharmaceutical or medical device company or any other possible conflict.

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 •• Of major importance

  1. 1.
    •• Teramoto T, Sasaki J, Ishibashi S, Birou S, Daida H, Dohi S, et al. Cardiovascular disease risk factors other than dyslipidemia. Executive summary of the Japan Atherosclerosis Society (JAS) guidelines for the diagnosis and prevention of atherosclerotic cardiovascular diseases in Japan - 2012 version. J Atheroscler Thromb. 2013;20(10):733–42 This executive summary succintly deals with nonlipid CV risk factors. CrossRefGoogle Scholar
  2. 2.
    Krintus M, Kozinski M, Kubica J, Sypniewska G. Critical appraisal of inflammatory markers in cardiovascular risk stratification. Crit Rev Clin Lab Sci. 2014;51(5):263–79.CrossRefGoogle Scholar
  3. 3.
    Hong MK, Mintz GS, Popma JJ, Kent KM, Pichard AD, Satler LF, et al. Limitations of angiography for analyzing coronary atherosclerosis progression or regression. Ann Intern Med. 1994;121(5):348–54.CrossRefGoogle Scholar
  4. 4.
    Marchioli R, Prieto JC, Tognoni G. Surrogate end-points: the case of trials on coronary atherosclerotic plaque regression. Clin Trials Metaanal. 1994;29(2–3):139–76.PubMedGoogle Scholar
  5. 5.
    Voros S, Rinehart S, Qian Z, Joshi P, Vazquez G, Fischer C, et al. Coronary atherosclerosis imaging by coronary CT angiography: current status, correlation with intravascular interrogation and meta-analysis. JACC Cardiovasc Imaging. 2011;4(5):537–48.CrossRefGoogle Scholar
  6. 6.
    Thomsen C, Abdulla J. Characteristics of high-risk coronary plaques identified by computed tomographic angiography and associated prognosis: a systematic review and meta-analysis. Eur Heart J Cardiovasc Imaging. 2016;17(2):120–9.CrossRefGoogle Scholar
  7. 7.
    Corti R, Badimon JJ. Biologic aspects of vulnerable plaque. Curr Opin Cardiol. 2002;17(6):616–25.CrossRefGoogle Scholar
  8. 8.
    Finn AV, Chandrashekhar Y, Narula J. Vulnerable plaques: from PROSPECT to prospects. JACC Cardiovasc Imaging. 2012;5(3):334–6.CrossRefGoogle Scholar
  9. 9.
    Bourantas CV, Garcia-Garcia HM, Torii R, Zhang YJ, Westwood M, Crake T, et al. Vulnerable plaque detection: an unrealistic quest or a feasible objective with a clinical value? Heart. 2016;102(8):581–9.CrossRefGoogle Scholar
  10. 10.
    Kullo IJ, Edwards WD, Schwartz RS. Vulnerable plaque: pathobiology and clinical implications. Ann Intern Med. 1998;129(12):1050–60.CrossRefGoogle Scholar
  11. 11.
    Nerlekar N, Brown AJ, Muthalaly RG, Talman A, Hettige T, Cameron JD, et al. Association of epicardial adipose tissue and high-risk plaque characteristics: a systematic review and meta-analysis. J Am Heart Assoc. 2017;6(8):e006379.Google Scholar
  12. 12.
    Finn AV, Nakano M, Narula J, Kolodgie FD, Virmani R. Concept of vulnerable/unstable plaque. Arterioscler Thromb Vasc Biol. 2010;30(7):1282–92.CrossRefGoogle Scholar
  13. 13.
    Naghavi M, Falk E, Hecht HS, Jamieson MJ, Kaul S, Berman D, et al. From vulnerable plaque to vulnerable patient--part III: executive summary of the screening for heart attack prevention and education (SHAPE) task force report. Am J Cardiol. 2006;98(2A):2H–15H.CrossRefGoogle Scholar
  14. 14.
    • Nissen SE. The vulnerable plaque "hypothesis": promise, but little progress. JACC Cardiovasc Imaging. 2009;2(4):483–5 Understanding the concept of the vulnerable plaque is critical and this is well summarized in this reference. CrossRefGoogle Scholar
  15. 15.
    Hecht HS, Cronin P, Blaha MJ, Budoff MJ, Kazerooni EA, Narula J, et al. 2016 SCCT/STR guidelines for coronary artery calcium scoring of noncontrast noncardiac chest CT scans: a report of the Society of Cardiovascular Computed Tomography and Society of Thoracic Radiology. J Thorac Imaging. 2017;32(5):W54–66.CrossRefGoogle Scholar
  16. 16.
    Schmermund A, Mohlenkamp S, Mathes P, Erbel R. Value of coronary artery calcium measurements in primary prevention. Z Kardiol. 2005;94(Suppl 3):III/79–87.Google Scholar
  17. 17.
    Hamilton-Craig CR, Chow CK, Younger JF, Jelinek VM, Chan J, Liew GY. Cardiac Society of Australia and New Zealand position statement executive summary: coronary artery calcium scoring. Med J Aust. 2017;207(8):357–61.CrossRefGoogle Scholar
  18. 18.
    Baillie GM, Sherer JT, Weart CW. Insulin and coronary artery disease: is syndrome X the unifying hypothesis? Ann Pharmacother. 1998;32(2):233–47.CrossRefGoogle Scholar
  19. 19.
    Nesto RW. Managing cardiovascular risk inpatients with metabolic syndrome. Clin Cornerstone. 2005;7(2–3):46–51.CrossRefGoogle Scholar
  20. 20.
    Haffner SM, Ruilope L, Dahlof B, Abadie E, Kupfer S, Zannad F. Metabolic syndrome, new onset diabetes, and new end points in cardiovascular trials. J Cardiovasc Pharmacol. 2006;47(3):469–75.PubMedGoogle Scholar
  21. 21.
    Kwasny C, Manuwald U, Kugler J, Rothe U. Systematic review of the epidemiology and natural history of the metabolic vascular syndrome and its coincidence with type 2 diabetes mellitus and cardiovascular diseases in different European countries. Horm Metab Res. 2018;50(3):201–8.CrossRefGoogle Scholar
  22. 22.
    Ju SY, Jeong HS, Kim DH. Blood vitamin D status and metabolic syndrome in the general adult population: a dose-response meta-analysis. J Clin Endocrinol Metab. 2014;99(3):1053–63.CrossRefGoogle Scholar
  23. 23.
    Booth GL, Wang EE. Preventive health care, 2000 update: screening and management of hyperhomocysteinemia for the prevention of coronary artery disease events. The Canadian Task Force on Preventive Health Care. CMAJ. 2000;163(1):21–9.PubMedPubMedCentralGoogle Scholar
  24. 24.
    Marti-Carvajal AJ, Sola I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017;8:CD006612.PubMedGoogle Scholar
  25. 25.
    •• 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. J Am Coll Cardiol. 2014;63(25 Pt B):2889–934 Whether in agreement or disagreement with, it is essential to be familiar with the 2013 ACC/AHA blood cholesterol guidelines. CrossRefGoogle Scholar
  26. 26.
    Bennet CS, Dahagam CR, Virani SS, Martin SS, Blumenthal RS, Michos ED, et al. Lipid management guidelines from the departments of veteran affairs and defense: a critique. Am J Med. 2016;129(9):906–12.CrossRefGoogle Scholar
  27. 27.
    Handelsman Y, Bloomgarden ZT, Grunberger G, Umpierrez G, Zimmerman RS, Bailey TS, et al. American association of clinical endocrinologists and american college of endocrinology - clinical practice guidelines for developing a diabetes mellitus comprehensive care plan - 2015. Endocr Pract. 2015;21(Suppl 1):1–87.CrossRefGoogle Scholar
  28. 28.
    Jacobson TA, Ito MK, Maki KC, Orringer CE, Bays HE, Jones PH, et al. National Lipid Association recommendations for patient-centered management of dyslipidemia: part 1 - executive summary. J Clin Lipidol. 2014;8(5):473–88.CrossRefGoogle Scholar
  29. 29.
    European Association for Cardiovascular P, Rehabilitation, Reiner Z, Catapano AL, De Backer G, Graham I, et al. ESC/EAS guidelines for the management of dyslipidaemias: the task force for the management of dyslipidaemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). Eur Heart J. 2011;32(14):1769–818.CrossRefGoogle Scholar
  30. 30.
    Whayne TF Jr. Is there an ideal low-density lipoprotein cholesterol level? Confusion regarding lipid guidelines, low-density lipoprotein cholesterol targets, and medical management. Int J Angiol. 2017;26(2):73–7.CrossRefGoogle Scholar
  31. 31.
    Whayne TF. Low-density lipoprotein cholesterol (LDL-C): how low? Curr Vasc Pharmacol. 2017;15(4):374–9.CrossRefGoogle Scholar
  32. 32.
    • 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 The lipid hypothesis was established by the Lipid Research Clinics study and references 32 and 33 are the definitive report of this major contribution to lipid management. Google Scholar
  33. 33.
    • The Lipid Research Clinics Coronary Primary Prevention Trial results. I. Reduction in incidence of coronary heart disease. JAMA. 1984;251(3):351–64. This a second basic reference on the contribution of the Lipid Research Clinics to prove the lipid hypothesis and the importance of LDL-C reduction. Google Scholar
  34. 34.
    Emerging Risk Factors C, Di Angelantonio E, Gao P, Pennells L, Kaptoge S, Caslake M, et al. Lipid-related markers and cardiovascular disease prediction. JAMA. 2012;307(23):2499–506.Google Scholar
  35. 35.
    Barter P. HDL-C: role as a risk modifier. Atheroscler Suppl. 2011;12(3):267–70.CrossRefGoogle Scholar
  36. 36.
    Barter P. Raising HDL-C can be achieved by both lifestyle changes and pharmacological means. Introduction Atheroscler Suppl. 2011;12(3):265–6.CrossRefGoogle Scholar
  37. 37.
    • Tsimikas S, Fazio S, Ferdinand KC, Ginsberg HN, Koschinsky ML, Marcovina SM, et al. NHLBI Working Group recommendations to reduce lipoprotein(a)-mediated risk of cardiovascular disease and aortic stenosis. J Am Coll Cardiol. 2018;71(2):177–92 This reference by Tsmikas et al. focuses on the renewed importance of Lp(a) in 2018. CrossRefGoogle Scholar
  38. 38.
    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.CrossRefGoogle Scholar
  39. 39.
    Alonso R, Andres E, Mata N, Fuentes-Jimenez F, Badimon L, Lopez-Miranda J, et al. Lipoprotein(a) levels in familial hypercholesterolemia: an important predictor of cardiovascular disease independent of the type of LDL receptor mutation. J Am Coll Cardiol. 2014;63(19):1982–9.CrossRefGoogle Scholar
  40. 40.
    Konishi H, Miyauchi K, Shitara J, Endo H, Wada H, Doi S, et al. Impact of lipoprotein(a) on long-term outcomes in patients with diabetes mellitus who underwent percutaneous coronary intervention. Am J Cardiol. 2016;118(12):1781–5.CrossRefGoogle Scholar
  41. 41.
    Gencer B, Kronenberg F, Stroes ES, Mach F. Lipoprotein(a): the revenant. Eur Heart J. 2017;38(20):1553–60.CrossRefGoogle Scholar
  42. 42.
    Pandey AK, Pandey S, Blaha MJ, Agatston A, Feldman T, Ozner M, et al. Family history of coronary heart disease and markers of subclinical cardiovascular disease: where do we stand? Atherosclerosis. 2013;228(2):285–94.CrossRefGoogle Scholar
  43. 43.
    Crouch MA, Gramling R. Family history of coronary heart disease: evidence-based applications. Prim Care. 2005;32(4):995–1010.CrossRefGoogle Scholar
  44. 44.
    •• Roberts R. Genetic risk stratification: tipping point for global primary prevention of coronary artery disease. Circulation. 2018;137(24):2554–6 This a key article that focuses on the current importance and place of genetics in the primary prevention of CAD in 2018. CrossRefGoogle Scholar
  45. 45.
    McPherson R, Tybjaerg-Hansen A. Genetics of coronary artery disease. Circ Res. 2016;118(4):564–78.CrossRefGoogle Scholar
  46. 46.
    Malik R, Mushtaque RS, Siddiqui UA, Younus A, Aziz MA, Humayun C, et al. Association between coronary artery disease and MicroRNA: literature review and clinical perspective. Cureus. 2017;9(4):e1188.PubMedPubMedCentralGoogle Scholar
  47. 47.
    Zhang HF, Zhong BL, Zhu WL, Xie SL, Qiu LX, Zhu LG, et al. CD14 C-260T gene polymorphism and ischemic heart disease susceptibility: a HuGE review and meta-analysis. Genet Med. 2009;11(6):403–8.CrossRefGoogle Scholar
  48. 48.
    Whayne TF. Epigenetics in the development, modification, and prevention of cardiovascular disease. Mol Biol Rep. 2015;42(4):765–76.CrossRefGoogle Scholar
  49. 49.
    Assimes TL, Roberts R. Genetics: implications for prevention and management of coronary artery disease. J Am Coll Cardiol. 2016;68(25):2797–818.CrossRefGoogle Scholar
  50. 50.
    Hou H, Ge S, Zhao L, Wang C, Wang W, Zhao X, et al. An updated systematic review and meta-analysis of association between adiponectin gene polymorphisms and coronary artery disease. OMICS. 2017;21(6):340–51.CrossRefGoogle Scholar
  51. 51.
    Wang Y, Chen XY, Wang K, Li S, Zhang XY. Myeloperoxidase polymorphism and coronary artery disease risk: a meta-analysis. Medicine (Baltimore). 2017;96(27):e7280.CrossRefGoogle Scholar
  52. 52.
    Zhou HY, Wei Q, Shi XD, Cao HY, Qin L. miR-146a rs2910164 polymorphism might be associated with coronary artery disease risk in Asians. Cell Mol Biol (Noisy-le-grand). 2017;63(8):27–9.CrossRefGoogle Scholar
  53. 53.
    Sjaarda J, Gerstein H, Chong M, Yusuf S, Meyre D, Anand SS, et al. Blood CSF1 and CXCL12 as causal mediators of coronary artery disease. J Am Coll Cardiol. 2018;72(3):300–10.CrossRefGoogle Scholar
  54. 54.
    Tikkanen E, Gustafsson S, Ingelsson E. Associations of fitness, physical activity, strength, and genetic risk with cardiovascular disease: longitudinal analyses in the UK biobank study. Circulation. 2018;137(24):2583–91.CrossRefGoogle Scholar
  55. 55.
    Song R, Lee H. Managing health habits for myocardial infarction (MI) patients. Int J Nurs Stud. 2001;38(4):375–80.CrossRefGoogle Scholar
  56. 56.
    Pischke CR, Scherwitz L, Weidner G, Ornish D. Long-term effects of lifestyle changes on well-being and cardiac variables among coronary heart disease patients. Health Psychol. 2008;27(5):584–92.CrossRefGoogle Scholar
  57. 57.
    Rees K, Hartley L, Flowers N, Clarke A, Hooper L, Thorogood M, et al. Mediterranean' dietary pattern for the primary prevention of cardiovascular disease. Cochrane Database Syst Rev. 2018;(8):Art. No.: CD009825.Google Scholar
  58. 58.
    Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Ruiz-Gutierrez V, Covas MI, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006;145(1):1–11.CrossRefGoogle Scholar
  59. 59.
    Sala-Vila A, Romero-Mamani ES, Gilabert R, Nunez I, de la Torre R, Corella D, et al. Changes in ultrasound-assessed carotid intima-media thickness and plaque with a Mediterranean diet: a substudy of the PREDIMED trial. Arterioscler Thromb Vasc Biol. 2014;34(2):439–45.CrossRefGoogle Scholar
  60. 60.
    Dahabreh IJ, Paulus JK. Association of episodic physical and sexual activity with triggering of acute cardiac events: systematic review and meta-analysis. JAMA. 2011;305(12):1225–33.CrossRefGoogle Scholar
  61. 61.
    Cleroux J, Feldman RD, Petrella RJ. Lifestyle modifications to prevent and control hypertension. 4. Recommendations on physical exercise training. Canadian Hypertension Society, Canadian Coalition for High Blood Pressure Prevention and Control, Laboratory Centre for Disease Control at Health Canada, Heart and Stroke Foundation of Canada. CMAJ. 1999;160(9 Suppl):S21–8.PubMedPubMedCentralGoogle Scholar
  62. 62.
    Pack QR, Rodriguez-Escudero JP, Thomas RJ, Ades PA, West CP, Somers VK, et al. The prognostic importance of weight loss in coronary artery disease: a systematic review and meta-analysis. Mayo Clin Proc. 2014;89(10):1368–77.CrossRefGoogle Scholar
  63. 63.
    Ray IB, Menezes AR, Malur P, Hiltbold AE, Reilly JP, Lavie CJ. Meditation and coronary heart disease: a review of the current clinical evidence. Ochsner J. 2014;14(4):696–703.PubMedPubMedCentralGoogle Scholar
  64. 64.
    Davis SK, Quarells R, Gibbons GH. A comprehensive cardiovascular disease lifestyle treatment controlled trial among high-risk African Americans. Open J Prev Med. 2013;3(9):526–33.CrossRefGoogle Scholar
  65. 65.
    Gupta A, Lau E, Varshney R, Hulten EA, Cheezum M, Bittencourt MS, et al. The identification of calcified coronary plaque is associated with initiation and continuation of pharmacological and lifestyle preventive therapies: a systematic review and meta-analysis. JACC Cardiovasc Imaging. 2017;10(8):833–42.CrossRefGoogle Scholar
  66. 66.
    Vranckx P, Boersma E, Garg S, Valgimigli M, Van Es GA, Goedhart D, et al. Cardiovascular risk profile of patients included in stent trials; a pooled analysis of individual patient data from randomised clinical trials: insights from 33 prospective stent trials in Europe. EuroIntervention. 2011;7(7):859–71.CrossRefGoogle Scholar
  67. 67.
    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.CrossRefGoogle Scholar
  68. 68.
    Sacks FM, Svetkey LP, Vollmer WM, Appel LJ, Bray GA, Harsha D, et al. Effects on blood pressure of reduced dietary sodium and the dietary approaches to stop hypertension (DASH) diet. DASH-sodium collaborative research group. N Engl J Med. 2001;344(1):3–10.CrossRefGoogle Scholar
  69. 69.
    Ornish D. Comparison of diets for weight loss and heart disease risk reduction. JAMA. 2005;293(13):1589–90 author reply 90-1.PubMedGoogle Scholar
  70. 70.
    Bazzano LA, He J, Ogden LG, Loria CM, Vupputuri S, Myers L, et al. Fruit and vegetable intake and risk of cardiovascular disease in US adults: the first National Health and Nutrition Examination Survey Epidemiologic Follow-up Study. Am J Clin Nutr. 2002;76(1):93–9.CrossRefGoogle Scholar
  71. 71.
    Barnes VA, Orme-Johnson DW. Prevention and treatment of cardiovascular disease in adolescents and adults through the transcendental meditation((R)) program: a research review update. Curr Hypertens Rev. 2012;8(3):227–42.CrossRefGoogle Scholar
  72. 72.
    Walton KG, Schneider RH, Nidich S. Review of controlled research on the transcendental meditation program and cardiovascular disease. Risk factors, morbidity, and mortality. Cardiol Rev. 2004;12(5):262–6.CrossRefGoogle Scholar
  73. 73.
    Buttar HS, Li T, Ravi N. Prevention of cardiovascular diseases: role of exercise, dietary interventions, obesity and smoking cessation. Exp Clin Cardiol. 2005;10(4):229–49.PubMedPubMedCentralGoogle Scholar
  74. 74.
    Chu P, Pandya A, Salomon JA, Goldie SJ, Hunink MG. Comparative effectiveness of personalized lifestyle management strategies for cardiovascular disease risk reduction. J Am Heart Assoc. 2016;5(3):e002737.CrossRefGoogle Scholar
  75. 75.
    Liu G, Li Y, Hu Y, Zong G, Li S, Rimm EB, et al. Influence of lifestyle on incident cardiovascular disease and mortality in patients with diabetes mellitus. J Am Coll Cardiol. 2018;71(25):2867–76.CrossRefGoogle Scholar
  76. 76.
    Gooding HC, Ning H, Gillman MW, Shay C, Allen N, Goff DC Jr, et al. Application of a lifestyle-based tool to estimate premature cardiovascular disease events in young adults: the coronary artery Risk development in young adults (CARDIA) study. JAMA Intern Med. 2017;177(9):1354–60.CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Gill Heart and Vascular InstituteUniversity of KentuckyLexingtonUSA
  2. 2.Gill Heart and Vascular InstituteLexingtonUSA

Personalised recommendations