Skip to main content

Advertisement

SpringerLink
Log in

Preventive Cardiology and Risk Assessment: Beyond LDL

  • Coronary Heart Disease (S. Virani and S. Naderi, Section Editor)
  • Published:
Current Atherosclerosis Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Risk assessment is the foundational cornerstone for cardiovascular prevention. The goal of this review is to apprise the reader of the latest evidence and guideline-based stepwise method for clinical risk assessment for future atherosclerotic events. We also discuss caveats to the current approach and review future directions including the promise of precision medicine.

Recent Findings

The most recent cholesterol and prevention guidelines improve upon the widely used pooled cohort equations by incorporating risk-enhancing factors to further personalize risk assessment. For those in whom uncertainty remains, there is mounting evidence for using the coronary calcium score to uncover subclinical disease to either up- or down-classify risk. Although still in its infancy, progress in high-throughput molecular analysis is edging the field closer to more precise risk stratification.

Summary

Atherosclerosis is the leading cause of global morbidity and mortality. Emphasis on cardiovascular prevention is essential to mitigate the burden of disease. Here, we introduce a “4 + 2” paradigm for approaching preventive cardiology based on recent guidelines. Risk stratification is performed in four steps: qualitative risk approximation to initiate counseling and education, quantitative risk estimation based on a validated model, personalization with risk-enhancing factors, and measurement of coronary artery calcium score in select patients. The two foundational principles of preventive management are to promote a healthy lifestyle in all and to escalate preventive pharmacotherapy based on increasing risk. Shared decision-making remains central throughout this process.

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

Similar content being viewed by others

References

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

  1. •• 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: Executive Summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;73:3168–209. https://doi.org/10.1016/j.jacc.2018.11.0022018 cholesterol guidelines.

    Article  PubMed  Google Scholar 

  2. •• 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: Executive Summary: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2019;74:1376–414 2019 cardiovascular prevention guidelines.

    Article  Google Scholar 

  3. Clark D, Virani SS. Cholesterol guidelines: key topics in primary prevention. Curr Atheroscler Rep Current Atherosclerosis Reports. 2018;2019:21.

    Google Scholar 

  4. • Roth GA, Johnson C, Abajobir A, Abd-Allah F, Abera SF, Abyu G, et al. Global, Regional, and national burden of cardiovascular diseases for 10 causes, 1990 to 2015. J Am Coll Cardiol. 2017;70:1–25 This article provides up-to-date estimates of the global burden of cardiovascular disease.

    Article  Google Scholar 

  5. Laslett LJ, Alagona P, Clark BA, Drozda JP, Saldivar F, Wilson SR, et al. The worldwide environment of cardiovascular disease: prevalence, diagnosis, therapy, and policy issues: a report from the American College of Cardiology. J Am Coll Cardiol. Elsevier Masson SAS. 2012:60.

  6. Wilkins JT, Ning H, Berry J, Zhao L, Dyer AR, Lloyd-Jones DM. Lifetime risk and years lived free of total cardiovascular disease. JAMA - J Am Med Assoc. 2012;308:1795–801.

    Article  CAS  Google Scholar 

  7. •• McClellan M, Brown N, Califf RM, Warner JJ. Call to Action: urgent challenges in cardiovascular disease: a presidential advisory from the American Heart Association. Circulation. 2019;139:E44–54 This article describes trends in cardiovascular care, identifies gaps in areas of cardiovascular disease prevention and treatment, highlights challenges with medical product innovation, and, finally, outlines a series of learning collaboratives that will aid in the development of road maps for transforming cardiovascular care.

    Article  Google Scholar 

  8. Yusuf PS, Hawken S, Ôunpuu 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.

  9. Farley TA, Dalal MA, Mostashari F, Frieden TR. Deaths preventable in the U.S. by improvements in use of clinical preventive services. Am J Prev Med. 2010.

  10. Smith SC, Collins A, Ferrari R, Holmes DR, Logstrup S, McGhie DV, et al. Our time: a call to save preventable death from cardiovascular disease (heart disease and stroke). Circulation. 2012;126:2769–75.

    Article  Google Scholar 

  11. Eckel RH, Jakicic JM, Ard JD, De Jesus JM, Houston Miller N, Hubbard VS, et al. 2013 AHA/ACC guideline on lifestyle management to reduce cardiovascular risk: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines. Circulation. 2014.

  12. Jensen MD, Ryan DH, Apovian CM, Ard JD, Comuzzie AG, Donato KA, et al. 2013 AHA/ACC/TOS guideline for the management of overweight and obesity in adults: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines and the Obesity Society. Circulation. 2014.

  13. Palinski W. Effect of maternal cardiovascular conditions and risk factors on offspring cardiovascular disease. Circulation. 2014.

  14. •• Libby P, Buring JE, Badimon L, Hansson GK, Deanfield J, Bittencourt MS, et al. Atherosclerosis. Nat Rev Dis Prim. 2019;5:1–18 In-depth review of atherosclerosis pathogenesis.

    Article  Google Scholar 

  15. Koskinas KC, Siontis GCM, Piccolo R, Mavridis D, Räber L, Mach F, et al. Effect of statins and non-statin LDL-lowering medications on cardiovascular outcomes in secondary prevention: a meta-analysis of randomized trials. Eur Heart J 2018;

  16. Navarese EP, Robinson JG, Kowalewski M, Kołodziejczak M, Andreotti F, Bliden K, et al. Association between baseline LDL-C level and total and cardiovascular mortality after LDL-C lowering a systematic review and meta-analysis. JAMA 2018;

  17. •• Whelton PK, Carey RM, Aronow WS, Casey DE, Collins KJ, Dennison Himmelfarb C, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA Guideline for the Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults. J Am Coll Cardiol. 2018. 2017 hypertension guidelines.

  18. 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.

  19. •• Michos ED, McEvoy JW, Blumenthal RS. Lipid management for the prevention of atherosclerotic cardiovascular disease. N Engl J Med. 2019;381:1557–67 Review of lipid management to prevent ASCVD.

    Article  CAS  Google Scholar 

  20. Patel SA, Winkel M, Ali MK, Narayan KMV, Mehta NK. Cardiovascular mortality associated with 5 leading risk factors: national and state preventable fractions estimated from survey data. Ann Intern Med. 2015.

  21. Savji N, Rockman CB, Skolnick AH, Guo Y, Adelman MA, Riles T, et al. Association between advanced age and vascular disease in different arterial territories: a population database of over 3.6 million subjects. J Am Coll Cardiol. 2013.

  22. Gulati M. Improving the cardiovascular health of women in the nation: moving beyond the bikini boundaries. Circulation. 2017;135:495–8.

    Article  Google Scholar 

  23. Berry JD, Dyer A, Cai X, Garside DB, Ning H, Thomas A, et al. Lifetime risks of cardiovascular disease. N Engl J Med. 2012.

  24. Vasan RS, Beiser A, Seshadri S, Larson MG, Kannel WB, D’Agostino RB, et al. Residual lifetime risk for developing hypertension in middle-aged women and men: the Framingham Heart Study. J Am Med Assoc 2002.

  25. Ramírez-Vélez R, Saavedra JM, Lobelo F, Celis-Morales CA, Pozo-Cruz B, del García-Hermoso A. Ideal cardiovascular health and incident cardiovascular disease among adults: a systematic review and meta-analysis. Mayo Clin Proc. 2018;93:1589–99. Mayo Foundation for Medical Education and Research Available from. https://doi.org/10.1016/j.mayocp.2018.05.035.

    Article  PubMed  Google Scholar 

  26. Third Report of the National Cholesterol Education Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult Treatment Panel III) final report. Circulation. 2002;

  27. McClelland RL, Jorgensen NW, Budoff M, Blaha MJ, Post WS, Kronmal RA, et al. 10-year coronary heart disease risk prediction using coronary artery calcium and traditional risk factors derivation in the MESA (Multi-Ethnic Study of Atherosclerosis) with validation in the HNR (Heinz Nixdorf Recall) Study and the DHS (Dallas Heart Stud. J Am Coll Cardiol 2015.

  28. Deanfield J, Sattar N, Simpson I, Wood D, Bradbury K, Fox K, et al. Joint British Societies’ consensus recommendations for the prevention of cardiovascular disease (JBS3). Heart. 2014.

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

  30. Yang X, Li J, Hu D, Chen J, Li Y, Huang J, et al. Predicting the 10-year risks of atherosclerotic cardiovascular disease in Chinese population: the China-PAR project (prediction for ASCVD risk in China). Circulation. 2016.

  31. Goff DC, Lloyd-Jones DM, Bennett G, Coady S, D’Agostino RB, Gibbons R, et al. 2013 ACC/AHA guideline on the assessment of cardiovascular risk. Circulation. 2014.

  32. Wilson PWF, D’Agostino RB, Levy D, Belanger AM, Silbershatz H, Kannel WB. Prediction of coronary heart disease using risk factor categories. Circulation. 1998.

  33. 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. 2008.

  34. 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. 2010.

  35. •• Lloyd-Jones DM, Braun LT, Ndumele CE, Smith SC, Sperling LS, Virani SS, et al. Use of risk assessment tools to guide decision-making in the primary prevention of atherosclerotic cardiovascular disease: a special report from the American Heart Association and American College of Cardiology. Circulation. 2019;139:E1162–77 Review of ASCVD risk stratification.

    Article  Google Scholar 

  36. Yeboah J, Young R, McClelland RL, Delaney JC, Polonsky TS, Dawood FZ, et al. Utility of Nontraditional Risk Markers in Atherosclerotic Cardiovascular Disease Risk Assessment. J Am Coll Cardiol. 2016.

  37. 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.

  38. Yeboah J, Polonsky TS, Young R, McClelland RL, Delaney JC, Dawood F, et al. Utility of nontraditional risk markers in individuals ineligible for statin therapy according to the 2013 American College of Cardiology/American Heart Association Cholesterol Guidelines. Circulation. 2015.

  39. Fudim M, Zalawadiya S, Patel DK, Egolum UO, Afonso L. Data on coronary artery calcium score performance and cardiovascular risk reclassification across gender and ethnicities. Data Br. 2016.

  40. Mahabadi AA, Möhlenkamp S, Lehmann N, Kälsch H, Dykun I, Pundt N, et al. CAC score improves coronary and CV risk assessment above statin indication by ESC and AHA/ACC Primary Prevention Guidelines. JACC Cardiovasc Imaging. 2017.

  41. Mortensen MB, Fuster V, Muntendam P, Mehran R, Baber U, Sartori S, et al. A simple disease-guided approach to personalize ACC/AHA-recommended statin allocation in elderly people: the BioImage study. J Am Coll Cardiol 2016.

  42. Shah R V., Spahillari A, Mwasongwe S, Carr JJ, Terry JG, Mentz RJ, et al. Subclinical atherosclerosis, statin eligibility, and outcomes in African American individuals: the Jackson Heart study. JAMA Cardiol 2017.

  43. Waheed S, Pollack S, Roth M, Reichek N, Guerci A, Cao JJ. Collective impact of conventional cardiovascular risk factors and coronary calcium score on clinical outcomes with or without statin therapy: the St Francis Heart Study. Atherosclerosis. 2016.

  44. Blaha MJ, Cainzos-Achirica M, Greenland P, McEvoy JW, Blankstein R, Budoff MJ, et al. Role of coronary artery calcium score of zero and other negative risk markers for cardiovascular disease : the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2016.

  45. Messenger B, Li D, Nasir K, Carr JJ, Blankstein R, Budoff MJ. Coronary calcium scans and radiation exposure in the multi-ethnic study of atherosclerosis. Int J Cardiovasc Imaging. 2016.

  46. Iribarren C, Hlatky MA, Chandra M, Fair JM, Rubin GD, Go AS, et al. Incidental pulmonary nodules on cardiac computed tomography: prognosis and use. Am J Med 2008.

  47. W.T. Q, Z. A, F. K, M.H. A-M. Prognostic value of extracardiac incidental findings on attenuation correction cardiac computed tomography. J Nucl Cardiol. 2016.

  48. Martin SS, Sperling LS, Blaha MJ, Wilson PWF, Gluckman TJ, Blumenthal RS, et al. Clinician-patient risk discussion for atherosclerotic cardiovascular disease prevention: importance to implementation of the 2013 ACC/AHA guidelines. J Am Coll Cardiol 2015.

  49. 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.

  50. 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.

  51. Tahir UA, Gerszten RE. Omics and cardiometabolic disease risk prediction. Annu Rev Med. 2020;71:163–75.

    Article  CAS  Google Scholar 

  52. Leon-Mimila P, Wang J, Huertas-Vazquez A. Relevance of multi-Omics studies in cardiovascular diseases. Front Cardiovasc Med 2019;6.

  53. Joyner MJ, Paneth N. Promises, promises, and precision medicine. J Clin Invest. 2019;129:946–8.

    Article  Google Scholar 

  54. Musunuru K, Kathiresan S. Genetics of common, complex coronary artery disease. Cell. 2019;177:132–45. Elsevier Inc.; Available from:. https://doi.org/10.1016/j.cell.2019.02.015.

    Article  CAS  PubMed  Google Scholar 

  55. Deloukas P, Kanoni S, Willenborg C, Farrall M, Assimes TL, Thompson JR, et al. Large-scale association analysis identifies new risk loci for coronary artery disease. Nat Genet. 2013.

  56. Nikpay M, Goel A, Won HH, Hall LM, Willenborg C, Kanoni S, et al. A comprehensive 1000 genomes-based genome-wide association meta-analysis of coronary artery disease. Nat Genet 2015.

  57. Khera A V., 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 2016.

  58. Khera A V., Chaffin M, Aragam KG, Haas ME, Roselli C, Choi SH, et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet 2018.

  59. Abraham G, Havulinna AS, Bhalala OG, Byars SG, De Livera AM, Yetukuri L, et al. Genomic prediction of coronary heart disease. Eur Heart J. 2016.

  60. Burgess S, Ference BA, Staley JR, Freitag DF, Mason AM, Nielsen SF, et al. Association of LPA variants with risk of coronary disease and the implications for lipoprotein(a)-lowering therapies: a mendelian randomization analysis. JAMA Cardiol. 2018;3:619–27.

    Article  Google Scholar 

  61. Ference BA, Bhatt DL, Catapano AL, Packard CJ, Graham I, Kaptoge S, et al. Association of genetic variants related to combined exposure to lower low-density lipoproteins and lower systolic blood pressure with lifetime risk of cardiovascular disease. JAMA - J Am Med Assoc. 2019;322:1381–91.

    Article  CAS  Google Scholar 

  62. • Aragam KG, Dobbyn A, Judy R, Chaffin M, Chaudhary K, Hindy G, et al. Limitations of contemporary guidelines for managing patients at high genetic risk of coronary artery disease. J Am Coll Cardiol. 2020;75:2769–80 Original research showing utility of a coronary disease polygenic risk score in a primary prevention population beyond traditional risk factors.

    Article  CAS  Google Scholar 

  63. Martin AR, Kanai M, Kamatani Y, Okada Y, Neale BM, Daly MJ. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Genet. 2019.

  64. Loos RJF, Janssens ACJW. Predicting polygenic obesity using genetic information. Cell Metab. 2017.

  65. Morris RW, Cooper JA, Shah T, Wong A, Drenos F, Engmann J, et al. Marginal role for 53 common genetic variants in cardiovascular disease prediction. Heart. 2016;102:1640–7.

    Article  Google Scholar 

  66. Jarinova O, Stewart AFR, Roberts R, Wells G, Lau P, Naing T, et al. Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus. Arterioscler Thromb Vasc Biol. 2009.

Download references

Author information

Authors and Affiliations

  1. Cleveland Clinic Foundation, Heart Vascular Institute, 9500 Euclid Avenue JB-1, Cleveland, OH, 44195, USA

    Amit Goyal & Leslie Cho

Authors
  1. Amit Goyal
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Leslie Cho
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Leslie Cho.

Ethics declarations

Conflict of Interest

Dr. Goyal has nothing to disclose.

Dr. Cho—research with Amgen, Novartis, Esperion (Lp(a), PCSK 9 trial, bempedoic acid). Consultant—Amgen, Esperion, AstraZeneca (Lp(a), bempedoic acid, statin) These do not pertain to the paper/risk stratification.

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 Coronary Heart Disease

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Goyal, A., Cho, L. Preventive Cardiology and Risk Assessment: Beyond LDL. Curr Atheroscler Rep 22, 56 (2020). https://doi.org/10.1007/s11883-020-00876-2

Download citation

  • Published:

  • DOI: https://doi.org/10.1007/s11883-020-00876-2

Keywords

Search

Navigation