Skip to main content
SpringerLink
Log in

Biomarkers

  • Chapter
  • First Online:
Precision Medicine in Cardiovascular Disease Prevention

  • 692 Accesses

Abstract

Biomarkers, which are often used in conjunction with traditional risk factors, are subclinical indicators of physiological and pathological processes. Elevation of cardiac-related biomarkers can help identify individuals at increased risk of cardiovascular disease (CVD) incidence and progression who may benefit from more intensive medical therapy. Newer lipid measures can provide additional insights into atherosclerotic CVD risk beyond total cholesterol and low-density lipoprotein cholesterol (LDL-C) levels. Additionally, other non-lipid biomarkers, including markers of inflammation, subclinical myocardial injury and wall stress, also appear to have utility in refining CVD risk estimation for a more patient-centered approach. Specifically, the 2019 American College of Cardiology/American Heart Association Guideline for the Primary Prevention of CVD has highlighted elevated high sensitivity C-reactive protein, triglycerides, apolipoprotein B, and lipoprotein(a) as the most helpful “risk-enhancing” factors, that if measured, would favor initiation or intensification of statin therapy among borderline or intermediate-risk individuals. In this chapter, we will review several key lipid-based biomarkers and non-lipid cardiac biomarkers. The goal is to provide clinicians a framework for how to best incorporate such biomarkers into clinical care for an individualized approach to CVD prevention and to identify gaps in knowledge that warrant further study.

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

Access this chapter

Log in via an institution
eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Similar content being viewed by others

References

  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. Circulation. 2019;139(25):e1046–81.

    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: a report of the American college of cardiology/American heart association task force on clinical practice guidelines. Circulation. 2019;140(11):e596-646.

    PubMed  PubMed Central  Google Scholar 

  3. Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020;41(1):111–88.

    Article  PubMed  Google Scholar 

  4. McEvoy JW, Diamond GA, Detrano RC, Kaul S, Blaha MJ, Blumenthal RS, et al. Risk and the physics of clinical prediction. Am J Cardiol. 2014;113(8):1429–35.

    Article  PubMed  Google Scholar 

  5. Pender A, Lloyd-Jones DM, Stone NJ, Greenland P. Refining statin prescribing in lower-risk individuals: informing risk/benefit decisions. J Am Coll Cardiol. 2016;68(15):1690–7.

    Article  PubMed  Google Scholar 

  6. Amin NP, Martin SS, Blaha MJ, Nasir K, Blumenthal RS, Michos ED. Headed in the right direction but at risk for miscalculation: a critical appraisal of the 2013 ACC/AHA risk assessment guidelines. J Am College Cardiol. 2014;63(25 Pt A):2789–94.

    Google Scholar 

  7. Biomarkers and surrogate endpoints. Preferred definitions and conceptual framework. Clin Pharmacol Ther. 2001;69(3):89–95.

    Article  Google Scholar 

  8. Vasan RS. Biomarkers of cardiovascular disease: molecular basis and practical considerations. Circulation. 2006;113(19):2335–62.

    Article  PubMed  Google Scholar 

  9. Osibogun O, Ogunmoroti O, Tibuakuu M, Benson EM, Michos ED. Sex differences in the association between ideal cardiovascular health and biomarkers of cardiovascular disease among adults in the United States: a cross-sectional analysis from the multiethnic study of atherosclerosis. BMJ Open. 2019;9(11):e031414.

    Google Scholar 

  10. Morrow DA, de Lemos JA. Benchmarks for the assessment of novel cardiovascular biomarkers. Circulation. 2007;115(8):949–52.

    Article  PubMed  Google Scholar 

  11. Kannel WB, Dawber TR, Kagan A, Revotskie N, Stokes J, 3rd. Factors of risk in the development of coronary heart disease--six year follow-up experience. The Framingham Study. Annals Internal Med. 1961;55:33–50.

    Google Scholar 

  12. Cholesterol Treatment Trialists C, Baigent C, Blackwell L, Emberson J, Holland LE, Reith C, 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 (London, England). 2010;376(9753):1670–81.

    Google Scholar 

  13. Cholesterol Treatment Trialists C, Mihaylova B, Emberson J, Blackwell L, Keech A, Simes J, 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.

    Google Scholar 

  14. Ference BA, Ginsberg HN, Graham I, Ray KK, Packard CJ, Bruckert E, et al. Low-density lipoproteins cause atherosclerotic cardiovascular disease. 1. Evidence from genetic, epidemiologic, and clinical studies. A consensus statement from the European Atherosclerosis Society Consensus Panel. Eur Heart J. 2017;38(32):2459–72.

    Google Scholar 

  15. Michos ED, McEvoy JW, Blumenthal RS. Lipid management for the prevention of atherosclerotic cardiovascular disease. New England J Med. 2019;381(16):1557–67.

    Article  CAS  Google Scholar 

  16. Castelli WP. Lipids, risk factors and ischaemic heart disease. Atherosclerosis. 1996;124(Suppl):S1-9.

    Article  CAS  PubMed  Google Scholar 

  17. Sabatine MS, Wiviott SD, Im K, Murphy SA, Giugliano RP. Efficacy and safety of further lowering of low-density lipoprotein cholesterol in patients starting with very low levels: a meta-analysis. JAMA Cardiol. 2018;3(9):823–8.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499–502.

    Article  CAS  PubMed  Google Scholar 

  19. Quispe R, Hendrani A, Elshazly MB, Michos ED, McEvoy JW, Blaha MJ, et al. Accuracy of low-density lipoprotein cholesterol estimation at very low levels. BMC Med. 2017;15(1):83.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Martin SS, Blaha MJ, Elshazly MB, Toth PP, Kwiterovich PO, Blumenthal RS, et al. Comparison of a novel method vs the friedewald equation for estimating low-density lipoprotein cholesterol levels from the standard lipid profile. JAMA. 2013;310(19):2061–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Pallazola VA, Sathiyakumar V, Ogunmoroti O, Fashanu O, Jones SR, Santos RD, et al. Impact of improved low-density lipoprotein cholesterol assessment on guideline classification in the modern treatment era-Results from a racially diverse Brazilian cross-sectional study. J Clin Lipidol. 2019;13(5):804–11 e2.

    Google Scholar 

  22. Chaen H, Kinchiku S, Miyata M, Kajiya S, Uenomachi H, Yuasa T, et al. Validity of a novel method for estimation of low-density lipoprotein cholesterol levels in diabetic patients. J Atheroscler Thromb. 2016;23(12):1355–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Lee J, Jang S, Son H. Validation of the Martin Method for Estimating Low-Density Lipoprotein Cholesterol Levels in Korean Adults: Findings from the Korea National Health and Nutrition Examination Survey, 2009–2011. PloS one. 2016;11(1):e0148147.

    Google Scholar 

  24. Mehta R, Reyes-Rodriguez E, Yaxmehen Bello-Chavolla O, Guerrero-Diaz AC, Vargas-Vazquez A, Cruz-Bautista I, et al. Performance of LDL-C calculated with Martin’s formula compared to the Friedewald equation in familial combined hyperlipidemia. Atherosclerosis. 2018;277:204–10.

    Article  CAS  PubMed  Google Scholar 

  25. Martin SS, Giugliano RP, Murphy SA, Wasserman SM, Stein EA, Ceska R, et al. Comparison of low-density lipoprotein cholesterol assessment by martin/hopkins estimation, friedewald estimation, and preparative ultracentrifugation: insights from the FOURIER trial. JAMA Cardiol. 2018;3(8):749–53.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Khan SU, Khan MU, Valavoor S, Khan MS, Okunrintemi V, Mamas MA, et al. Association of lowering apolipoprotein B with cardiovascular outcomes across various lipid-lowering therapies: Systematic review and meta-analysis of trials. Eur J Prev Cardiol. 2019:2047487319871733.

    Google Scholar 

  27. Martin SS, Michos ED. Are we moving towards concordance on the principle that lipid discordance matters? Circulation. 2014;129(5):539–41.

    Article  PubMed  Google Scholar 

  28. Cromwell WC, Otvos JD, Keyes MJ, Pencina MJ, Sullivan L, Vasan RS, et al. LDL particle number and risk of future cardiovascular disease in the framingham offspring study—implications for LDL management. J Clin Lipidol. 2007;1(6):583–92.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Otvos JD, Mora S, Shalaurova I, Greenland P, Mackey RH, Goff DC Jr. Clinical implications of discordance between low-density lipoprotein cholesterol and particle number. J Clin Lipidol. 2011;5(2):105–13.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Mora S, Buring JE, Ridker PM. Discordance of low-density lipoprotein (LDL) cholesterol with alternative LDL-related measures and future coronary events. Circulation. 2014;129(5):553–61.

    Article  CAS  PubMed  Google Scholar 

  31. Sniderman AD, St-Pierre AC, Cantin B, Dagenais GR, Despres JP, Lamarche B. Concordance/discordance between plasma apolipoprotein B levels and the cholesterol indexes of atherosclerotic risk. Am J Cardiol. 2003;91(10):1173–7.

    Article  CAS  PubMed  Google Scholar 

  32. Sniderman AD, Pencina M, Thanassoulis G. ApoB. Circ Res. 2019;124(10):1425–7.

    Google Scholar 

  33. Soedamah-Muthu SS, Chang YF, Otvos J, Evans RW, Orchard TJ, Pittsburgh Epidemiology of Diabetes Complications S. Lipoprotein subclass measurements by nuclear magnetic resonance spectroscopy improve the prediction of coronary artery disease in Type 1 diabetes. A prospective report from the Pittsburgh Epidemiology of Diabetes Complications Study. Diabetologia. 2003;46(5):674–82.

    Google Scholar 

  34. Sniderman AD, Williams K, McQueen MJ, Furberg CD. When is equal not equal? J Clin Lipidol. 2010;4(2):83–8.

    Article  PubMed  Google Scholar 

  35. Sniderman AD. Differential response of cholesterol and particle measures of atherogenic lipoproteins to LDL-lowering therapy: implications for clinical practice. J Clin Lipidol. 2008;2(1):36–42.

    Article  PubMed  Google Scholar 

  36. Sniderman AD, Islam S, Yusuf S, McQueen MJ. Discordance analysis of apolipoprotein B and non-high density lipoprotein cholesterol as markers of cardiovascular risk in the INTERHEART study. Atherosclerosis. 2012;225(2):444–9.

    Article  CAS  PubMed  Google Scholar 

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

    Google Scholar 

  38. Barter PJ, Ballantyne CM, Carmena R, Castro Cabezas M, Chapman MJ, Couture P, et al. Apo B versus cholesterol in estimating cardiovascular risk and in guiding therapy: report of the thirty-person/ten-country panel. J Intern Med. 2006;259(3):247–58.

    Article  CAS  PubMed  Google Scholar 

  39. Castelli WP. Cholesterol and lipids in the risk of coronary artery disease--the Framingham Heart Study. Can J Cardiol. 1988;4 Suppl A:5A-10A.

    Google Scholar 

  40. McQueen MJ, Hawken S, Wang X, Ounpuu S, Sniderman A, Probstfield J, et al. Lipids, lipoproteins, and apolipoproteins as risk markers of myocardial infarction in 52 countries (the INTERHEART study): a case-control study. Lancet (London, England). 2008;372(9634):224–33.

    Article  CAS  Google Scholar 

  41. Ridker PM, Rifai N, Cook NR, Bradwin G, Buring JE. Non-HDL cholesterol, apolipoproteins A-I and B100, standard lipid measures, lipid ratios, and CRP as risk factors for cardiovascular disease in women. JAMA. 2005;294(3):326–33.

    Article  CAS  PubMed  Google Scholar 

  42. Mora S, Otvos JD, Rifai N, Rosenson RS, Buring JE, Ridker PM. Lipoprotein particle profiles by nuclear magnetic resonance compared with standard lipids and apolipoproteins in predicting incident cardiovascular disease in women. Circulation. 2009;119(7):931–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Prospective Studies C, Lewington S, Whitlock G, Clarke R, Sherliker P, Emberson J, et al. Blood cholesterol and vascular mortality by age, sex, and blood pressure: a meta-analysis of individual data from 61 prospective studies with 55,000 vascular deaths. Lancet (London, England). 2007;370(9602):1829–39.

    Article  CAS  Google Scholar 

  44. Elshazly MB, Quispe R, Michos ED, Sniderman AD, Toth PP, Banach M, et al. Patient-level discordance in population percentiles of the total cholesterol to high-density lipoprotein cholesterol ratio in comparison with low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol: the very large database of lipids study (VLDL-2B). Circulation. 2015;132(8):667–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Elshazly MB, Nicholls SJ, Nissen SE, St John J, Martin SS, Jones SR, et al. Implications of total to high-density lipoprotein cholesterol ratio discordance with alternative lipid parameters for coronary atheroma progression and cardiovascular events. Am J Cardiol. 2016;118(5):647–55.

    Article  CAS  PubMed  Google Scholar 

  46. Quispe R, Elshazly MB, Zhao D, Toth PP, Puri R, Virani SS, et al. Total cholesterol/HDL-cholesterol ratio discordance with LDL-cholesterol and non-HDL-cholesterol and incidence of atherosclerotic cardiovascular disease in primary prevention: The ARIC study. Eur J Prev Cardiol. 2019:2047487319862401.

    Google Scholar 

  47. Mathews SC, Mallidi J, Kulkarni K, Toth PP, Jones SR. Achieving secondary prevention low-density lipoprotein particle concentration goals using lipoprotein cholesterol-based data. PloS one. 2012;7(3):e33692.

    Google Scholar 

  48. Gardner CD, Fortmann SP, Krauss RM. Association of small low-density lipoprotein particles with the incidence of coronary artery disease in men and women. JAMA. 1996;276(11):875–81.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  50. 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.

    Article  PubMed  Google Scholar 

  51. Schwartz GG, Olsson AG, Ezekowitz MD, Ganz P, Oliver MF, Waters D, et al. Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial. JAMA. 2001;285(13):1711–8.

    Article  CAS  PubMed  Google Scholar 

  52. 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. New England J Med. 2012;367(22):2089–99.

    Article  CAS  Google Scholar 

  53. Schwartz GG, Abt M, Bao W, DeMicco D, Kallend D, Miller M, et al. Fasting triglycerides predict recurrent ischemic events in patients with acute coronary syndrome treated with statins. J Am Coll Cardiol. 2015;65(21):2267–75.

    Article  CAS  PubMed  Google Scholar 

  54. Miller M, Cannon CP, Murphy SA, Qin J, Ray KK, Braunwald E, et al. Impact of triglyceride levels beyond low-density lipoprotein cholesterol after acute coronary syndrome in the PROVE IT-TIMI 22 trial. J Am Coll Cardiol. 2008;51(7):724–30.

    Article  CAS  PubMed  Google Scholar 

  55. Bhatt DL, Steg PG, Miller M, Brinton EA, Jacobson TA, Ketchum SB, et al. Cardiovascular risk reduction with Icosapent Ethyl for Hypertriglyceridemia. New England J Med. 2019;380(1):11–22.

    Article  CAS  Google Scholar 

  56. Group AS, Ginsberg HN, Elam MB, Lovato LC, Crouse JR, 3rd, Leiter LA, et al. Effects of combination lipid therapy in type 2 diabetes mellitus. New England J Med. 2010;362(17):1563–74.

    Google Scholar 

  57. Guyton JR, Slee AE, Anderson T, Fleg JL, Goldberg RB, Kashyap ML, et al. Relationship of lipoproteins to cardiovascular events: the AIM-HIGH Trial (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013;62(17):1580–4.

    Article  CAS  PubMed  Google Scholar 

  58. Nicholls SJ, Lincoff AM, Garcia M, Bash D, Ballantyne CM, Barter PJ, et al. Effect of high-dose omega-3 fatty acids vs corn oil on major adverse cardiovascular events in patients at high cardiovascular risk: the STRENGTH randomized clinical trial. JAMA. 2020;324(22):2268–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Gaudet D, Alexander VJ, Baker BF, Brisson D, Tremblay K, Singleton W, et al. Antisense inhibition of apolipoprotein C-III in patients with hypertriglyceridemia. New England J Med. 2015;373(5):438–47.

    Article  CAS  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  61. 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.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  Google Scholar 

  63. Crosby J, Peloso GM, Auer PL, Crosslin DR, Stitziel NO, Lange LA, et al. Loss-of-function mutations in APOC3, triglycerides, and coronary disease. New England J Med. 2014;371(1):22–31.

    Article  CAS  Google Scholar 

  64. Elshazly MB, Mani P, Nissen S, Brennan DM, Clark D, Martin S, et al. Remnant cholesterol, coronary atheroma progression and clinical events in statin-treated patients with coronary artery disease. Eur J Prev Cardiol. 2019:2047487319887578.

    Google Scholar 

  65. Varbo A, Nordestgaard BG. Remnant lipoproteins. Curr Opin Lipidol. 2017;28(4):300–7.

    Article  CAS  PubMed  Google Scholar 

  66. Faridi KF, Quispe R, Martin SS, Hendrani AD, Joshi PH, Brinton EA, et al. Comparing different assessments of remnant lipoprotein cholesterol: the very large database of lipids. J Clin Lipidol. 2019;13(4):634–44.

    Article  PubMed  Google Scholar 

  67. Spence JD, Koschinsky M. Mechanisms of lipoprotein(a) pathogenicity: prothrombotic, proatherosclerotic, or both? Arterioscler Thromb Vasc Biol. 2012;32(7):1550–1.

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  69. Nordestgaard BG, Langsted A. Lipoprotein (a) as a cause of cardiovascular disease: insights from epidemiology, genetics, and biology. J Lipid Res. 2016;57(11):1953–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  72. O’Donoghue ML, Fazio S, Giugliano RP, Stroes ESG, Kanevsky E, Gouni-Berthold I, et al. Lipoprotein(a), PCSK9 inhibition, and cardiovascular risk. Circulation. 2019;139(12):1483–92.

    Article  CAS  PubMed  Google Scholar 

  73. Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, Tardif JC, Baum SJ, Steinhagen-Thiessen E, et al. Lipoprotein(a) reduction in persons with cardiovascular disease. New England J Med. 2020;382(3):244–55.

    Article  CAS  Google Scholar 

  74. Tsimikas S. A test in context: lipoprotein(a): diagnosis, prognosis, controversies, and emerging therapies. J Am Coll Cardiol. 2017;69(6):692–711.

    Article  CAS  PubMed  Google Scholar 

  75. Albers JJ, Slee A, O’Brien KD, Robinson JG, Kashyap ML, Kwiterovich PO Jr, et al. Relationship of apolipoproteins A-1 and B, and lipoprotein(a) to cardiovascular outcomes: the AIM-HIGH trial (Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglyceride and Impact on Global Health Outcomes). J Am Coll Cardiol. 2013;62(17):1575–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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

    Article  PubMed  Google Scholar 

  77. Verbeek R, Sandhu MS, Hovingh GK, Sjouke B, Wareham NJ, Zwinderman AH, et al. Lipoprotein(a) improves cardiovascular risk prediction based on established risk algorithms. J Am Coll Cardiol. 2017;69(11):1513–5.

    Article  CAS  PubMed  Google Scholar 

  78. Kamstrup PR, Tybjaerg-Hansen A, Nordestgaard BG. Extreme lipoprotein(a) levels and improved cardiovascular risk prediction. J Am Coll Cardiol. 2013;61(11):1146–56.

    Article  CAS  PubMed  Google Scholar 

  79. Fogacci F, Cicero AF, D’Addato S, D’Agostini L, Rosticci M, Giovannini M, et al. Serum lipoprotein(a) level as long-term predictor of cardiovascular mortality in a large sample of subjects in primary cardiovascular prevention: data from the Brisighella heart study. Eur J Intern Med. 2017;37:49–55.

    Article  CAS  PubMed  Google Scholar 

  80. Xie H, Chen L, Liu H, Cui Y, Zhang Z, Cui L. Long-term prognostic value of lipoprotein(a) in symptomatic patients with nonobstructive coronary artery disease. Am J Cardiol. 2017;119(7):945–50.

    Article  CAS  PubMed  Google Scholar 

  81. Suwa S, Ogita M, Miyauchi K, Sonoda T, Konishi H, Tsuboi S, et al. Impact of lipoprotein (a) on long-term outcomes in patients with coronary artery disease treated with statin after a first percutaneous coronary intervention. J Atheroscler Thromb. 2017;24(11):1125–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Boden WE, Sidhu MS, Toth PP. The therapeutic role of niacin in dyslipidemia management. J Cardiovasc Pharmacol Ther. 2014;19(2):141–58.

    Google Scholar 

  83. 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(7):619–27.

    Article  PubMed  PubMed Central  Google Scholar 

  84. Wilson DP, Jacobson TA, Jones PH, Koschinsky ML, McNeal CJ, Nordestgaard BG, et al. Use of Lipoprotein(a) in clinical practice: a biomarker whose time has come. A scientific statement from the National Lipid Association. J Clin Lipidol. 2019;13(3):374–92.

    Google Scholar 

  85. Sharma S, Jackson PG, Makan J. Cardiac troponins. J Clin Pathol. 2004;57(10):1025–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Apple FS, Collinson PO, Biomarkers ITFoCAoC. Analytical characteristics of high-sensitivity cardiac troponin assays. Clin Chem. 2012;58(1):54–61.

    Google Scholar 

  87. Iwanaga Y, Nishi I, Furuichi S, Noguchi T, Sase K, Kihara Y, et al. B-type natriuretic peptide strongly reflects diastolic wall stress in patients with chronic heart failure: comparison between systolic and diastolic heart failure. J Am Coll Cardiol. 2006;47(4):742–8.

    Article  CAS  PubMed  Google Scholar 

  88. Brunner-La Rocca HP, Kaye DM, Woods RL, Hastings J, Esler MD. Effects of intravenous brain natriuretic peptide on regional sympathetic activity in patients with chronic heart failure as compared with healthy control subjects. J Am Coll Cardiol. 2001;37(5):1221–7.

    Article  CAS  PubMed  Google Scholar 

  89. Michos ED, Wilson LM, Yeh HC, Berger Z, Suarez-Cuervo C, Stacy SR, et al. Prognostic value of cardiac troponin in patients with chronic kidney disease without suspected acute coronary syndrome: a systematic review and meta-analysis. Ann Intern Med. 2014;161(7):491–501.

    Article  PubMed  Google Scholar 

  90. McCullough PA, Duc P, Omland T, McCord J, Nowak RM, Hollander JE, et al. B-type natriuretic peptide and renal function in the diagnosis of heart failure: an analysis from the breathing not properly multinational study. Am J Kidney Dis. 2003;41(3):571–9.

    Article  CAS  PubMed  Google Scholar 

  91. Ying W, Zhao D, Ouyang P, Subramanya V, Vaidya D, Ndumele CE, et al. Sex hormones and change in N-terminal Pro-B-type natriuretic peptide levels: the multi-ethnic study of atherosclerosis. J Clin Endocrinol Metabol. 2018;103(11):4304–14.

    Article  Google Scholar 

  92. Gore MO, Seliger SL, Defilippi CR, Nambi V, Christenson RH, Hashim IA, et al. Age- and sex-dependent upper reference limits for the high-sensitivity cardiac troponin T assay. J Am Coll Cardiol. 2014;63(14):1441–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Lee KK, Ferry AV, Anand A, Strachan FE, Chapman AR, Kimenai DM, et al. Sex-specific thresholds of high-sensitivity troponin in patients with suspected acute coronary syndrome. J Am Coll Cardiol. 2019;74(16):2032–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Keyzer JM, Hoffmann JJ, Ringoir L, Nabbe KC, Widdershoven JW, Pop VJ. Age- and gender-specific brain natriuretic peptide (BNP) reference ranges in primary care. Clin Chem Lab Med. 2014;52(9):1341–6.

    Article  CAS  PubMed  Google Scholar 

  95. Sherwood MW, Kristin Newby L. High-sensitivity troponin assays: evidence, indications, and reasonable use. J Am Heart Assoc. 2014;3(1):e000403.

    Google Scholar 

  96. Tate JR, Bunk DM, Christenson RH, Katrukha A, Noble JE, Porter RA, et al. Standardisation of cardiac troponin I measurement: past and present. Pathology. 2010;42(5):402–8.

    Article  CAS  PubMed  Google Scholar 

  97. Clerico A, Zaninotto M, Prontera C, Giovannini S, Ndreu R, Franzini M, et al. State of the art of BNP and NT-proBNP immunoassays: the CardioOrmoCheck study. Clin Chim Acta; Int J Clin Chem. 2012;414:112–9.

    Google Scholar 

  98. de Lemos JA, Drazner MH, Omland T, Ayers CR, Khera A, Rohatgi A, et al. Association of troponin T detected with a highly sensitive assay and cardiac structure and mortality risk in the general population. JAMA. 2010;304(22):2503–12.

    Article  PubMed  PubMed Central  Google Scholar 

  99. Martin Raymondi D, Garcia H, Alvarez I, Hernandez L, Molinero JP, Villamandos V. TUSARC: prognostic value of high-sensitivity cardiac troponin T assay in asymptomatic patients with high cardiovascular risk. Am J Med. 2019;132(5):631–8.

    Article  CAS  PubMed  Google Scholar 

  100. Ford I, Shah AS, Zhang R, McAllister DA, Strachan FE, Caslake M, et al. High-sensitivity cardiac troponin, statin therapy, and risk of coronary heart disease. J Am Coll Cardiol. 2016;68(25):2719–28.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  101. Jia X, Sun W, Hoogeveen RC, Nambi V, Matsushita K, Folsom AR, et al. High-sensitivity troponin i and incident coronary events, stroke, heart failure hospitalization, and mortality in the ARIC study. Circulation. 2019;139(23):2642–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Lan NSR, Bell DA, McCaul KA, Vasikaran SD, Yeap BB, Norman PE, et al. High-sensitivity cardiac troponin i improves cardiovascular risk prediction in older men: HIMS (The Health in Men Study). J Am Heart Assoc. 2019;8(5):e011818.

    Google Scholar 

  103. McEvoy JW, Chen Y, Nambi V, Ballantyne CM, Sharrett AR, Appel LJ, et al. High-sensitivity cardiac troponin T and risk of hypertension. Circulation. 2015;132(9):825–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  104. Pandey A, Patel KV, Vongpatanasin W, Ayers C, Berry JD, Mentz RJ, et al. Incorporation of biomarkers into risk assessment for allocation of antihypertensive medication according to the 2017 ACC/AHA high blood pressure guideline: a pooled cohort analysis. Circulation. 2019;140(25):2076–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  105. Kang DH, Park SJ, Lee SA, Lee S, Kim DH, Kim HK, et al. Early surgery or conservative care for asymptomatic aortic stenosis. New England J Med. 2020;382(2):111–9.

    Article  Google Scholar 

  106. Baumgartner H, Falk V, Bax JJ, De Bonis M, Hamm C, Holm PJ, et al. 2017 ESC/EACTS guidelines for the management of valvular heart disease. Eur Heart J. 2017;38(36):2739–91.

    Article  PubMed  Google Scholar 

  107. McCarthy CP, Donnellan E, Phelan D, Griffin BP, Enriquez-Sarano M, McEvoy JW. High sensitivity troponin and valvular heart disease. Trends Cardiovasc Med. 2017;27(5):326–33.

    Article  CAS  PubMed  Google Scholar 

  108. Chin CW, Shah AS, McAllister DA, Joanna Cowell S, Alam S, Langrish JP, et al. High-sensitivity troponin I concentrations are a marker of an advanced hypertrophic response and adverse outcomes in patients with aortic stenosis. Eur Heart J. 2014;35(34):2312–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  109. Ferrer-Sistach E, Lupon J, Cediel G, Teis A, Gual F, Serrano S, et al. High-sensitivity troponin T in asymptomatic severe aortic stenosis. Biomarkers. 2019;24(4):334–40.

    Article  CAS  PubMed  Google Scholar 

  110. Chin CW, Messika-Zeitoun D, Shah AS, Lefevre G, Bailleul S, Yeung EN, et al. A clinical risk score of myocardial fibrosis predicts adverse outcomes in aortic stenosis. Eur Heart J. 2016;37(8):713–23.

    Article  PubMed  Google Scholar 

  111. Velagaleti RS, Gona P, Larson MG, Wang TJ, Levy D, Benjamin EJ, et al. Multimarker approach for the prediction of heart failure incidence in the community. Circulation. 2010;122(17):1700–6.

    Article  PubMed  PubMed Central  Google Scholar 

  112. Saunders JT, Nambi V, de Lemos JA, Chambless LE, Virani SS, Boerwinkle E, et al. Cardiac troponin T measured by a highly sensitive assay predicts coronary heart disease, heart failure, and mortality in the atherosclerosis risk in communities study. Circulation. 2011;123(13):1367–76.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  113. Ledwidge M, Gallagher J, Conlon C, Tallon E, O’Connell E, Dawkins I, et al. Natriuretic peptide-based screening and collaborative care for heart failure: the STOP-HF randomized trial. JAMA. 2013;310(1):66–74.

    Article  CAS  PubMed  Google Scholar 

  114. McGrady M, Reid CM, Shiel L, Wolfe R, Boffa U, Liew D, et al. NT-proB natriuretic peptide, risk factors and asymptomatic left ventricular dysfunction: results of the SCReening evaluation of the evolution of new heart failure study (SCREEN-HF). Int J Cardiol. 2013;169(2):133–8.

    Article  PubMed  Google Scholar 

  115. Chow SL, Maisel AS, Anand I, Bozkurt B, de Boer RA, Felker GM, et al. Role of biomarkers for the prevention, assessment, and management of heart failure: a scientific statement from the american heart association. Circulation. 2017;135(22):e1054–91.

    Article  CAS  PubMed  Google Scholar 

  116. Libby P. Interleukin-1 beta as a target for atherosclerosis therapy: biological basis of CANTOS and beyond. J Am Coll Cardiol. 2017;70(18):2278–89.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. Esmon CT. Inflammation and thrombosis. J Thrombosis Haemostasis: JTH. 2003;1(7):1343–8.

    Article  CAS  Google Scholar 

  118. Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. New England J Med. 2000;342(12):836–43.

    Article  CAS  Google Scholar 

  119. Schonbeck U, Libby P. Inflammation, immunity, and HMG-CoA reductase inhibitors: statins as antiinflammatory agents? Circulation. 2004;109(21 Suppl 1):II18–26.

    Google Scholar 

  120. Labos C, Brophy JM, Smith GD, Sniderman AD, Thanassoulis G. Evaluation of the pleiotropic effects of statins: a reanalysis of the randomized trial evidence using egger regression-brief report. Arterioscler Thromb Vasc Biol. 2018;38(1):262–5.

    Article  CAS  PubMed  Google Scholar 

  121. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein. N Engl J Med. 2008;359(21):2195–207.

    Article  CAS  PubMed  Google Scholar 

  122. Ridker PM, Everett BM, Thuren T, MacFadyen JG, Chang WH, Ballantyne C, et al. Antiinflammatory therapy with Canakinumab for atherosclerotic disease. New England J Med. 2017;377(12):1119–31.

    Article  CAS  Google Scholar 

  123. Duprez DA, Otvos J, Sanchez OA, Mackey RH, Tracy R, Jacobs DR Jr. Comparison of the predictive value of GlycA and other biomarkers of inflammation for total death, incident cardiovascular events, noncardiovascular and noncancer inflammatory-related events, and total cancer events. Clin Chem. 2016;62(7):1020–31.

    Article  CAS  PubMed  Google Scholar 

  124. Quispe R, Michos ED, Martin SS, Puri R, Toth PP, Al Suwaidi J, et al. High-sensitivity C-reactive protein discordance with atherogenic lipid measures and incidence of atherosclerotic cardiovascular disease in primary prevention: the ARIC study. J Am Heart Assoc. 2020;9(3):e013600.

    Google Scholar 

  125. 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. 2007;297(6):611–9.

    Article  CAS  PubMed  Google Scholar 

  126. 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(22):2243–51, 4p following 51.

    Google Scholar 

  127. Michos ED, Martin SS, Blumenthal RS. Bringing back targets to “IMPROVE” atherosclerotic cardiovascular disease outcomes: the duel for dual goals; are two targets better than one? Circulation. 2015;132(13):1218–20.

    Article  PubMed  Google Scholar 

  128. Michos ED, Blumenthal RS. Treatment concentration of high-sensitivity C-reactive protein. Lancet (London, England). 2018;391(10118):287–9.

    Article  Google Scholar 

  129. Cardoso R, Kaul S, Okada DR, Blumenthal RS, Michos ED. A deeper dive into the CANTOS “Responders” Substudy. Mayo Clin Proc. 2018;93(7):830–3.

    Article  PubMed  Google Scholar 

  130. Ridker PM, Danielson E, Fonseca FA, Genest J, Gotto AM Jr, Kastelein JJ, et al. Reduction in C-reactive protein and LDL cholesterol and cardiovascular event rates after initiation of rosuvastatin: a prospective study of the JUPITER trial. Lancet (London, England). 2009;373(9670):1175–82.

    Article  CAS  Google Scholar 

  131. Ridker PM, Morrow DA, Rose LM, Rifai N, Cannon CP, Braunwald E. Relative efficacy of atorvastatin 80 mg and pravastatin 40 mg in achieving the dual goals of low-density lipoprotein cholesterol <70 mg/dl and C-reactive protein <2 mg/l: an analysis of the PROVE-IT TIMI-22 trial. J Am Coll Cardiol. 2005;45(10):1644–8.

    Article  CAS  PubMed  Google Scholar 

  132. Bohula EA, Giugliano RP, Cannon CP, Zhou J, Murphy SA, White JA, et al. Achievement of dual low-density lipoprotein cholesterol and high-sensitivity C-reactive protein targets more frequent with the addition of ezetimibe to simvastatin and associated with better outcomes in IMPROVE-IT. Circulation. 2015;132(13):1224–33.

    Article  CAS  PubMed  Google Scholar 

  133. Ridker PM, MacFadyen JG, Everett BM, Libby P, Thuren T, Glynn RJ, et al. Relationship of C-reactive protein reduction to cardiovascular event reduction following treatment with canakinumab: a secondary analysis from the CANTOS randomised controlled trial. Lancet (London, England). 2018;391(10118):319–28.

    Article  CAS  Google Scholar 

  134. Otvos JD, Shalaurova I, Wolak-Dinsmore J, Connelly MA, Mackey RH, Stein JH, et al. GlycA: a composite nuclear magnetic resonance biomarker of systemic inflammation. Clin Chem. 2015;61(5):714–23.

    Article  CAS  PubMed  Google Scholar 

  135. Akinkuolie AO, Buring JE, Ridker PM, Mora S. A novel protein glycan biomarker and future cardiovascular disease events. J Am Heart Assoc. 2014;3(5):e001221.

    Google Scholar 

  136. Akinkuolie AO, Glynn RJ, Padmanabhan L, Ridker PM, Mora S. Circulating N-linked glycoprotein side-Chain biomarker, rosuvastatin therapy, and incident cardiovascular disease: an analysis from the JUPITER trial. J Am Heart Assoc. 2016;5(7).

    Google Scholar 

  137. Fashanu OE, Oyenuga AO, Zhao D, Tibuakuu M, Mora S, Otvos JD, et al. GlycA, a novel inflammatory marker and its association with peripheral arterial disease and carotid plaque: the multi-ethnic study of atherosclerosis. Angiology. 2019;70(8):737–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  138. Gruppen EG, Riphagen IJ, Connelly MA, Otvos JD, Bakker SJ, Dullaart RP. GlycA, a Pro-inflammatory glycoprotein biomarker, and incident cardiovascular disease: relationship with C-reactive protein and renal function. PloS one. 2015;10(9):e0139057.

    Google Scholar 

  139. Lawler PR, Akinkuolie AO, Chandler PD, Moorthy MV, Vandenburgh MJ, Schaumberg DA, et al. Circulating N-linked glycoprotein acetyls and longitudinal mortality risk. Circ Res. 2016;118(7):1106–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  140. Jang S, Ogunmoroti O, Ndumele CE, Zhao D, Rao VN, Fashanu OE, et al. Association of the novel inflammatory marker GlycA and incident heart failure and its subtypes of preserved and reduced ejection fraction: the multi-ethnic study of atherosclerosis. Circ Heart Fail. 2020;13(8):e007067.

    Google Scholar 

  141. Benson EA, Tibuakuu M, Zhao D, Akinkuolie AO, Otvos JD, Duprez DA, et al. Associations of ideal cardiovascular health with GlycA, a novel inflammatory marker: the Multi-Ethnic Study of Atherosclerosis. Clin Cardiol. 2018;41(11):1439–45.

    Article  PubMed  PubMed Central  Google Scholar 

  142. Tibuakuu M, Fashanu OE, Zhao D, Otvos JD, Brown TT, Haberlen SA, et al. GlycA, a novel inflammatory marker, is associated with subclinical coronary disease. AIDS. 2019;33(3):547–57.

    Article  CAS  PubMed  Google Scholar 

  143. Joshi AA, Lerman JB, Aberra TM, Afshar M, Teague HL, Rodante JA, et al. GlycA is a novel biomarker of inflammation and subclinical cardiovascular disease in psoriasis. Circ Res. 2016;119(11):1242–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  144. Ezeigwe A, Fashanu OE, Zhao D, Budoff MJ, Otvos JD, Thomas IC, et al. The novel inflammatory marker GlycA and the prevalence and progression of valvular and thoracic aortic calcification: the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2019;282:91–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  145. Knight B, Xue Y, Maisel AS, de Boer RA. Galectin 3: newest marker of HF outcomes. Curr Emerg Hosp Med Rep. 2014;2(2):112–9.

    Google Scholar 

  146. Yu L, Ruifrok WP, Meissner M, Bos EM, van Goor H, Sanjabi B, et al. Genetic and pharmacological inhibition of galectin-3 prevents cardiac remodeling by interfering with myocardial fibrogenesis. Circ Heart Fail. 2013;6(1):107–17.

    Article  CAS  PubMed  Google Scholar 

  147. de Boer RA, van Veldhuisen DJ, Gansevoort RT, Muller Kobold AC, van Gilst WH, Hillege HL, et al. The fibrosis marker galectin-3 and outcome in the general population. J Intern Med. 2012;272(1):55–64.

    Article  PubMed  CAS  Google Scholar 

  148. McEvoy JW, Chen Y, Halushka MK, Christenson E, Ballantyne CM, Blumenthal RS, et al. Galectin-3 and risk of heart failure and death in blacks and whites. J Am Heart Assoc. 2016;5(5).

    Google Scholar 

  149. Maiolino G, Bisogni V, Rossitto G, Rossi GP. Lipoprotein-associated phospholipase A2 prognostic role in atherosclerotic complications. World J Cardiol. 2015;7(10):609–20.

    Article  PubMed  PubMed Central  Google Scholar 

  150. Ballantyne CM, Hoogeveen RC, Bang H, Coresh J, Folsom AR, Heiss G, et al. Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) study. Circulation. 2004;109(7):837–42.

    Article  CAS  PubMed  Google Scholar 

  151. Tibuakuu M, Kianoush S, DeFilippis AP, McEvoy JW, Zhao D, Guallar E, et al. Usefulness of lipoprotein-associated phospholipase A2 activity and C-reactive protein in identifying high-risk smokers for atherosclerotic cardiovascular disease (from the Atherosclerosis Risk in Communities Study). Am J Cardiol. 2018;121(9):1056–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Ridker PM, MacFadyen JG, Wolfert RL, Koenig W. Relationship of lipoprotein-associated phospholipase A(2) mass and activity with incident vascular events among primary prevention patients allocated to placebo or to statin therapy: an analysis from the JUPITER trial. Clin Chem. 2012;58(5):877–86.

    Article  CAS  PubMed  Google Scholar 

  153. Davidson MH, Corson MA, Alberts MJ, Anderson JL, Gorelick PB, Jones PH, et al. Consensus panel recommendation for incorporating lipoprotein-associated phospholipase A2 testing into cardiovascular disease risk assessment guidelines. Am J Cardiol. 2008;101(12A):51F-F57.

    Article  CAS  PubMed  Google Scholar 

  154. Wang J, Tan GJ, Han LN, Bai YY, He M, Liu HB. Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol. 2017;14(2):135–50.

    CAS  PubMed  PubMed Central  Google Scholar 

  155. Investigators S, White HD, Held C, Stewart R, Tarka E, Brown R, et al. Darapladib for preventing ischemic events in stable coronary heart disease. New England J Med. 2014;370(18):1702–11.

    Article  CAS  Google Scholar 

  156. Forte G, Minieri M, Cossa P, Antenucci D, Sala M, Gnocchi V, et al. Hepatocyte growth factor effects on mesenchymal stem cells: proliferation, migration, and differentiation. Stem Cells. 2006;24(1):23–33.

    Article  CAS  PubMed  Google Scholar 

  157. Rong S-l, Wang X-l, Wang Y-c, Wu H, Zhou X-d, Wang Z-k, et al. Anti-inflammatory activities of hepatocyte growth factor in post-ischemic heart failure. Acta Pharmacol Sinica. 2018;39(10):1613–21.

    Google Scholar 

  158. Bielinski SJ, Berardi C, Decker PA, Larson NB, Bell EJ, Pankow JS, et al. Hepatocyte growth factor demonstrates racial heterogeneity as a biomarker for coronary heart disease. Heart (British Cardiac Society). 2017;103(15):1185–93.

    CAS  Google Scholar 

  159. Morishita R, Aoki M, Yo Y, Ogihara T. Hepatocyte growth factor as cardiovascular hormone: role of HGF in the pathogenesis of cardiovascular disease. Endocr J. 2002;49(3):273–84.

    Article  CAS  PubMed  Google Scholar 

  160. Rajpathak Swapnil N, Wang T, Wassertheil-Smoller S, Strickler Howard D, Kaplan Robert C, McGinn Aileen P, et al. Hepatocyte growth factor and the risk of ischemic stroke developing among postmenopausal women. Stroke. 2010;41(5):857–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  161. Bell EJ, Larson NB, Decker PA, Pankow JS, Tsai MY, Hanson NQ, et al. Hepatocyte growth factor is positively associated with risk of stroke: the MESA (Multi-Ethnic Study of Atherosclerosis). Stroke. 2016;47(11):2689–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  162. Decker PA, Larson NB, Bell EJ, Pankow JS, Hanson NQ, Wassel CL, et al. Increased hepatocyte growth factor levels over 2 years are associated with coronary heart disease: the Multi-Ethnic Study of Atherosclerosis (MESA). Am Heart J. 2019;213:30–4.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Bell EJ, Decker PA, Tsai MY, Pankow JS, Hanson NQ, Wassel CL, et al. Hepatocyte growth factor is associated with progression of atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2018;272:162–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  164. Ferraro RA, Ogunmoroti O, Zhao D, Ndumele CE, Rao V, Pandey A, et al. Abstract 264: the association of hepatocyte growth factor with incident heart failure and its subtypes: the Multi-Ethnic Study of Atherosclerosis. Arterioscl. Thrombosis Vascul Biol. 2020;40(Suppl_1):A264-A.

    Google Scholar 

  165. Ferraro RA, Ogunmoroti O, Zhao D, Ndumele CE, Lima JAC, Subramanya V, et al. Abstract 13300: hepatocyte growth factor and 10-year change in left ventricular structure: the Multi-Ethnic Study of Atherosclerosis. Circulation. 2020;142(Suppl_3):A13300-A.

    Google Scholar 

  166. Rychli K, Richter B, Hohensinner PJ, Mahdy Ali K, Neuhold S, Zorn G, et al. Hepatocyte growth factor is a strong predictor of mortality in patients with advanced heart failure. Heart. 2011;97(14):1158.

    Article  PubMed  Google Scholar 

  167. Bancks MP, Bielinski SJ, Decker PA, Hanson NQ, Larson NB, Sicotte H, et al. Circulating level of hepatocyte growth factor predicts incidence of type 2 diabetes mellitus: the Multi-Ethnic Study of Atherosclerosis (MESA). Metabolism. 2016;65(3):64–72.

    Article  CAS  PubMed  Google Scholar 

  168. Fibrinogen Studies C, Danesh J, Lewington S, Thompson SG, Lowe GD, Collins R, et al. Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis. JAMA. 2005;294(14):1799–809.

    Google Scholar 

  169. Perk J, De Backer G, Gohlke H, Graham I, Reiner Z, Verschuren M, et al. European guidelines on cardiovascular disease prevention in clinical practice (version 2012). The fifth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of nine societies and by invited experts). Eur Heart J. 2012;33(13):1635–701.

    Google Scholar 

  170. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, et al. 2016 European guidelines on cardiovascular disease prevention in clinical practice: the sixth joint task force of the European society of cardiology and other societies on cardiovascular disease prevention in clinical practice (constituted by representatives of 10 societies and by invited experts) developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Atherosclerosis. 2016;252:207–74.

    Article  CAS  PubMed  Google Scholar 

  171. Lau WB, Ohashi K, Wang Y, Ogawa H, Murohara T, Ma XL, et al. Role of adipokines in cardiovascular disease. Circ J. 2017;81(7):920–8.

    Article  CAS  PubMed  Google Scholar 

  172. Dutheil F, Gordon BA, Naughton G, Crendal E, Courteix D, Chaplais E, et al. Cardiovascular risk of adipokines: a review. J Int Med Res. 2018;46(6):2082–95.

    Article  CAS  PubMed  Google Scholar 

  173. Wannamethee SG, Lowe GD, Rumley A, Cherry L, Whincup PH, Sattar N. Adipokines and risk of type 2 diabetes in older men. Diabetes Care. 2007;30(5):1200–5.

    Article  CAS  PubMed  Google Scholar 

  174. Muse ED, Feldman DI, Blaha MJ, Dardari ZA, Blumenthal RS, Budoff MJ, et al. The association of resistin with cardiovascular disease in the Multi-Ethnic Study of Atherosclerosis. Atherosclerosis. 2015;239(1):101–8.

    Article  CAS  PubMed  Google Scholar 

  175. Pischon T, Girman CJ, Hotamisligil GS, Rifai N, Hu FB, Rimm EB. Plasma adiponectin levels and risk of myocardial infarction in men. JAMA. 2004;291(14):1730–7.

    Article  CAS  PubMed  Google Scholar 

  176. Landecho MF, Tuero C, Valenti V, Bilbao I, de la Higuera M, Fruhbeck G. Relevance of Leptin and other Adipokines in obesity-associated cardiovascular risk. Nutrients. 2019;11(11).

    Google Scholar 

  177. Martin SS, Blaha MJ, Muse ED, Qasim AN, Reilly MP, Blumenthal RS, et al. Leptin and incident cardiovascular disease: the Multi-ethnic Study of Atherosclerosis (MESA). Atherosclerosis. 2015;239(1):67–72.

    Article  CAS  PubMed  Google Scholar 

  178. Fasshauer M, Bluher M, Stumvoll M. Adipokines in gestational diabetes. Lancet Diabetes Endocrinol. 2014;2(6):488–99.

    Article  CAS  PubMed  Google Scholar 

  179. Rodriguez CP, O. O, Quispe R, Osibogun OI, Ndumele CE, Echouffo Tcheugui JB, et al. Abstract 13525: The association between multiparity and Adipokine levels: the Multi-Ethnic Study of Atherosclerosis (MESA). Circulation. 2020;142(Suppl_3):A13525-A.

    Google Scholar 

  180. Jensen MK, Bertoia ML, Cahill LE, Agarwal I, Rimm EB, Mukamal KJ. Novel metabolic biomarkers of cardiovascular disease. Nat Rev Endocrinol. 2014;10(11):659–72.

    Article  CAS  PubMed  Google Scholar 

  181. Sattar N, Wannamethee G, Sarwar N, Tchernova J, Cherry L, Wallace AM, et al. Adiponectin and coronary heart disease: a prospective study and meta-analysis. Circulation. 2006;114(7):623–9.

    Article  CAS  PubMed  Google Scholar 

  182. Barouch LA, Berkowitz DE, Harrison RW, O’Donnell CP, Hare JM. Disruption of leptin signaling contributes to cardiac hypertrophy independently of body weight in mice. Circulation. 2003;108(6):754–9.

    Article  CAS  PubMed  Google Scholar 

  183. Ho JE, Lyass A, Courchesne P, Chen G, Liu C, Yin X, et al. Protein biomarkers of cardiovascular disease and mortality in the community. J Am Heart Assoc. 2018;7(14).

    Google Scholar 

  184. Acquarone E, Monacelli F, Borghi R, Nencioni A, Odetti P. Resistin: a reappraisal. Mech Ageing Dev. 2019;178:46–63.

    Article  CAS  PubMed  Google Scholar 

  185. Honigberg MC, Zekavat SM, Aragam K, Finneran P, Klarin D, Bhatt DL, et al. Association of premature natural and surgical menopause with incident cardiovascular disease. Jama. 2019.

    Google Scholar 

  186. Zhao D, Guallar E, Ouyang P, Subramanya V, Vaidya D, Ndumele CE, et al. Endogenous sex hormones and incident cardiovascular disease in post-menopausal women. J Am Coll Cardiol. 2018;71(22):2555–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  187. Subramanya V, Zhao D, Ouyang P, Lima JA, Vaidya D, Ndumele CE, et al. Sex hormone levels and change in left ventricular structure among men and post-menopausal women: the Multi-Ethnic Study of Atherosclerosis (MESA). Maturitas. 2018;108:37–44.

    Article  CAS  PubMed  Google Scholar 

  188. Subramanya V, Ambale-Venkatesh B, Ohyama Y, Zhao D, Nwabuo CC, Post WS, et al. Relation of sex hormone levels with prevalent and 10-year change in aortic distensibility assessed by MRI: the multi-ethnic study of atherosclerosis. Am J Hypertens. 2018;31(7):774–83.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  189. Subramanya V, Zhao D, Ouyang P, Ying W, Vaidya D, Ndumele CE, et al. Association of endogenous sex hormone levels with coronary artery calcium progression among post-menopausal women in the Multi-Ethnic Study of Atherosclerosis (MESA). J Cardiovascul Comp Tomography. 2019;13(1):41–7.

    Article  Google Scholar 

  190. Mathews L, Subramanya V, Zhao D, Ouyang P, Vaidya D, Guallar E, et al. Endogenous sex hormones and endothelial function in postmenopausal women and men: the multi-ethnic study of atherosclerosis. J Women’s Health (2002). 2019;28(7):900–9.

    Google Scholar 

  191. Jia X, Sun C, Tang O, Gorlov I, Nambi V, Virani SS, et al. Plasma dehydroepiandrosterone sulfate and cardiovascular disease risk in older men and women. J Clin Endocrinol Metabol. 2020;105(12).

    Google Scholar 

  192. Akishita M, Hashimoto M, Ohike Y, Ogawa S, Iijima K, Eto M, et al. Low testosterone level as a predictor of cardiovascular events in Japanese men with coronary risk factors. Atherosclerosis. 2010;210(1):232–6.

    Article  CAS  PubMed  Google Scholar 

  193. Menke A, Guallar E, Rohrmann S, Nelson WG, Rifai N, Kanarek N, et al. Sex steroid hormone concentrations and risk of death in US men. Am J Epidemiol. 2010;171(5):583–92.

    Article  PubMed  PubMed Central  Google Scholar 

  194. DeFilippis AP, Young R, McEvoy JW, Michos ED, Sandfort V, Kronmal RA, et al. Risk score overestimation: the impact of individual cardiovascular risk factors and preventive therapies on the performance of the American heart association-American college of cardiology-atherosclerotic cardiovascular disease risk score in a modern multi-ethnic cohort. Eur Heart J. 2017;38(8):598–608.

    CAS  PubMed  Google Scholar 

  195. Yeboah J, McClelland RL, Polonsky TS, Burke GL, Sibley CT, O’Leary D, et al. Comparison of novel risk markers for improvement in cardiovascular risk assessment in intermediate-risk individuals. JAMA. 2012;308(8):788–95.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  196. 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;67(2):139–47.

    Article  PubMed  PubMed Central  Google Scholar 

  197. 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;133(9):849–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  198. Michos ED, Blaha MJ, Blumenthal RS. Use of the coronary artery calcium score in discussion of initiation of statin therapy in primary prevention. Mayo Clin Proc. 2017;92(12):1831–41.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Ciccarone Center for Cardiovascular Disease Prevention, Johns Hopkins University School of Medicine, Baltimore, MD, USA

    Renato Quispe & Thomas Das

  2. Ciccarone Center for the Prevention of Cardiovascular Disease, Johns Hopkins Hospital, 600 N. Wolfe Street, Blalock 524-B, Baltimore, MD, 21287, USA

    Erin D. Michos

Authors
  1. Renato Quispe
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Thomas Das
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Erin D. Michos
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Erin D. Michos .

Editor information

Editors and Affiliations

  1. Digital Health Innovation Laboratory, Ciccarone Center for the Prevention of Cardiovascular Disease, Division of Cardiology, Department of Medicine, Johns Hopkins University School of Medicine, Johns Hopkins Hospital, Baltimore, MD, USA

    Seth S. Martin

Rights and permissions

Reprints and permissions

Copyright information

© 2021 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Quispe, R., Das, T., Michos, E.D. (2021). Biomarkers. In: Martin, S.S. (eds) Precision Medicine in Cardiovascular Disease Prevention. Springer, Cham. https://doi.org/10.1007/978-3-030-75055-8_2

Download citation

  • DOI: https://doi.org/10.1007/978-3-030-75055-8_2

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-030-75054-1

  • Online ISBN: 978-3-030-75055-8

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation