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Utility of Invasive and Non-invasive Cardiovascular Research Methodologies in Drug Development for Diabetes, Obesity and NAFLD/NASH

  • Gerardo Rodriguez-AraujoEmail author
  • Andrew J. Krentz
Chapter

Abstract

Mechanistic intersections between metabolic and cardiovascular disorders are increasingly appreciated. Novel pharmacotherapies for diabetes and obesity that may simultaneously impact metabolism and vascular function require careful evaluation from a cardiovascular safety perspective. This consideration extends to medications being developed for nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). Available methodologies, which may be classified as either invasive or non-invasive, are presently under-utilized in early phase clinical development programs.

Keywords

Cardiovascular disease Diabetes mellitus Obesity Drug development Early-phase clinical research 

References

  1. 1.
    Tiwari G, et al. Drug delivery systems: an updated review. Int J Pharm Investig. 2012;2:2–11.  https://doi.org/10.4103/2230-973X.96920.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Langer R. Implantable controlled release systems. Pharmacol Ther. 1983;21:35–51.CrossRefGoogle Scholar
  3. 3.
    Meng E, Hoang T. Micro- and nano-fabricated implantable drug-delivery systems. Ther Deliv. 2012;3:1457–67.  https://doi.org/10.4155/tde.12.132.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Zinman B, et al. Empagliflozin, cardiovascular outcomes, and mortality in type 2 diabetes. N Engl J Med. 2015;373:2117–28.  https://doi.org/10.1056/NEJMoa1504720.CrossRefGoogle Scholar
  5. 5.
    Abdul-Ghani M, Del Prato S, Chilton R, DeFronzo RA. SGLT2 inhibitors and cardiovascular risk: lessons learned from the EMPA-REG OUTCOME study. Diabetes Care. 2016;39:717–25.  https://doi.org/10.2337/dc16-0041.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Buse JB, the, L. S. C. Liraglutide and cardiovascular outcomes in type 2 diabetes. N Engl J Med. 2016;375:1798–9.  https://doi.org/10.1056/NEJMc1611289.CrossRefPubMedGoogle Scholar
  7. 7.
    Gerardo R-A, Hironori N. Pathophysiology of cardiovascular disease in diabetes mellitus. Cardiovascular Endocrinology & Metabolism. 2018;7:4–9.  https://doi.org/10.1097/XCE.0000000000000141.CrossRefGoogle Scholar
  8. 8.
    Andrew J., K. & Gerardo, R.-A. Cardiovascular outcome trials of diabetes and obesity drugs: implications for conditional approval and early phase clinical development. Pharm Med. 2017;31:399–421.  https://doi.org/10.1007/s40290-018-0224-z.CrossRefGoogle Scholar
  9. 9.
    Cefalu WT, et al. Cardiovascular outcomes trials in type 2 diabetes: where do we go from here? reflections from a diabetes care editors’ expert forum. Diabetes Care. 2018;41:14–31.  https://doi.org/10.2337/dci17-0057.CrossRefPubMedGoogle Scholar
  10. 10.
    Silvestre OM, et al. Cardiohepatic interactions – from humoral theory to organ transplantation. Arq Bras Cardiol. 2014;102:e65–7.PubMedPubMedCentralGoogle Scholar
  11. 11.
    Konerman MA, Jones JC, Harrison SA. Pharmacotherapy for NASH: current and emerging. J Hepatol. 2018;68:362–75.  https://doi.org/10.1016/j.jhep.2017.10.015.CrossRefPubMedGoogle Scholar
  12. 12.
    Mozos I, Luca CT. Crosstalk between oxidative and nitrosative stress and arterial stiffness. Curr Vasc Pharmacol. 2017;15:446–56.CrossRefGoogle Scholar
  13. 13.
    Donnelly R. Angiotensin-converting enzyme inhibitors and insulin sensitivity: metabolic effects in hypertension, diabetes, and heart failure. J Cardiovasc Pharmacol. 1992;20(Suppl 11):S38–44.CrossRefGoogle Scholar
  14. 14.
    Elliott WJ, Meyer PM. Incident diabetes in clinical trials of antihypertensive drugs: a network meta-analysis. Lancet. 2007;369:201–7.CrossRefGoogle Scholar
  15. 15.
    Sattar NA, et al. The use of statins in people at risk of developing diabetes mellitus: evidence and guidance for clinical practice. Atheroscler Suppl. 2014;15:1–15.  https://doi.org/10.1016/j.atherosclerosissup.2014.04.001.CrossRefPubMedGoogle Scholar
  16. 16.
    Nesto RW, et al. Thiazolidinedione use, fluid retention, and congestive heart failure: a consensus statement from the American Heart Association and American Diabetes Association. October 7, 2003. Circulation. 2003;108:2941–8.  https://doi.org/10.1161/01.CIR.0000103683.99399.7E.CrossRefPubMedGoogle Scholar
  17. 17.
    Nissen SE, Wolski K. Effect of rosiglitazone on the risk of myocardial infarction and death from cardiovascular causes. N Engl J Med. 2007;356:2457–71.CrossRefGoogle Scholar
  18. 18.
    Itoh N, Ohta H. Pathophysiological roles of FGF signaling in the heart. Front Physiol. 2013;4:247.  https://doi.org/10.3389/fphys.2013.00247.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Wente W, et al. Fibroblast growth factor-21 improves pancreatic beta-cell function and survival by activation of extracellular signal-regulated kinase 1/2 and Akt signaling pathways. Diabetes. 2006;55:2470–8.CrossRefGoogle Scholar
  20. 20.
    Pocai A. Action and therapeutic potential of oxyntomodulin. Mol Metab. 2014;3:241–51.  https://doi.org/10.1016/j.molmet.2013.12.001.CrossRefPubMedGoogle Scholar
  21. 21.
    Marso SP, et al. Semaglutide and cardiovascular outcomes in patients with type 2 diabetes. N Engl J Med. 2016;375:1834–44.  https://doi.org/10.1056/NEJMoa1607141.CrossRefPubMedGoogle Scholar
  22. 22.
    Vilsboll T, et al. Semaglutide, reduction in glycated haemoglobin and the risk of diabetic retinopathy. Diabetes Obes Metab. 2018;20:889–97.  https://doi.org/10.1111/dom.13172.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Neal B, et al. Canagliflozin and cardiovascular and renal events in type 2 Diabetes. N Engl J Med. 2017;377:644–57.  https://doi.org/10.1056/NEJMoa1611925.CrossRefGoogle Scholar
  24. 24.
    Mahaffey KW, et al. Canagliflozin for primary and secondary prevention of cardiovascular events: results from the CANVAS program (Canagliflozin Cardiovascular Assessment Study). Circulation. 2018;137:323–34.  https://doi.org/10.1161/CIRCULATIONAHA.117.032038.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Beckman JA, Creager MA. Vascular complications of diabetes. Circ Res. 2016;118:1771–85.  https://doi.org/10.1161/CIRCRESAHA.115.306884.CrossRefPubMedGoogle Scholar
  26. 26.
    Rawshani A, et al. Mortality and cardiovascular disease in type 1 and type 2 diabetes. N Engl J Med. 2017;376:1407–18.  https://doi.org/10.1056/NEJMoa1608664.CrossRefPubMedGoogle Scholar
  27. 27.
    Cannon CP. Mixed dyslipidemia, metabolic syndrome, diabetes mellitus, and cardiovascular disease: clinical implications. Am J Cardiol. 2008;102:5L–9L.  https://doi.org/10.1016/j.amjcard.2008.09.067.CrossRefPubMedGoogle Scholar
  28. 28.
    Reaven GM. Insulin resistance: the link between obesity and cardiovascular disease. Med Clin North Am. 2011;95:875–92.  https://doi.org/10.1016/j.mcna.2011.06.002.CrossRefPubMedGoogle Scholar
  29. 29.
    Saltiel AR, Olefsky JM. Inflammatory mechanisms linking obesity and metabolic disease. J Clin Invest. 2017;127:1–4.  https://doi.org/10.1172/JCI92035.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Bril F, Cusi K. Nonalcoholic fatty liver disease: the new complication of type 2 diabetes mellitus. Endocrinol Metab Clin N Am. 2016;45:765–81.  https://doi.org/10.1016/j.ecl.2016.06.005.CrossRefGoogle Scholar
  31. 31.
    Lonardo A, Sookoian S, Pirola CJ, Targher G. Non-alcoholic fatty liver disease and risk of cardiovascular disease. Metabolism. 2016;65:1136–50.  https://doi.org/10.1016/j.metabol.2015.09.017.CrossRefPubMedGoogle Scholar
  32. 32.
    Targher G, Byrne CD, Lonardo A, Zoppini G, Barbui C. Non-alcoholic fatty liver disease and risk of incident cardiovascular disease: a meta-analysis. J Hepatol. 2016;65:589–600.  https://doi.org/10.1016/j.jhep.2016.05.013.CrossRefPubMedGoogle Scholar
  33. 33.
    Ballestri S, et al. Risk of cardiovascular, cardiac and arrhythmic complications in patients with non-alcoholic fatty liver disease. World J Gastroenterol. 2014;20:1724–45.  https://doi.org/10.3748/wjg.v20.i7.1724.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Mantovani A. Nonalcoholic Fatty Liver Disease (NAFLD) and risk of cardiac arrhythmias: a new aspect of the liver-heart axis. J Clin Transl Hepatol. 2017;5:134–41.  https://doi.org/10.14218/JCTH.2017.00005.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Liu H, Lu HY. Nonalcoholic fatty liver disease and cardiovascular disease. World J Gastroenterol. 2014;20:8407–15.  https://doi.org/10.3748/wjg.v20.i26.8407.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Baldassarre MPA, Andersen A, Consoli A, Knop FK, Vilsboll T. Cardiovascular biomarkers in clinical studies of type 2 diabetes. Diabetes Obes Metab. 2018;  https://doi.org/10.1111/dom.13247.
  37. 37.
    Krentz AJ. Rosiglitazone: trials, tribulations and termination. Drugs. 2011;71:123–30.  https://doi.org/10.2165/11585300-000000000-00000.CrossRefPubMedGoogle Scholar
  38. 38.
    Barter PJ, et al. Effects of torcetrapib in patients at high risk for coronary events. N Engl J Med. 2007;357:2109–22.  https://doi.org/10.1056/NEJMoa0706628.CrossRefPubMedGoogle Scholar
  39. 39.
    Johns DG, Duffy J, Fisher T, Hubbard BK, Forrest MJ. On- and off-target pharmacology of torcetrapib: current understanding and implications for the structure activity relationships (SAR), discovery and development of cholesteryl ester-transfer protein (CETP) inhibitors. Drugs. 2012;72:491–507.  https://doi.org/10.2165/11599310-000000000-00000.CrossRefPubMedGoogle Scholar
  40. 40.
    Sandler H, Dodge HT. The use of single plane angiocardiograms for the calculation of left ventricular volume in man. Am Heart J. 1968;75:325–34.CrossRefGoogle Scholar
  41. 41.
    Lee KB, et al. Stem cell therapy in patients with thromboangiitis obliterans: assessment of the long-term clinical outcome and analysis of the prognostic factors. Int J Stem Cells. 2011;4:88–98.CrossRefGoogle Scholar
  42. 42.
    Nissen SE, et al. Effect of very high-intensity statin therapy on regression of coronary atherosclerosis: the ASTEROID trial. JAMA. 2006;295:1556–65.  https://doi.org/10.1001/jama.295.13.jpc60002.CrossRefGoogle Scholar
  43. 43.
    Yeung AC, et al. Clinical evaluation of the Resolute zotarolimus-eluting coronary stent system in the treatment of de novo lesions in native coronary arteries: the RESOLUTE US clinical trial. J Am Coll Cardiol. 2011;57:1778–83.  https://doi.org/10.1016/j.jacc.2011.03.005.CrossRefPubMedGoogle Scholar
  44. 44.
    Ma T, Zhou B, Hsiai TK, Shung KK. A review of intravascular ultrasound-based multimodal intravascular imaging: the synergistic approach to characterizing vulnerable plaques. Ultrason Imaging. 2016;38:314–31.  https://doi.org/10.1177/0161734615604829.CrossRefPubMedGoogle Scholar
  45. 45.
    Nicholls SJ, Puri R. Implications of GLAGOV study. Curr Opin Lipidol. 2017;  https://doi.org/10.1097/MOL.0000000000000458.
  46. 46.
    Elliott MR, Thrush AJ. Measurement of resolution in intravascular ultrasound images. Physiol Meas. 1996;17:259–65.CrossRefGoogle Scholar
  47. 47.
    Waxman S, et al. In vivo validation of a catheter-based near-infrared spectroscopy system for detection of lipid core coronary plaques: initial results of the SPECTACL study. JACC Cardiovasc Imaging. 2009;2:858–68.  https://doi.org/10.1016/j.jcmg.2009.05.001.CrossRefPubMedGoogle Scholar
  48. 48.
    Liang S, et al. Trimodality imaging system and intravascular endoscopic probe: combined optical coherence tomography, fluorescence imaging and ultrasound imaging. Opt Lett. 2014;39:6652–5.  https://doi.org/10.1364/OL.39.006652.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Jang IK, et al. Visualization of coronary atherosclerotic plaques in patients using optical coherence tomography: comparison with intravascular ultrasound. J Am Coll Cardiol. 2002;39:604–9.CrossRefGoogle Scholar
  50. 50.
    Allemang MT, et al. The use of dextran and carbon dioxide for optical coherence tomography in the superficial femoral artery. J Vasc Surg. 2014;59:238–40.  https://doi.org/10.1016/j.jvs.2013.03.006.CrossRefPubMedGoogle Scholar
  51. 51.
    Yang X, et al. Impact of ticagrelor and aspirin versus clopidogrel and aspirin in symptomatic patients with peripheral arterial disease: Thrombus burden assessed by optical coherence tomography. Cardiovasc Revasc Med. 2018;  https://doi.org/10.1016/j.carrev.2018.02.013.
  52. 52.
  53. 53.
    Jaguszewski M, Klingenberg R, Landmesser U. Intracoronary near-infrared spectroscopy (NIRS) imaging for detection of lipid content of coronary plaques: current experience and future perspectives. Curr Cardiovasc Imaging Rep. 2013;6:426–30.  https://doi.org/10.1007/s12410-013-9224-2.CrossRefPubMedPubMedCentralGoogle Scholar
  54. 54.
  55. 55.
  56. 56.
    Puri R, et al. Near-infrared spectroscopy enhances intravascular ultrasound assessment of vulnerable coronary plaque: a combined pathological and in vivo study. Arterioscler Thromb Vasc Biol. 2015;35:2423–31.  https://doi.org/10.1161/ATVBAHA.115.306118.CrossRefPubMedGoogle Scholar
  57. 57.
    Brugaletta S, et al. NIRS and IVUS for characterization of atherosclerosis in patients undergoing coronary angiography. JACC Cardiovasc Imaging. 2011;4:647–55.  https://doi.org/10.1016/j.jcmg.2011.03.013.CrossRefPubMedGoogle Scholar
  58. 58.
    Berry C, et al. Fractional flow reserve-guided management in stable coronary disease and acute myocardial infarction: recent developments. Eur Heart J. 2015;36:3155–64.  https://doi.org/10.1093/eurheartj/ehv206.CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Corcoran D, Hennigan B, Berry C. Fractional flow reserve: a clinical perspective. Int J Cardiovasc Imaging. 2017;33:961–74.  https://doi.org/10.1007/s10554-017-1159-2.CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
  61. 61.
    Pijls NH, et al. Measurement of fractional flow reserve to assess the functional severity of coronary-artery stenoses. N Engl J Med. 1996;334:1703–8.  https://doi.org/10.1056/NEJM199606273342604.CrossRefPubMedGoogle Scholar
  62. 62.
    Gotberg M, et al. Instantaneous wave-free ratio versus fractional flow reserve to guide PCI. N Engl J Med. 2017;376:1813–23.  https://doi.org/10.1056/NEJMoa1616540.CrossRefPubMedGoogle Scholar
  63. 63.
    Davies JE, et al. Use of the instantaneous wave-free ratio or fractional flow reserve in PCI. N Engl J Med. 2017;376:1824–34.  https://doi.org/10.1056/NEJMoa1700445.CrossRefPubMedGoogle Scholar
  64. 64.
    Abraham WT, et al. Wireless pulmonary artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet. 2011;377:658–66.  https://doi.org/10.1016/S0140-6736(11)60101-3.CrossRefPubMedGoogle Scholar
  65. 65.
    Selvaraj S, et al. Pulmonary hypertension is associated with a higher risk of heart failure hospitalization and mortality in patients with chronic kidney disease: the Jackson Heart Study. Circ Heart Fail. 2017;10.  https://doi.org/10.1161/CIRCHEARTFAILURE.116.003940.
  66. 66.
    Shin JT, Semigran MJ. Heart failure and pulmonary hypertension. Heart Fail Clin. 2010;6:215–22.  https://doi.org/10.1016/j.hfc.2009.11.007.CrossRefPubMedPubMedCentralGoogle Scholar
  67. 67.
  68. 68.
  69. 69.
  70. 70.
  71. 71.
    Ashley EA, Niebauer J. Cardiology explained. London, England: Remedica; 2004.Google Scholar
  72. 72.
    Anavekar NS, Oh JK. Doppler echocardiography: a contemporary review. J Cardiol. 2009;54:347–58.  https://doi.org/10.1016/j.jjcc.2009.10.001.CrossRefPubMedGoogle Scholar
  73. 73.
    Gonzalez-Vilcez F, Ares M, Ayuela J, Alonso L. Combined use of pulsed and color M-mode doppler echocardiography for the estimation of pulmonary capillary wedge pressure: an empirical approach based on an analytical relation. J Am Coll Cardiol. 1999;34  https://doi.org/10.1016/S0735-1097(99)00230-2.
  74. 74.
    Feigenbaum H. Role of M-mode technique in today’s echocardiography. J Am Soc Echocardiogr. 2010;23(240–257):335–247.  https://doi.org/10.1016/j.echo.2010.01.015.CrossRefGoogle Scholar
  75. 75.
    Edner M, et al. Long-term effects on cardiac output and peripheral resistance in patients treated with enalapril after acute myocardial infarction. CONSENSUS II Multi-Echo Study Group Cooperative New Scandinavian Enalapril Survival Study. Cardiology. 1998;89:291–6.  https://doi.org/10.1159/000006807.CrossRefPubMedGoogle Scholar
  76. 76.
    Mor-Avi V, Sugeng L, Lang RM. Real-time 3-dimensional echocardiography: an integral component of the routine echocardiographic examination in adult patients? Circulation. 2009;119:314–29.  https://doi.org/10.1161/CIRCULATIONAHA.107.751354.CrossRefPubMedGoogle Scholar
  77. 77.
    Yuan C, Oikawa M, Miller Z, Hatsukami T. MRI of carotid atherosclerosis. J Nucl Cardiol. 2008;15:266–75.  https://doi.org/10.1016/j.nuclcard.2008.02.001.CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Kerwin WS, Oikawa M, Yuan C, Jarvik GP, Hatsukami TS. MR imaging of adventitial vasa vasorum in carotid atherosclerosis. Magn Reson Med. 2008;59:507–14.  https://doi.org/10.1002/mrm.21532.CrossRefPubMedGoogle Scholar
  79. 79.
    Zhao XQ, et al. MR imaging of carotid plaque composition during lipid-lowering therapy a prospective assessment of effect and time course. JACC Cardiovasc Imaging. 2011;4:977–86.  https://doi.org/10.1016/j.jcmg.2011.06.013.CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Balu N, Chu B, Hatsukami TS, Yuan C, Yarnykh VL. Comparison between 2D and 3D high-resolution black-blood techniques for carotid artery wall imaging in clinically significant atherosclerosis. J Magn Reson Imaging. 2008;27:918–24.  https://doi.org/10.1002/jmri.21282.CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Hingwala D, Kesavadas C, Sylaja PN, Thomas B, Kapilamoorthy TR. Multimodality imaging of carotid atherosclerotic plaque: going beyond stenosis. Indian J Radiol Imaging. 2013;23:26–34.  https://doi.org/10.4103/0971-3026.113616.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Kozakova M, et al. Insulin sensitivity and carotid intima-media thickness: relationship between insulin sensitivity and cardiovascular risk study. Arterioscler Thromb Vasc Biol. 2013;33:1409–17.  https://doi.org/10.1161/ATVBAHA.112.300948.CrossRefPubMedGoogle Scholar
  83. 83.
    Petrie JR, et al. Cardiovascular and metabolic effects of metformin in patients with type 1 diabetes (REMOVAL): a double-blind, randomised, placebo-controlled trial. Lancet Diabetes Endocrinol. 2017;5:597–609.  https://doi.org/10.1016/S2213-8587(17)30194-8.CrossRefPubMedPubMedCentralGoogle Scholar
  84. 84.
    Sabarudin A, Sun Z. Coronary CT angiography: diagnostic value and clinical challenges. World J Cardiol. 2013;5:473–83.  https://doi.org/10.4330/wjc.v5.i12.473.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Patil R, Sood GK. Non-alcoholic fatty liver disease and cardiovascular risk. World J Gastrointest Pathophysiol. 2017;8:51–8.  https://doi.org/10.4291/wjgp.v8.i2.51.CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Sharma RK, et al. Cardiac risk stratification: role of the coronary calcium score. Vasc Health Risk Manag. 2010;6:603–11.CrossRefGoogle Scholar
  87. 87.
    Puri R, et al. Impact of statins on serial coronary calcification during atheroma progression and regression. J Am Coll Cardiol. 2015;65:1273–82.  https://doi.org/10.1016/j.jacc.2015.01.036.CrossRefGoogle Scholar
  88. 88.
    Pletcher MJ, et al. Using the coronary artery calcium score to guide statin therapy: a cost-effectiveness analysis. Circ Cardiovasc Qual Outcomes. 2014;7:276–84.  https://doi.org/10.1161/CIRCOUTCOMES.113.000799.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Wong ND, et al. Residual atherosclerotic cardiovascular disease risk in statin-treated adults: the Multi-Ethnic Study of Atherosclerosis. J Clin Lipidol. 2017;11:1223–33.  https://doi.org/10.1016/j.jacl.2017.06.015.CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Shah RR. The significance of QT interval in drug development. Br J Clin Pharmacol. 2002;54:188–202.CrossRefGoogle Scholar
  91. 91.
    Allen LA, Spertus JA. End points for comparative effectiveness research in heart failure. Heart Fail Clin. 2013;9:15–28.  https://doi.org/10.1016/j.hfc.2012.09.002.CrossRefPubMedGoogle Scholar
  92. 92.
    Wang J, et al. Novel biomarkers for cardiovascular risk prediction. J Geriatr Cardiol. 2017;14:135–50.  https://doi.org/10.11909/j.issn.1671-5411.2017.02.008.CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Tousoulis D, et al. Fibrinogen and cardiovascular disease: genetics and biomarkers. Blood Rev. 2011;25:239–45.  https://doi.org/10.1016/j.blre.2011.05.001.CrossRefPubMedGoogle Scholar
  94. 94.
    Kume N, Mitsuoka H, Hayashida K, Tanaka M. Pentraxin 3 as a biomarker for acute coronary syndrome: comparison with biomarkers for cardiac damage. J Cardiol. 2011;58:38–45.  https://doi.org/10.1016/j.jjcc.2011.03.006.CrossRefPubMedGoogle Scholar
  95. 95.
    Ganguly P, Alam SF. Role of homocysteine in the development of cardiovascular disease. Nutr J. 2015;14:6.  https://doi.org/10.1186/1475-2891-14-6.CrossRefPubMedPubMedCentralGoogle Scholar
  96. 96.
    Villacorta H, Maisel AS. Soluble ST2 testing: a promising biomarker in the management of heart failure. Arq Bras Cardiol. 2016;106:145–52.  https://doi.org/10.5935/abc.20150151.CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Tamura Y, et al. Human pentraxin 3 (PTX3) as a novel biomarker for the diagnosis of pulmonary arterial hypertension. PLoS One. 2012;7:e45834.  https://doi.org/10.1371/journal.pone.0045834.CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Heeschen C, et al. Soluble CD40 ligand in acute coronary syndromes. N Engl J Med. 2003;348:1104–11.  https://doi.org/10.1056/NEJMoa022600.CrossRefPubMedGoogle Scholar
  99. 99.
    Raber MN. In: Walker HK, Hall WD, Hurst JW, editors. Clinical methods: the history, physical, and laboratory examinations. Boston/London: Butterworths; 1990.Google Scholar
  100. 100.
    Watters K, Munro N, Feher M. QTc prolongation and diabetes therapies. Diabet Med. 2012;29:290–2.  https://doi.org/10.1111/j.1464-5491.2011.03520.x.CrossRefPubMedGoogle Scholar
  101. 101.
    Mizusawa Y, Wilde AA. Brugada syndrome. Circ Arrhythm Electrophysiol. 2012;5:606–16.  https://doi.org/10.1161/CIRCEP.111.964577.CrossRefPubMedGoogle Scholar
  102. 102.
    Vandenberk B, et al. Which QT correction formulae to use for QT monitoring? J Am Heart Assoc. 2016;5  https://doi.org/10.1161/JAHA.116.003264.
  103. 103.
    Isbister GK, Page CB. Drug induced QT prolongation: the measurement and assessment of the QT interval in clinical practice. Br J Clin Pharmacol. 2013;76:48–57.  https://doi.org/10.1111/bcp.12040.CrossRefPubMedGoogle Scholar
  104. 104.
    Lorenz M, et al. Differential effects of glucagon-like peptide-1 receptor agonists on heart rate. Cardiovasc Diabetol. 2017;16:6.  https://doi.org/10.1186/s12933-016-0490-6.CrossRefPubMedPubMedCentralGoogle Scholar
  105. 105.
    Cooney MT, et al. Elevated resting heart rate is an independent risk factor for cardiovascular disease in healthy men and women. Am Heart J. 2010;159:612–619 e613.  https://doi.org/10.1016/j.ahj.2009.12.029.CrossRefPubMedGoogle Scholar
  106. 106.
    Bethel MA, et al. Cardiovascular outcomes with glucagon-like peptide-1 receptor agonists in patients with type 2 diabetes: a meta-analysis. Lancet Diabetes Endocrinol. 2018;6:105–13.  https://doi.org/10.1016/S2213-8587(17)30412-6.CrossRefPubMedGoogle Scholar
  107. 107.
    van den Meiracker AH. Ambulatory blood pressure monitoring in clinical trials with antihypertensive agents. Neth J Med. 1995;46:99–105.CrossRefGoogle Scholar
  108. 108.
    Li C, et al. Clinical validation of a new wrist continuous noninvasive hemodynamic monitoring system in comparison with invasive radial artery measurement. Blood Press Monit. 2017;  https://doi.org/10.1097/MBP.0000000000000262.
  109. 109.
    Zucatti ATN, et al. Low levels of usual physical activity are associated with higher 24 h blood pressure in type 2 diabetes mellitus in a cross-sectional study. J Diabetes Res. 2017;6232674:2017.  https://doi.org/10.1155/2017/6232674.CrossRefGoogle Scholar
  110. 110.
  111. 111.
    Baker WL, et al. Effects of sodium-glucose cotransporter 2 inhibitors on 24-hour ambulatory blood pressure: a systematic review and meta-analysis. J Am Heart Assoc. 2017;6  https://doi.org/10.1161/JAHA.117.005686.
  112. 112.
    Nauck MA, Meier JJ, Cavender MA, Abd El Aziz M, Drucker DJ. Cardiovascular actions and clinical outcomes with glucagon-like peptide-1 receptor agonists and dipeptidyl peptidase-4 inhibitors. Circulation. 2017;136:849–70.  https://doi.org/10.1161/CIRCULATIONAHA.117.028136.CrossRefPubMedGoogle Scholar
  113. 113.
    Eguchi K. Ambulatory blood pressure monitoring in diabetes and obesity-a review. Int J Hypertens. 2011;2011:954757.  https://doi.org/10.4061/2011/954757.CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Knudsen ST, et al. Pulse pressure and diurnal blood pressure variation: association with micro- and macrovascular complications in type 2 diabetes. Am J Hypertens. 2002;15:244–50.CrossRefGoogle Scholar
  115. 115.
    Knudsen ST, et al. Ambulatory pulse pressure, decreased nocturnal blood pressure reduction and progression of nephropathy in type 2 diabetic patients. Diabetologia. 2009;52:698–704.  https://doi.org/10.1007/s00125-009-1262-6.CrossRefPubMedGoogle Scholar
  116. 116.
  117. 117.
    Hardman RL, Jazaeri O, Yi J, Smith M, Gupta R. Overview of classification systems in peripheral artery disease. Semin Interv Radiol. 2014;31:378–88.  https://doi.org/10.1055/s-0034-1393976.CrossRefGoogle Scholar
  118. 118.
    Rutherford RB, et al. Recommended standards for reports dealing with lower extremity ischemia: revised version. J Vasc Surg. 1997;26:517–38.CrossRefGoogle Scholar
  119. 119.
    Rosenfield K, et al. Trial of a paclitaxel-coated balloon for femoropopliteal artery disease. N Engl J Med. 2015;373:145–53.  https://doi.org/10.1056/NEJMoa1406235.CrossRefPubMedGoogle Scholar
  120. 120.
    Ahlqvist E, et al. Novel subgroups of adult-onset diabetes and their association with outcomes: a data-driven cluster analysis of six variables. Lancet Diabetes Endocrinol. 2018;  https://doi.org/10.1016/S2213-8587(18)30051-2.
  121. 121.
    Koo BK, et al. Additive effects of PNPLA3 and TM6SF2 on the histological severity of non-alcoholic fatty liver disease. J Gastroenterol Hepatol. 2017;  https://doi.org/10.1111/jgh.14056.
  122. 122.
    Quail MA, et al. A tale of three next generation sequencing platforms: comparison of Ion Torrent, Pacific Biosciences and Illumina MiSeq sequencers. BMC Genomics. 2012;13:341.  https://doi.org/10.1186/1471-2164-13-341.CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Schulte C, Zeller T. microRNA-based diagnostics and therapy in cardiovascular disease-Summing up the facts. Cardiovasc Diagn Ther. 2015;5:17–36.  https://doi.org/10.3978/j.issn.2223-3652.2014.12.03.CrossRefPubMedPubMedCentralGoogle Scholar
  124. 124.
    Mitra S, et al. Analysis of the intestinal microbiota using SOLiD 16S rRNA gene sequencing and SOLiD shotgun sequencing. BMC Genomics. 2013;14(Suppl 5):S16.  https://doi.org/10.1186/1471-2164-14-S5-S16.CrossRefPubMedPubMedCentralGoogle Scholar
  125. 125.
    Xu R, Tao A, Zhang S, Deng Y, Chen G. Association between patatin-like phospholipase domain containing 3 gene (PNPLA3) polymorphisms and nonalcoholic fatty liver disease: a HuGE review and meta-analysis. Sci Rep. 2015;5:9284.  https://doi.org/10.1038/srep09284.CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Zhou K, Pedersen HK, Dawed AY, Pearson ER. Pharmacogenomics in diabetes mellitus: insights into drug action and drug discovery. Nat Rev Endocrinol. 2016;12:337–46.  https://doi.org/10.1038/nrendo.2016.51.CrossRefPubMedGoogle Scholar
  127. 127.
    Pollastro C, Ziviello C, Costa V, Ciccodicola A. Pharmacogenomics of drug response in type 2 diabetes: toward the definition of tailored therapies? PPAR Res. 2015;2015:415149.  https://doi.org/10.1155/2015/415149.CrossRefPubMedPubMedCentralGoogle Scholar
  128. 128.
    He M, et al. Plasma microRNAs as potential noninvasive biomarkers for in-stent restenosis. PLoS One. 2014;9:e112043.  https://doi.org/10.1371/journal.pone.0112043.CrossRefPubMedPubMedCentralGoogle Scholar
  129. 129.
    Ji R, et al. MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation. Circ Res. 2007;100:1579–88.  https://doi.org/10.1161/CIRCRESAHA.106.141986.CrossRefPubMedGoogle Scholar
  130. 130.
    Harris RA, Nishiyama SK, Wray DW, Richardson RS. Ultrasound assessment of flow-mediated dilation. Hypertension. 2010;55:1075–85.  https://doi.org/10.1161/HYPERTENSIONAHA.110.150821.CrossRefPubMedPubMedCentralGoogle Scholar
  131. 131.
    Moroni L, Selmi C, Angelini C, Meroni PL. Evaluation of endothelial function by flow-mediated dilation: a comprehensive review in rheumatic disease. Arch Immunol Ther Exp (Warsz.). 2017;  https://doi.org/10.1007/s00005-017-0465-7.
  132. 132.
  133. 133.
    Axtell AL, Gomari FA, Cooke JP. Assessing endothelial vasodilator function with the Endo-PAT 2000. J Vis Exp. 2010;  https://doi.org/10.3791/2167.
  134. 134.
    Kuvin JT, et al. Assessment of peripheral vascular endothelial function with finger arterial pulse wave amplitude. Am Heart J. 2003;146:168–74.  https://doi.org/10.1016/S0002-8703(03)00094-2.CrossRefPubMedGoogle Scholar
  135. 135.
    Cosenso-Martin LN, et al. Twelve-week randomized study to compare the effect of vildagliptin vs. glibenclamide both added-on to metformin on endothelium function in patients with type 2 diabetes and hypertension. Diabetol Metab Syndr. 2015;7:70.  https://doi.org/10.1186/s13098-015-0062-z.CrossRefPubMedPubMedCentralGoogle Scholar
  136. 136.
    Laurent S, et al. Expert consensus document on arterial stiffness: methodological issues and clinical applications. Eur Heart J. 2006;27:2588–605.  https://doi.org/10.1093/eurheartj/ehl254.CrossRefPubMedGoogle Scholar
  137. 137.
    Williams B, et al. Differential impact of blood pressure-lowering drugs on central aortic pressure and clinical outcomes: principal results of the Conduit Artery Function Evaluation (CAFE) study. Circulation. 2006;113:1213–25.  https://doi.org/10.1161/CIRCULATIONAHA.105.595496.CrossRefPubMedGoogle Scholar
  138. 138.
    Covic A, Siriopol D. Pulse wave velocity ratio: the new “gold standard” for measuring arterial stiffness. Hypertension. 2015;65:289–90.  https://doi.org/10.1161/HYPERTENSIONAHA.114.04678.CrossRefPubMedGoogle Scholar
  139. 139.
    Calabia J, et al. Doppler ultrasound in the measurement of pulse wave velocity: agreement with the Complior method. Cardiovasc Ultrasound. 2011;9:13.  https://doi.org/10.1186/1476-7120-9-13.CrossRefPubMedPubMedCentralGoogle Scholar
  140. 140.
    Khan TH, Farooqui FA, Niazi K. Critical review of the ankle brachial index. Curr Cardiol Rev. 2008;4:101–6.  https://doi.org/10.2174/157340308784245810.CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Wild SH, Byrne CD, Smith FB, Lee AJ, Fowkes FG. Low ankle-brachial pressure index predicts increased risk of cardiovascular disease independent of the metabolic syndrome and conventional cardiovascular risk factors in the Edinburgh artery study. Diabetes Care. 2006;29:637–42.CrossRefGoogle Scholar
  142. 142.
    American Diabetes A. Peripheral arterial disease in people with diabetes. Diabetes Care. 2003;26:3333–41.CrossRefGoogle Scholar
  143. 143.
    Crawford F, Welch K, Andras A, Chappell FM. Ankle brachial index for the diagnosis of lower limb peripheral arterial disease. Cochrane Database Syst Rev. 2016;9:CD010680.  https://doi.org/10.1002/14651858.CD010680.pub2.CrossRefPubMedGoogle Scholar
  144. 144.
    Gerhard-Herman MD, et al. 2016 AHA/ACC guideline on the management of patients with lower extremity peripheral artery disease: a report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. J Am Coll Cardiol. 2017;69:e71–e126.  https://doi.org/10.1016/j.jacc.2016.11.007.CrossRefPubMedGoogle Scholar
  145. 145.
    Rac-Albu M, Iliuta L, Guberna SM, Sinescu C. The role of ankle-brachial index for predicting peripheral arterial disease. Maedica (Buchar). 2014;9:295–302.Google Scholar
  146. 146.
    Lew E, Nicolosi N, Botek G. Lower extremity amputation risk factors associated with elevated ankle brachial indices and radiographic arterial calcification. J Foot Ankle Surg. 2015;54:473–7.  https://doi.org/10.1053/j.jfas.2014.12.022.CrossRefPubMedGoogle Scholar
  147. 147.
    McDermott MM, et al. Six-minute walk is a better outcome than treadmill walking tests in therapeutic trials of patients with peripheral artery disease. Circulation. 2014;130:61–8.  https://doi.org/10.1161/CIRCULATIONAHA.114.007002.
  148. 148.
    Nordanstig J, et al. Vascular quality of life Questionnaire-6 facilitates health-related quality of life assessment in peripheral arterial disease. J Vasc Surg. 2014;59:700–7.  https://doi.org/10.1016/j.jvs.2013.08.099.CrossRefPubMedGoogle Scholar
  149. 149.
    Morgan MB, Crayford T, Murrin B, Fraser SC. Developing the vascular quality of life questionnaire: a new disease-specific quality of life measurement for use in lower limb ischemia. J Vasc Surg. 2001;33:679–87.  https://doi.org/10.1067/mva.2001.112326.
  150. 150.
    Treat-Jacobson D, et al. The PADQOL: development and validation of a PAD-specific quality of life questionnaire. Vasc Med. 2012;17:405–15.  https://doi.org/10.1177/1358863X12466708.CrossRefPubMedGoogle Scholar
  151. 151.
    Singh JS, et al. Research into the effect of SGLT2 inhibition on left ventricular remodelling in patients with heart failure and diabetes mellitus (REFORM) trial rationale and design. Cardiovasc Diabetol. 2016;15:97.  https://doi.org/10.1186/s12933-016-0419-0.CrossRefPubMedPubMedCentralGoogle Scholar
  152. 152.
    Hiatt WR, Rogers RK, Brass EP. The treadmill is a better functional test than the 6-minute walk test in therapeutic trials of patients with peripheral artery disease. Circulation. 2014;130:69–78.  https://doi.org/10.1161/CIRCULATIONAHA.113.007003.CrossRefPubMedGoogle Scholar
  153. 153.
    Labs KH, Nehler MR, Roessner M, Jaeger KA, Hiatt WR. Reliability of treadmill testing in peripheral arterial disease: a comparison of a constant load with a graded load treadmill protocol. Vasc Med. 1999;4:239–46.  https://doi.org/10.1177/1358836X9900400406.CrossRefPubMedGoogle Scholar
  154. 154.
    Beltz NM, et al. Graded exercise testing protocols for the determination of VO2max: historical perspectives, progress, and future considerations. J Sports Med (Hindawi Publ Corp). 2016;2016:3968393.  https://doi.org/10.1155/2016/3968393.CrossRefGoogle Scholar
  155. 155.
  156. 156.
    Nishio H, et al. Transcutaneous oxygen pressure as a surrogate index of lower limb amputation. Int Angiol. 2016;35:565–72.PubMedGoogle Scholar
  157. 157.
    Moon H, Gelly H, Strauss MB, La SS, Miller SS. The validity of transcutaneous oxygen measurements in predicting healing of diabetic foot ulcers. Undersea Hyperb Med. 2016;43:641–8.PubMedGoogle Scholar
  158. 158.
    Powell RJ, et al. Results of a double-blind, placebo-controlled study to assess the safety of intramuscular injection of hepatocyte growth factor plasmid to improve limb perfusion in patients with critical limb ischemia. Circulation. 2008;118:58–65.  https://doi.org/10.1161/CIRCULATIONAHA.107.727347.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.ProSciento, Inc.Chula VistaUSA
  2. 2.University of Arkansas for Medical Sciences, Graduate School of MedicineLittle RockUSA
  3. 3.Institute for Cardiovascular and Metabolic ResearchUniversity of ReadingReadingUK

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