Please ensure Javascript is enabled for purposes of website accessibility
REVIEW PAPER
Circulating biomarkers in the setting of stress test-induced myocardial ischemia – a review of potential candidates for introduction into clinical practice
 
More details
Hide details
1
Collegium Medicum, Jan Kochanowski University, Kielce, Poland
 
 
Submission date: 2023-06-08
 
 
Final revision date: 2023-08-14
 
 
Acceptance date: 2023-12-21
 
 
Publication date: 2024-03-28
 
 
Corresponding author
Łukasz Zandecki
Collegium Medicum, Jan Kochanowski University, Kielce, Poland
 
 
Medical Studies 2024;40(1):69-74
 
KEYWORDS
TOPICS
ABSTRACT
The essential goal in the diagnostic approach to chronic coronary syndromes is to identify patients with significant stenoses in the coronary arteries who could benefit from invasive treatment while avoiding exposure to unnecessary interventional treatments or diagnostic procedures for patients who are unlikely to have significant stenoses in their coronary arteries. Early myocardial ischemia leads to a dynamic molecular response in the affected myocardium. A promising minimally invasive strategy is to access changes of concentrations of certain biomarkers circulating in blood during stress test-induced myocardial ischemia. This novel approach may change the landscape of non-invasive assessment of cardiac ischemia. However, there is a need for careful selection of possible candidates to be evaluated in future clinical trials. Several biomarkers have been proposed as potentially useful in this context and they are discussed in this review paper.
REFERENCES (50)
1.
European Society of Cardiology: Cardiovascular Disease Statistics 2019: https://iris.unibocconi.it/ret....
 
2.
Knuuti J, Wijns W, Saraste A, Capodanno D, Barbato E, Funck-Brentano C, Prescott E, Storey RF, Deaton C, Cuisset T, Agewall S, Dickstein K, Edvardsen T, Escaned J, Gersh BJ, Svitil P, Gilard M, Hasdai D, Hatala R, Mah- foud F, Masip J, Muneretto C, Valgimigli M, Achenbach S, Bax JJ; ESC Scientific Document Group. 2019 ESC Guidelines for the diagnosis and management of chronic coronary syndromes. Eur Heart J 2020; 41: 407-477.
 
3.
Senior R, Monaghan MJ, Becher H, Mayet J, Nihoyannopoulos P; British Society of Echocardiography. Stress echocardiography for the diagnosis and risk stratification of patients with suspected or known coronary artery disease: a critical appraisal. Supported by the British Society of Echocardiography. Heart 2005; 91: 427-436.
 
4.
Siontis GC, Mavridis D, Greenwood JP, Coles B, Nikolakopoulou A, Juni P, Salanti G, Windecker S. Outcomes of non-invasive diagnostic modalities for the detection of coronary artery disease: network meta-analysis of diagnostic randomised controlled trials. BMJ 2018; 360: k504.
 
5.
Baweja P, Sweeney MJ, López-Candales A. A reminder that stress echocardiography is useful in diagnosing myocardial ischemia in nonobstructive coronary artery disease: case series. Cureus 2021; 13: e17763.
 
6.
Geleijnse ML, Krenning BJ, van Dalen BM, Nemes A, Soliman OI, Bosch JG, Galema TW, ten Cate FJ, Boersma E. Factors affecting sensitivity and specificity of diagnostic testing: dobutamine stress echocardiography. J Am Soc Echocardiogr 2009; 22: 1199-1208.
 
7.
Woodward W, Dockerill C, McCourt A, Upton R, O’Driscoll J, Balkhausen K, Chandrasekaran B, Firoozan S, Kardos A, Wong K, Woodward G, Sarwar R, Sabharwal N, Benedetto E, Spagou N, Sharma R, Augustine D, Tsiachristas A, Senior R, Leeson P, EVAREST Investigators; EVAREST Investigators; Boardman H, d’Arcy J, Abraheem A, Banypersad S, Boos C, Bulugahapitiya S, Butts J, Coles D, Easaw J, Hamdan H, Jamil-Copley S, Kanaganayagam G, Mwambingu T, Pantazis A, Papachristidis A, Rajani R, Rasheed MA, Razvi NA, Rekhraj S, Ripley DP, Rose K, Scheuermann-Freestone M, Schofield R, Sultan A. Real-world performance and accuracy of stress echocardiography: the EVAREST observational multi-centre study. Eur Heart J Cardiovasc Imaging 2022; 23: 689-698.
 
8.
Siriwardena M, Campbell V, Richards AM, Pemberton CJ. Cardiac biomarker responses to dobutamine stress echocardiography in healthy volunteers and patients with coronary artery disease. Clin Chem 2012; 58: 1492-1494.
 
9.
Hammadah M, Al Mheid I, Wilmot K, Ramadan R, Alkhoder A, Obideen M, Abdelhadi N, Fang S, Ibeanu I, Pim- ple P, Mohamed Kelli H, Shah AJ, Pearce B, Sun Y, Garcia EV, Kutner M, Long Q, Ward L, Bremner JD, Esteves F, Raggi P, Sheps D, Vaccarino V, Quyyumi AA. Association between high-sensitivity cardiac troponin levels and myocardial ischemia during mental stress and conventional stress. JACC Cardiovasc Imaging 2018; 11: 603-611.
 
10.
Omland T, de Lemos JA, Sabatine MS, Christophi CA, Rice MM, Jablonski KA, Tjora S, Domanski MJ, Gersh BJ, Rouleau JL, Pfeffer MA, Braunwald E. A sensitive cardiac troponin T assay in stable coronary artery disease. N Engl J Med 2009; 361: 2538-2547.
 
11.
Hoefer IE, Steffens S, Ala-Korpela M, Bäck M, Badimon L, Bochaton-Piallat ML, Boulanger CM, Caligiuri G, Dimmeler S, Egido J, Evans PC, Guzik T, Kwak BR, Landmes- ser U, Mayr M, Monaco C, Pasterkamp G, Tuńón J, Weber C; ESC Working Group Atherosclerosis and Vascular Biology. Novel methodologies for biomarker discovery in atherosclerosis. Eur Heart J 2015; 36: 2635-2642.
 
12.
Expert Group on Biomarkers. Biomarkers in cardiology - part 2: in coronary heart disease, valve disease and special situations. Arq Bras Cardiol 2015; 104: 337-346.
 
13.
Abaspour AR, Taghikhani M, Parizadeh SMR, Seyedi SMR, Ghazizadeh H, Kazemi E, Moohebati M, Ghafoori F, Mardannik M, Avan A, Ferns GA, Ghayour-Mobarhan M. HSP27 expression in the human peripheral blood mononuclear cells as an early prognostic biomarker in coronary artery disease patients. Diabetes Metab Syndr 2019; 13: 1791-1795.
 
14.
Santos-Junior VA, Lollo PCB, Cantero MA, Moura CS, Amaya-Farfan J, Morato PN. Heat shock proteins: protection and potential biomarkers for ischemic injury of cardiomyocytes after surgery. Braz J Cardiovasc Surg 2018; 33: 291-302.
 
15.
Rinaldi B, Corbi G, Boccuti S, Filippelli W, Rengo G, Leosco D, Rossi F, Filippelli A, Ferrara N. Exercise training affects age-induced changes in SOD and heat shock protein expression in rat heart. Exp Gerontol 2006; 41: 764-770.
 
16.
Rhee EP, Gerszten RE. Metabolomics and cardiovascular biomarker discovery. Clin Chem 2012; 58: 139-147.
 
17.
Wick G. The heat is on: heat-shock proteins and atherosclerosis. Circulation 2006; 114: 870-872.
 
18.
Zhang HL, Jia KY, Sun D, Yang M. Protective effect of HSP27 in atherosclerosis and coronary heart disease by inhibiting reactive oxygen species. J Cell Biochem 2019; 120: 2859-2868.
 
19.
Li Z, Song Y, Xing R, Yu H, Zhang Y, Li Z, Gao W. Heat shock protein 70 acts as a potential biomarker for early diagnosis of heart failure. PLoS One 2013; 8: e67964.
 
20.
Wu R, Gao W, Dong Z, Su Y, Ji Y, Liao J, Ma Y, Dai Y, Yao K, Ge J. Plasma heat shock protein 70 is associated with the onset of acute myocardial infarction and total occlusion in target vessels. Front Cardiovasc Med 2021; 8: 688702.
 
21.
Grundtman C, Kreutmayer SB, Almanzar G, Wick MC, Wick G. Heat shock protein 60 and immune inflammatory responses in atherosclerosis. Arterioscler Thromb Vasc Biol 2011; 31: 960-968.
 
22.
Veres A, Szamosi T, Ablonczy M, Szamosi Jr T, Singh M, Karadi I, Romics L, Füst G, Prohászka Z. Complement activating antibodies against the human 60 kDa heat shock protein as a new independent family risk factor of coronary heart disease. Eur J Clin Invest 2002; 32: 405-410.
 
23.
Li G, Lu WH, Ai R, Yang JH, Chen F, Tang ZZ. The relationship between serum hypoxia-inducible factor 1 and coronary artery calcification in asymptomatic type 2 diabetic patients. Cardiovasc Diabetol 2014; 13: 52.
 
24.
Szyldberg Ł, Bodnar M, Michalski J, Maciejewska M, Marszałek A. Inflammation and hypoxia in atherosclerosis, coronary artery disease, and heart failure. Med Res J 2015; 3: 46-54.
 
25.
Aljakna A, Fracasso T, Sabatasso S. Molecular tissue changes in early myocardial ischemia: from pathophysiology to the identification of new diagnostic markers. Int J Legal Med 2018; 132: 425-438.
 
26.
Semenza GL. Hypoxia-inducible factor 1 and cardiovascular disease. Annu Rev Physiol 2014; 76: 39-56.
 
27.
Akbaş F, Atmaca HU, Pişkinpaşa ME. Can HIF-1 alpha (hypoxia-inducible factor-1 alpha) be a new cardiac hypoxia marker in acute coronary ischemia? Bagcilar Med Bull 2021; 6: 168-173.
 
28.
Glatz JFC, Renneberg R. Added value of H-FABP as plasma biomarker for the early evaluation of suspected acute coronary syndrome. Clin Lipidol 2014; 9: 205-220.
 
29.
Okamoto F, Sohmiya K, Ohkaru Y, Kawamura K, Asayama K, Kimura H, Nishimura S, Ishii H, Sunahara N, Tanaka T. Human heart-type cytoplasmic fatty acid-binding protein (H-FABP) for the diagnosis of acute myocardial infarction. Clinical evaluation of H-FABP in comparison with myoglobin and creatine kinase isoenzyme MB. Clin Chem Lab Med 2000; 38: 231-238.
 
30.
Valle HA, Garcia-Castrillo Riesgo L, Bel MS, Gonzalo FE, Sanchez MS, Oliva LI. Clinical assessment of heart-type fatty acid binding protein in early diagnosis of acute coronary syndrome. Eur J Emerg Med 2008; 15: 140-144.
 
31.
O’Donoghue M, De Lemos J, Morrow DA, Murphy SA, Buros JL, Cannon CP, Sabatine MS. Prognostic utility of heart-type fatty acid binding protein in patients with acute coronary syndromes. Circulation 2006; 114: 550-557.
 
32.
Viswanathan K, Kilcullen N, Morrell C, Thistlethwaite SJ, Sivananthan MU, Hassan TB, Barth JH, Hall Alistair S. Heart-type fatty acid-binding protein predicts long-term mortality and re-infarction in consecutive patients with suspected acute coronary syndrome who are troponin-negative. J Am Coll Cardiol 2010; 55: 2590-2598.
 
33.
Ho SK, Wu YW, Tseng WK, Leu HB, Yin WH, Lin TH, Chang KC, Wang JH, Yeh HI, Wu CC, Chen JW. The prognostic significance of heart-type fatty acid binding protein in patients with stable coronary heart disease. Sci Rep 2018; 8: 14410.
 
34.
Akinci S, Balcioğlu AS, Taçoy G, Tavil Y, Gülbahar Ö, Özdemir M. Effect of dobutamine stress echocardiography on serum heart fatty acid binding protein levels. Acta Cardiol 2017; 72: 161-166.
 
35.
Castillero E, Akashi H, Wang C, Najjar M, Ji R, Kennel PJ, Sweeney HL, Schulze PC, George I. Cardiac myostatin upregulation occurs immediately after myocardial ischemia and is involved in skeletal muscle activation of atrophy. Biochem Biophys Res Commun 2015; 457: 106-111.
 
36.
Chiang JY, Lin L, Wu CC, Hwang JJ, Yang WS, Wu YW. Serum myostatin level is associated with myocardial scar burden by SPECT myocardial perfusion imaging. Clin Chim Acta 2022; 537: 9-15.
 
37.
Bish LT, Morine KJ, Sleeper MM, Sweeney HL. Myostatin is upregulated following stress in an Erk-dependent manner and negatively regulates cardiomyocyte growth in culture and in a mouse model. PLoS One 2010; 5: e10230.
 
38.
Meloux A, Rochette L, Maza M, Bichat F, Tribouillard L, Cottin Y, Zeller M, Vergely C. Growth differentiation factor-8 (GDF8)/myostatin is a predictor of troponin i peak and a marker of clinical severity after acute myocardial infarction. J Clin Med 2019; 9: 116.
 
39.
Zhang C, McFarlane C, Lokireddy S, Bonala S, Ge X, Masuda S, Gluckman PD, Sharma M, Kambadur R. Myostatin-deficient mice exhibit reduced insulin resistance through activating the AMP-activated protein kinase signalling pathway. Diabetologia 2011; 54: 1491-1501.
 
40.
Calmettes G, Ribalet B, John S, Korge P, Ping P, Weiss JN. Hexokinases and cardioprotection. J Mol Cell Cardiol 2015; 78: 107-115.
 
41.
Wu R, Smeele KM, Wyatt E, Ichikawa Y, Eerbeek O, Sun L, Chawla K, Hollmann MW, Nagpal V, Heikkinen S, Laakso M, Jujo K, Wasserstrom JA, Zuurbier CJ, Ardeha- li H. Reduction in hexokinase II levels results in decreased cardiac function and altered remodeling after ischemia/reperfusion injury. Circ Res 2011; 108: 60-69.
 
42.
Pan M, Han Y, Basu A, Dai A, Si R, Willson C, Balistrie- ri A, Scott BT, Makino A. Overexpression of hexokinase 2 reduces mitochondrial calcium overload in coronary endothelial cells of type 2 diabetic mice. Am J Physiol Cell Physiol 2018; 314: C732-C740.
 
43.
Goliasch G, Kleber ME, Richter B, Plischke M, Hoke M, Haschemi A, Marculescu R, Endler G, Grammer TB, Pilz S, Tomaschitz A, Silbernagel G, Maurer G, Wagner O, Hu- ber K, März W, Mannhalter C, Niessner A. Routinely available biomarkers improve prediction of long-term mortality in stable coronary artery disease: the Vienna and Ludwigshafen Coronary Artery Disease (VILCAD) risk score. Eur Heart J 2012; 33: 2282-2289.
 
44.
Kleber ME, Goliasch G, Grammer TB, Pilz S, Tomaschitz A, Silbernagel G, Maurer G, März W, Niessner A. Evolving biomarkers improve prediction of long-term mortality in patients with stable coronary artery disease: the BIO-VILCAD score. J Intern Med 2014; 276: 184-194.
 
45.
Netto J, Teren A, Burkhardt R, Willenberg A, Beutner F, Henger S, Schuler G, Thiele H, Isermann B, Thiery J, Scholz M, Kaiser T. Biomarkers for non-invasive stratification of coronary artery disease and prognostic impact on long-term survival in patients with stable coronary heart disease. Nutrients 2022; 14: 3433.
 
46.
Medina-Leyte DJ, Zepeda-García O, Domínguez-Pérez M, González-Garrido A, Villarreal-Molina T, Jacobo-Albave- ra L. Endothelial dysfunction, inflammation and coronary artery disease: potential biomarkers and promising therapeutical approaches. Int J Mol Sci 2021; 22: 3850.
 
47.
Carnac G, Vernus B, Bonnieu A. Myostatin in the pathophysiology of skeletal muscle. Curr Genomics 2007; 8: 415-422.
 
48.
Rizvi SF, Hasan A, Parveen S, Mir SS. Untangling the complexity of heat shock protein 27 in cancer and metastasis. Arch Biochem Biophys 2023; 736: 109537.
 
49.
Sha G, Jiang Z, Zhang W, Jiang C, Wang D, Tang D. The multifunction of HSP70 in cancer: guardian or traitor to the survival of tumor cells and the next potential therapeutic target. Int Immunopharmacol 2023; 122: 110492.
 
50.
Shukla SD, Walters EH, Simpson JL, Keely S, Wark PAB, O’Toole RF, Hansbro PM. Hypoxia-inducible factor and bacterial infections in chronic obstructive pulmonary disease. Respirology 2020; 25: 53-63.
 
eISSN:2300-6722
ISSN:1899-1874
Journals System - logo
Scroll to top