Association of C-Reactive Protein Velocity with Early Left Ventricular Dysfunction in Patients with First ST-Elevation Myocardial Infarction

Magdalena Holzknecht, Christina Tiller, Martin Reindl, Ivan Lechner, Priscilla Fink, Patrick Lunger, Agnes Mayr, Benjamin Henninger, Christoph Brenner, Gert Klug, Axel Bauer, Bernhard Metzler, Sebastian Johannes Reinstadler, Magdalena Holzknecht, Christina Tiller, Martin Reindl, Ivan Lechner, Priscilla Fink, Patrick Lunger, Agnes Mayr, Benjamin Henninger, Christoph Brenner, Gert Klug, Axel Bauer, Bernhard Metzler, Sebastian Johannes Reinstadler

Abstract

C-reactive protein velocity (CRPv) has been proposed as a very early and sensitive risk predictor in patients with ST-elevation myocardial infarction (STEMI). However, the association of CRPv with early left ventricular (LV) dysfunction after STEMI is unknown. The aim of this study was to investigate the relationship between CRPv and early LV dysfunction, either before or at hospital discharge, in patients with first STEMI. This analysis evaluated 432 STEMI patients that were included in the prospective MARINA-STEMI (Magnetic Resonance Imaging In Acute ST-elevation Myocardial Infarction. ClinicalTrials.gov Identifier: NCT04113356) cohort study. The difference of CRP 24 ± 8 h and CRP at hospital admission divided by the time (in h) that elapsed during the two examinations was defined as CRPv. Cardiac magnetic resonance (CMR) imaging was conducted at a median of 3 (IQR 2-4) days after primary percutaneous coronary intervention (PCI) for the determination of LV function and myocardial infarct characteristics. The association of CRPv with the CMR-derived LV ejection fraction (LVEF) was investigated. The median CRPv was 0.42 (IQR 0.21-0.76) mg/l/h and was correlated with LVEF (rS = -0.397, p < 0.001). In multivariable linear as well as binary logistic regression analysis (adjustment for biomarkers and clinical and angiographical parameters), CRPv was independently associated with LVEF (β: 0.161, p = 0.004) and LVEF ≤ 40% (OR: 1.71, 95% CI: 1.19-2.45; p = 0.004), respectively. The combined predictive value of peak cardiac troponin T (cTnT) and CRPv for LVEF ≤ 40% (AUC: 0.81, 95% CI 0.77-0.85, p < 0.001) was higher than it was for peak cTnT alone (AUC difference: 0.04, p = 0.009). CRPv was independently associated with early LV dysfunction, as measured by the CMR-determined LVEF, revealing an additive predictive value over cTnT after acute STEMI treated with primary PCI.

Keywords: C-reactive protein; ST-elevation myocardial infarction; cardiac magnetic resonance imaging; left ventricular function.

Conflict of interest statement

All authors have declared no conflict of interest.

Figures

Figure 1
Figure 1
Boxplot showing the relation between CRPv and LVEF. CRPv = C-reactive protein velocity, LVEF = left ventricular ejection fraction.

References

    1. Desta L., Jernberg T., Lofman I., Hofman-Bang C., Hagerman I., Spaak J., Persson H. Incidence, temporal trends, and prognostic impact of heart failure complicating acute myocardial infarction. The SWEDEHEART Registry (Swedish Web-System for Enhancement and Development of Evidence-Based Care in Heart Disease Evaluated According to Recommended Therapies): A study of 199,851 patients admitted with index acute myocardial infarctions, 1996 to 2008. JACC Heart Fail. 2015;3:234–242.
    1. Sutton N.R., Li S., Thomas L., Wang T.Y., de Lemos J.A., Enriquez J.R., Shah R.U., Fonarow G.C. The association of left ventricular ejection fraction with clinical outcomes after myocardial infarction: Findings from the Acute Coronary Treatment and Intervention Outcomes Network (ACTION) Registry-Get With the Guidelines (GWTG) Medicare-linked database. Am. Heart J. 2016;178:65–73. doi: 10.1016/j.ahj.2016.05.003.
    1. Ng V.G., Lansky A.J., Meller S., Witzenbichler B., Guagliumi G., Peruga J.Z., Brodie B., Shah R., Mehran R., Stone G.W. The prognostic importance of left ventricular function in patients with ST-segment elevation myocardial infarction: The HORIZONS-AMI trial. Eur. Heart J. Acute Cardiovasc. Care. 2014;3:67–77. doi: 10.1177/2048872613507149.
    1. Ponikowski P., Voors A.A., Anker S.D., Bueno H., Cleland J.G.F., Coats A.J.S., Falk V., Gonzalez-Juanatey J.R., Harjola V.P., Jankowska E.A., et al. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC) Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur. Heart J. 2016;37:2129–2200.
    1. Stumpf C., Sheriff A., Zimmermann S., Schaefauer L., Schlundt C., Raaz D., Garlichs C.D., Achenbach S. C-reactive protein levels predict systolic heart failure and outcome in patients with first ST-elevation myocardial infarction treated with coronary angioplasty. Arch. Med. Sci. 2017;13:1086–1093. doi: 10.5114/aoms.2017.69327.
    1. Reindl M., Reinstadler S.J., Feistritzer H.J., Klug G., Tiller C., Mair J., Mayr A., Jaschke W., Metzler B. Relation of inflammatory markers with myocardial and microvascular injury in patients with reperfused ST-elevation myocardial infarction. Eur. Heart J. Acute Cardiovasc. Care. 2017;6:640–649. doi: 10.1177/2048872616661691.
    1. Mather A.N., Fairbairn T.A., Artis N.J., Greenwood J.P., Plein S. Relationship of cardiac biomarkers and reversible and irreversible myocardial injury following acute myocardial infarction as determined by cardiovascular magnetic resonance. Int J. Cardiol. 2013;166:458–464. doi: 10.1016/j.ijcard.2011.11.004.
    1. Orn S., Manhenke C., Ueland T., Damas J.K., Mollnes T.E., Edvardsen T., Aukrust P., Dickstein K. C-reactive protein, infarct size, microvascular obstruction, and left-ventricular remodelling following acute myocardial infarction. Eur. Heart J. 2009;30:1180–1186. doi: 10.1093/eurheartj/ehp070.
    1. Yip H.K., Hang C.L., Fang C.Y., Hsieh Y.K., Yang C.H., Hung W.C., Wu C.J. Level of high-sensitivity C-reactive protein is predictive of 30-day outcomes in patients with acute myocardial infarction undergoing primary coronary intervention. Chest. 2005;127:803–808. doi: 10.1378/chest.127.3.803.
    1. Theroux P., Armstrong P.W., Mahaffey K.W., Hochman J.S., Malloy K.J., Rollins S., Nicolau J.C., Lavoie J., Luong T.M., Burchenal J., et al. Prognostic significance of blood markers of inflammation in patients with ST-segment elevation myocardial infarction undergoing primary angioplasty and effects of pexelizumab, a C5 inhibitor: A substudy of the COMMA trial. Eur. Heart J. 2005;26:1964–1970. doi: 10.1093/eurheartj/ehi292.
    1. Ortolani P., Marzocchi A., Marrozzini C., Palmerini T., Saia F., Taglieri N., Baldazzi F., Silenzi S., Bacchi-Reggiani M.L., Guastaroba P., et al. Predictive value of high sensitivity C-reactive protein in patients with ST-elevation myocardial infarction treated with percutaneous coronary intervention. Eur. Heart J. 2008;29:1241–1249. doi: 10.1093/eurheartj/ehm338.
    1. Kushner I., Broder M.L., Karp D. Control of the acute phase response. Serum C-reactive protein kinetics after acute myocardial infarction. J. Clin. Investig. 1978;61:235–242. doi: 10.1172/JCI108932.
    1. Mani P., Puri R., Schwartz G.G., Nissen S.E., Shao M., Kastelein J.J.P., Menon V., Lincoff A.M., Nicholls S.J. Association of Initial and Serial C-Reactive Protein Levels With Adverse Cardiovascular Events and Death After Acute Coronary Syndrome: A Secondary Analysis of the VISTA-16 Trial. JAMA Cardiol. 2019;4:314–320. doi: 10.1001/jamacardio.2019.0179.
    1. Swiatkiewicz I., Magielski P., Kubica J. C-Reactive Protein as a Risk Marker for Post-Infarct Heart Failure over a Multi-Year Period. Int. J. Mol. Sci. 2021;22:3169. doi: 10.3390/ijms22063169.
    1. Swiatkiewicz I., Taub P.R. The usefulness of C-reactive protein for the prediction of post-infarct left ventricular systolic dysfunction and heart failure. Kardiol. Pol. 2018;76:821–829. doi: 10.5603/KP.a2018.0091.
    1. Swiatkiewicz I., Magielski P., Kubica J., Zadourian A., DeMaria A.N., Taub P.R. Enhanced Inflammation is a Marker for Risk of Post-Infarct Ventricular Dysfunction and Heart Failure. Int. J. Mol. Sci. 2020;21:807. doi: 10.3390/ijms21030807.
    1. Swiatkiewicz I., Kozinski M., Magielski P., Fabiszak T., Sukiennik A., Navarese E.P., Odrowaz-Sypniewska G., Kubica J. Value of C-reactive protein in predicting left ventricular remodelling in patients with a first ST-segment elevation myocardial infarction. Mediat. Inflamm. 2012;2012:250867. doi: 10.1155/2012/250867.
    1. Ries W., Torzewski J., Heigl F., Pfluecke C., Kelle S., Darius H., Ince H., Mitzner S., Nordbeck P., Butter C., et al. C-Reactive Protein Apheresis as Anti-inflammatory Therapy in Acute Myocardial Infarction: Results of the CAMI-1 Study. Front. Cardiovasc. Med. 2021;8:591714. doi: 10.3389/fcvm.2021.591714.
    1. Holzknecht M., Tiller C., Reindl M., Lechner I., Troger F., Hosp M., Mayr A., Brenner C., Klug G., Bauer A., et al. C-reactive protein velocity predicts microvascular pathology after acute ST-elevation myocardial infarction. Int. J. Cardiol. 2021 doi: 10.1016/j.ijcard.2021.06.023.
    1. Zahler D., Merdler I., Rozenfeld K.L., Shenberg G., Milwidsky A., Berliner S., Banai S., Arbel Y., Shacham Y. C-Reactive Protein Velocity and the Risk of New Onset Atrial Fibrillation among ST Elevation Myocardial Infarction Patients. Isr. Med. Assoc. J. 2021;23:169–173.
    1. Milwidsky A., Ziv-Baran T., Letourneau-Shesaf S., Keren G., Taieb P., Berliner S., Shacham Y. CRP velocity and short-term mortality in ST segment elevation myocardial infarction. Biomarkers. 2017;22:383–386. doi: 10.1080/1354750X.2017.1279218.
    1. Zahler D., Rozenfeld K.L., Stein M., Milwidsky A., Berliner S., Banai S., Arbel Y., Shacham Y. C-reactive protein velocity and the risk of acute kidney injury among ST elevation myocardial infarction patients undergoing primary percutaneous intervention. J. Nephrol. 2019;32:437–443. doi: 10.1007/s40620-019-00594-2.
    1. Thygesen K., Alpert J.S., Jaffe A.S., Chaitman B.R., Bax J.J., Morrow D.A., White H.D., Group E.S.C.S.D. Fourth universal definition of myocardial infarction (2018) Eur. Heart J. 2019;40:237–269. doi: 10.1093/eurheartj/ehy462.
    1. Reinstadler S.J., Feistritzer H.J., Klug G., Mair J., Tu A.M., Kofler M., Henninger B., Franz W.M., Metzler B. High-sensitivity troponin T for prediction of left ventricular function and infarct size one year following ST-elevation myocardial infarction. Int. J. Cardiol. 2016;202:188–193. doi: 10.1016/j.ijcard.2015.09.001.
    1. Feistritzer H.J., Reinstadler S.J., Klug G., Reindl M., Wohrer S., Brenner C., Mayr A., Mair J., Metzler B. Multimarker approach for the prediction of microvascular obstruction after acute ST-segment elevation myocardial infarction: A prospective, observational study. BMC Cardiovasc. Disord. 2016;16:239. doi: 10.1186/s12872-016-0415-z.
    1. McDonagh T.A., Metra M., Adamo M., Gardner R.S., Baumbach A., Bohm M., Burri H., Butler J., Celutkiene J., Chioncel O., et al. 2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur. Heart J. 2021;42:3599–3726. doi: 10.1093/eurheartj/ehab368.
    1. Gavara J., Marcos-Garces V., Lopez-Lereu M.P., Monmeneu J.V., Rios-Navarro C., de Dios E., Perez N., Merenciano H., Gabaldon A., Canoves J., et al. Magnetic Resonance Assessment of Left Ventricular Ejection Fraction at Any Time Post-Infarction for Prediction of Subsequent Events in a Large Multicenter STEMI Registry. J. Magn. Reson. Imaging. 2021 doi: 10.1002/jmri.27789.
    1. Reinstadler S.J., Klug G., Feistritzer H.J., Mayr A., Harrasser B., Mair J., Bader K., Streil K., Hammerer-Lercher A., Esterhammer R., et al. Association of copeptin with myocardial infarct size and myocardial function after ST segment elevation myocardial infarction. Heart. 2013;99:1525–1529. doi: 10.1136/heartjnl-2013-303975.
    1. Holzknecht M., Reindl M., Tiller C., Reinstadler S.J., Lechner I., Pamminger M., Schwaiger J.P., Klug G., Bauer A., Metzler B., et al. Global longitudinal strain improves risk assessment after ST-segment elevation myocardial infarction: A comparative prognostic evaluation of left ventricular functional parameters. Clin. Res. Cardiol. 2021;110:1599–1611. doi: 10.1007/s00392-021-01855-6.
    1. Lechner I., Reindl M., Tiller C., Holzknecht M., Troger F., Fink P., Mayr A., Klug G., Bauer A., Metzler B., et al. Impact of COVID-19 pandemic restrictions on ST-segment elevation myocardial infarction: A cardiac MRI study. Eur. Heart J. 2021:ehab621. doi: 10.1093/eurheartj/ehab621.
    1. Reindl M., Reinstadler S.J., Feistritzer H.J., Theurl M., Basic D., Eigler C., Holzknecht M., Mair J., Mayr A., Klug G., et al. Relation of Low-Density Lipoprotein Cholesterol with Microvascular Injury and Clinical Outcome in Revascularized ST-Elevation Myocardial Infarction. J. Am. Heart Assoc. 2017;6:e006957. doi: 10.1161/JAHA.117.006957.
    1. Bondarenko O., Beek A.M., Hofman M.B., Kuhl H.P., Twisk J.W., van Dockum W.G., Visser C.A., van Rossum A.C. Standardizing the definition of hyperenhancement in the quantitative assessment of infarct size and myocardial viability using delayed contrast-enhanced CMR. J. Cardiovasc. Magn. Reson. 2005;7:481–485. doi: 10.1081/JCMR-200053623.
    1. DeLong E.R., DeLong D.M., Clarke-Pearson D.L. Comparing the areas under two or more correlated receiver operating characteristic curves: A nonparametric approach. Biometrics. 1988;44:837–845. doi: 10.2307/2531595.
    1. Rice M.E., Harris G.T. Comparing effect sizes in follow-up studies: ROC Area, Cohen’s d, and r. Law Hum. Behav. 2005;29:615–620. doi: 10.1007/s10979-005-6832-7.
    1. Fanola C.L., Morrow D.A., Cannon C.P., Jarolim P., Lukas M.A., Bode C., Hochman J.S., Goodrich E.L., Braunwald E., O’Donoghue M.L. Interleukin-6 and the Risk of Adverse Outcomes in Patients After an Acute Coronary Syndrome: Observations From the SOLID-TIMI 52 (Stabilization of Plaque Using Darapladib-Thrombolysis in Myocardial Infarction 52) Trial. J. Am. Heart Assoc. 2017;6:e005637. doi: 10.1161/JAHA.117.005637.
    1. Sheriff A., Kayser S., Brunner P., Vogt B. C-Reactive Protein Triggers Cell Death in Ischemic Cells. Front. Immunol. 2021;12:630430. doi: 10.3389/fimmu.2021.630430.
    1. Vanhaverbeke M., Veltman D., Pattyn N., De Crem N., Gillijns H., Cornelissen V., Janssens S., Sinnaeve P.R. C-reactive protein during and after myocardial infarction in relation to cardiac injury and left ventricular function at follow-up. Clin. Cardiol. 2018;41:1201–1206. doi: 10.1002/clc.23017.
    1. Tiller C., Reindl M., Holzknecht M., Lechner I., Simma F., Schwaiger J., Mayr A., Klug G., Bauer A., Reinstadler S.J., et al. High sensitivity C-reactive protein is associated with worse infarct healing after revascularized ST-elevation myocardial infarction. Int. J. Cardiol. 2020;328:191–196. doi: 10.1016/j.ijcard.2020.12.006.
    1. de Waha S., Patel M.R., Granger C.B., Ohman E.M., Maehara A., Eitel I., Ben-Yehuda O., Jenkins P., Thiele H., Stone G.W. Relationship between microvascular obstruction and adverse events following primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: An individual patient data pooled analysis from seven randomized trials. Eur. Heart J. 2017;38:3502–3510. doi: 10.1093/eurheartj/ehx414.
    1. Reinstadler S.J., Stiermaier T., Eitel C., Fuernau G., Saad M., Poss J., de Waha S., Mende M., Desch S., Metzler B., et al. Impact of Atrial Fibrillation During ST-Segment-Elevation Myocardial Infarction on Infarct Characteristics and Prognosis. Circ. Cardiovasc. Imaging. 2018;11:e006955. doi: 10.1161/CIRCIMAGING.117.006955.
    1. Montone R.A., La Vecchia G. Interplay between inflammation and microvascular obstruction in ST-segment elevation myocardial infarction: The importance of velocity. Int J. Cardiol. 2021;339:7–9. doi: 10.1016/j.ijcard.2021.07.041.
    1. . CRP Apheresis in STEMI. [(accessed on 27 September 2021)]; Available online: .
    1. Broch K., Anstensrud A.K., Woxholt S., Sharma K., Tollefsen I.M., Bendz B., Aakhus S., Ueland T., Amundsen B.H., Damas J.K., et al. Randomized Trial of Interleukin-6 Receptor Inhibition in Patients with Acute ST-Segment Elevation Myocardial Infarction. J. Am. Coll. Cardiol. 2021;77:1845–1855. doi: 10.1016/j.jacc.2021.02.049.
    1. Toldo S., Abbate A. The NLRP3 inflammasome in acute myocardial infarction. Nat. Rev. Cardiol. 2018;15:203–214. doi: 10.1038/nrcardio.2017.161.
    1. Abbate A., Toldo S., Marchetti C., Kron J., Van Tassell B.W., Dinarello C.A. Interleukin-1 and the Inflammasome as Therapeutic Targets in Cardiovascular Disease. Circ. Res. 2020;126:1260–1280. doi: 10.1161/CIRCRESAHA.120.315937.
    1. Abbate A., Kontos M.C., Grizzard J.D., Biondi-Zoccai G.G., Van Tassell B.W., Robati R., Roach L.M., Arena R.A., Roberts C.S., Varma A., et al. Interleukin-1 blockade with anakinra to prevent adverse cardiac remodeling after acute myocardial infarction (Virginia Commonwealth University Anakinra Remodeling Trial [VCU-ART] Pilot study) Am. J. Cardiol. 2010;105:1371–1377.e1. doi: 10.1016/j.amjcard.2009.12.059.
    1. Everett B.M., Cornel J.H., Lainscak M., Anker S.D., Abbate A., Thuren T., Libby P., Glynn R.J., Ridker P.M. Anti-Inflammatory Therapy with Canakinumab for the Prevention of Hospitalization for Heart Failure. Circulation. 2019;139:1289–1299. doi: 10.1161/CIRCULATIONAHA.118.038010.
    1. El-Menyar A., Zubaid M., AlMahmeed W., Sulaiman K., AlNabti A., Singh R., Al Suwaidi J. Killip classification in patients with acute coronary syndrome: Insight from a multicenter registry. Am. J. Emerg. Med. 2012;30:97–103. doi: 10.1016/j.ajem.2010.10.011.
    1. Overtchouk P., Barthelemy O., Hauguel-Moreau M., Guedeney P., Rouanet S., Zeitouni M., Silvain J., Collet J.P., Vicaut E., Zeymer U., et al. Angiographic predictors of outcome in myocardial infarction patients presenting with cardiogenic shock: A CULPRIT-SHOCK angiographic substudy. EuroIntervention. 2021;16:e1237–e1244. doi: 10.4244/EIJ-D-20-00139.
    1. Gibson C.M., Schomig A. Coronary and myocardial angiography: Angiographic assessment of both epicardial and myocardial perfusion. Circulation. 2004;109:3096–3105. doi: 10.1161/01.CIR.0000134278.50359.CB.

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