Camporotondo R.

Cornara S.

Crimi G.

De Ferrari G. M.

Demarchi A.

Ferlini M.

Ferrario M.

Gnecchi M.

Mandurino-Mirizzi A.

Oltrona Visconti L.

Ruffinazzi M.

Somaschini A.

English

Archivio Istituzionale della Ricerca - Università degli Studi di Pavia

Downloadedfromhttps://journals.lww.com/jcardiovascularmedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3SN2oLfdKwVf4sWVOkLYfcVKZFilXJTN1iXGFIas9AC4=on03/12/2020Downloadedfromhttps://journals.lww.com/jcardiovascularmedicinebyBhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3SN2oLfdKwVf4sWVOkLYfcVKZFilXJTN1iXGFIas9AC4=on03/12/2020Serum uric acid may modulate the inflammatory responseafter primary percutaneous coronary intervention in patientswith ST-elevation myocardial infarctionAlessandro Mandurino-Mirizzia,b, Andrea Demarchia,b, Marta Ruffinazzia,b,Stefano Cornaraa,b, Alberto Somaschinia,b, Gabriele Crimia, Marco Ferlinia,Rita Camporotondoc, Massimiliano Gnecchib,c, Maurizio Ferrarioa,Luigi Oltrona Viscontia and Gaetano Maria De Ferrarib,cJ Cardiovasc Med 2020, 21:337–339aDivision of Cardiology, Fondazione IRCCS Policlinico San Matteo, bUniversity ofPavia, and cCoronary care unit, Fondazione IRCCS Policlinico San Matteo, Pavia,ItalyCorrespondence to Alessandro Mandurino-Mirizzi, MD, Cardiology Department,University of Pavia, Fondazione IRCCS Policlinico San Matteo, Pavia, PiazzaleGolgi 1, 27100 Pavia, ItalyTel: +39 0382 503158; e-mail: ale.mandurinomirizzi@gmail.comReceived 17 April 2019 Revised 4 December 2019Accepted 7 December 2019Elevated serum uric acid (SUA) has been associated withimpaired myocardial reperfusion and adverse outcomesin ST-segment elevation myocardial infarction (STEMI)patients treated with primary percutaneous coronaryintervention (pPCI).1–5 The mechanisms underlyingthese relationships are poorly investigated. Inflammationplays a central role in the pathogenesis of ischemia/reperfusion damage after pPCI.6–8 Preclinical studiesshowed that SUA may induce the inflammasome,enhancing the synthesis of IL-1b.8,9 The aim of our studywas to explore the relationship between SUA and theinflammatory response in patients with STEMI under-going pPCI.MethodsOur study included consecutive patients presentingwith STEMI within 12 h of symptom onset, treated withpPCI, between 2013 and 2014. SUA level was assessed onadmission; high-sensitivity C-reactive protein (hs-CRP)and interleukin-6 (IL-6) were measured before pPCI andafter 6, 12, 24, and 36 h. Angiographical parameters ofcoronary and myocardial reperfusion were evaluatedimmediately after the PCI as previously described.10Angiographic microvascular obstruction was defined asTIMI flow grade 2 or less or TIMI flow grade 3 withmyocardial blush grade less than 2. ST-resolution (STr)was assessed according to literature.11Elevated (e)SUA was defined as more than 6.8 mg/dl inagreement with previous reports.2,5,12 Categorical datawere expressed as count (percentage), continuous data asmeanSD or median (interquartile range); they werecompared with the Fisher exact test and with t-test,respectively. Correlations between SUA, hs-CRP andIL-6 were adjusted for potential confounders using mul-tiple linear regression model including age, sex, hyper-tension and myocardial infarct size as covariates. SUA,hs-CRP and IL-6 were log-normalized for statisticaltests.ResultsWe enrolled 44 STEMI patients. Overall age was 61 13years, 31 were man (70%), 7 had diabetes mellitus (16%).Twenty (45%) had an anterior myocardial infarction.Angiographic analyses are shown in Table 1. STroccurred less frequently in patients with eSUA as com-pared with patients with normal SUA (P¼ 0.016).Patients with eSUA had higher hs-CRP and IL-6 peakvalues (respectively, P¼ 0.004 and P¼ 0.006) (Table 1).In the overall population, there was a significant linearcorrelation between SUA levels and both Lnhs-CRP andLnIL-6 peak values (respectively, R¼ 0.366, P¼ 0.015and R¼ 0.484, P¼ 0.001; Fig. 1). The associationsbetween SUA and hs-CRP peak (b¼ 0.39, P¼ 0.019)and between SUA and IL-6 peak (b¼ 0.56, P¼ 0.001)were maintained after adjusting for covariates.CommentAmong patients with STEMI treated with pPCI wefound that: eSUA was associated with a greater inflam-matory response; in the overall population, there weresignificant correlations between baseline SUA levels andhs-CRP and IL-6 peak values. Previous findings sug-gested that SUA may induce the inflammasome8,9 andthis possible link may explain the association betweeneSUA and adverse outcomes after STEMI.2–4eSUA has been linked with worse myocardial reperfusionand larger infarct size after pPCI.4,5 We did not find anysignificant difference in angiographic parameters of reper-fusion between the groups, maybe because of the good finalResearch letter1558-2027  2020 Italian Federation of Cardiology - I.F.C. All rights reserved. DOI:10.2459/JCM.0000000000000926© 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.338 Journal of Cardiovascular Medicine 2020, Vol 21 No 4Fig. 1LnCRP0.001.00 1.20 1.40 1.60 1.80 2.00 2.20 1.00 1.20 1.40 1.60 1.80 2.00 2.201.003.004.005.006.002.00–2.00–1.001.002.003.000.00LnIL-6LnSUA LnSUALinear correlations between LnSUA–LnhsCRP and LnSUA–LnIL-6. CRP, C-reactive protein; IL-6, interleukin-6; SUA, serum uric acid. In the overallpopulation, there was a significant linear correlation between LnSUA and LnhsCRP (R2, 0.134, P ¼ 0.015) and between LnSUA and LnIL-6 peakvalues (R2 ¼ 0.235, P ¼ 0.001).Table 1 Angiographic analysesSUA6.8mg/dl (n¼14) SUA<6.8mg/dl (n¼30) P valueAge (years) 70 (8.9) 60 (15.3) 0.065Male 13 (92.9) 24 (80) 0.27Familiarity for CAD 3 (21.4) 8 (26.7) 0.51Dyslipidemia 8 (57.1) 16 (53.3) 0.53Hypertension 11 (78.6) 13 (43.3) 0.03Active smokers 3 (21.4) 20 (66.7) 0.01Diabetes 4 (28.6) 3 (10) 0.13Previous myocardial infarction 2 (14.3) 6 (20) 0.49Previous coronary intervention 1 (7.1) 6 (20) 0.27Serum creatinine 0.90 (0.19) 0.77 (0.27) 0.2Pain to balloon time (h) 4.17 (3.45) 3.75 (2.38) 0.17Multivessels disease 10 (71.4) 19 (63.3) 0.43Anterior MI 7 (50) 13 (44.8) 0.463Culprit vessel 0.93LAD 7 (50) 13 (44.8)CFX 2 (14.4) 4 (13.8)RCA 5 (32.6) 12 (41.4)Anti-GP IIb/IIIa 6 (42.9) 10 (33.3) 0.38Aspirin at baseline 6 (42.9) 8 (28.6) 0.27Statin at baseline 4 (28.6) 2 (6.7) 0.07Anti-inflammatory therapy at baseline 0 (0) 0 (0) 1SUA-lowering therapy at baseline 0 (0) 0 (0) 1Basal TIMI flow grade 10 14 (100) 30 (100)Final TIMI flow grade 13 14 (100) 30 (100)TIMI frame count, frames 13.8 (5.6) 12.9 (8.9) 0.57MBG 0.1760/1 5 (45.5) 7 (24.1)2 6 (54.5) 22 (75.9)Angiographic MVO 5 (45.5) 7 (24.1) 0.176ST-resolution 50% 5 (38.5) 8 (61.5) 0.016LVEF 41 (11.2) 44.8 (7.8) 0.068TNI peak (ng/ml) 48.7 (33.7–113.2) 49.1 (22.1–126.2) 0.614hs-CRP peak (mg/dl) 1.6 (0.7–2.5) 0.67 (0.46–1.1) 0.0038IL-6 peak (pg/ml) 23.4 (17.5–30.1) 13.6 (5.7–19) 0.006Values are mean ( standard deviation) or n (%); TNI, hs-CRP and IL-6 peak values are median (IQR). CAD, coronary artery disease; CFX, circumflex artery; hs-CRP, high-sensitivity C-reactive protein; LAD, left anterior descendent artery; LVEF, left ventricular ejection fraction; MBG, myocardial blush grade; MI, myocardial infarction; MVO,microvascular obstruction; RCA, right coronary artery; SUA, serum uric acid; TIMI, thrombolysis in myocardial infarction; TNI, troponin I.© 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.procedural result in the whole population and to thesmall sample size. Nevertheless, we found a significantdifference in STr between the groups, suggesting apossible relationship between eSUA and myocardialreperfusion impairment after technically successfulpPCI in STEMI.The main limitation of our study is the limited samplesize. However, we considered unselected STEMIpatients and we performed seriate dosages of hs-CRPand IL-6 to accurately estimate the inflammatoryresponse; additionally, we used multivariable analysisto adjust for possible confounders.Our findings put the spotlight on a possible pathophysio-logical role of SUA in STEMI treated with pPCI andwarrant further investigation. With anti-inflammatoryagents potentially available, eSUA may represent aneasily obtainable risk marker to identify good candidatesfor this novel therapeutic approach.AcknowledgementsThe authors take responsibility for all aspects of thereliability and freedom from bias of the data presentedand their discussed interpretation.Conflicts of interestThere are no conflicts of interest.References1 Bos MJ, Koudastaal PJ, Hofman A, Witteman JC, Breteler MM. Uric acid is arisk factor for myocardial infarction and stroke: the Rotterdam study. Stroke2006; 37:1503–1507.2 Kaya MG, Uyarel H, Akpek M, et al. Prognostic value of uric acid in patientswith ST-elevated myocardial infarction undergoing primary coronaryintervention. Am J Cardiol 2012; 109:486–491.3 Levantesi G, Marfisi RM, Franzosi MG, et al. Uric acid: a cardiovascular riskfactor in patients with recent myocardial infarction. Int J Cardiol 2013;167:262–269.4 Lazzeri C, Valente S, Chiostri M, Sori A, Bernardo P, Gensini GF. Uricacid in the acute phase of ST elevation myocardial infarction submitted toprimary PCI: its prognostic role and relation with inflammatory markers: asingle center experience. Int J Cardiol 2010; 138:206–209.5 Mandurino-Mirizzi A, Crimi G, Raineri C, et al. Elevated serum uric acidaffects myocardial reperfusion and infarct size in patients with ST-segmentelevation myocardial infarction undergoing primary percutaneouscoronary intervention. J Cardiovasc Med (Hagerstown) 2018; 19:240–246.6 Frangogiannis C, Smith CW, Entman ML. The inflammatory response inmyocardial infarction. Cardiovasc Res 2002; 53:31–47.7 Frangogiannis NG, Youker KA, Rossen RD, et al. Cytokines and themicrocirculation in ischemia and reperfusion. J Mol Cell Cardiol 1998;12:2567–2576.8 Libby P. Interleukin-1 beta as a target for atherosclerosis therapy. J Am CollCardiol 2017; 70:2278–2289.9 Martinon F, Petrilli V, Mayor A, et al. Gout-associated uric acid crystalsactivate the NALP3 inflammasome. Nature 2006; 440:237–241.10 van ’t Hof AW, Liem A, Suryapranata H, Hoorntje JC, de Boer MJ, Zijlstra F.Angiographic assessment of myocardial reperfusion in patients treatedwith primary angioplasty for acute myocardial infarction: myocardial blushgrade. Zwolle Myocardial Infarction Study Group. Circulation 1998;97:2302–2306.11 Schroder R. Prognostic impact of early ST-segment resolution in acute ST-elevation myocardial infarction. Circulation 2004; 110:e506–e510.12 Grassi D, Ferri L, Desideri G, et al. Chronic hyperuricemia, uric acid depositand cardiovascular risk. Curr Pharm Des 2013; 19:2432–2438.Uric acid and inflammatory response after myocardial infarction Mandurino-Mirizzi et al. 339© 2020 Italian Federation of Cardiology - I.F.C. All rights reserved.

Serum uric acid may modulate the inflammatory response after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction

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Serum uric acid may modulate the inflammatory response after primary percutaneous coronary intervention in patients with ST-elevation myocardial infarction

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