Evaluation of Hematological and Biochemical Parameters that Predict the No-reflow Phenomenon in Patients Undergoing Primary Percutaneous Coronary Intervention
Restricted accessResearch articleFirst published online November, 2025
Evaluation of Hematological and Biochemical Parameters that Predict the No-reflow Phenomenon in Patients Undergoing Primary Percutaneous Coronary Intervention
Acute coronary syndromes (ACS) are one of the most common causes of morbidity and mortality worldwide. Primary percutaneous coronary intervention (pPCI) is the main treatment strategy to restore myocardial perfusion. However, the no-reflow phenomenon (NRP) may block coronary flow. The present study focused on assessing and contrasting predictive parameters for NRP in ACS patients. Our research is a retrospective analysis. We assessed the parameters significantly associated with NRP using Cox regression and Receiver operating characteristic (ROC) Curve analysis. The study included 5122 patients who met the criteria. The average age of the patients was 63.9 + 13.2, and 74.4% were male. It was observed that NRP developed in 1.8% of all patients. Age, hemoglobin (Hb), white blood cell (WBC), glucose and low density lipoprotein cholesterol (LDL-C) were determined to be independent predictors of NRP. The power of these parameters to predict NRP was similar, and WBC was the most predictive (Area Under Curve (AUC): 0.605 95% CI: 0.539–0.671, P = .001). We believe that the use of these simple, practical, and routinely used hematological and biochemical parameters will help us predict the risk of developing NRP before pPCI. This information should improve management.
GBD 2017 Causes of Death Collaborators. Global, regional, and national age-sex-specific mortality for 282 causes of death in 195 countries and territories, 1980-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet. 2018;392:1736-88.
2.
TimmisAVardasPTownsendN, et al. European Society of Cardiology: cardiovascular disease statistics 2021. Eur Heart J. 2022;43:716-99.
3.
ByrneRARosselloXCoughlanJJ, et al. 2023 ESC Guidelines for the management of acute coronary syndromes. Eur Heart J. 2023;44:3720-826.
4.
KaurGBaghdasaryanPNatarajanB, et al. Pathophysiology, diagnosis, and management of coronary no-reflow phenomenon. Int J Angiol. 2021;30:15-21.
5.
RezkallaSHStankowskiRVHannaJKlonerRA.Management of no-reflow phenomenon in the catheterization laboratory. JACC Cardiovasc Interv. 2017;10:215-23.
6.
GalassoGSchiekoferSD’AnnaC, et al. No-reflow phenomenon: pathophysiology, diagnosis, prevention, and treatment. A review of the current literature and future perspectives. Angiology. 2014;65:180-9.
7.
WuXMintzGSXuK, et al. The relationship between attenuated plaque identified by intravascular ultrasound and no-reflow after stenting in acute myocardial infarction: the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial. JACC Cardiovasc Interv. 2011;4:495-502.
8.
BekkersSCYazdaniSKVirmaniRWaltenbergerJ.Microvascular obstruction: underlying pathophysiology and clinical diagnosis. J Am Coll Cardiol. 2010;55:1649-60.
9.
ChandrashekharYAlexanderTMullasariA, et al. Resource and infrastructure-appropriate management of ST-segment elevation myocardial infarction in low- and middle-income countries. Circulation. 2020;141:2004-25.
10.
RefaatHTantawyAGamalASRadwanH.Novel predictors and adverse long-term outcomes of No-reflow phenomenon in patients with acute ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Indian Heart J. 2021;73:35-43.
11.
Nair RajeshGJayaprasadNMadhavanS, et al. Predictors and prognosis of no-reflow during primary percutaneous coronary intervention. Proc (Bayl Univ Med Cent). 2019;32:30-3.
12.
de WahaSPatelMRGrangerCB, et al. 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;38:3502-10.
13.
NiccoliGRigattieriSDe VitaMR, et al. Open-label, randomized, placebo-controlled evaluation of intracoronary adenosine or nitroprusside after thrombus aspiration during primary percutaneous coronary intervention for the prevention of microvascular obstruction in acute myocardial infarction: the REOPEN-AMI study (Intracoronary Nitroprusside Versus Adenosine in Acute Myocardial Infarction). JACC Cardiovasc Interv. 2013;6:580-9.
14.
ThygesenKAlpertJSJaffeAS, et al. Fourth universal definition of myocardial infarction (2018). Eur Heart J. 2019;40:237-69.
15.
GibsonCMCannonCPMurphySA, et al. Relationship of the TIMI myocardial perfusion grades, flow grades, frame count, and percutaneous coronary intervention to long-term outcomes after thrombolytic administration in acute myocardial infarction. Circulation. 2002;105:1909-13.
ManciniJGFilionKBWindleSBHabibBEisenbergMJ.Meta-analysis of the long-term effect of routine aspiration thrombectomy in patients undergoing primary percutaneous coronary intervention. Am J Cardiol. 2016;118:23-31.
18.
ZhouHHeXYZhuangSW, et al. Clinical and procedural predictors of no-reflow in patients with acute myocardial infarction after primary percutaneous coronary intervention. World J Emerg Med. 2014;5:96-102.
19.
AshrafTKhanMNAfaqueSM, et al. Clinical and procedural predictors and short-term survival of the patients with no reflow phenomenon after primary percutaneous coronary intervention. Int J Cardiol. 2019;294:27-31.
20.
AlidoostiMLotfiRLotfi-TokaldanyM, et al. Correlates of the “no-reflow” or “slow-flow” phenomenon in patients undergoing primary percutaneous coronary intervention. J Tehran Heart Cent. 2018;13:108-14.
21.
FajarJKHeriansyahTRohmanMS.The predictors of no reflow phenomenon after percutaneous coronary intervention in patients with ST elevation myocardial infarction: a meta-analysis. Indian Heart J. 2018;70:S406-18.
22.
MazharJMashicharanMFarshidA.Predictors and outcome of no-reflow post primary percutaneous coronary intervention for ST elevation myocardial infarction. Int J Cardiol Heart Vasc. 2016;10:8-12.
23.
ShakibaMSalariAMirboloukFSotudehNNikfarjamS.Clinical, laboratory, and procedural predictors of no-reflow in patients undergoing primary percutaneous coronary intervention. J Tehran Heart Cent. 2020;15:50-6.
24.
AggarwalPRekwalLSinhaSKNathRKKhanraDSinghAP.Predictors of no-reflow phenomenon following percutaneous coronary intervention for ST-segment elevation myocardial infarction. Ann Cardiol Angeiol (Paris). 2021;70:136-42.
25.
YangLCongHLuYChenXLiuY.Prediction of no-reflow phenomenon in patients treated with primary percutaneous coronary intervention for ST-segment elevation myocardial infarction. Medicine (Baltimore). 2020;99:e20152.
26.
YaylakBAltintasBOzcanKS, et al. Relation of hemoglobin level to no-reflow in patients with ST-segment elevation myocardial infarction undergoing primary coronary intervention. Postepy Kardiol Interwencyjnej. 2018;14:383-90.
27.
VaratMAAdolphRJFowlerNO.Cardiovascular effects of anemia. Am Heart J. 1972;83:415-26.
28.
MostASRuoccoNAJrGewirtzH.Effect of a reduction in blood viscosity on maximal myocardial oxygen delivery distal to a moderate coronary stenosis. Circulation. 1986;74:1085-92.
29.
TwomleyKMRaoSVBeckerRC.Proinflammatory, immunomodulating, and prothrombotic properties of anemia and red blood cell transfusions. J Thromb Thrombolysis. 2006;21:167-74.
30.
SalvagnoGLSanchis-GomarFPicanzaALippiG.Red blood cell distribution width: a simple parameter with multiple clinical applications. Crit Rev Clin Lab Sci. 2015;52:86-105.
31.
LappeJMHorneBDShahSH, et al. Red cell distribution width, C-reactive protein, the complete blood count, and mortality in patients with coronary disease and a normal comparison population. Clin Chim Acta. 2011;412:2094-9.
32.
UyarelHErgelenMCicekG, et al. Red cell distribution width as a novel prognostic marker in patients undergoing primary angioplasty for acute myocardial infarction. Coron Artery Dis. 2011;22:138-44.
33.
DvornikSZaninovic JurjevicTJurjevicNLekicAZaputovicL.Prognostic factors for in-hospital mortality of patients hospitalized for acutely decompensated heart failure. Acta Clin Belg. 2018;73:199-206.
34.
SahinkusSCakarMYaylaciS, et al. Hematological markers of the no-reflow phenomen on in-patients undergoing primary percutaneous coronary intervention. Georgian Med News. 2016;254:26-32.
35.
IsikTKurtMAyhanETanbogaIHErgelenMUyarelH.The impact of admission red cell distribution width on the development of poor myocardial perfusion after primary percutaneous intervention. Atherosclerosis. 2012;224:143-9.
36.
ZhangEGaoMGaoJ, et al. Inflammatory and hematological indices as simple, practical severity predictors of microdysfunction following coronary intervention: a systematic review and meta-analysis. Angiology. 2020;71:349-59.
37.
SunYRenJLiLWangCYaoH.RDW as a predictor for no-reflow phenomenon in DM patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. J Clin Med. 2023;12:807.
38.
LibbyP.Mechanisms of acute coronary syndromes and their implications for therapy. N Engl J Med. 2013;368:2004-13.
39.
LibbyPNahrendorfMSwirskiFK.Leukocytes link local and systemic inflammation in ischemic cardiovascular disease: an expanded “cardiovascular continuum”. J Am Coll Cardiol. 2016;67:1091-103.
40.
OttINeumannFJKenngottSGawazMSchomigA.Procoagulant inflammatory responses of monocytes after direct balloon angioplasty in acute myocardial infarction. Am J Cardiol. 1998;82:938-42.
41.
WongDTPuriRRichardsonJDWorthleyMIWorthleySG.Myocardial ‘no-reflow’—diagnosis, pathophysiology and treatment. Int J Cardiol. 2013;167:1798-806.
42.
NunezJMinanaGBodiV, et al. Low lymphocyte count and cardiovascular diseases. Curr Med Chem. 2011;18:3226-33.
43.
BlumAYeganehS.The role of T-lymphocyte subpopulations in acute myocardial infarction. Eur J Intern Med. 2003;14:407-10.
44.
LeyKMillerYIHedrickCC.Monocyte and macrophage dynamics during atherogenesis. Arterioscler Thromb Vasc Biol. 2011;31:1506-16.
45.
AultKACannonCPMitchellJ, et al. Platelet activation in patients after an acute coronary syndrome: results from the TIMI-12 trial. Thrombolysis in myocardial infarction. J Am Coll Cardiol. 1999;33:634-9.
46.
TsiaraSElisafMJagroopIAMikhailidisDP.Platelets as predictors of vascular risk: is there a practical index of platelet activity?Clin Appl Thromb Hemost. 2003;9:177-90.
47.
WangZRenLLeiLYeHPengJ.The relationship between neutrophil counts on admission and angiographic no-reflow after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Acta Cardiol. 2016;71:241-6.
48.
TianJLiuYLiuY, et al. Prognostic Association of circulating neutrophil count with no-reflow in patients with ST-segment elevation myocardial infarction following successful primary percutaneous intervention. Dis Markers. 2017;2017:8458492.
49.
CelikTBaltaSMikhailidisDP, et al. The relation between no-reflow phenomenon and complete blood count parameters. Angiology. 2017;68:381-8.
50.
TamhaneUUAnejaSMontgomeryDRogersEKEagleKAGurmHS.Association between admission neutrophil to lymphocyte ratio and outcomes in patients with acute coronary syndrome. Am J Cardiol. 2008;102:653-7.
51.
OsadnikTWasilewskiJLekstonA, et al. The platelet-to-lymphocyte ratio as a predictor of all-cause mortality in patients with coronary artery disease undergoing elective percutaneous coronary intervention and stent implantation. J Saudi Heart Assoc. 2015;27:144-51.
52.
WangDYangJXCaoDY, et al. Preoperative neutrophil-lymphocyte and platelet-lymphocyte ratios as independent predictors of cervical stromal involvement in surgically treated endometrioid adenocarcinoma. Onco Targets Ther. 2013;6:211-6.
53.
ChoKIAnnSHSinghGBHerAYShinES.Combined usefulness of the platelet-to-lymphocyte ratio and the neutrophil-to-lymphocyte ratio in predicting the long-term adverse events in patients who have undergone percutaneous coronary intervention with a drug-eluting stent. PLoS One. 2015;10:e0133934.
54.
ChenHLiMLiuLDangXZhuDTianG.Monocyte/lymphocyte ratio is related to the severity of coronary artery disease and clinical outcome in patients with non-ST-elevation myocardial infarction. Medicine (Baltimore). 2019;98:e16267.
55.
WagdySSobhyMLoutfiM.Neutrophil/lymphocyte ratio as a predictor of in-hospital major adverse cardiac events, new-onset atrial fibrillation, and no-reflow phenomenon in patients with ST elevation myocardial infarction. Clin Med Insights Cardiol. 2016;10:19-22.
56.
ZhangQHuMSunJMaS.The combination of neutrophil-to-lymphocyte ratio and platelet correlation parameters in predicting the no-reflow phenomenon after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Scand Cardiovasc J. 2020;54:352-7.
57.
LeeMJParkSDKwonSW, et al. Relation between neutrophil-to-lymphocyte ratio and index of microcirculatory resistance in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Am J Cardiol. 2016;118:1323-8.
58.
KurtulAMuratSNYarliogluesM, et al. Increased neutrophil-to-lymphocyte ratio predicts persistent coronary no-flow after wire insertion in patients with ST-elevation myocardial infarction undergoing primary percutaneous coronary intervention. Clinics (Sao Paulo). 2015;70:34-40.
59.
RostamiATajlilASeparhamA, et al. Association between neutrophil-to-lymphocyte ratio and the systemic inflammatory immunologic index and the angiographic SYNTAX score and the TIMI flow grade in acute STEMI: a cohort study. J Tehran Heart Cent. 2021;16:147-55.
60.
AkpekMKayaMGLamYY, et al. Relation of neutrophil/lymphocyte ratio to coronary flow to in-hospital major adverse cardiac events in patients with ST-elevated myocardial infarction undergoing primary coronary intervention. Am J Cardiol. 2012;110:621-7.
61.
CelikTBaltaSDemirM, et al. Predictive value of admission red cell distribution width-platelet ratio for no-reflow phenomenon in acute ST segment elevation myocardial infarction undergoing primary percutaneous coronary intervention. Cardiol J. 2016;23:84-92.
62.
ZhangSDiaoJQiC, et al. Predictive value of neutrophil to lymphocyte ratio in patients with acute ST segment elevation myocardial infarction after percutaneous coronary intervention: a meta-analysis. BMC Cardiovasc Disord. 2018;18:75.
63.
KarahanZUcamanBUlugAV, et al. Effect of hematologic parameters on microvascular reperfusion in patients with ST-segment elevation myocardial infarction treated with primary percutaneous coronary intervention. Angiology. 2016;67:151-6.
64.
KurtulAYarliogluesMMuratSN, et al. Usefulness of the platelet-to-lymphocyte ratio in predicting angiographic reflow after primary percutaneous coronary intervention in patients with acute ST-segment elevation myocardial infarction. Am J Cardiol. 2014;114:342-7.
65.
YildizAYukselMOylumluM, et al. The utility of the platelet-lymphocyte ratio for predicting no reflow in patients with ST-segment elevation myocardial infarction. Clin Appl Thromb Hemost. 2015;21:223-8.
66.
BadranHMFatahAASoltanG.Platelet/lymphocyte ratio for prediction of no-reflow phenomenon in ST-elevation myocardial infarction managed with primary percutaneous coronary intervention. J Clin Transl Res. 2020;6:20-6.
67.
KurtulAYarliogluesMCelikIE, et al. Association of lymphocyte-to-monocyte ratio with the no-reflow phenomenon in patients who underwent a primary percutaneous coronary intervention for ST-elevation myocardial infarction. Coron Artery Dis. 2015;26:706-12.
68.
LiuYYeTChenL, et al. Systemic immune-inflammation index predicts the severity of coronary stenosis in patients with coronary heart disease. Coron Artery Dis. 2021;32:715-20.
69.
EsenbogaKKurtulAYamanturkYYTanTSTutarDE.Systemic immune-inflammation index predicts no-reflow phenomenon after primary percutaneous coronary intervention. Acta Cardiol. 2022;77:59-65.
70.
CelikMCKarayigitOOzkanCDoluAKKalcikM.Relationship between systemic inflammation index and no-reflow phenomenon in patients with ST-segment elevation myocardial infarction. Angiology. 2023;74:387-94.
71.
PolatNOylumluMIsikMA, et al. Prognostic significance of serum albumin in patients with acute coronary syndrome. Angiology. 2020;71:903-8.
72.
PlakhtYGilutzHShiyovichA.Decreased admission serum albumin level is an independent predictor of long-term mortality in hospital survivors of acute myocardial infarction. Soroka Acute Myocardial Infarction II (SAMI-II) project. Int J Cardiol. 2016;219:20-4.
73.
FaircloughECairnsEHamiltonJKellyC.Evaluation of a modified early warning system for acute medical admissions and comparison with C-reactive protein/albumin ratio as a predictor of patient outcome. Clin Med (Lond). 2009;9:30-3.
74.
RanzaniOTZampieriFGForteDNAzevedoLCParkM.C-reactive protein/albumin ratio predicts 90-day mortality of septic patients. PLoS One. 2013;8:e59321.
75.
KalyoncuogluMDurmusG.Relationship between C-reactive protein-to-albumin ratio and the extent of coronary artery disease in patients with non-ST-elevated myocardial infarction. Coron Artery Dis. 2020;31:130-6.
76.
KarabagYCagdasMRencuzogullariI, et al. Usefulness of the C-reactive protein/albumin ratio for predicting no-reflow in ST-elevation myocardial infarction treated with primary percutaneous coronary intervention. Eur J Clin Invest. 2018;48:e12928.
77.
Rodi TosuACinarTKalyoncuogluM, et al. Predictive value of C-reactive protein/albumin ratio for no-reflow in patients with non-ST-elevation myocardial infarction. J Cardiovasc Thorac Res. 2022;14:214-9.
78.
KanalYSeyda KanalHEYakutI, et al. CRP albumin ratio may predict no reflow in patients undergoing percutaneous coronary intervention for saphenous vein graft stenosis. Angiology. 2023;74:55-61.
79.
KurtulAAcikgozSK.Usefulness of mean platelet volume-to-lymphocyte ratio for predicting angiographic no-reflow and short-term prognosis after primary percutaneous coronary intervention in patients with ST-segment elevation myocardial infarction. Am J Cardiol. 2017;120:534-41.
80.
LazzeriCValenteSChiostriMAttanaPPicarielloCGensiniGF.The prognostic role of in-hospital peak glycemia in stemi patients with and without diabetes. Acta Diabetol. 2012;49:379-86.
81.
BolkJvan der PloegTCornelJHArnoldAESepersJUmansVA.Impaired glucose metabolism predicts mortality after a myocardial infarction. Int J Cardiol. 2001;79:207-14.
82.
LiuFHuangRLiYZhaoSGongYXuZ.In-hospital peak glycemia in predicting no-reflow phenomenon in diabetic patients with STEMI treated with primary percutaneous coronary intervention. J Diabetes Res. 2021;2021:6683937.
83.
IwakuraKItoHIkushimaM, et al. Association between hyperglycemia and the no-reflow phenomenon in patients with acute myocardial infarction. J Am Coll Cardiol. 2003;41:1-7.
84.
DoganNBOzpelitEAkdenizSBilginMBarisN.Simple clinical risk score for no-reflow prediction in patients undergoing primary percutaneous coronary intervention with acute STEMI. Pak J Med Sci. 2015;31:576-81.
85.
CaiGLiuWLvS, et al. Gender-specific associations between atherogenic index of plasma and the presence and severity of acute coronary syndrome in very young adults: a hospital-based observational study. Lipids Health Dis. 2019;18:99.
86.
DuranEKAdayAWCookNRBuringJERidkerPMPradhanAD.Triglyceride-rich lipoprotein cholesterol, small dense LDL cholesterol, and incident cardiovascular disease. J Am Coll Cardiol. 2020;75:2122-35.
87.
SuleymanogluMRencuzogullariIKarabagY, et al. The relationship between atherogenic index of plasma and no-reflow in patients with acute ST-segment elevation myocardial infarction who underwent primary percutaneous coronary intervention. Int J Cardiovasc Imaging. 2020;36:789-96.
88.
WanKZhaoJHuangH, et al. The association between triglyceride/high-density lipoprotein cholesterol ratio and all-cause mortality in acute coronary syndrome after coronary revascularization. PLoS One. 2015;10:e0123521.
89.
TadaHNoharaAKawashiriMA.Serum triglycerides and atherosclerotic cardiovascular disease: insights from clinical and genetic studies. Nutrients. 2018;10:1789.
90.
WongNKPNichollsSJTanJTMBursillCA. The role of high-density lipoproteins in diabetes and its vascular complications. Int J Mol Sci. 2018;19:1680.
91.
OlsonJD.D-dimer: an overview of hemostasis and fibrinolysis, assays, and clinical applications. Adv Clin Chem. 2015;69:1-46.
92.
MuellerC.Biomarkers and acute coronary syndromes: an update. Eur Heart J. 2014;35:552-6.
93.
DiaoYYinMZhangBSunB.Predictive value of N-terminal pro-B-type natriuretic peptide (NT-pro BNP) combined with D-dimer for no-reflow phenomenon in patients with acute coronary syndrome after emergency of percutaneous coronary intervention. Bioengineered. 2021;12:8614-21.
94.
GongXLeiXHuangZ, et al. D-dimer level predicts angiographic no-reflow phenomenon after percutaneous coronary intervention within 2-7 days of symptom onset in patients with ST-segment elevation myocardial infarction. J Cardiovasc Transl Res. 2021;14:728-34.
95.
ZhangHQiuBZhangY, et al. The value of pre-infarction angina and plasma D-dimer in predicting no-reflow after primary percutaneous coronary intervention in ST-segment elevation acute myocardial infarction patients. Med Sci Monit. 2018;24:4528-35.
