High-sensitivity troponin I (hsTnI) and N-terminal pro-brain natriuretic peptide (NT-pro-BNP) are predictors of coronary artery disease. Recently, routine hematological parameters emerged as mortality predictors. We examined the predictive value of hematological parameters (from the Utrecht Patient Oriented Database) and hsTnI and NT-pro-BNP for mortality in a coronary angiography population (Utrecht Coronary Biobank n = 1913). Using Cox regression, receiver operating characteristics, integrated discrimination improvement (IDI), and continuous net reclassification improvement (cNRI) analysis, we compared the predictive properties of hematological parameters with hsTnI and NT-pro-BNP for mortality. During a median follow-up duration of 1.8 years, 77 deaths occurred. A panel of 7 hematological parameters (leukocyte count, reticulocyte mean corpuscular hemoglobin concentration, red blood cell [RBC] green (FL1) fluorescence, %neutrophils, %large [>120 fL] RBCs, %monocytes, and coefficient of variation of neutrophil complexity) was highly predictive. Added to clinical characteristics, hematological parameters (area under the curve [AUC]: 0.855, P < .001; IDI: 0.04, P = .02; cNRI: 0.41, P < .001) were better predictors than hsTnI (AUC: 0.818) or NT-pro-BNP (AUC: 0.834) alone or combined (AUC: 0.834). Hematological parameters may provide mortality risk information following coronary angiography and may be superior to hsTnI and/or NT-pro-BNP.
KellerTZellerTPeetzD. Sensitive troponin I assay in early diagnosis of acute myocardial infarction. N Engl J Med. 2009;361(9):868–77.
2.
HobbsFDRDavisRCRoalfeAKHareRDaviesMKKenkreJE. Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis of heart failure: cohort study in representative and high risk community populations. BMJ. 2002;324(7352):1498.
3.
BonacaMPO’MalleyRGMurphySA. Prognostic performance of a high-sensitivity assay for cardiac troponin I after non-ST elevation acute coronary syndrome: analysis from MERLIN-TIMI 36. Eur Heart J Acute Cardiovasc Care. 2014;4(5):431–40.
4.
GrodinJLNealeSWuYHazenSLTangWHW. Prognostic comparison of different sensitivity cardiac troponin assays in stable heart failure. Am J Med. 2015;128(3):276–82.
5.
HochholzerWValinaCMStratzC. High-sensitivity cardiac troponin for risk prediction in patients with and without coronary heart disease. Int J Cardiol. 2014;176(2):444–9.
6.
SchnabelRLubosERupprechtHJ. B-type natriuretic peptide and the risk of cardiovascular events and death in patients with stable angina: results from the AtheroGene study. J Am Coll Cardiol. 2006;47(3):552–8.
7.
JamesSKLindahlBSiegbahnA. N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a GUSTO-IV substudy. Circulation. 2003;108(3):275–81.
8.
YildirirAAcikelSErtanCAydinalpAOzinBMuderrisogluH. Value of peri-procedural B-type natriuretic peptide levels in predicting cardiac events after elective percutaneous coronary intervention. Acta Cardiol. 2008;63(1):47–52.
9.
ó HartaighBBoschJAThomasGN. Which leukocyte subsets predict cardiovascular mortality? From the LUdwigshafen RIsk and Cardiovascular Health (LURIC) Study. Atherosclerosis. 2012;224(1):161–69.
10.
GijsbertsCMEllenbroekGHTen BergMJ. Routinely analyzed leukocyte characteristics improve prediction of mortality after coronary angiography. Eur J Prev Cardiol. 2016;23(11):1211–20.
11.
GijsbertsCMden RuijterHMde KleijnDPV. Hematological parameters improve prediction of mortality and secondary adverse events in coronary angiography patients. Medicine (Baltimore). 2015;94(45):e1992.
12.
MüllerRMellorsIJohannessenB. European multi-center evaluation of the Abbott Cell-Dyn sapphire hematology analyzer. Lab Hematol. 2006;12(1):15–31.
13.
ten BergMJHuismanAvan den BemtPMLASchobbenAFAMEgbertsACGvan SolingeWW. Linking laboratory and medication data: new opportunities for pharmacoepidemiological research. Clin Chem Lab Med. 2007;45(1):13–19.
14.
GijsbertsCMSeneviratnaAde CarvalhoLP. Ethnicity modifies associations between cardiovascular risk factors and disease severity in parallel Dutch and Singapore coronary cohorts. PLoS One. 2015;10(7):e0132278.
15.
HarrisPJBeharVSConleyMJ. The prognostic significance of 50% coronary stenosis in medically treated patients with coronary artery disease. Circulation. 1980;62(2):240–8.
16.
LamSWLeenenLPHVan SolingeWWHietbrinkFHuismanA. Evaluation of hematological parameters on admission for the prediction of 7-day in-hospital mortality in a large trauma cohort. Clin Chem Lab Med. 2011;49(3):493–9.
17.
PavlouMAmblerGSeamanSR. How to develop a more accurate risk prediction model when there are few events. BMJ. 2015;351:h3868.
UnoHTianLCaiTKohaneISWeiLJ. A unified inference procedure for a class of measures to assess improvement in risk prediction systems with survival data. Stat Med. 2013;32(14):2430–42.
20.
PencinaMJD’AgostinoRBSteyerbergEW. Extensions of net reclassification improvement calculations to measure usefulness of new biomarkers. Stat Med. 2011;30(1):11–21.
21.
SnidermanADD’AgostinoRBPencinaMJ. The role of physicians in the era of predictive analytics. JAMA. 2015;314(1):25–26.
22.
SteyerbergEWVickersAJCookNR. Assessing the performance of prediction models. Epidemiology. 2010;21(1):128–38.
23.
R Core Team. R: A Language and Environment for Statistical Computing. Vienna, Austria; 2014. R Foundation for Statistical Computing. http://www.R-project.org/. Accessed October 14, 2015.
24.
CampoGValgimigliMGemmatiD. Value of platelet reactivity in predicting response to treatment and clinical outcome in patients undergoing primary coronary intervention: insights into the STRATEGY study. J Am Coll Cardiol. 2006;48(11):2178–85.
25.
RengaBScavizziF. Platelets and cardiovascular risk. Acta Cardiol. 2017;72(1):2–8.
26.
GhattasAGriffithsHRDevittALipGYHShantsilaE. Monocytes in coronary artery disease and atherosclerosis: where are we now?J Am Coll Cardiol. 2013;62(17):1541–51.
27.
MadjidMFatemiO. Components of the complete blood count as risk predictors for coronary heart disease: in-depth review and update. Tex Heart Inst J. 2013;40(1):17–29.
28.
KatoATakitaTFuruhashiMMaruyamaYKumagaiHHishidaA. Blood monocyte count is a predictor of total and cardiovascular mortality in hemodialysis patients. Nephron Clin Pract. 2008;110(4):c235–43.
29.
ZerneckeABotIDjalali-TalabY. Protective role of CXC receptor 4/CXC ligand 12 unveils the importance of neutrophils in atherosclerosis. Circ Res. 2008;102(2):209–17.
30.
NarukoTUedaMHazeK. Neutrophil infiltration of culprit lesions in acute coronary syndromes. Circulation. 2002;106(23):2894–900.
31.
SeebachJDMorantRRüeggRSeifertBFehrJ. The diagnostic value of the neutrophil left shift in predicting inflammatory and infectious disease. Am J Clin Pathol. 1997;107(5):582–91.
32.
van HoutGPJvan SolingeWWGijsbertsCM. Elevated mean neutrophil volume represents altered neutrophil composition and reflects damage after myocardial infarction. Basic Res Cardiol. 2015;110(6):58.
33.
TsuboiSMiyauchiKKasaiT. Impact of red blood cell distribution width on long-term mortality in diabetic patients after percutaneous coronary intervention. Circ J. 2013;77(2):456–61.
34.
NúñezJNúñezERizopoulosD. Red blood cell distribution width is longitudinally associated with mortality and anemia in heart failure patients. Circ J. 2014;78(2):410–8.
35.
PerlsteinTSWeuveJPfefferMABeckmanJA. Red blood cell distribution width and mortality risk in a community-based prospective cohort. Arch Intern Med. 2009;169(6):588–94.
36.
PatelHHPatelHRHigginsJM. Modulation of red blood cell population dynamics is a fundamental homeostatic response to disease. Am J Hematol. 2015;90(5):422–8.
37.
MaozARosenbergSLekerRR. Increased high-sensitivity troponin-T levels are associated with mortality after ischemic stroke. J Mol Neurosci. 2015;57(2):160–5.
38.
Lurati BuseGALBolligerDSeebergerE. Troponin T and B-type natriuretic peptide after on-pump cardiac surgery: prognostic impact on 12-month mortality and major cardiac events after adjustment for postoperative complications. Circulation. 2014;130(12):948–57.
39.
de AntonioMLupónJGalánA. Head-to-head comparison of high-sensitivity troponin T and sensitive-contemporary troponin I regarding heart failure risk stratification. Clin Chim Acta. 2013;426:18–24.
40.
OmlandTPerssonANgL. N-terminal pro-B-type natriuretic peptide and long-term mortality in acute coronary syndromes. Circulation. 2002;106(23):2913–8.
41.
NigroNWildiKMuellerC. BNP but not s-cTnln is associated with cardioembolic aetiology and predicts short and long term prognosis after cerebrovascular events. PLoS One. 2014;9(7):e102704.
42.
KarinoSWillcoxBJFongKLoSAbbottRMasakiKH. Total and differential white blood cell counts predict eight-year incident coronary heart disease in elderly Japanese-American men: the Honolulu Heart Program. Atherosclerosis. 2014;238(2):153–8.
43.
GuastiLDentaliFCastiglioniL. Neutrophils and clinical outcomes in patients with acute coronary syndromes and/or cardiac revascularization: a systematic review on more than 34,000 subjects. Thromb Haemost. 2011;106(4):591–9.
44.
JaumdallyRJLipGYHVarmaCBlannAD. Impact of high-dose atorvastatin on endothelial, platelet, and angiogenic indices: effect of ethnicity, cardiovascular disease, and diabetes. Angiology. 2011;62(7):571–8.
45.
AkınFAyçaBKöseN. Effect of atorvastatin on hematologic parameters in patients with hypercholesterolemia. Angiology. 2013;64(8):621–5.
46.
MadjidMAwanIWillersonJTCasscellsSW. Leukocyte count and coronary heart disease: implications for risk assessment. J Am Coll Cardiol. 2004;44(10):1945–56.
47.
WangXZhangGJiangXZhuHLuZXuL. Neutrophil to lymphocyte ratio in relation to risk of all-cause mortality and cardiovascular events among patients undergoing angiography or cardiac revascularization: a meta-analysis of observational studies. Atherosclerosis. 2014;234(1):206–13.
Supplementary Material
Please find the following supplemental material available below.
For Open Access articles published under a Creative Commons License, all supplemental material carries the same license as the article it is associated with.
For non-Open Access articles published, all supplemental material carries a non-exclusive license, and permission requests for re-use of supplemental material or any part of supplemental material shall be sent directly to the copyright owner as specified in the copyright notice associated with the article.
