Advertisement

Leukocytes and coronary heart disease

      Abstract

      Inflammation has been demonstrated to be an important risk factor for the development of cardiovascular events. Patients with elevated white blood cell counts have been shown to be in a higher risk of developing acute myocardial infarction and acute coronary and vascular events. We review the clinical data of high white blood cell counts and the prognosis, and demonstrate several possible mechanisms. It is possible that measuring white blood cell count and subpopulations could be used for a better way of risk stratification of patients admitted with acute vascular events.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Freidman G.D.
        • Klatsky A.L.
        • Siegelaub A.B.
        The leukocyte count as a predictor of myocardial infarction.
        New Engl. J. Med. 1974; 290: 1275-1278
        • Zalokar J.B.
        • Richards J.L.
        • Blaude J.R.
        Leukocyte count, smoking, and myocardial infarction.
        New Engl. J. Med. 1981; 394: 465-468
        • Prentice R.L.
        • Shimizu Y.
        • Lin C.H.
        • et al.
        Leukocyte counts and coronary heart disease in a Japanese cohort.
        Am. J. Epidemiol. 1982; 116: 496-506
        • Prentice R.L.
        • Szatrowski T.P.
        • Kato H.
        • et al.
        Leukocyte counts and cerebrovascular disease.
        J. Chronic Dis. 1982; 35: 703-714
        • Grimm R.H.
        • Neaton J.D.
        • Ludwig W.
        Prognostic importance of the white blood cell count for coronary, cancer and all-cause mortality.
        J. Am. Med. Assoc. 1985; 254: 1932-1937
        • Cole D.R.
        • Singian E.B.
        • Kate L.N.
        The long-term prognosis following myocardial infarction, and some factors which affect it.
        Circulation. 1954; 9: 321-334
        • Maisel A.S.
        • Gilpin A.
        • Lewinter M.
        • et al.
        Initial leukocyte count during acute myocardial infarction independently predicts early ventricular fibrillation.
        Circulation. 1985; 72: 414
        • Furman M.I.
        • Becker R.C.
        • Yarzebski J.
        • Savegeau J.
        • Gore J.M.
        • Goldberg R.J.
        Effect of elevated leukocyte count on in-hospital mortality following acute myocardial infarction.
        Am. J. Cardiol. 1996; 78: 945-948
        • Spodick D.H.
        Inflammation and the onset of myocardial infarction.
        Ann. Intern. Med. 1985; 102: 699-702
        • Reizenstein P.
        The hematological stress syndrome.
        Br. J. Hematol. 1979; 43: 329-334
        • Stuart J.
        • George A.J.
        • Davies A.J.
        Hematological stress syndrome in atherosclerosis.
        J. Clin. Pathol. 1981; 34: 464-467
        • Friedman M.
        • St George S.
        • Byers S.O.
        Excretion of catecholamines, 17-ketosteroids, 17-hydroxycorticoids and 5-hydroxyindole in men exhibiting a particular behavior pattern A associated with high incidence of clinical coronary artery disease.
        J. Clin. Invest. 1960; 39: 758-764
        • Bagge U.
        • Skalak R.
        • Attefors R.
        Granulocyte rheology: experimental studies in an in-vitro micro-flow system.
        Adv. Microcirc. 1977; 7: 29-49
        • Lichtman M.A.
        Rheology of leukocytes, leukocyte suspensions and blood in leukemia.
        J. Clin. Invest. 1973; 52: 350-358
        • Schmid-Schonbein G.W.
        • Sung K.-L.P.
        • Tozeren H.
        Influence of physicochemical factors on rheology of human neutrophils.
        Biophys. J. 1982; 39: 101-106
        • Asano M.
        • Branemark P.-I.
        • Castenholz A.
        A comparative study of continuous qualitative and quantitative analysis of microcirculation in man: microchymography and microphotoelectric plethysmography applied to microvascular investigation.
        Adv. Microcirc. 1973; 5: 1-31
        • Craddock P.R.
        • Hammerschmidt D.E.
        • White J.G.
        Complement (C5a) induced granulocyte aggregation in vitro: a possible mechanism of complement mediated leukostasis and leukopenia.
        J. Clin. Invest. 1977; 60: 261-264
        • Skubitz K.M.
        • Craddock P.R.
        • Hammerschmidt D.E.
        • et al.
        Corticosteroids block binding of chemotactic peptide to its receptor on granulocytes and cause disaggregation of granulocytes in vitro.
        J. Clin. Invest. 1981; 68: 13-20
        • Given W.P.
        • Edelson H.S.
        • Kaplan H.B.
        • et al.
        Generation of C5-derived peptides and other immune reactants in the sera of patients with systemic lupus erythematosus.
        Arthritis Rheum. 1984; 27: 631-637
        • Aisen P.S.
        • Haines K.A.
        • Given W.
        • et al.
        Circulating hydroxy fatty acids in familial Mediterranean fever.
        Proc. Natl. Acad. Sci. USA. 1985; 82: 1232-1236
        • Hammerschmidt D.E.
        • Harris P.D.
        • Wayland J.H.
        • et al.
        Complement induced granulocyte aggregation in vivo.
        Am. J. Pathol. 1981; 102: 146-150
        • Weissman G.
        • Smolen J.E.
        • Korchak H.M.
        Release of inflammatory mediators from stimulated neutrophils.
        New Engl. J. Med. 1980; 303: 27-34
        • Harlan J.M.
        • Killen P.D.
        • Harker L.A.
        • et al.
        Neutrophil mediated endothelial injury in vitro: mechanisms of cell detachment.
        J. Clin. Invest. 1981; 68: 1394-1403
        • Rasp F.L.
        • Clawson C.C.
        • Repine J.E.
        Platelets increase neutrophil adherence in vitro to nylon fiber.
        J. Lab. Clin. Med. 1981; 97: 812-819
        • Redl H.
        • Hammerschmidt D.E.
        • Schlag G.
        Augmentation by platelets of granulocyte aggregation in response to chemotaxins: studies utilizing an improved cell preparation technique.
        Blood. 1983; 61: 125-131
        • Boogaerts M.A.
        • Yamada O.
        • Jacob H.S.
        • et al.
        Enhancement of granulocyte adherence and granulocyte-induced cytotoxicity by platelet release products.
        Proc. Natl. Acad. Sci. USA. 1982; 79: 7019-7024
        • Vercellotti G.M.
        • McCarthy J.
        • Furcht L.T.
        • et al.
        Inflamed fibronectin: an altered fibronectin enhances neutrophil adherence.
        Blood. 1983; 62: 1063-1069
        • Weiss S.J.
        • Regiani S.
        Neutrophils degrade subendothelial matrices in the presence of alpha-1-proteinase inhibitor: cooperative use of lysosomal proteinases and oxygen metabolites.
        J. Clin. Invest. 1984; 73: 1297-1303
        • Ott I.
        • Neumann F.J.
        • Kenngott S.
        • et al.
        Procoagulant inflammatory responses of monocytes after direct balloon angioplasty in acute myocardial infarction.
        Am. J. Cardiol. 1998; 82: 938-942
        • Engler R.L.
        • Schmid-Schonbein G.W.
        • Pavelec R.S.
        Leokocyte capillary plugging in myocardial ischemia and reperfusion in the dog.
        Am. J. Pathol. 1983; 111: 98-111
        • Mann D.L.
        • Young J.B.
        Basic mechanisms in congestive heart failure: recognizing the role of proinflammatory cytokines.
        Chest. 1994; 105: 897-904
        • Marx N.
        • Neuman F.J.
        • Ott I.
        • et al.
        Induction of cytokine expression in leukocytes in acute myocardial infarction.
        J. Am. Coll. Cardiol. 1997; 30: 165-170
        • Neuman F.J.
        • Ott I.
        • Marx N.
        • et al.
        Effect of human recombinant interleukin-6 and interleukin-8 on monocyte procoagulant activity.
        Arterioscler. Thromb. Vasc. Biol. 1997; 17: 3399-3405
        • Neuman F.J.
        • Ott I.
        • Gawaz M.
        • et al.
        Cardiac release of cytokines and inflammatory responses in acute myocardial infarction.
        Circulation. 1995; 92: 748-755
        • Ikeda U.
        • Ikeda M.
        • Kano S.
        • Shimada K.
        Neutrophil adherence to rat cardiac myocytes by proinflammatory cytokines.
        J. Cardiovasc. Pharmacol. 1994; 23: 647-652
        • Youker K.
        • Smith C.W.
        • Anderson D.C.
        • et al.
        Neitrophil adherence to isolated adult cardiac myocytes.
        J. Clin. Invest. 1992; 89: 602-609
        • Ivey C.L.
        • Williams F.M.
        • Collins P.D.
        • Jose P.J.
        • Williams T.J.
        Neutrophil chemoattractants generated in two phases during reperfusion of ischemic myocardium in the rabbit.
        J. Clin. Invest. 1995; 95: 2720-2728
        • Dinarello C.A.
        The biological properties of interleukin-1.
        Eur. Cytokine Netw. 1994; 5: 517-531
        • Mantovani A.
        • Bussolino F.
        • Dejana E.
        Cytokine regulation of endothelial cell function.
        FASEB J. 1992; 6: 2591-2599
        • Sica A.
        • Matsushima K.
        • Van Damme J.
        • et al.
        IL-1 transcriptionally activates the neutrophil chemotactic factor/IL-8 gene in endothelial cells.
        Immunology. 1990; 69: 548-553
        • Molad Y.
        • Haines K.A.
        • Anderson D.C.
        • Buyon J.P.
        • Cronstein B.N.
        Immunocomplexes stimulate different signaling events to chemoattractants in the neutrophil and regulate L-selectin and β2-integrin expression differently.
        Biochem. J. 1994; 299: 881-887
        • Schroder J.M.
        • Mrowitz U.
        • Christophers E.
        Purification and partial biologic characterization of human lymphocyte-derived peptide with potent neutrophil-stimulating activity.
        J. Immunol. 1988; 140: 3534-3540
        • Akira S.
        • Hirano T.
        • Taga T.
        • Kishimoto T.
        Biology of multifunctional cytokines: IL-6 and related molecules (IL-1 and TNF).
        FASEB J. 1990; 4: 2860-2867
        • Diacovo T.G.
        • Roth S.J.
        • Buccola J.M.
        • et al.
        Neutrophil rolling, arrest, and transmigration across activated, surface-adherent platelets via sequential action of P-selectin and the beta 2-integrin CD11b/CD18.
        Blood. 1996; 88: 146-157
        • de Gaetano G.
        • Cerletti C.
        • Eangelista V.
        Recent advances in platelet–polymorphonuclear leukocyte interaction.
        Haemostasis. 1999; 29: 41-49
        • Gibson C.M.
        • Cannon C.P.
        • Murphy S.A.
        • et al.
        Relationship of TIMI myocardial perfusion grade to mortality after administration of thrombolytic drugs.
        Circulation. 2000; 101: 125-130
        • Horwitz L.D.
        • Kaufman D.
        • King Y.
        An antibody to leukocyte integrins attenuates coronary vascular injury due to ischemia and reperfusion in dogs.
        Am. J. Physiol. 1997; 272: H618-H624
        • Kloner R.A.
        • Giacomelli F.
        • Alker K.J.
        • et al.
        Influx of neutrophils into the walls of large epicardial coronary arteries in response to ischemia/reperfusion.
        Circulation. 1991; 84: 1758-1772
        • Ma X.L.
        • Tsao P.S.
        • Lefer A.M.
        Antibody to CD-18 exerts endothelial and cardiac protective effects in myocardial ischemia and reperfusion.
        J. Clin. Invest. 1991; 88: 1237-1243
        • Murohara T.
        • Kamijikkoku S.
        • Honda T.
        Increased circulating soluble intercellular adhesion molecule-1 in acute myocardial infarction: a possible predictor of reperfusion ventricular arrhythmias.
        Crit. Care Med. 2000; 28: 1861-1864
        • Hojo Y.
        • Ikeda U.
        • Zhu Y.
        • Okada M.
        • Ueno S.
        • Arakawa H.
        • Fujikawa H.
        • Katsuki T.
        • Shimada K.
        Expression of vascular endothelial growth factor in patients with acute myocardial infarction.
        J. Am. Coll. Cardiol. 2000; 35: 968-973
        • Meisel S.R.
        • Shapiro H.
        • Radnay J.
        • Neuman Y.
        • Khaskia A.R.
        • Gruener N.
        • Pauzner H.
        • David D.
        Increased expression of neutrophil and monocyte adhesion molecules LFA-1 and Mac-1 and their ligand ICAM-1 and VLA-4 throughout the acute phase of myocardial infarction: possible implications for leukocyte aggregation and microvascular plugging.
        J. Am. Coll. Cardiol. 1998; 31: 120-125
        • Blum A.
        • Sclarovsky S.
        • Rehavia E.
        • Shohat B.
        Levels of T-lymphocyte subpopulations, interleukin-1β, and soluble interleukin-2 receptor in acute myocardial infarction.
        Am. Heart J. 1994; 127: 1226-1230
        • Gabay C.
        • Kushner I.
        Acute phase proteins and other systemic responses to inflammation.
        New Engl. J. Med. 1999; 340: 448-454
        • Du Clos T.W.
        Function of C-reactive protein.
        Ann. Med. 2000; 32: 274-278
        • Mold C.
        • Gewurz H.
        • Clos T.W.
        Regulation of complement activation by C-reactive protein.
        Immunopharmacology. 1999; 42: 23-30
        • Pasceri V.
        • Willerson J.T.
        • Yeh E.T.
        Direct proinflammatory effect of C-reactive protein on human endothelial cells.
        Circulation. 2000; 102: 2165-2168
        • Pasceri V.
        • Chang J.
        • Willerson J.T.
        • et al.
        Modulation of c-reactive protein mediated monocyte chemoattractant protein-1 induction in human endothelial cells by anti-atherosclerosis drugs.
        Circulation. 2001; 103: 2531-2534
        • Verma S.
        • Li S.H.
        • Badiawala M.V.
        • et al.
        Endothelin antagonism and interleukin-6 inhibition attenuate proatherogenic effects of C-reactive protein.
        Circulation. 2002; 105: 1890-1896
        • Verma S.
        • Wang C.H.
        • Li S.H.
        • et al.
        A self-fulfilling prophecy: C reactive protein attenuates nitric oxide production and inhibits angiogenesis.
        Circulation. 2002; 106: 913-919
        • Venugopal S.K.
        • Devaraj S.
        • Yuhanna I.
        • et al.
        Demonstration that C-reactive protein decreases eNOS expression and bioactivity in human aortic endothelial cells.
        Circulation. 2002; 106: 1439-1441
        • Zwaka T.P.
        • Hombach V.
        • Torzewski J.
        C-reactive protein mediated low density lipoprotein uptake by macrophages: implications for atherosclerosis.
        Circulation. 2001; 103: 1194-1197
        • Biasucci L.M.
        • Liuzzo G.
        • Grillo R.L.
        • et al.
        Elevated levels of C-reactive protein at discharge in patients with unstable angina predict recurrent instability.
        Circulation. 1999; 99: 855-860
        • Liuzzo G.
        • Biasucci L.M.
        • Gallimore J.R.
        • et al.
        The prognostic value of C-reactive protein and serum amyloid a protein in severe unstable angina.
        New Engl. J. Med. 1994; 331: 417-424
        • Ridker P.M.
        • Cushman M.
        • Stampfer M.J.
        • et al.
        Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men.
        New Engl. J. Med. 1997; 336: 973-999