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Thromb Haemost 2019; 119(02): 340-347
DOI: 10.1055/s-0038-1676563
Atherosclerosis and Ischaemic Disease
Georg Thieme Verlag KG Stuttgart · New York

Prognostic Impact of Soluble P-Selectin on Long-Term Adverse Cardiovascular Outcomes in Patients Undergoing Percutaneous Coronary Intervention

Maximilian Tscharre
1   3rd Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenspital, Vienna, Austria
2   Institute for Cardiometabolic Diseases, Karl Landsteiner Society, St. Pölten, Austria
,
Birgit Vogel
1   3rd Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenspital, Vienna, Austria
3   The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
,
Ioannis Tentzeris
1   3rd Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenspital, Vienna, Austria
,
Matthias K. Freynhofer
1   3rd Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenspital, Vienna, Austria
4   Sigmund Freud University Medical School, Sigmund Freud University, Vienna, Austria
,
Miklos Rohla
1   3rd Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenspital, Vienna, Austria
2   Institute for Cardiometabolic Diseases, Karl Landsteiner Society, St. Pölten, Austria
,
Johann Wojta
5   Division of Cardiology, Department of Internal Medicine 2, Medical University of Vienna, Vienna, Austria
6   Core Facilities, Medical University of Vienna, Vienna, Austria
7   Ludwig Boltzmann Cluster for Cardiovascular Research, Vienna, Austria
,
Thomas W. Weiss
1   3rd Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenspital, Vienna, Austria
2   Institute for Cardiometabolic Diseases, Karl Landsteiner Society, St. Pölten, Austria
4   Sigmund Freud University Medical School, Sigmund Freud University, Vienna, Austria
,
Cihan Ay
8   Clinical Division of Haematology and Haemostaseology, Department of Medicine 1, Medical University of Vienna, Vienna, Austria
9   I.M. Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia
,
Kurt Huber
1   3rd Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenspital, Vienna, Austria
4   Sigmund Freud University Medical School, Sigmund Freud University, Vienna, Austria
,
Serdar Farhan
1   3rd Medical Department, Cardiology and Intensive Care Medicine, Wilhelminenspital, Vienna, Austria
3   The Zena and Michael A. Wiener Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, New York, United States
› Author Affiliations Funding This work was supported by the Association for the Promotion of Research in Atherosclerosis, Thrombosis and Vascular Biology (ATVB), and by the Ludwig Boltzmann Foundation for Cardiovascular Research, Vienna, Austria.
Further Information

Publication History

22 June 2018

01 November 2018

Publication Date:
28 December 2018 (online)

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Abstract

Background Soluble P-selectin (sP-selectin), a biomarker of inflammatory pathologies including cardiovascular disease, is known to have pro-atherosclerotic effects such as the ability to increase leukocyte recruitment and modulate thrombotic response. We aimed to assess the impact of sP-selectin on long-term major adverse cardiovascular events (MACE) in patients after coronary stenting for coronary artery disease.

Methods We analysed 733 patients of a single-centre registry undergoing percutaneous coronary intervention (PCI) between 2003 and 2006. Plasma samples were analysed for sP-selectin antigen concentration with an enzyme-linked immunoassay. The study population was categorized according to sP-selectin quartiles. Endpoint of the study was long-term MACE, a composite of all-cause death, myocardial infarction (MI) and stroke.

Results Of the total patient cohort, 361 (49.2%) patients were admitted for stable coronary artery disease and 372 (50.8%) for acute coronary syndrome. Median age was 64 years and 70.7% were male. After a mean follow-up period of 9.7 years, MACE occurred in 344 (46.9%) patients. The primary endpoint components of all-cause death occurred in 211 (28.8%), MI in 88 (12.0%) and ischaemic stroke in 45 (6.1%) patients. After adjustment for confounders, patients in the 2nd, 3rd and 4th quartile were at higher risk for MACE compared with the 1st quartile (hazard ration [HR], 1.234 [0.899–1.695], p = 0.193; HR, 1.480 [1.085–2.019], p = 0.013; and HR, 1.571 [1.115–2.152], p = 0.004). sP-selectin as continuous variable model was significantly associated with MACE after adjustment (HR per 1 ng/mL increase of 1.009 [95% confidence interval, 1.002–1.017]; p = 0.016).

Conclusion Elevated levels of sP-selectin were associated with increased risk for long-term MACE in patients undergoing PCI.

Keywords

soluble P-selectin - percutaneous coronary intervention - long-term major adverse cardiovascular outcome
 

  • References

  • 1 World Health Organization. Health statistics and information systems. Cause-specific mortality. Estimates for 2000. World Heal Stat 2012; 2012: 2012
    PubMedGoogle Scholar
  • 2 Santos-Gallego CG, Picatoste B, Badimón JJ. Pathophysiology of acute coronary syndrome. Curr Atheroscler Rep 2014; 16 (04) 401
    CrossrefPubMedGoogle Scholar
  • 3 Stenberg PE, McEver RP, Shuman MA, Jacques YV, Bainton DF. A platelet alpha-granule membrane protein (GMP-140) is expressed on the plasma membrane after activation. J Cell Biol 1985; 101 (03) 880-886
    CrossrefPubMedGoogle Scholar
  • 4 McEver RP, Beckstead JH, Moore KL, Marshall-Carlson L, Bainton DF. GMP-140, a platelet alpha-granule membrane protein, is also synthesized by vascular endothelial cells and is localized in Weibel-Palade bodies. J Clin Invest 1989; 84 (01) 92-99
    CrossrefPubMedGoogle Scholar
  • 5 Blann AD, Nadar SK, Lip GYH. The adhesion molecule P-selectin and cardiovascular disease. Eur Heart J 2003; 24 (24) 2166-2179
    CrossrefPubMedGoogle Scholar
  • 6 Zhang N, Liu Z, Yao L, Mehta-D'souza P, McEver RP. P-selectin expressed by a human SELP transgene is atherogenic in apolipoprotein E-deficient mice. Arterioscler Thromb Vasc Biol 2016; 36 (06) 1114-1121
    CrossrefPubMedGoogle Scholar
  • 7 Mayadas TN, Johnson RC, Rayburn H, Hynes RO, Wagner DD. Leukocyte rolling and extravasation are severely compromised in P selectin-deficient mice. Cell 1993; 74 (03) 541-554
    CrossrefPubMedGoogle Scholar
  • 8 Ramos CL, Huo Y, Jung U. , et al. Direct demonstration of P-selectin- and VCAM-1-dependent mononuclear cell rolling in early atherosclerotic lesions of apolipoprotein E-deficient mice. Circ Res 1999; 84 (11) 1237-1244
    CrossrefPubMedGoogle Scholar
  • 9 Ishiwata N, Takio K, Katayama M. , et al. Alternatively spliced isoform of P-selectin is present in vivo as a soluble molecule. J Biol Chem 1994; 269 (38) 23708-23715
    CrossrefPubMedGoogle Scholar
  • 10 Fox JE. Shedding of adhesion receptors from the surface of activated platelets. Blood Coagul Fibrinolysis 1994; 5 (02) 291-304
    CrossrefPubMedGoogle Scholar
  • 11 Woollard KJ, Kling D, Kulkarni S, Dart AM, Jackson S, Chin-Dusting J. Raised plasma soluble P-selectin in peripheral arterial occlusive disease enhances leukocyte adhesion. Circ Res 2006; 98 (01) 149-156
    CrossrefPubMedGoogle Scholar
  • 12 Woollard KJ, Suhartoyo A, Harris EE. , et al. Pathophysiological levels of soluble P-selectin mediate adhesion of leukocytes to the endothelium through Mac-1 activation. Circ Res 2008; 103 (10) 1128-1138
    CrossrefPubMedGoogle Scholar
  • 13 Woollard KJ, Lumsden NG, Andrews KL. , et al. Raised soluble P-selectin moderately accelerates atherosclerotic plaque progression. Ma X-L. , ed. PLoS One 2014. 9: e97422
    Google Scholar
  • 14 Kisucka J, Chauhan AK, Zhao B-Q. , et al. Elevated levels of soluble P-selectin in mice alter blood-brain barrier function, exacerbate stroke, and promote atherosclerosis. Blood 2009; 113 (23) 6015-6022
    CrossrefPubMedGoogle Scholar
  • 15 André P, Hartwell D, Hrachovinová I, Saffaripour S, Wagner DD. Pro-coagulant state resulting from high levels of soluble P-selectin in blood. Proc Natl Acad Sci U S A 2000; 97 (25) 13835-13840
    CrossrefPubMedGoogle Scholar
  • 16 Blann AD, McCollum CN. Increased soluble P-selectin in peripheral artery disease: a new marker for the progression of atherosclerosis. Thromb Haemost 1998; 80 (06) 1031-1032
    Article in Thieme ConnectPubMedGoogle Scholar
  • 17 Varughese GI, Patel JV, Tomson J, Blann AD, Hughes EA, Lip GY. Prognostic value of plasma soluble P-selectin and von Willebrand factor as indices of platelet activation and endothelial damage/dysfunction in high-risk patients with hypertension: a sub-study of the Anglo-Scandinavian Cardiac Outcomes Trial. J Intern Med 2007; 261 (04) 384-391
    CrossrefPubMedGoogle Scholar
  • 18 Ay C, Simanek R, Vormittag R. , et al. High plasma levels of soluble P-selectin are predictive of venous thromboembolism in cancer patients: results from the Vienna Cancer and Thrombosis Study (CATS). Blood 2008; 112 (07) 2703-2708
    CrossrefPubMedGoogle Scholar
  • 19 Ay C, Jungbauer LV, Sailer T. , et al. High concentrations of soluble P-selectin are associated with risk of venous thromboembolism and the P-selectin Thr715 variant. Clin Chem 2007; 53 (07) 1235-1243
    CrossrefPubMedGoogle Scholar
  • 20 Dunkler D, Plischke M, Leffondré K, Heinze G. Augmented backward elimination: a pragmatic and purposeful way to develop statistical models. PLoS One 2014; 9 (11) e113677
    Google Scholar
  • 21 Bursac Z, Gauss CH, Williams DK, Hosmer DW. Purposeful selection of variables in logistic regression. Source Code Biol Med 2008; 3: 17
    CrossrefPubMedGoogle Scholar
  • 22 Levey AS, Stevens LA, Schmid CH. , et al; CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration). A new equation to estimate glomerular filtration rate. Ann Intern Med 2009; 150 (09) 604-612
    CrossrefPubMedGoogle Scholar
  • 23 Lim HS, Blann AD, Lip GYH. Soluble CD40 ligand, soluble P-selectin, interleukin-6, and tissue factor in diabetes mellitus: relationships to cardiovascular disease and risk factor intervention. Circulation 2004; 109 (21) 2524-2528
    CrossrefPubMedGoogle Scholar
  • 24 Bielinski SJ, Berardi C, Decker PA. , et al. P-selectin and subclinical and clinical atherosclerosis: the Multi-Ethnic Study of Atherosclerosis (MESA). Atherosclerosis 2015; 240 (01) 3-9
    CrossrefPubMedGoogle Scholar
  • 25 Ridker PM, Buring JE, Rifai N. Soluble P-selectin and the risk of future cardiovascular events. Circulation 2001; 103 (04) 491-495
    CrossrefPubMedGoogle Scholar
  • 26 Hillis GS, Terregino C, Taggart P. , et al. Elevated soluble P-selectin levels are associated with an increased risk of early adverse events in patients with presumed myocardial ischemia. Am Heart J 2002; 143 (02) 235-241
    CrossrefPubMedGoogle Scholar
  • 27 Zamani P, Schwartz GG, Olsson AG. , et al; Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) Study Investigators. Inflammatory biomarkers, death, and recurrent nonfatal coronary events after an acute coronary syndrome in the MIRACL study. J Am Heart Assoc 2013; 2 (01) e003103-e003103
    PubMedGoogle Scholar
  • 28 Mulvihill NT, Foley JB, Murphy RT, Curtin R, Crean PA, Walsh M. Risk stratification in unstable angina and non-Q wave myocardial infarction using soluble cell adhesion molecules. Heart 2001; 85 (06) 623-627
    CrossrefPubMedGoogle Scholar
  • 29 Kozinski M, Kubica J, Sukiennik A. , et al. Periprocedural soluble P- and E-selectin levels fail as predictors of clinical restenosis in patients treated with elective coronary stenting. Int J Mol Med 2007; 19 (01) 187-195
    PubMedGoogle Scholar
  • 30 Malik I, Danesh J, Whincup P. , et al. Soluble adhesion molecules and prediction of coronary heart disease: a prospective study and meta-analysis. Lancet 2001; 358 (9286): 971-976
    CrossrefPubMedGoogle Scholar
  • 31 Blann AD, Faragher EB, McCollum CN. Increased soluble P-selectin following myocardial infarction: a new marker for the progression of atherosclerosis. Blood Coagul Fibrinolysis 1997; 8 (07) 383-390
    CrossrefPubMedGoogle Scholar
  • 32 Dunlop LC, Skinner MP, Bendall LJ. , et al. Characterization of GMP-140 (P-selectin) as a circulating plasma protein. J Exp Med 1992; 175 (04) 1147-1150
    CrossrefPubMedGoogle Scholar
  • 33 Fijnheer R, Frijns CJ, Korteweg J. , et al. The origin of P-selectin as a circulating plasma protein. Thromb Haemost 1997; 77 (06) 1081-1085
    Article in Thieme ConnectPubMedGoogle Scholar
  • 34 Bickel C, Rupprecht HJ, Blankenberg S. , et al; AtheroGene Group. Influence of HMG-CoA reductase inhibitors on markers of coagulation, systemic inflammation and soluble cell adhesion. Int J Cardiol 2002; 82 (01) 25-31
    CrossrefPubMedGoogle Scholar
  • 35 Romano M, Mezzetti A, Marulli C. , et al. Fluvastatin reduces soluble P-selectin and ICAM-1 levels in hypercholesterolemic patients: role of nitric oxide. J Investig Med 2000; 48 (03) 183-189
    PubMedGoogle Scholar
  • 36 Tardif J-C, Tanguay J-F, Wright SR. , et al. Effects of the P-selectin antagonist inclacumab on myocardial damage after percutaneous coronary intervention for non-ST-segment elevation myocardial infarction: results of the SELECT-ACS trial. J Am Coll Cardiol 2013; 61 (20) 2048-2055
    CrossrefPubMedGoogle Scholar