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C-Reactive Protein and Lipoprotein-Associated Phospholipase A2 in Smokers and Nonsmokers of the Ludwigshafen Risk and Cardiovascular Health Study

  • M. E. KleberEmail author
  • R. Siekmeier
  • G. Delgado
  • T. B. Grammer
  • B. R. Winkelmann
  • H. Scharnagl
  • B. O. Boehm
  • W. März
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 832)

Abstract

Measurement of high sensitivity CRP (hsCRP) and lipoprotein-associated phospholipase A2 (LpPLA2) provides information on systemic inflammation and stability of atherosclerotic plaques. Data analyzing the effect of smoking on these parameters are sparse. The aim of our study was the analysis of these parameters in active smokers and never-smokers. The study included 777 smokers and 1,178 never-smokers, of whom 221 and 302 died during a follow-up, respectively. The values of LpPLA2 and hsCRP were significantly higher in smokers than in never-smokers. Mortality was highest in smokers and never-smokers with elevation of both biomarkers. Multivariate adjusted hazard ratios for patients in the highest tertile of both hsCRP and LpPLA2 compared with patients in the lowest tertile of both markers were 1.85 (1.04–3.28) in never-smokers and 1.94 (1.10–3.45) in smokers. Our data confirmed the predictive value of hsCRP and LpPLA2. However, there were a relevant number of patients with an increase of only one of these parameters. Therefore, beside other risk factors for cardiovascular disease, both parameters should be determined at least in high risk patients.

Keywords

Cardiovascular disease hsCRP Inflammation LpPLA2 Mortality Plaque stability Smoking 

Notes

Acknowledgements

We extend our appreciation to the participants of the LURIC study. We thank the LURIC study team who were either temporarily or permanently involved in patient recruitment as well as sample and data handling, in addition to the laboratory staff at the Ludwigshafen General Hospital and the Universities of Freiburg and Ulm, Germany. LURIC has received funding from the 6th Framework Program (integrated project Bloodomics, grant LSHM-CT-2004-503485) and from the 7th Framework Program (Atheroremo, grant agreement number 201668 and RiskyCAD, grant agreement number 305739) of the European Union.

Conflicts of Interest

The authors declare no conflicts of interest in relation to this article.

References

  1. Ballantyne CM, Hoogeveen RC, Bang H, Coresh J, Folsom AR, Heiss G, Sharrett AR (2004) Lipoprotein-associated phospholipase A2, high-sensitivity C-reactive protein, and risk for incident coronary heart disease in middle-aged men and women in the Atherosclerosis Risk in Communities (ARIC) Study. Circulation 109:837–842PubMedCrossRefGoogle Scholar
  2. Barua RS, Ambrose JA (2013) Mechanisms of coronary thrombosis in cigarette smoke exposure. Thromb Vasc Biol 33:1460–1467CrossRefGoogle Scholar
  3. Corson MA, Jones PH, Davidson MH (2008) Review of the evidence for the clinical utility of lipoprotein-associated phospholipase A2 as a cardiovascular risk marker. Am J Cardiol 101:41F–50FPubMedCrossRefGoogle Scholar
  4. Craig WY, Palomaki GE, Haddow JE (1989) Cigarette smoking and serum lipid and lipoprotein concentrations: an analysis of published data. BMJ 298:784–788PubMedCentralPubMedCrossRefGoogle Scholar
  5. Danaei G, Ding EL, Mozaffarian D, Taylor B, Rehm J, Murray CJL, Ezzati M (2009) The preventable causes of death in the United States: comparative risk assessment of dietary, lifestyle and metabolic risk factors. PLoS Med 6:e1000058PubMedCentralPubMedCrossRefGoogle Scholar
  6. Fröhlich M, Sund M, Löwel H, Imhof A, Hoffmeister A, Koenig W (2003) Independent association of various smoking characteristics with markers of systemic inflammation in men. Results from a representative sample of the general population (MONICA Augsburg Survey 1994/95). Eur Heart J 24:1365–1372PubMedCrossRefGoogle Scholar
  7. Genser B, Grammer TB, Stojakovic T, Siekmeier R, März W (2008) Effect of HMG CoA reductase inhibitors on low-density lipoprotein cholesterol and C-reactive protein: systematic review and meta-analysis. Int J Clin Pharmacol Ther 46:497–510PubMedCrossRefGoogle Scholar
  8. Hastie CE, Haw S, Pell JP (2008) Impact of smoking cessation and lifetime exposure on C-reactive protein. Nicotine Tob Res 10:637–642PubMedCrossRefGoogle Scholar
  9. Kleber ME, Wolfert RL, De Moissl GD, Grammer TB, Dietz S, Winkelmann BR, Boehm BO, März W (2011) Lipoprotein associated phospholipase A2 concentration predicts total and cardiovascular mortality independently of established risk factors (The Ludwigshafen Risk and Cardiovascular Health Study). Clin Lab 57:659–667PubMedGoogle Scholar
  10. Lavi S, Prasad A, Yang EH, Mathew V, Simari RD, Rihal CS, Lerman LO, Lerman A (2007) Smoking is associated with epicardial coronary endothelial dysfunction and elevated white blood cell count in patients with chest pain and early coronary artery disease. Circulation 115:2621–2627PubMedCrossRefGoogle Scholar
  11. Libby P (2002) Inflammation in atherosclerosis. Nature 420:868–874PubMedCrossRefGoogle Scholar
  12. Mao J, Liu J, Pang X, Li M, Song J, Han C, Wu D, Wang S (2012) Nicotine indices the expression of C-reactive protein via MAPK-dependent signal pathway in U937 macrophages. Mol Cells 34:457–461PubMedCentralPubMedCrossRefGoogle Scholar
  13. National Cholesterol Education Program Expert Panel on Detection E, treatment of high blood cholesterol in A: third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III) final report. Circulation 106:3143–3421, 2002Google Scholar
  14. Packard CJ, O’Reilly DSJ, Caslake MJ, McMahon AD, Ford I, Cooney J, Macphee CH, Suckling KE, Krishna M, Wilkinson FE, Rumley A, Lowe GDO, The West of Scotland Coronary Prevention Study Group (2000) Lipoprotein-associated phospholipase A2 as an independent predictor of coronary heart disease. N Engl J Med 343:1148–1155PubMedCrossRefGoogle Scholar
  15. Price JF, Mowbray PI, Lee AJ, Rumley A, Lowe GDO, Fowkes FGR (1999) Relationship between smoking and cardiovascular risk factors in the development of peripheral arterial disease and coronary artery disease. Eur Heart J 20:344–353PubMedCrossRefGoogle Scholar
  16. Ridker PM (2003) Clinical application of C-reactive protein for cardiovascular disease detection and prevention. Circulation 107:363–369PubMedCrossRefGoogle Scholar
  17. Ridker PM (2009) C-reactive protein: eighty years from discovery to emergence as a major risk marker for cardiovascular disease. Clin Chem 55:209–215PubMedCrossRefGoogle Scholar
  18. Ross R (1999) Atherosclerosis: an inflammatory disease. N Engl J Med 340:115–126PubMedCrossRefGoogle Scholar
  19. Stafforini DM (2009) Biology of platelet-activating factor acetylhydrolase (PAF-AH, lipoprotein associated phospholipase A2). Cardiovasc Drugs Ther 23:73–83PubMedCrossRefGoogle Scholar
  20. Sudhir K (2005) Clinical review: lipoprotein-associated phospholipase A2, a novel inflammatory biomarker and independent risk predictor for cardiovascular disease. J Clin Endocrinol Metab 90:3100–3105PubMedCrossRefGoogle Scholar
  21. Tselepis AD, Panagiotakos DB, Pitsavos C, Tellis CC, Chrysohoou C, Stefanadis C (2009) Smoking induces lipoprotein-associated phospholipase A2 in cardiovascular disease free adults: the ATTICA Study. Atherosclerosis 206:303–308PubMedCrossRefGoogle Scholar
  22. U.S. Department of Health and Human Services (2006) The health consequences of involuntary exposure to tobacco smoke: a report of the Surgeon General. U.S. Department of Health and Human Services, Centers for Disease Control and Prevention, Coordinating Center for Health Promotion, National Center for Chronic Disease Prevention and Health Promotion, Office on Smoking and Health, Atlanta, GA, pp 1–710Google Scholar
  23. Wallner-Liebmann SJ, Grammer TB, Siekmeier R, Mangge H, März W, Renner W (2013) Smoking denial in cardiovascular disease studies. Adv Exp Med Biol 788:35–38PubMedCrossRefGoogle Scholar
  24. Wannamethee SG, Lowe GDO, Shape AG, Rumley A, Lennon L, Whincup PH (2005) Associations between cigarette smoking, pipe/cigar smoking, and smoking cessation, and haemostatic and inflammatory markers for cardiovascular disease. Eur Heart J 26:1765–1773PubMedCrossRefGoogle Scholar
  25. Winkelmann BR, März W, Boehm BO, Zotz R, Hager J, Hellstern P, Senges J (2001) Rationale and design of the LURIC study – a resource for functional genomics and long-term prognosis of cardiovascular disease. Pharmacogenomics 2(Suppl 1):S1–S73PubMedCrossRefGoogle Scholar
  26. Yanbaeva D, Dentener MA, Creutzberg EC, Wesseling G, Wouters EFM (2007) Systemic effects of smoking. Chest 131:1557–1566PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing Switzerland 2014

Authors and Affiliations

  • M. E. Kleber
    • 1
    Email author
  • R. Siekmeier
    • 2
  • G. Delgado
    • 1
  • T. B. Grammer
    • 1
  • B. R. Winkelmann
    • 3
  • H. Scharnagl
    • 4
  • B. O. Boehm
    • 5
    • 6
  • W. März
    • 1
    • 4
    • 7
  1. 1.Fifth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of MannheimHeidelberg UniversityMannheimGermany
  2. 2.Drug Regulatory AffairsUniversity of BonnBonnGermany
  3. 3.Cardiology GroupFrankfurt-SachsenhausenGermany
  4. 4.Clinical Institute of Medical and Chemical Laboratory DiagnosticsMedical University GrazGrazAustria
  5. 5.Division of Endocrinology, Department of MedicineUniversity HospitalUlmGermany
  6. 6.LKC School of MedicineImperial College London and Nanyang Technological UniversitySingaporeSingapore
  7. 7.Synlab AcademyMannheimGermany

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