Background: Low-grade inflammation has been associated with cardiovascular disease (CVD) and chronic heart failure (CHF). The aim of the present study was to investigate the potential usefulness of the inflammatory protein calprotectin as a biomarker in CHF.
Methods: Plasma calprotectin was measured in 193 CHF patients with left ventricular function <45% and in 100 healthy controls at baseline. Patients with CHF were followed for a median period of 2.6 years according to mortality.
Results: The levels of plasma calprotectin were significantly increased in the CHF patients compared to the control group (P < 0.01), primarily due to elevated levels in the patients with New York Heart Association (NYHA) class III and IV. Furthermore, plasma calprotectin was a superior biomarker of high NYHA classes than other parameters reflecting CHF severity, OR 2.2 (1.1–4.3) (P = 0.019). After the follow-up period, 46 patients had died. Plasma calprotectin levels did not predict mortality in CHF patients.
Conclusions: Plasma calprotectin is increased in CHF patients, indicating that inflammatory activity is upregulated in CHF and may be associated with the severity of CHF.
YndestadADamasJKOieEUelandTGullestadLAukrustP. Systemic inflammation in heart failure–the whys and wherefores. Heart Fail Rev2006; 11: 83–92.
2.
CummingsDMKingDEMainousAGGeeseyME. Combining serum biomarkers: the association of C-reactive protein, insulin sensitivity, and homocysteine with cardiovascular disease history in the general US population. Eur J Cardiovasc Prev Rehabil2006; 13: 180–185.
3.
DeswalAPetersenNJFeldmanAMYoungJBWhiteBGMannDL. Cytokines and cytokine receptors in advanced heart failure: an analysis of the cytokine database from the Vesnarinone trial (VEST). Circulation2001; 103: 2055–2059.
4.
TestaMYehMLeePFanelliRLoperfidoFBermanJW. Circulating levels of cytokines and their endogenous modulators in patients with mild to severe congestive heart failure due to coronary artery disease or hypertension. J Am Coll Cardiol1996; 28: 964–971.
5.
Torre-AmioneGKapadiaSBenedictCOralHYoungJBMannDL. Proinflammatory cytokine levels in patients with depressed left ventricular ejection fraction: a report from the Studies of Left Ventricular Dysfunction (SOLVD). J Am Coll Cardiol1996; 27: 1201–1216.
6.
HessianPAEdgeworthJHoggN. MRP-8 and MRP-14, two abundant Ca(2+)-binding proteins of neutrophils and monocytes. J Leukoc Biol1993; 53: 197–204.
7.
AltweggLANeidhartMHersbergerMMullerSEberliFRCortiR. Myeloid-related protein 8/14 complex is released by monocytes and granulocytes at the site of coronary occlusion: a novel, early, and sensitive marker of acute coronary syndromes. Eur Heart J2007; 28: 941–948.
8.
HealyAMPickardMDPradhanADWangYChenZCroceK. Platelet expression profiling and clinical validation of myeloid-related protein-14 as a novel determinant of cardiovascular events. Circulation2006; 113: 2278–2284.
9.
MorrowDAWangYCroceKSakumaMSabatineMSGaoH. Myeloid-related protein 8/14 and the risk of cardiovascular death or myocardial infarction after an acute coronary syndrome in the Pravastatin or Atorvastatin Evaluation and Infection Therapy: Thrombolysis in Myocardial Infarction (PROVE IT-TIMI 22) trial. Am Heart J2008; 155: 49–55.
10.
JensenLJPedersenSBjerreMMogelvangRJensenJSFlyvbjergA. Plasma calprotectin predicts mortality in patients with ST segment elevation myocardial infarction treated with primary percutaneous coronary intervention. J Interv Cardiol2010; 23: 123–129.
11.
BoydJHKanBRobertsHWangYWalleyKR. S100A8 and S100A9 mediate endotoxin-induced cardiomyocyte dysfunction via the receptor for advanced glycation end products. Circ Res2008; 102: 1239–1246.
12.
GalatiusSGustafssonFNielsenPHAtarDHildebrandtPR. An integrated approach to diagnosis and therapeutic management of patients with systolic heart failure in the Copenhagen metropolitan area. Am Heart J2002; 144: E2–E2.
13.
KistorpCGalatiusSGustafssonFFaberJCorellPHildebrandtP. Prevalence and characteristics of diabetic patients in a chronic heart failure population. Int J Cardiol2005; 100: 281–287.
14.
RaymondIPedersenFBusch-SørensenMGreenAHildebrandtPR. The Frederiksberg Heart Failure Study: rationale, design and methodology, with special emphasis on the sampling procedure for the study population and its comparison to the background population. Heart Drug2002; 2: 167–174.
15.
KarlJBorgyaAGallusserAHuberEKruegerKRollingerW. Development of a novel, N-terminal-proBNP (NT-proBNP) assay with a low detection limit. Scand J Clin Lab Invest Suppl1999; 230: 177–181.
16.
EdgeworthJGormanMBennettRFreemontPHoggN. Identification of p8,14 as a highly abundant heterodimeric calcium binding protein complex of myeloid cells. J Biol Chem1991; 266: 7706–7713.
17.
FoellDFroschMSorgCRothJ. Phagocyte-specific calcium-binding S100 proteins as clinical laboratory markers of inflammation. Clin Chim Acta2004; 344: 37–51.
18.
LamblinNMouquetFHennacheBDagornJSusenSBautersC. High-sensitivity C-reactive protein: potential adjunct for risk stratification in patients with stable congestive heart failure. Eur Heart J2005; 26: 2245–2250.
19.
VasanRSSullivanLMRoubenoffRDinarelloCAHarrisTBenjaminEJ. Inflammatory markers and risk of heart failure in elderly subjects without prior myocardial infarction: the Framingham Heart Study. Circulation2003; 107: 1486–1491.
20.
ViemannDStreyAJanningAJurkKKlimmekKVoglT. Myeloid-related proteins 8 and 14 induce a specific inflammatory response in human microvascular endothelial cells. Blood2005; 105: 2955–2962.
21.
HofmannMADrurySFuCQuWTaguchiALuY. RAGE mediates a novel proinflammatory axis: a central cell surface receptor for S100/calgranulin polypeptides. Cell1999; 97: 889–901.
22.
Alonso-MartinezJLLlorente-DiezBEchegaray-AgaraMOlaz-PreciadoFUrbieta-EchezarretaMGonzalez-ArencibiaC. C-reactive protein as a predictor of improvement and readmission in heart failure. Eur J Heart Fail2002; 4: 331–336.
23.
MassonSLatiniRAnandISBarleraSAngeliciLVagoT. Prognostic value of changes in N-terminal pro-brain natriuretic peptide in Val-HeFT (Valsartan Heart Failure Trial). J Am Coll Cardiol2008; 52: 997–1003.
24.
SchouMGustafssonFKistorpCNCorellPKjaerAHildebrandtPR. Prognostic usefulness of anemia and N-terminal pro-brain natriuretic peptide in outpatients with systolic heart failure. Am J Cardiol2007; 100: 1571–1576.
25.
BockJSGottliebSS. Cardiorenal syndrome: new perspectives. Circulation2010; 121: 2592–2600.
26.
SchulzeMBRimmEBLiTRifaiNStampferMJHuFB. C-reactive protein and incident cardiovascular events among men with diabetes. Diabetes Care2004; 27: 889–894.
