Markers of hypercoagulability and inflammation predict mortality in patients with heart failure.
OBJECTIVE
Plasma levels of inflammatory markers are increased in chronic heart failure (HF) and are also subclinical indicators of future HF. Inflammation is strictly correlated with clotting activation, but the association between inflammation, hypercoagulability and prognosis in HF has not been previously reported.


RESULTS
Markers of inflammation (interleukin-6; IL-6, and C-reactive protein; CRP) and hypercoagulability (D-dimer; DD, and thrombin-antithrombin III complex; TAT) were prospectively assessed in 214 subjects with New York Heart Association (NYHA) functional class II-IV HF. During a median follow-up of 8.5 months, 32 patients had an event: 13 died and 19 were hospitalized because of worsening of HF. IL-6, DD and TAT levels were all significantly associated with increased risk of death after adjustment for other known HF prognostic factors (age, gender, traditional cardiovascular risk factors, NYHA class, systolic left ventricular function, renal failure, hemoglobin, serum sodium) in a Cox multivariate proportional hazard model (P = 0.003, P = 0.01 and P = 0.02, respectively). When these markers were added simultaneously to the known prognostic factors in a new Cox multivariate model, only DD levels were significant predictors of mortality (hazard ratio [95% confidence interval; CI]: 11 [2.7-45.1], P = 0.001). The Kaplan-Meier curve revealed a significantly better outcome in patients with DD below 450 ng mL(-1). NT-pro-BNP was the only significant predictor of rehospitalization (HR [95% CI]: 5.3 [2.0-13.8], P < 0.001).


CONCLUSIONS
Hypercoagulability and inflammation, as assessed by DD, TAT and IL-6 levels, are associated with an increased mortality risk in HF.
Marcucci
R
R
Department of Heart and Vessels, Azienda Ospedaliero-Universitaria Careggi, University of Florence, Viale Morgagni 85, 50134 Florence, Italy. r.marcucci@dac.unifi.it
Gori
A M
AM
Giannotti
F
F
Baldi
M
M
Verdiani
V
V
Del Pace
S
S
Nozzoli
C
C
Abbate
R
R
D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood*; D001778:Blood Coagulation Disorders; D002097:C-Reactive Protein / Q000378:metabolism*; D002303:Cardiac Output, Low / Q000097:blood* / Q000188:drug therapy / Q000401:mortality; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism*; D006334:Heart Function Tests; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000097:blood*; D008297:Male; D020097:Natriuretic Peptide, Brain / Q000097:blood; D010447:Peptide Hydrolases / Q000097:blood*; D012307:Risk Factors
D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D015850:Interleukin-6; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D020097:Natriuretic Peptide, Brain; D000990:Antithrombin III; D002097:C-Reactive Protein; D010447:Peptide Hydrolases