Elevated D-dimer level is an independent risk factor for cardiovascular death in out-patients with symptoms compatible with heart failure

 

 Buy Article Permissions and Reprints

Summary

D-dimer, a marker of fibrin turnover, exhibits many interesting properties as a biological marker of thrombosis. Some of the properties of D-dimer might also be used to provide additional information about patients with heart failure. In this study, we evaluate the prognostic information acquired from D-dimer concerning increased risk of cardiovascular mortality in an elderly population with symptoms associated with heart failure. A cardiologist examined 458 elderly patients, out of 548 invited, attending primary care for symptoms of dyspnoea, fatigue and/or peripheral oedema and assessed NYHA functional class and cardiac function. Abnormal systolic function was defined as EF <40% on Doppler echocardiography. Abnormal diastolic function was defined as reduced E/A ratio and/or an abnormal pattern of pulmonary venous flow. Blood samples were drawn, and BNP and D-dimer were analysed. D-dimer was analysed using an automated micro-latex assay. A statistical analysis was performed to identify the prognostic value of increased plasma concentration of D-dimer. Results showed that during a median follow-up period of 5.5 years, 68 (14%) patients died of cardiovascular disease. No gender difference was noted. A plasma concentration of D-dimer >0.25mg/L increased the risk almost 4-fold. In conclusion, D-dimer is an independent risk factor for cardiovascular mortality that may be used to risk-stratify patients with heart failure.

• References

• 1 Rich MW, Nease RF. Cost-effectiveness analysis in clinical practice: the case of heart failure. Arch Intern Med 1999; 159: 1690-700.
  CrossrefPubMedGoogle Scholar
• 2 Stewart S, MacIntyre K, Hole DJ. et al. More ‘malignant’ than cancer? Five-year survival following a first admission for heart failure. Eur J Heart Fail 2001; 03: 315-22.
  CrossrefPubMedGoogle Scholar
• 3 Stewart S, Horowitz JD. Home-based intervention in congestive heart failure: long-term implications on readmission and survival. Circulation 2002; 105: 2861-6.
  CrossrefPubMedGoogle Scholar
• 4 Mosterd A, Cost B, Hoes AW. et al. The prognosis of heart failure in the general population: The Rotterdam Study. Eur Heart J 2001; 22: 1318-27.
  CrossrefPubMedGoogle Scholar
• 5 Rector TS, Cohn JN. Prognosis in congestive heart failure. Annu Rev Med 1994; 45: 341-50.
  CrossrefPubMedGoogle Scholar
• 6 Marder VJ. Identification and purification of fibrinogen degradation products produced by plasmin: considerations on the structure of fibrinogen. Scand J Haematol Suppl 1971; 13: 21-36.
  PubMedGoogle Scholar
• 7 Kupari M, Lindroos M, Iivanainen AM. et al. Congestive heart failure in old age: prevalence, mechanisms and 4-year prognosis in the Helsinki Ageing Study. J Intern Med 1997; 241: 387-94.
  CrossrefPubMedGoogle Scholar
• 8 Cicoira M, Davos CH, Florea V. et al. Chronic heart failure in the very elderly: clinical status, survival, and prognostic factors in 188 patients more than 70 years old. Am Heart J 2001; 142: 174-80.
  CrossrefPubMedGoogle Scholar
• 9 Cohn JN, Levine TB, Olivari MT. et al. Plasma norepinephrine as a guide to prognosis in patients with chronic congestive heart failure. N Engl J Med 1984; 311: 819-23.
  CrossrefPubMedGoogle Scholar
• 10 Talwar S, Squire IB, Downie PF. et al. Profile of plasma N-terminal proBNP following acute myocardial infarction; correlation with left ventricular systolic dysfunction. Eur Heart J 2000; 21: 1514-21.
  CrossrefPubMedGoogle Scholar
• 11 Hall C, Rouleau JL, Moye L. et al. N-terminal proatrial natriuretic factor. An independent predictor of long-term prognosis after myocardial infarction. Circulation 1994; 89: 1934-42.
  CrossrefPubMedGoogle Scholar
• 12 Jernberg T, Stridsberg M, Venge P. et al. N-terminal pro brain natriuretic peptide on admission for early risk stratification of patients with chest pain and no ST-segment elevation. J Am Coll Cardiol 2002; 40: 437-45.
  CrossrefPubMedGoogle Scholar
• 13 de Lemos JA, Morrow DA, Bentley JH. et al. The prognostic value of B-type natriuretic peptide in patients with acute coronary syndromes. N Engl J Med 2001; 345: 1014-21.
  CrossrefPubMedGoogle Scholar
• 14 Choy AM, Darbar D, Lang CC. et al. Detection of left ventricular dysfunction after acute myocardial infarction: comparison of clinical, echocardiographic, and neurohormonal methods. Br Heart J 1994; 72: 16-22.
  CrossrefPubMedGoogle Scholar
• 15 McDonagh TA, Robb SD, Murdoch DR. et al. Biochemical detection of left-ventricular systolic dysfunction. Lancet 1998; 351: 9-13.
  CrossrefPubMedGoogle Scholar
• 16 Lip GY, Rumley A, Dunn FG. et al. Plasma fibrinogen and fibrin D-dimer in patients with atrial fibrillation: effects of cardioversion to sinus rhythm. Int J Cardiol 1995; 51: 245-51.
  CrossrefPubMedGoogle Scholar
• 17 Kamath S, Chin BS, Blann AD. et al. A study of platelet activation in paroxysmal, persistent and permanent atrial fibrillation. Blood Coagul Fibrinolysis 2002; 13: 627-36.
  CrossrefPubMedGoogle Scholar
• 18 Giansante C, Fiotti N, Miccio M. et al. Coagulation indicators in patients with paroxysmal atrial fibrillation: effects of electric and pharmacologic cardioversion. Am Heart J 2000; 140: 423-9.
  CrossrefPubMedGoogle Scholar
• 19 Dempfle CE, Kontny F, Abildgaard U. Predictive value of coagulation markers concerning clinical outcome 90 days after anterior myocardial infarction. Thromb Haemost 1999; 81: 701-4.
  Article in Thieme ConnectPubMedGoogle Scholar
• 20 Galvani M, Ferrini D, Ottani F. et al. Early risk stratification of unstable angina/non-Q myocardial infarction: biochemical markers of coronary thrombosis. Int J Cardiol 1999; 68 (Suppl. 01) S55-61.
  CrossrefPubMedGoogle Scholar
• 21 Fiotti N, Di Chiara A, Altamura N. et al. Coagulation indicators in chronic stable effort angina and unstable angina: relationship with acute phase reactants and clinical outcome. Blood Coagul Fibrinolysis 2002; 13: 247-55.
  CrossrefPubMedGoogle Scholar
• 22 Alehagen U, Eriksson H, Nylander E. et al. Heart failure in the elderly. Characteristics of a Swedish primary health care population. Heart Drug 2002; 02: 211-220.
  CrossrefPubMedGoogle Scholar
• 23 Kamath S, Blann AD, Chin BS. et al. A study of platelet activation in atrial fibrillation and the effects of antithrombotic therapy. Eur Heart J 2002; 23: 1788-95.
  CrossrefPubMedGoogle Scholar
• 24 Li-Saw-Hee FL, Blann AD, Lip GY. Effects of fixed low-dose warfarin, aspirin-warfarin combination therapy, and dose-adjusted warfarin on thrombogenesis in chronic atrial fibrillation. Stroke 2000; 31: 828-33.
  CrossrefPubMedGoogle Scholar
• 25 Jensen-Urstad K, Bouvier F, Hojer J. et al. Comparison of different echocardiographic methods with radionuclide imaging for measuring left ventricular ejection fraction during acute myocardial infarction treated by thrombolytic therapy. Am J Cardiol 1998; 81: 538-44.
  CrossrefPubMedGoogle Scholar
• 26 van Royen N, Jaffe CC, Krumholz HM. et al. Comparison and reproducibility of visual echocardiographic and quantitative radionuclide left ventricular ejection fractions. Am J Cardiol 1996; 77: 843-50.
  CrossrefPubMedGoogle Scholar
• 27 Dempfle CE, Zips S, Ergul H. et al. The fibrin assay comparison trial (FACT): correlation of soluble fibrin assays with D-dimer. Thromb Haemost 2001; 86: 1204-9.
  Article in Thieme ConnectPubMedGoogle Scholar
• 28 van der Graaf F, van den Borne H, van der Kolk M. et al. Exclusion of deep venous thrombosis with D-dimer testing – comparison of 13 D-dimer methods in 99 outpatients suspected of deep venous thrombosis using venography as reference standard. Thromb Haemost 2000; 83: 191-8.
  Article in Thieme ConnectPubMedGoogle Scholar
• 29 Knecht MF, Heinrich F. Clinical evaluation of an immunoturbidimetric D-dimer assay in the diagnostic procedure of deep vein thrombosis and pulmonary embolism. Thromb Res 1997; 88: 413-7.
  CrossrefPubMedGoogle Scholar
• 30 Mastoroberto P, Chello M, Perticone F. Elevated Circulating Levels of von Willebrand Factor and D-dimer in Patients with Heart Failure and Mechanical Prosthesis. Scand J Thor Cardiovasc Surg 1996; 30: 77-81.
  PubMedGoogle Scholar
• 31 Pitt B, Segal R, Martinez FA. et al. Randomised trial of losartan versus captopril in patients over 65 with heart failure (Evaluation of Losartan in the Elderly Study, ELITE). Lancet 1997; 349: 747-52.
  CrossrefPubMedGoogle Scholar
• 32 Swedberg K, Kjekshus J. Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). Am J Cardiol 1988; 62: 60A-66A.
  CrossrefPubMedGoogle Scholar
• 33 Parameshwar J, Shackell MM, Richardson A. et al. Prevalence of heart failure in three general practices in north west London. Br J Gen Pract 1992; 42: 287-9.
  PubMedGoogle Scholar
• 34 De Lorenzo F, Newberry D, Scully M. et al. Low molecular weight heparin (bemiparin sodium) and the coagulation profile of patients with heart failure. Am Heart J 2002; 143: 689.
  PubMedGoogle Scholar