Abnormalities of Hemorheological, Endothelial, and Platelet Function in Patients With Chronic Heart Failure in Sinus Rhythm: Effects of Angiotensin-Converting Enzyme Inhibitor and &bgr;-Blocker Therapy

BackgroundTo investigate the hypothesis that abnormalities of hemorheological (fibrinogen, plasma viscosity), endothelial (von Willebrand factor [vWF]), and platelet (soluble P-selectin) function would exist in patients with chronic heart failure (CHF) who are in sinus rhythm, we conducted a cross-sectional study of 120 patients with stable CHF (median ejection fraction 30%). We also hypothesized that ACE inhibitors and &bgr;-blockers would beneficially affect the measured indices. Methods and ResultsIn the cross-sectional analysis, plasma viscosity (P =0.001), fibrinogen (P =0.02), vWF (P <0.0001), and soluble P-selectin (P <0.001) levels were elevated in patients with CHF compared with healthy controls. Women demonstrated greater abnormalities of hemorheological indices and vWF than males (all P <0.05). Plasma viscosity (P =0.009) and fibrinogen (P =0.0014) levels were higher in patients with more severe symptoms (New York Heart Association [NYHA] class III–IV), but there was no relationship with left ventricular ejection fraction. When ACE inhibitors were introduced, there was a reduction in fibrinogen (repeated-measures ANOVA, P =0.016) and vWF (P =0.006) levels compared with baseline. There were no significant changes in hemorheological, endothelial, or platelet markers after the introduction of &bgr;-blocker therapy, apart from a rise in mean platelet count (P <0.001). ConclusionsAbnormal levels of soluble P-selectin, vWF, and hemorheological indices may contribute to a hypercoagulable state in CHF, especially in female patients and in those with more severe NYHA class. Treatment with ACE inhibitors improved the prothrombotic state in CHF, whereas the addition of &bgr;-blockers did not. These positive effects of ACE inhibitors may offer an explanation for the observed reduction in ischemic events in clinical trials.

[1]  J. Hetzel,et al.  Plasma viscosity and fibrinogen in relation to haemodynamic findings in chronic congestive heart failure , 1999, European journal of heart failure.

[2]  C. O'connor,et al.  Usefulness of soluble and surface-bound P-selectin in detecting heightened platelet activity in patients with congestive heart failure. , 1999, The American journal of cardiology.

[3]  G. Lip,et al.  Does heart failure confer a hypercoagulable state? Virchow's triad revisited. , 1999, Journal of the American College of Cardiology.

[4]  R. Fogari,et al.  ACE inhibition but not angiotensin II antagonism reduces plasma fibrinogen and insulin resistance in overweight hypertensive patients. , 1998, Journal of cardiovascular pharmacology.

[5]  J. Cleland,et al.  Influence of concomitant disease on patterns of hospitalization in patients with heart failure discharged from Scottish hospitals in 1995. , 1998, European heart journal.

[6]  Aj Lee.  The role of rheological and haemostatic factors in hypertension , 1997, Journal of Human Hypertension.

[7]  G. Lamas,et al.  Ventricular dysfunction and the risk of stroke after myocardial infarction. , 1997, The New England journal of medicine.

[8]  T. Meade.  Fibrinogen and cardiovascular disease. , 1997, Journal of clinical pathology.

[9]  M. Trovati,et al.  Role of catecholamines in platelet function: pathophysiological and clinical significance , 1996, European journal of clinical investigation.

[10]  I. Sartori.  Hemostatic Factors and the Risk of Myocardial Infarction or Sudden Death in Patients with Angina Pectoris , 1996 .

[11]  G. Lip,et al.  Soluble adhesion molecule P-selectin and endothelial dysfunction in essential hypertension: implications for atherogenesis? A preliminary report. , 1995, Journal of hypertension.

[12]  G. Lip,et al.  von Willebrand factor and its relevance to cardiovascular disorders. , 1995, British heart journal.

[13]  G. Lip.  Does atrial fibrillation confer a hypercoagulable state? , 1995, The Lancet.

[14]  G. Lowe,et al.  Effects of warfarin therapy on plasma fibrinogen, von Willebrand factor, and fibrin D-dimer in left ventricular dysfunction secondary to coronary artery disease with and without aneurysms. , 1995, The American journal of cardiology.

[15]  S. Yusuf,et al.  Overview of Randomized Trials of Angiotensin-Converting Enzyme Inhibitors on Mortality and Morbidity in Patients With Heart Failure , 1995 .

[16]  G. Lip.  Fibrinogen and cardiovascular disorders. , 1995, QJM : monthly journal of the Association of Physicians.

[17]  S. Yusuf,et al.  Natural history and patterns of current practice in heart failure , 1993 .

[18]  J. Cohn,et al.  Incidence of Thromboembolic Events in Congestive Heart Failure , 1993, Circulation.

[19]  J. Jansson,et al.  von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death , 1992, British heart journal.

[20]  H. Tunstall-Pedoe,et al.  Epidemiology of haematocrit, white cell count, red cell aggregation and fibrinogen: The Glasgow MONICA study , 1992 .

[21]  J. Jansson,et al.  von Willebrand factor in plasma: a novel risk factor for recurrent myocardial infarction and death. , 1991, British heart journal.

[22]  T. Rector,et al.  Endothelium‐Dependent Vasodilation Is Attenuated in Patients With Heart Failure , 1991, Circulation.

[23]  V. Tkachuk,et al.  Relationship between the inhibition of receptor-induced increase in cytosolic free calcium concentration and the vasodilator effects of nitrates in patients with congestive heart failure. , 1990, International journal of cardiology.

[24]  J. Yudkin,et al.  Increased mean platelet volume after acute myocardial infarction relates to diabetes and to cardiac failure. , 1988, Diabetes research and clinical practice.

[25]  K. Swedberg,et al.  Effects of enalapril on mortality in severe congestive heart failure: results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). , 1988, The American journal of cardiology.

[26]  P. Kyrle,et al.  Prevention of Arterial and Pulmonary Embolism by Oral Anticoagulants in Patients with Dilated Cardiomyopathy , 1985, Thrombosis and Haemostasis.

[27]  C. Furberg,et al.  β-Adrenergic Blockade for Survivors of Acute Myocardial Infarction , 1984 .

[28]  C. Furberg,et al.  Beta-adrenergic blockade for survivors of acute myocardial infarction. , 1984, The New England journal of medicine.

[29]  P. Lundborg,et al.  The peripheral platelet count and ADP-induced platelet aggregation in response to metoprolol and propranolol as studied in young healthy male volunteers. , 2009, Scandinavian journal of haematology.

[30]  J. V. Nixon,et al.  Left ventricular mural thrombus. , 1983, Archives of internal medicine.

[31]  V. Fuster,et al.  The natural history of idiopathic dilated cardiomyopathy. , 1981, The American journal of cardiology.

[32]  J. Mehta,et al.  Platelet Function Studies in Heart Disease: VI. Enhanced Platelet Aggregate Formation Activity in Congestive Heart Failure Inhibition by Sodium Nitroprusside , 1979, Circulation.

[33]  P. Lundborg,et al.  The peripheral platelet count in response to adrenergic alpha-and beta-1-receptor stimulation. , 2009, Scandinavian journal of haematology.

[34]  W. P. Harvey,et al.  Idiopathic cardiomyopathy: clinical features, prognosis and therapy. , 1978, Current problems in cardiology.

[35]  A. Gooch,et al.  Primary Myocardial Disease: Report of Fifty Cases and Review of the Subject , 1965, Circulation.

[36]  F. J. Moore,et al.  A study of the beneficial effects of anticoagulant therapy in congestive heart failure. , 1952, Annals of internal medicine.