Prospective study of markers of hemostatic function with risk of ischemic stroke. The Atherosclerosis Risk in Communities (ARIC) Study Investigators.

BACKGROUND Several markers of hemostatic function and inflammation have been associated with increased risk of coronary heart disease, but prospective evidence for their role in ischemic stroke is scant. METHODS AND RESULTS The Atherosclerosis Risk in Communities (ARIC) Study measured several of these markers in more than 14 700 participants 45 to 64 years old who were free of cardiovascular disease and were followed up for 6 to 9 years for occurrence of ischemic stroke (n=191). There was no apparent association between ischemic stroke incidence and factor VIIc, antithrombin III, platelet count, or activated partial thromboplastin time. After adjustment for multiple cardiovascular risk factors, von Willebrand factor, factor VIIIc, fibrinogen, and white blood cell count were positively associated and protein C was negatively but nonsignificantly associated with ischemic stroke incidence in regression analyses based on either continuous variables or fourths of the variable distributions. The adjusted relative risk (and 95% CI) for ischemic stroke in those in the highest versus lowest fourth were: von Willebrand factor, 1.71 (1.1 to 2.7); factor VIIIc, 1.93 (1.2 to 3.1); white blood cell count, 1.50 (0.9 to 2.4); fibrinogen, 1.26 (0.8 to 2.0); and protein C, 0.65 (0.4 to 1.0). CONCLUSIONS This study offers modest support for the hypothesis that some markers of hemostatic function and inflammation can identify groups of middle-aged adults at increased risk of stroke. These factors may play a role in the pathogenesis of ischemic stroke.

[1]  A. Folsom,et al.  Stroke incidence and survival among middle-aged adults: 9-year follow-up of the Atherosclerosis Risk in Communities (ARIC) cohort. , 1999, Stroke.

[2]  A. Döring,et al.  C-Reactive protein, a sensitive marker of inflammation, predicts future risk of coronary heart disease in initially healthy middle-aged men: results from the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992. , 1999, Circulation.

[3]  P. Ridker,et al.  Prospective study of C-reactive protein and the risk of future cardiovascular events among apparently healthy women. , 1998, Circulation.

[4]  R Peto,et al.  Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease: meta-analyses of prospective studies. , 1998, JAMA.

[5]  A. Rumley,et al.  Hemostatic factors as predictors of ischemic heart disease and stroke in the Edinburgh Artery Study. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[6]  A. Folsom,et al.  Prospective study of hemostatic factors and incidence of coronary heart disease: the Atherosclerosis Risk in Communities (ARIC) Study. , 1997, Circulation.

[7]  J. Barrett,et al.  von Willebrand Factor and Factor VIII: C in Acute Cerebrovascular Disease , 1997, Thrombosis and Haemostasis.

[8]  P. Ridker,et al.  Inflammation, aspirin, and the risk of cardiovascular disease in apparently healthy men. , 1997, The New England journal of medicine.

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

[10]  P. Savage,et al.  Fibrinogen and factor VIII, but not factor VII, are associated with measures of subclinical cardiovascular disease in the elderly. Results from The Cardiovascular Health Study. , 1995, Arteriosclerosis, thrombosis, and vascular biology.

[11]  J. Fisher,et al.  Long-term outcomes and modes of death of patients treated with nonthoracotomy implantable defibrillators. , 1995, The American journal of cardiology.

[12]  R. Prineas,et al.  Relation between electrocardiography and echocardiography for left ventricular mass in mild systemic hypertension (results from Treatment of Mild Hypertension Study). , 1995, The American journal of cardiology.

[13]  R. Gillum,et al.  White blood cell count and stroke incidence and death. The NHANES I epidemiologic follow-up study. , 1994, American journal of epidemiology.

[14]  J. Manson,et al.  Prospective study of endogenous tissue plasminogen activator and risk of stroke , 1994, The Lancet.

[15]  A. Folsom,et al.  Association of hemostatic variables with prevalent cardiovascular disease and asymptomatic carotid artery atherosclerosis. The Atherosclerosis Risk in Communities (ARIC) Study Investigators. , 1993, Arteriosclerosis and thrombosis : a journal of vascular biology.

[16]  A. Blann.  von Willebrand factor and the endothelium in vascular disease. , 1993, British journal of biomedical science.

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

[18]  A. Folsom,et al.  Short-term intraindividual variability in hemostasis factors. The ARIC Study. Atherosclerosis Risk in Communities Intraindividual Variability Study. , 1992, Annals of epidemiology.

[19]  E. Ernst,et al.  Fibrinogen and Viscosity as Risk Factors for Subsequent Cardiovascular Events in Stroke Survivors , 1992, Annals of Internal Medicine.

[20]  J. Ware,et al.  Structure and Function of von Willebrand Factor , 1992, Thrombosis and Haemostasis.

[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]  P C Elwood,et al.  Fibrinogen, Viscosity, and White Blood Cell Count Are Major Risk Factors for Ischemic Heart Disease: The Caerphilly and Speedwell Collaborative Heart Disease Studies , 1991, Circulation.

[23]  Aric Invest.  The Atherosclerosis Risk in Communities (ARIC) Study: design and objectives. The ARIC investigators , 1989 .

[24]  K. Wu,et al.  ARICHemostasis Study - I. Development of a Blood Collection and Processing System Suitable for Multicenter Hemostatic Studies , 1989, Thrombosis and Haemostasis.

[25]  R. D'Agostino,et al.  Fibrinogen and risk of cardiovascular disease. The Framingham Study. , 1987, JAMA.

[26]  Leukocytes and the risk of ischemic diseases. , 1987, JAMA.

[27]  S. Thompson,et al.  HAEMOSTATIC FUNCTION AND ISCHAEMIC HEART DISEASE: PRINCIPAL RESULTS OF THE NORTHWICK PARK HEART STUDY , 1986, The Lancet.

[28]  L. Wilhelmsen,et al.  Fibrinogen as a risk factor for stroke and myocardial infarction. , 1984, The New England journal of medicine.

[29]  J E Frijters,et al.  A short questionnaire for the measurement of habitual physical activity in epidemiological studies. , 1982, The American journal of clinical nutrition.

[30]  R. Prentice,et al.  Leukocyte counts and cerebrovascular disease. , 1982, Journal of chronic diseases.

[31]  S. Thompson,et al.  HÆMOSTATIC FUNCTION AND CARDIOVASCULAR DEATH: EARLY RESULTS OF A PROSPECTIVE STUDY , 1980, The Lancet.

[32]  S. Thompson,et al.  Haemostatic function and cardiovascular death: early results of a prospective study. , 1980, Lancet.

[33]  R. Levy,et al.  Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. , 1972, Clinical chemistry.