Chronobiology of hemostasis and inferences for the chronotherapy of coagulation disorders and thrombosis prevention.

The hemostatic system in its multiple components displays an intricate organization in time which is characterized by circadian (approximately 24-hour), circaseptan (approximately 7-day), menstrual (approximately monthly), and circannual (approximately yearly) bioperiodicities. The interaction of the rhythms of the variables participating in hemostasis determine transient risk states of thromboembolic events, including myocardial infarction and stroke, and of hemorrhage and hemorrhagic events, each with a unique timing. The circadian staging of the rhythms in vascular, cellular, and coagulation factors that favors blood coagulation and thrombosis coincides with the daily minimum in fibrinolytic activity; as a result there is elevated risk in the morning of acute myocardial infarction and stroke. Similar hemostatic rhythms may determine the epidemiology of thromboembolic and hemorrhagic events during the week, month and year. This article focuses on the large-amplitude circadian rhythms operative in the hemostatic system. Their implication for preventive and curative pharmacotherapy of hemostatic disorders is presented, with discussion of related problems.

[1]  F. Fleury-Olela,et al.  Restricted feeding uncouples circadian oscillators in peripheral tissues from the central pacemaker in the suprachiasmatic nucleus. , 2000, Genes & development.

[2]  E. Haus,et al.  Circadian variations in blood coagulation parameters, alpha-antitrypsin antigen and platelet aggregation and retention in clinically healthy subjects. , 1990, Chronobiology international.

[3]  K. Okumura,et al.  Circadian variation in fibrinolytic activity in patients with variant angina. , 1994, British heart journal.

[4]  M. Alessi,et al.  PAI-1, Obesity, Insulin Resistance and Risk of Cardiovascular Events , 1997, Thrombosis and Haemostasis.

[5]  C. Kluft,et al.  Plasminogen activator inhibitors. , 1987, Blood.

[6]  E. Haus,et al.  Principles of Clinical Chronobiology , 1992 .

[7]  D. Maiman,et al.  Is chronic spinal cord injury associated with increased risk of venous thromboembolism? , 1993, The Journal of the American Paraplegia Society.

[8]  C. Jern,et al.  Regulation of local availability of active tissue‐type plasminogen activator in vivo in man , 2004, Journal of thrombosis and haemostasis : JTH.

[9]  D. Levy,et al.  Association between increased estrogen status and increased fibrinolytic potential in the Framingham Offspring Study. , 1995, Circulation.

[10]  S. Ameriso,et al.  Morning reduction of cerebral vasomotor reactivity , 1994, Neurology.

[11]  J. Hirsh,et al.  A standard heparin nomogram for the management of heparin therapy. , 1991, Archives of internal medicine.

[12]  E. Granieri,et al.  Patient demographic and clinical features and circadian variation in onset of ischemic stroke. , 2002, Archives of neurology.

[13]  K. Yagita,et al.  Angiotensin II Induces Circadian Gene Expression of Clock Genes in Cultured Vascular Smooth Muscle Cells , 2001, Circulation.

[14]  L. Korkmaz,et al.  Circadian variation in circulating platelet aggregates. , 1989, Annals of medicine.

[15]  P. Stone.  Triggers of transient myocardial ischemia: circadian variation and relation to plaque rupture and coronary thrombosis in stable coronary artery disease. , 1990, The American journal of cardiology.

[16]  S. Haffner,et al.  Elevated levels of acute-phase proteins and plasminogen activator inhibitor-1 predict the development of type 2 diabetes: the insulin resistance atherosclerosis study. , 2002, Diabetes.

[17]  H. Kwaan.  Changes in Blood Coagulation, Platelet Function, and Plasminogen-Plasmin System in Diabetes , 1992, Diabetes.

[18]  Y Sakaki,et al.  Resetting central and peripheral circadian oscillators in transgenic rats. , 2000, Science.

[19]  R. C. Hermida,et al.  Variación estacional del fibrinógeno plasmático en pacientes dippers y no dippers con hipertensión arterial esencial ligera-moderada , 2003 .

[20]  M. Mclaren,et al.  Circadian rhythm of white blood cell aggregation and free radical status in healthy volunteers. , 1992, Free radical research communications.

[21]  Julio A. Panza,et al.  Circadian variation in vascular tone and its relation to α-sympathetic vasoconstrictor activity , 1991 .

[22]  C. Shimazu,et al.  Reference values of hemostasis related factors of healthy Japanese adults. I: Circadian fluctuation. , 1990, Thrombosis research.

[23]  G. Casale,et al.  Antithrombin III and circadian rhythms in the aged and in myocardial infarction. , 1983, Haematologica.

[24]  S. M. de la Monte,et al.  CLIF, a Novel Cycle-like Factor, Regulates the Circadian Oscillation of Plasminogen Activator Inhibitor-1 Gene Expression* , 2000, The Journal of Biological Chemistry.

[25]  M. Alessi,et al.  Plasminogen Activator Inhibitor-1 Expression in Human Liver and Healthy or Atherosclerotic Vessel Walls , 1994, Thrombosis and Haemostasis.

[26]  C. Johnson,et al.  Regulation of the PAI-1 promoter by circadian clock components: differential activation by BMAL1 and BMAL2. , 2003, Journal of molecular and cellular cardiology.

[27]  R. Mangiafico,et al.  Daily modifications of plasma fibrinogen platelets aggregation, Howell's time, PTT, TT, and antithrombin II in normal subjects and in patients with vascular disease. , 1982, Chronobiologia.

[28]  M. Rousseau,et al.  Risk factors for deep venous thrombosis in tetraparesic mentally retarded patients , 2001, Brain injury.

[29]  J. Henry.  Clinical diagnosis and management by laboratory methods , 1979 .

[30]  L. Weinehall,et al.  High plasminogen activator inhibitor and tissue plasminogen activator levels in plasma precede a first acute myocardial infarction in both men and women: evidence for the fibrinolytic system as an independent primary risk factor. , 1998, Circulation.

[31]  M. Alessi,et al.  Increased plasma plasminogen activator inhibitor 1 levels. A possible link between insulin resistance and atherothrombosis , 1991, Diabetologia.

[32]  D. Redwood,et al.  Blood Fibrinolytic Activity in Man: Diurnal Variation and the Response to Varying Intensities of Exercise , 1970, Circulation research.

[33]  B. Kudielka,et al.  Relationship between overnight neuroendocrine activity and morning haemostasis in working men. , 2004, Clinical science.

[34]  M. Straume,et al.  Day/night rhythms in gene expression of the normal murine heart , 2004, Journal of Molecular Medicine.

[35]  D. Lawrence,et al.  Fibrinolytic system of cultured endothelial cells: Regulation by plasminogen activator inhibitor , 1986, Journal of cellular biochemistry.

[36]  E. Braunwald,et al.  Morning resistance to thrombolytic therapy. , 1995, Circulation.

[37]  B. Wiman,et al.  Kinetics of the inhibition of plasminogen activators by the plasminogen-activator inhibitor. Evidence for 'second-site' interactions. , 1988, The Biochemical journal.

[38]  S. Fava,et al.  Absence of circadian variation in the onset of acute myocardial infarction in diabetic subjects. , 1995, British heart journal.

[39]  E. Haus,et al.  Biologic Rhythms in Clinical and Laboratory Medicine , 1992, Springer Berlin Heidelberg.

[40]  U. Zeymer,et al.  Recombinant hirudin (HBW 023) produces stable anticoagulation unaffected by circadian variation in patients with thrombolysis for acute myocardial infarction. , 1996, European heart journal.

[41]  C. Dollery,et al.  Heparin Kinetics in Venous Thrombosis and Pulmonary Embolism , 1976, Circulation.

[42]  T. Pringle,et al.  Circadian variation of tissue plasminogen activator and its inhibitor, von Willebrand factor antigen, and prostacyclin stimulating factor in men with ischaemic heart disease. , 1993, British heart journal.

[43]  S. Reppert,et al.  Molecular analysis of mammalian circadian rhythms. , 2001, Annual review of physiology.

[44]  Y. Ouchi,et al.  Modulation of endothelium-dependent flow-mediated dilatation of the brachial artery by sex and menstrual cycle. , 1995, Circulation.

[45]  R. Peters.  Propranolol and the morning increase in sudden cardiac death: (the beta-blocker heart attack trial experience). , 1990, The American journal of cardiology.

[46]  D. Vaughan,et al.  Effect of activation and inhibition of the renin-angiotensin system on plasma PAI-1. , 1998, Hypertension.

[47]  I. Nilsson,et al.  On fibrinolysis in diabetes mellitus. , 2009, Acta medica Scandinavica.

[48]  P. Quehenberger,et al.  The formation of platelet–leukocyte aggregates varies during the menstrual cycle , 2006, Platelets.

[49]  A. S. Douglas,et al.  Circannual Rhythm of Arterial and Venous Thromboembolic Disease , 1979, Scottish medical journal.

[50]  K. Schmidt,et al.  Acute Platelet Activation Induced by Smoking , 1984, Thrombosis and Haemostasis.

[51]  A. Meinders,et al.  Diurnal Rhythm in Anticoagulant Effect of Heparin during a Low Dose Constant Rate Infusion , 1992, Thrombosis and Haemostasis.

[52]  A. Michelson,et al.  Effect of Strenuous Exercise on Platelet Activation State and Reactivit , 1993, Circulation.

[53]  P. Marckmann,et al.  Dietary effects on circadian fluctuation in human blood coagulation factor VII and fibrinolysis. , 1993, Atherosclerosis.

[54]  Y. Hirota,et al.  Circadian variations of onset of acute myocardial infarction and efficacy of thrombolytic therapy. , 1996, Journal of the American College of Cardiology.

[55]  C. Shaw,et al.  The intrinsic circadian clock within the cardiomyocyte. , 2005, American journal of physiology. Heart and circulatory physiology.

[56]  J. Hirsh,et al.  Heparin: mechanism of action, pharmacokinetics, dosing considerations, monitoring, efficacy, and safety. , 1992, Chest.

[57]  R. Colman.  Hemostasis and thrombosis: Basic principles and clinical practice , 1987 .

[58]  S. Thompson,et al.  Fibrinolytic factors and the risk of myocardial infarction or sudden death in patients with angina pectoris. ECAT Study Group. European Concerted Action on Thrombosis and Disabilities. , 1996, Circulation.

[59]  R. Nohara,et al.  Modification of the circadian variation of symptom onset of acute myocardial infarction in diabetes mellitus , 1995, Coronary artery disease.

[60]  H. Altunbas,et al.  Circadian Variations in Natural Coagulation Inhibitors Protein C, Protein S and Antithrombin in Healthy Men: A Possible Association with Interleukin-6 , 1999, Thrombosis and Haemostasis.

[61]  P. Fratino,et al.  Impaired Circadian Modulation of Sympathovagal Activity in Diabetes: A Possible Explanation for Altered Temporal Onset of Cardiovascular Disease , 1992, Circulation.

[62]  V. Dietz,et al.  Loss of circadian blood pressure variability in complete tetraplegia. , 1996, Journal of human hypertension.

[63]  R. Levin.  The puzzle of aspirin and sex. , 2005, The New England journal of medicine.

[64]  J. Mehta,et al.  Effects of smoking on platelets and on plasma thromboxane-prostacyclin balance in man. , 1982, Prostaglandins, leukotrienes, and medicine.

[65]  C. Jern,et al.  Endothelium-dependent vasodilation and tissue-type plasminogen activator release in borderline hypertension. , 1997, Arteriosclerosis, thrombosis, and vascular biology.

[66]  A. Jovicic,et al.  Circadian variations of platelet aggregability and fibrinolytic activity in healthy subjects. , 1991, Thrombosis research.

[67]  E. Braunwald,et al.  Circadian variation in the frequency of onset of acute myocardial infarction. , 1985, The New England journal of medicine.

[68]  E. Mammen,et al.  Circadian variation in platelet function in healthy volunteers. , 1992, The American journal of cardiology.

[69]  A. Quyyumi,et al.  Effect of systemic alpha-2 adrenergic blockade on the morning increase in platelet aggregation in normal subjects. , 1999, The American journal of cardiology.

[70]  P. Kurnik.  Circadian variation in the efficacy of tissue-type plasminogen activator. , 1995, Circulation.

[71]  J. Gris,et al.  Circadian changes in anticoagulant effect of heparin infused at a constant rate. , 1985, British medical journal.

[72]  T. Meade,et al.  Seasonal variations of plasma fibrinogen and factor VII activity in the elderly: winter infections and death from cardiovascular disease , 1994, The Lancet.

[73]  M. Prins,et al.  Heparin Binding to Plasma Proteins, an Important Mechanism for Heparin Resistance , 1992, Thrombosis and Haemostasis.

[74]  B. Osterud,et al.  The effect of physical conditioning suggests adaptation in procoagulant and fibrinolytic potential. , 1997, Thrombosis research.

[75]  A H Goodall,et al.  Activation of haemostasis by exercise, mental stress and adrenaline: effects on platelet sensitivity to thrombin and thrombin generation. , 1999, Clinical science.

[76]  H. Brogren,et al.  Platelets synthesize large amounts of active plasminogen activator inhibitor 1. , 2004, Blood.

[77]  B. Jilma,et al.  Morning hypercoagulability and hypofibrinolysis. Diurnal variations in circulating activated factor VII, prothrombin fragment F1+2, and plasmin-plasmin inhibitor complex. , 1997, Circulation.

[78]  U. Hodoğlugil,et al.  SEASONAL VARIATION IN THE EFFECT OF A FIXED DOSE OF HEPARIN ON ACTIVATED CLOTTING TIME IN PATIENTS PREPARED FOR OPEN-HEART SURGERY* , 2001, Chronobiology international.

[79]  P. Grant,et al.  Plasminogen-activator inhibitor type 1 and coronary artery disease. , 2000, The New England journal of medicine.

[80]  N. Mcintyre,et al.  Diurnal pattern of variceal bleeding in cirrhotic patients. , 1993, Journal of Hepatology.

[81]  L. Rabbani,et al.  Dynamic variability of hemostatic and fibrinolytic factors in young women. , 2004, The Journal of clinical endocrinology and metabolism.

[82]  V. Fuster,et al.  Daily and seasonal variation in sudden cardiac death, Rochester, Minnesota, 1950-1975. , 1982, Mayo Clinic proceedings.

[83]  T. Okumura,et al.  Circadian gene expression of clock genes and plasminogen activator inhibitor-1 in heart and aorta of spontaneously hypertensive and Wistar–Kyoto rats , 2003, Journal of hypertension.

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

[85]  M. Winniford,et al.  Speculation regarding mechanisms responsible for acute ischemic heart disease syndromes. , 1986, Journal of the American College of Cardiology.

[86]  D. Vaughan,et al.  Bradykinin stimulates tissue plasminogen activator release in human vasculature. , 1999, Hypertension.

[87]  A. Hamsten,et al.  Allele-specific increase in basal transcription of the plasminogen-activator inhibitor 1 gene is associated with myocardial infarction. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[88]  B. Wiman,et al.  Tissue plasminogen activator (tPA) antigen in plasma: correlation with different tPA/inhibitor complexes. , 1998, Scandinavian journal of clinical and laboratory investigation.

[89]  A. Hofman,et al.  Seasonal Variation in Fibrinogen in the Rotterdam Study , 1997, Thrombosis and Haemostasis.

[90]  E. Haus,et al.  Circadian Variation in Stroke Onset: Identical Temporal Pattern in Ischemic and Hemorrhagic Events , 2005, Chronobiology international.

[91]  L. Bolondi,et al.  Circadian occurrence of variceal bleeding in patients with liver cirrhosis , 1996, Journal of gastroenterology and hepatology.

[92]  A. Quyyumi,et al.  Mechanisms underlying the morning increase in platelet aggregation: a flow cytometry study. , 1996, Journal of the American College of Cardiology.

[93]  J. Belch.  The role of the white blood cell in arterial disease. , 1990, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[94]  H P Schultheiss,et al.  Diurnal, weekly and seasonal variation of sudden death. Population-based analysis of 24,061 consecutive cases. , 2000, European heart journal.

[95]  V. Fuster,et al.  Platelet-active drugs: the relationships among dose, effectiveness, and side effects. , 2004, Chest.

[96]  J. Dawes.  Comparison of the pharmacokinetics of enoxaparin (Clexane) and unfractionated heparin. , 1990, Acta chirurgica Scandinavica. Supplementum.

[97]  A. Meinders,et al.  Diurnal changes in heparin effect during continuous constant‐rate infusion. A study in nine patients with venous thromboembolism , 1994, Journal of internal medicine.

[98]  M. Scully,et al.  MEASUREMENT OF HEPARIN IN PLASMA: INFLUENCE OF INTER-SUBJECT AND CIRCADIAN VARIABILITY IN HEPARIN SENSITIVITY ACCORDING TO METHOD , 1987, Thrombosis and Haemostasis.

[99]  M. Kaneko,et al.  Circadian variation in human peripheral blood flow levels and exercise responses. , 1968, Journal of applied physiology.

[100]  T. Pringle,et al.  Circadian variation of white blood cell aggregation and free radical indices in men with ischaemic heart disease. , 1992, European heart journal.

[101]  K. Shimada,et al.  Thrombin generation as an acute effect of cigarette smoking. , 1994, American heart journal.

[102]  D. Grobbee,et al.  The 4G5G polymorphism in the gene for PAI-1 and the circadian oscillation of plasma PAI-1. , 2003, Blood.

[103]  B. Lemmer,et al.  Physiology and Pharmacology of Biological Rhythms , 1997, Handbook of Experimental Pharmacology.

[104]  V. Fuster,et al.  The pathogenesis of coronary artery disease and the acute coronary syndromes (2). , 1992, The New England journal of medicine.

[105]  U. Ikeda,et al.  Effect of a Change in the Sleep/Wake Cycle on the Diurnal Variation of Fibrinolytic Parameters , 1998, Journal of Thrombosis and Thrombolysis.

[106]  K. Huber,et al.  Circadian Fluctuations of Plasminogen Activator Inhibitor and Tissue Plasminogen Activator Levels in Plasma of Patients with Unstable Coronary Artery Disease and Acute Myocardial Infarction , 1988, Thrombosis and Haemostasis.

[107]  R. Sothern,et al.  Weekly and yearly rhythms in plasma fibrinogen in hospitalized male military veterans. , 1995, The American journal of cardiology.

[108]  N. Ruderman,et al.  Impaired fibrinolytic response to exercise in type II diabetes: effects of exercise and physical training. , 1988, Metabolism: clinical and experimental.

[109]  L. Bolondi,et al.  Cirrhosis does not shift the circadian phase of plasma fibrinolysis. , 2002 .

[110]  J. Geleijnse,et al.  Diurnal Variation in PAI-1 Activity Predominantly Confined to the 4G-allele of the PAI-1 Gene , 2002, Thrombosis and Haemostasis.

[111]  M. Dalby,et al.  Diurnal variation in platelet aggregation iwth the PFA-100 platelet function analyser. , 2000, Platelets.

[112]  R. Couch.  Travel, Time Zones, and Sudden Cardiac Death: Emporiatric Pathology , 1990, The American journal of forensic medicine and pathology.

[113]  E. Gilpin,et al.  Differing circadian patterns of symptom onset in subgroups of patients with acute myocardial infarction. , 1989, Circulation.

[114]  J. Dimsdale,et al.  Relation of nocturnal blood pressure dipping to cellular adhesion, inflammation and hemostasis , 2004, Journal of hypertension.

[115]  A. Hillis,et al.  In cirrhotic patients variceal bleeding is more frequent in the evening and correlates with severity of liver disease. , 1999, Hepato-gastroenterology.

[116]  F. Marín,et al.  Hypofibrinolysis in atrial fibrillation. , 1998, American heart journal.

[117]  A. Burger,et al.  Circadian patterns of heart rate variability, fibrinolytic activity, and hemostatic factors in type I diabetes mellitus with cardiac autonomic neuropathy. , 1999, The American journal of cardiology.

[118]  M. Mclaren,et al.  Circadian variation of endothelial cell function, red blood cell deformability and dehydro‐thromboxane B2 in healthy volunteers , 1991, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[119]  P. Kurnik,et al.  Practical implications of circadian variations in thrombolytic and antithrombotic activities. , 1996, Cardiology clinics.

[120]  H. Décousus,et al.  Chrono-Pharmacological Study of Once Daily Curative Dose of a Low Molecular Weight Heparin (200IU antiXa/kg of Dalteparin) in Ten Healthy Volunteers , 1995, Thrombosis and Haemostasis.

[121]  J. Loscalzo,et al.  Effects on platelet aggregation and fibrinolytic activity during upright posture and exercise in healthy men. , 1992, The American journal of cardiology.

[122]  D. Rijken.  Plasminogen activators and plasminogen activator inhibitors: biochemical aspects. , 1995, Bailliere's clinical haematology.

[123]  C. Jern,et al.  Sympathoadrenal Activation and Muscarinic Receptor Stimulation Induce Acute Release of Tissue-Type Plasminogen Activator but not von Willebrand Factor across the Human Forearm , 1997, Thrombosis and Haemostasis.

[124]  M. Pfisterer,et al.  Effect of early intravenous heparin on coronary patency, infarct size, and bleeding complications after alteplase thrombolysis: results of a randomised double blind European Cooperative Study Group trial. , 1992, British heart journal.

[125]  A. Loeckinger,et al.  About 8-Hour Variation of Circulating Human Endothelin-1 , 1998, Peptides.

[126]  J. Dimsdale,et al.  Effects of Psychological Stress and Psychiatric Disorders on Blood Coagulation and Fibrinolysis: A Biobehavioral Pathway to Coronary Artery Disease? , 2001, Psychosomatic medicine.

[127]  S. Koh,et al.  Hemostatic Status and Fibrinolytic Response Potential at Different Phases of the Menstrual Cycle , 2005, Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis.

[128]  G. Lip,et al.  A cross-sectional and diurnal study of thrombogenesis among patients with chronic atrial fibrillation. , 2000, Journal of the American College of Cardiology.

[129]  A. Reinberg,et al.  Circadian Rhythm in Duration of Salicylate Excretion Referred To Phase of Excretory Rhythms and Routine.∗ , 1967, Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine.

[130]  Ming-Wei Lin,et al.  Variations of prothrombin time and international normalized ratio in patients treated with warfarin. , 2002, Thrombosis research.

[131]  P. Iversen,et al.  Impaired circadian variations of haemostatic and fibrinolytic parameters in tetraplegia , 2002, British journal of haematology.

[132]  J. Fiessinger,et al.  Circulating Activities During Constant Infusion of Heparin or a Low Molecular Weight Derivative (Enoxaparine): Failure to Demonstrate any Circadian Variations , 1987, Thrombosis and Haemostasis.

[133]  F. Rivera,et al.  Circadian variations of portal pressure and variceal hemorrhage in patients with cirrhosis , 1994, Hepatology.

[134]  A. Maseri,et al.  Major circadian fluctuations in fibrinolytic factors and possible relevance to time of onset of myocardial infarction, sudden cardiac death and stroke. , 1988, The American journal of cardiology.

[135]  L. Sackett,et al.  Seasonal (circannual) periodicity of spontaneous intracerebral hemorrhage in minnesota , 1980, Annals of Neurology.

[136]  M. Kaste,et al.  The effect of acute ingestion of a large dose of alcohol on the hemostatic system and its circadian variation. , 2000, Stroke.

[137]  F. Andreotti,et al.  Circadian variation of fibrinolytic activity in blood. , 1991, Chronobiology international.

[138]  M. Blombäck,et al.  PLASMINOGEN ACTIVATOR INHIBITOR IN PLASMA: RISK FACTOR FOR RECURRENT MYOCARDIAL INFARCTION , 1987, The Lancet.

[139]  S. Willich,et al.  Platelet alpha 2 adrenoceptor characteristics during the morning increase in platelet aggregability. , 1992, European heart journal.

[140]  W. Chandler,et al.  Diurnal variation of tissue-type plasminogen activator and its rapid inhibitor (PAI-1). , 1989, Circulation.

[141]  A. Sehgal,et al.  Regulation of CLOCK and MOP4 by Nuclear Hormone Receptors in the Vasculature A Humoral Mechanism to Reset a Peripheral Clock , 2001, Cell.

[142]  K. Kugiyama,et al.  Menstrual cyclic variation of endothelium-dependent vasodilation of the brachial artery: possible role of estrogen and nitric oxide. , 1996, Proceedings of the Association of American Physicians.

[143]  V. Feigin,et al.  Diurnal, weekly, and seasonal variations in stroke occurrence in a population-based study in Auckland, New Zealand. , 2004, The New Zealand medical journal.

[144]  M Popescu,et al.  Circadian, weekly, and seasonal variations in cardiac mortality, blood pressure, and catecholamine excretion. , 1991, Chronobiology international.

[145]  E. Gilpin,et al.  Subgroups of patients with atypical circadian patterns of symptom onset in acute myocardial infarction. , 1990, The American journal of cardiology.

[146]  P. Morange,et al.  The insulin resistance syndrome: implications for thrombosis and cardiovascular disease , 2002, Pathophysiology of Haemostasis and Thrombosis.

[147]  G. Fearnley,et al.  Evidence of a diurnal fibrinolytic rhythm; with a simple method of measuring natural fibrinolysis. , 1957, Clinical science.

[148]  F. Marín,et al.  Diurnal variation in the intensity of anticoagulation in atrial fibrillation. , 2002, Stroke.

[149]  A. Burroughs,et al.  Diurnal changes of fibrinolysis in patients with liver cirrhosis and esophageal varices , 2000, Hepatology.

[150]  Yung-Yee Chang,et al.  Serial Changes in Platelet Activation in Patients After Ischemic Stroke: Role of Pharmacodynamic Modulation , 2004, Stroke.

[151]  J. Dimsdale,et al.  Effect of beta2-adrenergic receptor functioning and increased norepinephrine on the hypercoagulable state with mental stress. , 2002, American heart journal.

[152]  G. Cornelissen,et al.  Prophylactic aspirin treatment: the merits of timing. International Womb-to-Tomb Chronome Study Group. , 1991, JAMA.

[153]  F. Bernardi,et al.  Daily and Circadian Rhythms of Tissue Factor Pathway Inhibitor and Factor VII Activity , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[154]  B. Gullberg,et al.  Circadian distribution of onset of acute myocardial infarction in subgroups from analysis of 10,791 patients treated in a single center. , 1992, The American journal of cardiology.

[155]  H. Décousus.  Chronobiology in Hemostastis , 1992 .

[156]  E. Jaffe,et al.  Cell biology of endothelial cells. , 1987, Human pathology.

[157]  T. Meade,et al.  Day-by-day variation in fibrinolytic activity and in mortality from ischaemic heart disease. , 1987, International journal of epidemiology.

[158]  D. Cardinali,et al.  Inhibition of human platelet aggregation and thromboxane-B2 production by melatonin: evidence for a diurnal variation. , 1990, The Journal of clinical endocrinology and metabolism.

[159]  A. Gatta,et al.  Circadian variation in the frequency of acute variceal bleeding in cirrhosis. Gruppo Triveneto per l'Ipertensione Portale. , 1994, Journal of hepatology.

[160]  K. Okumura,et al.  Circadian variation of plasma fibrinopeptide A level in patients with variant angina. , 1989, Circulation.

[161]  J. McCord,et al.  Oxygen-derived free radicals in postischemic tissue injury. , 1985, The New England journal of medicine.

[162]  N. Ishida,et al.  Light‐induced phase‐shifts in the circadian expression rhythm of mammalian Period genes in the mouse heart , 2000, The European journal of neuroscience.

[163]  G. Labrecque,et al.  Temporal variation in the effects of warfarin on the vitamin K cycle. , 1990, Chronobiology international.

[164]  J. Alpert,et al.  Circadian variation in thrombolytic response to recombinant tissue-type plasminogen activator in acute myocardial infarction , 1988 .

[165]  G. Lip,et al.  Diurnal variation in stroke onset in atrial fibrillation. , 2001, Stroke.

[166]  D. Vaughan.  PAI‐1 and atherothrombosis , 2005, Journal of thrombosis and haemostasis : JTH.

[167]  J. Manson,et al.  Circadian variation of acute myocardial infarction and the effect of low-dose aspirin in a randomized trial of physicians. , 1990, Circulation.

[168]  W. Little,et al.  Potential precipitating factors of the onset of myocardial infarction. , 1992, The American journal of the medical sciences.

[169]  A. Jovicić,et al.  Circadian variations of platelet aggregability and fibrinolytic activity in patients with ischemic stroke. , 1991, Thrombosis research.

[170]  S. Hampton,et al.  Biological rhythms, endothelial health and cardiovascular disease. , 2003, Medical science monitor : international medical journal of experimental and clinical research.

[171]  E. Antman,et al.  Analysis of possible triggers of acute myocardial infarction (the MILIS study). , 1990, The American journal of cardiology.

[172]  I-Min Lee,et al.  A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women , 2005 .

[173]  K. Yagita,et al.  Alterations of Circadian Expressions of Clock Genes in Dahl Salt-Sensitive Rats Fed a High-Salt Diet , 2003, Hypertension.

[174]  E. Braunwald,et al.  Modifiers of timing and possible triggers of acute myocardial infarction in the Thrombolysis in Myocardial Infarction Phase II (TIMI II) Study Group. , 1992, Journal of the American College of Cardiology.

[175]  M. Fujita,et al.  Circadian variation in the success rate of intracoronary thrombolysis for acute myocardial infarction. , 1993, The American journal of cardiology.

[176]  C A Czeisler,et al.  Morning increase in platelet aggregability. Association with assumption of the upright posture. , 1988, Circulation.

[177]  J. Emeis.  Regulation of the Acute Release of Tissue‐type Plasminogen Activator from the Endothelium by Coagulation Activation Products , 1992, Annals of the New York Academy of Sciences.

[178]  Michael Smolensky,et al.  Biological Clocks and Shift Work: Circadian Dysregulation and Potential Long-term Effects , 2006, Cancer Causes & Control.

[179]  K. Winther,et al.  The circadian variation in fibrinolytic activity is not related to posture. , 1994, Thrombosis research.

[180]  W. Koenig,et al.  Exercise and thrombosis , 2000, Coronary artery disease.

[181]  Mylan C. Cohen,et al.  Meta-analysis of the morning excess of acute myocardial infarction and sudden cardiac death. , 1997, The American journal of cardiology.

[182]  C. Johnson,et al.  Alternative splicing yields novel BMAL2 variants: tissue distribution and functional characterization. , 2002, American journal of physiology. Cell physiology.

[183]  J. Hung,et al.  Cigarette smoking acutely increases platelet thrombus formation in patients with coronary artery disease taking aspirin. , 1995, Circulation.

[184]  S. Bode-Böger,et al.  Role of endogenous nitric oxide in circadian blood pressure regulation in healthy humans and in patients with hypertension or atherosclerosis. , 2000, Journal of investigative medicine : the official publication of the American Federation for Clinical Research.

[185]  E. Kruithof,et al.  Diurnal Variation of the Fibrinolytic System , 1988, Thrombosis and Haemostasis.

[186]  S. Palacios.  Current perspectives on the benefits of HRT in menopausal women. , 1999, Maturitas.

[187]  I. Kriszbacher,et al.  Aspirin for stroke prevention taken in the evening? , 2004, Stroke.

[188]  P. Bonini,et al.  Effect of clot-detection methods and reagents on activated partial thromboplastin time (APTT). Implications in heparin monitoring by APTT. , 1990, American journal of clinical pathology.

[189]  G. Labrecque,et al.  Time-Dependent Variations in the Coagulation Factors II, VII, IX, and X in Young and Elderly Volunteers , 1995 .

[190]  A. Timmis,et al.  Attenuation or absence of circadian and seasonal rhythms of acute myocardial infarction. , 1997, Heart.

[191]  V. Fuster,et al.  Coronary artery disease: pathogenesis and acute coronary syndromes. , 2001, The Mount Sinai journal of medicine, New York.

[192]  E. Granieri,et al.  Circadian variability in hemorrhagic stroke. , 2002, JAMA.

[193]  D. Melchart,et al.  Circadian variation of the phagocytic activity of polymorphonuclear leukocytes and of various other parameters in 13 healthy male adults. , 1992, Chronobiology international.

[194]  G. Cornelissen,et al.  Prophylactic Aspirin Treatment: The Merits of Timing , 1991 .

[195]  A. van de Wiel,et al.  Acute inhibitory effect of alcohol on fibrinolysis , 2001, European journal of clinical investigation.

[196]  B. Kingwell,et al.  Variations in endothelial function and arterial compliance during the menstrual cycle. , 2001, The Journal of clinical endocrinology and metabolism.

[197]  S. Willich,et al.  Cold Monday mornings prove dangerous: epidemiology of sudden cardiac death , 2001, Current opinion in critical care.

[198]  A. Ehrly,et al.  Circadian rhythm of human blood viscosity. , 1973, Biorheology.

[199]  H. R. Andersen,et al.  Variation in risk indicators of cardiovascular disease during the menstrual cycle: an investigation of within-subject variations in glutathione peroxidase, haemostatic variables, lipids and lipoproteins in healthy young women. , 1996, Scandinavian journal of clinical and laboratory investigation.