Exercise and the Prothrombotic State
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《动脉硬化血栓血管生物学》
From the Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham B18 7QH, England.
Correspondence to Professor G.Y.H. Lip, University Department of Medicine, City Hospital, Birmingham B18 7QH, England. E-mail g.y.h.lip@bham.ac.uk
Cardiovascular disease (CVD) is still a major cause of mortality and morbidity in the western world. The importance of a healthy lifestyle in reducing the risk of CVD cannot be over-emphasized, with many guidelines offering recommendations on lifestyle issues such as smoking, diet, alcohol, and physical activity. With regard to the latter, some official recommendations suggest that each individual should participate in a minimum of 30 minutes of "moderate intensity" activity at least five days a week.1 The latest Health Survey for England, however, highlights the vast discrepancies between targets and reality, demonstrating that up to three quarters of adults do far less than the recommended amount of physical activity.2 The concept that lifestyle and daily activities can be implicated in either increasing or decreasing the risk of development/progression of CVD has been highlighted by a variety of anecdotal and epidemiological evidence. In their original description of acute myocardial infarction (MI), Obraztsov and Strazhesko3 were the first to report that "direct events" (such as exercise) often precipitated the disease. Many years later, Tofler et al4 demonstrated that in a population of patients who had experienced a MI, nearly half (48.5%) reported one or more potential trigger, with the most common reported being moderate/heavy physical activity (22.8%) followed by emotional upset (18.4%). In contrast, we found that only 21% of patients admitted with MI were engaged in physical activity at chest pain onset, with most patients being engaged in sedentary activities, including lying in bed (25%), sitting (19%), watching television (14%), and sleeping (6%); however, no ethnic differences in activity at chest pain onset were observed.5
See page 454
In view of the possible links between acute stimulus and thrombotic event, investigators speculated that intense physical activity may trigger acute coronary thrombosis and coronary artery occlusion(s) in sedentary individuals or those with preexisting vascular disease by disrupting the delicate balance between the coagulation and fibrinolysis systems, as well as upregulating platelet activity. Subsequent to this, numerous studies examining the effect of acute exercise and physical training on hemostasis were undertaken in an attempt to confirm or refute this hypothesis.6,7 A recent systematic review7 suggested the plausibility of acute exercise inducing a prothrombotic state associated with abnormal fibrinolysis and platelet activation, but because of the large discrepancies in methodology between studies an element of caution was needed before drawing strong conclusions. With the large discrepancies in findings, investigators speculated that the hemostatic response to exercise may be influenced by numerous factors such as intensity of exercise, baseline fitness/sedentary status, and whether the exercise stimulus was acute or chronic.7,8 Indeed, Weiss et al9 demonstrated that the hemostatic response to acute exercise may be intensity-dependant, illustrating that moderate exercise (68%VO2Max) yielded an enhancement of fibrinolysis without a concomitant increase in markers of blood coagulation, whereas very heavy exercise (83%VO2Max) activated both systems simultaneously. Wang et al10 also demonstrated a similar trend in platelet reactivity, showing that in a sedentary population, platelet adhesiveness and aggregation could be upregulated by strenuous exercise, whereas moderate intensity (50% to 55% VO2Max) exercise had the potential to decrease the aforementioned below resting levels.
Hemodynamic factors may also influence changes in the prothrombotic state associated with acute exercise. Indeed, as exercise is associated with increased flow in both arterial and venous circulation, shear-induced platelet aggregation (SIPA) may have an important role to play in the triggering of arterial thrombogenesis and vessel occlusion. When compared with a nonstenosed vessel, shear stress in stenosed arteries is accentuated (between 60 to 3300 dynes/cm2) because of the complex pattern of hydrodynamics, characterized by an initial increase in shear stress in the throat of the stenosed followed by a rapid decrease in the post stenosis circulation region.11 When the pathophysiological conditions of shear stress are recreated in a controlled in vitro environment using a rotational viscometer,12 an alternating monophasic flow pattern induced greater levels of SIPA than either low (10 dynes/cm2) or high flow (150 dynes/cm2) alone. Although the effects of acute exercise on in vitro SIPA have not been fully elucidated, Wang et al,10 in agreement with Tokuue et al,13 demonstrated that intense exercise (>80% VO2Max) had the potential to increase SIPA, P-selectin, and GPIIb/IIIa expression and von Willebrand factor (vWF) binding to platelets. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Wang et al14 extend these observations further by verifying the effects of short-term strenuous exercise, as well as examining the effect of exercise training and deconditioning, on alternating shear-induced platelet aggregation (ASIPA). The authors used broadly similar methodology to that of Merton et al,12 and not only confirm previous findings that intense exercise (VO2Max) can increase ASIPA, but provided additional evidence to show that compared with a sedentary control group (exercise
From the available literature, it would appear that on one hand, regular habitual exercise can reduce the risk of CVD by improving an individual’s hemostatic profile both at rest and during exertion, but on the other hand, vigorous exercise may provoke sudden cardiac death in individuals with preexisting vascular disease.18 Indeed, this "paradox" of vigorous versus regular habitual exercise raises the possibility that a "two-edged sword" of exercise may exist in relation to activation of the hemostatic system and enhanced thrombogenesis.8 The findings by Wang et al14 link well with the current recommendations with regards to regular physical activity. Their training program, which closely mirrors the current recommendations, provides further evidence to support the health promotion drive to get the large number of sedentary individuals into regular physical activity, potentially reducing the large number of deaths related to CVD.
References
Department of Health. At least five a week: Evidence on the impact of physical activity and its relation to health. Department of Health 2004; London, UK.
Office for National Statistics. National diet and nutritional survey: adults aged 16 to 64 years. Nutritional status (anthropometrics and blood analysis), blood pressure and physical activity. The Stationary Office 2004(Vol. 4); London, UK.
Obraztsov VP, Strazhesko ND. The symptomatology and diagnosis of coronary thrombosis. In: Vorobeva VA, Konchalovski MP (eds). Works of the First Congress of Russian Therapists. 1910; 26–43.
Tofler GH, Stone PH, Maclure M, Edelman E, Davis VG, Robertson T, Antman EM, Muller JE. Analysis of possible triggers of acute myocardial infarction (the MILIS study). Am J Cardiol. 1990; 66: 22–27.
Lip GYH, Cader MZ, Lee F, Munir SM, Beevers DG. Ethnic differences in pre admission levels of physical activity in patients admitted with myocardial infarction. Int J Cardiol. 1996; 56: 169–175.
El-Sayed MS, Sale C, Jones PG, Chester M. Blood haemostasis in exercise and training. Med Sci Sports Exerc. 2000; 32: 918–925.
Lee KW, Lip GY. Effects of lifestyle on haemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med. 2003; 163: 2368–2392.
Lee KW, Lip GYH. Acute versus habitual exercise, thrombogenesis and exercise intensity. Thromb Haemost. 2004; 91: 416–419.
Weiss C, Welsch B, Albert M, Friedmann B, Strobel G, Jost J, Nawroth P, Bartsch P. Coagulation and thrombomodulin in response to exercise of different type and duration. Med Sci Sports Exerc. 1998; 30: 1205–1210.
Wang JS, Jen CJ, Kung HC, Lin LJ, Hsiue TR, Chen HI. Different effects of strenuous exercise and moderate exercise on platelet function in men. Circulation. 1994; 90: 2877–2885.
Strony J, Beaudoin A, Brands D, Adelman B. Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis. Am J Physiol. 1993; 265: H1787–H1787.
Merten M, Chow T, Hellums JD, Thiagarajan P. A new role for P-selectin in shear-induced platelet aggregation. Circulation. 2000; 102: 2045–2050.
Tokuue J, Hayashi J, Hata Y, Nakaharra K, Ikeda Y. Enhanced platelet aggregability under high shear stress after treadmill exercise in patients with effort angina. Thromb Haemost. 1996; 75: 833–837.
Wang JS, Li-Yu San, Chan JC, Chen YW. Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arteriosler Thromb Vasc Biol. 2005: 25: 454–460.
Li Saw Hee FL, Blann AD, Edmunds E, Gibbs CR, Lip GYH. Effect of acute exercise on the raised plasma fibrinogen, soluble P-selectin and von Willebrand factor levels in chronic atrial fibrillation. Clinical Cardiology. 2001; 24: 409–414.
Steptoe A, Magid K, Edwards S, Brydon L, Hong Y, Erusalimsky J. The influence of psychological stress and socioeconomic status on platelet activation in men. Atherosclerosis. 2003; 168: 57–63.
Camacho A, Dimsdale JE. Platelets and psychiatry: lessons learned from old and new studies. Psychosom Med. 2000; 62: 326–336.
Albert CM, Mittleman MA, Chae CU, Lee IM, Hennekens CH, Manson JE. Triggering of sudden death from cardiac cause by vigorous exercise. N Engl J Med. 2000; 343: 1355–1361.(Graham Thrall; Gregory Y.)
Correspondence to Professor G.Y.H. Lip, University Department of Medicine, City Hospital, Birmingham B18 7QH, England. E-mail g.y.h.lip@bham.ac.uk
Cardiovascular disease (CVD) is still a major cause of mortality and morbidity in the western world. The importance of a healthy lifestyle in reducing the risk of CVD cannot be over-emphasized, with many guidelines offering recommendations on lifestyle issues such as smoking, diet, alcohol, and physical activity. With regard to the latter, some official recommendations suggest that each individual should participate in a minimum of 30 minutes of "moderate intensity" activity at least five days a week.1 The latest Health Survey for England, however, highlights the vast discrepancies between targets and reality, demonstrating that up to three quarters of adults do far less than the recommended amount of physical activity.2 The concept that lifestyle and daily activities can be implicated in either increasing or decreasing the risk of development/progression of CVD has been highlighted by a variety of anecdotal and epidemiological evidence. In their original description of acute myocardial infarction (MI), Obraztsov and Strazhesko3 were the first to report that "direct events" (such as exercise) often precipitated the disease. Many years later, Tofler et al4 demonstrated that in a population of patients who had experienced a MI, nearly half (48.5%) reported one or more potential trigger, with the most common reported being moderate/heavy physical activity (22.8%) followed by emotional upset (18.4%). In contrast, we found that only 21% of patients admitted with MI were engaged in physical activity at chest pain onset, with most patients being engaged in sedentary activities, including lying in bed (25%), sitting (19%), watching television (14%), and sleeping (6%); however, no ethnic differences in activity at chest pain onset were observed.5
See page 454
In view of the possible links between acute stimulus and thrombotic event, investigators speculated that intense physical activity may trigger acute coronary thrombosis and coronary artery occlusion(s) in sedentary individuals or those with preexisting vascular disease by disrupting the delicate balance between the coagulation and fibrinolysis systems, as well as upregulating platelet activity. Subsequent to this, numerous studies examining the effect of acute exercise and physical training on hemostasis were undertaken in an attempt to confirm or refute this hypothesis.6,7 A recent systematic review7 suggested the plausibility of acute exercise inducing a prothrombotic state associated with abnormal fibrinolysis and platelet activation, but because of the large discrepancies in methodology between studies an element of caution was needed before drawing strong conclusions. With the large discrepancies in findings, investigators speculated that the hemostatic response to exercise may be influenced by numerous factors such as intensity of exercise, baseline fitness/sedentary status, and whether the exercise stimulus was acute or chronic.7,8 Indeed, Weiss et al9 demonstrated that the hemostatic response to acute exercise may be intensity-dependant, illustrating that moderate exercise (68%VO2Max) yielded an enhancement of fibrinolysis without a concomitant increase in markers of blood coagulation, whereas very heavy exercise (83%VO2Max) activated both systems simultaneously. Wang et al10 also demonstrated a similar trend in platelet reactivity, showing that in a sedentary population, platelet adhesiveness and aggregation could be upregulated by strenuous exercise, whereas moderate intensity (50% to 55% VO2Max) exercise had the potential to decrease the aforementioned below resting levels.
Hemodynamic factors may also influence changes in the prothrombotic state associated with acute exercise. Indeed, as exercise is associated with increased flow in both arterial and venous circulation, shear-induced platelet aggregation (SIPA) may have an important role to play in the triggering of arterial thrombogenesis and vessel occlusion. When compared with a nonstenosed vessel, shear stress in stenosed arteries is accentuated (between 60 to 3300 dynes/cm2) because of the complex pattern of hydrodynamics, characterized by an initial increase in shear stress in the throat of the stenosed followed by a rapid decrease in the post stenosis circulation region.11 When the pathophysiological conditions of shear stress are recreated in a controlled in vitro environment using a rotational viscometer,12 an alternating monophasic flow pattern induced greater levels of SIPA than either low (10 dynes/cm2) or high flow (150 dynes/cm2) alone. Although the effects of acute exercise on in vitro SIPA have not been fully elucidated, Wang et al,10 in agreement with Tokuue et al,13 demonstrated that intense exercise (>80% VO2Max) had the potential to increase SIPA, P-selectin, and GPIIb/IIIa expression and von Willebrand factor (vWF) binding to platelets. In this issue of Arteriosclerosis, Thrombosis, and Vascular Biology, Wang et al14 extend these observations further by verifying the effects of short-term strenuous exercise, as well as examining the effect of exercise training and deconditioning, on alternating shear-induced platelet aggregation (ASIPA). The authors used broadly similar methodology to that of Merton et al,12 and not only confirm previous findings that intense exercise (VO2Max) can increase ASIPA, but provided additional evidence to show that compared with a sedentary control group (exercise
From the available literature, it would appear that on one hand, regular habitual exercise can reduce the risk of CVD by improving an individual’s hemostatic profile both at rest and during exertion, but on the other hand, vigorous exercise may provoke sudden cardiac death in individuals with preexisting vascular disease.18 Indeed, this "paradox" of vigorous versus regular habitual exercise raises the possibility that a "two-edged sword" of exercise may exist in relation to activation of the hemostatic system and enhanced thrombogenesis.8 The findings by Wang et al14 link well with the current recommendations with regards to regular physical activity. Their training program, which closely mirrors the current recommendations, provides further evidence to support the health promotion drive to get the large number of sedentary individuals into regular physical activity, potentially reducing the large number of deaths related to CVD.
References
Department of Health. At least five a week: Evidence on the impact of physical activity and its relation to health. Department of Health 2004; London, UK.
Office for National Statistics. National diet and nutritional survey: adults aged 16 to 64 years. Nutritional status (anthropometrics and blood analysis), blood pressure and physical activity. The Stationary Office 2004(Vol. 4); London, UK.
Obraztsov VP, Strazhesko ND. The symptomatology and diagnosis of coronary thrombosis. In: Vorobeva VA, Konchalovski MP (eds). Works of the First Congress of Russian Therapists. 1910; 26–43.
Tofler GH, Stone PH, Maclure M, Edelman E, Davis VG, Robertson T, Antman EM, Muller JE. Analysis of possible triggers of acute myocardial infarction (the MILIS study). Am J Cardiol. 1990; 66: 22–27.
Lip GYH, Cader MZ, Lee F, Munir SM, Beevers DG. Ethnic differences in pre admission levels of physical activity in patients admitted with myocardial infarction. Int J Cardiol. 1996; 56: 169–175.
El-Sayed MS, Sale C, Jones PG, Chester M. Blood haemostasis in exercise and training. Med Sci Sports Exerc. 2000; 32: 918–925.
Lee KW, Lip GY. Effects of lifestyle on haemostasis, fibrinolysis, and platelet reactivity: a systematic review. Arch Intern Med. 2003; 163: 2368–2392.
Lee KW, Lip GYH. Acute versus habitual exercise, thrombogenesis and exercise intensity. Thromb Haemost. 2004; 91: 416–419.
Weiss C, Welsch B, Albert M, Friedmann B, Strobel G, Jost J, Nawroth P, Bartsch P. Coagulation and thrombomodulin in response to exercise of different type and duration. Med Sci Sports Exerc. 1998; 30: 1205–1210.
Wang JS, Jen CJ, Kung HC, Lin LJ, Hsiue TR, Chen HI. Different effects of strenuous exercise and moderate exercise on platelet function in men. Circulation. 1994; 90: 2877–2885.
Strony J, Beaudoin A, Brands D, Adelman B. Analysis of shear stress and hemodynamic factors in a model of coronary artery stenosis and thrombosis. Am J Physiol. 1993; 265: H1787–H1787.
Merten M, Chow T, Hellums JD, Thiagarajan P. A new role for P-selectin in shear-induced platelet aggregation. Circulation. 2000; 102: 2045–2050.
Tokuue J, Hayashi J, Hata Y, Nakaharra K, Ikeda Y. Enhanced platelet aggregability under high shear stress after treadmill exercise in patients with effort angina. Thromb Haemost. 1996; 75: 833–837.
Wang JS, Li-Yu San, Chan JC, Chen YW. Effects of exercise training and deconditioning on platelet aggregation induced by alternating shear stress in men. Arteriosler Thromb Vasc Biol. 2005: 25: 454–460.
Li Saw Hee FL, Blann AD, Edmunds E, Gibbs CR, Lip GYH. Effect of acute exercise on the raised plasma fibrinogen, soluble P-selectin and von Willebrand factor levels in chronic atrial fibrillation. Clinical Cardiology. 2001; 24: 409–414.
Steptoe A, Magid K, Edwards S, Brydon L, Hong Y, Erusalimsky J. The influence of psychological stress and socioeconomic status on platelet activation in men. Atherosclerosis. 2003; 168: 57–63.
Camacho A, Dimsdale JE. Platelets and psychiatry: lessons learned from old and new studies. Psychosom Med. 2000; 62: 326–336.
Albert CM, Mittleman MA, Chae CU, Lee IM, Hennekens CH, Manson JE. Triggering of sudden death from cardiac cause by vigorous exercise. N Engl J Med. 2000; 343: 1355–1361.(Graham Thrall; Gregory Y.)