- Email: [email protected]
Platelet activation with exercise and risk of cardiac events
knowledge to develop novel non-hormonal methods of male contraception. T B Hargrea ve Department of Urology, Western General Hospital, Edinburgh EH4 2XU,UK 1
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Short RV. The testis, the witness of the mating system, the site of mutation and the engine of desire. Acta Paediatr 1997; 422 (suppl): 3–7. Cooke HJ, Hargreave TB, Elliot DJ. Understanding the genes involved in spermatogenesis: a progress report. Fertil Steril 1998; 69: 989–95. Berta P, Hawkins JR, Sinclair AH, et al. Genetic evidence equating SRY and the testis-determining factor. Nature 1990; 348: 448–50. Ma K, Inglis JD, Sharkey A, et al. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 1993; 75: 1–20. Reijo R, Lee TY, Salo P, et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet 1995; 10: 383–93. Brown GM, Furlong RA, Sargent CA, et al. Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene. Hum Mol Genet 1998; 7: 97–107. Ma K, Sharkey A ,K i rsch S, et al. Towards the molecular localisation of the AZF locus: mapping of microdeletions in azoospermic men within 14 subintervals of interval 6 of the human Y chromosome. Hum Mol Genet 1992; 1: 29–33. Pryor JL, Kent-First M, Muallem A, et al. Microdeletions in the Y chromosome of infertile men (see comments). N Engl J Med 1997; 336: 534–39. Kobayashi K, Mizuno K, Hida A, et al. PCR analysis of the Y chromosome long arm in azoospermic patients—evidence for a second locus required for spermatogenesis. Hum Mol Genet 1994; 3: 1965–67. Silber SJ, Alagappan R, Brown LG, Page DC.Y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction. Hum Reprod 1998; 13: 3332–37. Stuppia L, Gatta V, Mastroprimiano G. Clustering of Y chromosome deletions in subinterval E of interval 6 supports the existence of an oligozoospermia critical region outside the DAZ gene. J Med Genet 1997; 34: 881–83. Kuroki Y, Iwamoto T, Lee J, et al. Spermatogenic ability is different among males in different Y chromosome lineage. Hum Genet 1999; 44: 289–92.
Platelet activation with exercise and risk of cardiac events An individual unaccustomed to habitual physical activity has about a 50-fold increase in the risk of sudden death and a 100-fold increase in the risk of acute myocardial infarction when he or she undertakes vigorous exercise, such as jogging, heavy gardening, or housework, compared with remaining at rest.1,2 The risks associated with vigorous exercise can be substantially reduced by regular physical training but still remain somewhat raised (two to five fold). The overall risk of a cardiovascular event, however, is greatly reduced by training compared with inactivity. About 70% of the sudden deaths occurring with exercise in people over 35 years of age and most myocardial infarctions can be attributed to the occlusion of coronary arteries by platelet-rich thrombi.3,4 Therefore, if exercise activates platelets and blood coagulation, how does this activation fit with the known preventive effects of regular exercise for cardiovascular mortality? A recent study by Håkan Wallén and colleagues5 found that vigorous exercise causes platelet activation and aggregation, and increases formation of thrombin and fibrin. Vigorous exercise has long been known also to increase platelet counts, shorten coagulation times in vitro, and increase plasma concentrations of factor VIII. Many studies have found that after strenuous exercise there is increased in-vitro aggregation of platelets in
THE LANCET • Vol 354 • November 20, 1999
response to various stimuli.6 These earlier findings do not indicate whether activation of platelets and coagulation occur in vivo during exercise. Wallén and colleagues, however, used techniques that can indicate in-vivo activation of haemostasis, such as ex-vivo filtration for detection of platelet aggregates, and flow cytometry for detection of receptors expressed on activated platelets. Immunoassays were used to measure cleaved fragments of coagulation factors that indicate formation of thrombin (prothrombin fragment 1+2) and fibrin (fibrinopetide A), and thrombin inactivated by antithrombin III (TAT complexes). The extent of the exercise-induced in-vivo activation of haemostasis is small, and the measured variables are generally within established normal ranges in this and other studies.5-7 Although the exact mechanisms of activation with exercise are not understood, factors that are probably important include the large increase in sheer stress and increased concentrations of epinephrine and norepinephrine—all known platelet activators.6 Exercise may also increase thrombin formation by activating the intrinsic or extrinsic coagulation pathway and thereby reinforce platelet activation. Despite exercise-induced activation of haemostasis, reports of venous or arterial thrombosis after vigorous exercise are rare except for cardiac events. Accordingly, sudden death with exercise below the age of 35 is rarely caused by thrombosis of a coronary artery; most cases are due to hypertrophic cardiomyopathy and anomalies of coronary arteries and valves.3 Thus, vigorous exercise probably does not present an increased risk of thrombosis to healthy individuals with normal haemostasis. This result may be attributed to an intact endothelium with normal antithrombotic properties and an increase in fibrinolytic activity with exercise.6,7 This conclusion is, however, not the case for patients with coronary-artery disease, in whom platelet-rich thrombus overlying a plaque fissure or rupture is the principal cause of acute myocardial infarction.4 Intense exercise in patients with coronary-artery disease leads to a several-fold increase in coronary blood flow and an increase in catecholamine concentrations and may thereby favour occurrence of acute myocardial infarction. Increased shear stress and mechanical strain on the coronary arteries may trigger fissuring or rupture of plaques. Shear stress and increased epinephrine and norepinephrine concentrations increase platelet activation and may increase thrombus formation over small plaque lesions whereas their contribution to occlusions of coronary arteries after large ruptures is probably negligible considering the amount of thrombogenic material exposed with these lesions. Thus, plaque injury may be more important than activation of haemostasis for cardiac events with vigorous exercise, and activation of fibrinolysis with exercise cannot prevent such events. How then does regular physical activity reduce the risk of sudden death and onset of myocardial infarction with vigorous exercise? Part of the effect may be attributed to the beneficial effects of training on the principal risk factors of cardiovascular disease such as hypertension, cholesterol, and diabetes mellitus. However, after adjustment for these factors, individuals who undertake regular exercise still have a significantly lower risk of myocardial infarction with vigorous exercise than those who are sedentary.8 A substantial benefit of regular physical activity is an increase in work capacity. Thus, a 1747
given work load that may trigger acute myocardial infarction, such as strenuous daily activities, will, with training, result in a lower level of exertion and consequently in less haemodynamic stress and in lower plasma concentrations of catecholamines.9 One crosssectional study10 and one controlled prospective study11 found that endurance training decreased the platelet response to acute exercise.Thus,higher exercise tolerance with lower catecholamine concentrations and less responsive platelets probably contribute to the lower risk of myocardial infarction and sudden death found among people who exercise regularly. Moderate levels of exercise to 50–80% of a maximum heart rate do not increase platelet adhesion, or the release of platelet proteins (when related to the increase in platelet count), or in-vivo thrombin formation in healthy individuals, although fibrinolysis increases.7,12 Similar results were found among patients with coronary-artery disease who underwent a rehabilitative exercise session and achieved about 80% of maximum heart rate.13 These investigations suggest that exercise at levels recommended for development of cardiovascular fitness has no detrimental effects on haemostasis. Activation of fibrinolysis by exercise and lower platelet activation induced by endurance training may be additional factors by which regular exercise can help to reduce the development of atherosclerosis. Thus, to minimise the risks of acute exercise and to reap the benefits from regular exercise, people above the age of 35 years, especially those who have not been active and patients with coronary-artery disease, should train predominantly at moderate intensities and avoid heavy exertion. Peter Bärtsch Department of Internal Medicine,Division of Sports Medicine,University of Heidelberg, Heidelberg 3–69115, Germany 1
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Siscovick DS, Weiss NS, Fletcher RH, Lasky T. The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 1984; 311: 874–77. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE. Triggering of acute myocardial infarction by heavy physical exercise. N Engl J Med 1993; 329: 1677–83. Maron BJ, Epstein SE, Roberts WC. Causes of sudden death in competitive athletes. J Am Coll Cardiol 1986; 7: 204–14. Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med 1984; 310: 1137–40. Wallén NH, Goodall AH, Li N, Hjemdahl P. Activation of haemostasis by exercise, mental stress and adrenaline: effects on platelet sensitivity to thrombin and thrombin generation. Clin Sci (Colch) 1999; 97: 27–35. Streiff M, Bell WR. Exercise and hemostasis in humans. Semin Hematol 1994; 31: 155–65. Weiss C, Seitel G, Bärtsch P. Coagulation and fibrinolysis after moderate and very heavy exercise in healthy male subjects. Med Sci Sports Exerc 1998; 30: 246–51. Willich SN, Lewis M, Löwel H, Arntz H-R, Schubert F, Schröder R. Physical exertion as a trigger of acute myocardial infarction. N Engl J Med 1993; 329: 1684–90. Winder WW, Hagberg JM, Hickson RC, Ehsani AA, McLane JA. Time course of sympathoadrenal adaptation to endurance exercise training in man. J Appl Physiol 1978; 45: 370–74. Kestin AS, Ellis PA, Barnard MR, Errichetti A, Rosner BA, Michelson AD. Effect of strenuous exercise on platelet activation state and reactivity. Circulation 1993; 88: 1502–11. Wang JS, Jen CJ, Chen HI. Effects of exercise training and deconditioning on platelet function in men. Arterioscler Thromb Vasc Biol 1995; 15: 1668–74. 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: 2877–85. Weiss C, Velich T, Niebauer J, et al. Activation of coagulation and fibrinolysis after rehabilitative exercise in patients with coronary artery disease. Am J Cardiol 1998; 81: 672–77.
1748
Spinal-cord stimulation in management of angina Many patients continue to experience severe angina despite maximum medical and surgical treatment. This group of patients, who have what is commonly termed chronic refractory angina, are generally those who have survived several myocardial infarctions, have undergone several surgical or percutaneous revascularisation procedures, or are deemed “unsuitable” for further revascularisation. Most are severely restricted in their daily activities and require repeated admissions for acute coronary syndromes. Doctors who look after these patients commonly experience a sense of helplessness and sometimes find it difficult to prevent their frustration from being transmitted to the unfortunate patients. The unconventional methods of treatment proposed for these patients include percutaneous or transmyocardial laser revascularisation, enhanced external counterpulsation, and, rarely, transplantation and neuromodulation. Each method has its proponents, but many clinicians remain sceptical about the benefits. One specific method of neuromodulation is spinal-cord stimulation (SCS). Its use in the management of angina was first described in 1987.1 Since then supportive evidence has been accumulating. The procedure involves the insertion of a specially designed electrode into the epidural space, under radiographic guidance.2 This electrode is positioned to produce a prickling sensation in the region where the patient generally feels the anginal pain, in most cases C7–T2. The electrode is then connected to a pulse generator placed in a subcutaneous pouch, commonly in the subcostal abdominal wall.The patient can activate the device with a magnet for prophylactic therapy. To deal with severe attacks of angina, the output can be increased by adjusting how long the magnet is held over the device. The morbidity and mortality from the insertion procedure are negligible in skilled hands. The bulk of the evidence suggests that SCS improves patients’ symptoms, mainly in terms of the frequency and severity of anginal attacks.3,4 More precise markers of effect, such as use of short-acting nitrates, time to angina, degree and duration of ST-segment depression, and exercise capacity, also show favourable effects (panel).2–6 An observational study has shown that there is a significant reduction in rate of hospital admissions.7 In a properly randomised study among patients with increased surgical risk or whose long-term survival is unlikely to be extended by surgery,2 SCS was as good as coronary-artery bypass surgery in alleviating symptoms, with no detrimental effect on mortality, and it was associated with less cerebrovascular morbidity. The primary aim of therapy is to improve the patient’s quality of life by reducing angina, and success rates of up to 80% are reported, in terms of frequency and severity.2 This figure compares very favourably with all other options. These studies lead to the conclusion that SCS not only reduces the patient’s perception of angina but also has antiischaemic actions. The pain-modifying properties of neuromodulation are based on the gate theory of pain.8 According to this theory, stimulation of those fibres of the spinal cord that do not transmit pain to the brain will reduce the input to the brain from those fibres that do. The anti-ischaemic properties are more difficult to explain.Theories include
THE LANCET • Vol 354 • November 20, 1999
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Short RV. The testis, the witness of the mating system, the site of mutation and the engine of desire. Acta Paediatr 1997; 422 (suppl): 3–7. Cooke HJ, Hargreave TB, Elliot DJ. Understanding the genes involved in spermatogenesis: a progress report. Fertil Steril 1998; 69: 989–95. Berta P, Hawkins JR, Sinclair AH, et al. Genetic evidence equating SRY and the testis-determining factor. Nature 1990; 348: 448–50. Ma K, Inglis JD, Sharkey A, et al. A Y chromosome gene family with RNA-binding protein homology: candidates for the azoospermia factor AZF controlling human spermatogenesis. Cell 1993; 75: 1–20. Reijo R, Lee TY, Salo P, et al. Diverse spermatogenic defects in humans caused by Y chromosome deletions encompassing a novel RNA-binding protein gene. Nat Genet 1995; 10: 383–93. Brown GM, Furlong RA, Sargent CA, et al. Characterisation of the coding sequence and fine mapping of the human DFFRY gene and comparative expression analysis and mapping to the Sxrb interval of the mouse Y chromosome of the Dffry gene. Hum Mol Genet 1998; 7: 97–107. Ma K, Sharkey A ,K i rsch S, et al. Towards the molecular localisation of the AZF locus: mapping of microdeletions in azoospermic men within 14 subintervals of interval 6 of the human Y chromosome. Hum Mol Genet 1992; 1: 29–33. Pryor JL, Kent-First M, Muallem A, et al. Microdeletions in the Y chromosome of infertile men (see comments). N Engl J Med 1997; 336: 534–39. Kobayashi K, Mizuno K, Hida A, et al. PCR analysis of the Y chromosome long arm in azoospermic patients—evidence for a second locus required for spermatogenesis. Hum Mol Genet 1994; 3: 1965–67. Silber SJ, Alagappan R, Brown LG, Page DC.Y chromosome deletions in azoospermic and severely oligozoospermic men undergoing intracytoplasmic sperm injection after testicular sperm extraction. Hum Reprod 1998; 13: 3332–37. Stuppia L, Gatta V, Mastroprimiano G. Clustering of Y chromosome deletions in subinterval E of interval 6 supports the existence of an oligozoospermia critical region outside the DAZ gene. J Med Genet 1997; 34: 881–83. Kuroki Y, Iwamoto T, Lee J, et al. Spermatogenic ability is different among males in different Y chromosome lineage. Hum Genet 1999; 44: 289–92.
Platelet activation with exercise and risk of cardiac events An individual unaccustomed to habitual physical activity has about a 50-fold increase in the risk of sudden death and a 100-fold increase in the risk of acute myocardial infarction when he or she undertakes vigorous exercise, such as jogging, heavy gardening, or housework, compared with remaining at rest.1,2 The risks associated with vigorous exercise can be substantially reduced by regular physical training but still remain somewhat raised (two to five fold). The overall risk of a cardiovascular event, however, is greatly reduced by training compared with inactivity. About 70% of the sudden deaths occurring with exercise in people over 35 years of age and most myocardial infarctions can be attributed to the occlusion of coronary arteries by platelet-rich thrombi.3,4 Therefore, if exercise activates platelets and blood coagulation, how does this activation fit with the known preventive effects of regular exercise for cardiovascular mortality? A recent study by Håkan Wallén and colleagues5 found that vigorous exercise causes platelet activation and aggregation, and increases formation of thrombin and fibrin. Vigorous exercise has long been known also to increase platelet counts, shorten coagulation times in vitro, and increase plasma concentrations of factor VIII. Many studies have found that after strenuous exercise there is increased in-vitro aggregation of platelets in
THE LANCET • Vol 354 • November 20, 1999
response to various stimuli.6 These earlier findings do not indicate whether activation of platelets and coagulation occur in vivo during exercise. Wallén and colleagues, however, used techniques that can indicate in-vivo activation of haemostasis, such as ex-vivo filtration for detection of platelet aggregates, and flow cytometry for detection of receptors expressed on activated platelets. Immunoassays were used to measure cleaved fragments of coagulation factors that indicate formation of thrombin (prothrombin fragment 1+2) and fibrin (fibrinopetide A), and thrombin inactivated by antithrombin III (TAT complexes). The extent of the exercise-induced in-vivo activation of haemostasis is small, and the measured variables are generally within established normal ranges in this and other studies.5-7 Although the exact mechanisms of activation with exercise are not understood, factors that are probably important include the large increase in sheer stress and increased concentrations of epinephrine and norepinephrine—all known platelet activators.6 Exercise may also increase thrombin formation by activating the intrinsic or extrinsic coagulation pathway and thereby reinforce platelet activation. Despite exercise-induced activation of haemostasis, reports of venous or arterial thrombosis after vigorous exercise are rare except for cardiac events. Accordingly, sudden death with exercise below the age of 35 is rarely caused by thrombosis of a coronary artery; most cases are due to hypertrophic cardiomyopathy and anomalies of coronary arteries and valves.3 Thus, vigorous exercise probably does not present an increased risk of thrombosis to healthy individuals with normal haemostasis. This result may be attributed to an intact endothelium with normal antithrombotic properties and an increase in fibrinolytic activity with exercise.6,7 This conclusion is, however, not the case for patients with coronary-artery disease, in whom platelet-rich thrombus overlying a plaque fissure or rupture is the principal cause of acute myocardial infarction.4 Intense exercise in patients with coronary-artery disease leads to a several-fold increase in coronary blood flow and an increase in catecholamine concentrations and may thereby favour occurrence of acute myocardial infarction. Increased shear stress and mechanical strain on the coronary arteries may trigger fissuring or rupture of plaques. Shear stress and increased epinephrine and norepinephrine concentrations increase platelet activation and may increase thrombus formation over small plaque lesions whereas their contribution to occlusions of coronary arteries after large ruptures is probably negligible considering the amount of thrombogenic material exposed with these lesions. Thus, plaque injury may be more important than activation of haemostasis for cardiac events with vigorous exercise, and activation of fibrinolysis with exercise cannot prevent such events. How then does regular physical activity reduce the risk of sudden death and onset of myocardial infarction with vigorous exercise? Part of the effect may be attributed to the beneficial effects of training on the principal risk factors of cardiovascular disease such as hypertension, cholesterol, and diabetes mellitus. However, after adjustment for these factors, individuals who undertake regular exercise still have a significantly lower risk of myocardial infarction with vigorous exercise than those who are sedentary.8 A substantial benefit of regular physical activity is an increase in work capacity. Thus, a 1747
given work load that may trigger acute myocardial infarction, such as strenuous daily activities, will, with training, result in a lower level of exertion and consequently in less haemodynamic stress and in lower plasma concentrations of catecholamines.9 One crosssectional study10 and one controlled prospective study11 found that endurance training decreased the platelet response to acute exercise.Thus,higher exercise tolerance with lower catecholamine concentrations and less responsive platelets probably contribute to the lower risk of myocardial infarction and sudden death found among people who exercise regularly. Moderate levels of exercise to 50–80% of a maximum heart rate do not increase platelet adhesion, or the release of platelet proteins (when related to the increase in platelet count), or in-vivo thrombin formation in healthy individuals, although fibrinolysis increases.7,12 Similar results were found among patients with coronary-artery disease who underwent a rehabilitative exercise session and achieved about 80% of maximum heart rate.13 These investigations suggest that exercise at levels recommended for development of cardiovascular fitness has no detrimental effects on haemostasis. Activation of fibrinolysis by exercise and lower platelet activation induced by endurance training may be additional factors by which regular exercise can help to reduce the development of atherosclerosis. Thus, to minimise the risks of acute exercise and to reap the benefits from regular exercise, people above the age of 35 years, especially those who have not been active and patients with coronary-artery disease, should train predominantly at moderate intensities and avoid heavy exertion. Peter Bärtsch Department of Internal Medicine,Division of Sports Medicine,University of Heidelberg, Heidelberg 3–69115, Germany 1
2
3 4
5
6 7
8
9
10
11
12
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Siscovick DS, Weiss NS, Fletcher RH, Lasky T. The incidence of primary cardiac arrest during vigorous exercise. N Engl J Med 1984; 311: 874–77. Mittleman MA, Maclure M, Tofler GH, Sherwood JB, Goldberg RJ, Muller JE. Triggering of acute myocardial infarction by heavy physical exercise. N Engl J Med 1993; 329: 1677–83. Maron BJ, Epstein SE, Roberts WC. Causes of sudden death in competitive athletes. J Am Coll Cardiol 1986; 7: 204–14. Davies MJ, Thomas A. Thrombosis and acute coronary-artery lesions in sudden cardiac ischemic death. N Engl J Med 1984; 310: 1137–40. Wallén NH, Goodall AH, Li N, Hjemdahl P. Activation of haemostasis by exercise, mental stress and adrenaline: effects on platelet sensitivity to thrombin and thrombin generation. Clin Sci (Colch) 1999; 97: 27–35. Streiff M, Bell WR. Exercise and hemostasis in humans. Semin Hematol 1994; 31: 155–65. Weiss C, Seitel G, Bärtsch P. Coagulation and fibrinolysis after moderate and very heavy exercise in healthy male subjects. Med Sci Sports Exerc 1998; 30: 246–51. Willich SN, Lewis M, Löwel H, Arntz H-R, Schubert F, Schröder R. Physical exertion as a trigger of acute myocardial infarction. N Engl J Med 1993; 329: 1684–90. Winder WW, Hagberg JM, Hickson RC, Ehsani AA, McLane JA. Time course of sympathoadrenal adaptation to endurance exercise training in man. J Appl Physiol 1978; 45: 370–74. Kestin AS, Ellis PA, Barnard MR, Errichetti A, Rosner BA, Michelson AD. Effect of strenuous exercise on platelet activation state and reactivity. Circulation 1993; 88: 1502–11. Wang JS, Jen CJ, Chen HI. Effects of exercise training and deconditioning on platelet function in men. Arterioscler Thromb Vasc Biol 1995; 15: 1668–74. 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: 2877–85. Weiss C, Velich T, Niebauer J, et al. Activation of coagulation and fibrinolysis after rehabilitative exercise in patients with coronary artery disease. Am J Cardiol 1998; 81: 672–77.
1748
Spinal-cord stimulation in management of angina Many patients continue to experience severe angina despite maximum medical and surgical treatment. This group of patients, who have what is commonly termed chronic refractory angina, are generally those who have survived several myocardial infarctions, have undergone several surgical or percutaneous revascularisation procedures, or are deemed “unsuitable” for further revascularisation. Most are severely restricted in their daily activities and require repeated admissions for acute coronary syndromes. Doctors who look after these patients commonly experience a sense of helplessness and sometimes find it difficult to prevent their frustration from being transmitted to the unfortunate patients. The unconventional methods of treatment proposed for these patients include percutaneous or transmyocardial laser revascularisation, enhanced external counterpulsation, and, rarely, transplantation and neuromodulation. Each method has its proponents, but many clinicians remain sceptical about the benefits. One specific method of neuromodulation is spinal-cord stimulation (SCS). Its use in the management of angina was first described in 1987.1 Since then supportive evidence has been accumulating. The procedure involves the insertion of a specially designed electrode into the epidural space, under radiographic guidance.2 This electrode is positioned to produce a prickling sensation in the region where the patient generally feels the anginal pain, in most cases C7–T2. The electrode is then connected to a pulse generator placed in a subcutaneous pouch, commonly in the subcostal abdominal wall.The patient can activate the device with a magnet for prophylactic therapy. To deal with severe attacks of angina, the output can be increased by adjusting how long the magnet is held over the device. The morbidity and mortality from the insertion procedure are negligible in skilled hands. The bulk of the evidence suggests that SCS improves patients’ symptoms, mainly in terms of the frequency and severity of anginal attacks.3,4 More precise markers of effect, such as use of short-acting nitrates, time to angina, degree and duration of ST-segment depression, and exercise capacity, also show favourable effects (panel).2–6 An observational study has shown that there is a significant reduction in rate of hospital admissions.7 In a properly randomised study among patients with increased surgical risk or whose long-term survival is unlikely to be extended by surgery,2 SCS was as good as coronary-artery bypass surgery in alleviating symptoms, with no detrimental effect on mortality, and it was associated with less cerebrovascular morbidity. The primary aim of therapy is to improve the patient’s quality of life by reducing angina, and success rates of up to 80% are reported, in terms of frequency and severity.2 This figure compares very favourably with all other options. These studies lead to the conclusion that SCS not only reduces the patient’s perception of angina but also has antiischaemic actions. The pain-modifying properties of neuromodulation are based on the gate theory of pain.8 According to this theory, stimulation of those fibres of the spinal cord that do not transmit pain to the brain will reduce the input to the brain from those fibres that do. The anti-ischaemic properties are more difficult to explain.Theories include
THE LANCET • Vol 354 • November 20, 1999