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107. Haemostatic factors and the risk of perioperative myocardial infarction in peripheral vascular surgery
3rd International Fibrinogen Symposium
106. Plasma homocyst(e)ine [H(e)] as a risk factor for arterial occlusive diseases (AOD) M. R. Malinow
Oregon Regional Primate Research Center, Beaverton, OR 97006; The Oregon Health Sciences University, Portland, OR 97215; Providence St. Vincent Medical Center, Portland, OR 97225, USA Data resulting from collaboration with several investigators demonstrated: (1) H(e) is elevated in subsets of patients with coronary heart disease (CHD), stroke, intermittent claudication, and carotid thickening assessed by ultrasonography; (2) H(e) is a graded risk for CHD after adjustment for a number of risk factors for atherosclerosis; (3) significant association between CHD and H(e) is found in retrospective and prospective observations; (4) family members of CHD patients, as well as data from mono- and dizygotic twins suggest that H(e) is at least partially under genetic control; (5) H(e) shows significant correlation with folate, but not with methionine intake; (6) H(e) is lower in subjects ingesting multi-vitamins or folic acid supplements; (7) subjects with homozygous genetic mutation (C677T) of methylenetrahydrofolate reductase have elevated H(e) levels, but the frequency of the mutation is similar in CHD- and non CHDsubjects; (8) reduction of H(e) by folate supplements is observed in homozygous and heterozygous subjects with the C677T mutation. Vitamin intake may alter levels of plasma H(e) and thereby correct a biochemical abnormality frequently found in patients with arterial occlusive diseases. Whether vitamin supplements affect the evolution of arterial diseases needs to be established in controlled clinical trials.
107. Haemostatic factors and the risk of perioperative myocardial infarction in peripheral vascular surgery N. M a m o d e , A. Rumley, G. D. O. Lowe, S. M. Cobbe, J. G. Pollock
Depts. of Peripheral Vascular Surgery, Medicine and Cardiology, Glasgow Royal Infirmary, Glasgow, UK Perioperative myocardial infarction has a high incidence in patients undergoing peripheral vascular surgery, but its aetiology is uncertain. Raised levels of fibrinogen, factor VII, yon Willebrand factor, plasma viscosity and FDPs have been shown to predict cardiac events in community studies. The aim of this study was to determine whether raised levels of these thrombotic mediators preoperatively predicted the occurrence of perioperative myocardial infarction. 291 consecutive patients undergoing peripheral vascular surgery were studied. Patients were screened for a perioperarive myocardial infarction with CK-MB isoenzymes and ECGs for the first three postoperative days. A perioperative cardiac event was defined as a myocardial infarction or cardiac death within 30 days of surgery. There were 18 perioperative cardiac events. Plasma viscosity, fibrinogen, yon Willebrand factor and Factor VII did not correlate with perioperative cardiac events. However, D-Dimer levels showed a correlation; in 264 patients not on anticoagulants, with 17 events, mean logFDP was 6.23 in those with an event, and 5.68 in those without (p=0.03, 95% C.I. for diff. of means 0.05, 1.05). Patients with an event showed no difference in smoking history or sex distribution, but were older (mean © Pearson Professional Ltd 1996
33
age 69 years v 65 years, p=0.006, C.I. 1.3-7.2). Only 4 of those with events had critical limb ischaemia. D-Dimer levels are predictive of perioperative myocardial infarction, and may be useful in the selection of high risk patients. The hypercoagulability indicated by raised FDPs may partly explain the aetiology of perioperative myocardial infarction and suggests the possibility of selective preventive intervention with anticoagulants.
108. The C677T mutation of the 5, lOmethylenetetrahydropholate reductase gene (MTHFR)and moderate hyperhomocysteinemia in young thrombophilic patients F. P. Mancini, R. De Franchis, A. D'Angelo, G. Sebastio, I. Fermo, V. De Stefano, M. Margaglione, G. Mazzola, A. M. Cerbone, L. Soriente, G. Andria, G. Di Minno
Dipartimenti di Biochimica e Clinica Medica, di Pediatria, Universita "FedericoII; NapolL Medicina di Laboratorio, IRCCS, Ospedale S. Raffaele, Milano, Unita di Aterosclerosi e TrombosL IRCCS CSS, S. Giovanni Rotondo, Italy Moderate hyperhomocysteinemia is an independent risk factor for thrombotic vascular disease. A C677T substitution of the MTHFR gene has been reported as the leading cause of moderate hyperhomocysteinemia. We have evaluated the frequency of the C677T mutation of the MTHFR gene in 64 unrelated young thrombophilic patients. In 29 (16 men, 13 women, 37.6_+13.8 yrs old, 7 with arterial and 22 with venous thrombosis) fasting total plasma homocysteine was above the 95th percentile of the distribution (19.5 mM in men and 15 mM in women). These patients were matched for sex, age, type of event and age at first thrombotic event with the other 35. In all cases, nutrient-related disturbances of vitamin B 12 and folate and abnormalities of cystathionine b-synthase enzyme were excluded. Normal subjects (258) free of vascular disease served as controls. Homozygosity for the C677T mutation (+/+) was found in 15% of controls (95% C.I.=I 1-20%). Among the 35% patients with normal homocysteinemia, one only was homozygous for the mutation. In contrast the +/+ genotype was found in 18/29 (62%) of those with hyperhomocysteinemia (9 men, 9 women, 5 with arterial and 13 with venous thrombosis). Plasma homocystein was not significantly different in the 18 patients homozygous for the mutation (32_+19 mM) and in the remaining 11 hyperhomocysteinemic patients (23_+5 mM, p>0.01). These results indicate that in young thrombophilic patients homozygosity for the C677T mutation of the MTHFR gene is the prevalent cause of moderate fasting hyperhomocysteinemia. These data also suggest that in a high proportion of these thrombophilic patients, factors other than C677T mutations are responsible for moderate hyperhomocysteinemia.
109. Comparison of plasma lipoprotein (a) levels between individuals attending a metabolic ward with and without a history of ischemic stroke M. Margaglione, E. Grandone, E. Celentano, G. Vecchione, G. Cappucci, M. Grflli, F. P. Mancini, A. Fibrinolysis (1996) 10, Suppl. 1, 1-58
106. Plasma homocyst(e)ine [H(e)] as a risk factor for arterial occlusive diseases (AOD) M. R. Malinow
Oregon Regional Primate Research Center, Beaverton, OR 97006; The Oregon Health Sciences University, Portland, OR 97215; Providence St. Vincent Medical Center, Portland, OR 97225, USA Data resulting from collaboration with several investigators demonstrated: (1) H(e) is elevated in subsets of patients with coronary heart disease (CHD), stroke, intermittent claudication, and carotid thickening assessed by ultrasonography; (2) H(e) is a graded risk for CHD after adjustment for a number of risk factors for atherosclerosis; (3) significant association between CHD and H(e) is found in retrospective and prospective observations; (4) family members of CHD patients, as well as data from mono- and dizygotic twins suggest that H(e) is at least partially under genetic control; (5) H(e) shows significant correlation with folate, but not with methionine intake; (6) H(e) is lower in subjects ingesting multi-vitamins or folic acid supplements; (7) subjects with homozygous genetic mutation (C677T) of methylenetrahydrofolate reductase have elevated H(e) levels, but the frequency of the mutation is similar in CHD- and non CHDsubjects; (8) reduction of H(e) by folate supplements is observed in homozygous and heterozygous subjects with the C677T mutation. Vitamin intake may alter levels of plasma H(e) and thereby correct a biochemical abnormality frequently found in patients with arterial occlusive diseases. Whether vitamin supplements affect the evolution of arterial diseases needs to be established in controlled clinical trials.
107. Haemostatic factors and the risk of perioperative myocardial infarction in peripheral vascular surgery N. M a m o d e , A. Rumley, G. D. O. Lowe, S. M. Cobbe, J. G. Pollock
Depts. of Peripheral Vascular Surgery, Medicine and Cardiology, Glasgow Royal Infirmary, Glasgow, UK Perioperative myocardial infarction has a high incidence in patients undergoing peripheral vascular surgery, but its aetiology is uncertain. Raised levels of fibrinogen, factor VII, yon Willebrand factor, plasma viscosity and FDPs have been shown to predict cardiac events in community studies. The aim of this study was to determine whether raised levels of these thrombotic mediators preoperatively predicted the occurrence of perioperative myocardial infarction. 291 consecutive patients undergoing peripheral vascular surgery were studied. Patients were screened for a perioperarive myocardial infarction with CK-MB isoenzymes and ECGs for the first three postoperative days. A perioperative cardiac event was defined as a myocardial infarction or cardiac death within 30 days of surgery. There were 18 perioperative cardiac events. Plasma viscosity, fibrinogen, yon Willebrand factor and Factor VII did not correlate with perioperative cardiac events. However, D-Dimer levels showed a correlation; in 264 patients not on anticoagulants, with 17 events, mean logFDP was 6.23 in those with an event, and 5.68 in those without (p=0.03, 95% C.I. for diff. of means 0.05, 1.05). Patients with an event showed no difference in smoking history or sex distribution, but were older (mean © Pearson Professional Ltd 1996
33
age 69 years v 65 years, p=0.006, C.I. 1.3-7.2). Only 4 of those with events had critical limb ischaemia. D-Dimer levels are predictive of perioperative myocardial infarction, and may be useful in the selection of high risk patients. The hypercoagulability indicated by raised FDPs may partly explain the aetiology of perioperative myocardial infarction and suggests the possibility of selective preventive intervention with anticoagulants.
108. The C677T mutation of the 5, lOmethylenetetrahydropholate reductase gene (MTHFR)and moderate hyperhomocysteinemia in young thrombophilic patients F. P. Mancini, R. De Franchis, A. D'Angelo, G. Sebastio, I. Fermo, V. De Stefano, M. Margaglione, G. Mazzola, A. M. Cerbone, L. Soriente, G. Andria, G. Di Minno
Dipartimenti di Biochimica e Clinica Medica, di Pediatria, Universita "FedericoII; NapolL Medicina di Laboratorio, IRCCS, Ospedale S. Raffaele, Milano, Unita di Aterosclerosi e TrombosL IRCCS CSS, S. Giovanni Rotondo, Italy Moderate hyperhomocysteinemia is an independent risk factor for thrombotic vascular disease. A C677T substitution of the MTHFR gene has been reported as the leading cause of moderate hyperhomocysteinemia. We have evaluated the frequency of the C677T mutation of the MTHFR gene in 64 unrelated young thrombophilic patients. In 29 (16 men, 13 women, 37.6_+13.8 yrs old, 7 with arterial and 22 with venous thrombosis) fasting total plasma homocysteine was above the 95th percentile of the distribution (19.5 mM in men and 15 mM in women). These patients were matched for sex, age, type of event and age at first thrombotic event with the other 35. In all cases, nutrient-related disturbances of vitamin B 12 and folate and abnormalities of cystathionine b-synthase enzyme were excluded. Normal subjects (258) free of vascular disease served as controls. Homozygosity for the C677T mutation (+/+) was found in 15% of controls (95% C.I.=I 1-20%). Among the 35% patients with normal homocysteinemia, one only was homozygous for the mutation. In contrast the +/+ genotype was found in 18/29 (62%) of those with hyperhomocysteinemia (9 men, 9 women, 5 with arterial and 13 with venous thrombosis). Plasma homocystein was not significantly different in the 18 patients homozygous for the mutation (32_+19 mM) and in the remaining 11 hyperhomocysteinemic patients (23_+5 mM, p>0.01). These results indicate that in young thrombophilic patients homozygosity for the C677T mutation of the MTHFR gene is the prevalent cause of moderate fasting hyperhomocysteinemia. These data also suggest that in a high proportion of these thrombophilic patients, factors other than C677T mutations are responsible for moderate hyperhomocysteinemia.
109. Comparison of plasma lipoprotein (a) levels between individuals attending a metabolic ward with and without a history of ischemic stroke M. Margaglione, E. Grandone, E. Celentano, G. Vecchione, G. Cappucci, M. Grflli, F. P. Mancini, A. Fibrinolysis (1996) 10, Suppl. 1, 1-58