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Genetic variation of factor VII in Hong Kong Chinese diabetic patients
Thursday 13 October 1994: Poster Abstracts Hemostasis
from population registers of three geographical areas of Finland. The participation rate was 83.2%. Of the 1241 women, 359 (29%) were current users of HRT. After adjustment for age, study area, years of education, current smoking, BMI and diabetes, HRT users had significantly lower TC and higher HDL-C than non-users. No difference was observed in triglycerides or blood pressure. Fasting blood glucose and insulin were significantly lower among users than non-users. Of the hemostatic factors, HRT users had lower fibrinogen (3.35 vs 3.55 g/l, P < O.OOOl),but higher factor VII antigen (111.3 vs 107.0% P= 0.04). and higher plasminogen (118.3 vs 113.1%. P < 0.0001) concentration than non-users. No difference was observed in factor VII coagulant activity (FVII:C) or in lipoprotein (a). In this cross-sectional study, the positive association of TC with age was significantly weaker among HRT users than among non-users (P = 0.005 for age by HRT interaction-term). HRT did not, however, modify the association of age with other risk factors. In conclusion, the data suggest that the effect of HRT on serum lipid profile is clearly favorable, but its effects on hemostatic factors are mixed and their clinical significance needs further study. Genetic variation of factor VII in Hong Kong Chinese 1 diabetic patients Janus Ep, Ma GCK, Bourke C, Chan LC, Lam KSL, Dept. of Clinical Biochemistry, Queen Mary Hospital, Hong Kong
269
quent thrombosis of small and medium caliber arteries and veins. We recently have treated 7 patients with atherosclerosis (ASO) of the large LE from the literature. These were predominantly males of young age (mean 42.3 years) with cardiovascular risk factors and rapidly progressive lower limb-threatening ischemia. They had multiple tevascularizations, experienced frequent early graft thrombosis and responded poorly to thrombolytic and/or anticoagulation therapy. The association of premature AS0 with APLA prompted a literature search for additional cases of large LE arteriopathy related to APLA. We review here 31 such patients with SLE (n = 10, mean age 34.3 years), lupus-like APS (n = 10, 37.2 years) and PAPS (n = 11, 42.2 years), and compared them with 11 AS0 patients. Anticardiohpin antibodies and circulating lupus anticoagulants were found in 75% and 45% of patients respectively; 75% of 26 patients studied had associated clotting abnormalities. Of 40 (95%) patients treated surgically, 57% had acute graft thrombosis and 17 (43%) patients needed major amputations. Patients with SLE had higher incidence of female gender (P < 0.01) distal arterial disease (P < 0.01) and amputation rate (P < 0.05). Patients with APSs demonstrated striking similarity in demographics, clinical symptoms and outcome of treatment to those with ASO. These observations may raise speculation of an existing common pathway in reviewed arterial disorders, probably of the immune nature, which culminates in atherothrombosis in younger patients with risk factors for ASO. Prospective determination of hypercoagtdable states (HCS) in patients with premature lower extremity atherosclerosis (PLEA) Lcvv PJ, Gonzalez MF, Hornung CA, Depts. of Surgery and
1 The objective of this study was to determine, in diabetic patients, the effect on factor VII coagulant activity (VIIc) of the MspI polymorphism. The Arg353 + Glu mutation leads to loss of an Mspl restriction site (M2 allele) which results in lower factor VIIc and antigen levels [l]. Factor VIIc was measured by onestage biological assay and genotyping was performed [I] in 276 Chinese diabetes patients (IDDM and NIDDM) and 204 controls. In both diabetic and control Chinese subjects the allele frequencies were Ml = 0.95, M2 = 0.05 compared with reported frequencies in Caucasians (Ml = 0.89, M2 = 0.11, P < 0.05). Factor VIIc levels were 20% lower (0.9 4 0.22, mean f SD vs 1.16 + 0.23 II-l/ml, P-e 0.01) in Chinese controls with MlM2 vs MlMl genotype, a finding similar to that in Caucasians. A similar trend was also evident in diabetic patients: 1.25 f. 0.30 IU/ml for MIMI vs 1.15 f 0.40 IUlml for MlM2 (ns). Factor VIIc levels were higher in diabetic patients (1.24 * 0.31 Ill/ml) than controls (1.14 f 0.24 IUlml, P < 0.01). In NIDDM patients levels were higher (1.29 f 0.31 IUlml) than in IDDM patients (1.15 ? 0.29 IU/ml, P < 0.001). The same trends were noted in MlMl controls and diabetic patients (1.16 f 0.23 vs 1.25 rt 0.30 IU/ml, P < 0.01) and in MlM2 controls and diabetic patients (0.91 + 0.22 vs 1.15 + 0.40 IU/ml, ns). In conclusion the M2 allele is less common in Chinese than Caucasians. In diabetes its effects operate in the presence of higher factor VIIc levels than in controls. High factor VIIc levels and genotype effects am likely contributors to the increased cardiovascular risk in diabetes. [l] Green et al Arterioscler Thromb 1991; 11: 540-546. Antiphospholipid antibodies, antiphospholipid syndromes and atherosclerosis of the large lower extremity (LE) arteries: a clinical observation Levv PI, Homung CA, Gonzalez MF, Olin JW, Dept. of Med.,
El
Univ. of South Carolina, Dept. of Vascular Med. Ave., Cleveland, OH 44195, USA
In the past decade, antiphospholipid antibodies (APLA) were reported in various clinical syndromes, i.e. SLE, lupus-like disease and primary antiphospholipid syndrome (PAPS), with fre-
Med., Univ. of South Carolina, 2 Medical Park, Columbia, SC
29203, USA. ” Premature peripheral atherosclerosis (ASO) is characterized by rapid progression of ischemic symptoms, low graft patency, in part related to early thrombosis and high amputation rates. In order to test the association of PLEA with HCS, we studied prospectively, between 1992 and 1993, 43 consecutive patients with PLEA (23 males, 20 females) ~45 years of age (mean 40.1 years) and followed them for a mean of 8.6 months. HCS was defined by decreased fibrinolytic activity (FLA) (studied at baseline and after venous occlusion), or concentration of natural anticoagulants (NAC); by high levels of lipoprotein(a) (LP(a)), fibrinogen and/or antiphospholipid antibodies (APLA). The majority of patients (63%) had limb-threatening ischemia, significant aorto-iliac AS0 (78%) and only l/3 had previous revascularizations. Thirty-five (82%) patients had HCS: deficient FLA (n = 22). high LP(a) (20), low NAC (6) high fibrinogen (4) and elevated APLA (2); 19 patients had more than one clotting abnormality. All 8 patients with previous deep vein thrombosis had HCS. Upon entry into the study, 29 (67%) patients underwent surgical treatment (ST), e.g. 16 patients, 80% of whom had HCS, underwent urgent and 13 had elective revascularizations (68% with HCS); and 14 patients had conservative treatment (CT) (88% had HCS). All patients with HCS were anticoagulated. Of 23 patients with ST and HCS, 17 (74%) experienced early (~7 days) graft thrombosis and 13 (57%) had amputations. None with CT needed operation. 20 of 35 patients with HCS were restudied: 17 (85%) remained with HCS (11 of them had different clotting abnormality); and 3 had a normal study. We conclude that PLEA is frequently associated with HCS, especially with deficient fibrinolysis. Young patients with PLEA require appropriate laboratory evaluation of hypercoagulability even if scheduled for nonsurgical treatment. 1
Intravenous nitroglycerin induces heparln resistance in patients with unstable angina and acute myoeardial infarction
Atherosclerosis X, Montreal, October 1994
from population registers of three geographical areas of Finland. The participation rate was 83.2%. Of the 1241 women, 359 (29%) were current users of HRT. After adjustment for age, study area, years of education, current smoking, BMI and diabetes, HRT users had significantly lower TC and higher HDL-C than non-users. No difference was observed in triglycerides or blood pressure. Fasting blood glucose and insulin were significantly lower among users than non-users. Of the hemostatic factors, HRT users had lower fibrinogen (3.35 vs 3.55 g/l, P < O.OOOl),but higher factor VII antigen (111.3 vs 107.0% P= 0.04). and higher plasminogen (118.3 vs 113.1%. P < 0.0001) concentration than non-users. No difference was observed in factor VII coagulant activity (FVII:C) or in lipoprotein (a). In this cross-sectional study, the positive association of TC with age was significantly weaker among HRT users than among non-users (P = 0.005 for age by HRT interaction-term). HRT did not, however, modify the association of age with other risk factors. In conclusion, the data suggest that the effect of HRT on serum lipid profile is clearly favorable, but its effects on hemostatic factors are mixed and their clinical significance needs further study. Genetic variation of factor VII in Hong Kong Chinese 1 diabetic patients Janus Ep, Ma GCK, Bourke C, Chan LC, Lam KSL, Dept. of Clinical Biochemistry, Queen Mary Hospital, Hong Kong
269
quent thrombosis of small and medium caliber arteries and veins. We recently have treated 7 patients with atherosclerosis (ASO) of the large LE from the literature. These were predominantly males of young age (mean 42.3 years) with cardiovascular risk factors and rapidly progressive lower limb-threatening ischemia. They had multiple tevascularizations, experienced frequent early graft thrombosis and responded poorly to thrombolytic and/or anticoagulation therapy. The association of premature AS0 with APLA prompted a literature search for additional cases of large LE arteriopathy related to APLA. We review here 31 such patients with SLE (n = 10, mean age 34.3 years), lupus-like APS (n = 10, 37.2 years) and PAPS (n = 11, 42.2 years), and compared them with 11 AS0 patients. Anticardiohpin antibodies and circulating lupus anticoagulants were found in 75% and 45% of patients respectively; 75% of 26 patients studied had associated clotting abnormalities. Of 40 (95%) patients treated surgically, 57% had acute graft thrombosis and 17 (43%) patients needed major amputations. Patients with SLE had higher incidence of female gender (P < 0.01) distal arterial disease (P < 0.01) and amputation rate (P < 0.05). Patients with APSs demonstrated striking similarity in demographics, clinical symptoms and outcome of treatment to those with ASO. These observations may raise speculation of an existing common pathway in reviewed arterial disorders, probably of the immune nature, which culminates in atherothrombosis in younger patients with risk factors for ASO. Prospective determination of hypercoagtdable states (HCS) in patients with premature lower extremity atherosclerosis (PLEA) Lcvv PJ, Gonzalez MF, Hornung CA, Depts. of Surgery and
1 The objective of this study was to determine, in diabetic patients, the effect on factor VII coagulant activity (VIIc) of the MspI polymorphism. The Arg353 + Glu mutation leads to loss of an Mspl restriction site (M2 allele) which results in lower factor VIIc and antigen levels [l]. Factor VIIc was measured by onestage biological assay and genotyping was performed [I] in 276 Chinese diabetes patients (IDDM and NIDDM) and 204 controls. In both diabetic and control Chinese subjects the allele frequencies were Ml = 0.95, M2 = 0.05 compared with reported frequencies in Caucasians (Ml = 0.89, M2 = 0.11, P < 0.05). Factor VIIc levels were 20% lower (0.9 4 0.22, mean f SD vs 1.16 + 0.23 II-l/ml, P-e 0.01) in Chinese controls with MlM2 vs MlMl genotype, a finding similar to that in Caucasians. A similar trend was also evident in diabetic patients: 1.25 f. 0.30 IU/ml for MIMI vs 1.15 f 0.40 IUlml for MlM2 (ns). Factor VIIc levels were higher in diabetic patients (1.24 * 0.31 Ill/ml) than controls (1.14 f 0.24 IUlml, P < 0.01). In NIDDM patients levels were higher (1.29 f 0.31 IUlml) than in IDDM patients (1.15 ? 0.29 IU/ml, P < 0.001). The same trends were noted in MlMl controls and diabetic patients (1.16 f 0.23 vs 1.25 rt 0.30 IU/ml, P < 0.01) and in MlM2 controls and diabetic patients (0.91 + 0.22 vs 1.15 + 0.40 IU/ml, ns). In conclusion the M2 allele is less common in Chinese than Caucasians. In diabetes its effects operate in the presence of higher factor VIIc levels than in controls. High factor VIIc levels and genotype effects am likely contributors to the increased cardiovascular risk in diabetes. [l] Green et al Arterioscler Thromb 1991; 11: 540-546. Antiphospholipid antibodies, antiphospholipid syndromes and atherosclerosis of the large lower extremity (LE) arteries: a clinical observation Levv PI, Homung CA, Gonzalez MF, Olin JW, Dept. of Med.,
El
Univ. of South Carolina, Dept. of Vascular Med. Ave., Cleveland, OH 44195, USA
In the past decade, antiphospholipid antibodies (APLA) were reported in various clinical syndromes, i.e. SLE, lupus-like disease and primary antiphospholipid syndrome (PAPS), with fre-
Med., Univ. of South Carolina, 2 Medical Park, Columbia, SC
29203, USA. ” Premature peripheral atherosclerosis (ASO) is characterized by rapid progression of ischemic symptoms, low graft patency, in part related to early thrombosis and high amputation rates. In order to test the association of PLEA with HCS, we studied prospectively, between 1992 and 1993, 43 consecutive patients with PLEA (23 males, 20 females) ~45 years of age (mean 40.1 years) and followed them for a mean of 8.6 months. HCS was defined by decreased fibrinolytic activity (FLA) (studied at baseline and after venous occlusion), or concentration of natural anticoagulants (NAC); by high levels of lipoprotein(a) (LP(a)), fibrinogen and/or antiphospholipid antibodies (APLA). The majority of patients (63%) had limb-threatening ischemia, significant aorto-iliac AS0 (78%) and only l/3 had previous revascularizations. Thirty-five (82%) patients had HCS: deficient FLA (n = 22). high LP(a) (20), low NAC (6) high fibrinogen (4) and elevated APLA (2); 19 patients had more than one clotting abnormality. All 8 patients with previous deep vein thrombosis had HCS. Upon entry into the study, 29 (67%) patients underwent surgical treatment (ST), e.g. 16 patients, 80% of whom had HCS, underwent urgent and 13 had elective revascularizations (68% with HCS); and 14 patients had conservative treatment (CT) (88% had HCS). All patients with HCS were anticoagulated. Of 23 patients with ST and HCS, 17 (74%) experienced early (~7 days) graft thrombosis and 13 (57%) had amputations. None with CT needed operation. 20 of 35 patients with HCS were restudied: 17 (85%) remained with HCS (11 of them had different clotting abnormality); and 3 had a normal study. We conclude that PLEA is frequently associated with HCS, especially with deficient fibrinolysis. Young patients with PLEA require appropriate laboratory evaluation of hypercoagulability even if scheduled for nonsurgical treatment. 1
Intravenous nitroglycerin induces heparln resistance in patients with unstable angina and acute myoeardial infarction
Atherosclerosis X, Montreal, October 1994