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Plasma homocyteine and lipoprotein profile in patients with peripheral arterial occlusive disease
202
71st EAS Meeting Abstracts acceptedfor presentation in the abstract book
PLASMA HOMOCYTEINE AND LIPOPROTEIN PROFILE IN PATIENTS WITH PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
ANTIPHOSPHOLIPID ANTIBODIES IN PATIENTS WITH STROKE G.S. Gulizia, E. Vinci, G. Pistone, I. Di Fazio, I. Giugno, P. Ruello, M. Malaguarnera. lnstitufe of Internal Medicine and Geriatrics, Universi~.,
E Rassoul, V. Richter, B. K16tzer 1, C. Janke, S. Quast 2, J. Geisel 2, W. Herrmann 2. Department of Clinical Chemist~ and Pathobiochemisto,;
of Catania, Italy
I Clinic of Sargery 11. Unioersity of Leipzig; 2Central LaboratoO, of the University of Saaland, Homburg/S.. German),
Institute of Internal Medicine and Geriatrics - University of CATANIA Italy Antiphospholipid antibodies (aPL) are a heterogeneous group of immunoglobulins against different protein-phospholipids complexes. Recently the serum aPL levels are considered as risk factors for stroke. Aim: We studied a population composed of patients with stroke in order to verify whether aPL are present and are an independent risk factor for acute cerebrovascular accidents. Patients and Methods: Our study was carried out on 55 subjects imean age 70.4-t-8.3 years) of whom 23 males and 32 females with acute cerebral strike: 36 cases were ischemic stroke as well as 12 were transitory ischemic attacks and 7 were hemorrhagic. We evaluated renal and hepatic functions, coagulation parameters, glucose, total cholesterol, HDL cholesteroladd triglycerides with common laboratory methods. LDL cholesterol was evaluated by Friedewald formula. Lp(a) was determined by ELISA method, using EIA reader mod. 2550 and Immunozyme reactive (ImmunoVienna). aPL serum levels were determined by ELISA anti-phosphatidyl serine, antiphosphatidyl inositol and anti-phosphatidic acid, ORGenTec Diagnostika GmbH- Germany. Statystical analysis of the obtained data was performed by Spearman rank sum test, non parametric data Wilcoxon test and multivariate analysis (multiple regression test). Results: aPL mean serum level was 6.57+6.96 IU, with a median value of 3.98. All of other assessed parameters were within the normal range. On the basis of the etiology of the stroke, mean serum level of aPL was 7.16 + 7.5 IU in patients with ischemic stroke, as well as 6.3±7.3 UI in those with hemorrhagic disease, while in TIA patients this value was 4.9+4.05 UI. These values did not show statystical significant differences, aPL did not correlate with age, sex or lipid pattern neither with coagulation parameters. Multivariate analysis showed that none of the assessed variables was an independent risk factor for the various types of stroke. Conclusions: In our study-series, aPL positive patients with previous cerebrovascular events were two-fold the aPL negative patients with the same disease (28% vs 14% respectively). Our study did not show that aPL are an indipendent risk factor for stroke, as their serum levels resulted just slightly elevated in the population studied. Likely, other simultaneous factors associated to aPL (i.e. diabetes or hypertension) play some important role in the development of cerebmvascular disease.
Several studies have identified moderate hyperhomocysteinemia (HCy) as an independent risk factor for atherosclerosis. The purpose o f this case-control study was to determine lipoprotein profile and homocysteine concentration in serum of 85 male patients with peripheral arterial occlusive disease (PAOD) and in 51 normolipidemic age-matched male controls. Cholesterol, triglycerides and phospholipids, HDL-cholesterol as well as subfractions HDL2- and HDL3-cholesterol, LDL-cholesterol, apo B, apo A-l, lipoprotein particles LpA-I and LpA-I:A-II were measured in serum. Homocysteine, folio acid, vitamin B6 and BI2 were determined with the help of high pressure liquid chromatography. The 677 C --, T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was analysed in PAOD patients. Patients with peripheral arterial occlusive disease showed a significantly higher mean concentration of homocysteine than control subjects (P > 0.001). There was a negative correlation between the levels of homocysteine and vitamin BI2 as well as folic acid (for vitamin BI2: r = -0.40 and for folic acid: r = -0.38). The prevalence of hyperhomocysteinemia (Hcy > 16 I-tmol/1) in the patients was 45% in contrast to 8% in controls. HDL cholesterol, HDL3 cholesterol, Apo A1 and Lp A-I were significantly reduced in patients and triglycerides were elevated. The elevated plasma homocysteine concentration is frequently seen in homozygous carriers of a point mutation (677 C ~ T; A ~ V) in the methylenetetrahydrofolate reductase gene, as the product of this gene is an enzyme, participating in homocystein remethylation. The homozygous state for the 677 C ~ T mutation was found in 13.3% PAOD patients. LP(a), LIPIDIC PATTERN AND HEPATOCELLULAR CARCINOMA A.M. Franzone, M. Motta, G. Pistone, E Ruello, M. Rizzo, M.P. Panebianco, A. Marino, I. Giugno, M. Malaguarnera. Institute of Internal Medicine and
Geriatrics-Uniuersity of Catania. Italy Hepatocellular carcinoma (HCC) is a malignance with a high incidence worldwide. Lp(a) is a genetic variant of LDL-c and is synthesized by the liver. We assessed a group of patients affected by HCC, in order to evaluate the serum Lp(a) and 1L-6 levels changes. We studied 40 patients (25 males and 15 females, mean age 65.4+5.68 years) affected by primary HCC and 25 control subjects (12 males and 13 females, mean age 51.1+15.3 years). 32 patients were HCV positive, 5 were only HBsAb positive, while in 3 it was not possible to find etiologic agent. Only five patients referred high alcohol consttmption (more than 150 gr/dl/die). In HCC patients we evaluated the following serological parameters: IL-6, total cholesterol, HDL-c, triglycerides, albumin, CHE, AST, ALT, ¥-GT, ALP, ferritin, a-fetoprotein, partial tromboplastin time, Quick time, prothrombinic activity and fibrinogen, using common laboratory methods. Serum LDLc level was evaluated using Friedewald's formula. Lp(a) was evaluated by ELISA method (lmmunozym reactive). Serum IL-6 levels have been determined by immunoenzymatic method (EIA) for quantitative analysis (Techno-Genetics). Statistical analysis of obtained data was performed using the variance analysis (ANOVA method) and Student's t for non-paired data test. For Lp(a), Wilcoxon's non parametric test was used. The correlations between examined parameters were performed by Pearson's correlation test. In the patients with HCC, mean serum total cholesterol, HDL-c, triglycerides and Lp(a) levels were significantly lower than in controls. HDL-c did not show a statistically significant difference between the two groups studied. In HCC patients, IL-6 showed a serum level significantly higher than in controls (p = 0.01 ). Furthermore, we found a significant positive correlation between: IL-6 and tumoral size, Lp(a) and CHE, Lp(a) and albumin. A significant negative correlation between Lp(a) and alpha fetoprotein, ferritin, IL-6, tumoral size respectively was present. On the basis of relationship between ct-fetoprotein, tumoral size and Lp(a), the latter seems to correlate to the severity of the disease and to the clinical impairment o f the patients.
ANGIOTENSIN CONVERTING ENZYME, Lp(a), LIPIDS AND FIBRINOGEN IN PATIENTS WITH RENAL ARTERY STENOSIS K. Kuczyfiska, H. Berent, B. Wocial, B. Symonides, B. lgnatowskaSwitalska, W. Januszewicz. Department of Internal Medicine and
Hypertension Academy of Medicine, Warsaw;Poland Objective: To evaluate Angiotensin Converting Enzyme (ACE), Lp(a), lipids and fibrinogen concentration in blood of patients with renal artery stenosis (A-RAS). Material and Methods: The study included l0 patients with renal artery stenosis (5 female, 5 male) in mean age 48.6+5.7 yrs and 12 healthy oormotensive volunteers (6 female, 6 male) in mean age 44.7+11.5 yrs. The diagnosis was confirmed by arteriography. ACE activity was determined by spectrophotometric method, Lp(a) by ELISA and fibrioogen by Clause methods. Total cholesterol (CH total), HDL and TG were estimated by Boehringer-Mannheim kit and atberogennic index (A.I.) was calculated. Results: Age Lw]
ACE Lp(a) CHtotal LDL HDL TG Fb A.I. {ltmol/ {mg*/,l (mg*/*] [m$*/ol [mg%] [mg*/.1 Img*/*l mVmin]
A-KAS
48.6
38.4
49.5
244,7
153,5
51,5
217,1
359,7
n = 10
+5.7
:t:13.0
+33.4
4.58.6
+64.0
+18.6
+116.9
-/-72.5
4.1.9
Healthy
44.7
18.0
17.5
188.1
113.2
54.1
104.4
234.5
2.1
n = 12
4.11.5
+5.0
+16.3
+47.5
+31.9
4.16.1
+51.3
-1-49.2
4-0.5
p
NS
<0.001
<0,02
<0,05
NS
NS
<0.02
<0,001
<0.5
3.4
Conclusion: Increased ACE activity co-existing with lipid disorders, increased Lp(a) and Fb concentration may cause the augmentation of vascular lesions and the appearance of restenosis.
71st EAS Congress and Satellite Symposia
71st EAS Meeting Abstracts acceptedfor presentation in the abstract book
PLASMA HOMOCYTEINE AND LIPOPROTEIN PROFILE IN PATIENTS WITH PERIPHERAL ARTERIAL OCCLUSIVE DISEASE
ANTIPHOSPHOLIPID ANTIBODIES IN PATIENTS WITH STROKE G.S. Gulizia, E. Vinci, G. Pistone, I. Di Fazio, I. Giugno, P. Ruello, M. Malaguarnera. lnstitufe of Internal Medicine and Geriatrics, Universi~.,
E Rassoul, V. Richter, B. K16tzer 1, C. Janke, S. Quast 2, J. Geisel 2, W. Herrmann 2. Department of Clinical Chemist~ and Pathobiochemisto,;
of Catania, Italy
I Clinic of Sargery 11. Unioersity of Leipzig; 2Central LaboratoO, of the University of Saaland, Homburg/S.. German),
Institute of Internal Medicine and Geriatrics - University of CATANIA Italy Antiphospholipid antibodies (aPL) are a heterogeneous group of immunoglobulins against different protein-phospholipids complexes. Recently the serum aPL levels are considered as risk factors for stroke. Aim: We studied a population composed of patients with stroke in order to verify whether aPL are present and are an independent risk factor for acute cerebrovascular accidents. Patients and Methods: Our study was carried out on 55 subjects imean age 70.4-t-8.3 years) of whom 23 males and 32 females with acute cerebral strike: 36 cases were ischemic stroke as well as 12 were transitory ischemic attacks and 7 were hemorrhagic. We evaluated renal and hepatic functions, coagulation parameters, glucose, total cholesterol, HDL cholesteroladd triglycerides with common laboratory methods. LDL cholesterol was evaluated by Friedewald formula. Lp(a) was determined by ELISA method, using EIA reader mod. 2550 and Immunozyme reactive (ImmunoVienna). aPL serum levels were determined by ELISA anti-phosphatidyl serine, antiphosphatidyl inositol and anti-phosphatidic acid, ORGenTec Diagnostika GmbH- Germany. Statystical analysis of the obtained data was performed by Spearman rank sum test, non parametric data Wilcoxon test and multivariate analysis (multiple regression test). Results: aPL mean serum level was 6.57+6.96 IU, with a median value of 3.98. All of other assessed parameters were within the normal range. On the basis of the etiology of the stroke, mean serum level of aPL was 7.16 + 7.5 IU in patients with ischemic stroke, as well as 6.3±7.3 UI in those with hemorrhagic disease, while in TIA patients this value was 4.9+4.05 UI. These values did not show statystical significant differences, aPL did not correlate with age, sex or lipid pattern neither with coagulation parameters. Multivariate analysis showed that none of the assessed variables was an independent risk factor for the various types of stroke. Conclusions: In our study-series, aPL positive patients with previous cerebrovascular events were two-fold the aPL negative patients with the same disease (28% vs 14% respectively). Our study did not show that aPL are an indipendent risk factor for stroke, as their serum levels resulted just slightly elevated in the population studied. Likely, other simultaneous factors associated to aPL (i.e. diabetes or hypertension) play some important role in the development of cerebmvascular disease.
Several studies have identified moderate hyperhomocysteinemia (HCy) as an independent risk factor for atherosclerosis. The purpose o f this case-control study was to determine lipoprotein profile and homocysteine concentration in serum of 85 male patients with peripheral arterial occlusive disease (PAOD) and in 51 normolipidemic age-matched male controls. Cholesterol, triglycerides and phospholipids, HDL-cholesterol as well as subfractions HDL2- and HDL3-cholesterol, LDL-cholesterol, apo B, apo A-l, lipoprotein particles LpA-I and LpA-I:A-II were measured in serum. Homocysteine, folio acid, vitamin B6 and BI2 were determined with the help of high pressure liquid chromatography. The 677 C --, T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene was analysed in PAOD patients. Patients with peripheral arterial occlusive disease showed a significantly higher mean concentration of homocysteine than control subjects (P > 0.001). There was a negative correlation between the levels of homocysteine and vitamin BI2 as well as folic acid (for vitamin BI2: r = -0.40 and for folic acid: r = -0.38). The prevalence of hyperhomocysteinemia (Hcy > 16 I-tmol/1) in the patients was 45% in contrast to 8% in controls. HDL cholesterol, HDL3 cholesterol, Apo A1 and Lp A-I were significantly reduced in patients and triglycerides were elevated. The elevated plasma homocysteine concentration is frequently seen in homozygous carriers of a point mutation (677 C ~ T; A ~ V) in the methylenetetrahydrofolate reductase gene, as the product of this gene is an enzyme, participating in homocystein remethylation. The homozygous state for the 677 C ~ T mutation was found in 13.3% PAOD patients. LP(a), LIPIDIC PATTERN AND HEPATOCELLULAR CARCINOMA A.M. Franzone, M. Motta, G. Pistone, E Ruello, M. Rizzo, M.P. Panebianco, A. Marino, I. Giugno, M. Malaguarnera. Institute of Internal Medicine and
Geriatrics-Uniuersity of Catania. Italy Hepatocellular carcinoma (HCC) is a malignance with a high incidence worldwide. Lp(a) is a genetic variant of LDL-c and is synthesized by the liver. We assessed a group of patients affected by HCC, in order to evaluate the serum Lp(a) and 1L-6 levels changes. We studied 40 patients (25 males and 15 females, mean age 65.4+5.68 years) affected by primary HCC and 25 control subjects (12 males and 13 females, mean age 51.1+15.3 years). 32 patients were HCV positive, 5 were only HBsAb positive, while in 3 it was not possible to find etiologic agent. Only five patients referred high alcohol consttmption (more than 150 gr/dl/die). In HCC patients we evaluated the following serological parameters: IL-6, total cholesterol, HDL-c, triglycerides, albumin, CHE, AST, ALT, ¥-GT, ALP, ferritin, a-fetoprotein, partial tromboplastin time, Quick time, prothrombinic activity and fibrinogen, using common laboratory methods. Serum LDLc level was evaluated using Friedewald's formula. Lp(a) was evaluated by ELISA method (lmmunozym reactive). Serum IL-6 levels have been determined by immunoenzymatic method (EIA) for quantitative analysis (Techno-Genetics). Statistical analysis of obtained data was performed using the variance analysis (ANOVA method) and Student's t for non-paired data test. For Lp(a), Wilcoxon's non parametric test was used. The correlations between examined parameters were performed by Pearson's correlation test. In the patients with HCC, mean serum total cholesterol, HDL-c, triglycerides and Lp(a) levels were significantly lower than in controls. HDL-c did not show a statistically significant difference between the two groups studied. In HCC patients, IL-6 showed a serum level significantly higher than in controls (p = 0.01 ). Furthermore, we found a significant positive correlation between: IL-6 and tumoral size, Lp(a) and CHE, Lp(a) and albumin. A significant negative correlation between Lp(a) and alpha fetoprotein, ferritin, IL-6, tumoral size respectively was present. On the basis of relationship between ct-fetoprotein, tumoral size and Lp(a), the latter seems to correlate to the severity of the disease and to the clinical impairment o f the patients.
ANGIOTENSIN CONVERTING ENZYME, Lp(a), LIPIDS AND FIBRINOGEN IN PATIENTS WITH RENAL ARTERY STENOSIS K. Kuczyfiska, H. Berent, B. Wocial, B. Symonides, B. lgnatowskaSwitalska, W. Januszewicz. Department of Internal Medicine and
Hypertension Academy of Medicine, Warsaw;Poland Objective: To evaluate Angiotensin Converting Enzyme (ACE), Lp(a), lipids and fibrinogen concentration in blood of patients with renal artery stenosis (A-RAS). Material and Methods: The study included l0 patients with renal artery stenosis (5 female, 5 male) in mean age 48.6+5.7 yrs and 12 healthy oormotensive volunteers (6 female, 6 male) in mean age 44.7+11.5 yrs. The diagnosis was confirmed by arteriography. ACE activity was determined by spectrophotometric method, Lp(a) by ELISA and fibrioogen by Clause methods. Total cholesterol (CH total), HDL and TG were estimated by Boehringer-Mannheim kit and atberogennic index (A.I.) was calculated. Results: Age Lw]
ACE Lp(a) CHtotal LDL HDL TG Fb A.I. {ltmol/ {mg*/,l (mg*/*] [m$*/ol [mg%] [mg*/.1 Img*/*l mVmin]
A-KAS
48.6
38.4
49.5
244,7
153,5
51,5
217,1
359,7
n = 10
+5.7
:t:13.0
+33.4
4.58.6
+64.0
+18.6
+116.9
-/-72.5
4.1.9
Healthy
44.7
18.0
17.5
188.1
113.2
54.1
104.4
234.5
2.1
n = 12
4.11.5
+5.0
+16.3
+47.5
+31.9
4.16.1
+51.3
-1-49.2
4-0.5
p
NS
<0.001
<0,02
<0,05
NS
NS
<0.02
<0,001
<0.5
3.4
Conclusion: Increased ACE activity co-existing with lipid disorders, increased Lp(a) and Fb concentration may cause the augmentation of vascular lesions and the appearance of restenosis.
71st EAS Congress and Satellite Symposia