- Email: [email protected]
Relationship between major hemostasis parameters and metabolic syndrome components in men with moderate arterial hypertension
Milionis
•
6
-
•
ALL ATHEROSCLEROTIC PATIENTS ARE EQUAL, BUT SOME MORE EQUAL THAN OTHERS. THE 'AIRVAG' COHORT. 3. RISK FACTOR CONTROL AND TREATMENT
N. Mesa 1'6, I. Gonzalez-Anglada 1, M.L. Casas2, L. Lopez-Bescos3, C. Sanchez4, E. Puras 5, C. Martin 1, M.L. Edista 2, M.A. Trevino 6, J. Jimenez 3, S. Lujan 5, E Barriga4, R. Barba 1, H. Martin 1, C. Guijarro 1.
1Unidad de Medicina Interna, 2Area de Laboratorio, 3Unidad de Cardiologia, 4Unidad de Neurologia, SUnidad de Cirugia Vascular, 6Instituto de Investigacion, Fundacion Hospital Alcorcon, Madrid, Spain Background: In spite of similar recommendations for all vascular symptomatic patients, risk factor (RF) control varies. Patients and Methods: AIRVAG Cohort of 222 consecutive patients aged 35 70, (July 2000-February 2002) with an acute atherothrombotic event: coronary [CHD 56%], cerebral [CVD 32%] or peripheral [PVD 13%]. One month after the ischemic event, treatment and RF control were assessed. Results are m e a n s i S D or %. Comparisons were done by the chi2 and ANOVA. Results: Casual systolic/diastolic blood pressure (BP) were CHD 125 ±20/ 77±11, CVD 132±21/82±11, PVD 133±16/81±10 mmHg (p<0.05 for both). Ambulatory BP monitoring CHD 120±16/73±8, CVD 127±18/ 77±9, PVD 132±18/80±9 mmHg (p<0.01 for both). Globally BP was ~>140/90 in CHD 24% CVD 41% PVD 39% (p<0.01). Total cholesterol was CHD 181±36 CVD 203±44, PVD 218±40 mg/dl (p<0.01); LDLcholesterol was CHD 110±28 CVD 132±40, PVD 144±34 mg/dl (p<0.01). Apo B CHD 90±21 CVD 99±25, PVD 109±27 mg/dl (p<0.01). HDLcholesterol 45±11 mg/dl, apo A1 135±32 mg/dl, median TG 117 mg/dl, median Lp(a) 21 mg/dl did not differ between groups. LDL-cholesterol was >130 mg/dl in CHD 22% CVD 36% PVD 61% (p<0.01); >100 mg/dl CHD 54% CVD 77% PVD 82% (p<0.01). Active smoking was present in CHD 7% CVD 20% PVD 50% (p<0.01). Virtually all cases were on antiplatelet agents (97%) whereas statin treatment differed CHD 77% CVD 33% PVD 32% (p
[46-1] RELATIONSHIP BETWEEN M A J O R HEMOSTASIS PARAMETERS AND METABOLIC SYNDROME COMPONENTS IN MEN W I T H MODERATE ARTERIAL HYPERTENSION V.A. Metelskaya, L.A. Ratnikova, M.N. Mamedov, A.M. Olferiev, I.E. Petrichenko, N.V. Perova. National Research Center for Preventive
Medicine, Moscow, Russia This study aimed to analyze hemostasis parameters in men with moderate arterial hypertension (AH), either isolated or combined with one or two metabolic syndrome components. All patients (pts, n-90) were stratified according to insulin resistance (IR) index (glucose/insulin ratio < or > than 6.0) and according to presence or absence of abdominal obesity (AO), or hypertriglyceridemia, or low HDL C level. The following series of groups of AH pts were made up: (1) normo/hypertriglyceridemia with or without IR; (2) normal/low HDL C with or without IR; (3) normal BMI/AO with or without IR. In the first series, only in group with combination of IR with hypertriglyceridemia ECLT was higher than in pts with isolated AH: 286±47 vs 245±52 min. FVII activity was also higher: 156±74 in group with combination of IR and hypertriglyceridemia, and 114±65% in pts with AH only. In the second series, pts with combination of IR and low HDL C also had higher ECLT than those with AH: 289±50 vs 247±57 min. In the third series, pts with combination of IR and AO had significantly higher than pts with isolated AH fibrinogen level: 328±109 vs 266±55 mg/dl and FVII activity: 173±74 vs 124±60%. Thus, while in hypertensive pts insulin resistance, hypertriglyceridemia, low HDL C level or abdominal obesity per se were not associated with any changes in hemostasis, the combination of IR even with one of these metabolic factors was accompanied by delayed clot lysis and hypercoagulation due to elevation of FVII activity or fibrinogen level.
•6--•
165
SEVERE HYPOALPHALIPOPROTEINEMIA, IMPAIRED CHOLESTEROL EFFLUX AND INCREASED SUSCEPTIBILITY TO ATHEROSCLEROSIS IN APOA1/C3/A4 KNOCKOUT MICE
H. Mezdour 1, G. Castro 1, J. Fruchart 1, M. Rouis 1, G. Torpier 1, N. Maeda 2.
]Institut Pasteur de Lille, France," 2University of North Carolina at Chapel Hill, NC, USA Human patients with apolipoprotein (apo)AI/CIII/AIV deficiency have very low high-density lipoproteins (HI)L) concentration in plasma and suffer from premature atherosclerosis. The apolipoprotein APOA1/C3/A4 gene cluster have been reported to play a pivotal role in reverse cholesterol transport, a mechanism postulated to prevent peripheral tissues from accumulating excess cholesterol and atherogenesis. To test this hypothesis, we have generated mice lacking APOA1/C3/A4 gene cluster by gene targeting. In homozygous mutant mice (ACA - / - ) fed a chow diet, apolipoprotein AI, CIII and AIV were totally absent from plasma. Fasted plasma total cholesterol (TC), ItDL cholesterol (ItDLc) and triglycerides (TG) in mutants vs wild-type controls were reduced to 20.5±11.2 vs 61.2±13.5 mg/dl (-66.5%), 6.3±2 vs 38.4±9.8 mg/dl (-83.6%) and 41.7±7.8 vs 59.3±14 mg/dl (-29.7%), respectively. On high-fat Western-style (HFW) diet, TC was increased in mutants vs controls to 29.3±11.2 (+42.3%) vs 100.8±42 mg/dl (+64.7%), and ItDLc decreased to 1.8 mg/dl (-71.4%) vs 43.4 (+13%), respectively. Plasma from homozygous mutants showed reduced capacity in promoting cholesterol efflux, in-vitro, to about 26M6%, in Fu5AH hepatoma cell line model, and 65 71% in J774 macrophage cell line model. LCAT activity was also reduced to about 38 55% of controls. Interestingly, preliminary data showed that ACA - / - mutants with 129xB6 mixed genetic background, developed small aortic lesions when fed HFW diet. In conclusion, these results support an essential role of the cluster in ItDL metabolism, and are consistent with a redundancy of function of apoAI and apoAIV in peripheral cholesterol homeostasis. ~--3] LIPID PARAMETERS IN ELDERLY PATIENTS SUFFERING FIRST ACUTE ISCHEMIC STROKE H. Milionis, E. Liberopoulos, G. Miltiadous, C. Tzallas, E. Bairaktari, M. Elisaf. Department of Internal Medicine, Medical School, University of
Ioannina, Greece We analyzed the lipid profile along with other risk factors in elderly patients admitted for nonhemorrhagic stroke. A total of 163 elderly patients (78.1±4.6 years old) (88 men and 75 women) successively hospitalized for first thrombotic stroke were studied in comparison with 166 age and sex-matched healthy volunteers without history of cardiovascular disease. Stroke patients exhibited a more atherogenic lipid profile compared to controls. Specifically, patients and controls had similar serum total cholesterol levels (207.3±48.7 vs 208.1±43.5 mg/dl), LDL cholesterol (132.4±42.3 vs 132.1±45.3 mg/dl), and ApoB levels (131.6±24.3 vs 126.8±25.6 mg/dl). Nevertheless, stroke patients had higher values of triglycerides (174.7 ±74.3 vs 124.8±79.8 mg/dl, p<0.001), and Lp(a) (median value 15.7 vs 7.1 mg/dl, p<0.001), whereas they displayed lower concentrations of HDL cholesterol (40±11.5 vs 51±11.5 mg/dl, p<0.001), and ApoA-I (130±24.3 mg/dl vs 150±22 mg/dl, p<0.001). Furthermore, stroke patients had increased serum uric acid (5.6±1.7 vs 4.8±1.4 mg/dl, p<0.001), and plasma fibrinogen levels (405.8±99.7 vs 305.7±105, p<0.001) compared to controls. In conclusion, elderly patients experiencing first non-hemorrhagic stroke exhibit a more atherogenic lipid profile compared to age and sex-matched subjects without history of prior cardiovascular disease. These patients tend to have higher levels of TG, Lp(a), uric acid and fibrinogen in addition to lower values of HDL-cholesterol and Apo A-I. ~-~
LIPOPROTEIN (A) LEVELS AND APOLIPOPROTEIN (A) ISOFORM SIZE IN PATIENTS W I T H SUBCLINICAL HYPOTHYROIDISM: EFFECT OF TREATMENT W I T H L-THYROXINE
H. Milionis, Z. Efstathiadou, A. Tselepis, C. Tzallas, E. Bairaktari, A. Tsatsoulis, M. Elisaf. Department of Internal Medicine, Medical School,
University of loannina, Greece The increased risk of premature cardiovascular disease (CVD) in patients with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information with regard to the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of CVD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)]
73rd EAS Congress
•
6
-
•
ALL ATHEROSCLEROTIC PATIENTS ARE EQUAL, BUT SOME MORE EQUAL THAN OTHERS. THE 'AIRVAG' COHORT. 3. RISK FACTOR CONTROL AND TREATMENT
N. Mesa 1'6, I. Gonzalez-Anglada 1, M.L. Casas2, L. Lopez-Bescos3, C. Sanchez4, E. Puras 5, C. Martin 1, M.L. Edista 2, M.A. Trevino 6, J. Jimenez 3, S. Lujan 5, E Barriga4, R. Barba 1, H. Martin 1, C. Guijarro 1.
1Unidad de Medicina Interna, 2Area de Laboratorio, 3Unidad de Cardiologia, 4Unidad de Neurologia, SUnidad de Cirugia Vascular, 6Instituto de Investigacion, Fundacion Hospital Alcorcon, Madrid, Spain Background: In spite of similar recommendations for all vascular symptomatic patients, risk factor (RF) control varies. Patients and Methods: AIRVAG Cohort of 222 consecutive patients aged 35 70, (July 2000-February 2002) with an acute atherothrombotic event: coronary [CHD 56%], cerebral [CVD 32%] or peripheral [PVD 13%]. One month after the ischemic event, treatment and RF control were assessed. Results are m e a n s i S D or %. Comparisons were done by the chi2 and ANOVA. Results: Casual systolic/diastolic blood pressure (BP) were CHD 125 ±20/ 77±11, CVD 132±21/82±11, PVD 133±16/81±10 mmHg (p<0.05 for both). Ambulatory BP monitoring CHD 120±16/73±8, CVD 127±18/ 77±9, PVD 132±18/80±9 mmHg (p<0.01 for both). Globally BP was ~>140/90 in CHD 24% CVD 41% PVD 39% (p<0.01). Total cholesterol was CHD 181±36 CVD 203±44, PVD 218±40 mg/dl (p<0.01); LDLcholesterol was CHD 110±28 CVD 132±40, PVD 144±34 mg/dl (p<0.01). Apo B CHD 90±21 CVD 99±25, PVD 109±27 mg/dl (p<0.01). HDLcholesterol 45±11 mg/dl, apo A1 135±32 mg/dl, median TG 117 mg/dl, median Lp(a) 21 mg/dl did not differ between groups. LDL-cholesterol was >130 mg/dl in CHD 22% CVD 36% PVD 61% (p<0.01); >100 mg/dl CHD 54% CVD 77% PVD 82% (p<0.01). Active smoking was present in CHD 7% CVD 20% PVD 50% (p<0.01). Virtually all cases were on antiplatelet agents (97%) whereas statin treatment differed CHD 77% CVD 33% PVD 32% (p
[46-1] RELATIONSHIP BETWEEN M A J O R HEMOSTASIS PARAMETERS AND METABOLIC SYNDROME COMPONENTS IN MEN W I T H MODERATE ARTERIAL HYPERTENSION V.A. Metelskaya, L.A. Ratnikova, M.N. Mamedov, A.M. Olferiev, I.E. Petrichenko, N.V. Perova. National Research Center for Preventive
Medicine, Moscow, Russia This study aimed to analyze hemostasis parameters in men with moderate arterial hypertension (AH), either isolated or combined with one or two metabolic syndrome components. All patients (pts, n-90) were stratified according to insulin resistance (IR) index (glucose/insulin ratio < or > than 6.0) and according to presence or absence of abdominal obesity (AO), or hypertriglyceridemia, or low HDL C level. The following series of groups of AH pts were made up: (1) normo/hypertriglyceridemia with or without IR; (2) normal/low HDL C with or without IR; (3) normal BMI/AO with or without IR. In the first series, only in group with combination of IR with hypertriglyceridemia ECLT was higher than in pts with isolated AH: 286±47 vs 245±52 min. FVII activity was also higher: 156±74 in group with combination of IR and hypertriglyceridemia, and 114±65% in pts with AH only. In the second series, pts with combination of IR and low HDL C also had higher ECLT than those with AH: 289±50 vs 247±57 min. In the third series, pts with combination of IR and AO had significantly higher than pts with isolated AH fibrinogen level: 328±109 vs 266±55 mg/dl and FVII activity: 173±74 vs 124±60%. Thus, while in hypertensive pts insulin resistance, hypertriglyceridemia, low HDL C level or abdominal obesity per se were not associated with any changes in hemostasis, the combination of IR even with one of these metabolic factors was accompanied by delayed clot lysis and hypercoagulation due to elevation of FVII activity or fibrinogen level.
•6--•
165
SEVERE HYPOALPHALIPOPROTEINEMIA, IMPAIRED CHOLESTEROL EFFLUX AND INCREASED SUSCEPTIBILITY TO ATHEROSCLEROSIS IN APOA1/C3/A4 KNOCKOUT MICE
H. Mezdour 1, G. Castro 1, J. Fruchart 1, M. Rouis 1, G. Torpier 1, N. Maeda 2.
]Institut Pasteur de Lille, France," 2University of North Carolina at Chapel Hill, NC, USA Human patients with apolipoprotein (apo)AI/CIII/AIV deficiency have very low high-density lipoproteins (HI)L) concentration in plasma and suffer from premature atherosclerosis. The apolipoprotein APOA1/C3/A4 gene cluster have been reported to play a pivotal role in reverse cholesterol transport, a mechanism postulated to prevent peripheral tissues from accumulating excess cholesterol and atherogenesis. To test this hypothesis, we have generated mice lacking APOA1/C3/A4 gene cluster by gene targeting. In homozygous mutant mice (ACA - / - ) fed a chow diet, apolipoprotein AI, CIII and AIV were totally absent from plasma. Fasted plasma total cholesterol (TC), ItDL cholesterol (ItDLc) and triglycerides (TG) in mutants vs wild-type controls were reduced to 20.5±11.2 vs 61.2±13.5 mg/dl (-66.5%), 6.3±2 vs 38.4±9.8 mg/dl (-83.6%) and 41.7±7.8 vs 59.3±14 mg/dl (-29.7%), respectively. On high-fat Western-style (HFW) diet, TC was increased in mutants vs controls to 29.3±11.2 (+42.3%) vs 100.8±42 mg/dl (+64.7%), and ItDLc decreased to 1.8 mg/dl (-71.4%) vs 43.4 (+13%), respectively. Plasma from homozygous mutants showed reduced capacity in promoting cholesterol efflux, in-vitro, to about 26M6%, in Fu5AH hepatoma cell line model, and 65 71% in J774 macrophage cell line model. LCAT activity was also reduced to about 38 55% of controls. Interestingly, preliminary data showed that ACA - / - mutants with 129xB6 mixed genetic background, developed small aortic lesions when fed HFW diet. In conclusion, these results support an essential role of the cluster in ItDL metabolism, and are consistent with a redundancy of function of apoAI and apoAIV in peripheral cholesterol homeostasis. ~--3] LIPID PARAMETERS IN ELDERLY PATIENTS SUFFERING FIRST ACUTE ISCHEMIC STROKE H. Milionis, E. Liberopoulos, G. Miltiadous, C. Tzallas, E. Bairaktari, M. Elisaf. Department of Internal Medicine, Medical School, University of
Ioannina, Greece We analyzed the lipid profile along with other risk factors in elderly patients admitted for nonhemorrhagic stroke. A total of 163 elderly patients (78.1±4.6 years old) (88 men and 75 women) successively hospitalized for first thrombotic stroke were studied in comparison with 166 age and sex-matched healthy volunteers without history of cardiovascular disease. Stroke patients exhibited a more atherogenic lipid profile compared to controls. Specifically, patients and controls had similar serum total cholesterol levels (207.3±48.7 vs 208.1±43.5 mg/dl), LDL cholesterol (132.4±42.3 vs 132.1±45.3 mg/dl), and ApoB levels (131.6±24.3 vs 126.8±25.6 mg/dl). Nevertheless, stroke patients had higher values of triglycerides (174.7 ±74.3 vs 124.8±79.8 mg/dl, p<0.001), and Lp(a) (median value 15.7 vs 7.1 mg/dl, p<0.001), whereas they displayed lower concentrations of HDL cholesterol (40±11.5 vs 51±11.5 mg/dl, p<0.001), and ApoA-I (130±24.3 mg/dl vs 150±22 mg/dl, p<0.001). Furthermore, stroke patients had increased serum uric acid (5.6±1.7 vs 4.8±1.4 mg/dl, p<0.001), and plasma fibrinogen levels (405.8±99.7 vs 305.7±105, p<0.001) compared to controls. In conclusion, elderly patients experiencing first non-hemorrhagic stroke exhibit a more atherogenic lipid profile compared to age and sex-matched subjects without history of prior cardiovascular disease. These patients tend to have higher levels of TG, Lp(a), uric acid and fibrinogen in addition to lower values of HDL-cholesterol and Apo A-I. ~-~
LIPOPROTEIN (A) LEVELS AND APOLIPOPROTEIN (A) ISOFORM SIZE IN PATIENTS W I T H SUBCLINICAL HYPOTHYROIDISM: EFFECT OF TREATMENT W I T H L-THYROXINE
H. Milionis, Z. Efstathiadou, A. Tselepis, C. Tzallas, E. Bairaktari, A. Tsatsoulis, M. Elisaf. Department of Internal Medicine, Medical School,
University of loannina, Greece The increased risk of premature cardiovascular disease (CVD) in patients with subclinical hypothyroidism (SH) has been partly attributed to dyslipidemia. There is limited information with regard to the effect of SH on lipoprotein (a) [Lp(a)], which is considered a significant predictor of CVD. Serum Lp(a) levels are predominantly regulated by apolipoprotein [apo(a)]
73rd EAS Congress