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The effect of valsartan on the endothelial function of the retinal capillary bed in elderly hypertensive subjects
62A
POSTERS: Cerebrovascular Disease/Stroke
P-82 THE EFFECT OF VALSARTAN ON THE ENDOTHELIAL FUNCTION OF THE RETINAL CAPILLARY BED IN ELDERLY HYPERTENSIVE SUBJECTS Sebastian Oehmer, Joanna Harazny, Christian Delles, Thomas Schwarz, Renate Handrock, Georg Michelson, Roland E. Schmieder. Department of Nephrology, University of Erlangen-Nuernberg, Erlangen, Germany; Department of Ophthalmology, University of Erlangen-Nuernberg, Erlangen, Germany. Background: Arterial hypertension is the major risk factor for stroke. In Patients with known manifestation of hypertensive disease we examined nitric oxide activity in vivo of the retinal vasculature considered as a model of cerebral vasculature. Methods: In an open pilot study 20 elderly patients with arterial hypertension were treated additionally with the AT1- blocker Valsartan (160 mg o.d.) for 8 days. All participants were males, non-smokers, non-diabetics and had no treatment with ACE-inhibitors or other AT1blockers. Perfusion of the central retinal artery and retinal capillary flow was measured before and after treatment. The perfusion of the central retinal artery was assessed with pulsed wave Doppler sonography at rest and during flicker light stimulation which is known to stimulate nitric oxide release. Retinal capillary flow was assessed with scanning laser Doppler flowmetry at rest and following infusion of NG-monomethylL-arginine (L-NMMA), an inhibitor of endothelial NO synthase. Results: At rest perfusion of the central retinal artery and retinal capillary flow were similar before and after treatment with Valsartan. The mean blood flow velocity increased in response to flicker light (p⬍0.001), but this response was similar before and after treatment (⌬17 ⫾33% vs. ⌬27 ⫾ 38 % n.s.). Increase in retinal capillary flow after L-NMMA was not changed by treatment (⌬ 4.7 ⫾ 22 % before and ⌬4.5 ⫾23 % after valsartan, n.s.). The response of retinal capillary flow to L-NMMA depended on the serum LDL cholesterol level of the subjects. The group with LDL above average (⬎136 mg/dl) tended to have an increased response to L-NMMA after Valsartan treatment compared to before treatment ([Delta13 ⫾ 26 %vs. ⌬0.4⫾17 % p⫽0.08) and the change of L-NMMA induced vasoconstiction in the high LDL group before and after treatment differed from that observed in the low LDL group (⌬ ⫺13 ⫾ 20% vs. ⌬12 ⫾16% p⫽0.01). Blood pressure was not a confounding determinant since in the high and low LDL group the change in blood pressure in response to L-NMMA was similar before and after treatment (⌬ 2.4 ⫾ 8.4 mmHg vs. ⌬ ⫺2.1 ⫾ 5.8 mmHg p⫽0.2). Conclusion: Our pilot study suggests that Valsartan improves the basal NO-availability in the retinal capillary bed taken as a mirror of cerebral circulation in hypertensive patients with high LDL. Key Words: Retinal Perfusion, Valsartan, LDL
P-83 THE SIGNIFICANCE OF HYPERTENSION AND LIPIDS ON LATTER THROMBOEMBOLIC STROKE IN GREEK POPULATION Spyridon Paximadas, Stamata Pagoni, Marios Kosmidis, Athanasios Papadimitriou, Nausika Sakarellou. First Deparment of Internal Medicine, General Hospital of Athens ELPIS, Dimitsanis 7, Ampelokipi, Athens, Athens, Greece; Third Department of Internal Medicine, General Hospital of Athens G.GENNIMATAS, Mesogeion 154,, Athens, Athens, Greece. Epidemiological evidence provides that the elevated blood pressure (B.P.) and the increase of lipid levels are associated with significant cardiovascular risk and are established risk factors both for stroke and coronary heart disease. Purpose: The aim of this study was to investigate the exact impact of B.P. and lipidemic profile on patients with latter acute thrombolic or embolic stroke episode in Greek population.
AJH–May 2004 –VOL. 17, NO. 5, PART 2
Material and Methods: 730 inpatients with latter acute thrombolic or embolic stroke episodes, 398 females (F) and 332 males (M) aged 76⫾10 years (40 –100 years) were studied during the last three years. Investigated the lipid profile as Total Cholesterol (TC), Triglycerides (TG), HDL-Cholesterol (HDL-C), and LDL-Cholesterol (LDL-C), relative to B.P. and recorded the presence diabetes mellitus (D.M.). All patients belong to our Internal Medicine Clinic and results were analyzed in the same laboratory. The proportion of death was 17%. Results: 76,5% from all patients had B.P. (52% F - 48% M, p⫽0,435) and 39 % had D.M., while 34,1% were coexistence between B.P. and M.D. and 16,3% were had not B.P. or D.M. (p⫽0,027). The lipid profile of patients with and without B.P., was TC 217⫾47 – 231⫾85 mg/dl (p⫽0,008), TG 129⫾67 – 133⫾64 mg/dl (p⫽0,76), HDL 47⫾14 41⫾10 mg/dl (p⫽0,24) and LDL 145⫾43 – 168⫾89 mg/dl (p⫽,001). Conclusion: The study shows that in patients with latter thromboembolic stroke a) the hypertension there was in more from 3⁄4 of patients and in 3⁄4 of patients was coexistence and D.M. statistically significant, b) the hypertension was similar between females and males and c) the TC and LDL cholesterol were increased statistically significant in patients without blood pressure. Key Words: Hypertension, Lipids, Stroke
P-84 A MOLECULAR VARIANT OF THE AT1R GENE IS A RISK FACTOR FOR ISCHEMIC STROKE IN HYPERTENSIVE SUBJECTS Speranza Rubattu, Emanuele Di Angelantonio, Rosita Stanzione, Bastianina Zanda, Anna Evangelista, Paola De Paolis, Angelo Pirisi, Massimo Volpe. Cardiology, IRCCS Neuromed, Pozzilli (Isernia), Italy; Cardiology, University La Sapienza, 2nd Faculty of Medicine, Rome, Italy; Department of Internal Medicine, University La Sapienza, 1rst Faculty of Medicine, Rome, Italy; Neurology, University of Sassari, Sassari, Italy. The role of the renin angiotensin aldosterone system (RAAS) on predisposition to develop stroke is still under investigation. In the present study we characterized the contributory role of RAAS genes into the individual susceptibility to develop ischemic stroke in a population of 216 cases and 236 controls selected in Sardinia, a large Mediterranean island with a well known segregated population. Presence/absence of cardiovascular risk factors was assessed and the following gene polymorphisms were characterized: AGT M235T, ACE D/I, Ang II type 1 receptor (AT1R) A1166C, Aldosterone synthase/Cyp 11b-T344C. Univariate and multivariate analysis was performed to assess the contribution of each risk factor and of RAAS genes to ischemic stroke. Two predisposing conditions were identified: hypertension (P⫽0.001) and hypercholesterolemia (P⫽0.001). Among the genes tested, a significant association of the AT1R gene with stroke occurrence was found when assuming a dominant mode of transmission (OR⫽1.49, 95% CI 1.02–2.21, P⫽0.004 after adjustment for the predisposing risk factors). Furthermore, in the subgroup of hypertensive subjects (135 cases and 110 controls) a much more significant effect of the AT1R gene molecular variant was found (OR⫽3.4, 95% CI 1.16 –10.07, P⫽0.026 in the recessive model and OR⫽2.1, 95% CI 1.25–3.69, P⫽0.006 in the dominant model of transmission after adjustment for the confounders). Thus, the AT1R gene molecular variant is a significant risk factor for ischemic stroke in our Sardinian population. In particular, its effect appears to be more powerful among the hypertensive patients. Key Words: Ischemic Stroke, Genetic, Angiotensin Receptor
POSTERS: Cerebrovascular Disease/Stroke
P-82 THE EFFECT OF VALSARTAN ON THE ENDOTHELIAL FUNCTION OF THE RETINAL CAPILLARY BED IN ELDERLY HYPERTENSIVE SUBJECTS Sebastian Oehmer, Joanna Harazny, Christian Delles, Thomas Schwarz, Renate Handrock, Georg Michelson, Roland E. Schmieder. Department of Nephrology, University of Erlangen-Nuernberg, Erlangen, Germany; Department of Ophthalmology, University of Erlangen-Nuernberg, Erlangen, Germany. Background: Arterial hypertension is the major risk factor for stroke. In Patients with known manifestation of hypertensive disease we examined nitric oxide activity in vivo of the retinal vasculature considered as a model of cerebral vasculature. Methods: In an open pilot study 20 elderly patients with arterial hypertension were treated additionally with the AT1- blocker Valsartan (160 mg o.d.) for 8 days. All participants were males, non-smokers, non-diabetics and had no treatment with ACE-inhibitors or other AT1blockers. Perfusion of the central retinal artery and retinal capillary flow was measured before and after treatment. The perfusion of the central retinal artery was assessed with pulsed wave Doppler sonography at rest and during flicker light stimulation which is known to stimulate nitric oxide release. Retinal capillary flow was assessed with scanning laser Doppler flowmetry at rest and following infusion of NG-monomethylL-arginine (L-NMMA), an inhibitor of endothelial NO synthase. Results: At rest perfusion of the central retinal artery and retinal capillary flow were similar before and after treatment with Valsartan. The mean blood flow velocity increased in response to flicker light (p⬍0.001), but this response was similar before and after treatment (⌬17 ⫾33% vs. ⌬27 ⫾ 38 % n.s.). Increase in retinal capillary flow after L-NMMA was not changed by treatment (⌬ 4.7 ⫾ 22 % before and ⌬4.5 ⫾23 % after valsartan, n.s.). The response of retinal capillary flow to L-NMMA depended on the serum LDL cholesterol level of the subjects. The group with LDL above average (⬎136 mg/dl) tended to have an increased response to L-NMMA after Valsartan treatment compared to before treatment ([Delta13 ⫾ 26 %vs. ⌬0.4⫾17 % p⫽0.08) and the change of L-NMMA induced vasoconstiction in the high LDL group before and after treatment differed from that observed in the low LDL group (⌬ ⫺13 ⫾ 20% vs. ⌬12 ⫾16% p⫽0.01). Blood pressure was not a confounding determinant since in the high and low LDL group the change in blood pressure in response to L-NMMA was similar before and after treatment (⌬ 2.4 ⫾ 8.4 mmHg vs. ⌬ ⫺2.1 ⫾ 5.8 mmHg p⫽0.2). Conclusion: Our pilot study suggests that Valsartan improves the basal NO-availability in the retinal capillary bed taken as a mirror of cerebral circulation in hypertensive patients with high LDL. Key Words: Retinal Perfusion, Valsartan, LDL
P-83 THE SIGNIFICANCE OF HYPERTENSION AND LIPIDS ON LATTER THROMBOEMBOLIC STROKE IN GREEK POPULATION Spyridon Paximadas, Stamata Pagoni, Marios Kosmidis, Athanasios Papadimitriou, Nausika Sakarellou. First Deparment of Internal Medicine, General Hospital of Athens ELPIS, Dimitsanis 7, Ampelokipi, Athens, Athens, Greece; Third Department of Internal Medicine, General Hospital of Athens G.GENNIMATAS, Mesogeion 154,, Athens, Athens, Greece. Epidemiological evidence provides that the elevated blood pressure (B.P.) and the increase of lipid levels are associated with significant cardiovascular risk and are established risk factors both for stroke and coronary heart disease. Purpose: The aim of this study was to investigate the exact impact of B.P. and lipidemic profile on patients with latter acute thrombolic or embolic stroke episode in Greek population.
AJH–May 2004 –VOL. 17, NO. 5, PART 2
Material and Methods: 730 inpatients with latter acute thrombolic or embolic stroke episodes, 398 females (F) and 332 males (M) aged 76⫾10 years (40 –100 years) were studied during the last three years. Investigated the lipid profile as Total Cholesterol (TC), Triglycerides (TG), HDL-Cholesterol (HDL-C), and LDL-Cholesterol (LDL-C), relative to B.P. and recorded the presence diabetes mellitus (D.M.). All patients belong to our Internal Medicine Clinic and results were analyzed in the same laboratory. The proportion of death was 17%. Results: 76,5% from all patients had B.P. (52% F - 48% M, p⫽0,435) and 39 % had D.M., while 34,1% were coexistence between B.P. and M.D. and 16,3% were had not B.P. or D.M. (p⫽0,027). The lipid profile of patients with and without B.P., was TC 217⫾47 – 231⫾85 mg/dl (p⫽0,008), TG 129⫾67 – 133⫾64 mg/dl (p⫽0,76), HDL 47⫾14 41⫾10 mg/dl (p⫽0,24) and LDL 145⫾43 – 168⫾89 mg/dl (p⫽,001). Conclusion: The study shows that in patients with latter thromboembolic stroke a) the hypertension there was in more from 3⁄4 of patients and in 3⁄4 of patients was coexistence and D.M. statistically significant, b) the hypertension was similar between females and males and c) the TC and LDL cholesterol were increased statistically significant in patients without blood pressure. Key Words: Hypertension, Lipids, Stroke
P-84 A MOLECULAR VARIANT OF THE AT1R GENE IS A RISK FACTOR FOR ISCHEMIC STROKE IN HYPERTENSIVE SUBJECTS Speranza Rubattu, Emanuele Di Angelantonio, Rosita Stanzione, Bastianina Zanda, Anna Evangelista, Paola De Paolis, Angelo Pirisi, Massimo Volpe. Cardiology, IRCCS Neuromed, Pozzilli (Isernia), Italy; Cardiology, University La Sapienza, 2nd Faculty of Medicine, Rome, Italy; Department of Internal Medicine, University La Sapienza, 1rst Faculty of Medicine, Rome, Italy; Neurology, University of Sassari, Sassari, Italy. The role of the renin angiotensin aldosterone system (RAAS) on predisposition to develop stroke is still under investigation. In the present study we characterized the contributory role of RAAS genes into the individual susceptibility to develop ischemic stroke in a population of 216 cases and 236 controls selected in Sardinia, a large Mediterranean island with a well known segregated population. Presence/absence of cardiovascular risk factors was assessed and the following gene polymorphisms were characterized: AGT M235T, ACE D/I, Ang II type 1 receptor (AT1R) A1166C, Aldosterone synthase/Cyp 11b-T344C. Univariate and multivariate analysis was performed to assess the contribution of each risk factor and of RAAS genes to ischemic stroke. Two predisposing conditions were identified: hypertension (P⫽0.001) and hypercholesterolemia (P⫽0.001). Among the genes tested, a significant association of the AT1R gene with stroke occurrence was found when assuming a dominant mode of transmission (OR⫽1.49, 95% CI 1.02–2.21, P⫽0.004 after adjustment for the predisposing risk factors). Furthermore, in the subgroup of hypertensive subjects (135 cases and 110 controls) a much more significant effect of the AT1R gene molecular variant was found (OR⫽3.4, 95% CI 1.16 –10.07, P⫽0.026 in the recessive model and OR⫽2.1, 95% CI 1.25–3.69, P⫽0.006 in the dominant model of transmission after adjustment for the confounders). Thus, the AT1R gene molecular variant is a significant risk factor for ischemic stroke in our Sardinian population. In particular, its effect appears to be more powerful among the hypertensive patients. Key Words: Ischemic Stroke, Genetic, Angiotensin Receptor