102 lvarez-Sala Miscellaneous activator, fenofibrate (15 mg/day) during 8 weeks and then endothelium- dependent relaxations of aorta and small mesenteric arteries (SMA) were studied. Concentrations of cholesterol, LDL and triglycerides in plasma were significantly reduced after treatrnent with fenofibrate. Fenofibrate treatrnent improved endothelium-dependent vasodilatation in the SMA whereas it leduced this response in the aorta fi'om aged rats. In resistance m'teries fi'om aged rats a greater paa'ticipation of endothelial vasoconstrictor products fi'om cyclo-oxygenase (COX), sensitive to COX-1 and COX-2 and acting on Tp receptor was chm'acterised. The improvement of endothelial function after treatrnent with fenofibrate was linked to a decrease in the generation of these COX products. Also in the SMA, the endothelial NO mediated vasodilatation was significantly enhanced upon fenofibrate treatment. Sua: prisingly, the specific inhibitor of the inducible NO synthase, compound 1400w, potentiated acetylcholine-induced relaxation in control. This effect of compound 1400w was blunted in SMA fi'om fenofibrate-treated rats. In- terestingly, the combined addition of the superoxide anion and the hydrogen peroxide scavengers, SOD and catalase increased relaxation to acetylcholine in the SMA taken fi'om control, but not in that fi'om fenofibrate-treated rat. The plesent study suggests that fenofibrate improves endothelial function in resistance arteries fi'om aged rats by both enhancing NO vasodilatation and decleasing COX products. These effects were associated with increased anti-oxidant capacity of the vessel wall. M•-.4•] LIPID PROFILE AND NUMBER OF CARDIOVASCULAR RISK FACTORS (CVRF) IN THE PREVENCAT STUDY L. lvarez-Sala, J. Ord ez, T. Mantilla, L. Ruilope, R. Gomis, E. Esmatjes, C. Su fez, J. Banegas. Hospital Gregorio Mara n, EAP Mar B ltico y Hortaleza, Servicio de Nefrolog a, Hospital 12 de Octubre, Hospital La Princesa, Dpto. Medicina Preventiva y Salud P blica, Facultad de Medicina, Universidad Aut noma de Madrid, Madrid; Hospital de la Santa Creu i Sant Pau, Hospital CI nic i Provincial, Barcelona, Spain Objective: To assess the relationship between lipid profile (LP) and the CVRF in the PREVENCAT study. Methods: Cross-sectional study with 267 participating physicians fi'om l:h'imary Care in Spain, who recruited the first ten consecutive attending patients with previously known hypertension, diabetes and/or hypercholes- terolemia as CVRF, which also included cuaxent smoking, obesity (BMI> 25 kg/m2) and sedentmism. Simple lineal" regression was used to investigate the dependence of LP values on the number of CVRF (nCVRF). The Cochrane-Arrnitage trend test was used to assess the relationship between nCVRF and the fi'equency of drug treatrnent. Results: 2649 patients, aged 64 (11) yem's, 52.0% female and 24% with previous CHD history, were recruited. There were 254 patients with 1 (9.6%), 701 with 2 (26.4%), 871 with 3 (32.9%), 580 with 4 (21.9%), 223 with 5 (8.4%) and 20 with 6 CVRF (0.8%), respectively. Mean total cholesterol incleased fi'om 212 if nCVRF was =1 to 226 mg/dl when nCVRF=6 (p<0.0001 for trend), similaa'ly mean LDL-cholesterol increased fi'om 133 in the nCVRF=I category to 144 mg/dl among patients with nCVRF=6 (p<0.0086). Mean HDL-cholesterol ranged fi'om 57 in the nCVRF=I category to 44 mg/dl in patients with nCVRF=6 (p<0.0001). Median tryglicerides ranged fi'om 100 in the nCVRF=I category to 197 mg/dl in patients with nCVRF=6 (p<0.0001). In the hypercholesterolemic patients subset, the fi'equency of lipid-lowering drug treatrnent increased fi'om 69% in nCVRF=I to 95% in nCVRF=6 (p=0.0018). Conclusions: The lipid profile worsened, whereas the fi'equency of lipid-lowering drug treatrnent increased depending on the nCVRF. Acknowledgments to the PREVENCAT Study Group. •] PREECLAMPSIA AS A RISK FACTOR OF CORONARY HEART DISEASE: INVOLVEMENT OF OXIDATIVE STRESS ? F. Amraei-Davijani, B. Schauf, H. Heinle. Institute of Physiology, Clinics of Gynecology, University o f T bingen, T bingen, Germany Objectives: Ca. 5% of all pregnancies show preeclampsia and it is known that preeclampsia is an important risk factor for heart and cfl'culatory diseases apart fi'om hyperlipidemia, diabetes, adipositas and smoking. Therefore it is interesting whether oxidative stress in plasma can be detected in preeclampsia. Methods: Total flee radical trapping antioxidant potential (TRAP) by measurement of the luminol-enhanced chemiluminescence of the AAPH [2,21-azobis(2-amidinopropane)hydrochloride] leaction, the concentration of malondialdehyde (MDA) after reaction with thiobm'bituric acid, and the concentration of nitrite/nitrate were determined in lithium-hepm'in-plasma of healthy pregnant women (nl= 18) and in patients with preeclampsia (n2=17). Results: The peak intensity of the AAPH-reaction, which is more indica- tive for oxidative stress, is lower in the patients compm'ed to healthy subjects, whereas TRAP is increased in plasma. The concentration of nitrite/nitrate was increased in plasma of preeclamptic women as compared to the control group, the same is valid for the concentration of MDA. Conclusion: Although the AAPH-reaction shows incleased TRAP, prob- ably due to increased plasma levels of uric acid, which indicates impafl-ed function of the kidney, MDA and the peak intensity of AAPH-reaction reveal significant symptoms of oxidative stress under preeclampsia. The increased nitrite/nitrate concentration could be explained either by reduced renal clemence or by increased compensatory endothelial mechanisms and should be studied in further experiments. ~ FLUVASTATIN SLOWS PROGRESSION OF ATHEROSCLEROSIS AND LEFT VENTRICULAR HYPERTROPHY IN DYSLIPIDEMIC HYPERTENSIVE MEN: THE HYPERTENSION HIGH RISK MANAGEMENT TRIAL (HYRIM) S. Anderssen, A. Hjelstuen, I. Holme, K. Bjerkan, I. Hjermann. Center of Preventive Medicine and Department of Cardiology, Ullev l University Hospital, Oslo, Norway Background: Hypertension and dyslipidemia are common co-morbidities that lead to increased cardiovascular complications via atherosclerosis and left ventricular hypertrophy (LVH). The Hypertension High Risk Manage- ment trial (HYRIM) is the first study to assess the effects of statin and lifestyle intervention in drug-treated hypertensive patients. Methods: HYRIM was a randomized, 2x2 factorial controlled trial. A total of 568 male drug-treated hypertensives aged 40-74 years with total cholesterol 4.5-8.0 mmol/L (174-308 mg/dL), triglycerides < 4.5 mmol/L (398 mg/dL), body mass index 25-33 kg/m2, and a sedentary lifestyle were randomized to receive either fluvastatin, 40 mg daily, or placebo (double- blind), and either intensive lifestyle intervention (structured physical activity and diet) or usual care (single-blind). The study primary endpoint was the 4-year change in carotid intima-media thickness (IMT) assessed by B-mode ultrasound imaging. Results: In the usual care population, fluvastatin reduced 4-year pro- gression of carotid IMT as compared with placebo (-0.29 ram, 95% CI -0.055, -0.003; P = 0.0297). Fluvastatin treatment with or without lifestyle intervention also reduced the 2-year development of LVH compared with placebo (P = 0.014). Fluvastatin was well tolerated. Lifestyle intervention had no significant effect on carotid IMT or LVH in either the fluvastatin or placebo groups. In contrast with fluvastatin, achieving long-term adherence to lifestyle intervention programs is difficult, and this may explain the results. Condusions: In drug-tleated hypertensive patients in a usual care setting, fluvastatin treatment reduces progression of atherosclerosis (IMT) and LVH. • GALLIC ACID IS A POTENT ANTAGONIST OF P-SELECTIN: IMPLICATIONS FOR THE FRENCH PARADOX C. Appeldoorn, A. Bonnefoy, B. Lutters, K. Daenens, T. van Berkel, M. Hoylaerts, E. Biessen. LACDR, Leiden University, Center for Molecular and Vascular Biology, University of Leuven, Leiden, The Netherlands Current paradigm attributes the 'French paradox' to the high anti-oxidant and anti-inflammatory activity of red wine polyphenols, but the actual mech- anism underlying such anti-inflammatory activity remains elusive. We have investigated whether P-selectin, a key molecule in the initial development of atherosclerosis, plays a role in this phenomenon by acting as polyphenol receptor. In vitro, gallic acid, an abundant red wine polyphenol, appeared to antagonize P-selectin binding in two different competition assays (IC50 = 7-85 I~M). Under dynamic flow conditions, gallic acid attenuated the rolling of PSGL-1 expressing HL60 macrophages over P-selectin trans- fected CHO cells, while increasing the P-selectin dependent rolling velocity of human blood leukocytes over a platelet monolayer at dietary relevant concentrations. Gallic acid inhibited TRAP induced platelet aggregation in a dose-dependent fashion to up to 90% at 500 I~M. The use of gallic acid in vivo in animal models of platelet-assisted inflammation revealed that gallic 74th EAS Congress, 17-20 April 2004, Seville, Spain