Vascular Resistance (units) Insulin Resistance Impairs Arterial Stiffness and Peripheral Vascular Resistance in Metabolic Syndrome Patients Program Nº:652.16 Abstract Nº: 7226 Besides autonomic alterations, metabolic syndrome (MetS) causes changes in the vascular system directly related to cardiovascular events and death. Since insulin resistance is strongly associated with sympathetic hiperactivation, we tested the hypothesis that the presence of impaired fasting glucose (IFG) is the main cause of structural and functional worsening on large and small vessels. Never treated, newly diagnosed MetS (ATP-III) patients were divided into: fasting glucose >100mg/dL (MetS+IFG, n=28, 49.1±1.3 yrs) and fasting glucose <100mg/dL (MetS-IFG, n=22, 46.1±1.4 yrs). A healthy control group was also involved (C, n=17, 49.6±1.4 yrs). We measured the arterial stiffness (PWV, pulse wave velocity), muscle sympathetic nerve activity (MSNA, microneurography), forearm blood flow (plethysmography), mean blood pressure (MBP, oscillometric), and peripheral vascular resistance (VR=MBP/forearm blood flow). MetS+IFG had similar PWV vs. MetS-IFG, but had higher PWV than C (9.6±0.3, 9.1±0.2, and 8.7±0.2, P=0.02). Similarly, MetS+IFG had no different VR vs. MetS-IFG, albeit had higher VR vs. C group (72.1±3.9, 57.5±5.4 and 47.4±9.2, P=0.01). Further analysis showed that PWV was correlated with MSNA (R=0.47; P<0.01). In conclusion, sympathetic hyperactivation may be, at least partially, the base mechanism that increase arterial stiffness. Impaired fasting glucose appears to be the main factor to aggravate the cardiovascular risk in metabolic syndrome patients. Acknowledgements This study was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP# 2011/17533-6 ) and, in part, by Fundação Zerbini. Sara Rodrigues was supported by FAPESP# 2013/15323-0. Carlos Eduardo Negrão, Maria U.P.B. Rondon and Edgar Toschi-Dias were supported by Conselho Nacional de Pesquisa (CNPq # 301867/2010-0, # 308068/2011-4 and #140643/2009-5 respectively). Ivani C Trombetta was supported by Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP #2008/03714-6) and Cristiane Maki-Nunes and Felipe X Cepeda were supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior-CAPES. INTRODUCTION Besides autonomic alterations, metabolic syndrome (MetS) causes changes in the vascular system directly related to cardiovascular events and death. Insulin resistance is strongly associated with sympathetic hyperactivation and both are associated with vascular damage. METHODS OBJECTIVE We tested the hypothesis that the presence of impaired fasting glucose (IFG) is the main cause of structural and functional worsening on large and small vessels. RESULTS Conclusion Sympathetic hyperactivation may explain, at least partially, the increased arterial stiffness. Impaired fasting glucose appears to be the main factor to aggravate the cardiovascular risk in metabolic syndrome patients. Sara Rodrigues1, Felipe X Cepeda MS1, Akothirene CB Dutra-Marques1, Jefferson C Carvalho1, Edgar Toschi-Dias PhD1, Cristiane Maki-Nunes PhD1, Luiz A Bortolotto MD PhD1, Valéria Costa-Hong PhD1, Maria Urbana PB Rondon PhD1,2, Maria Janieire NN Alves MD PhD1, Carlos Eduardo Negrão PhD1,2, Ivani C Trombetta PhD1,3 1 Heart Institute (InCor), University of São Paulo Medical School, São Paulo, SP, Brazil. 2 School of Physical Education and Sports, University of São Paulo, São Paulo, SP, Brazil. 3 Universidade Nove de Julho (UNINOVE), São Paulo, SP, Brazil. MSNA vs. PWV Screening MetS n=50 MetS+IFG n=28 MetS-IFG n=22 C n=17 MetS= metabolic syndrome; IFG= impaired fasting glucose ≥ 100mg/dL; M= male; F= female; BMI= body mass index; SBP= systolic blood pressure; DBP= diastolic blood pressure; WC= waist circumference; HDL-c= high density level cholesterol; MSNA= muscle sympathetic nerve activity *P<0.05 vs. C † P<0.05 vs. MetS-IFG MetS: According to ATPIII MetS+IFG: MetS patients with fasting glucose ≥100mg/dL MetS-IFG: MetS patients with fasting glucose <100mg/dL C: Control healthy subjects Arterial stiffness - pulse wave velocity (PWV ) Muscle sympathetic nerve activity (MSNA) - microneurography Peripheral vascular resistance (VR) VR=MBP/forearm blood flow Mean blood pressure (MBP)- oscillometric Forearm blood flow - plethysmography Control healthy nerve MetS +IFG patient nerve MetS -IFG patient nerve 10 20 30 40 50 60 70 80 1 2 3 *P < 0.05 VASCULAR RESISTANCE VASCULAR RESISTANCE - IFG * Vascular Resistance (units) N=28 N=22 N=17 GENDER (M/F) (14/14) (7/15) (6/11) AGE (years) 49 ± 46 BMI (kg/m ) 33 1* 32 27 SBP (mmHg) 125 2 * 131 2* 111 DBP 81 83 WC (cm) 106 105 95 HDL c (mg/dL) 44 42 58 4 TR IGLYCERIDES 158 14* 186 15* 98 17 GLUCOSE † 93 92 MSNA (bursts/min) 26 18