1. SERUM VISFATIN CONCENTRATION IS ASSOCIATED WITH AN ATHEROGENIC METABOLIC PROFILE T.D. Filippatos 1, A. Liontos 1, F. Barkas 1, E. Klouras 1, V. Tsimihodimos 1, M. Georgoula 1, Z. Mitrogianni 1, AD Tselepis 2, MS Elisaf 1 1Department of Internal Medicine, School of Medici1ne, University of Ioannina, Ioannina, Greece 2Laboratory of Biochemistry, Department of Chemistry, University of Ioannina, Ioannina, Greece

2. Background  Human visfatin has been implicated in the pathogenesis of type 2 diabetes mellitus, obesity, dyslipidaemia, and hypertension and generally of atherosclerosis-related diseases.  Controversial results exist regarding the expression, circulating levels and the role of visfatin in the atherosclerosis-related diseases.

3. Aim of the study Aim of the present study was to assess in non-diabetic individuals the association of plasma visfatin levels with cardiovascular disease (CVD) risk and the atherosclerosis - related metabolic variables.

4. Methods (1)  Non-diabetic subjects (n = 179) attending the Outpatient Lipid Clinic of the University Hospital of Ioannina participated in the present study.  No participant had symptomatic ischemic heart disease or any other clinically evident vascular disease (assessed by history, physical examination, electrocardiogram and routine biochemical check). Exclusion criteria  Symptomatic ischemic heart disease or any other clinically evident vascular disease  Abnormal hepatic function (aminotransferase activity > 3 times the upper limit of normal, and/or history of chronic liver disease, such as cirrhosis or alcoholic liver disease)  Impaired renal function (serum creatinine levels > 159 μmol/L, 1.8 mg/dL)  Raised thyroid-stimulating hormone (TSH) levels (> 5.0 μU/L)  Drugs that may interfere with glucose or lipid metabolism.

5. Results (1) Baseline demographic characteristics of study patients N (females/males)179 (107/72) Age, years49 ± 11 (range 27 – 78) Current smokers, %22.3 Body weight, kg82 ± 18 BMI, kg/m 2 31.6 ± 7.7 Waist circumference, cm101 ± 15 Diastolic BP, mm Hg84 ± 10 Systolic BP, mm Hg132 ± 18 Visfatin, ng/ml Tertile 112.2 (7.0 – 16.0) Tertile 219.0 (16.2 – 23.0) Tertile 331.0 (23.6 – 57.0) BMI = body mass index; BP = blood pressure Values are expressed as mean ± SD, except visfatin which is expressed as median (range).

6. Results (2) Ten-year Framingham risk scores for coronary heart disease (CHD), myocardial infarction (MI), stroke and cardiovascular disease (CVD) according to visfatin tertiles Parameter Tertile 1 N = 61 Tertile 2 N = 59 Tertile 3 N = 59 p (ANOVA) CHD (%)5.68.08.8 a 0.02 MI (%)2.54.14.2 a 0.04 STROKE (%)1.22.0 NS CVD (%)8.112.1 a 13.0 a 0.007

7. Results (3) Anthropometric variables according to visfatin tertiles BMI = body mass index a = p < 0.05 vs tertile 1 (post-hoc analysis) b = p < 0.05 vs tertile 2 (post-hoc analysis) Visfatin tertiles

8. Results (4) Blood pressure according to visfatin tertiles SBP = systolic blood pressure; DBP = diastolic blood pressure a = p < 0.05 vs tertile 1 (post-hoc analysis) Visfatin tertiles

9. Results (5) Metabolic variables according to visfatin tertiles Visfatin tertiles

10. Results (6) Anthropometric and biochemical variables according to visfatin tertiles Parameter Tertiles p (ANOVA or χ 2 ) Age (years)47 ± 11 (29 -73)50 ± 11 (27 -78)51 ± 12 (29 -74)NS Gender (females/males) 34/2740/1933/26NS HOMA index1.9 (0.4 – 12.0)2.8 (0.9 – 18.2) a 2.6 (0.9 – 19.8) a 0.01 Uric acid (mg/dl)4.8 ± 1.64.9 ± 1.55.5 ± 1.5 a 0.03 apoE (mg/L)33 ± 1538 ± 1445 ± 27 a 0.01 Lp(a) (mg/L)8.9 (0 -73)10.5 (0 – 113) a 10.5 (0 – 102) a 0.04

11. Results (7) LDL subclasses according to visfatin tertiles

12. Results (8) HDL subclasses according to visfatin tertiles

13. Conclusions Our results support a role for visfatin in the detection of subjects with many metabolic abnormalities, which result in an increased CVD risk.