1. Inflammation, arterial stiffness and vascular events in patients on renal replacement therapy Vaia D.Raikou 1st Dpt of Medicine - Propaedaetic, National & Kapodistrian University of Athens, School of Medicine. General Hospital LAΪKO, ΑΤΗΕΝS, GREECE

2. Background Chronic inflammation and arterial stiffness contribute to enhanced cardiovascular morbitity and mortality of patients with chronic renal failure. Chronic inflammation and arterial stiffness contribute to enhanced cardiovascular morbitity and mortality of patients with chronic renal failure. Cardiovascular complications (heart failure, coronary disease, cerebrovascular events, peripheral vascular disease) have underlying disease Cardiovascular complications (heart failure, coronary disease, cerebrovascular events, peripheral vascular disease) have underlying disease 1. Left ventricular hypertrophy (LVH), 2. Plaque formation, 3. Arterial stiffening, 4. Endothelial dysfunction and 5. inflammation

3. Aim The consideration of the relationship between inflammatory and cardiovascular derangements in patients on different hemodialysis (HD) modalities The consideration of the relationship between inflammatory and cardiovascular derangements in patients on different hemodialysis (HD) modalities

4. Subjects and Methods We studied 96 dialyzed patients, (62 males/34 females), on mean age 62,1 14,27 years old. Treatment modalities : 34 HD, 42 HDF και οι 20 CAPD Treatment modalities : 34 HD, 42 HDF και οι 20 CAPD Treatment duration : median hemod. time : 5 ± 3-10 years Treatment duration : median hemod. time : 5 ± 3-10 years mean time on PD : 2,8 ± 1,61 years mean time on PD : 2,8 ± 1,61 years Coronary disease : n=30 (31,3%) Coronary disease : n=30 (31,3%) Heart failure (injection fraction 50%) : n=26 (27,1%) Heart failure (injection fraction 50%) : n=26 (27,1%) Peripheral vascular disease : n=39 (40,6%) Peripheral vascular disease : n=39 (40,6%) LVH (LVMI 125g/m 2 for males and 110g/m 2 for females) : n=54 (56,3%) LVH (LVMI 125g/m 2 for males and 110g/m 2 for females) : n=54 (56,3%) Smoking : n=21 (21,9%) Smoking : n=21 (21,9%)

5. Laboratory parameters Kt/V for urea, nPCR, BMI Kt/V for urea, nPCR, BMI β2-microglobulin (β2M) serum levels by radioimmunoassay β2-microglobulin (β2M) serum levels by radioimmunoassay Removal of β2Μ by Κt/V for β2Μ (only in hemodialyzed patients) Removal of β2Μ by Κt/V for β2Μ (only in hemodialyzed patients) Cholesterol, triglycerides, HDL, LDL, cholesterol/HDL Cholesterol, triglycerides, HDL, LDL, cholesterol/HDL Na+ removal (hemodialysis) : percent sodium removal (PSR) : (Na+pre - Na+ post / Na+pre ) x 100. Na+ removal (hemodialysis) : percent sodium removal (PSR) : (Na+pre - Na+ post / Na+pre ) x 100. Na+ removal (peritoneal dialysis) : Na+ removal (peritoneal dialysis) : Na rem = C Na,end x V D,end - M Na (0) Na rem = C Na,end x V D,end - M Na (0) PE-test : n=15 high transporters, n=5 low transporters PE-test : n=15 high transporters, n=5 low transporters Monocyte chemoattractant protein-1 (MCP-1) serum levels by ELISA Monocyte chemoattractant protein-1 (MCP-1) serum levels by ELISA hsCRP serum levels by ELISA hsCRP serum levels by ELISA Insulin resistance was calculated by HOMA-IR Insulin resistance was calculated by HOMA-IR

6. Hemodynamic parameters ΗΚΓ ΗΚΓ Echocardiographic examination Echocardiographic examination carotid-femoral pulse wave velocity (c-f PWV) and carotid augmentation index (AIx) using SphygmoCor system® carotid-femoral pulse wave velocity (c-f PWV) and carotid augmentation index (AIx) using SphygmoCor system® Central systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean blood pressure (cMBP) and pulse pressure (PP) Central systolic blood pressure (cSBP), diastolic blood pressure (cDBP), mean blood pressure (cMBP) and pulse pressure (PP) Peripheral SBP, DBP and MBP (systolic BP + diastolic BP)/2. Peripheral SBP, DBP and MBP (systolic BP + diastolic BP)/2. Unkle-brachial blood pressure index using Doppler (ΑΒΡΙ < 0,9 ) Unkle-brachial blood pressure index using Doppler (ΑΒΡΙ < 0,9 )

7. RESULTS Characteristicminimummaximum Mean or median ±SD or IR Age (years) 2487 62,1 ± 14,27 Haemodialysis duration (years) 0,527 6.3 ± 5.6 Body mass index ( Kg/m2 ) 18,143,5 25,08 ± 3,86 beta2-microglobulin ( mg/L ) 8,29138 25,98 ± 16,1 – 32,77 K t/V for b2M in hemodialysis - 1,08 2,78 0,89 ± 0,83 Kt/V for urea (n=96) 0,813,63 1,51 ± 0,50 nPCR, g /Kg /day ) (n=96) nPCR, g /Kg /day ) (n=96)0,974,31 2,28 ± 0,67 Urine volume ( ml / day ) 1001500 119.47 ± 242.4 cholesterol ( mg / dl ) 90,0398 163,4 ± 45,35 Triglycerides ( mg / dl ) 49445 172,15 ± 87,12 Chol / HDL 1,848,47 3,97 ± 3,36 – 5,02 HOMA-IR1.050.88 5.86 ± 6.68 hsCRP ( mg/L) 0.1221.35 8.65 ± 5.96 Monocyte chem protein 1 (MCP-1, pg/ml) 45.5866.4 278.55 ± 170.56

8. RESULTS Characteristicminimummaximum Mean or median ±SD or IR Percent sodium removal (PSR,%) - 3,73 7,69 2,14 ± 0,73 – 2,86 Sodium removal in perit dial (mmol) 98,90235.90 184.27 ± 41.08 Albumin (gr/dl) 1.404.6 3.88±0.44 SBP (mmHg) 80.0192.0 131.69±23.76 DBP (mmHg) 55.0100.0 80.86±10.52 MBP (mmHg) 67.50146.0 106.28±16.16 c-f PWV (m/s) c-f PWV (m/s)8,315,2 11,29 ± 1,87 Pulse pressure ( PP, mmHg ) 20118 57,17 ± 20,55 ABPI0.162.18 1.088 ± 0.43

9. Patients with coronary dis (n=30) Patients without coronary dis. (n=66) Patients with peripheral vascular dis. (n=39) Patients without peripheral vascular dis. (n=57) Age (years) 68,9±10,36 * 59,0±14,764,3±12,0660,5±15,5 Sex (M / F) 20 / 10 42 / 24 26 / 13 36 / 21 36 / 21 Dial.duration (years) 6,2± 4,5 6,37 ± 6,14 6,5±6,026,21±5,45 BMI 24,8 ± 2,6 25,16 ± 4,32 25,5±4,524,7±3,33 Kt / V 1,45 ± 0,53 1,53 ± 0,47 1,42±0,401,56±0,53 Logbeta2M 1,49 ± 0,29 1,38 ± 0,24 1,42±0,241,42±0,27 Smoking (%) 7 (23,3%) 14 (21,2%) 10 (25,6%) 11 (19,2%) Hypertension (%) 14 (46,6%) 26 (39,3%) 15 (38,46%) 25 (43.8%) c-fPWV 12,25±1,73 * 10,84±1,77 11,81±1,93 * 10,92±1,75 AIx 25,06±1,94 * 23,76±2,44 24,7±2,27 * 23,77±2,36 PP 64,13±21,8 * 54,01±19,3 62,46±23,8 * 53,5±17,2 ABPI1,08±0,461,09±0,411,05±0,461,11±0,40 Cholesterol (mg/dl) 168,0±47,4153,16±39,2165,12±46,9160,9±43,3 Triglycerides (mg/dl) 182,2±91,0150,03±74,6174,7±93,8168,3±77,3 HDL (mg/dl) 38,13±9,940,56±9,0938,3±9,6139,6±9,87 LDL (mg/dl) 93,4±38,783,9±33,291,7±39,0388,62±34,7 * p < 0.05 vs patients with coronary or peripheral vascular disease

10. Differences between groups of dialyzed patients with vs without left ventricular hypertrophy, with vs without heart failure and with vs without peripheral vascular disease

11. Bivariate Correlations of c-fPWV, PP, hsCRP and MCP-1 with other variables

12. Correlation between hsCRP serum levels and c-f PWV in hemodialysis patients (n=76)

13. Collinearity statistics for the association between c-fPWV and age, PP and hsCRP

14. Association between coronary disease and cfPWV after adjustment for age, hsCRP and beta2M

15. Impact of beta2M levels on coronary disease after adjustment for lipid levels and cfPWV BS.E.WalddfSig.Exp(B) 95% C.I.for EXP(B) Lowe r Upper Step 1 a logb2m1,780,8973,9361,0475,9311,02234,431 Chol / HDL -,563,2246,3191,012,570,367,883 Constant-,9851,473,4471,504,373 BS.E.WalddfSig.Exp(B) 95% C.I.for EXP(B) LowerUpper Step 1 a logb2m1,707,9843,0121,0835,515,80237,929 Chol / HDL -,614,2366,7591,009,541,341,860 cfPWV,444,1508,7621,0031,5581,1622,090 Constant-5,7232,2196,6541,010,003

16. Impact of beta2M levels on LVH after adjustment for PP, c-fPWV, dialysis modality and dialysis duration BS.E.WalddfSig.Exp(B) 95% C.I.for EXP(B) LowerUpper Step 1 a logb2m2,6561,1405,4241,02014,2401,523133,126 PP,030,0154,1151,0421,0311,0011,061 cfPWV-,112,148,5741,448,894,6691,194 Dialysismodality-,112,337,1111,739,894,4611,731 Dialysisduration,017,046,1341,7151,017,9301,112 Constant-3,7602,0213,4631,063,023

17. p=0.01

18. p = NS

19. Conclusions hsCRP, as an inflammatory marker, associated with beta2-microglobulin levels, may contribute in arterial stiffness defined by high c-fPWV in patients on renal replacement therapies especially with coronary disease hsCRP, as an inflammatory marker, associated with beta2-microglobulin levels, may contribute in arterial stiffness defined by high c-fPWV in patients on renal replacement therapies especially with coronary disease Despite pulse pressure is particularly influenced by hydration status, acts as independent factor on increased cfPWV in compination with the age and hsCRP. Despite pulse pressure is particularly influenced by hydration status, acts as independent factor on increased cfPWV in compination with the age and hsCRP. MCP-1 was mainly associated with lipid levels. MCP-1 was mainly associated with lipid levels.

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