Differential effects on aortic segments could provide novel insights into the pathophysiology of increased arterial stiffness in CKD and potentially in various disease states. The powerful prognostic significance of increased arterial stiffness is well recognized [3,5], Failure to buffer adequately intermittent left ventricular ejection into the arterial system results in left ventricular hypertrophy and fibrosis, cerebrovascular disease and further renal damage [3,5]. Many potential mechanisms have been postulated to contribute to the increased arterial stiffness associated with CKD [3]. Our results suggest that past infection with CMV may be a potentially modifiable CV risk factor. The effects of CMV on arterial wall function might be mediated via actions within the arterial media, either by changing VSMC properties or by causing inflammation and fibrosis. Histopathological studies have reported evidence of CMV particles in the whole human vascular tree in CMV seropositive patients [20?4]. Vascular smooth muscle cells can be infected by CMV leading to aCMV Seropositivity and Arterial StiffnessTable 2. Patient demographics for 60 patient pairs matched for gender and age.CMV positive n = 60 Male ( ) Age (years) eGFR (ml/min/1.73 m2) hsCRP (mg/mL)* Brachial SBP (mmHg) Brachial DBP (mmHg) Central 
SBP (mmHg) Central DBP (mmHg) 24-hour SBP (mmHg) 24-hour DBP (mmHg) AIx ( ) AIx75 ( ) PWV (m/s) Ascending AoD (61023 mmHg21) Proximal descending AoD (61023 mmHg21) Distal descending AoD (61023 mmHg21) 26 (43) 5569 50617 2.68 (1.01?.62) 132620 76610 124620 77610 124612 7469 31612 26610 9.262.1 2.2461.59 2.8361.34 3.8361.CMV negative n = 60 26 (43) 5569 50616 1.39 (0.50?.52) 12761 7569 118615 7669 122611 7368 2769 2269 8.261.3 2.6661.56 3.5261.44 4.8662.P 1.0 1.0 1.0 0.2 0.1 0.4 0.07 0.4 0.2 0.6 0.04 0.02 0.03 0.2 0.01 0.*log transformed before analysis. CMV, cytomegalovirus; eGFR, estimated glomerular filtration rate; hsCRP, high sensitive C-reactive protein; SBP, systolic blood pressure; DBP, diastolic blood pressure; AIx, augmentation index; AIx75, augmentation index Epigenetic Reader Domain adjusted to heart rate of 75 bpm; PWV, pulse wave velocity; AoD, aortic distensibility. doi:10.1371/journal.pone.0055686.tTable 3. Multiple stepwise regression analysis for (A) pulse wave velocity, (B) ascending aortic distensibility, (C) proximal descending aortic distensibility and (D) distal descending aortic distensibility.Unstandardised Epigenetics coefficients B (A) Pulse wave velocity (adjusted R2 for model 0.49) Age (years) Central PP (mmHg) CMV seropositivity 0.01 0.05 0.67 0.01 0.01 0.31 SEStandardised coefficients bTP0.49 0.29 0.7.64 4.54 2.,0.001 ,0.001 0.Independent variables: age, central PP, CMV seropositivity (yes = 1), eGFR, log PTH, log ACR, log hsCRP (B) Ascending aortic distensibility (adjusted R2 for model 0.54) Age (years) Central PP (mmHg) Gender 20.09 20.03 0.59 0.01 
0.01 0.28 20.61 20.20 0.15 27.94 22.63 2.16 ,0.001 0.01 0.Independent variables: age, central PP, CMV seropositivity (yes = 1), gender (male = 1), serum calcium (C) Proximal descending aortic distensibility (adjusted R2 for model 0.33) Age (years) Central PP (mmHg) CMV seropositivity 20.05 20.02 20.55 0.01 0.01 0.02 20.39 20.22 20.17 25.64 23.27 22.73 ,0.001 0.001 0.Independent variables: age, central PP, CMV seropositivity (yes = 1), log hsCRP (D) Distal descending aortic distensibility (adjusted R2 for model 0.31) Age (years) Central PP (mmHg) CMV seropositivity 20.05 20.04 20.74 0.01 0.01 0.27 20.33 20.27.Differential effects on aortic segments could provide novel insights into the pathophysiology of increased arterial stiffness in CKD and potentially in various disease states. The powerful prognostic significance of increased arterial stiffness is well recognized [3,5], Failure to buffer adequately intermittent left ventricular ejection into the arterial system results in left ventricular hypertrophy and fibrosis, cerebrovascular disease and further renal damage [3,5]. Many potential mechanisms have been postulated to contribute to the increased arterial stiffness associated with CKD [3]. Our results suggest that past infection with CMV may be a potentially modifiable CV risk factor. The effects of CMV on arterial wall function might be mediated via actions within the arterial media, either by changing VSMC properties or by causing inflammation and fibrosis. Histopathological studies have reported evidence of CMV particles in the whole human vascular tree in CMV seropositive patients [20?4]. Vascular smooth muscle cells can be infected by CMV leading to aCMV Seropositivity and Arterial StiffnessTable 2. Patient demographics for 60 patient pairs matched for gender and age.CMV positive n = 60 Male ( ) Age (years) eGFR (ml/min/1.73 m2) hsCRP (mg/mL)* Brachial SBP (mmHg) Brachial DBP (mmHg) Central SBP (mmHg) Central DBP (mmHg) 24-hour SBP (mmHg) 24-hour DBP (mmHg) AIx ( ) AIx75 ( ) PWV (m/s) Ascending AoD (61023 mmHg21) Proximal descending AoD (61023 mmHg21) Distal descending AoD (61023 mmHg21) 26 (43) 5569 50617 2.68 (1.01?.62) 132620 76610 124620 77610 124612 7469 31612 26610 9.262.1 2.2461.59 2.8361.34 3.8361.CMV negative n = 60 26 (43) 5569 50616 1.39 (0.50?.52) 12761 7569 118615 7669 122611 7368 2769 2269 8.261.3 2.6661.56 3.5261.44 4.8662.P 1.0 1.0 1.0 0.2 0.1 0.4 0.07 0.4 0.2 0.6 0.04 0.02 0.03 0.2 0.01 0.*log transformed before analysis. CMV, cytomegalovirus; eGFR, estimated glomerular filtration rate; hsCRP, high sensitive C-reactive protein; SBP, systolic blood pressure; DBP, diastolic blood pressure; AIx, augmentation index; AIx75, augmentation index adjusted to heart rate of 75 bpm; PWV, pulse wave velocity; AoD, aortic distensibility. doi:10.1371/journal.pone.0055686.tTable 3. Multiple stepwise regression analysis for (A) pulse wave velocity, (B) ascending aortic distensibility, (C) proximal descending aortic distensibility and (D) distal descending aortic distensibility.Unstandardised coefficients B (A) Pulse wave velocity (adjusted R2 for model 0.49) Age (years) Central PP (mmHg) CMV seropositivity 0.01 0.05 0.67 0.01 0.01 0.31 SEStandardised coefficients bTP0.49 0.29 0.7.64 4.54 2.,0.001 ,0.001 0.Independent variables: age, central PP, CMV seropositivity (yes = 1), eGFR, log PTH, log ACR, log hsCRP (B) Ascending aortic distensibility (adjusted R2 for model 0.54) Age (years) Central PP (mmHg) Gender 20.09 20.03 0.59 0.01 0.01 0.28 20.61 20.20 0.15 27.94 22.63 2.16 ,0.001 0.01 0.Independent variables: age, central PP, CMV seropositivity (yes = 1), gender (male = 1), serum calcium (C) Proximal descending aortic distensibility (adjusted R2 for model 0.33) Age (years) Central PP (mmHg) CMV seropositivity 20.05 20.02 20.55 0.01 0.01 0.02 20.39 20.22 20.17 25.64 23.27 22.73 ,0.001 0.001 0.Independent variables: age, central PP, CMV seropositivity (yes = 1), log hsCRP (D) Distal descending aortic distensibility (adjusted R2 for model 0.31) Age (years) Central PP (mmHg) CMV seropositivity 20.05 20.04 20.74 0.01 0.01 0.27 20.33 20.27.