4 International Journal of Nephrology Table 2: Clinical characteristics of the study subjects classiﬁed by the presence/absence of proteinuria. Pro (+) Pro (−) P-value eGFR < 60 eGFR ≥ 60 P value Number 65 2179 48 2196 Age (y) 43 ± 10 44 ± 9 .69 54 ± 8 44 ± 9 <.01 Height (cm) 172 ± 6 172 ± 6 .21 172 ± 6 172 ± 6 .92 BMI 25.1 ± 4.1 23.9 ± 3.0 <.05 24.6 ± 2.6 23.9 ± 3.0 <.05 WC (cm) 87 ± 11 84 ± 8 <.05 86 ± 6 84 ± 8 .09 Smoking (%) 30 (46) 677 (31) <.01 7 (15) 700 (32) <.01 ALC (N/LM/H)(%) 12/34/19 (18/52/30) 279/1352/548 (13/62/25) .25 5/32/11 (10/67/23) 286/1354/556 (13/62/25) .76 SBP (mmHg) 126 ± 15 122 ± 14 <.05 130 ± 15 122 ± 14 <.01 DBP (mmHg) 79 ± 12 76 ± 11 <.05 84 ± 12 76 ± 11 <.01 Pulse rate (bpm) 71 ± 9 68 ± 10 <.05 71 ± 9 68 ± 10 .07 baPWV (m/s) 13.7 ± 2.1 12.9 ± 1.8 <.01 14.5 ± 2.3 12.9 ± 1.8 <.01 radial AI (%) 74 ± 10 71 ± 13 <.05 73 ± 14 71 ± 13 .12 SBP 2 (mmHg) 117 ± 17 111 ± 16 <.01 120 ± 19 111 ± 16 <.01 TC (mmol/L) 5.5 ± 1.0 5.3 ± 0.9 .19 5.9 ± 1.0 5.3 ± 0.9 <.01 HDL (mmol/L ) 1.4 ± 0.4 1.6 ± 0.4 <.01 1.5 ± 0.4 1.6 ± 0.4 .16 TG (mmol/L) 1.6 ± 1.7 1.4 ± 1.0 .31 1.8 ± 1.0 1.4 ± 1.0 <.01 FPG (mmol/Ll) 5.2 ± 0.5 4.9 ± 0.5 .12 5.1 ± 0.5 4.9 ± 0.5 <.01 eGFR (mL/min per 1.73 m2) 85 ± 15 82 ± 12 .10 56 ± 4 82 ± 12 <.01 eGFR < 60 (%) 1 (1.5) 64 (2.9) .59 — — — Proteinuria (%) — — — 1 (2.0) 47 (2.1) .75 Abbreviations. Pro (+): subjects with proteinuria; Pro (−): subjects without proteinuria; eGFR < 60: subjects with eGFR of 15 to 59 mL/min per 1.73 m2; eGFR ≥ 60: subjects with eGFR ≥ 60 mL/min per 1.73 m2; BMI: body mass index; WC: waist circumference; smoking: number of subjects who were smoking; ALC: (N: nondrinker, LM: light-to-moderate drinker (ethanol intake: 1–29 g/day), and H: heavy drinker (ethanol intake: ≥30 g/day)); SBP: systolic blood pressure; DBP: diastolic blood pressure; baPWV: brachial-ankle pulse wave velocity; radial AI: radial augmentation index; SBP2: second peak of the radial pressure waveform; TC: serum total cholesterol; HDL: serum high-density lipoprotein cholesterol; TG: serum triglycerides; FPG: fasting plasma glucose; eGFR: estimated glomerular ﬁltration rate; eGFR < 60 mL/min per 1.73 m2: number of subjects with eGFR < 60 mL/min per 1.73 m2; proteinuria: number of subjects with proteinuria. After the adjustments (basic covariates plus eGFR, mean blood pressure, and pulse rate obtained at the time of measurement of the radial AI), the value of the radial AI was higher in the subjects with proteinuria than in those without proteinuria (Figure 1(a)). However, the adjusted (basic covariates plus presence/absence proteinuria, mean blood pressure, and pulse rate obtained at the time of measurement of the radial AI) value was similar between the subjects with an eGFR of 15 to 59 mL/min per 1.73 m2 and those with an eGFR ≥60 mL/min per 1.73 m2. Furthermore, the adjusted (basic covariates plus eGFR, pulse rate obtained at the measurement of radial AI) value of SBP2 was also higher in the subjects with proteinuria than in those without proteinuria (Figure 1(b)). On the other hand, after the adjustments (basic covariates plus eGFR, mean blood pressure, and pulse rate obtained at the time of measurement of brachial-ankle PWV), the value of the brachial-ankle PWV was higher in the subjects with proteinuria than in those without proteinuria. The adjusted (basic covariates plus presence/absence proteinuria, mean blood pressure, and pulse rate obtained at the measurement of brachial- ankle PWV) value of the brachial-ankle PWV was also higher in the subjects with eGFR of 15 to 59 mL/min per 1.73 m2 than in those with eGFR ≥ 60 mL/min per 1.73 m2 (Figure 1(c)). 4. Discussion The present study was conducted to examine the eﬀect of proteinuria and that of moderate-to-severe impairment of the eGFR (15 to 59 mL/min per 1.73 m2) on the central hemodynamics and PWV in healthy subjects (i.e., those who were not receiving any medication for cardiovascular disease or cardiovascular risk factors). Central hemodynamics and PWV are markers reﬂect- ing the pathophysiological abnormalities related to arterial stiﬀness [4, 5, 14]. Vascular damage of the systemic arte- rial tree aﬀects the central hemodynamics, while vascular damage of the large- to middle-sized arteries are major determinants of the brachial-ankle PWV [4, 5, 14]. Few studies have simultaneously examined the eﬀects of impaired GFR and proteinuria on the central hemodynamics and arterial stiﬀness, especially central arterial stiﬀness [8, 9]. The Framingham study demonstrated that the presence of microalbuminuria, but not the eGFR, was related to an increased AI and increased carotid-femoral PWV, the golden standard as a marker of the central arterial stiﬀness [8]. The Hoon study demonstrated that while microalbuminuria was related to increased AI and increased carotid arterial stiﬀness, impaired eGFR was related to only increased carotid arterial stiﬀness [9]. However, in both studies,