Table 2.
(a) Final measurements at 6 months with comparisons between Vitamin E and placebo group and results of interaction test with haptoglobin genotype. (b) Subgroup analysis of final measurements at 6 months with comparisons between haptoglobin genotype and Vitamin E and placebo group.
| Variables | Overall | Interaction test | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Vitamin E | Placebo | Diff (95% CI) | p value | Hp 2-2 | Non-Hp 2-2 | p value | |||
| Vitamin E | Placebo | Vitamin E | Placebo | ||||||
| (a) Final measurements at 6 months with comparisons between Vitamin E and placebo group and results of interaction test with haptoglobin genotype | |||||||||
| Number (%) | 84 (50.6) | 82 (49.4) | 42 (25.30) | 44 (26.51) | 42 (25.30) | 38 (22.89) | |||
| Time from baseline to completion visit days, Median (IQR) | 176.00 (12.00) | 177.00 (14.00) | 0.329b | 176.50 (13.00) | 177.00 (14.00) | 175.50 (12.00) | 177.00 (14.00) | ||
| Physical measurements | |||||||||
| BMI Kg/m2, mean (SD) | 27.55 (4.93) | 27.23 (5.03) | −0.32 (−1.84, 1.21) | 0.684a | 27.79 (5.33) | 27.96 (5.36) | 27.30 (4.54) | 26.39 (4.54) | 0.482f |
| Waist circumference cm, mean (SD) | 92.97 (10.27) | 94.10 (11.18) | 1.12 (−2.16, 4.41) | 0.500a | 91.78 (9.94) | 95.17 (11.11) | 94.17 (10.57) | 92.85 (11.30) | 0.160f |
| Systolic BP (Peripheral) mmHg, mean (SD) | 133.27 (15.05) | 129.62 (13.51) | −3.66 (−8.04, 0.73) | 0.102a | 133.21 (13.63) | 128.92 (14.08) | 133.33 (16.51) | 130.42 (12.96) | 0.758f |
| Diastolic BP (Peripheral) mmHg, mean (SD) | 74.18 (8.66) | 71.95 (6.90) | −2.23 (−4.63, 0.18) | 0.069a | 74.61 (8.30) | 72.78 (7.51) | 73.75 (9.09) | 70.99 (6.07) | 0.701f |
| Metabolic parameters | |||||||||
| HbA1c %, mean (SD) | 7.75 (1.19) | 7.99 (1.37) | 0.25 (−0.15, 0.64) | 0.219a | 7.79 (1.26) | 8.29 (1.67) | 7.70 (1.13) | 7.65 (0.80) | 0.169f |
| Total cholesterol mmol/L, Median (IQR) | 4.10 (1.08) | 3.90 (1.30) | −0.20 (−0.52, 0.12) | *0.034b | 4.30 (1.23) | 4.20 (1.10) | 4.10 (0.93) | 3.60 (1.25) | 0.303f |
| LDL cholesterol mmol/L, Median (IQR) | 2.40 (0.83) | 2.10 (1.00) | −0.30 (−0.52, −0.08) | *0.014b | 2.40 (1.13) | 2.30 (0.80) | 2.30 (0.70) | 1.90 (0.75) | 0.569f |
| HDL cholesterol mmol/L, Median (IQR) | 1.10 (0.40) | 1.10 (0.30) | 0.00 (−0.08, 0.08) | 0.628b | 1.10 (0.23) | 1.10 (0.28) | 1.10 (0.40) | 1.10 (0.30) | 0.960f |
| Triglycerides mmol/L, Median (IQR) | 1.40 (1.15) | 1.20 (1.10) | −0.20 (−0.51, 0.11) | 0.348b | 1.35 (0.75) | 1.30 (1.25) | 1.40 (1.30) | 1.10 (0.90) | 0.069f |
| Renal parameters | |||||||||
| Creatinine μmol/L, mean (SD) | 71.69 (19.97) | 78.59 (25.01) | 6.91 (−1.13, 14.94) | 0.092a | 66.52 (18.89) | 78.27 (24.62) | 77.03 (19.95) | 78.94 (25.82) | 0.225f |
| eGFR ml/min/1.72m2, mean (SD) | 93.07 (17.33) | 84.62 (21.44) | −8.46 (−15.35, −1.57) | *0.017a | 97.49 (16.75) | 85.18 (22.97) | 88.51 (16.99) | 84.02 (20.06) | 0.263f |
| ACR mg/mmol, Median (IQR) | 1.50 (3.45) | 2.20 (4.30) | 0.70 (−0.81, 2.21) | 0.147b | 1.25 (3.18) | 1.75 (5.45) | 2.15 (4.63) | 2.90 (4.25) | 0.484f |
| Haematological parameters | |||||||||
| Haptoglobin mg/dL, mean (SD) | 109.67 (52.03) | 115.76 (48.14) | 6.09 (−9.28, 21.46) | 0.435a | 98.98 (44.44) | 101.50 (39.12) | 120.36 (57.20) | 132.26 (52.66) | 0.536f |
| Ferritin μg/L, Median (IQR) | 72.00 (83.00) | 58.50 (93.00) | −13.50 (−40.01, 14.01) | 0.322b | 57.50 (70.00) | 58.50 (107.00) | 79.00 (94.00) | 58.00 (90.00) | 0.213f |
| Transferrin g/L, mean (SD) | 91.42 (77.24) | 85.26 (78.16) | −6.16 (−29.98, 17.66) | 0.610a | 2.51 (0.40) | 2.46 (0.36) | 2.35 (0.41) | 2.46 (0.40) | 0.210f |
| Fe Concentration μmol/L, mean (SD) | 12.89 (5.30) | 12.75 (4.48) | −0.15 (−1.86, 1.57) | 0.865a | 12.90 (4.87) | 11.72 (4.68) | 12.89 (5.73) | 13.81 (4.07) | 0.226f |
| Alpha-tocopherol, μg/ml,Median (IQR) | 44.02 (44.32) | 43.20 (36.74) | −1.02 (−13.54, 11.51) | 0.682b | 38.25 (38.04) | 39.22 (33.56) | 52.04 (46.30) | 45.53 (44.10) | 0.829f |
| Vascular markers | |||||||||
| hsCRP mg/L, Median (IQR) | 1.45 (2.95) | 1.50 (2.50) | 0.05 (−0.76, 0.76) | 0.982b | 1.90 (3.08) | 1.4 (2.95) | 1.20 (1.93) | 1.65 (2.43) | 0.356f |
| dROMS, Median (IQR) | 275.00 (85.00) | 275.50 (115.00) | 0.50 (−18.87, 22.87) | 0.768b | 293.50 (87.00) | 270.5 (120.00) | 266.50 (85.00) | 280.50 (115.0) | 0.226f |
| BAPs uM, Median (IQR) | 2231.00 (311.0) | 2191.50 (354.0) | −39.50 (−125.63, 51.63) | 0.836b | 2218.0 (315.00) | 2192.5 (393.00) | 2252.5 (326.0) | 2186.5 (418.0) | 0.458f |
| CIMT: Average of left and right mm, mean (SD) | 0.67 (0.14) | 0.67 (0.12) | −0.004 (−0.04, 0.04) | 0.822a | 0.66 (0.12) | 0.67 (0.13) | 0.69 (0.15) | 0.67 (0.12) | 0.531f |
| CIMT: Maximum of left and right mm, mean (SD) | 0.82 (0.16) | 0.81 (0.15) | −0.01 (−0.06, 0.04) | 0.737a | 0.80 (0.14) | 0.81 (0.15) | 0.84 (0.18) | 0.82 (0.15) | 0.558f |
| EndoPAT: LnRHI, mean (SD) | 0.66 (0.27) | 0.65 (0.25) | −0.02 (−0.10, 0.06) | 0.690a | 0.64 (0.26) | 0.68 (0.23) | 0.69 (0.28) | 0.61 (0.26) | 0.128f |
| EndoPAT: Augmentation index 75bpm%,mean (SD) | 20.23 (17.52) | 15.89 (12.03) | −4.34 (−8.94, 0.26) | 0.064a | 19.90 (16.66) | 18.48 (13.23) | 20.55 (18.53) | 12.89 (9.80) | 0.184f |
| Pulse Wave Analysis: Systolic BP mmHg, mean (SD) | 118.98 (14.42) | 115.32 (12.18) | −3.66 (−7.75, 0.44) | 0.079a | 119.62 (12.64) | 115.95 (12.32) | 118.33 (16.13) | 114.58 (12.13) | 0.983f |
| Pulse Wave Analysis: Diastolic BP mmHg,mean (SD) | 77.81 (9.76) | 75.70 (8.38) | −2.11 (−4.91, 0.68) | 0.137a | 77.83 (8.68) | 76.59 (8.51) | 77.79 (10.84) | 74.66 (8.22) | 0.508f |
| Pulse Wave Velocity m/s, mean (SD) | 8.48 (1.58) | 8.41 (1.64) | −0.07 (−0.56, 0.42) | 0.776a | 8.34 (1.56) | 8.51 (1.72) | 8.62 (1.61) | 8.29 (1.55) | 0.330f |
| SphygmoCor: Augmentation index %, mean (SD) | 29.71 (13.77) | 29.26 (9.96) | −0.46 (−4.15, 3.24) | 0.808a | 30.85 (9.07) | 29.48 (9.77) | 28.60 (17.21) | 29.00 (10.31) | 0.637f |
| Oxidised LDL IU/L, Median (IQR) | 55.30 (23.98) | 61.35 (25.16) | −6.05 (−15.22, 2.97) | *0.033b | 62.10 (23.55) | 59.88 (23.80) | 60.11 (27.86) | 49.22 (21.50) | 0.309f |
| Variables | Hp 2-2 | Non-Hp 2-2 | ||||||
|---|---|---|---|---|---|---|---|---|
| Vitamin E | Placebo | Diff (95% CI) | p value | Vitamin E | Placebo | Diff (95% CI) | p value | |
| (b) Subgroup analysis of final measurements at 6 months with comparisons between haptoglobin genotype and Vitamin E and placebo group | ||||||||
| Number (%) | 42 (25.30) | 44 (26.51) | 42 (25.30) | 38 (22.89) | ||||
| Time from baseline to completion visit days, Median (IQR) | 176.50 (13.00) | 177.00 (14.00) | 0.595b | 175.50 (12.00) | 177.00 (14.00) | 0.417b | ||
| Physical measurements | ||||||||
| BMI Kg/m2, mean (SD) | 27.79 (5.33) | 27.96 (5.36) | 0.17 (−2.12, 2.46) | 0.882a | 27.30 (4.54) | 26.39 (4.54) | −0.92 (−2.94, 1.11) | 0.370a |
| Waist circumference cm, mean (SD) | 91.78 (9.94) | 95.17 (11.11) | 3.39 (−1.14, 7.92) | 0.140a | 94.17 (10.57) | 92.85 (11.30) | −1.31 (−6.18, 3.55) | 0.592a |
| Systolic BP (Peripheral) mmHg, mean (SD) | 133.21 (13.63) | 128.92 (14.08) | −4.29 (−10.24, 1.65) | 0.155a | 133.33 (16.51) | 130.42 (12.96) | −2.91 (−9.57, 3.74) | 0.386a |
| Diastolic BP (Peripheral) mmHg, mean (SD) | 74.61 (8.30) | 72.78 (7.51) | −1.82 (−5.21, 1.57) | 0.288a | 73.75 (9.09) | 70.99 (6.07) | −2.76 (−6.24, 0.72) | 0.118a |
| Metabolic parameters | ||||||||
| HbA1c %, mean (SD) | 7.79 (1.26) | 8.29 (1.67) | 0.49 (−0.14, 1.13) | 0.127a | 7.70 (1.13) | 7.65 (0.80) | −0.05 (−0.49, 0.39) | 0.820a |
| Total cholesterol mmol/L, Median (IQR) | 4.30 (1.23) | 4.20 (1.10) | −0.10 (−0.59, 0.39)e | 0.473b | 4.10 (0.93) | 3.60 (1.25) | −0.50 (−0.94, −0.06)e | *0.016b |
| LDL cholesterol mmol/L, Median (IQR) | 2.40 (1.13) | 2.30 (0.80) | −0.10 (−0.52, 0.32)e | 0.410b | 2.30 (0.70) | 1.90 (0.75) | −0.40 (−0.72, −0.08)e | *0.006b |
| HDL cholesterol mmol/L, Median (IQR) | 1.10 (0.23) | 1.10 (0.28) | 0.00 (−0.10, 0.10)e | 0.972b | 1.10 (0.40) | 1.10 (0.30) | 0.00 (−0.15, 0.15) e | 0.478b |
| Triglycerides mmol/L, Median (IQR) | 1.35 (0.75) | 1.30 (1.25) | −0.05 (−0.49, 0.29)e | 0.819b | 1.40 (1.30) | 1.10 (0.90) | −0.30 (−0.83, 0.23)e | 0.110b |
| Renal parameters | ||||||||
| Creatinine μmol/L, mean (SD) | 66.52 (18.89) | 78.27 (24.62) | 11.76 (0.74, 22.77) | *0.037a | 77.03 (19.95) | 78.94 (25.82) | 1.90 (−9.95,13.75) | 0.749a |
| eGFR ml/min/1.72m2, mean (SD) | 97.49 (16.75) | 85.18 (22.97) | −12.32 (−22.42,−2.22) | *0.017a | 88.51 (16.99) | 84.02 (20.06) | −4.48 (−14.02,5.06) | 0.351a |
| ACR mg/mmol, Median (IQR) | 1.25 (3.18) | 1.75 (5.45) | 0.50 (−1.53, 2.73)e | 0.093b | 2.15 (4.63) | 2.90 (4.25) | 0.75 (−0.46, 2.86)e | 0.691b |
| Haematological parameters | ||||||||
| Haptoglobin mg/dL, mean (SD) | 98.98 (44.44) | 101.50 (39.12) | 2.52 (−15.41, 20.46) | 0.780a | 120.36 (57.20) | 132.26 (52.66) | 11.91 (12.65,36.4) | 0.337a |
| Ferritin μg/L, Median (IQR) | 57.50 (70.00) | 58.50 (107.00) | 1.0 (−33.55, 37.55)e | 0.701b | 79.00 (94.00) | 58.00 (90.00) | 21.0 (−60.28,22.28)e | 0.089b |
| Transferrin g/L, mean (SD) | 2.51 (0.40) | 2.46 (0.36) | −0.04 (−0.21, 0.12) | 0.597a | 2.35 (0.41) | 2.46 (0.40) | 0.11 (−0.07, 0.29) | 0.228a |
| Fe Concentration μmol/L, mean (SD) | 12.90 (4.87) | 11.72 (4.68) | −1.18 (−3.59, 1.22) | 0.329a | 12.89 (5.73) | 13.81 (4.07) | 0.92 (−1.55, 3.40) | 0.460a |
| Alpha-tocopherol, μg/ml,Median (IQR) | 38.25 (38.04) | 39.22 (33.56) | 0.97 (−15.21,16.98)e | 0.789b | 52.04 (46.30) | 45.53 (44.10) | −6.51 (−27.12,13.4)e | 0.765b |
| Vascular markers | ||||||||
| hsCRP mg/L, Median (IQR) | 1.90 (3.08) | 1.4 (2.95) | −0.50 (−1.74, 0.74)e | 0.441b | 1.20 (1.93) | 1.65 (2.43) | 0.45 (−0.48, 1.48)e | 0.390b |
| dROMS, Median (IQR) | 293.50 (87.00) | 270.5 (120.00) | −23.0 (−59.08, 25.08)e | 0.267b | 266.50 (85.00) | 280.50 (115.0) | 14.0 (−28.45,50.45)e | 0.544b |
| BAPs uM, Median (IQR) | 2218.0 (315.00) | 2192.5 (393.00) | −25.5 (−169.9,105.87)e | 0.717b | 2252.5 (326.0) | 2186.5 (418.0) | −66.0 (−206.8,87.8)e | 0.965b |
| CIMT: Average of left and right mm, mean (SD) | 0.66 (0.12) | 0.67 (0.13) | 0.01 (−0.05, 0.06) | 0.754a | 0.69 (0.15) | 0.67 (0.12) | −0.02 (−0.08, 0.04) | 0.579a |
| CIMT: Maximum of left and right mm, mean (SD) | 0.80 (0.14) | 0.81 (0.15) | 0.01 (−0.06, 0.07) | 0.839a | 0.84 (0.18) | 0.82 (0.15) | −0.02 (−0.09, 0.05) | 0.556a |
| EndoPAT: LnRHI, mean (SD) | 0.64 (0.26) | 0.68 (0.23) | 0.04 (−0.06, 0.15) | 0.418a | 0.69 (0.28) | 0.61 (0.26) | −0.08 (−0.20, 0.04) | 0.194a |
| EndoPAT: Augmentation index 75bpm%,mean (SD) | 19.90 (16.66) | 18.48 (13.23) | −1.43 (−7.86, 5.01) | 0.660a | 20.55 (18.53) | 12.89 (9.80) | −7.65 (−14.36,−0.95) | *0.022a |
| Pulse Wave Analysis: Systolic BP mmHg, mean (SD) | 119.62 (12.64) | 115.95 (12.32) | −3.67 (−9.02, 1.69) | 0.177a | 118.33 (16.13) | 114.58 (12.13) | −3.75 (−10.16,2.65) | 0.247a |
| Pulse Wave Analysis: Diastolic BP mmHg,mean (SD) | 77.83 (8.68) | 76.59 (8.51) | −1.24 (−4.93, 2.45) | 0.505a | 77.79 (10.84) | 74.66 (8.22) | −3.13 (−7.45, 1.19) | 0.153a |
| Pulse Wave Velocity m/s, mean (SD) | 8.34 (1.56) | 8.51 (1.72) | 0.17 (−0.54, 0.87) | 0.641a | 8.62 (1.61) | 8.29 (1.55) | −0.32 (−1.03, 0.38) | 0.362a |
| SphygmoCor: Augmentation index %, mean (SD) | 30.85 (9.07) | 29.48 (9.77) | −1.38 (−5.45, 2.70) | 0.503a | 28.60 (17.21) | 29.00 (10.31) | 0.41 (−6.00, 6.81) | 0.900a |
| Oxidised LDL IU/L, Median (IQR) | 62.10 (23.55) | 59.88 (23.80) | −2.22 (−11.43,7.05)e | 0.484b | 60.11 (27.86) | 49.22 (21.50) | −10.89 (−22.2,−0.75) e | *0.012b |
DM Diabetes mellitus, BMI body mass index, BP blood pressure, eGFR estimated glomerular filtration rate by CKD-EPI formula, ACR albumin creatinine ratio, LDL-C low density lipoprotein cholesterol, HDL-C high density lipoprotein cholesterol, Fe iron, hsCRP highly sensitive c-reactive protein, dROMS derivatives of reactive-oxygen species, BAP Biological antioxidant potential, CIMT carotid artery intima media thickness, LnRHI log reactive-hyperaemia index.
aIndependent Sample T test.
bMann–Whitney U test.
cPearson Chi-Square test.
dFisher Exact test.
eThe median difference was derived by quantile regression.
fInteraction test between hp genotype and Vitamin E placebo group. *P < 0.05.