Introduction
Subjects and methods
Study design
Laboratory analyses
Statistical analyses
Results
Characteristics of the study population
Parameter | Entire cohort (n = 2968) | M (n = 2066) | F (n = 902) | p value |
---|---|---|---|---|
Anthropometric data | ||||
M (%) | 69.6 | – | – | |
Age (years) | 63.5 (47.9–75.7) | 62.5 (46.9–74.7) | 65.2 (50.9–76.9) | < 0.001 |
Physical examination | ||||
BMI (kg/m2) | 27.0 (22.9–32.8) | 27.1 (23.4–32.5) | 26.9 (21.9–33.5) | 0.015 |
SBP (mmHg) | 140 (112–173) | 140 (112–173) | 142 (110–173) | 0.496 |
DBP (mmHg) | 81 (66–96) | 81 (67–97) | 79 (65–94) | < 0.001 |
Biochemical parameters | ||||
White blood cells (× 103/µL) | 6.8 (4.8–9.8) | 6.9 (5.0–9.9) | 6.5 (4.6–9.5) | < 0.001 |
Hemoglobin (g/dL) | 13.9 (11.9–15.6) | 14.3 (12.4–15.9) | 13.0 (11.3–14.4) | < 0.001 |
Glucose (mg/dL) | 102 (88–154) | 103 (88–152) | 101 (87–159) | 0.030 |
HbA1c (%) | 6.0 (5.2–7.8) | 6.0 (5.2–7.7) | 6.0 (5.3–8.1) | 0.005 |
Creatinine (mg/dL) | 0.9 (0.7–1.2) | 1.0 (0.8–1.2) | 0.8 (0.7–1.1) | < 0.001 |
Markers of inflammation | ||||
hs-CRP (mg/L) | 3.4 (0.7–21.5) | 3.3 (0.6–22.6) | 3.6 (0.7–19.6) | 0.103 |
IL-6 (pg/mL) | 3.2 (1.2–11.1) | 3.3 (1.2–11.9) | 3.1 (1.1–10.0) | 0.051 |
Vitamin B and related metabolites | ||||
Vitamin B6 (µg/L) | 8.9 (3.5–22.3) | 9.3 (3.8–22.9) | 8.0 (3.1–20.7) | < 0.001 |
Vitamin B6 < 5 µg/L (%) | 21 | 19 | 25 | |
Vitamin B12 (pmol/L) | 344 (197–636) | 340 (197–616) | 354 (200–692) | 0.044 |
Vitamin B9 (µg/L) | 7.8 (4.7–12.0) | 7.6 (4.6–11.8) | 8.2 (5.0–12.4) | < 0.001 |
HCY (µmol/L) | 12.3 (8.1–19.8) | 12.6 (8.4–19.8) | 11.5 (7.5–19.6) | < 0.001 |
HCY < 12 µmol/L (%) | 48 | 45 | 55 | |
Relative telomere length | ||||
RTL | 1.79 (0.46–4.95) | 1.76 (0.46–4.90) | 1.86 (0.46–5.11) | 0.564 |
Age-corrected RTL | 0.0280 (0.0070–0.0865) | 0.0280 (0.0071–0.0877) | 0.0279 (0.0069–0.0841) | 0.428 |
Vitamin B6, HCY, and mortality
All-cause mortality | N° deceased (%)/alive (%) patients | Model 1 HR (95%) | p value | Model 2 HR (95%) | p value | Model 3 HR (95%) | p value |
---|---|---|---|---|---|---|---|
HCY quartiles (n = 2968) | |||||||
1st (< 9.8 µmol/L, n = 756) | 146 (19)/610 (81) | Ref. | Ref. | Ref. | |||
2nd (9.9–12.4 µmol/L, n = 774) | 210 (27)/564 (73) | 1.48 (1.20–1.83) | < 0.001 | 1.28 (1.04–1.58) | 0.022 | 1.43 (1.12–1.82) | 0.004 |
3rd (12.5–15.5 µmol/L, n = 701) | 217 (31)/484 (69) | 1.73 (1.40–2.13) | < 0.001 | 1.44 (1.16–1.78) | 0.001 | 1.49 (1.16–1.90) | 0.002 |
4th (> 15.6 µmol/L, n = 737) | 327 (44)/410 (56) | 2.77 (2.28–3.37) | < 0.001 | 2.03 (1.66–2.49) | < 0.001 | 2.13 (1.69–2.70) | < 0.001 |
Vitamin B6 quartiles (n = 2968) | |||||||
1st (< 5.6 µg/L, n = 742) | 312 (42)/430 (58) | Ref. | Ref. | Ref. | |||
2nd (5.7–8.9 µg/L, n = 760) | 223 (29)/537 (71) | 0.62 (0.52–0.73) | < 0.001 | 0.72 (0.61–0.86) | < 0.001 | 0.70 (0.57–0.85) | < 0.001 |
3rd (9.0–14.1 µg/L, n = 719) | 213 (30)/506 (70) | 0.62 (0.52–0.74) | < 0.001 | 0.75 (0.62–0.90) | 0.002 | 0.75 (0.61–0.93) | 0.008 |
4th (> 14.2 µg/L, n = 747) | 152 (20)/595 (80) | 0.41 (0.33–0.49) | < 0.001 | 0.54 (0.44–0.67) | < 0.001 | 0.55 (0.44–0.70) | < 0.001 |
CVD mortality | Model 1 HR (95%) | p value | Model 2 HR (95%) | p value | Model 3 HR (95%) | p value |
---|---|---|---|---|---|---|
HCY quartiles | ||||||
1st (< 9.8 µmol/L, n = 756) | Ref. | Ref. | Ref. | |||
2nd (9.9–12.4 µmol/L, n = 774) | 1.50 (1.21–1.86) | < 0.001 | 1.30 (1.05–1.61) | 0.017 | 1.46 (1.14–1.87) | 0.002 |
3rd (12.5–15.5 µmol/L, n = 701) | 1.74 (1.41–2.16) | < 0.001 | 1.45 (1.17–1.79) | 0.001 | 1.50 (1.16–1.92) | 0.002 |
4th (> 15.6 µmol/L, n = 737) | 2.78 (2.29–3.39) | < 0.001 | 2.04 (1.66–2.51) | < 0.001 | 2.16 (1.71–2.74) | < 0.001 |
Vitamin B6 quartiles | ||||||
1st (< 5.6 µg/L, n = 742) | Ref. | Ref. | Ref. | |||
2nd (5.7–8.9 µg/L, n = 760) | 0.62 (0.52–0.74) | < 0.001 | 0.72 (0.60–0.86) | < 0.001 | 0.70 (0.57–0.85) | < 0.001 |
3rd (9.0–14.1 µg/L, n = 719) | 0.63 (0.53–0.75) | < 0.001 | 0.75 (0.63–0.91) | 0.003 | 0.76 (0.61–0.93) | 0.001 |
4th (> 14.2 µg/L, n = 747) | 0.40 (0.33–0.49) | < 0.001 | 0.54 (0.44–0.67) | < 0.001 | 0.55 (0.43–0.70) | < 0.001 |
Vitamin B6, HCY, and telomere biology
Age-corrected RTL quartiles | 1st (n = 739) < 0.0140 | 2nd (n = 748) 0.0141–0.0280 | 3rd (n = 738) 0.0281–0.0509 | 4th (n = 743) > 0.0510 | p value | p value 1–3 vs 4 |
---|---|---|---|---|---|---|
HCY (µmol/L) | 12.8 (8.5–20.1) | 12.4 (8.1–19.9) | 12.2 (7.9–21.2) | 11.7 (7.8–18.6) | < 0.001 | < 0.001 |
12.5 (8.1–20.3) | ||||||
Vitamin B6 (µg/L) | 8.8 (3.7–21.7) | 8.6 (3.4–22.4) | 8.4 (3.4–21.7) | 9.7 (3.6–23.6) | 0.004 | 0.001 |
8.6 (3.5–21.9) | ||||||
hs-CRP (mg/L) | 3.19 (0.66–21.66) | 3.54 (0.71–24.20) | 3.55 (0.73–20.60) | 3.05 (0.53–20.25) | 0.067 | 0.017 |
3.43 (0.70–21.90) | ||||||
IL-6 (pg/mL) | 3.34 (1.23–11.50) | 3.43 (1.22–11.95) | 3.26 (1.17–11.59) | 2.82 (1.07–9.87) | 0.001 | < 0.001 |
3.34 (1.21–11.59) |
RTL quartiles | 1st (n = 739) < 0.8915 | 2nd (n = 748) 0.8916–1.7881 | 3rd (n = 738) 1.7882–3.1088 | 4th (n = 743) > 3.1089 | p value | p value 1–3 vs 4 |
---|---|---|---|---|---|---|
HCY (µmol/L) | 12.6 (8.3–19.6) | 12.3 (8.14–19.7) | 12.2 (7.8–20.7) | 12.0 (8.1–19.1) | 0.085 | 0.298 |
12.4 (8.1–20.0) | ||||||
Vitamin B6 (µg/L) | 9.0 (3.8–22.0) | 8.6 (3.3–21.7) | 8.7 (3.5–22.0) | 9.4 (3.4–23.6) | 0.244 | 0.328 |
8.7 (3.5–21.9) | ||||||
hs-CRP (mg/L) | 3.08 (0.66–21.87) | 3.47 (0.66–22.90) | 3.72 (0.74–19.67) | 3.06 (0.59–21.50) | 0.110 | 0.166 |
3.43 (0.69–21.60) | ||||||
IL-6 (pg/mL) | 3.31 (1.21–11.47) | 3.32 (1.15–11.21) | 3.33 (1.26–11.16) | 2.91 (1.10–10.72) | 0.026 | 0.001 |
3.32 (1.21–11.29) |
Vitamin B6, HCY, telomere biology, and markers of inflammation
Predictor variables | Unstandardized B | 95% CI for B | Standardized β | t | p value |
---|---|---|---|---|---|
A) Dependent variable: RTL | |||||
Age | − 0.004 | − 0.005 to − 0.002 | − 0.084 | − 3.954 | < 0.001 |
B) Dependent variable: age-corrected RTL | |||||
HCY | − 0.187 | − 0.311 to − 0.063 | − 0.063 | − 2.960 | 0.003 |
IL-6 | − 0.048 | − 0.101 to − 0.004 | − 0.039 | − 1.821 | 0.069 |
C) Dependent variable: vitamin B6 | |||||
HCY | − 0.301 | − 0.378 to − 0.224 | − 0.152 | − 7.644 | < 0.001 |
IL-6 | − 0.051 | − 0.090 to − 0.011 | − 0.061 | − 2.536 | 0.011 |
hs-CRP | − 0.133 | − 0.159 to − 0.107 | − 0.240 | − 10.084 | < 0.001 |
α-Tocopherol | 0.004 | 0.003–0.005 | 0.144 | 7.270 | < 0.001 |
γ-Tocopherol | − 0.036 | − 0.049 to − 0.022 | − 0.102 | − 5.150 | < 0.001 |
Vitamin C | − 1.471E−7 | 0.000–0.000 | − 0.043 | − 2.205 | 0.028 |
D) Dependent variable: HCY | |||||
IL-6 | 0.039 | 0.022–0.057 | 0.093 | 4.361 | < 0.001 |
MTHFR genotype | 0.013 | 0.004–0.023 | 0.057 | 2.764 | 0.006 |
Age-corrected RTL | − 0.020 | − 0.033 to − 0.006 | − 0.058 | − 2.786 | 0.005 |
Vitamin B6 | − 0.083 | − 0.104 to − 0.062 | − 0.164 | − 7.699 | < 0.001 |