HRs and 95% CI for associations of circulating liver enzyme levels with all-cause, cancer and cardiovascular diseases (CVD) mortality, crude and multivariable adjusted*
| Quartile 1 | Quartile 2 | Quartile 3 | Quartile 4 | P value cat. | HR continuous | P value cont. | |
| All-cause mortality | |||||||
| ALP, range (U/L) | 9–58 | 59–69 | 70–85 | 86–261 | |||
| Number of cases | 210 | 222 | 326 | 417 | |||
| Crude model | Ref | 0.99 (0.78 to 1.26) | 1.46 (1.16 to 1.83) | 1.66 (1.33 to 2.08) | <0.0001 | 1.83 (1.50 to 2.23) | <0.0001 |
| Adjusted model | Ref | 0.91 (0.70 to 1.18) | 1.33 (1.04 to 1.69) | 1.31 (1.02 to 1.67) | 0.003 | 1.44 (1.17 to 1.79) | <0.001 |
| GGT, range (U/L) | 5–15 | 16–24 | 25–41 | 42–430 | |||
| Number of cases | 250 | 259 | 291 | 467 | |||
| Crude model | Ref | 1.12 (0.90 to 1.40) | 1.09 (0.87 to 1.35) | 1.75 (1.42 to 2.15) | <0.0001 | 1.35 (1.25 to 1.46) | <0.0001 |
| Adjusted model | Ref | 0.99 (0.77 to 1.26) | 0.88 (0.69 to 1.12) | 1.20 (0.95 to 1.52) | 0.046 | 1.19 (1.09 to 1.30) | <0.001 |
| AST, range (U/L) | 7–19 | 20–23 | 24–28 | 29–119 | |||
| Number of cases | 268 | 288 | 230 | 396 | |||
| Crude model | Ref | 1.16 (0.94 to 1.44) | 1.05 (0.84 to 1.32) | 1.62 (1.32 to 2.00) | <0.0001 | 1.78 (1.47 to 2.15) | <0.0001 |
| Adjusted model | Ref | 1.11 (0.87 to 1.41) | 1.12 (0.88 to 1.43) | 1.45 (1.15 to 1.82) | 0.003 | 1.47 (1.19 to 1.82) | <0.001 |
| ALT, range (U/L) | 6–18 | 19–23 | 24–33 | 34–231 | |||
| Number of cases | 341 | 251 | 273 | 343 | |||
| Crude model | Ref | 0.87 (0.70 to 1.08) | 0.86 (0.70 to 1.07) | 1.18 (0.96 to 1.45) | 0.105 | 1.15 (1.01 to 1.30) | 0.033 |
| Adjusted model | Ref | 0.87 (0.69 to 1.10) | 0.78 (0.61 to 0.99) | 1.00 (0.79 to 1.26) | 0.998 | 1.02 (0.89 to 1.18) | 0.758 |
| AST/ALT, range | −5.2 to −0.39 | −0.40 to −0.07 | −0.08 to 0.21 | 0.22 to 2.64 | |||
| Number of cases | 251 | 313 | 269 | 342 | |||
| Crude model | Ref | 1.14 (0.92 to 1.41) | 1.01 (0.81 to 1.27) | 1.38 (1.11 to 1.71) | 0.010 | 1.34 (1.13 to 1.61) | 0.001 |
| Adjusted model | Ref | 1.16 (0.92 to 1.46) | 1.12 (0.87 to 1.43) | 1.60 (1.25 to 2.04) | <0.001 | 1.40 (1.15 to 1.70) | 0.001 |
| Cancer mortality | |||||||
| ALP, range (U/L) | 9–58 | 59–69 | 70–85 | 86–261 | |||
| Number of cases | 115 | 116 | 176 | 198 | |||
| Crude model | Ref | 0.94 (0.70 to 1.26) | 1.40 (1.07 to 1.84) | 1.41 (1.08 to 1.86) | 0.002 | 1.53 (1.21 to 1.93) | <0.001 |
| Adjusted model | Ref | 0.89 (0.65 to 1.21) | 1.30 (0.98 to 1.73) | 1.17 (0.88 to 1.56) | 0.102 | 1.26 (0.99 to 1.61) | 0.059 |
| GGT, range (U/L) | 5–15 | 16–24 | 25–41 | 42–430 | |||
| Number of cases | 149 | 134 | 169 | 200 | |||
| Crude model | Ref | 0.98 (0.75 to 1.28) | 1.05 (0.81 to 1.36) | 1.24 (0.97 to 1.60) | 0.069 | 1.16 (1.05 to 1.27) | 0.003 |
| Adjusted model | Ref | 0.89 (0.67 to 1.18) | 0.90 (0.68 to 1.17) | 0.94 (0.71 to 1.23) | 0.797 | 1.04 (0.94 to 1.16) | 0.408 |
| AST, range (U/L) | 7–19 | 20–23 | 24–28 | 29–119 | |||
| Number of cases | 146 | 162 | 112 | 191 | |||
| Crude model | Ref | 1.20 (0.93 to 1.56) | 0.94 (0.71 to 1.25) | 1.41 (1.10 to 1.81) | 0.040 | 1.35 (1.08 to 1.69) | 0.009 |
| Adjusted model | Ref | 1.18 (0.90 to 1.55) | 0.99 (0.74 to 1.33) | 1.34 (1.02 to 1.74) | 0.126 | 1.21 (0.95 to 1.54) | 0.122 |
| ALT, range (U/L) | 6–18 | 19–23 | 24–33 | 34–231 | |||
| Number of cases | 196 | 133 | 137 | 154 | |||
| Crude model | Ref | 0.81 (0.63 to 1.05) | 0.75 (0.58 to 0.97) | 0.91 (0.71 to 1.16) | 0.398 | 0.94 (0.81 to 1.10) | 0.449 |
| Adjusted model | Ref | 0.82 (0.63 to 1.07) | 0.71 (0.54 to 0.94) | 0.83 (0.63 to 1.09) | 0.136 | 0.89 (0.75 to 1.06) | 0.186 |
| AST/ALT, range | −5.2 to −0.39 | −0.40 to −0.07 | −0.08 to 0.21 | 0.22 to 2.64 | |||
| Number of cases | 125 | 149 | 143 | 188 | |||
| Crude model | Ref | 1.11 (0.85 to 1.46) | 1.12 (0.85 to 1.47) | 1.58 (1.21 to 2.05) | <0.001 | 1.46 (1.18 to 1.81) | <0.001 |
| Adjusted model | Ref | 1.09 (0.82 to 1.46) | 1.17 (0.87 to 1.57) | 1.67 (1.26 to 2.23) | <0.001 | 1.44 (1.15 to 1.80) | 0.001 |
| CVD mortality | |||||||
| ALP, range (U/L) | 9–58 | 59–69 | 70–85 | 86–261 | |||
| Number of cases | 49 | 50 | 75 | 102 | |||
| Crude model | Ref | 0.94 (0.61 to 1.45) | 1.48 (1.00 to 2.21) | 1.70 (1.16 to 2.49) | <0.001 | 1.83 (1.33 to 2.52) | <0.001 |
| Adjusted model | Ref | 0.76 (0.46 to 1.25) | 1.22 (0.77 to 1.94) | 1.10 (0.70 to 1.74) | 0.268 | 1.25 (0.85 to 1.84) | 0.261 |
| GGT, range (U/L) | 5–15 | 16–24 | 25–41 | 42–430 | |||
| Number of cases | 49 | 61 | 66 | 124 | |||
| Crude model | Ref | 1.32 (0.88 to 1.98) | 1.25 (0.84 to 1.86) | 2.32 (1.60 to 3.34) | <0.0001 | 1.42 (1.25 to 1.61) | <0.0001 |
| Adjusted model | Ref | 1.03 (0.64 to 1.65) | 0.74 (0.46 to 1.20) | 1.21 (0.75 to 1.93) | 0.194 | 1.16 (0.97 to 1.39) | 0.095 |
| AST, range (U/L) | 7–19 | 20–23 | 24–28 | 29–119 | |||
| Number of cases | 57 | 77 | 50 | 90 | |||
| Crude model | Ref | 1.47 (1.01 to 2.14) | 1.07 (0.71 to 1.62) | 1.79 (1.24 to 2.60) | 0.015 | 1.75 (1.28 to 2.41) | 0.001 |
| Adjusted model | Ref | 1.35 (0.88 to 2.08) | 1.07 (0.66 to 1.73) | 1.41 (0.91 to 2.19) | 0.299 | 1.36 (0.91 to 2.03) | 0.132 |
| ALT, range (U/L) | 6–18 | 19–23 | 24–33 | 34–231 | |||
| Number of cases | 66 | 65 | 61 | 93 | |||
| Crude model | Ref | 1.13 (0.77 to 1.64) | 1.00 (0.68 to 1.46) | 1.69 (1.18 to 2.41) | 0.006 | 1.40 (1.14 to 1.72) | 0.001 |
| Adjusted model | Ref | 1.21 (0.77 to 1.90) | 0.80 (0.50 to 1.29) | 1.24 (0.80 to 1.93) | 0.384 | 1.14 (0.88 to 1.48) | 0.328 |
| AST/ALT, range | −5.2 to −0.39 | −0.40 to −0.07 | −0.08 to 0.21 | 0.22 to 2.64 | |||
| Number of cases | 71 | 80 | 62 | 60 | |||
| Crude model | Ref | 0.96 (0.67 to 1.38) | 0.76 (0.52 to 1.11) | 0.79 (0.54 to 1.16) | 0.143 | 0.91 (0.67 to 1.24) | 0.554 |
| Adjusted model | Ref | 1.17 (0.77 to 1.77) | 0.90 (0.58 to 1.42) | 1.11 (0.70 to 1.77) | 0.858 | 1.07 (0.75 to 1.52) | 0.721 |
The values given in bold are significant when p<0.05.
*Crude model adjusted for sex and age at blood draw. Multivariable model additionally adjusted for baseline height, waist, body mass index, lifetime alcohol consumption, smoking history, education, diabetes and physical activity. Models with CVD death as an endpoint were additionally adjusted for total and high-density lipoprotein cholesterol, triglycerides and C reactive protein. Quartile ranges are sex specific and based on the distribution in the subcohort.
ALP, alkaline phosphatase; ALT, alanine aminotransferase; AST, aspartate aminotransferase; AST/ALT, De Ritis ratio; GGT, gamma-glutamyltransferase; HR continuous, continuous HR for a doubling in biomarker concentration; p-value cat, p-trend over lipid biomarker levels based on the median of each quartile category; p-value cont, p-trend continuously.