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. 2020 Mar 8;10(3):e033532. doi: 10.1136/bmjopen-2019-033532

Table 3.

HRs and 95% CI for associations of circulating liver enzyme levels with incident cardiovascular diseases, crude and multivariable adjusted*

Quartile 1 Quartile 2 Quartile 3 Quartile 4 P value cat. HR continuous P value cont.
MI
 ALP, range (U/L) 9–58 59–69 70–85 86–261
 Number of cases 61 105 125 138
 Crude model Ref 1.72 (1.21 to 2.44) 2.07 (1.47 to 2.91) 2.16 (1.53 to 3.04) <0.0001 1.75 (1.36 to 2.24) <0.0001
 Adjusted model Ref 1.44 (0.96 to 2.17) 1.61 (1.10 to 2.37) 1.25 (0.84 to 1.87) 0.662 1.06 (0.78 to 1.44) 0.717
 GGT, range (U/L) 5–15 16–24 25–41 42–430
 Number of cases 91 106 137 143
 Crude model Ref 1.27 (0.93 to 1.75) 1.50 (1.11 to 2.03) 1.57 (1.16 to 2.13) 0.013 1.19 (1.08 to 1.31) <0.001
 Adjusted model Ref 0.99 (0.67 to 1.46) 1.00 (0.68 to 1.46) 1.00 (0.66 to 1.51) 0.846 1.02 (0.89 to 1.17) 0.772
 AST, range (U/L) 7–19 20–23 24–28 29–119
 Number of cases 120 110 95 104
 Crude model Ref 0.96 (0.71 to 1.30) 0.98 (0.72 to 1.33) 0.98 (0.73 to 1.33) 0.792 0.98 (0.73 to 1.31) 0.873
 Adjusted model Ref 1.00 (0.71 to 1.41) 1.05 (0.73 to 1.52) 0.82 (0.57 to 1.17) 0.277 0.80 (0.57 to 1.12) 0.200
 ALT, range (U/L) 6–18 19–23 24–33 34–231
 Number of cases 108 106 115 112
 Crude model Ref 1.17 (0.87 to 1.59) 1.18 (0.88 to 1.60) 1.23 (0.91 to 1.66) 0.231 1.15 (0.97 to 1.35) 0.111
 Adjusted model Ref 1.41 (0.98 to 2.03) 0.97 (0.66 to 1.42) 0.97 (0.66 to 1.41) 0.562 0.93 (0.75 to 1.15) 0.524
 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 107 132 90 94
 Crude model Ref 1.14 (0.85 to 1.54) 0.79 (0.58 to 1.09) 0.86 (0.63 to 1.18) 0.150 0.77 (0.59 to 1.00) 0.046
 Adjusted model Ref 1.40 (0.99 to 1.98) 0.98 (0.67 to 1.43) 1.16 (0.79 to 1.71) 0.739 0.90 (0.66 to 1.22) 0.499
Stroke
 ALP, range (U/L) 9–58 59–69 70–85 86–261
 Number of cases 49 69 62 77
 Crude model Ref 1.26 (0.84 to 1.87) 1.17 (0.78 to 1.75) 1.26 (0.85 to 1.88) 0.338 1.15 (0.85 to 1.56) 0.365
 Adjusted model Ref 1.19 (0.77 to 1.86) 0.99 (0.64 to 1.54) 0.90 (0.57 to 1.42) 0.384 0.82 (0.58 to 1.17) 0.271
 GGT, range (U/L) 5–15 16–24 25–41 42–430
 Number of cases 59 61 70 88
 Crude model Ref 1.12 (0.76 to 1.65) 1.12 (0.77 to 1.64) 1.39 (0.96 to 2.00) 0.039 1.24 (1.09 to 1.42) 0.002
 Adjusted model Ref 0.95 (0.62 to 1.45) 0.85 (0.55 to 1.31) 0.94 (0.61 to 1.46) 0.567 1.13 (0.95 to 1.33) 0.159
 AST, range (U/L) 7–19 20–23 24–28 29–119
 Number of cases 59 73 50 74
 Crude model Ref 1.36 (0.94 to 1.99) 1.05 (0.70 to 1.58) 1.37 (0.94 to 2.00) 0.222 1.25 (0.90 to 1.74) 0.185
 Adjusted model Ref 1.40 (0.93 to 2.08) 1.13 (0.73 to 1.77) 1.25 (0.84 to 1.88) 0.461 1.12 (0.78 to 1.60) 0.545
 ALT, range (U/L) 6–18 19–23 24–33 34–231
 Number of cases 67 67 66 65
 Crude model Ref 1.21 (0.83 to 1.75) 1.06 (0.73 to 1.53) 1.12 (0.77 to 1.63) 0.724 1.12 (0.91 to 1.38) 0.291
 Adjusted model Ref 1.38 (0.91 to 2.08) 0.97 (0.63 to 1.49) 0.95 (0.63 to 1.45) 0.514 1.01 (0.80 to 1.27) 0.939
 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 62 70 56 67
 Crude model Ref 1.01 (0.70 to 1.47) 0.87 (0.59 to 1.29) 1.08 (0.74 to 1.58) 0.784 1.04 (0.78 to 1.39) 0.780
 Adjusted model Ref 1.21 (0.80 to 1.81) 0.97 (0.63 to 1.49) 1.28 (0.84 to 1.95) 0.376 1.11 (0.82 to 1.50) 0.491

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, physical activity, 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; AST, aspartate aminotransferase; AST/ALT, De Ritis ratio; GGT, gamma-glutamyltransferase; HR continuous, continuous HR for a doubling in biomarker concentration; MI, myocardial infarction; p-value cat, p-trend over lipid biomarker levels based on the median of each quartile category; p-value cont, p-trend continuously.