Table 2. Adjusted hazard ratios for incident CVD, CHD, stroke, and their subtypes according to serum ALP levels in men and women.
| Outcomes† | Quartiles of ALP levels＊, U/L | p for trend§ | Natural log- transformed continuous | |||
|---|---|---|---|---|---|---|
| Q1 | Q2 | Q3 | Q4 | |||
| Men | ||||||
| CVD | ||||||
| No. of cases/person years | 746/19,226 | 857/20,390 | 997/21,269 | 920/19,110 | ||
| Model 1 | 1.00 (Ref) | 1.08 (0.98-1.19) | 1.22 (1.11-1.34) | 1.27 (1.15-1.40) | ＜0.001 | 1.34 (1.20-1.51) |
| Model 2 | 1.00 (Ref) | 1.09 (0.98-1.20) | 1.21 (1.10-1.33) | 1.23 (1.11-1.35) | ＜0.001 | 1.27 (1.13-1.43) |
| Model 3 | 1.00 (Ref) | 1.08 (0.98-1.19) | 1.20 (1.09-1.32) | 1.22 (1.11-1.34) | ＜0.001 | 1.26 (1.12-1.42) |
| CHD | ||||||
| No. of cases/person years | 567/19,877 | 638/21,138 | 751/21,921 | 651/19,908 | ||
| Model 1 | 1.00 (Ref) | 1.05 (0.94-1.18) | 1.22 (1.09-1.36) | 1.18 (1.05-1.32) | ＜0.001 | 1.19 (1.04-1.36) |
| Model 2 | 1.00 (Ref) | 1.06 (0.95-1.19) | 1.20 (1.08-1.34) | 1.15 (1.02-1.29) | 0.007 | 1.14 (1.00-1.30) |
| Model 3 | 1.00 (Ref) | 1.06 (0.94-1.18) | 1.20 (1.07-1.34) | 1.14 (1.02-1.28) | 0.01 | 1.13 (0.99-1.29) |
| ACS | ||||||
| No. of cases/person years | 203/18,085 | 290/19,418 | 348/19,976 | 274/17,993 | ||
| Model 1 | 1.00 (Ref) | 1.33 (1.11-1.59) | 1.58 (1.33-1.88) | 1.39 (1.16-1.66) | ＜0.001 | 1.43 (1.15-1.76) |
| Model 2 | 1.00 (Ref) | 1.33 (1.11-1.59) | 1.54 (1.29-1.83) | 1.33 (1.11-1.59) | 0.004 | 1.33 (1.08-1.64) |
| Model 3 | 1.00 (Ref) | 1.32 (1.10-1.58) | 1.53 (1.28-1.82) | 1.31 (1.09-1.57) | 0.007 | 1.31 (1.06-1.62) |
| Stroke | ||||||
| No. of cases/person years | 179/21,130 | 219/22,498 | 246/23,692 | 269/21,221 | ||
| Model 1 | 1.00 (Ref) | 1.15 (0.94-1.40) | 1.24 (1.02-1.50) | 1.53 (1.26-1.84) | ＜0.001 | 1.84 (1.45-2.32) |
| Model 2 | 1.00 (Ref) | 1.15 (0.94-1.40) | 1.21 (0.99-1.46) | 1.44 (1.19-1.75) | ＜0.001 | 1.70 (1.34-2.15) |
| Model 3 | 1.00 (Ref) | 1.14 (0.94-1.39) | 1.20 (0.99-1.45) | 1.43 (1.18-1.73) | ＜0.001 | 1.68 (1.33-2.13) |
| Ischemic stroke | ||||||
| No. of cases/person years | 151/20,990 | 173/22,303 | 197/23,449 | 217/21,011 | ||
| Model 1 | 1.00 (Ref) | 1.08 (0.86-1.34) | 1.18 (0.96-1.46) | 1.46 (1.19-1.80) | ＜0.001 | 1.75 (1.35-2.28) |
| Model 2 | 1.00 (Ref) | 1.09 (0.87-1.35) | 1.15 (0.93-1.43) | 1.39 (1.12-1.71) | 0.001 | 1.62 (1.25-2.11) |
| Model 3 | 1.00 (Ref) | 1.08 (0.87-1.34) | 1.15 (0.93-1.42) | 1.37 (1.11-1.70) | 0.002 | 1.61 (1.24-2.09) |
| Hemorrhagic stroke | ||||||
| No. of cases/person years | 28/20,359 | 46/21,700 | 49/22,755 | 52/20,248 | ||
| Model 1 | 1.00 (Ref) | 1.54 (0.96-2.46) | 1.58 (0.99-2.52) | 1.91 (1.21-3.02) | 0.009 | 2.27 (1.33-3.90) |
| Model 2 | 1.00 (Ref) | 1.50 (0.94-2.41) | 1.52 (0.95-2.42) | 1.77 (1.11-2.81) | 0.03 | 2.09 (1.22-3.58) |
| Model 3 | 1.00 (Ref) | 1.49 (0.93-2.39) | 1.51 (0.94-2.40) | 1.75 (1.10-2.79) | 0.03 | 2.06 (1.20-3.55) |
| Women | ||||||
| CVD | ||||||
| No. of cases/person years | 694/27,881 | 772/27,868 | 974/28,805 | 1055/28,401 | ||
| Model 1 | 1.00 (Ref) | 0.97 (0.88-1.08) | 1.12 (1.01-1.24) | 1.18 (1.07-1.30) | ＜0.001 | 1.19 (1.06-1.32) |
| Model 2 | 1.00 (Ref) | 0.96 (0.87-1.07) | 1.11 (1.00-1.22) | 1.12 (1.01-1.23) | 0.003 | 1.11 (1.00-1.24) |
| Model 3 | 1.00 (Ref) | 0.96 (0.87-1.07) | 1.11 (1.00-1.22) | 1.12 (1.01-1.23) | 0.003 | 1.11 (1.00-1.24) |
| CHD | ||||||
| No. of cases/person years | 592/28,243 | 661/28,245 | 821/29,308 | 880/28,951 | ||
| Model 1 | 1.00 (Ref) | 0.98 (0.88-1.10) | 1.11 (1.00-1.23) | 1.16 (1.04-1.29) | ＜0.001 | 1.15 (1.02-1.29) |
| Model 2 | 1.00 (Ref) | 0.97 (0.87-1.08) | 1.10 (0.99-1.22) | 1.10 (0.99-1.23) | 0.01 | 1.09 (0.97-1.22) |
| Model 3 | 1.00 (Ref) | 0.97 (0.87-1.08) | 1.10 (0.99-1.22) | 1.10 (0.99-1.23) | 0.02 | 1.08 (0.96-1.22) |
| ACS | ||||||
| No. of cases/person years | 197/26,220 | 250/25,953 | 292/26,413 | 344/25,925 | ||
| Model 1 | 1.00 (Ref) | 1.09 (0.90-1.31) | 1.17 (0.97-1.40) | 1.32 (1.11-1.58) | 0.001 | 1.28 (1.05-1.57) |
| Model 2 | 1.00 (Ref) | 1.06 (0.88-1.28) | 1.15 (0.95-1.37) | 1.24 (1.04-1.48) | 0.01 | 1.19 (0.98-1.45) |
| Model 3 | 1.00 (Ref) | 1.06 (0.88-1.28) | 1.14 (0.95-1.37) | 1.23 (1.03-1.47) | 0.01 | 1.18 (0.96-1.44) |
| Stroke | ||||||
| No. of cases/person years | 102/29,877 | 111/30,069 | 153/31,807 | 175/31,371 | ||
| Model 1 | 1.00 (Ref) | 0.95 (0.72-1.24) | 1.15 (0.89-1.48) | 1.27 (0.99-1.63) | 0.02 | 1.41 (1.06-1.88) |
| Model 2 | 1.00 (Ref) | 0.94 (0.72-1.23) | 1.13 (0.88-1.46) | 1.18 (0.92-1.51) | 0.07 | 1.29 (0.98-1.71) |
| Model 3 | 1.00 (Ref) | 0.94 (0.72-1.23) | 1.13 (0.88-1.45) | 1.18 (0.92-1.51) | 0.08 | 1.29 (0.97-1.71) |
| Ischemic stroke | ||||||
| No. of cases/person years | 82/29,788 | 82/29,929 | 123/31,639 | 133/31,178 | ||
| Model 1 | 1.00 (Ref) | 0.86 (0.63-1.17) | 1.13 (0.85-1.49) | 1.17 (0.89-1.55) | 0.08 | 1.34 (0.97-1.85) |
| Model 2 | 1.00 (Ref) | 0.85 (0.63-1.16) | 1.11 (0.84-1.48) | 1.10 (0.83-1.45) | 0.21 | 1.24 (0.91-1.71) |
| Model 3 | 1.00 (Ref) | 0.85 (0.63-1.16) | 1.11 (0.84-1.47) | 1.10 (0.83-1.45) | 0.22 | 1.24 (0.90-1.70) |
| Hemorrhagic stroke | ||||||
| No. of cases/person years | 20/29,485 | 29/29,650 | 30/31,247 | 42/30,721 | ||
| Model 1 | 1.00 (Ref) | 1.33 (0.75-2.36) | 1.24 (0.70-2.20) | 1.70 (0.99-2.93) | 0.06 | 1.71 (0.93-3.16) |
| Model 2 | 1.00 (Ref) | 1.32 (0.74-2.34) | 1.20 (0.68-2.12) | 1.54 (0.89-2.64) | 0.15 | 1.50 (0.82-2.74) |
| Model 3 | 1.00 (Ref) | 1.32 (0.74-2.33) | 1.20 (0.68-2.13) | 1.54 (0.90-2.65) | 0.14 | 1.51 (0.82-2.76) |
＊The quartiles of ALP levels in men were Q1 (＜69 U/L), Q2 (69-84 U/L), Q3 (84-100 U/L), and Q4 (＞100 U/L), while the quartiles of ALP levels in women were Q1 (＜71 U/L), Q2 (71-87 U/L), Q3 (87-105 U/L), and Q4 (＞105 U/L), respectively.
†Model 1 were adjusted for age and admission batch. Model 2 were additionally adjusted for BMI, smoking status, drinking status, physical activity, hypertension, hyperlipidemia, diabetes, aspirin usage, anticoagulants usage, menopausal status (women only), family history of CVD, and eGFR. Model 3 were further adjusted for WBC.
§p for trend was obtained by assigning the median value to each group and used this as a continuous variable in Cox regression models.
Abbreviations: ACS, acute coronary syndrome; ALP, alkaline phosphatase; BMI, body mass index; CHD, coronary heart disease; CI, coefficient interval; CVD, cardiovascular disease; eGFR, estimated glomerular filtration rate; HR, hazard ratio; SD, standard deviation; WBC, white blood cell.