Sub-hazard ratios for first event after entry by thirds of biomarkers in a competing risk model for 1112 fasting men with no CVD at entry and complete data
| MI/IHD | Stroke | Congestive heart failure | ||||||||
| Sub-hazard ratio (95% CI) | Sub-hazard ratio (95% CI) | Sub-hazard ratio95% CI) | ||||||||
| n | Events | Crude* | Adjusted† | Events | Crude* | Adjusted† | Events | Crude* | Adjusted† | |
| Troponin | ||||||||||
| Low <4.9 pg/mL | 358 | 40 | 1.00‡ | 1.00‡ | 42 | 1.00 | 1.00 | 7 | 1.00‡ | 1.00‡ |
| Mid 4.9–6.4 pg/mL | 341 | 50 | 1.35 (0.89 to 2.05) | 1.09 (0.71 to 1.67) | 39 | 0.90 (0.58 to 1.38) | 0.93 (0.58 to 1.49) | 12 | 1.73 (0.70 to 4.30) | 1.80 (0.70 to 4.60) |
| High >6.4 pg/mL | 360 | 84 | 2.22 (1.53 to 3.22) | 1.63 (1.10 to 2.41) | 35 | 0.73 (0.46 to 1.16) | 0.68 (0.41 to 1.13) | 27 | 3.68 (1.63 to 8.30) | 3.37 (1.39 to 8.14) |
| BNP | ||||||||||
| Low <15.8 pg/mL | 348 | 54 | 1.00 | 1.00 | 26 | 1.00 | 1.00 | 8 | 1.00 ‡ | 1.00 ‡ |
| Mid 15.8–27.8 pg/mL | 345 | 53 | 0.99 (0.67 to 1.45) | 0.95 (0.64 to 1.40) | 36 | 1.27 (0.75 to 2.13) | 1.26 (0.74 to 2.15) | 11 | 1.31 (0.52 to 3.30) | 1.26 (0.50 to 3.15) |
| High >27.8 pg/mL | 355 | 66 | 1.21 (0.84 to 1.73) | 1.20 (0.83 to 1.73) | 53 | 1.81 (1.11 to 2.94) | 1.75 (1.06 to 2.88) | 29 | 3.36 (1.50 to 7.52) | 3.23 (1.45 to 7.23) |
| CRP | ||||||||||
| Low <1.49 mg/L | 349 | 42 | 1.00 | 1.00 | 35 | 1.00 | 1.00 | 10 | 1.00 | 1.00 |
| Mid 1.49–3.32 mg/L | 354 | 65 | 1.54 (1.04 to 2.27) | 1.28 (0.86 to 1.92) | 41 | 1.14 (0.72 to 1.79) | 1.11 (0.70 to 1.75) | 20 | 1.94 (0.91 to 4.12) | 1.62 (0.74 to 3.56) |
| High >3.32 mg/L | 356 | 69 | 1.62 (1.10 to 2.40) | 1.25 (0.83 to 1.91) | 41 | 1.06 (0.67 to 1.68) | 1.03 (0.64 to 1.68) | 16 | 1.47 (0.66 to 3.26) | 1.10 (0.49 to 2.46) |
| IL-6 | ||||||||||
| Low <1.64 pg/mL | 351 | 53 | 1.00 | 1.00 | 30 | 1.00 | 1.00 | 14 | 1.00 | 1.00 |
| Mid 1.64–2.76 pg/mL | 356 | 65 | 1.22 (0.85 to 1.76) | 1.04 (0.71 to 1.52) | 42 | 1.36 (0.85 to 2.17) | 1.35 (0.85 to 2.13) | 18 | 1.23 (0.61 to 2.46) | 1.17 (0.57 to 2.40) |
| High >2.76 pg/mL | 354 | 58 | 1.07 (0.73 to 1.57) | 0.89 (0.60 to 1.32) | 45 | 1.39 (0.87 to 2.23) | 1.32 (0.82 to 2.11) | 14 | 0.89 (0.41 to 1.92) | 0.71 (0.31 to 1.61) |
| IL-6 receptor | ||||||||||
| Low <32.9 ng/mL | 353 | 58 | 1.00 | 1.00 | 45 | 1.00 | 1.00 | 14 | 1.00 | 1.00 |
| Mid 32.9–42.3 ng/mL | 351 | 54 | 0.93 (0.65 to 1.35) | 0.90 (0.62 to 1.32) | 31 | 0.69 (0.43 to 1.09) | 0.68 (0.42 to 1.10) | 16 | 1.15 (0.56 to 2.36) | 1.23 (0.60 to 2.51) |
| High >42.3 ng/mL | 357 | 64 | 1.09 (0.77 to 1.56) | 1.03 (0.71 to 1.48) | 40 | 0.84 (0.55 to 1.29) | 0.85 (0.55 to 1.32) | 16 | 1.10 (0.53 to 2.30) | 1.09 (0.53 to 2.26) |
| Cholesterol | ||||||||||
| Low <5.7 mmol/L | 363 | 35 | 1.00‡ | 1.00‡ | 42 | 1.00 | 1.00 | 17 | 1.00 | 1.00 |
| Mid 5.7–6.5 mmol/L | 358 | 59 | 1.79 (1.18 to 2.72) | 1.77 (1.15 to 2.70) | 49 | 1.21 (0.80 to 1.83) | 1.21 (0.80 to 1.84) | 15 | 0.91 (0.45 to 1.81) | 1.04 (0.51 to 2.14) |
| High >6.5 mmol/L | 391 | 90 | 2.62 (1.77 to 3.87) | 2.48 (1.63 to 3.77) | 36 | 0.80 (0.51 to 1.24) | 0.78 (0.49 to 1.23) | 18 | 1.00 (0.51 to 1.93) | 1.27 (0.62 to 2.61) |
| Triglyceride | ||||||||||
| Low <1.3 mmol/L | 362 | 46 | 1.00‡ | 1.00 | 39 | 1.00 | 1.00 | 17 | 1.00 | 1.00 |
| Mid 1.3–1.9 mmol/L | 373 | 63 | 1.36 (0.93 to 1.98) | 1.09 (0.73 to 1.62) | 49 | 1.26 (0.83 to 1.91) | 1.31 (0.84 to 2.05) | 20 | 1.17 (0.61 to 2.23) | 0.93 (0.49 to 1.77) |
| High >1.9 mmol/L | 377 | 75 | 1.67 (1.16 to 2.42) | 1.17 (0.77 to 1.78) | 39 | 1.03 (0.66 to 1.60) | 1.03 (0.65 to 1.63) | 13 | 0.77 (0.38 to 1.56) | 0.59 (0.28 to 1.26) |
| Lp-a | ||||||||||
| Low <5.0 mg/dL | 354 | 45 | 1.00‡ | 1.00‡ | 46 | 1.00 | 1.00 | 22 | 1.00 | 1.00 |
| Mid 5.0–13.6 mg/dL | 350 | 55 | 1.26 (0.85 to 1.86) | 1.39 (0.93 to 2.09) | 36 | 0.78 (0.50 to 1.20) | 0.80 (0.52 to 1.24) | 11 | 0.49 (0.24 to 1.01) | 0.41 (0.19 to 0.86) |
| High >13.6 mg/dL | 350 | 76 | 1.81 (1.25 to 2.61) | 1.84 (1.26 to 2.69) | 35 | 0.76 (0.49 to 1.19) | 0.81 (0.52 to 1.27) | 13 | 0.59 (0.30 to 1.18) | 0.52 (0.25 to 1.08) |
| VCAM-1 | ||||||||||
| Low <1195 ng/mL | 349 | 69 | 1.00 | 1.00 | 32 | 1.00 | 1.00 | 10 | 1.00 | 1.00 |
| Mid 1195–1379 ng/mL | 357 | 49 | 0.66 (0.46 to 0.95) | 0.64 (0.44 to 0.93) | 43 | 1.29 (0.82 to 2.04) | 1.30 (0.81 to 2.06) | 19 | 1.82 (0.84 to 3.93) | 1.84 (0.86 to 3.94) |
| High >1379 ng/mL | 355 | 58 | 0.78 (0.55 to 1.11) | 0.84 (0.59 to 1.20) | 42 | 1.21 (0.76 to 1.91) | 1.12 (0.70 to 1.80) | 17 | 1.56 (0.70 to 3.46) | 1.76 (0.78 to 3.97) |
| E-selectin | ||||||||||
| Low <21.8 ng/mL | 358 | 64 | 1.00 | 1.00 | 33 | 1.00 | 1.00 | 14 | 1.00 | 1.00 |
| Mid 21.8–31.0 ng/mL | 355 | 55 | 0.85 (0.59 to 1.23) | 0.79 (0.55 to 1.15) | 40 | 1.28 (0.81 to 2.04) | 1.26 (0.79 to 2.02) | 13 | 0.96 (0.45 to 2.04) | 0.89 (0.42 to 1.90) |
| High >31.0 ng/mL | 349 | 57 | 0.90 (0.63 to 1.28) | 0.78 (0.53 to 1.13) | 44 | 1.49 (0.95 to 2.34) | 1.38 (0.87 to 2.19) | 19 | 1.48 (0.75 to 2.93) | 1.32 (0.65 to 2.68) |
| Alkaline phosphatase | ||||||||||
| Low <76 IU/L | 384 | 61 | 1.00 | 1.00 | 33 | 1.00 | 1.00 | 18 | 1.00 | 1.00 |
| Mid 76–96 IU/L | 369 | 63 | 1.05 (0.74 to 1.50) | 0.93 (0.65 to 1.34) | 44 | 1.36 (0.87 to 2.14) | 1.42 (0.90 to 2.25) | 16 | 0.91 (0.47 to 1.80) | 0.84 (0.42 to 1.68) |
| High >96 IU/L | 352 | 59 | 1.04 (0.72 to 1.48) | 0.85 (0.58 to 1.24) | 50 | 1.57 (1.00 to 2.47) | 1.50 (0.95 to 2.38) | 16 | 0.90 (0.45 to 1.81) | 0.87 (0.43 to 1.76) |
| Aspartate transaminase | ||||||||||
| Low <20 IU/L | 380 | 74 | 1.00 | 1.00 | 61 | 1.00 | 1.00 | 14 | 1.00 | 1.00 |
| Mid 20–24 IU/L | 347 | 60 | 0.88 (0.62 to 1.23) | 0.96 (0.68 to 1.35) | 29 | 0.50 (0.32 to 0.78) | 0.54 (0.34 to 0.85) | 14 | 1.11 (0.53 to 2.34) | 1.04 (0.48 to 2.29) |
| High >24 IU/L | 372 | 47 | 0.63 (0.44 to 0.91) | 0.68 (0.46 to 0.99) | 37 | 0.62 (0.41 to 0.93) | 0.63 (0.41 to 0.96) | 21 | 1.60 (0.82 to 3.15) | 1.63 (0.82 to 3.22) |
| Alanine transaminase | ||||||||||
| Low <19 IU/L | 364 | 59 | 1.00 | 1.00 | 39 | 1.00 | 1.00 | 17 | 1.00 | 1.00 |
| Mid 19–25 IU/L | 382 | 64 | 1.05 (0.73 to 1.50) | 0.98 (0.68 to 1.42) | 54 | 1.43 (0.94 to 2.17) | 1.44 (0.92 to 2.25) | 17 | 1.01 (0.51 to 1.99) | 0.91 (0.45 to 1.82) |
| High >25 IU/L | 360 | 59 | 1.02 (0.71 to 1.47) | 0.93 (0.62 to 1.39) | 34 | 0.99 (0.62 to 1.59) | 0.96 (0.57 to 1.62) | 16 | 1.07 (0.54 to 2.13) | 1.00 (0.49 to 2.02) |
| Gamma-GT | ||||||||||
| Low <23 IU/L | 354 | 56 | 1.00 | 1.00 | 40 | 1.00 | 1.00 | 12 | 1.00 | 1.00 |
| Mid 23–35 IU/L | 378 | 61 | 1.02 (0.71 to 1.47) | 0.88 (0.61 to 1.28) | 44 | 1.04 (0.68 to 1.59) | 1.04 (0.67 to 1.61) | 24 | 1.95 (0.98 to 3.88) | 1.79 (0.86 to 3.71) |
| High >35 IU/L | 380 | 67 | 1.13 (0.79 to 1.61) | 0.80 (0.54 to 1.18) | 43 | 1.05 (0.68 to 1.62) | 0.99 (0.62 to 1.58) | 14 | 1.14 (0.53 to 2.42) | 0.97 (0.45 to 2.13) |
| Glutamate dehydrogenase | ||||||||||
| Low <1.41 IU/L | 179 | 35 | 1.00 | 1.00 | 21 | 1.00 | 1.00 | 7 | 1.00 | 1.00 |
| Mid 1.41–2.80 IU/L | 175 | 28 | 0.82 (0.50 to 1.34) | 0.81 (0.48 to 1.35) | 17 | 0.84 (0.44 to 1.60) | 0.88 (0.46 to 1.68) | 8 | 1.20 (0.43 to 3.35) | 1.25 (0.41 to 3.78) |
| High >2.80 IU/L | 179 | 36 | 1.07 (0.68 to 1.70) | 1.03 (0.63 to 1.68) | 22 | 1.11 (0.61 to 2.03) | 1.15 (0.62 to 2.15) | 8 | 1.23 (0.43 to 3.49) | 1.23 (0.43 to 3.56) |
| White cell count | ||||||||||
| Low <5.40×109/L | 367 | 49 | 1.00† | 1.00 | 38 | 1.00 | 1.00 | 17 | 1.00 | 1.00 |
| Mid 5.40–6.79×109/L | 369 | 57 | 1.18 (0.81 to 1.73) | 1.13 (0.77 to 1.64) | 37 | 0.98 (0.62 to 1.53) | 0.95 (0.60 to 1.49) | 12 | 0.70 (0.34 to 1.47) | 0.75 (0.35 to 1.58) |
| High >6.79×109/L | 369 | 78 | 1.65 (1.16 to 2.36) | 1.44 (1.00 to 2.09) | 51 | 1.37 (0.90 to 2.08) | 1.43 (0.90 to 2.27) | 20 | 1.18 (0.62 to 2.26) | 1.30 (0.61 to 2.74) |
| Viscosity | ||||||||||
| Low <1.65 mPa.s | 388 | 46 | 1.00‡ | 1.00 | 39 | 1.00 | 1.00 | 14 | 1.00 | 1.00 |
| Mid 1.65–1.71 mPa.s | 335 | 62 | 1.58 (1.08 to 2.31) | 1.41 (0.95 to 2.08) | 34 | 0.97 (0.61 to 1.53) | 0.98 (0.61 to 1.58) | 13 | 1.03 (0.48 to 2.20) | 1.02 (0.48 to 2.17) |
| High >1.71 mPa.s | 378 | 75 | 1.70 (1.17 to 2.46) | 1.29 (0.87 to 1.92) | 53 | 1.28 (0.85 to 1.95) | 1.25 (0.81 to 1.94) | 22 | 1.48 (0.74 to 2.96) | 1.44 (0.72 to 2.91) |
| Fibrinogen | ||||||||||
| Low <3.6 g/L | 359 | 50 | 1.00 | 1.00 | 32 | 1.00 | 1.00 | 18 | 1.00 | 1.00 |
| Mid 3.6–4.3 g/L | 367 | 60 | 1.17 (0.81 to 1.70) | 1.07 (0.74 to 1.57) | 49 | 1.45 (0.93 to 2.27) | 1.57 (0.98 to 2.50) | 13 | 0.67 (0.33 to 1.36) | 0.60 (0.29 to 1.26) |
| High >4.3 g/L | 369 | 73 | 1.46 (1.02 to 2.10) | 1.32 (0.92 to 1.91) | 44 | 1.22 (0.77 to 1.93) | 1.27 (0.79 to 2.06) | 18 | 0.89 (0.47 to 1.71) | 0.90 (0.46 to 1.74) |
| Ferritin | ||||||||||
| Low <83 ng/mL | 355 | 54 | 1.00 | 1.00 | 37 | 1.00 | 1.00 | 13 | 1.00 | 1.00 |
| Mid 83–161 ng/mL | 352 | 67 | 1.30 (0.91 to 1.85) | 1.18 (0.82 to 1.69) | 40 | 1.12 (0.71 to 1.75) | 1.13 (0.71 to 1.78) | 12 | 0.95 (0.43 to 2.08) | 0.86 (0.38 to 1.91) |
| High >161 ng/mL | 352 | 54 | 1.02 (0.70 to 1.49) | 0.89 (0.60 to 1.30) | 39 | 1.09 (0.69 to 1.71) | 1.04 (0.65 to 1.67) | 21 | 1.70 (0.84 to 3.44) | 1.66 (0.78 to 3.51) |
| GDF-15 | ||||||||||
| Low <591 pg/mL | 358 | 53 | 1.00 | 1.00 | 35 | 1.00 | 1.00 | 12 | 1.00 | 1.00 |
| Mid 591–813 pg/mL | 350 | 63 | 1.18 (0.81 to 1.71) | 1.03 (0.70 to 1.51) | 40 | 1.05 (0.66 to 1.66) | 1.00 (0.63 to 1.59) | 15 | 1.19 (0.55 to 2.56) | 1.10 (0.49 to 2.45) |
| High >813 pg/mL | 354 | 60 | 1.10 (0.75 to 1.61) | 0.91 (0.60 to 1.38) | 42 | 1.01 (0.63 to 1.62) | 0.89 (0.54 to 1.47) | 19 | 1.39 (0.62 to 3.08) | 1.18 (0.50 to 2.78) |
| PAPP-A | ||||||||||
| Low <6.00 ng/mL | 353 | 61 | 1.00 | 1.00 | 32 | 1.00 | 1.00 | 9 | 1.00 | 1.00 |
| Mid 6.00–8.52 ng/mL | 351 | 57 | 0.90 (0.62 to 1.29) | 0.91 (0.63 to 1.32) | 40 | 1.23 (0.77 to 1.95) | 1.23 (0.76 to 1.98) | 20 | 2.17 (0.99 to 4.74) | 2.39 (1.08 to 5.30) |
| High >8.52 ng/mL | 356 | 58 | 0.89 (0.62 to 1.27) | 1.04 (0.72 to 1.50) | 45 | 1.32 (0.84 to 2.08) | 1.31 (0.82 to 2.11) | 17 | 1.78 (0.80 to 3.96) | 2.19 (0.97 to 4.94) |
| Cystatin | ||||||||||
| Low <0.79 mg/L | 357 | 53 | 1.00 | 1.00 | 28 | 1.00 | 1.00 | 16 | 1.00 | 1.00 |
| Mid 0.79–0.89 mg/L | 340 | 54 | 1.06 (0.72 to 1.55) | 1.06 (0.71 to 1.56) | 45 | 1.62 (1.01 to 2.59) | 1.64 (1.02 to 2.64) | 10 | 0.61 (0.28 to 1.35) | 0.53 (0.24 to 1.16) |
| High >0.89 mg/L | 362 | 69 | 1.26 (0.87 to 1.82) | 1.02 (0.69 to 1.52) | 44 | 1.37 (0.84 to 2.24) | 1.36 (0.80 to 2.29) | 20 | 1.09 (0.52 to 2.24) | 0.99 (0.48 to 2.04) |
| Creatinine | ||||||||||
| Low <0.90 mg/dL | 353 | 72 | 1.00 | 1.00 | 43 | 1.00 | 1.00 | 14 | 1.00 | 1.00 |
| Mid 0.90–0.99 mg/dL | 363 | 53 | 0.71 (0.50 to 1.01) | 0.73 (0.51 to 1.04) | 42 | 0.95 (0.62 to 1.45) | 0.96 (0.63 to 1.47) | 14 | 0.97 (0.46 to 2.03) | 1.00 (0.46 to 2.17) |
| High >0.99 mg/dL | 339 | 51 | 0.73 (0.51 to 1.04) | 0.73 (0.50 to 1.05) | 32 | 0.74 (0.47 to 1.18) | 0.78 (0.49 to 1.26) | 18 | 1.30 (0.65 to 2.63) | 1.44 (0.66 to 3.14) |
| Glucose | ||||||||||
| Low <5.1 mmol/L | 369 | 58 | 1.00 | 1.00 | 37 | 1.00 | 1.00 | 14 | 1.00 | 1.00 |
| Mid 5.1–5.5 mmol/L | 373 | 55 | 0.94 (0.65 to 1.36) | 0.92 (0.63 to 1.34) | 39 | 1.05 (0.67 to 1.65) | 1.04 (0.67 to 1.64) | 17 | 1.22 (0.60 to 2.48) | 1.25 (0.61 to 2.57) |
| High >5.5 mmol/L | 363 | 71 | 1.26 (0.89 to 1.79) | 1.19 (0.80 to 1.76) | 51 | 1.43 (0.93 to 2.18) | 1.26 (0.79 to 2.01) | 19 | 1.38 (0.69 to 2.76) | 1.14 (0.56 to 2.32) |
| RBP-4 | ||||||||||
| Low <27.6 mg/L | 357 | 62 | 1.00 | 1.00 | 46 | 1.00 | 1.00 | 18 | 1.00 | 1.00 |
| Mid 27.6–35.0 mg/L | 348 | 54 | 0.92 (0.63 to 1.32) | 0.87 (0.60 to 1.27) | 40 | 0.93 (0.61 to 1.42) | 0.94 (0.60 to 1.46) | 16 | 0.94 (0.48 to 1.84) | 0.96 (0.48 to 1.89) |
| High >35.0 mg/L | 355 | 60 | 0.99 (0.70 to 1.41) | 0.86 (0.60 to 1.23) | 30 | 0.67 (0.42 to 1.06) | 0.69 (0.42 to 1.15) | 12 | 0.68 (0.33 to 1.40) | 0.67 (0.32 to 1.38) |
| Fetuin-A | ||||||||||
| Low <236 mg/L | 357 | 57 | 1.00 | 1.00 | 37 | 1.00 | 1.00 | 9 | 1.00 | 1.00 |
| Mid 236–289 mg/L | 348 | 52 | 0.93 (0.64 to 1.36) | 0.93 (0.64 to 1.37) | 37 | 1.05 (0.67 to 1.66) | 1.05 (0.66 to 1.66) | 19 | 2.21 (1.00 to 4.88) | 2.41 (1.10 to 5.27) |
| High >289 mg/L | 354 | 67 | 1.20 (0.84 to 1.71) | 1.06 (0.74 to 1.52) | 42 | 1.18 (0.76 to 1.84) | 1.24 (0.78 to 1.96) | 18 | 2.08 (0.93 to 4.64) | 1.93 (0.87 to 4.28) |
| Uric acid | ||||||||||
| Low <31 mg/L | 369 | 61 | 1.00 | 1.00 | 43 | 1.00 | 1.00 | 15 | 1.00 | 1.00 |
| Mid 31–36 mg/L | 360 | 61 | 1.05 (0.74 to 1.49) | 1.01 (0.71 to 1.44) | 39 | 0.93 (0.60 to 1.43) | 0.98 (0.63 to 1.52) | 15 | 1.04 (0.51 to 2.13) | 1.09 (0.50 to 2.38) |
| High >36 mg/L | 382 | 62 | 0.99 (0.70 to 1.41) | 0.88 (0.60 to 1.29) | 45 | 1.04 (0.68 to 1.57) | 1.08 (0.66 to 1.75) | 20 | 1.31 (0.68 to 2.55) | 1.42 (0.69 to 2.88) |
| Vitamin B6 | ||||||||||
| Low <33.1 nmol/L | 346 | 56 | 1.00 | 1.00 | 39 | 1.00 | 1.00 | 14 | 1.00 | 1.00 |
| Mid 33.1–48.8 nmol/L | 353 | 60 | 1.06 (0.74 to 1.53) | 1.09 (0.75 to 1.59) | 40 | 1.05 (0.67 to 1.63) | 1.06 (0.68 to 1.64) | 20 | 1.47 (0.74 to 2.90) | 1.62 (0.78 to 3.33) |
| High >48.8 nmol/L | 355 | 57 | 0.99 (0.69 to 1.43) | 1.00 (0.67 to 1.48) | 34 | 0.88 (0.56 to 1.40) | 0.91 (0.57 to 1.47) | 15 | 1.09 (0.53 to 2.24) | 1.27 (0.59 to 2.74) |
*Adjusted for age only.
†Adjusted for age, smoking, diabetes, systolic blood pressure, total cholesterol, total triglycerides, body mass index and family history of premature CHD.
‡Significant test for trend in sub-hazard ratio (P<0.01).
BNP, B-type natriuretic peptide; CHD, coronary heart disease; CRP, C reactive protein; CVD, cardiovascular disease; GDF-15, growth differentiation factor-15; IHD, ischaemic heart disease; IL, interleukin; Lp-a, lipoprotein-a; MI, myocardial infarction; PAPP-A, pregnancy- associated plasma protein-A; RBP-4, retinol binding protein-4; VCAM-1, vascular cell adhesion molecule-1.