Table 3. Crude and Adjusted HRs for All Cardiovascular Events Between Patients and Matched Controls.
| Characteristic | No. of patients | HR (95% CI) | ||
|---|---|---|---|---|
| Crude | Adjusted simple modela | Adjusted full modelb | ||
| All patients | 3408 | 1.13 (0.95-1.36) | 1.58 (1.23-2.01) | 1.69 (1.30-2.19) |
| Male | 2305 | 1.04 (0.84-1.30) | 1.39 (1.03-1.89) | 1.55 (1.12-2.13) |
| Female | 1103 | 1.34 (0.99-1.81) | 2.05 (1.36-3.08) | 2.05 (1.31-3.20) |
| Patients with SGA | 672 | 1.27 (0.87-1.85) | 1.84 (1.21-2.80) | 1.97 (1.28-3.04) |
| Male | 423 | 1.14 (0.70-1.88) | 1.60 (0.93-2.77) | 1.78 (1.02-3.09) |
| Female | 249 | 1.47 (0.81-2.68) | 2.40 (1.24-4.63) | 2.39 (1.17-4.88) |
| Patients with GHD | 1837 | 1.16 (0.92-1.46) | 1.60 (1.19-2.13) | 1.66 (1.21-2.26) |
| Male | 1312 | 1.07 (0.81-1.42) | 1.41 (0.99-2.01) | 1.55 (1.06-2.25) |
| Female | 525 | 1.38 (0.92-2.07) | 2.10 (1.28-3.47) | 1.94 (1.11-3.39) |
| Patients with GHD (maximum growth hormone level, 0-4 ng/mL)c | 485 | 1.28 (0.86-1.90) | 1.77 (1.15-2.73) | 1.79 (1.12-2.87) |
| Male | 349 | 1.13 (0.69-1.85) | 1.51 (0.88-2.58) | 1.64 (0.92-2.92) |
| Female | 136 | 1.70 (0.87-3.32) | 2.52 (1.22-5.21) | 2.16 (0.94-4.94) |
| Patients with GHD (maximum growth hormone level, 5-9 ng/mL)c | 1352 | 1.11 (0.84-1.47) | 1.52 (1.09-2.12) | 1.60 (1.12-2.28) |
| Male | 963 | 1.05 (0.74-1.48) | 1.37 (0.91-2.05) | 1.51 (0.98-2.31) |
| Female | 389 | 1.26 (0.77-2.06) | 1.94 (1.09-3.44) | 1.84 (0.97-3.47) |
| Patients with ISS | 899 | 0.97 (0.67-1.42) | 1.34 (0.89-2.01) | 1.55 (1.01-2.37) |
| Male | 570 | 0.90 (0.56-1.45) | 1.20 (0.72-2.01) | 1.38 (0.81-2.35) |
| Female | 329 | 1.13 (0.61-2.12) | 1.69 (0.87-3.28) | 2.00 (1.00-4.02) |
| Duration of treatment, yd | ||||
| 0-2 | 925 | 0.71 (0.43-1.18) | 0.98 (0.57-1.69) | 1.05 (0.59-1.88) |
| 3-6 | 1522 | 0.99 (0.74-1.32) | 1.35 (0.95-1.91) | 1.58 (1.10-2.28) |
| ≥7 | 961 | 1.45 (1.01-2.08) | 1.94 (1.29-2.93) | 2.08 (1.35-3.20) |
| P value for trend | NA | .02 | .01 | .01 |
| Mean growth hormone dose, μg/kg/dd | ||||
| 0-29 | 402 | 1.10 (0.53-2.31) | 1.49 (0.70-3.19) | 1.76 (0.82-3.77) |
| 30-39 | 2383 | 1.09 (0.85-1.40) | 1.50 (1.10-2.05) | 1.64 (1.18-2.28) |
| 40-49 | 337 | 0.73 (0.36-1.47) | 0.99 (0.48-2.05) | 1.25 (0.60-2.59) |
| ≥50 | 279 | 0.94 (0.50-1.75) | 1.28 (0.68-2.47) | 1.51 (0.79-2.91) |
| P value for trend | NA | .55 | .47 | .51 |
| Cumulative dose, mgd | ||||
| 0-1499 | 1015 | 0.86 (0.54-1.37) | 1.16 (0.70-1.90) | 1.34 (0.80-2.25) |
| 1500-2999 | 954 | 1.20 (0.85-1.69) | 1.64 (1.11-2.42) | 1.76 (1.16-2.68) |
| 3000-4499 | 902 | 0.85 (0.56-1.28) | 1.16 (0.73-1.84) | 1.36 (0.84-2.18) |
| ≥4500 | 381 | 1.35 (0.82-2.21) | 1.86 (1.10-3.16) | 2.05 (1.18-3.55) |
| P value for trend | NA | .43 | .25 | .24 |
Abbreviations: GHD, growth hormone deficiency; HR, hazard ratio; ISS, idiopathic short stature; SGA, small for gestational age.
SI conversion factor: To convert growth hormone to μg/L, multiply by 1.
a
Adjusted only for age at start, height at start, and sex (if not stratified for sex).
b
Adjusted for gestational age, birth length, birth weight, age at start, height at start, parental educational level, family income, and sex (if not stratified for sex).
c
Maximum indicates growth hormone peak level on either provocation test (mainly arginine-insulin tolerance test) or during spontaneous 12- or 24-hour growth hormone secretion profiles.
d
Analysis with 2-year lag-period after end of treatment to avoid reversed causality (protopathic bias).