INTRODUCTION
1. Risk factors of LBP
2. Aims of the study
MATERIALS AND METHODS
1. Study design and cohort description
2. Data extraction and candidate predictors
3. Assessment of covariates
4. Outcomes and exclusion criteria
5. Statistical analysis
1) Models derivation
2) Measures of predictive performance
RESULTS
1. Cohort baseline characteristics
Table 1
2. Model derivation
Table 2
Covariate | Unadjusteda | Adjustedb | ||||
---|---|---|---|---|---|---|
|
|
|||||
β (SE) | HR (95% CI) | P value | β (SE) | HR (95% CI) | P value | |
Sex | ||||||
F | 0.351 (0.005) | 1.42 (1.41-1.44) | < 0.001 | 0.331 (0.007) | 1.39 (1.37-1.41) | < 0.001 |
Age (yr) | ||||||
< 45 | Reference | Reference | Reference | Reference | ||
45-54 | 0.501 (0.007) | 1.65 (1.63-1.67) | < 0.001 | 0.505 (0.007) | 1.66 (1.63-1.68) | < 0.001 |
55-64 | 0.805 (0.007) | 2.24 (2.21-2.27) | < 0.001 | 0.810 (0.008) | 2.25 (2.22-2.28) | < 0.001 |
≥ 65 | 1.07 (0.009) | 2.91 (2.86-2.97) | < 0.001 | 1.061 (0.009) | 2.89 (2.84-2.94) | < 0.001 |
Income/Insurance premium (%) | ||||||
High (> 60) | Reference | Reference | Reference | Reference | ||
Medium (30-60) | 0.001 (0.006) | 1.00 (0.99-1.01) | 0.8166 | 0.054 (0.006) | 1.06 (1.04-1.07) | < 0.001 |
Low (< 30) | 0.065 (0.008) | 1.07 (1.05-1.08) | < 0.001 | 0.029 (0.008) | 1.03 (1.01-1.05) | < 0.001 |
Physical activity (times/wk) | ||||||
High (≥ 4) | Reference | Reference | Reference | Reference | ||
Moderate (1-3) | –0.028 (0.012) | 0.97 (0.95-0.99) | < 0.001 | –0.006 (0.012) | 0.99 (0.97-1.02) | 0.0012 |
Low (none) | 0.074 (0.011) | 1.08 (1.05-1.10) | < 0.001 | 0.005 (0.011) | 1.01 (0.98-1.03) | 0.0693 |
Smoking status | ||||||
Never | Reference | Reference | Reference | Reference | ||
Former | –0.248 (0.014) | 0.78 (0.76-0.80) | < 0.001 | –0.007 (0.014) | 0.99 (0.97-1.02) | 0.6060 |
Current smoker | –0.331 (0.006) | 0.72 (0.71-0.73) | < 0.001 | –0.016 (0.008) | 0.98 (0.96-1.00) | 0.0519 |
Alcohol consumption (times/mo) | ||||||
Rarely (< 2) | Reference | Reference | Reference | Reference | ||
Moderate (2-3) | –0.253 (0.006) | 0.78 (0.77-0.79) | < 0.001 | –0.031 (0.006) | 0.97 (0.96-0.98) | < 0.001 |
Heavy (≥ 4) | –0.287 (0.010) | 0.75 (0.74-0.77) | < 0.001 | –0.007 (0.011) | 0.99 (0.97-1.01) | 0.5157 |
BMI (kg/m2) | ||||||
< 18.5 | –0.278 (0.012) | 0.76 (0.74-0.78) | < 0.001 | –0.24452 (0.013) | 0.783 (0.764-0.802) | < 0.001 |
18.5-24.9 | Reference | Reference | Reference | Reference | ||
25.0-29.9 | 0.160 (0.006) | 1.17 (1.16-1.19) | < 0.001 | 0.105 (0.006) | 1.11 (1.10-1.12) | < 0.001 |
≥ 30.0 | 0.211 (0.016) | 1.24 (1.20-1.27) | < 0.001 | 0.134 (0.016) | 1.14 (1.11-1.18) | < 0.001 |
Total cholesterol (mg/dL) | ||||||
< 200 | Reference | Reference | Reference | Reference | ||
200-239 | 0.141 (0.006) | 1.15 (1.14-1.17) | < 0.001 | 0.035 (0.006) | 1.04 (1.02-1.05) | < 0.001 |
≥ 240 | 0.202 (0.008) | 1.22 (1.20-1.24) | < 0.001 | 0.007 (0.009) | 1.01 (0.99-1.02) | 0.4208 |
Fasting blood glucose (mg/dL) | ||||||
< 100 | Reference | Reference | Reference | Reference | ||
100-125 | 0.082 (0.006) | 1.09 (1.07-1.10) | < 0.001 | 0.008 (0.006) | 1.01 (1.00-1.02) | 0.1885 |
> 126 or Tx | 0.139 (0.008) | 1.15 (1.13-1.17) | < 0.001 | –0.018 (0.008) | 0.98 (0.97-0.99) | 0.0318 |
Diagnosed HTN (mmHg) | ||||||
SBP < 120 and DBP < 80 | Reference | Reference | Reference | Reference | ||
SBP 120-139 or DBP 80-89 | 0.110 (0.006) | 1.12 (1.10-1.13) | < 0.001 | 0.028 (0.006) | 1.03 (1.02-1.04) | < 0.001 |
SBP 140-159 or DBP 90-99 | 0.200 (0.009) | 1.22 (1.20-1.24) | < 0.001 | –0.010 (0.010) | 0.99 (0.97-1.01) | 0.2894 |
SBP ≥ 160 or DBP ≥ 100 or Rx | 0.244 (0.023) | 1.28 (1.22-1.34) | < 0.001 | –0.043 (0.024) | 0.96 (0.92-1.00) | 0.0706 |
BMI (kg/m2) | 0.037 (0.0008) | 1.037 (1.036-1.039) | < 0.001 | 0.027 (0.00082) | 1.027 (1.025-1.029) | < 0.001 |
Fasting blood glucose (mg/dL) | 0.002 (0.00009) | 1.002 (1.002-1.002) | < 0.001 | –0.00004 (0.00009) | 1.000 (1.000-1.000) | 0.6896 |
Total cholesterol (mg/dL) | 0.002 (0.00007) | 1.002 (1.002-1.003) | < 0.001 | 0.0004 (0.00007) | 1.000 (1.000-1.001) | < 0.001 |
SBP (mmHg) | 0.006 (0.00015) | 1.006 (1.005-1.006) | < 0.001 | 0.0005 (0.0002) | 1.000 (1.000-1.001) | 0.0048 |
DBP (mmHg) | 0.005 (0.0002) | 1.005 (1.004-1.005) | < 0.001 | 0.0006 (0.00024) | 1.001 (1.000-1.001) | 0.0081 |
Premorbid diseases | ||||||
History of diabetes | 0.474 (0.012) | 1.61 (1.57-1.65) | < 0.001 | 0.111 (0.013) | 1.12 (1.09-1.15) | < 0.001 |
History of hypertension | 0.530 (0.008) | 1.70 (1.67-1.73) | < 0.001 | 0.101 (0.009) | 1.11 (1.09-1.13) | < 0.001 |
Diagnosed IHD | 0.542 (0.022) | 1.72 (1.65-1.80) | < 0.001 | 0.177 (0.023) | 1.19 (1.14-1.25) | < 0.001 |
Diagnosed IVDD | 0.781 (0.009) | 2.18 (2.14-2.22) | < 0.001 | 0.587 (0.009) | 1.80 (1.77-1.83) | < 0.001 |
History of back injury | 0.680 (0.030) | 1.97 (1.86-2.09) | < 0.001 | 0.541 (0.030) | 1.72 (1.62-1.82) | < 0.001 |
Spinal stenosis | 1.07 (0.020) | 2.93 (2.81-3.05) | < 0.001 | 0.591 (0.021) | 1.81 (1.74-1.88) | < 0.001 |
BMD disorders | 0.887 (0.012) | 2.43 (2.37-2.48) | < 0.001 | 0.383 (0.012) | 1.47 (1.43-1.50) | < 0.001 |
Spondylolisthesis | 0.979 (0.072) | 2.66 (2.31-3.07) | < 0.001 | 0.563(0.072) | 1.76 (1.52-2.02) | < 0.001 |
HR: hazard ratio, CI: confidence interval, SE: standard error, BMI: body mass index, Tx: medication due to diabetes, HTN: hypertension, SBP: systolic blood pressure, DBP: diastolic blood pressure, Rx: medication due to HTN, IHD: ischemic heart disease, IVDD: intervertebral disc degeneration, BMD: bone mineral density.
a Univariate analysis. bFully adjusted accounting for age, sex, income grade, physical activity, smoking status, alcohol consumption, and each of the other risk factors (fasting blood glucose/diabetes, total cholesterol, blood pressure/HTN, prior history of [diabetes, HTN, IHD, IVDD, history of back injury, spinal stenosis, BMD disorders, spondylolisthesis]).
Table 3
Covariate | β (SE) | HR (95% CI) | P value | Risk pointa |
---|---|---|---|---|
Sex | ||||
M | Reference | Reference | 0 | |
F | 0.315 (0.008) | 1.37 (1.35-1.39) | < 0.001 | 32 |
Age (yr) | ||||
< 45 | Reference | Reference | 0 | |
45-54 | 0.437 (0.009) | 1.55 (1.52-1.58) | < 0.001 | 44 |
55-64 | 0.729 (0.010) | 2.07 (2.04-2.11) | < 0.001 | 73 |
≥ 65 | 0.979 (0.012) | 2.66 (2.60-2.72) | < 0.001 | 98 |
Income/Insurance premium (%) | ||||
High (> 60) | Reference | Reference | 0 | |
Medium (30-60) | 0.063 (0.008) | 1.07 (1.05-1.08) | < 0.001 | 6 |
Low (< 30) | 0.036 (0.010) | 1.04 (1.02-1.06) | < 0.001 | 4 |
Physical activity (times/wk) | ||||
High (≥ 4) | Reference | Reference | 0 | |
Moderate (1-3) | –0.007 (0.014) | 0.99 (0.97-1.02) | 0.0030 | –1 |
Low (none) | 0.017 (0.014) | 1.02 (0.99-1.05) | 0.0589 | 2 |
Alcohol consumption (times/mo) | ||||
Rarely (< 2) | Reference | Reference | 0 | |
Moderate drinker (2-3) | –0.041 (0.008) | 0.96 (0.95-0.97) | < 0.001 | –4 |
Heavy drinker (≥ 4) | –0.021 (0.013) | 0.98 (0.95-1.01) | 0.1243 | –2 |
BMI (kg/m2) | ||||
< 18.5 | –0.231 (0.015) | 0.79 (0.77-0.82) | < 0.001 | –23 |
18.5-24.9 | Reference | Reference | 0 | |
25.0-29.9 | 0.104 (0.007) | 1.11 (1.09-1.13) | < 0.001 | 10 |
≥ 30 | 0.121 (0.019) | 1.13 (1.09-1.17) | < 0.001 | 12 |
Blood pressure/HTN | ||||
SBP < 120 and DBP < 80 | Reference | Reference | 0 | |
SBP 120-139 or DBP 80-89 | 0.0004 (0.007) | 1.00 (0.99-1.02) | 0.9570 | 0 |
SBP 140-159 or DBP 90-99 | –0.036 (0.012) | 0.97 (0.94-0.99) | 0.0031 | –4 |
SBP ≥ 160 or DBP ≥ 100 or Rx | –0.082 (0.030) | 0.92 (0.87-0.98) | 0.0054 | –8 |
Total cholesterol (mg/dL) | ||||
< 200 | Reference | Reference | 0 | |
200-239 | 0.014 (0.007) | 1.01 (1.00-1.03) | 0.0513 | 1 |
≥ 240 | –0.029 (0.011) | 0.97 (0.95-0.99) | 0.0053 | –3 |
Diagnosed IVDD | ||||
No | Reference | Reference | 0 | |
Yes | 0.532 (0.012) | 1.70 (1.67-1.74) | < 0.001 | 53 |
Spinal stenosis | ||||
No | Reference | Reference | 0 | |
Yes | 0.207 (0.028) | 1.23 (1.17-1.30) | < 0.001 | 21 |
History of BMD disorders | ||||
No | Reference | Reference | 0 | |
Yes | 0.254 (0.016) | 1.29 (1.25-1.33) | < 0.001 | 25 |
3. Model performance evaluation
Table 4
Model and risk score performance metrics | Derivation cohort | Validation cohort |
---|---|---|
Model based performance | ||
Brier scorea | 0.293 | 0.294 |
Nam–D’Agostino testb | χ2 = 7.5930, P = 0.3031 | χ2 = 7.6178, P = 0.3407 |
Harrell’s C statistic (95% CI)c | 0.810 (0.805-0.816) | 0.812 (0.804-0.820) |
Sensitivity (95% CI) | 0.442 (0.439-0.446) | 0.443 (0.438-0.447) |
Specificity (95% CI) | 0.954 (0.953-0.955) | 0.954 (0.953-0.956) |
Positive predictive value (95% CI) | 0.825 (0.822-0.828) | 0.825 (0.821-0.830) |
Negative predictive value (95% CI) | 0.777 (0.776-0.778) | 0.777 (0.776-0.779) |
Accuracy (95% CI) | 0.786 (0.784-0.787) | 0.786 (0.784-0.788) |
Risk score performance | ||
Sensitivity (95% CI) | 0.209 (0.207-0.212) | 0.211 (0.207-0.215) |
Specificity (95% CI) | 0.928 (0.927-0.929) | 0.929 (0.928-0.931) |
Positive predictive value (95% CI) | 0.590 (0.585-0.595) | 0.597 (0.590-0.604) |
Negative predictive value (95% CI) | 0.705 (0.704-0.705) | 0.705 (0.704-0.706) |
Accuracy (95% CI) | 0.692 (0.690-0.693) | 0.693 (0.690-0.695) |
a Measures both discrimination and calibration; lower values indicate higher accuracy. bA modification of Hosmer–Lemeshow test suited for survival data; measure of calibration that is specific to censored survival data (lower χ2 and higher P values) indicate better calibration. cA measure of discrimination for which higher values indicate better discrimination.