Table 2.
Association of the MOFA factors and cardiovascular disease risk (Cox regression): Model 1, adjusted for cell-type counts and one surrogate variable; Model 2, additionally adjusted for age and sex; Model 3, additionally adjusted for total cholesterol, HDL-C levels, glucose, smoking status and systolic and diastolic blood pressure
| Model | Association with CVD incidence | Predictive capacity of the Framingham CVR function | ||||||
|---|---|---|---|---|---|---|---|---|
| HRa (95% CIa) | p-value | FDR correction | C-statistic classical function | C-statistic classical function + factor | p-valueCa | NRIa (95% CI) | Clinical NRIa (95% CIa) | |
| F9a—Model 1 | 2.05 (1.69, 2.48) | 3.04 × 10−13 | 9.44 × 10−12 | – | – | – | – | – |
| F9—Model 2 | 1.56 (1.26, 1.93) | 3.48 × 10−5 | 2.7 × 10−4 | – | – | – | – | – |
| F9—Model 3 | 1.42 (1.15, 1.77) | 1.37 × 10−3 | 8.46 × 10−3 | 0.73 | 0.73 | 0.97 | − 2.12 (− 8.17, 3.89) | − 2.38 (− 10.74, 5.98) |
| F19a—Model 1 | 1.42 (1.26, 1.61) | 9.10 × 10−9 | 7.05 × 10−8 | – | – | – | – | – |
| F19—Model 2 | 1.21 (1.06, 1.38) | 4.61 × 10−3 | 2.38 × 10−2 | – | – | – | – | – |
| F19—Model 3 | 1.20 (1.05, 1.37) | 9 × 10−3 | 4.65 × 10−2 | 0.73 | 0.74 | 0.20 | 0.21 (− 8.01, 8.01) | 1.85 (− 8.83, 12.54) |
| F21a Ma—Model 1 | 1.24 (1.02, 1.51) | 3.22 × 10−2 | 6.65 × 10−2 | – | – | – | – | – |
| F21 M—Model 2 | 1.21 (1.00, 1.48) | 5.56 × 10−2 | 0.13 | – | – | – | – | – |
| F21 M—Model 3 | 1.21 (0.99, 1.48) | 6.38 × 10−2 | 0.15 | 0.71 | 0.72 | 0.30 | 2.92 (− 8.03, 13.49) | 6.61 (− 9.53, 22.76) |
| F21 Wa—Model 1 | 1.81 (1.44, 2.29) | 5.52 × 10−7 | 3.42 × 10−6 | – | – | – | – | – |
| F21 W—Model 2 | 1.71 (1.36, 2.15) | 5.54 × 10−6 | 5.72 × 10−5 | – | – | – | – | – |
| F21 W—Model 3 | 1.77 (1.39, 2.24) | 2.40 × 10−6 | 3.72 × 10−5 | 0.75 | 0.79 | 0.01 | 20.85 (5.04, 37.38) | 24.00 (4.55, 43.43) |
| F27a—Model 1 | 1.38 (1.25, 1.53) | 5.98 × 10−10 | 9.28 × 10−9 | – | – | – | – | – |
| F27—Model 2 | 1.38 (1.25, 1.54) | 4.48 × 10−10 | 1.39 × 10−8 | – | – | – | – | – |
| F27—Model 3 | 1.36 (1.22, 1.51) | 1.08 × 10−8 | 3.35 × 10−7 | 0.73 | 0.75 | 0.01 | 1.23 (− 6.48, 8.44) | 4.90 (− 4.37, 14.17) |
Cell-type counts and one surrogate variable were used as covariates in the three models. Factor 21 was stratified by sex, as the interaction between this factor and sex was statistically significant. The predictive added-value of each factor when included in the Framingham risk function is also shown in terms of discrimination improvement (C-statistic) and reclassification (Net Reclassification Improvement)
aCVD, cardiovascular disease; HR, hazard ratio; CI, confidence interval; p-valueC, p-value of the c-statistic comparison; NRI, net reclassification improvement; F9, factor 9; F19, factor 19; F21, factor 21; F27, factor 27; M, men; W, women