Table 2.
FGF23 and Risk of Incident Heart Failure
| FGF23 and Incident HFpEF Hazard Ratio (95%CI) |
|||||||
|---|---|---|---|---|---|---|---|
| Total N (events) | ln(FGF23) | FGF23 Q1 | FGF23 Q2 | FGF23 Q3 | FGF23 Q4 | P for Trend | |
| N, events | 3,502 (295) | 295 | 38 | 58 | 84 | 115 | |
| Unadjusted | 3,502 (295) | 1.70 (1.54-1.87) | Reference | 1.62 (1.08-2.45) | 2.66 (1.81-3.91) | 4.43 (3.07-6.41) | <0.001 |
| Model 1 | 3,502 (295) | 1.75 (1.57-1.94) | Reference | 1.47 (0.97-2.22) | 2.40 (1.63-3.55) | 4.10 (2.80-6.00) | <0.001 |
| Model 2 | 3,336 (283) | 1.49 (1.31-1.69) | Reference | 1.26 (0.83-1.93) | 1.66 (1.10-2.51) | 2.34 (1.53-3.60) | <0.001 |
| Model 3 | 3,214 (274) | 1.37 (1.19-1.58) | Reference | 1.08 (0.71-1.65) | 1.19 (0.78-1.82) | 1.54 (0.99-2.41) | 0.04 |
| Model 4 | 3,079 (264) | 1.41 (1.21-1.64) | Reference | 1.18 (0.76-1.84) | 1.31 (0.84-2.04) | 1.66 (1.03-2.66) | 0.03 |
| FGF23 and Incident HFrEF Hazard Ratio (95%CI) | |||||||
| Total N (events) | ln(FGF23) | FGF23 Q1 | FGF23 Q2 | FGF23 Q3 | FGF23 Q4 | P for trend | |
| N, events | 3,502 (242) | 242 | 38 | 49 | 73 | 82 | |
| Unadjusted | 3,502 (242) | 1.51 (1.34-1.70) | Reference | 1.39 (0.91-2.12) | 2.37 (1.60-3.51) | 3.30 (2.24-4.86) | <0.001 |
| Model 1 | 3,502 (242) | 1.64 (1.44-1.86) | Reference | 1.29 (0.84-1.98) | 2.37 (1.59-3.54) | 3.68 (2.47-5.49) | <0.001 |
| Model 2 | 3,336 (222) | 1.32 (1.13-1.55) | Reference | 1.10 (0.71-1.72) | 1.53 (0.99-2.37) | 1.97 (1.23-3.14) | 0.001 |
| Model 3 | 3,214 (210) | 1.24 (1.04-1.47) | Reference | 1.01 (0.64-1.60) | 1.27 (0.80-2.02) | 1.49 (0.90-2.47) | 0.06 |
| Model 4 | 3,079 (204) | 1.27 (1.05-1.53) | Reference | 1.03 (0.64-1.64) | 1.37 (0.85-2.21) | 1.64 (0.97-2.77) | 0.03 |
| FGF23 and Incident HFuEF Hazard Ratio (95%CI) | |||||||
| Total N (events) | ln(FGF23) | FGF23 Q1 | FGF23 Q2 | FGF23 Q3 | FGF23 Q4 | P for trend | |
| N, events | 3,502 (156) | 156 | 21 | 29 | 41 | 65 | |
| Unadjusted | 3,502 (156) | 1.67 (1.46-1.92) | Reference | 1.46 (0.84-2.57) | 2.35 (1.39-3.98) | 4.66 (2.85-7.64) | <0.001 |
| Model 1 | 3,502 (156) | 1.69 (1.45-1.97) | Reference | 1.37 (0.78-2.40) | 2.20 (1.29-3.77) | 4.32 (2.59-7.19) | <0.001 |
| Model 2 | 3,336 (148) | 1.56 (1.31-1.85) | Reference | 1.26 (0.71-2.23) | 1.68 (0.95-2.96) | 3.24 (1.83-5.73) | <0.001 |
| Model 3 | 3,214 (146) | 1.44 (1.19-1.74) | Reference | 1.11 (0.61-2.00) | 1.36 (0.76-2.44) | 2.32 (1.27-4.23) | 0.002 |
| Model 4 | 3,079 (136) | 1.40 (1.13-1.73) | Reference | 1.08 (0.59-1.99) | 1.24 (0.67-2.30) | 2.03 (1.07-3.84) | 0.02 |
Note: Risks modeled separately for each heart failure type with the use of cause-specific Cox models. Results are reported as hazard ratio per 1 standard deviation increase in natural log (ln) of fibroblast growth factor 23 (FGF23) or hazard ratio in relation to the reference quartile. Model 1: adjusted for age, sex, race, ethnicity, and study site; Model 2: Model 1 plus estimated glomerular filtration rate, and 24H urine protein; Model 3: Model 2 plus body mass index, diabetes, smoking, systolic blood pressure, any cardiovascular disease, total cholesterol, statins, number of blood pressure medications, phosphate, and parathyroid hormone; Model 4: Model 3 plus calcium, CRP (log-transformed), TSAT, and ferritin (log-transformed).
Abbreviations: HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction,; HFuEF, heart failure with unknown ejection fraction.