Table 3.
Replication Analysis of Associations of the Top 40 Late-Life Protein Biomarkers Measured in Mid-life with Incident Atrial Fibrillation, ARIC, 1993-2010
| Model 1 | Model 2 | ||||
|---|---|---|---|---|---|
| Protein Target Name | Gene Name | HR (95% CI) |
p value |
HR (95% CI) |
p value |
| N-terminal pro-BNP | NPPB | 1.40 (1.32-1.47) | 3.29E-35 ‡ | 1.37 (1.30-1.45) | 2.92E-31 ‡ |
| Angiopoietin-2 | ANGPT2 | 1.77 (1.55-2.02) | 3.54E-17 ‡ | 1.73 (1.51-1.98) | 6.42E-16 ‡ |
| Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1 | SVEP1 | 1.57 (1.36-1.80) | 3.11E-10 ‡ | 1.57 (1.36-1.81) | 4.20E-10 ‡ |
| Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1 | SVEP1 | 1.52 (1.33-1.74) | 6.99E-10 ‡ | 1.52 (1.33-1.74) | 9.91E-10 ‡ |
| Triggering receptor expressed on myeloid cells 1 | TREM1 | 1.49 (1.30-1.71) | 1.14E-08 ‡ | 1.46 (1.26-1.68) | 1.73E-07 ‡ |
| Insulin-like growth factor-binding protein 2 | IGFBP2 | 1.26 (1.16-1.37) | 7.11E-08 ‡ | 1.25 (1.15-1.36) | 1.91E-07 ‡ |
| Ribonuclease pancreatic | RNASE1 | 1.32 (1.21-1.45) | 2.49E-09 ‡ | 1.31 (1.18-1.45) | 3.80E-07 ‡ |
| EGF-containing fibulin-like extracellular matrix protein 1 | EFEMP1 | 1.83 (1.47-2.27) | 3.86E-08 ‡ | 1.75 (1.40-2.18) | 6.58E-07 ‡ |
| Transgelin | TAGLN | 1.50 (1.30-1.74) | 6.20E-08 ‡ | 1.46 (1.25-1.70) | 2.33E-06 ‡ |
| Natriuretic peptides B | NPPB | 1.25 (1.13-1.38) | 7.82E-06 ‡ | 1.23 (1.12-1.36) | 2.52E-05 ‡ |
| Protein SET | SET | 0.56 (0.42-0.73) | 2.12E-05 ‡ | 0.58 (0.44-0.75) | 7.90E-05 ‡ |
| Gamma-aminobutyric acid receptor-associated protein | GABARAP | 1.69 (1.36-2.11) | 2.37E-06 ‡ | 1.58 (1.25-2.00) | 1.17E-04 ‡ |
| Gamma-aminobutyric acid receptor-associated protein-like 1 | GABARAPL1 | 1.48 (1.24-1.76) | 1.14E-05 ‡ | 1.42 (1.18-1.70) | 2.49E-04 ‡ |
| Hepatitis A virus cellular receptor 2 | HAVCR2 | 1.34 (1.16-1.54) | 5.11E-05 ‡ | 1.29 (1.12-1.49) | 4.43E-04 ‡ |
| Microfibril-associated glycoprotein 4 | MFAP4 | 1.21 (1.08-1.34) | 5.41E-04 ‡ | 1.21 (1.09-1.35) | 4.56E-04 ‡ |
| Cartilage intermediate layer protein 2 | CILP2 | 0.77 (0.67-0.89) | 3.87E-04 ‡ | 0.77 (0.67-0.89) | 4.98E-04 ‡ |
| Endostatin | COL18A1 | 1.45 (1.21-1.74) | 7.41E-05 ‡ | 1.39 (1.15-1.68) | 7.77E-04 ‡ |
| Antileukoproteinase | SLPI | 1.46 (1.21-1.76) | 8.97E-05 ‡ | 1.38 (1.13-1.68) | 1.32E-03 |
| R-spondin-4 | RSPO4 | 1.37 (1.14-1.64) | 6.87E-04 ‡ | 1.34 (1.12-1.61) | 1.44E-03 |
| Scavenger receptor class F member 1 | SCARF1 | 1.37 (1.13-1.66) | 1.10E-03 ‡ | 1.34 (1.11-1.63) | 2.91E-03 |
| Chordin-like protein 1 | CHRDL1 | 1.38 (1.13-1.68) | 1.52E-03 | 1.33 (1.09-1.63) | 5.16E-03 |
| R-spondin-1 | RSPO1 | 1.23 (1.08-1.40) | 1.64E-03 | 1.21 (1.06-1.38) | 5.36E-03 |
| Spondin-1 | SPON1 | 1.29 (1.07-1.56) | 6.51E-03 | 1.28 (1.06-1.55) | 9.41E-03 |
| Protein delta homolog 1 | DLK1 | 0.91 (0.83-1.00) | 4.96E-02 | 0.88 (0.80-0.97) | 1.10E-02 |
| Protein delta homolog 1 | DLK1 | 0.91 (0.82-1.00) | 5.22E-02 | 0.88 (0.79-0.97) | 1.24E-02 |
| A disintegrin and metalloproteinase with thrombospondin motifs 13 | ADAMTS13 | 0.81 (0.70-0.93) | 3.70E-03 | 0.83 (0.72-0.96) | 1.39E-02 |
| Metalloproteinase inhibitor 4 | TIMP4 | 1.19 (1.04-1.35) | 1.06E-02 | 1.16 (1.02-1.33) | 2.29E-02 |
| Slit homolog 2 protein | SLIT2 | 1.15 (1.00-1.31) | 4.96E-02 | 1.15 (1.01-1.32) | 3.96E-02 |
| Shadow of prion protein | SPRN | 1.15 (0.99-1.35) | 6.63E-02 | 1.17 (1.00-1.36) | 4.56E-02 |
| Lysosomal Pro-X carboxypeptidase | PRCP | 0.81 (0.69-0.96) | 1.42E-02 | 0.84 (0.71-1.00) | 4.84E-02 |
| Regenerating islet-derived protein 3-alpha | REG3A | 1.12 (1.02-1.22) | 1.19E-02 | 1.09 (1.00-1.19) | 5.64E-02 |
| Growth/differentiation factor 11/8 | GDF11 MSTN |
0.88 (0.74-1.04) | 1.30E-01 | 0.87 (0.73-1.03) | 1.05E-01 |
| Macrophage-capping protein | CAPG | 1.12 (1.01-1.25) | 2.72E-02 | 1.09 (0.98-1.21) | 1.06E-01 |
| Sodium/potassium-transporting ATPase subunit beta-1 | ATP1B1 | 0.90 (0.79-1.02) | 8.61E-02 | 0.91 (0.80-1.03) | 1.26E-01 |
| Bone sialoprotein 2 | IBSP | 1.05 (0.95-1.15) | 2.78E-01 | 1.06 (0.97-1.17) | 1.98E-01 |
| CMRF35-like molecule 2 | CD300E | 1.08 (0.93-1.24) | 3.06E-01 | 1.09 (0.93-1.26) | 2.39E-01 |
| Atrial natriuretic factor | NPPA | 1.11 (0.92-1.34) | 2.82E-01 | 1.11 (0.91-1.34) | 2.99E-01 |
| Coagulation Factor X | F10 | 0.87 (0.71-1.06) | 1.71E-01 | 0.96 (0.77-1.20) | 7.30E-01 |
| Endothelial cell-specific molecule 1 | ESM1 | 1.03 (0.89-1.18) | 7.15E-01 | 1.02 (0.89-1.17) | 7.52E-01 |
| Coagulation factor Xa | F10 | 0.88 (0.72-1.08) | 2.08E-01 | 0.98 (0.78-1.22) | 8.24E-01 |
Model 1: adjusted for age, sex, race/center, current cigarette smoking, height, weight, systolic and diastolic blood pressure, the use of hypertension medications, diabetes, prevalent myocardial infarction and prevalent heart failure. Model 2: adjusted for Model 1 + estimated glomerular filtration rate, antiarrhythmic medication use, beta blocker medication use, and anticoagulation use
†
Hazard ratio (HR) expressed as the risk of incident AF per doubling of the protein value
‡
Significance level of P<0.05/40 = 1.25 x 10−3. These 40 proteins are ordered by smallest to largest p-value for Model 2.