Table 2.
Protein Biomarkers Associated with Incident Atrial Fibrillation in Late-life, ARIC, 2011-2018
| Model 1 | Model 2 | ||||
|---|---|---|---|---|---|
| Protein Name | Gene Name | HR (95% CI) |
p value | HR (95% CI) |
p value |
| N-terminal pro-BNP | NPPB | 1.82 (1.68-1.98) | 2.91E-45 ‡ | 1.75 (1.60-1.91) | 4.59E-35 ‡ |
| Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1 | SVEP1 | 2.01 (1.71-2.36) | 2.39E-17 ‡ | 1.89 (1.61-2.23) | 2.47E-14 ‡ |
| Sushi, von Willebrand factor type A, EGF and pentraxin domain-containing protein 1 | SVEP1 | 1.92 (1.65-2.24) | 2.90E-17 ‡ | 1.84 (1.57-2.16) | 3.31E-14 ‡ |
| Natriuretic peptides B | NPPB | 1.52 (1.36-1.70) | 3.10E-13 ‡ | 1.46 (1.30-1.65) | 4.58E-10 ‡ |
| Transgelin | TAGLN | 1.88 (1.54-2.29) | 3.21E-10 ‡ | 2.01 (1.56-2.59) | 6.41E-08 ‡ |
| Angiopoietin-2 | ANGPT2 | 1.86 (1.53-2.25) | 2.88E-10 ‡ | 1.74 (1.42-2.14) | 1.62E-07 ‡ |
| Protein delta homolog 1 | DLK1 | 0.72 (0.63-0.84) | 1.73E-05 | 0.68 (0.58-0.79) | 7.22E-07 ‡ |
| Slit homolog 2 protein | SLIT2 | 1.44 (1.25-1.65) | 2.90E-07 ‡ | 1.41 (1.23-1.62) | 7.66E-07 ‡ |
| CMRF35-like molecule 2 | CD300E | 1.51 (1.27-1.80) | 2.28E-06 ‡ | 1.52 (1.28-1.80) | 1.68E-06 ‡ |
| Protein delta homolog 1 | DLK1 | 0.73 (0.63-0.85) | 3.33E-05 | 0.68 (0.55-0.80) | 1.81E-06 ‡ |
| Antileukoproteinase | SLPI | 1.97 (1.54-2.51) | 6.66E-08 ‡ | 1.92 (1.46-2.52) | 2.43E-06 ‡ |
| Bone sialoprotein 2 | IBSP | 1.37 (1.22-1.54) | 1.05E-07 ‡ | 1.33 (1.18-1.50) | 2.59E-06 ‡ |
| Microfibril-associated glycoprotein 4 | MFAP4 | 1.54 (1.31-1.80) | 1.22E-07 ‡ | 1.47 (1.25-1.72) | 3.13E-06 ‡ |
| Shadow of prion protein | SPRN | 1.53 (1.26-1.84) | 1.14E-05 | 1.57 (1.30-1.90) | 3.50E-06 ‡ |
| R-spondin-4 | RSPO4 | 1.65 (1.35-2.02) | 1.45E-06 ‡ | 1.63 (1.33-2.01) | 3.67E-06 ‡ |
| Chordin-like protein 1 | CHRDL1 | 1.86 (1.47-2.37) | 3.17E-07 ‡ | 1.79 (1.39-2.31) | 7.64E-06 ‡ |
| Spondin-1 | SPON1 | 1.93 (1.49-2.49) | 6.24E-07 ‡ | 1.81 (1.39-2.34) | 7.70E-06 ‡ |
| Endothelial cell-specific molecule 1 | ESM1 | 1.76 (1.40-2.20) | 7.77E-07 ‡ | 1.66 (1.32-2.07) | 1.08E-05 |
| R-spondin-1 | RSPO1 | 1.65 (1.36-1.99) | 2.64E-07 ‡ | 1.57 (1.28-1.92) | 1.26E-05 |
| Macrophage-capping protein | CAPG | 1.53 (1.31-1.77) | 3.28E-08 ‡ | 1.44 (1.22-1.70) | 1.59E-05 |
| Scavenger receptor class F member 1 | SCARF1 | 1.81 (1.42-2.32) | 2.51E-06 ‡ | 1.78 (1.37-2.31) | 1.77E-05 |
| Atrial natriuretic factor | NPPA | 1.72 (1.42-2.09) | 3.03E-08 ‡ | 1.54 (1.26-1.88) | 2.30E-05 |
| Insulin-like growth factor-binding protein 2 | IGFBP2 | 1.40 (1.21-1.62) | 7.27E-06 ‡ | 1.35 (1.16-1.57) | 9.30E-05 |
| Growth/differentiation factor 11/8 | GDF11 MSTN |
0.55 (0.42-0.72) | 9.54E-06 ‡ | 0.59 (0.45-0.77) | 9.78E-05 |
| Triggering receptor expressed on myeloid cells 1 | TREM1 | 1.56 (1.30-1.87) | 1.14E-06 ‡ | 1.50 (1.22-1.84) | 1.00E-04 |
| A disintegrin and metalloproteinase with thrombospondin motifs 13 | ADAMTS13 | 0.55 (0.43-0.71) | 2.56E-06 ‡ | 0.60 (0.46-0.71) | 1.15E-04 |
| Metalloproteinase inhibitor 4 | TIMP4 | 1.52 (1.26-1.82) | 7.03E-06 ‡ | 1.43 (1.19-1.73) | 1.58E-04 |
| Ribonuclease pancreatic | RNASE1 | 1.29 (1.17-1.44) | 1.49E-06 ‡ | 1.38 (1.17-1.64) | 1.60 E-04 |
| EGF-containing fibulin-like extracellular matrix protein 1 | EFEMP1 | 2.13 (1.57-2.90) | 1.24E-06 ‡ | 1.94 (1.37-2.75) | 1.70E-04 |
| Regenerating islet-derived protein 3-alpha | REG3A | 1.30 (1.16-1.46) | 4.81E-06 ‡ | 1.26 (1.12-1.43) | 2.01E-04 |
| Lysosomal Pro-X carboxypeptidase | PRCP | 0.56 (0.43-0.72) | 9.07E-06 ‡ | 0.60 (0.46-0.79) | 2.13E-04 |
| Cartilage intermediate layer protein 2 | CILP2 | 0.64 (0.53-0.78) | 6.27E-06 ‡ | 0.69 (0.57-0.84) | 2.15E-04 |
| Sodium/potassium-transporting ATPase subunit beta-1 | ATP1B1 | 0.62 (0.50-0.76) | 9.74E-06 ‡ | 0.66 (0.53-0.82) | 2.50E-04 |
| Hepatitis A virus cellular receptor 2 | HAVCR2 | 1.60 (1.31-1.95) | 3.57E-06 ‡ | 1.51 (1.21-1.88) | 3.05E-04 |
| Endostatin | COL18A1 | 1.93 (1.47-2.55) | 3.14E-06 ‡ | 1.90 (1.33-2.72) | 4.07E-04 |
| Protein SET | SET | 0.36 (0.23-0.55) | 4.36E-06 ‡ | 0.45 (0.28-0.71) | 5.88E-04 |
| Gamma-aminobutyric acid receptor-associated protein-like 1 | GABARAPL1 | 1.80 (1.41-2.31) | 2.60E-06 ‡ | 1.65 (1.23-2.21) | 8.44E-04 |
| Gamma-aminobutyric acid receptor-associated protein | GABARAP | 1.95 (1.46-2.60) | 6.88E-06 ‡ | 1.73 (1.22-2.47) | 2.30E-03 |
| Coagulation Factor X | F10 | 0.51 (0.40-0.64) | 3.09E-08 ‡ | 0.69 (0.47-0.99) | 4.50E-02 |
| Coagulation factor Xa | F10 | 0.52 (0.41-0.66) | 8.99E-08 ‡ | 0.71 (0.50-1.01) | 5.95E-02 |
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<0.05/4877 = 1.025 x 10−5. These 40 proteins are ordered by smallest to largest p-value for Model 2.
All proteins listed are novel associations with incident AF except for NT-proBNP and ADAMTS13 which have been previously published.