Introduction
Methods
Study cohort
Whole-genome sequencing (WGS)
Somatic mutation identifying
IL-6 inhibition genetic proxy
Statistical analysis
Results
Characteristics of the participants
Association between CHIP and baseline characteristics
Characteristic | Total (n = 3396) | Non-CHIP (n = 3286) | CHIP (n = 110) | p value |
---|---|---|---|---|
Age (y), median (IQR) | 62.0 (54.0–69.0) | 62.0 (54.0–69.0) | 68.5 (64.0–76.0) | <0.001 |
Age, n (%) | <0.001 | |||
< 40 | 71 (2.1) | 71 (2.2) | 0 | |
40–49 | 368 (10.8) | 364 (11.1) | 4 (3.6) | |
50–59 | 912 (26.9) | 900 (27.4) | 12 (10.9) | |
60–69 | 1199 (35.3) | 1157 (35.2) | 42 (38.2) | |
70–79 | 682 (20.1) | 648 (19.7) | 34 (30.9) | |
≥ 80 | 164 (4.8) | 146 (4.4) | 18 (16.4) | |
Female, n (%) | 989 (29.1) | 945 (28.8) | 44 (40.0) | 0.01 |
BMI (kg/m2), mean ± SD | 24.9 ± 3.3 | 24.9 ± 3.3 | 24.7 ± 3.5 | 0.51 |
Current smoking, n (%) | 1165 (34.3) | 1142 (34.8) | 23 (20.9) | 0.003 |
Drinking, n (%) | 594 (17.5) | 582 (17.7) | 12 (10.9) | 0.06 |
Medical history, n (%) | ||||
IS/TIA | 743 (21.9) | 717 (21.8) | 26 (23.6) | 0.65 |
CHD | 334 (9.8) | 322 (9.8) | 12 (10.9) | 0.70 |
Hypertension | 2178 (64.1) | 2102 (64.0) | 76 (69.1) | 0.27 |
Diabetes mellitus | 841 (24.8) | 817 (24.9) | 24 (21.8) | 0.47 |
Hypercholesterolemia | 277 (8.2) | 270 (8.2) | 7 (6.4) | 0.48 |
NIHSS | ||||
Median (IQR) | 3.0 (1.0–5.0) | 3.0 (1.0–5.0) | 3.0 (1.0–5.0) | 0.80 |
TOAST | 0.23 | |||
LAA | 1483 (43.7) | 1430 (43.5) | 53 (48.2) | |
CE | 332 (9.8) | 318 (9.7) | 14 (12.7) | |
SAO | 1581 (46.6) | 1538 (46.8) | 43 (39.1) | |
Laboratory index | ||||
hsCRP | 5.6 ± 18.8 | 5.6 ± 19.1 | 3.4 ± 5.7 | 0.53 |
HGB | 142.2 ± 16.2 | 142.3 ± 16.2 | 138.9 ± 15.1 | 0.01 |
WBC | 7.1 ± 2.1 | 7.1 ± 2.1 | 7.2 ± 2.3 | 0.70 |
MONO | 0.4 ± 0.2 | 0.4 ± 0.2 | 0.4 ± 0.2 | 0.53 |
NEUT | 4.7 ± 2.1 | 4.7 ± 1.9 | 5.3 ± 5.6 | 0.64 |
TG | 1.6 ± 1.0 | 1.6 ± 1.0 | 1.5 ± 0.6 | 0.59 |
LDL | 2.5 ± 1.0 | 2.4 ± 1.0 | 2.6 ± 1.1 | 0.21 |
HDL | 1.0 ± 0.3 | 1.0 ± 0.3 | 1.0 ± 0.3 | 0.09 |
CHOL | 4.1 ± 1.2 | 4.1 ± 1.2 | 4.2 ± 1.2 | 0.55 |
HCY | 19.4 ± 12.9 | 19.4 ± 12.8 | 20.0 ± 15.5 | 0.98 |
Time from symptom onset to arrival at hospital, day(s) | ||||
Median (IQR) | 2.0 (1.0–4.0) | 2.0 (1.0–4.0) | 2.0 (1.0–4.0) | 0.81 |
Association of CHIP with the risk of unfavorable functional outcome
CHIP, n (%) | No CHIP, n (%) | Unadjusted OR (95%CI) | p value | aAdjusted OR (95%CI) | p value | pinteraction | |
---|---|---|---|---|---|---|---|
ALL | |||||||
hsCRP > median | 18/52 (34.6) | 409/1644 (24.9) | 1.60 (0.89–2.86) | 0.11 | 1.53 (0.83–2.80) | 0.17 | 0.33 |
hsCRP ≤ median | 7/58 (12.1) | 237/1642 (14.4) | 0.81 (0.37–1.81) | 0.61 | 0.95 (0.46–1.98) | 0.90 | |
LAA | |||||||
hsCRP > median | 10/21 (47.6) | 238/720 (33.1) | 1.84 (0.89–2.86) | 0.17 | 2.45 (1.00–5.98) | 0.049 | 0.01 |
hsCRP ≤ median | 4/32 (12.5) | 140/710 (19.7) | 0.58 (0.20–1.69) | 0.32 | 0.30 (0.08–1.13) | 0.08 | |
CE | |||||||
hsCRP > median | 4/6 (66.7) | 54/160 (33.8) | 3.93 (0.70–22.12) | 0.12 | 2.29 (0.28–19.02) | 0.44 | 0.49 |
hsCRP ≤ median | 2/8 (25.0) | 23/158 (14.6) | 1.96 (0.37–10.29) | 0.43 | 0.78 (0.08–7.43) | 0.83 | |
SAO | |||||||
hsCRP > median | 3/24 (12.5) | 113/765 (14.8) | 0.82 (0.24–2.81) | 0.76 | 0.62 (0.16–2.45) | 0.49 | 0.71 |
hsCRP ≤ median | 2/19 (10.5) | 78/773 (10.1) | 1.05 (0.24–4.62) | 0.95 | 0.92 (0.18–4.73) | 0.92 |
Genetic IL-6 signaling deficiency attenuates the risk of unfavorable functional outcome in patients with CHIP
IL6R p.Asp358Ala n (%) | No IL6R p.Asp358Ala n (%) | Unadjusted OR (95%CI) | p value | aAdjusted OR (95%CI) | p value | pinteraction | |
---|---|---|---|---|---|---|---|
ALL | |||||||
CHIP | 10/68 (14.7) | 15/42 (35.7) | 0.31 (0.12–0.78) | 0.01 | 0.30 (0.12–0.76) | 0.01 | 0.02 |
No CHIP | 421/2162 (19.5) | 225/1124 (20.0) | 0.97 (0.81–1.16) | 0.71 | 0.96 (0.80–1.15) | 0.68 | |
LAA | |||||||
CHIP | 3/32 (9.28) | 11/21 (52.4) | 0.09 (0.02–0.41) | 0.002 | 0.10 (0.02–0.42) | 0.002 | 0.001 |
No CHIP | 253/903 (33.1) | 125/500 (25.0) | 1.12 (0.87–1.44) | 0.37 | 1.10 (0.85–1.42) | 0.46 | |
CE | |||||||
CHIP | 4/10 (40.0) | 2/4 (50.0) | 0.67 (0.07–6.87) | 0.73 | 0.66 (0.07–6.44) | 0.72 | 0.83 |
No CHIP | 51/221 (23.1) | 26/97 (26.8) | 0.82 (0.47–1.42) | 0.48 | 0.85 (0.49–1.47) | 0.56 | |
SAO | |||||||
CHIP | 3/26 (11.5) | 2/17 (11.8) | 0.98 (0.15–6.57) | 0.98 | 0.93 (0.14–6.23) | 0.94 | 0.87 |
No CHIP | 117/1011 (11.6) | 74/527 (14.0) | 0.80 (0.59–1.10) | 0.16 | 0.79 (0.58–1.07) | 0.13 |