Baseline Characteristics
Among the total of 77,461 participants enrolled in our study with a median age of 51.19 years, 53,571 (69.16%) participants were found to be free of fatty liver, 23,890 (30.83%) participants had NAFLD, including 15,581 (20.11%) mild NAFLD, 6,839 (8.83%) moderate NAFLD and 1,470 (1.90%) severe NAFLD. The distribution of baseline demographic and clinical characteristics according to the severity of NAFLD are showed in Table 1. Patients with more severe NAFLD at baseline were more likely to have elder age, higher levels of BMI, FBG, LDL-C, TG, ALT and hs-CRP, lower level of HDL-C, higher systolic blood pressure, more likely to suffer from diabetes, hypertension and dyslipidemia, and have higher proportions of current antihypertensive, antidiabetic and lipid-lowering agents use. A total of 692 ICH cases were identified during the 848,579 person-year of follow-up.
Table 1. Baseline Characteristics According to Severity of NAFLD
Variable
|
Nonfatty liver
|
Mild NAFLD
|
Moderate NAFLD
|
Severe NADLD
|
P value
|
N (%)
|
53571 (69.16)
|
15581 (20.11)
|
6839 (8.83)
|
1470 (1.90)
|
|
Age, years
|
50.72 (42.08-58.36)
|
52.08 (44.36-58.82)
|
52.18 (44.09-58.60)
|
52.33 (44.11-58.63)
|
<0.0001
|
Male, n (%)
|
39616 (73.95)
|
12148 (77.97)
|
5305 (77.57)
|
1106 (75.24)
|
<0.0001
|
High school or above, n (%)
|
11357 (21.38)
|
3068 (20.00)
|
1270 (18.76)
|
278 (19.11)
|
<0.0001
|
Income >1000 RMB/m, n (%)
|
3334 (6.28)
|
1046 (6.82)
|
493 (7.29)
|
112 (7.70)
|
0.0008
|
Body mass index, kg/m2
|
23.88 (21.83-25.91)
|
26.79 (24.91-28.73)
|
28.04 (26.12-30.18)
|
29.76 (27.36-32.32)
|
<0.0001
|
Physical activity≥3 times/week, n (%)
|
7185 (13.53)
|
1921 (12.53)
|
941 (13.92)
|
255 (17.54)
|
<0.0001
|
Current or previous smoking, n (%)
|
15739 (29.40)
|
4950 (31.79)
|
1987 (29.08)
|
443 (30.18)
|
<0.0001
|
Fasting blood glucose, mmol/L
|
5.02 (4.60-5.53)
|
5.30 (4.80-6.01)
|
5.38 (4.83-6.30)
|
5.48 (4.88-6.69)
|
<0.0001
|
LDL-C, mmol/L
|
2.30 (1.78-2.80)
|
2.35 (1.86-2.82)
|
2.40 (1.94-2.80)
|
2.45 (2.10-2.87)
|
<0.0001
|
HDL-C, mmol/L
|
1.51 (1.28-1.76)
|
1.48 (1.27-1.74)
|
1.48 (1.25-1.74)
|
1.47 (1.23-1.73)
|
<0.0001
|
TC, mmol/L
|
4.81 (4.20-5.44)
|
5.06 (4.42-5.74)
|
5.03 (4.35-5.78)
|
5.01 (4.31-5.78)
|
<0.0001
|
TG, mmol/L
|
1.11 (0.80-1.57)
|
1.64 (1.17-2.44)
|
1.92 (1.35-2.98)
|
1.98 (1.41-3.12)
|
<0.0001
|
PLT, 10^9/L
|
199.00 (168.00-235.00)
|
203.00 (171.00-240.00)
|
202.00 (169.00-237.00)
|
202.00 (169.00-244.00)
|
<0.0001
|
ALT, U/L
|
16.20 (12.00-22.00)
|
20.50 (15.00-28.00)
|
23.00 (18.00-33.00)
|
25.00 (19.00-40.00)
|
<0.0001
|
ALB, g/L
|
47.00 (44.80-48.70)
|
47.00 (46.00-49.00)
|
47.00 (45.00-48.00)
|
48.00 (48.00-49.00)
|
0.0297
|
TBIL, μmol/L
|
12.10 (9.70-15.00)
|
12.30 (10.00-15.00)
|
11.80 (9.60-14.80)
|
12.10 (10.20-15.20)
|
<0.0001
|
DBIL, μmol/L
|
5.00 (4.00-7.35)
|
4.55 (3.20-8.00)
|
4.50 (3.30-8.00)
|
8.00 (3.40-8.00)
|
0.4604
|
Systolic blood pressure, mm Hg
|
121.70 (110.70-140.00)
|
130.00 (120.00-149.30)
|
140.00 (122.00-150.00)
|
140.00 (129.30-159.30)
|
<0.0001
|
hs CRP, mg/L
|
0.65 (0.24-1.74)
|
1.08 (0.43-2.70)
|
1.30 (0.58-3.10)
|
1.67 (0.72-3.62)
|
<0.0001
|
Diabetes Mellitus, n (%)
|
1190 (2.22)
|
682 (4.38)
|
337 (4.93)
|
102 (6.94)
|
<0.0001
|
Hypertension, n (%)
|
4432 (8.27)
|
2457 (15.77)
|
1297 (18.96)
|
361 (24.56)
|
<0.0001
|
Dyslipidemia, n (%)
|
1957 (3.65)
|
1256 (8.06)
|
658 (9.62)
|
196 (13.33)
|
<0.0001
|
Antihypertensive agents, n (%)
|
3801 (7.10)
|
2154 (3.53)
|
1134 (15.28)
|
332 (22.59)
|
<0.0001
|
Antidiabetic agents, n (%)
|
906 (1.69)
|
530 (3.40)
|
269 (3.93)
|
89 (6.05)
|
<0.0001
|
Lipid-lowering agents, n (%)
|
267 (0.50)
|
194 (1.25)
|
116 (1.70)
|
22 (1.50)
|
<0.0001
|
Antiplatelet agents, n (%)
|
46 (0.09)
|
14 (0.09)
|
11 (0.16)
|
4 (0.27)
|
0.0978
|
NAFLD, nonalcoholic fatty liver disease; FBG, fasting blood glucose; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; TC, total cholesterol; TG, triglycerides; PLT, platelet; ALT, aminoleucine transferase; ALB, Albumin; TBIL, total bilirubin; DBIL, direct bilirubin; hs CRP, high-sensitivity C-reactive protein.
NAFLD and ICH
During a median of 11-year follow-up, 0.82% (437 out of 53,571) participants without NAFLD, and 1.07% (255 out of 23,890) participants with NAFLD developed ICH. After adjusted for age, sex, BMI, smoking status, physical activity, education levels, history of diabetes, hypertension, dyslipidemia, antidiabetic agents, antihypertensive agents, lipid lowering agents, antiplatelet and anticoagulants agents, TG, TC, LDL-C, HDL-C, FBG and hs-CRP, NAFLD was not significantly associated with increased risk of ICH. Compared with participants without NAFLD, the HR values for those with NAFLD were 1.10 (95% CI, 0.93-1.31), 1.07 (95% CI, 0.90-1.27) and 1.05 (95% CI, 0.88 to 1.26) in three models (Table 2).
Table 2. HRs (95% CI) for ICH in participants with/without NAFLD.
|
|
Nonfatty liver
|
NAFLD
|
Cases, n (%)
|
437 (0.82)
|
255 (1.07)
|
Model 1
|
Reference
|
1.10 (0.93-1.31)
|
Model 2
|
Reference
|
1.07 (0.90-1.27)
|
Model 3
|
Reference
|
1.05 (0.88-1.26)
|
Model 1 was adjusted for age, sex, BMI, smoking status and physical activity. Model 2 was adjusted for model 1 plus education levels, history of diabetes, hypertension, dyslipidemia, antidiabetic agents, antihypertensive agents, lipid lowering agents, antiplatelet and anticoagulants agents. Model 3 was further adjusted for TG, TC, LDL-C, HDL-C, FBG and hs-CRP. BMI, body mass index; TG, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; FBG, fasting blood glucose; hs CRP, hypersensitive C-reactive protein.
|
NAFLD severity and ICH
During the follow-up period, 0.82% (437 out of 53,571) of nonfatty liver participants, 0.95% (148 out of 15,581) participants with mild NAFLD, 1.26% (86 out of 6,839) participants with moderate NAFLD and 1.43% (21 out of 1,470) participants with severe NAFLD developed ICH. Participants with more severe NAFLD tended to have a higher risk of ICH. But this trend was not statistic significant after adjusting potential covariates. In the fully adjusted model, compared with participants without NAFLD, the HR values for participants with mild NAFLD, moderate and severe NAFLD were 0.98 (95% CI, 0.80 to 1.20), 1.19 (95% CI, 0.92 to 1.54) and 1.29 (95% CI, 0.81 to 2.06), respectively. The P value was 0.1828 in the trend test (Table 3).
Table 3. HRs (95% CI) for ICH according to different severities of NAFLD.
|
NAFLD severity
|
Cases, n (%)
|
Model 1
|
Model 2
|
Model 3
|
Nonfatty liver
|
437 (0.82)
|
Reference
|
Reference
|
Reference
|
Mild NAFLD
|
148 (0.95)
|
1.02 (0.84-1.25)
|
1.00 (0.81-1.21)
|
0.98 (0.80-1.20)
|
Moderate NAFLD
|
86 (1.26)
|
1.25 (0.97-1.61)
|
1.21 (0.94-1.56)
|
1.19 (0.92-1.54)
|
Severe NAFLD
|
21 (1.43)
|
1.42 (0.90-2.25)
|
1.31 (0.83-2.08)
|
1.29 (0.81-2.06)
|
P for trend
|
|
0.0557
|
0.1352
|
0.1828
|
Continuous Scale
|
|
1.11 (0.98-1.23)
|
1.08 (0.98-1.21)
|
1.08 (0.97-1.20)
|
Model 1 was adjusted for age, sex, BMI, smoking status and physical activity. Model 2 was adjusted for model 1 plus education levels, history of diabetes, hypertension, dyslipidemia, antidiabetic agents, antihypertensive agents, lipid lowering agents, antiplatelet and anticoagulants agents. Model 3 was further adjusted for TG, TC, LDL-C, HDL-C, FBG and hs-CRP. BMI, body mass index; TG, triglycerides; TC, total cholesterol; LDL-C, low-density lipoprotein cholesterol; HDL-C, high-density lipoprotein cholesterol; FBG, fasting blood glucose; hs-CRP, hypersensitive C-reactive protein.
|