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Baseline characteristics were similar between the two groups according to the ABI category, except that those with PAD (ABI < 0.90 or > 1.40) were more likely to have higher levels of BMI and WBC than those with the normal range of ABI (0.90–1.40; Table 1). The mean ± SD values for NFS were −1.77 ± 1.13 for all the study patients at baseline, −1.69 ± 1.18 for those with an ABI of < 0.90 or > 1.40, and −1.78 ± 1.12 for those with the normal range of ABI.
Characteristics ABI P value 0.90–1.40 < 0.90 or > 1.40 Number 1,486 124 Age (years) 58.0 ± 8.0 57.5 ± 8.5 0.51 Men [n (%)] 453 (30.48) 43 (34.68) 0.33 Current smoker [n (%)] 221 (14.87) 21 (16.93) 0.52 Current drinker [n (%)] 40 (3.36) 5 (4.03) 0.39 Hypertension [n (%)] 1,111 (74.81) 85 (68.55) 0.13 Diabetes [n (%)] 494 (33.24) 40 (32.26) 0.82 Physical activity* (MET-h/week) 23.1 (0, 69.3) 23.1 (4.1, 74.2) 0.50 BMI (kg/m2) 27.4 ± 2.9 28.3 ± 3.3 0.002 WC (cm) 88.5 ± 7.6 89.5 ± 8.6 0.15 SBP (mmHg) 146.6 ± 18.9 145.1 ± 19.2 0.40 Diastolic blood pressure (mmHg) 85.7 ± 10.2 86.3 ± 10.6 0.56 Fasting plasma glucose (mmol/L) 6.08 ± 1.96 6.12 ± 2.24 0.81 Triglycerides* (mmol/L) 1.85 (1.35, 2.59) 1.99 (1.41, 2.66) 0.47 Total cholesterol (mmol/L) 5.52 ± 1.10 5.46 ± 1.05 0.59 HDL cholesterol (mmol/L) 1.21 ± 0.26 1.19 ± 0.29 0.37 LDL cholesterol (mmol/L) 3.32 ± 0.91 3.26 ± 0.85 0.44 Albumin (g/L) 49.13 ± 2.23 48.94 ± 2.50 0.35 ALT* (U/L) 23.1 (17.4, 33.3) 24.4 (17.5, 34.8) 0.66 AST* (U/L) 22.3 (19.0, 27.3) 22.5 (18.7, 27.1) 0.86 GGT* (U/L) 28 (20, 44) 31 (21, 41) 0.60 White blood cell (×109/L) 6.13 ± 1.47 6.55 ± 1.46 0.002 HOMA-IR* 2.62 (1.81, 3.84) 2.61 (1.82, 3.63) 0.90 NFS −1.78 ± 1.12 −1.69 ± 1.18 0.40 Note. Data are presented as mean ± SD, median (interquartile range), or number (percentage). P-values were calculated by one-way analysis of variance for continuous variables and chi-square test for categorical variables. *Variables were log-transformed before analysis. Abbreviations: ABI, ankle-brachial index; BMI, body mass index; WC, waist circumference; MET, metabolic equivalent; SBP; systolic blood pressure; HDL, high-density lipoprotein; LDL, low-density lipoprotein; ALT, alanine aminotransferase; AST, aspartate aminotransferase; GGT, gamma-glutamyl transpeptidase; HOMA-IR, homeostasis model assessment of insulin resistance; NAFLD, nonalcoholic fatty liver disease; NFS, NAFLD fibrosis score. Table 1. Baseline characteristics of NAFLD patients according to ABI category
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Table 2 shows the association of PAD with the risk of fibrosis deterioration. The mean ± SD value for NFS at follow-up was −0.91 ± 1.12. Of all the 1,610 NAFLD patients at baseline, 618 (38%) patients developed fibrosis deterioration. When stratified by baseline NFS status, 494 patients progressed from low to intermediate or high and 124 from intermediate to high.
Fibrosis deterioration PAD No. events / participants Model 1 Model 2 Model 3 OR (95% CI) P OR (95% CI) P OR (95% CI) P Total No 561/1,486 1.00 0.01 1.00 0.003 1.00 0.003 Yes 57/124 1.69 (1.12, 2.56) 1.93 (1.25, 2.98) 1.92 (1.24, 2.98) Intermediate to high No 108/577 1.00 0.03 1.00 0.03 1.00 0.03 Yes 16/52 2.19 (1.10, 4.35) 2.27 (1.06, 4.84) 2.24 (1.05, 4.80) Low to intermediate or high No 453/909 1.00 0.14 1.00 0.04 1.00 0.04 Yes 41/72 1.47 (0.89, 2.44) 1.72 (1.00, 2.94) 1.74 (1.02, 3.00) Note. Data are presented as OR and 95% CI.
Model 1 was adjusted for age, sex, and baseline nonalcoholic fatty liver disease fibrosis score.
Model 2 was further adjusted for central obesity, physical activity, current smoking, current drinking, diabetes, hypertension, triglycerides, HDL cholesterol, LDL cholesterol, and white blood cell based on Model 1.
Model 3 was further adjusted for the homeostasis model assessment of IR based on Model 2.
Abbreviation: PAD, peripheral artery disease; IR, insulin resistance; HDL, high-density lipoprotein; LDL, low-density lipoprotein.Table 2. Association of PAD with risk of fibrosis deterioration
As compared with the normal range of ABI, those with an ABI of < 0.90 or > 1.40 were associated with a 69% increased risk of fibrosis deterioration (95% CI: 1.12, 2.56) after adjustments for age, sex, and baseline NFS (Model 1). Further adjusting for conventional metabolic risk factors (Model 2) did not substantially change the results (OR = 1.93, 95% CI: 1.25, 2.98, P = 0.003). To explore whether IR mediated the association, further analysis was performed with adjustments for HOMA-IR (Model 3), and the results slightly decreased but remained significant (OR = 1.92, 95% CI: 1.24, 2.98, P = 0.003).
Then, we grouped the fibrosis deterioration status by baseline NFS category (Table 2). There was a 1.47-fold (95% CI: 0.89, 2.44) increased risk of progression from low to intermediate or high NFS and a 2.19-fold (95% CI: 1.10, 4.35) increased risk of progression from intermediate to high. The results did not change appreciably in Model 2 (low NFS at baseline: OR = 1.72, 95% CI: 1.00, 2.94, P = 0.04; intermediate NFS at baseline: OR = 2.27, 95% CI: 1.06, 4.84, P = 0.03). For further adjustments for HOMA-IR (Model 3), the associations were statistically significant (low NFS at baseline: OR = 1.74, 95% CI: 1.02, 3.00, P = 0.04; intermediate NFS at baseline: OR = 2.24, 95% CI: 1.05, 4.80, P = 0.03).
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In stratified analyses, the risk of fibrosis deterioration with PAD remarkably increased among patients with IR (OR = 3.23, 95% CI: 1.72, 6.04, P = 0.0003), whereas no association was found among those without IR (OR = 1.20, 95% CI: 0.62, 2.32, P = 0.58). There was a significant multiplicative interaction between PAD and IR (P for interaction = 0.03; Figure 2).
Given the observed interaction between PAD and IR, we then explored the joint effect of PAD and IR on fibrosis deterioration (Table 3). Patients with both PAD and IR had a dramatically increased risk of fibrosis deterioration, compared with those with neither PAD nor IR, after adjusting for confounders (OR = 3.85, 95% CI: 2.06, 7.18, P < 0.0001). The similar results were observed among those with progression from low to intermediate or high NFS (OR = 4.20, 95% CI: 1.75, 10.09, P = 0.001) and those with progression from intermediate to high NFS (OR = 2.82, 95% CI: 1.07, 7.42, P = 0.03).
Deterioration of fibrosis PAD IR OR (95% CI) P No. events/participants Total No No 1.00 246/696 No Yes 1.27 (0.97, 1.65) 0.09 315/790 Yes No 1.16 (0.61, 2.23) 0.65 19/56 Yes Yes 3.85 (2.06, 7.18) < 0.0001 38/68 Intermediate to high No No 1.00 40/233 No Yes 0.86 (0.50, 1.46) 0.57 68/344 Yes No 1.13 (0.30, 4.30) 0.86 4/18 Yes Yes 2.82 (1.07, 7.42) 0.03 12/34 Low to intermediate or high No No 1.00 206/463 No Yes 1.42 (1.04, 1.94) 0.03 247/446 Yes No 1.12 (0.53, 2.37) 0.78 15/38 Yes Yes 4.20 (1.75, 10.09) 0.001 26/34 Note. Data are presented as OR and 95% CI.
P-values were assessed from the logistic regression analyses, after adjustments for age, sex, baseline nonalcoholic fatty liver disease fibrosis score, central obesity, physical activity, current smoking, current drinking, diabetes, hypertension, triglycerides, HDL cholesterol, LDL cholesterol, and white blood cell.
IR: homeostasis model assessment of IR ≥ 2.5 was defined as Yes.
Abbreviation: PAD, peripheral artery disease; IR, insulin resistance; HDL, high-density lipoprotein; LDL, low-density lipoprotein.Table 3. Joint effect of PAD and IR on fibrosis deterioration
Peripheral Artery Disease and Risk of Fibrosis Deterioration in Nonalcoholic Fatty Liver Disease: A Prospective Investigation
doi: 10.3967/bes2020.031
- Received Date: 2019-10-08
- Accepted Date: 2020-01-14
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Key words:
- Ankle-brachial index /
- Nonalcoholic fatty liver disease /
- Fibrosis deterioration /
- NAFLD fibrosis score /
- Insulin resistance
Abstract:
Citation: | ZHU Wen, DENG Chan Juan, XUAN Li Ping, DAI Hua Jie, ZHAO Zhi Yun, WANG Tian Ge, LI Mian, LU Jie Li, XU Yu, CHEN Yu Hong, WANG Wei Qing, BI Yu Fang, XU Min. Peripheral Artery Disease and Risk of Fibrosis Deterioration in Nonalcoholic Fatty Liver Disease: A Prospective Investigation[J]. Biomedical and Environmental Sciences, 2020, 33(4): 217-226. doi: 10.3967/bes2020.031 |