Baseline characteristics
The baseline characteristics of the study population stratified by WWI tertiles are shown in Table 1. A total of 7,344 participants (males: 50.60%; females: 49.40%) with an average age of 60.18 ± 13.03 years were included in this study. The mean WWI was 11.16 ± 0.78 cm/√kg, and the ranges of tertiles 1-3 were 8.36- 10.81, 10.81-11.49, and 11.49-15.52 cm/√kg, respectively. Moreover, the prevalence of PAD was 7.84% (576 participants), which was respectively 3.72% (91 participants), 7.23% (177 participants), and 12.58% (308 participants) in WWI tertiles 1-3 (P <0.001). Individuals in the highest WWI tertile were predominated by older participants, and had higher BMI, WC, SBP, HbA1c, TC, TG, and SUA; higher prevalence of HTN, DM, and CHD; less alcohol intake; and lower educational level and DBP values (all P <0.001).
Table 1. Baseline characteristics of the study population according to weight-adjusted-waist index tertiles.
Characteristics
|
Overall
|
Tertile categories of WWI (cm/√kg)
|
P value
|
T1 (8.36-10.81)
|
T2 (10.81-11.49)
|
T3 (11.49-15.52)
|
Participants
|
7344
|
2448
|
2448
|
2448
|
|
Age (years)
|
60.18 ± 13.03
|
54.06 ± 11.55
|
60.15 ± 12.30
|
66.32 ± 12.23
|
<0.001
|
Gender (%)
|
|
|
|
|
<0.001
|
Male
|
3716 (50.60%)
|
1278 (52.21%)
|
1373 (56.09%)
|
1065 (43.50%)
|
|
Female
|
3628 (49.40%)
|
1170 (47.79%)
|
1075 (43.91%)
|
1383 (56.50%)
|
|
Race (%)
|
|
|
|
|
<0.001
|
Mexican American
|
1540 (20.97%)
|
350 (14.30%)
|
523 (21.36%)
|
667 (27.25%)
|
|
Other Hispanic
|
285 (3.88%)
|
68 (2.78%)
|
115 (4.70%)
|
102 (4.17%)
|
|
Non-Hispanic White
|
3968 (54.03%)
|
1343 (54.86%)
|
1298 (53.02%)
|
1327 (54.21%)
|
|
Non-Hispanic Black
|
1326 (18.06%)
|
620 (25.33%)
|
430 (17.57%)
|
276 (11.27%)
|
|
Other Race
|
225 (3.06%)
|
67 (2.74%)
|
82 (3.35%)
|
76 (3.10%)
|
|
Educational level (%)
|
|
|
|
|
<0.001
|
Less than high school
|
2468 (33.67%)
|
572 (23.42%)
|
788 (32.26%)
|
1108 (45.32%)
|
|
High school or GED
|
1726 (23.55%)
|
543 (22.24%)
|
609 (24.93%)
|
574 (23.48%)
|
|
More than high school
|
3136 (42.78%)
|
1327 (54.34%)
|
1046 (42.82%)
|
763 (31.21%)
|
|
BMI (kg/m2)
|
28.40 ± 5.58
|
26.03 ± 4.80
|
28.64 ± 5.24
|
30.57 ± 5.72
|
<0.001
|
WC (cm)
|
98.97 ± 13.87
|
89.31 ± 10.81
|
99.87 ± 11.22
|
107.71 ± 12.80
|
<0.001
|
WWI (cm/√kg)
|
11.16 ± 0.78
|
10.32 ± 0.40
|
11.14 ± 0.20
|
12.01 ± 0.43
|
<0.001
|
SBP (mmHg)
|
133.83 ± 22.28
|
127.57 ± 20.49
|
133.83 ± 21.59
|
140.15 ± 22.93
|
<0.001
|
DBP (mmHg)
|
72.96 ± 14.37
|
74.37 ± 13.02
|
73.24 ± 13.76
|
71.27 ± 16.04
|
<0.001
|
Smoking status (at least 100 cigarettes in life) (n, %)
|
3948 (53.77%)
|
1288 (52.61%)
|
1325 (54.13%)
|
1335 (54.56%)
|
0.453
|
Alcohol intake (at least 12
alcohol drinks per year) (n, %)
|
4809 (66.99%)
|
1732 (72.14%)
|
1630 (68.09%)
|
1447 (60.70%)
|
<0.001
|
Hemoglobin A1c (%)
|
5.77 ± 1.14
|
5.51 ± 0.89
|
5.75 ± 1.06
|
6.06 ± 1.34
|
<0.001
|
TBiL (umol/L)
|
11.93 ± 4.86
|
12.25 ± 5.02
|
12.09 ± 5.04
|
11.44 ± 4.45
|
<0.001
|
AST (U/L)
|
26.00 ± 25.81
|
26.36 ± 39.14
|
26.22 ± 16.84
|
25.42 ± 13.70
|
0.408
|
ALT (U/L)
|
26.06 ± 31.12
|
26.04 ± 45.26
|
27.01 ± 23.59
|
25.11 ± 17.43
|
0.111
|
Total cholesterol (mmol/L)
|
5.38 ± 1.07
|
5.32 ± 1.01
|
5.41 ± 1.08
|
5.40 ± 1.10
|
0.004
|
Triglycerides (mmol/L)
|
1.75 ± 1.69
|
1.50 ± 1.74
|
1.76 ± 1.53
|
1.99 ± 1.74
|
<0.001
|
Serum uric acid (µmol/L)
|
327.25 ± 86.40
|
308.59 ± 82.06
|
333.89 ± 85.95
|
339.20 ± 88.00
|
<0.001
|
Serum creatinine (µmol/L)
|
78.96 ± 38.69
|
77.65 ± 31.88
|
79.25 ± 40.79
|
79.99 ± 42.52
|
0.107
|
Hypertension (%)
|
3075 (42.04%)
|
733 (30.08%)
|
1033 (42.39%)
|
1309 (53.65%)
|
<0.001
|
Diabetes mellitus (%)
|
956 (13.02%)
|
158 (6.45%)
|
273 (11.15%)
|
525 (21.45%)
|
<0.001
|
Coronary heart disease (%)
|
467 (6.36%)
|
85 (3.47%)
|
179 (7.31%)
|
203 (8.29%)
|
<0.001
|
Peripheral arterial disease (%)
|
576 (7.84%)
|
91 (3.72%)
|
177 (7.23%)
|
308 (12.58%)
|
<0.001
|
Abbreviations: WWI, weight-adjusted-waist index; BMI, body mass index; WC, waist circumference; SBP, systolic blood pressure; DBP, diastolic blood pressure; TBiL, total bilirubin; AST, aspartate transaminase; ALT, alanine transaminase.
Associations between WWI and PAD
As shown in Table 2, elevated WWI was associated with an increased likelihood of PAD. After full adjustment (Model 3), every one unit increase in WWI was associated with 25% increased odds of PAD (OR = 1.25; 95% CI: 1.06-1.48). We further transformed WWI into categorical variables for sensitivity analysis. The adjusted OR was 1.53 (95% CI: 1.10-2.12) for Tertile 2 and 1.77 (95% CI: 1.26-2.49) for Tertile 3, indicating a stable positive association between WWI and increased risk of PAD with statistical significance (P for trend = 0.002).
Table 2. The association between weight-adjusted-waist index and peripheral arterial disease in total samples.
WWI
(cm/√kg)
|
Events (%)
|
PAD, OR (95%CI), P value
|
Model 1
|
Model 2
|
Model 3
|
Per 1cm/√kg increase
|
576 (7.84)
|
1.94 (1.74, 2.17), <0.001
|
1.39 (1.19, 1.63), <0.001
|
1.25 (1.06, 1.48), 0.009
|
Tertiles
|
|
|
|
|
T1 (8.36-10.81)
|
91 (3.72)
|
Reference
|
Reference
|
Reference
|
T2 (10.81-11.49)
|
177 (7.23)
|
2.02 (1.56, 2.62), <0.001
|
1.62 (1.20, 2.21), 0.002
|
1.53 (1.10, 2.12), 0.011
|
T3 (11.49-15.52)
|
308 (12.58)
|
3.73 (2.93, 4.74), <0.001
|
2.09 (1.52, 2.88), <0.001
|
1.77 (1.26, 2.49), 0.001
|
P for trend
|
|
<0.001
|
<0.001
|
0.002
|
Abbreviations: WWI, weight-adjusted-waist index; PAD, peripheral arterial disease; 95% CI: 95% confidence interval; OR: odds ratio;
Model 1: No covariates were adjusted.
Model 2: Adjusted for gender, age, race, education level, body mass index, systolic and diastolic blood pressure.
Model 3: Adjusted for model 2 + smoking status, alcohol intake, hemoglobin A1c, total bilirubin, aspartate transaminase, alanine transaminase, total cholesterol, triglycerides, serum creatinine, serum uric acid, hypertension, diabetes mellitus, and coronary heart disease.
Besides, the smooth curve fitting indicated that there was a nearly linear relationship between WWI and the risk of PAD in the total population (Figure 1).
Subgroup analysis
Subgroup analyses were conducted to explore the robustness of the association between WWI and PAD in different population settings. None of the stratifications, including gender (male and female), age (<60 years and ≥60 years), race (Mexican American, other Hispanic, non-Hispanic black, non-Hispanic white, and other races), education level (< high school, high school, and > high school), BMI (<30 kg/m2 and ≥30 kg/m2), HTN (yes and no), DM (yes and no), and CHD (yes and no), significantly modified the association between WWI and PAD prevalence (all P for interaction > 0.05). The results indicated that the positive WWI-PAD association was stable in stratified subgroups and could be appropriate for various populations (Figure 2).
Non-linear positive association of WWI and PAD in females
Given the difference in body composition between males and females, analyses stratified by sex were further conducted. As shown in Table S1 (Supplementary Information), a significantly positive association between WWI and PAD prevalence was observed in male participants (Model 3: OR = 1.35, 95% CI: 1.01-1.82). Although there were similar trends in female participants, the difference was not statistically significant (Model 3: OR = 1.23, 95% CI: 0.99-1.52).
We then used GAM and smooth curve fitting to evaluate the non-linearity for different sexes. The results show that there was a non-linear relationship between WWI and the prevalence of PAD in female participants, with a log-likelihood ratio test of 0.021 (Table 3; Figure 3). The inflection point was determined to be 10.98 cm/√kg using the two-piecewise linear regression model. On the left of the inflection point, a positive association between WWI and PAD was observed, with the adjusted OR being 2.71 (95% CI: 1.27-5.78). Nevertheless, no relationship with statistical significance was observed on the right of the inflection point (OR = 1.01, 95% CI: 0.77-1.33). Unlike females, a nearly linear relationship was detected in males (OR = 1.35, 95% CI: 1.01-1.82), with a log-likelihood ratio test of 0.317 (Table 3; Figure 3).
Table 3. Threshold effect analysis of WWI on PAD using a two-piecewise linear regression model.
WWI
(cm/√kg)
|
*Adjusted OR (95% CI), P value
|
Male
|
Female
|
All participants
|
Fitting by standard linear model
|
1.35 (1.01, 1.82), 0.043
|
1.23 (0.99, 1.52), 0.058
|
1.25 (1.06, 1.48), 0.009
|
Fitting by two-piecewise linear model
|
|
|
|
Inflection point (K)
|
11.44
|
10.98
|
11.64
|
< K Effect size
|
0.77 (0.26, 2.30), 0.645
|
2.71 (1.27, 5.78), 0.010
|
1.50 (1.14, 1.97), 0.004
|
> K Effect size
|
1.44 (1.05, 1.98), 0.024
|
1.01 (0.77, 1.33), 0.930
|
1.00 (0.72, 1.37), 0.986
|
Log likelihood ratio test P-value
|
0.317
|
0.021
|
0.093
|
Abbreviations: WWI, weight-adjusted-waist index; PAD, peripheral arterial disease; 95% CI: 95% confidence interval; OR: odds ratio.
*Adjusted for gender (only for all participants), age, race, education level, body mass index, systolic and diastolic blood pressure, smoking status, alcohol intake, hemoglobin A1c, total bilirubin, aspartate transaminase, alanine transaminase, total cholesterol, triglycerides, serum creatinine, serum uric acid, hypertension, diabetes mellitus, and coronary heart disease.
WWI predicts PAD better than BMI and WC
The ROC curves were used to evaluate the discriminative ability of different indicators for PAD. As shown in Table 4 and Figure S2 (Supplementary Information), WWI showed the highest area under the curve (AUC) in both males (0.647; 95% CI: 0.615-0.680) and females (0.654; 95% CI: 0.623-0.685), with cut-off values of 11.12 and 11.36 cm/√kg, respectively.
Table 4. Comparison of the ability of different obesity-related indices to predict peripheral artery disease.
Test
|
AUC (95% CI)
|
Cut-off
|
Specificity
|
Sensitivity
|
Youden index
|
Males
|
|
|
|
|
|
BMI
|
0.567 (0.532, 0.602)
|
28.55
|
0.424
|
0.703
|
0.127
|
WC
|
0.501 (0.466, 0.536)
|
112.75
|
0.819
|
0.208
|
0.027
|
WWI
|
0.647 (0.615, 0.680)
|
11.12
|
0.554
|
0.698
|
0.252
|
Females
|
|
|
|
|
|
BMI
|
0.505 (0.470, 0.540)
|
31.16
|
0.700
|
0.333
|
0.033
|
WC
|
0.559 (0.526, 0.592)
|
97.05
|
0.564
|
0.559
|
0.123
|
WWI
|
0.654 (0.623, 0.685)
|
11.36
|
0.588
|
0.653
|
0.241
|
Abbreviations: WWI, weight-adjusted-waist index; BMI, body mass index; WC, waist circumference; AUC, area under the curve; 95% CI, 95% confidence interval.