Association of interleg difference of ankle brachial index with overall and cardiovascular mortality in chronic hemodialysis patients

Figures & data

Figure 1. Frequency distribution of interleg ABI difference in study patients.

Figure 2. The Kaplan–Meier survival curves of all-cause by interleg ABI difference. The difference of survival across the four groups, including interleg difference in ABI of <0.05, 0.05–0.10, 0.10–0.15 and ≥0.15 was statistically significant with respect to all-cause mortality (χ²= 26.36, p < 0.001) using the log-rank test.

Table 1. Comparison of baseline characteristics between patients with and without an interleg difference in ABI ≥ 0.15.

Characteristic	All patients (N = 369)	Interleg ABI difference <0.15 (N = 320)	Interleg ABI difference ≥0.15 (N = 49)	p Value
Age (yr)	62.0 ± 13.2	61.4 ± 13.0	66.0 ± 13.7	0.022
Male (%)	171 (46.0%)	146 (45.6%)	25 (51.0%)	0.539
Duration of dialysis (yr)	7.9 ± 5.4	7.6 ± 5.3	9.7 ± 6.0	0.014
Diabetes mellitus (%)	124 (33.4%)	100 (31.2%)	24 (48.9%)	0.014
Coronary artery disease	61 (16.4%)	53 (16.5)	8 (16.3%)	0.967
Cerebrovascular disease	14 (3.7%)	12 (3.7%)	2 (4.0%)	0.910
Hypertension	250 (67.3%)	220 (68.7%)	30 (61.2%)	0.294
ABI <0.9	103 (27.7)	67 (20.9%)	36 (73.4%)	<0.001
Brachial-ankle PWV (m/s)	18.6 ± 7.3	17.9 ± 3.9	23.4 ± 16.9	<0.001
Mena artery pressure (mmHg)	97 ± 23	99 ± 22	81 ± 25	<0.001
Pulse pressure (mmHg)	66 ± 25	68 ± 24	54 ± 30	<0.001
Body mass index (kg/m^2)	22.2 ± 4.0	22.3 ± 4.1	21.2 ± 3.5	0.074
Cardio-thoracic ratio >50%	215 (57.9%)	183 (57.1%)	32 (65.3%)	0.351
Laboratory parameter
Albumin level (g/dL)	4.0 ± 0.7	4.1 ± 0.3	4.0 ± 0.3	0.871
Triglyceride (mg/dL)	144 ± 111	147 ± 111	146 ± 106	0.829
Cholesterol level (mg/dL)	170 ± 47	173 ± 41	174 ± 42	0.434
Kt/V	1.6 ± 0.3	1.6 ± 0.2	16 ± 0.1	0.987
Creatinine (mg/dL)	9.5 ± 2.1	9.6 ± 2.1	8.6 ± 1.9	0.004
BUN	68.1 ± 17.8	68.3 ± 17.3	66.5 ± 20.6	0.574
Ca × P (mg/dL)^2	46.7 ± 15.2	47.7 ± 13.3	46.6 ± 18.2	0.999
Hemoglobin (g/dL)	10.4 ± 1.3	10.4 ± 1.3	10.2 ± 1.4	0.452
iPTH (pg/mL)	225 ± 236	232 ± 223	227 ± 322	0.991
Uric acid (mg/dL)	7.0 ± 1.3	7.0 ± 1.3	6.9 ± 1.1	0.511

Note: ABI, ankle-brachial index; PWV, pulse wave velocity; BUN, blood urea nitrogen; iPTH, intact parathyroid hormone; Ca×P, calcium-phosphate product.

Table 2. Determinants of an inter-leg difference in ABI ≥ 0.15.

	Crude		Multivariable
Parameter	OR (95% CI)	p Value	OR (95% CI)	p Value
Age (per yr)	1.02 (1.00, 1.05)	0.023	0.99 (0.95, 1.02)	0.567
Male (vs. female)	1.24 (0.68, 2.26)	0.481	2.46 (1.05, 5.75)	0.038
Duration of dialysis (per yr)	1.06 (1.01, 1.12)	0.015	1.08 (1.00, 1.16)	0.051
Diabetes mellitus	2.11 (1.15, 3.87)	0.016	0.78 (0.32, 1.92)	0.601
Cardiovascular disease	1.02 (0.48, 2.16)	0.947	0.70 (0.29, 1.72)	0.448
Hypertension	0.71 (0.38, 1.33)	0.295	0.87 (0.39, 1.94)	0.744
Mean artery pressure (per mmHg)	0.96 (0.95, 0.98)	<0.001	0.97 (0.94, 1.00)	0.144
Pulse pressure (per mmHg)	0.97 (0.96, 0.98)	<0.001	1.01 (0.99, 1.04)	0.133
ABI <0.9	10.45 (5.2, 20.8)	<0.001	10.7 (3.77, 30.8)	<0.001
Brachial-ankle PWV (per m/s)	1.08 (1.02, 1.14)	0.005	1.07 (0.99, 1.14)	0.054
Body mass index (per kg/m^2)	0.92 (0.85, 1.00)	0.075	0.93 (0.84, 1.04)	0.267
Albumin level (per g/dL)	0.96 (0.64, 1.45)	0.870	0.79 (0.25, 2.47)	0.687
Triglyceride (per mg/dL)	1.00 (0.99, 1.00)	0.829	0.99 (0.99, 1.00)	0.380
Cholesterol level (per mg/dL)	1.00 (0.99, 1.00)	0.433	1.00 (0.99, 1.01)	0.560
Creatinine (per mg/dL)	0.87 (0.69, 0.93)	0.005	0.99 (0.78, 1.27)	0.975
Ca × P product (per mg^2/dL^2)	1.00 (0.98, 1.02)	0.999	1.01 (0.98, 1.03)	0.455
Cardio-thoracic ratio >50%	1.39 (0.74, 2.62)	0.295	1.45 (0.62, 3.35)	0.382

Note: OR, odds ratio; CI, confidence interval; ABI, ankle-brachial index; PWV, pulse wave velocity.

Figure 3. The Kaplan-Meier survival curves of all-cause (A) and CV mortality (B) by an interleg ABI difference of ≥0.15. The difference of survival across the two groups was statistically significant with respect to all-cause (χ²= 25.56, p < 0.001) and CV (χ²= 18.89, p < 0.001) mortality using the log-rank test.

Table 3. Relation of an inter-leg difference in ABI of <0.15 or ≥0.15 to overall and cardiovascular mortality using the Cox proportional hazards model.

	Overall mortality		Cardiovascular mortality
Inter-leg ABI difference (≥0.15 vs. <0.15)	HR (95% CI)	p Value	HR (95% CI)	p Value
Unadjusted	3.00 (1.91, 4.71)	<0.001	3.13 (1.82, 5.38)	<0.001
Multivariate adjusted model 1	2.17 (1.34, 3.51)	0.001	2.16 (1.21, 3.86)	0.009
Multivariate adjusted model 2	2.04 (1.22, 3.39)	0.006	2.08 (1.12, 3.87)	0.020
Multivariate adjusted model 3	1.77 (1.03, 3.05)	0.036	1.75 (0.90, 3.40)	0.094

Notes: Multivariate model 1 is adjusted for age, sex, diabetes mellitus, hypertension, cardiovascular artery disease, and hemodialysis time. Multivariate model 2 comprises model 1 as well as mean artery pressure, pulse pressure, cardiomegaly, albumin, triglyceride, total cholesterol, hemoglobin, creatinine, BUN, uric acid, and calcium-phosphorous product. Multivariate model 3 comprises model 2 as well as ABI < 0.9, and brachial-ankle PWV. HR, hazard ratio; CI, confidence interval; ABI, ankle-brachial index; PWV, pulse wave velocity.

Table 4. The predictability of overall and cardiovascular mortality between ABI<0.9 and interleg ABI difference of ≥0.15.

	Overall mortality		Cardiovascular mortality
Parameters	Difference in likelihood ratio	p	Difference in likelihood ration	p
ABI<0.9	2.83	0.092	0.98	0.323
Interleg ABI difference	4.10	0.043	2.65	0.104
	Category-less NRI Index statistics (95% CI)		Category-less NRI Index statistics (95% CI)
ABI<0.9	0.128 (−0.137–0.282)	0.199	0.094 (−0.200–0.244)	0.637
Interleg ABI difference	0.094 (−0.175–0.216)	0.488	0.123 (−0.010–0.295)	0.537

Notes: p Value was based on the incremental value compared with the previous model. The full model was adjusted for age, sex, diabetes mellitus, hypertension, cardiovascular disease and hemodialysis time, mean artery pressure, pulse pressure, cardiomegaly, albumin, triglyceride, total cholesterol, hemoglobin, creatinine, BUN, uric acid, calcium-phosphorous product, PWV, ABI < 0.9 and interleg ABI difference. NRI, net reclassification improvement; CI, confidence interval; ABI, ankle-brachial index; PWV, pulse wave velocity.

Table 5. The hazard ratio of an interleg difference in ABI of ≥0.15 (vs. of <0.15) of overall and cardiovascular mortality in subgroup analysis.

			Overall mortality		Cardiovascular mortality
Subgroup	Interleg ABI difference <0.15 (N)	Interleg ABI difference ≥0.15 (N)	HR (95% CI)	p Value	HR (95% CI)	p Value
All	320	49	1.77 (1.03, 3.05)	0.036	1.75 (0.90, 3.40)	0.094
Diabetes mellitus
Yes	100	24	1.79 (0.79, 4.02)	0.158	1.75 (0.62, 4.90)	0.284
No	220	25	1.69 (0.74, 3.88)	0.212	1.98 (0.71, 5.51)	0.189
Age
<60	147	13	0.51 (0.05, 5.21)	0.576	0.49 (0.01, 2.86)	0.147
≥60	173	36	2.29 (1.28, 4.11)	0.005	2.38 (1.18, 4.81)	0.015
Sex
Male	146	25	1.45 (0.58, 3.60)	0.419	1.26 (0.43, 3.62)	0.667
Female	174	24	2.66 (1.20, 5.88)	0.016	3.06 (1.06, 8.84)	0.039
Hypertension
Yes	220	30	1.93 (0.96, 3.88)	0.063	2.23 (0.93, 5.36)	0.071
No	100	19	1.70 (0.57, 5.08)	0.337	1.25 (0.32, 4.88)	0.746
ABI <0.9
Yes	67	36	2.70 (1.26, 5.79)	0.011	2.49 (1.03, 6.03)	0.042
No	253	13	0.53 (0.11, 2.46)	0.423	0.48 (0.04, 5.38)	0.558

Notes: Multivariate model is adjusted for age, sex, diabetes mellitus, hypertension, coronary artery disease and hemodialysis time, mean artery pressure, pulse pressure, cardiomegaly, albumin, triglyceride, total cholesterol, hemoglobin, creatinine, BUN, uric acid and calcium-phosphorous product, ABI < 0.9 and PWV. ABI, ankle-brachial index; PWV, pulse wave velocity.