Association of dietary total antioxidant capacity with all-cause and cardiovascular mortality in patients with chronic kidney disease: based on two retrospective cohort studies of NHANES

Figures & data

Figure 1. Flowchart for the selection of the study population, NHANES (2007–2018). A total of 6401 participants for VCEAC cohort and 6379 for CDAI cohort were separately eligible for criteria. After the exclusion of those pregnant or lactating women, and those with TAC values more than five standard deviations from the mean, 6330 participants with CKD were included in the final VECAC cohort analysis and 6300 participants with CKD were included in the final CDAI cohort analysis.

Figure 2. Restricted cubic spline models for the relationship between dietary total antioxidant capacity with all-cause (top) and CVD (bottom) mortality. (A) CKD 1–2 stage, VCEAC and all-cause mortality. (B) CKD 3–5 stage, VCEAC and all-cause mortality (C) CKD 1–2 stage, CDAI and all-cause mortality. (D) CKD 3–5 stage, CDAI and all-cause mortality (E) CKD 1–2 stage, VCEAC and CVD mortality. (F) CKD 3–5 stage, VCEAC and CVD mortality. (G) CKD 1–2 stage, CDAI and CVD mortality. (H) CKD 3–5 stage, CDAI and CVD mortality. Adjusted for age, sex, ethnicity, income, education level, potassium intake, protein intake, carbohydrate intake, dietary fiber intake, total fat intake, alcohol intake, total energy intake via the residual method, smoking, MET-PA, diabetes, hypertension, CVD and cancer, urine albumin, eGFR, and BMI. The first quartile of VCEAC/CDAI was used as reference as it yields a hazard ratio of 0. The first and last knots were placed at the 0.01 quantile and 0.99 quantile of DTAC. Shading indicates the 95% confidence interval.

Table 1. Association of VCEAC and CDAI with all-cause mortality among patients with CKD in the NHANES (2007–2018).

	VCEAC							CDAI
	Q1	Q2		Q3		Q4		Q1	Q2		Q3		Q4
		HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value		HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value
CKD 1–2 stage
Model1	Ref	0.86(0.67–1.09)	.203	0.87(0.68–1.12)	.291	0.91(0.70–1.17)	.448	Ref	0.72(0.56–0.91)	.007	0.69(0.53–0.90)	.006	0.66(0.50–0.86)	.002
Model2	Ref	0.88(0.68–1.13)	.303	0.72(0.55–0.93)	.011	0.74(0.57–0.95)	.019	Ref	0.74(0.56–0.98)	.035	0.82(0.62–1.09)	.175	0.78(0.57–1.07)	.122
Model3	Ref	0.91(0.71–1.17)	.463	0.69(0.53–0.90)	.005	0.70(0.54–0.91)	.009	Ref	0.69(0.52–0.91)	.008	0.79(0.60–1.05)	.110	0.73(0.53–1.00)	.053
CKD 3–5 stage
Model1	Ref	0.78(0.58–1.04)	.091	0.75(0.54–1.03)	.072	0.74(0.53–1.02)	.068	Ref	0.73(0.55–0.96)	.024	0.71(0.53–0.94)	.018	0.73(0.55–0.97)	.028
Model2	Ref	0.76(0.55–1.05)	.099	0.63(0.47–0.87)	.004	0.83(0.61–1.14)	.246	Ref	0.80(0.61–1.07)	.130	0.75(0.55–1.02)	.066	0.87(0.63–1.20)	.392
Model3	Ref	0.75(0.54–1.04)	.081	0.61(0.44–0.83)	.002	0.81(0.59–1.12)	.210	Ref	0.89(0.66–1.19)	.432	0.81(0.60–1.10)	.186	0.93(0.68–1.29)	.678

VCEAC: Vitamin C Equivalent Antioxidant Capacity; CDAI: Component Dietary Antioxidant Index; HR: hazard ratio; CI: confidence interval; Q: quartile.

Note: Model1: adjusted for age, sex, ethnicity, income, and education level. Model 2: Model1 + potassium, protein, carbohydrates, dietary fiber, total fat, alcohol intake, smoking, and MET-PA, and total energy intake was adjusted via the residual method; Model3: Model2 + diabetes, hypertension, CVD and cancer, urine albumin, eGFR, BMI.

Table 2. Association of VECAC and CDAI with CVD mortality among patients with CKD in the NHANES (2007–2018).

	VCEAC							CDAI
	Q1	Q2		Q3		Q4		Q1	Q2		Q3		Q4
		HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value		HR (95% CI)	p Value	HR (95% CI)	p Value	HR (95% CI)	p Value
CKD 1–2 stage
Model1	Ref	0.74(0.49–1.10)	.135	0.77(0.52–1.13)	.184	0.83(0.55–1.25)	.364	Ref	1.01(0.68–1.51)	.957	1.12(0.72–1.74)	.620	1.11(0.70–1.76)	.661
Model2	Ref	0.76(0.51–1.13)	.172	0.55(0.35–0.87)	.010	0.69(0.45–1.04)	.077	Ref	0.85(0.51–1.40)	.520	0.75(0.44–1.27)	.278	0.84(0.48–1.49)	.559
Model3	Ref	0.82(0.54–1.25)	.352	0.51(0.32–0.81)	.004	0.64(0.40–1.01)	.057	Ref	0.82(0.50–1.36)	.444	0.73(0.43–1.24)	.244	0.82(0.46–1.47)	.501
CKD 3–5 stage
Model1	Ref	0.95(0.53–1.71)	.858	1.05(0.56–1.97)	.884	1.10(0.56–2.15)	.791	Ref	1.36(0.80–2.32)	.251	1.64(0.97–2.79)	.066	1.64(0.97–2.77)	.066
Model2	Ref	1.04(0.55–1.96)	.902	0.87(0.51–1.48)	.604	1.01(0.55–1.87)	.969	Ref	1.14(0.68–1.90)	.615	1.44(0.84–2.48)	.186	1.29(0.73–2.27)	.381
Model3	Ref	1.08(0.55–2.13)	.813	0.79(0.46–1.39)	.418	1.01(0.50–2.02)	.981	Ref	1.27(0.75–2.13)	.370	1.58(0.92–2.71)	.097	1.36(0.79–2.36)	.267

VCEAC: Vitamin C Equivalent Antioxidant Capacity; CDAI: Component Dietary Antioxidant Index; HR: hazard ratio; CI: confidence interval; Q: quartile.

Notes: Model1: adjusted for age, sex, ethnicity, income, and education level. Model 2: Model1 + potassium, protein, carbohydrates, dietary fiber, total fat, alcohol intake, smoking, and MET-PA, and total energy intake was adjusted via the residual method; Model3: Model2 + diabetes, hypertension, CVD and cancer, urine albumin, eGFR, BMI.

Figure 3. Subgroup analyses of multi-variable adjusted association of VCEAC or CDAI with all-cause (top) and CVD (bottom) mortality in the NHANES (2007–2018), stratified by selected patients’ characteristics. (A) VCEAC and CDAI with all-cause mortality. (B) VCEAC and CDAI with CVD mortality. Abbreviations: HRs: hazard ratios; CI: confidence intervals; CVD: cardiovascular disease; CDAI: Component Dietary Antioxidant Index; VCEAC: Vitamin C Equivalent Antioxidant Capacity. Adjusted for ethnicity, income, and education level, smoking status, potassium intake, protein intake, alcohol intake, total dietary fat intake, carbohydrate intake, and total energy intake was adjusted via the residual method, BMI, MET-PA, with exception of stratifying factors.

Table 3. Mediation analysis of VCEAC with mortality of CKD.

	All-cause mortality				CVD mortality
	Total effects (95%CI)	ACME (95%CI)	Mediation proportion (%)	p Value	Total effects (95%CI)	ACME (95%CI)	Mediation proportion (%)	p Value
Vitamin A	0.12(0.03–0.22)	−0.02(−0.07–0.03)	–	.43	0.12(0.03–0.22)	−0.02(−0.08–0.03)	–	.408
Vitamin C	0.12(0.03–0.21)	0.01(−0.02–0.03)	–	.67	0.12(0.02–0.21)	0.01(−0.02–0.03)	–	.676
Vitamin E	0.12(0.02–0.22)	0.04(0.01–0.07)	32.28	.01	0.12(0.03–0.21)	0.04(0.01–0.07)	32.47	.012
Beta-carotene	0.12(0.02–0.21)	−0.02(−0.19–0.14)	–	.84	0.12(0.02–0.21)	−0.02(−0.18–0.15)	–	.802
Alpha-carotene	0.11(0.02–0.20)	−0.08(−0.19–0.04)	–	.20	0.11(0.02–0.21)	−0.07(−0.18–0.04)	–	.208
Beta-cryptoxanthin	0.12(0.03–0.22)	0.03(0.00–0.06)	21.90	.03	0.13(0.03–0.23)	0.03(0.00–0.06)	22.01	.020
Lycopene	0.12(0.03–0.21)	0.01(−0.02–0.04)	–	.61	0.11(0.03–0.21)	0.01(−0.02–0.04)	–	.536
Lutein_zeaxanthin	0.12(0.03–0.22)	−0.01(−0.06–0.04)	–	.71	0.12(0.03–0.22)	−0.01(−0.06–0.04)	–	.732
Carotenoids	0.12(0.03–0.22)	0.01(−0.02–0.03)	–	.59	0.12(0.03–0.21)	0.01(−0.02–0.03)	–	.556
Isoflavones	0.12(0.03–0.21)	0.00(0.00–0.00)	–	.74	0.12(0.03–0.21)	0.00(0.00–0.00)	–	.770
Anthocyanidins	0.12(0.03–0.22)	0.01(0.00–0.02)	8.23	.03	0.13(0.03–0.22)	0.01(0.00–0.02)	8.21	.026
Flavan-3-ols	0.12(0.03–0.21)	0.00(−0.02–0.03)	–	.79	0.12(0.02–0.21)	0.00(−0.02–0.02)	–	.844
Flavanones	0.12(0.03–0.21)	0.00(−0.01–0.00)	–	.66	0.12(0.03–0.21)	0.00(−0.01–0.00)	–	.660
Flavones	0.12(0.03–0.22)	0.03(0.00–0.07)	25.67	.04	0.12(0.03–0.22)	0.03(0.01–0.07)	27.12	.046
Flavonols	0.12(0.03–0.21)	0.02(−0.01–0.05)	–	.23	0.12(0.03–0.22)	0.02(−0.01–0.05)	–	.228

ACME: average causal mediation effects.

Table 4. Mediation analysis of CDAI with mortality of CKD.

	All-cause mortality				CVD mortality
	Total effects (95%CI)	ACME (95%CI)	Mediation proportion (%)	p Value	Total effects (95%CI)	ACME (95%CI)	Mediation proportion (%)	p Value
Vitamin C	3.11(0.69–5.34)	0.12(−0.59–0.80)	–	0.710	−0.42(−14.57–12.72)	0.06(−4.04–4.08)	–	0.990
Vitamin E	3.23(1.05–5.70)	0.80(0.07–1.59)	24.21	0.040	0.51(−12.13–14.51)	3.91(−0.13–9.49)	–	0.952
Selenium	3.18(0.90–5.56)	0.00(−0.04–0.04)	–	0.936	−0.01(−13.07–11.80)	−0.09(−0.52–0.24)	–	0.976
Magnesium	3.43(1.02–5.88)	1.93(1.02–3.04)	55.94	0.008	0.30(−13.20–13.53)	5.87(0.37–13.49)	–	0.944
Zinc	3.28(0.93–5.71)	−0.14(−0.36–0.05)	–	0.140	−0.23(−12.91–11.60)	−0.41(−1.70–0.67)	–	0.986
Carotenoids	3.37(1.03–5.96)	−1.76(−4.82–1.16)	–	0.252	−0.48(−13.57–12.11)	−3.15(−20.55–12.65)	–	0.966
Isoflavones	3.06(0.70–5.42)	−0.50(−1.09–−0.01)	–	0.044	0.75(−11.62–13.13)	−2.27(−4.88–−0.53)	–	0.882
Anthocyanidins	3.41(0.87–5.89)	0.96(−0.20–2.15)	–	0.092	−0.28(−12.76–12.57)	2.72(−2.40–9.18)	–	0.960
Flavan-3-ols	3.32(0.96–5.91)	−2.15(−5.12–0.72)	–	0.160	−0.58(−14.16–12.06)	−1.33(−19.10–14.42)	–	0.986
Flavanones	3.16(0.92–5.47)	−0.21(−0.62–0.17)	–	0.308	−0.09(−13.66–13.36)	0.95(−1.48–3.73)	–	0.984
Flavones	3.27(0.95–5.88)	1.05(−0.04–2.29)	–	0.080	0.90(−11.95–14.54)	6.87(−0.42–15.81)	–	0.842
Flavonols	3.13(0.78–5.42)	−0.11(−3.14–2.79)	–	0.942	−0.33(−13.87–12.58)	−4.64(−21.48–11.32)	–	1.000

ACME: average causal mediation effects.

Data availability statement

The data that support the findings of this study are openly available in NHANES at http://www.cdc.gov/nhanes. Additional data are available from the corresponding author on reasonable request.