Intraindividual Interleukin-6 Variations on the Cardiovascular Prognosis of Patients with Chronic Renal Disease

Figures & data

Figure 1.  Flow chart.

Table 1.  Demographic and analytical characteristics of patients included in the study: baseline characteristics.

Baseline parameters
Age (years)^a	72 (63–77)
Cr (mg/dL)	1.8 ± 0.7
Diabetes (yes/no)	10/80
Ischaemic heart disease (yes/no)	11/79
PVD (yes/no)	12/78
Hb (g/dL)^a	13 (12–14)
Uric acid (mg/dL)	7.6 ± 2.2
Cholesterol (mg/dL)	216 ± 37
HDL-cholesterol (mg/dL)	56 ± 17
LDL-cholesterol (mg/dL)	135 ± 35
Triglycerides (mg/dL)	143 ± 56

Notes: ^aValues expressed as median and range. Cr, serum creatinine; PVD, peripheric vascular disease; HB, serum hemoglobin; HDL, high-density lipoproteins; LDL, low-density lipoproteins.

Table 2.  Inflammatory parameters: baseline inflammatory parameters.

	Events
	Yes (N = 61)	No (N = 29)	p
Baseline IL-6 (pg/mL)	7.55 ± 8.9	5.36 ± 3.27	0.05
Mean IL-6 (pg/mL)	7.46 ± 5.42	5.09 ± 2.47	0.005
Baseline IL-1β (pg/mL)	1.77 ± 0.77	1.61 ± 0.66	Ns
Mean IL-1β (pg/mL)	1.59 ± 0.63	1.46 ± 0.65	Ns
Baseline TNF-α (pg/mL)	7.48 ± 3.99	7.17 ± 3.22	Ns
Mean TNF-α (pg/mL)	6.90 ± 2.94	6.88 ± 2.72	Ns
Baseline CRP (mg/L)	8.11 ± 8.48	5.49 ± 4.69	0.05
Mean CRP (mg/L)	6.41 ± 5.97	4.82 ± 3.79	Ns
Albuminuria (mg/day)^a	22.0 (0.0–607.8)	38.0 (0.0–263.1)	Ns

Notes: ^aValues are expressed as median (interquartile range). Ns, nonsignificant; IL-6, interleukin-6; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α; CRP, C-reactive protein.

Table 3.  Inflammatory parameters as a function of chronic kidney disease stages.

	hs-CRP (mg/L)	IL-1β (pg/mL)	IL-6 (pg/mL)	TNF-α (pg/mL)
Stage 1 or 2 (n = 9)	7.65 ± 4.9	1.55 ± 0.65	3.93 ± 2.64	6.25 ± 2.84
Stage 3 (n = 48)	6.20 ± 6.20	1.69 ± 0.73	6.75 ± 7.23	7.07 ± 3.5
Stage 4 (n = 33)	5.23 ± 5.32	1.72 ± 0.67	5.10 ± 3.05	7.77 ± 3.83

Note: IL-6, interleukin-6; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α; hs-CRP, high-sensitive C-reactive protein.

Table 4.  Demographic and analytical characteristics of patients included in the study: Differences between patients who suffered and not suffered cardiovascular events. Univariable analysis (Student’s t).

	Events
	Yes (N = 61)	No (N = 29)	p
SBP (mmHg)	155 ± 25	151 ± 20	NS
DBP (mmHg)	78 ± 12	80 ± 11	NS
Creatinine (mg/dL)	1.72 ± 0.62	1.83 ± 0.73	NS
MDRD (mL/min/1.73 m2)	39.4 ± 19.6	45.0 ± 23.3	NS
Cholesterol (mg/dL)	212 ± 35	217 ± 38	NS
HDL cholesterol (mg/dL)	54 ± 15	56 ± 17	NS
LDL cholesterol (mg/dL)	134 ± 34	135 ± 35	NS
Triglycerides (mg/dL)	130 ± 46	148 ± 60	NS
Uric acid (mg/dL)	7.4 ± 2.4	7.6 ± 2.1	NS
Age (years)	73.6 ± 9.8	66.2 ± 13.5	0.007
PVD (%)	75%	25%	0.001

Note: SBP, systolic blood pressure; DBP, diastolic blood pressure; MDRD, Modification Diet Renal Disease; PVD, peripheric vascular disease.

Table 5.  Inflammatory parameters: Inflammatory parameters in patients who had cardiovascular events versus patients without cardiovascular events. Univariate Analysis.

Inflammatory parameters
Baseline IL-6 (pg/mL)	4.8 (3.3–7.1)
Mean IL-6 (pg/mL)	5.8 ± 3.8
Baseline IL-1β (pg/mL)	1.6 ± 0.6
Median IL-1β (pg/mL)	1.5 ± 0.6
Baseline TNF-α (pg/mL)	7.2 ± 3.4
Median TNF-α (pg/mL)	6.8 ± 2.7
Baseline CRP^a (mg/L)	4.0 (2.3–6.9)
Mean CRP^a (mg/L)	3.8 (2.0–6.0)
Albuminuria^a (mg/day)	22 (0–300)

Notes: ^aValues expressed as median and range. IL-6, interleukin-6; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α; CRP, C-reactive protein.

Table 6.  Cox regression models for evaluating the predictive value of the different model of inflammatory parameters.

		HR (95% CI)	p
IL-6 (pg/mL)	Baseline	0.991 (0.905–1.084)	0.838
	Mean	1.203 (1.032–1.402)	0.018
	Variation	0.662 (0.339–1.289)	0.225
	Age	1.051 (1.004–1.101)	0.034
IL-1β (pg/mL)	Baseline	1.728 (0.671–4.450)	0.257
	Mean	0.708 (0.277–1.813)	0.472
	Variation	0.489 (0.174–1.373)	0.175
	Age	1.064 (1.019–1.110)	0.005
TNF-α (pg/mL)	Baseline	1.029 (0.782–1.354)	0.838
	Mean	1.031 (0.773–1.375)	0.837
	Variation	1.079 (0.362–3.218)	0.891
	Age	1.053 (1.010–1.099)	0.016
CRP (mg/L)	Baseline	1.118 (0.955–1.309)	0.165
	Mean	0.626 (0.771–1.170)	0.626
	Variation	0.706 (0.246–2.022)	0.516
	Age	1.044 (1.001–1.088)	0.047

Note: HR, hazard ratio; 95% CI, 95% confidence interval; IL-6, interleukin-6; IL-1β, interleudin 1β; TNF-α, tumor necrosis factor-α; CRP, C-reactive proteinuiria.

Figure 2.  Kaplan-Meyer for intra-individual variation in inflammation markers after treatment with statins or olmesartan and association with cardiovascular events. (A) = IL-1; (B) = IL-6; (C) = TNF; (D) = PCR. P = ns.

Figure 3.  Cox regression for free-cardiovascular event survival in patients with mean of IL-6 over and under 6 pg/mL, adjusted for age, renal function, albuminuria and history of cardiovascular disease.