Pulmonary hypertension in patients with advanced heart failure is associated with increased levels of interleukin-6

Figures & data

Table 1. Baseline clinical characteristics.

Age (years)	56.2 ± 8.98 SD
Females (%)	5 (17)
Sinus rhythm (%)	16 (53)
Ischemic etiology (%)	11 (37)
Arterial hypertension (%)	13 (43)
Diabetes (%)	10 (33)
Hyperlipidemia (%)	7 (23)
Renal failure (%)	6 (20)
COPD (%)	3 (10)
Beta blocker (%)	28 (93)
ACEI/ARB (%)	29 (97)
Loop diuretic (%)	25 (83)
Spironolactone (%)	28 (93)
Statin (%)	15 (50)
ASA (%)	13 (43)
Clopidogrel (%)	3 (10)
Warfarin (%)	13 (43)
6MWT distance, meters	355 ± 111 SD

SD, standard deviation; COPD, chronic obstructive pulmonary disease; ACEI, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; ASA, acetylsalicylic acid; and 6MWT, six-minute walking test.

Table 2. Baseline echocardiographic and hemodynamic characteristics.

LV EDD, mm	68.9 ± 10.2 SD
LV ESD, mm	59.7 ± 11.8 SD
LV EDV, ml	254.3 ± 84.1 SD
LV ESV, ml	189.5 ± 79.8 SD
LV SV, ml	65.1 ± 20.8 SD
LV EF, %	26.4 ± 11.5 SD
Sm, cm/s	3.7 ± 1.4 SD
RV longitudinal diameter, mm	93.3 ± 11.1 SD
RV basal diameter, mm	40.0 ± 7.8 SD
RV mid cavity diameter, mm	44.2 ± 8.2 SD
FAC, %	26.1 ± 10.7 SD
TAPSE, mm	15.1 ± 5.9 SD
St, cm/s	9.0 ± 2.8 SD
Systolic PAP, mmHg	56.17 ± 14.74 SD
Diastolic PAP, mmHg	25.23 ± 8.18 SD
Mean PAP, mmHg	36.20 ± 10.11 SD
PCWP, mmHg	23.97 ± 8.63 SD
TPG, mmHg	12.07 ± 4.55 SD

LV, left ventricular; EDD, end diastolic diameter; SD, standard deviation; ESD, end systolic diameter; EDV, end diastolic volume; ESV, end systolic volume; SV, stroke volume; EF, ejection fraction; Sm, peak systolic septal mitral annular velocity; RV, right ventricular; FAC, fractional area change, TAPSE, tricuspid annular plane systolic excursion; St, peak systolic tricuspid annular velocity; PAP; pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; and TPG, transpulmonary pressure gradient.

Table 3. Differences in measured levels of biomarkers in peripheral vein and pulmonary artery samples.

	Peripheral vein (mean ± SD)	Pulmonary artery (mean ± SD)
IL-6, ng/L	8.89 ± 4.58	8.71 ± 4.55
TNF α, ng/L	2.87 ± 1.19	2.86 ± 1.19
hsCRP, mg/L	7.69 ± 6.73	7.53 ± 6.59
ET-1, pmol/L	5.90 ± 6.16	6.23 ± 6.33
NT-proBNP, pg/mL	4989 ± 3961	4950 ± 3997

SD, standard deviation; IL-6, interleukin 6; TNF-α, tumor necrosis factor α; hsCRP, high-sensitivity C-reactive protein; ET-1, endothelin 1; and NT-proBNP, N-terminal prohormone of brain natriuretic peptide.

Table 4. Differences in measured levels of biomarkers in peripheral vein and pulmonary artery regarding heart failure etiology.

	Non-ischemic etiology (mean ± SD)	Ischemic etiology (mean ± SD)
Peripheral vein
IL-6, ng/L	9.75 ± 4.67	7.39 ± 4.21
TNF α, ng/L	2.88 ± 1.39	2.84 ± 0.78
hsCRP, mg/L	9.01 ± 7.79	5.55 ± 3.96
ET-1, pmol/L	5.12 ± 5.09	7.17 ± 7.71
NT-proBNP, pg/mL	5518 ± 4595	4074 ± 2458
Pulmonary artery
IL-6, ng/L	9.61 ± 4.69	7.16 ± 4.04
TNF α, ng/L	2.85 ± 1.38	2.88 ± 0.85
hsCRP, mg/L	8.79 ± 7.62	5.45 ± 3.91
ET-1, pmol/L	5.15 ± 4.72	7.90 ± 8.21
NT-proBNP, pg/mL	5489 ± 4688	4020 ± 2294

SD, standard deviation; IL-6, interleukin 6; TNF-α, tumor necrosis factor α; hsCRP, high-sensitivity C-reactive protein; ET-1, endothelin 1; and NT-proBNP, N-terminal prohormone of brain natriuretic peptide.

Table 5. Correlation coefficients in univariate analysis of pulmonary pressures and biomarker levels.

	IL-6		TNF α		hsCRP		ET-1		NT-proBNP
	v	pa	v	pa	v	pa	v	pa	v	pa
sPAP	0.608	0.654	0.284	0.344	0.459	0.477	0.178	0.233	0.291	0.282
	p = 0.001	p = 0.000	p = 0.151	p = 0.079	p = 0.016	p = 0.012	p = 0.375	p = 0.242	p = 0.140	p = 0.154
dPAP	0.469	0.398	0.362	0.334	0.429	0.433	0.216	0.021	0.393	0.387
	p = 0.014	p = 0.040	p = 0.064	p = 0.089	p = 0.025	p = 0.024	p = 0.279	p = 0.918	p = 0.043	p = 0.046
mPAP	0.555	0.528	0.399	0.368	0.511	0.521	0.221	0.168	0.401	0.394
	p = 0.003	p = 0.005	p = 0.040	p = 0.059	p = 0.007	p = 0.005	p = 0.267	p = 0.401	p = 0.038	p = 0.042
PCWP	0.525	0.418	0.422	0.466	0.503	0.514	0.232	0.164	0.459	0.444
	p = 0.005	p = 0.030	p = 0.028	p = 0.014	p = 0.008	p = 0.006	p = 0.245	p = 0.414	p = 0.016	p = 0.020
TPG	0.154	0.299	0.096	–0.055	0.189	0.190	0.047	0.078	0.006	0.022
	p = 0.442	p = 0.130	p = 0.633	p = 0.787	p = 0.344	p = 0.342	p = 0.816	p = 0.701	p = 0.975	p = 0.913

IL-6, interleukin 6; TNF-α, tumor necrosis factor α; hsCRP, high-sensitivity C-reactive protein; ET-1, endothelin 1; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; v, peripheral vein sample; pa, pulmonary artery sample; sPAP, systolic pulmonary artery pressure; dPAP, diastolic pulmonary artery pressure; mPAP, mean pulmonary artery pressure; PCWP, pulmonary capillary wedge pressure; and TPG, transpulmonary pressure gradient.

p Values of less than 0.05 are in bold.

Figure 1. Interleukin 6 and systolic pulmonary artery pressure correlation.

Table 6. Summary of multiple linear regression analysis.

	Beta	Tolerance	R ^2	T	p Level
IL-6 v	−0.747	0.092	0.908	−1.518	0.143
IL-6 pa	1.095	0.102	0.898	2.348	0.028
hsCRP v	−4.006	0.003	0.997	−1.492	0.149
hsCRP pa	4.201	0.003	0.997	1.545	0.137
NT-proBNP v	2.177	0.005	0.995	1.053	0.304
NT-proBNP pa	−1.889	0.005	0.995	−0.913	0.371

IL-6, interleukin 6; TNF-α, tumor necrosis factor α; hsCRP, high-sensitivity C-reactive protein; NT-proBNP, N-terminal prohormone of brain natriuretic peptide; v, peripheral vein sample; and pa, pulmonary artery sample.

n = 30; R ² = 0.511; adjusted R ² = 0.378; F = 3.830; df = 6.22; p = 0.009.