C-reactive Protein, Lung Hyperinflation and Heart Rate Variability in Chronic Obstructive Pulmonary Disease –A Pilot Study

Figures & data

Table 1:  Characteristics of the sample according to BODE Index.

		BODE 1		BODE 2		BODE 3–4
		[13 patients]		[8 patients]		[9 patients]
Indice s		Mean	SD	Mean	SD	Mean	SD	P
Males	[n]	11		7		7
Age	[yrs]	64.8	9.3	69.9	7.0	64.0	12.2	0.410
VC	[% pred.]	102.7	11.2	87.1	12.5	81.7	18.1	0.004
FEV1	[% pred.]	62.9	15.2	42.3	6.1	30.6	10.2	0.000
FEV1	[liters]	1.7	0.5	1.1	0.3	0.9	0.4	0.000
FEV1/FVC	[%]	50.4	10.0	41.0	7.9	33.4	9.9	0.001
FEF25–75	[liters/sec]	0.7	0.4	0.3	0.1	0.3	0.1	0.007
FEF25–75	[% pred.]	20.8	10.7	11.5	2.8	9.1	2.8	0.002
RV/TLC	[%]	37.8	6.6	53.6	7.6	52.4	10.2	0.000
FRC/TLC	[%]	55.2	4.4	67.7	4.8	68.1	7.1	0.000
IC/TLC	[%]	46.4	5.4	31.8	5.2	34.0	9.0	0.000
Kco	[% pred.]	56.5	16.9	53.5	18.8	38.4	25.3	0.104
PaO2	[mmHg]	69.7	12.0	72.1	9.7	68.9	9.9	0.830
PaC02	[mmHg]	40.2	2.8	39.5	4.6	44.9	4.1	0.009
Sat02	[%]	92.6	3.2	93.8	2.0	92.5	2.9	0.584
Sp02 Baseline	[%]	91.9	7.2	94.8	1.7	93.7	2.6	0.444
Sp02 6mWT	[%]	90.3	7.3	90.7	3.9	88.4	3.7	0.646
Sp02 Recovery	[%]	94.8	2.9	94.8	2.5	92.6	3.9	0.209
Distance	[m]	460.4	104.0	429.4	104.0	335.6	113.0	0.037
NT_proBNP	[pg/mL]	70.2	54.7	79.5	60.3	120.1	110.5	0.321
CRP	[mg/L]	5.2	5.5	6.0	2.3	7.6	6.0	0.548

Table 2.  Baseline values (geometric mean and 95% Confidence Intervals) of HRV parameters according to BODE group.

		BODE 1				BODE 2				BODE 3–4						2vs 1	3–4 vs 1
	Units	Mean	95% C.I.			Mean	95% C.I.			Mean	95% C.I.			F	P	P	P
NN	msec	819.18	757.41	to	885.98	744.19	670.62	to	825.84	720.61	668.34	to	776.89	3.44	0.046	0.086	0.020
SDNN	msec.	46.80	34.49	to	63.48	29.89	21.18	to	42.17	26.29	17.61	to	39.26	4.28	0.024	0.051	0.011
r-MSSD	msec.	21.45	13.62	to	33.77	24.07	17.40	to	33.30	17.95	12.83	to	25.10	0.54	0.587
TFA	msec.	42.06	31.70	to	55.81	23.28	16.55	to	32.77	24.62	15.50	to	39.11	4.71	0.018	0.014	0.020
VLF	msec.	31.21	23.94	to	40.68	15.41	10.23	to	23.20	15.83	10.61	to	23.63	7.73	0.002	0.003	0.003
LF	msec.	19.72	15.31	to	25.40	11.81	7.57	to	18.42	13.43	7.04	to	25.63	2.11	0.140
HF	msec.	11.25	7.50	to	16.87	9.81	7.22	to	13.33	8.99	5.65	to	14.30	0.41	0.670
LF/HF		1.77	1.32	to	2.37	1.21	0.82	to	1.77	1.51	0.90	to	2.53	1.23	0.307

Figure 1.  Change of HRV parameters according to IC/TLC ratio.

Table 3.  Adjusted means of HRV parameters at baseline according to the categories of IC/TLC ratio and CRP.

		SDNN					r-MSSD					TFA					VLF
		Mean	95%		C.I.	p value vs Ref.	Mean	95%		C.I.	p value vs Ref.	Mean	95%		C.I.	p value vs Ref.	Mean	95%		C.I.	p value vs Ref.
IC/TLC [%]	>44%	47.35	35.34	to	63.44		25.66	17.93	to	36.71		45.60	34.01	to	61.13		31.90	23.71	to	42.93
	36–43%	35.70	26.63	to	47.88		17.40	12.15	to	24.92		29.42	21.93	to	39.48	0.047	20.47	15.20	to	27.57	0.047
	<36%	25.20	19.04	to	33.36	0.004	20.64	14.64	to	29.10		21.34	16.11	to	28.27	0.001	14.37	10.81	to	19.10	0.001
CRP [mg/L]	<5	37.63	29.42	to	48.12		27.40	20.26	to	37.07		32.34	25.02	to	41.81		21.39	16.65	to	27.48
	5.1–10	38.01	28.86	to	50.08		17.97	12.81	to	25.21	0.079	33.22	24.92	to	44.30		24.24	18.31	to	32.10
	>10	17.15	9.98	to	29.46	0.013	10.19	5.24	to	19.81	0.011	16.66	9.47	to	29.31	0.04	11.26	6.49	to	19.55	0.041
		LF					HF					LF/HF
		Mean	95%		C.I.		Mean	95%		C.I.		Mean	95%		C.I.
IC/TLC [%]	> 44%	20.85	14.69	to	29.60		13.48	9.32	to	19.50		1.58	1.14	to	2.18
	36–43%	16.50	11.61	to	23.45		8.86	6.12	to	12.82		1.87	1.35	to	2.58
	< 36%	10.46	7.48	to	14.64	0.007	8.73	6.13	to	12.44	0.093	1.20	0.88	to	1.64
CRP [mg/L]	<5	15.98	11.72	to	21.80		12.11	8.83	to	16.60		1.34	1.02	to	1.76
	5.1–10	16.06	11.34	to	22.74		9.36	6.57	to	13.32		1.71	1.26	to	2.32
	>10	10.30	5.20	to	20.39		5.77	2.88	to	11.55	0.059	1.82	1.00	to	3.32

The model included oxygen saturation, NT_proBNP, IC/TLC ratio categories and CRP.

Table 4.  Changes of HRV parameters during 6mWT within each BODE group.

			BODE 1			BODE 2			BODE 3–4
	Units	Period	Mean	P1	P2	Mean	P1	P2	Mean	P1	P2
NN	msec	Baseline	819.18	0.000		744.19	0.000		720.61	0.000
		6 mwt	532.35		0.0000	566.80		0.000	590.93		0.000
		Recovery	640.66		0.0000	651.32		0.001	659.84		0.008
SDNN	msec.	Baseline	46.80	0.028		29.89	0.031		26.29	0.005
		6 mwt	44.22		0.699	43.69		0.077	37.54		0.054
		Recovery	65.09		0.032	53.88		0.010	51.34		0.001
r-MSSD	msec.	Baseline	21.45	0.063		24.07	0.449		17.95	0.704
		6 mwt	16.27			21.58			18.50
		Recovery	16.31			19.23			21.07
TFA	msec.	Baseline	42.06	0.033		23.28	0.037		24.62	0.055
		6 mwt	33.95		0.129	26.73		0.422	27.92		0.484
		Recovery	49.70		0.232	37.29		0.014	38.58		0.021
VLF	msec.	Baseline	31.21	0.010		15.41	0.082		15.83	0.009
		6 mwt	22.25		0.053	18.33			20.42		0.160
		Recovery	38.66		0.209	26.55			29.35		0.003
LF	msec.	Baseline	19.72	0.000		11.81	0.000		13.43	0.023
		6 mwt	6.53		0.000	4.53		0.000	6.92		0.025
		Recovery	13.82		0.019	11.18		0.701	14.88		0.706
HF	msec.	Baseline	11.25	0.001	0.001	9.81	0.077		8.99	0.619
		6 mwt	6.43	0.447		6.91			7.67
		Recovery	10.08			8.89			9.74
LF/HF		Baseline	1.77	0.002		1.21	0.003		1.51	0.006
		6 mwt	1.00		0.000	0.66		0.003	0.90		0.005
		Recovery	1.36		0.070	1.25		0.841	1.51		0.992

p1 is the p value of the Anova. whereas p2 refers to the p value of the comparison with baseline.

Table 5:  Univariate linear regression analysis between lung function parameters and CRP and change of HRV parameters.

		SDNN				r-MSSD				TFA				VLF
		Beta	SE	p	R2	Beta	SE	P	R2	Beta	SE	p	R2	Beta	SE	p	R2
FEV1	[Liters]	–24.79	8.04	0.005	0.25	–7.93	5.95	0.193	0.06	–18.40	6.55	0.009	0.22	–17.82	5.59	0.004	0.27
FEV1 pred	[%]	–0.62	0.27	0.031	0.15	–0.20	0.19	0. 298	0.04	–0.45	0.22	0.050	0.13	–0.53	0.18	0.007	0.23
FEV1/FVC	[%]	–1.24	0.40	0.004	0.26	–0.33	0.29	0. 278	0.04	–1.04	0.31	0.002	0.29	–1.04	0.26	0.000	0.37
FEF25–75	[L/sec]	–51.42	13.97	0.001	0.33	–14.04	10.89	0. 208	0.06	–43.99	10.71	0.000	0.38	–40.60	9.13	0.000	0.41
FRC/TLC	[%]	0.91	0.63	0.161	0.07	1.07	0.38	0. 009	0.22	0.84	0.50	0.102	0.09	0.75	0.44	0.095	0.10
RV/TLC	[%]	0.55	0.49	0.266	0.04	0.58	0.31	0. 071	0.11	0.52	0.38	0.186	0.06	0.46	0.34	0.183	0.06
IC/TLC	[%]	–0.90	0.55	0.112	0.08	–1.17	0.65	0. 082	0.10	–0.85	0.43	0.059	0.12	–0.76	0.38	0.054	0.12
CRP	[mg/L]	0.84	1.07	0.440	0.20	–0.62	0.71	0. 390	0.03	–0.87	0.85	0.310	0.03	–0.95	0.74	0.210	0.06
		LF				HF				LF/HF
		Beta	SE	p	R2	Beta	SE	p	R2	Beta	SE	p	R2
FEV1	[Liters]	–2.01	2.90	0.495	0.02	–3.24	2.35	0.179	0.04	0.19	0.29	0.530	0.01
FEV1 pred	[%]	0.16	0.09	0.860	0.00	–0.08	0.08	0.308	0.04	0.01	0.01	0.477	0.02
FEV1/FVC	[%]	–0.08	0.14	0.608	0.01	2.05	1.60	0.387	0.03	–0.01	0.01	0.675	0.01
FEF25–75	[L/sec]	–3.18	5.32	0.550	0.01	–6.45	4.27	0.142	0.08	0.39	0.53	0.468	0.02
FRC/TLC	[%]	0.56	0.18	0.004	0.26	0.38	0.15	0.020	0.18	0.02	0.02	0.430	0.02
RV/TLC	[%]	0.37	0.14	0.014	0.20	0.21	0.12	0.100	0.09	0.01	0.02	0.472	0.02
IC/TLC	[%]	–0.42	0.16	0.016	0.19	–0.30	0.14	0.035	0.15	–0.01	0.02	0.689	0.01
CRP	[mg/L]	–0.32	0.34	0.350	0.03	–0.23	0.28	0.400	0.02	0.01	0.03	0.790	0.01