Disconnection of pulmonary and systemic arterial stiffness in COPD

Figures & data

Table 1 Demographics of the COPD and healthy control cohorts

Demographics	Healthy controls	COPD cohort	p-value
n	20	56
Age (years)	60.1±4.9	67.5±9.3	<0.001
Sex (male)	9 (45%)	29 (52%)	0.60
BMI (kg/m^2)	24.6±2.5	26.8±5.3	0.02
Heart rate (bpm)	64.4±12.1	74.0±20.7	0.061
Systolic BP (mmHg)	128.5±13.7	130.8±20.4	0.65
Diastolic BP (mmHg)	75.0±7.9	75.1±8.6	0.95
Pulse pressure (mmHg)	53.5±9.4	55.7±18.7	0.63
SpO2	98.4±1.3	96.3±2.5	0.001
Hypertension	2 (10%)	24 (43%)	0.012
Hypercholesterolemia	3 (15%)	3 (5%)	0.18
Diabetes	0 (0%)	9 (16%)	0.1
Smoking status
Current smoker	2 (10%)	17 (30%)	0.08
Ex-smoker	7 (35%)	39 (70%)	0.009
Never smoker	11 (55%)	0 (0%)	<0.001
Pack-years	4.92±7.5	48.5±23.6	<0.001
Medications
Aspirin	1 (5%)	9 (16%)	0.28
β-blocker	1 (5%)	3 (5%)	1
Diuretic	0 (0%)	9 (16%)	0.10
Calcium channel blocker	1 (5%)	15 (27%)	0.055
ACEi/ARB	0 (0%)	8 (14%)	0.10
Statin	4 (20%)	14 (25%)	0.77
GOLD (FEV1) status
I		11 (20%)
II		31 (55%)
III		13 (23%)
IV		1 (2%)
mMRC grade
0		5 (9%)
1		26 (46%)
2		13 (23%)
3		10 (18%)
4		2 (4%)

Abbreviations: ACEi, angiotensin converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; BP, blood pressure; FEV₁, forced expiratory volume in 1 second; GOLD, Global Initiative for Chronic Obstructive Lung Disease; mMRC, modified Medical Research Council.

Table 2 Ventricular quantification, measures of PWV, and bio-markers in the healthy control and COPD cohort

	Healthy controls	COPD cohort	p-value
n	20	56
Right ventricle
RVEDV (mL/m^1.7)	58.7±12.1	53.6±11.2	0.09
RVESV (mL/m^1.7)	22.2±8.2	21.9±7.4	0.87
RVSV (mL/m^1.7)	36.6±5.9	31.7±7.0	0.007
RVEF (%)	63.3±7.9	59.6±7.9	0.08
RVM (g/m^1.7)	14.7±2.4	15.2±3.2	0.50
RVMVR (g/mL)	0.25±0.04	0.29±0.05	0.012
Left ventricle
LVEDV (mL/m^1.7)	59.0±9.2	56.1±12.1	0.33
LVESV (mL/m^1.7)	23.4±6.1	23.4±9.4	0.99
LVSV (mL/m^1.7)	35.6±4.8	32.7±6.7	0.09
LVEF (%)	60.7±6.0	59.1±8.6	0.46
LVM (g/m^1.7)	41.0±7.4	43.3±9.5	0.33
LVMVR (g/mL)	0.70±0.09	0.78±0.13	0.009
Pulse wave velocity
Aortic PWV (m/s)	7.35±2.1	8.67±2.7	0.06
Pulmonary PWV (m/s)	1.76±0.7	2.63±1.3	0.006
Biomarkers
CML (pg/mL)	210±84	260±191	0.27
MMP-9 (ng/mL)	50.2±18.9	121.1±72.2	<0.001
FGF-23 (pg/mL)	26.2±18.2	22.9±6.8	0.27
CC-16 (ng/mL)	24.6±8.5	19.8±10.3	0.07
SPD (ng/mL)	9.12±5.41	16.90±12.71	0.001
hsCRP (mg/L)	2.49±2.84	6.41±7.68	0.002
IL-6 (pg/mL)	0.58±0.66	1.38±1.38	0.018
Fibrinogen (mg/mL)	4.01±1.09	3.89±1.52	0.73
TC (mmol/L)	5.92±0.92	5.41±1.18	0.09
HDL (mmol/L)	1.38±0.58	1.52±0.60	0.39
LDL (mmol/L)	2.93±1.21	2.58±1.44	0.35
Triglycerides (mmol/L)	1.86±0.99	1.60±0.96	0.31
hsTrop I (pg/mL)	0.92±0.49	2.27±1.90	<0.001
NT-proBNP (pg/mL)	198±165	602±839	0.001

Abbreviations: CC-16, club cell secretory protein-16; CML, carboxymethyllysine; FGF-23, fibroblast growth factor-23; HDL, high-density lipoprotein; hsCRP, high-sensitivity C-reactive protein; hsTrop I, high-sensitivity troponin I; IL-6, interleukin-6; LDL, low-density lipoprotein; LVEDV, left ventricular end diastolic volume; LVEF, left ventricular ejection fraction; LVESV, left ventricular end systolic volume; LVM, left ventricular mass; LVMVR, left ventricular mass/volume ratio; LVSV, left ventricular stroke volume; MMP-9, metalloproteinase-9; NT-proBNP, N-terminal pro-brain natriuretic peptide; PWV, pulse wave velocity; RVEDV, right ventricular end diastolic volume; RVEF, right ventricular ejection fraction; RVESV, right ventricular end systolic volume; RVM, right ventricular mass; RVMVR, right ventricular mass/volume ratio; RVSV, right ventricular stroke volume; SPD, surfactant protein D; TC, total cholesterol.

Figure 1 Scatterplots of (A) aortic PWV against pulmonary PWV; (B) pulmonary PWV against RVMVR; and (C) aortic PWV against LVMVR.

Abbreviations: LVMVR, left ventricular mass/volume ratio; PWV, pulse wave velocity; RVMVR, right ventricular mass/volume ratio.

Table S1 Intra-assay and interassay CoV for the biomarkers

Variable	Manufacturer details	Interassay (plate-to-plate CoV, %)	Intra-assay (CoV, %)
Surfactant protein D	Bio-Techne, Minneapolis, MN, USA	9.1	4.0
Club cell protein-16	Cloud-Clone Corp., Katy, TX, USA	5.4	10.4
Fibroblast growth factor-23	Cloud-Clone Corp.	9.6	6.2
hsCRP	Kalon Biological Ltd., Guildford, UK	5.3	3.8
hsTrop I	Quanterix, Lexington, MA, USA	8.5	7.7
NT-proBNP	Meso Scale Discovery, Rockville, MD, USA	10.5	5.2
Fibrinogen	Cusabio, Houston, TX, USA	4.1	3.1
IL-6	Meso Scale Discovery	4.2	4.8
MMP-9	Bio-Techne	8.3	5.6
Carboxymethyllysine	Cusabio	10.2	5.5

Abbreviations: CoV, coefficient of variation; hsCRP, high-sensitivity C-reactive protein; hsTrop I, high-sensitivity troponin I; IL-6, interleukin-6; MMP-9, metalloproteinase-9; NT-proBNP, N-terminal pro-brain natriuretic peptide.

Table S2 Correlation coefficients between aortic PWV and pulmonary PWV and demographic and ventricular measures

Variable	Pulmonary PWV		Aortic PWV
	ρ	p-value	ρ	p-value
Age	0.03	0.81	0.45	<0.001
BMI (kg/m^2)	−0.28	0.036	−0.04	0.78
Heart rate (bpm)	0.21	0.15	0.02	0.91
Systolic BP (mmHg)	0.15	0.29	0.31	0.03
Diastolic BP (mmHg)	0.36	0.01	0.22	0.12
Pulse pressure (mmHg)	0.000	1	0.24	0.09
SpO2 (%)	−0.06	0.68	−0.07	0.64
Pack-years	0.004	0.98	−0.13	0.36
FEV1, % predicted	−0.15	0.28	0.05	0.70
FVC, % predicted	−0.06	0.64	−0.03	0.85
FEV1/FVC	−0.17	0.21	0.07	0.64
KCO, % predicted	−0.08	0.56	0.46	0.001
RLV, % predicted	0.25	0.08	−0.10	0.50
TLC, % predicted	0.28	0.046	−0.05	0.71
VC, % predicted	−0.02	0.90	0.03	0.83
RLV/TLC	0.20	0.15	0.12	0.40
CML	−0.15	0.29	0.15	0.31
MMP-9	0.10	0.47	0.09	0.55
FGF-23	0.14	0.33	0.06	0.69
CC-16	−0.18	0.21	0.31	0.028
SPD	−0.26	0.07	0.05	0.72
hsCRP	−0.28	0.04	−0.007	0.96
IL-6	−0.26	0.07	−0.02	0.92
Fibrinogen	0.001	0.99	0.16	0.26
TC	0.28	0.044	0.33	0.019
HDL	−0.12	0.40	0.06	0.70
LDL	0.15	0.28	0.32	0.023
Triglycerides	−0.09	0.53	0.12	0.39
hsTrop I	−0.15	0.29	0.17	0.23

Abbreviations: BMI, body mass index; BP, blood pressure; CC-16, club cell secretory protein-16; CML, carboxymethyllysine; FEV₁, forced expiratory volume in 1 second; FGF-23, fibroblast growth factor-23; FVC, forced vital capacity; HDL, high-density lipoprotein; hsCRP, high-sensitivity C-reactive protein; hsTrop I, high-sensitivity troponin I; IL-6, interleukin-6; LDL, low-density lipoprotein; MMP-9, metalloproteinase-9; NT-proBNP, N-terminal pro-brain natriuretic peptide; PWV, pulse wave velocity; RLV, residual lung volume; SPD, surfactant protein D; TC, total cholesterol; TLC, total lung capacity; VA, alveolar volume.