Impact of beta2-agonists, beta-blockers, and their combination on cardiac function in elderly male patients with chronic obstructive pulmonary disease

Figures & data

Table 1 Baseline characteristics

Characteristic	β2-agonists (n = 32)	β-blockers (n = 81)	β-blockers + β-agonists (n = 31)	Control (n = 76)	P-value
Demographics
Age (years)	84.8 ± 6.4	84.6 ± 6.2	86.0 ± 4.6	82.6 ± 8.5	0.135
COPD severity
FEV1, predicted (%)	58.9 ± 21.6	80.4 ± 19.9	74.7 ± 18.0	81.6 ± 22.7	<0.001
FEV1/FVC (%)	50.6 ± 11.5	62.7 ± 6.7	56.5 ± 9.6	60.7 ± 8.5	<0.001
Mild, n (%)	3 (9.4)	41 (50.6)	12 (38.7)	44 (57.9)	<0.001
Moderate, n (%)	17 (53.1)	36 (44.4)	17 (54.8)	27 (35.5)	0.192
Severe, n (%)	12 (37.5)	4 (4.9)	2 (6.5)	5 (6.6)	<0.001
Cardiovascular history
Coronary artery disease, n (%)	21 (65.6)	70 (86.4)	26 (83.9)	48 (69.2)	0.001
Heart failure, n (%)	9 (28.1)	19 (23.5)	9 (29.0)	13 (17.1)	0.616
NYHA functional class, n (%)
NYHA I	20 (62.5)	55 (67.9)	17 (54.8)	60 (78.9)	0.068
NYHA II	9 (28.1)	19 (23.5)	9 (29.0)	14 (18.4)	0.575
NYHA III	3 (9.4)	7 (8.6)	6 (19.4)	2 (2.6)	0.030
Myocardial infarction	0 (0.0)	11 (13.6)	3 (9.7)	1 (1.3)	0.004
Clinical characteristics
BMI (kg/m^2)	22.7 ± 3.1	24.7 ± 2.6	23.9 ± 2.9	24.1 ± 3.0	0.009
Systolic BP (mmHg)	130.1 ± 16.7	131.9 ± 16.4	130.4 ± 11.4	129.1 ± 15.1	0.927
Diastolic BP (mmHg)	67.4 ± 8.7	70.1 ± 10.8	66.8 ± 8.7	69.8 ± 9.8	0.292
Heart rate (bpm)	78.2 ± 16.3	72.7 ± 12.4	74.0 ± 7.5	71.3 ± 9.9	0.068
Current smoker, n (%)	9 (28.1)	25 (30.9)	8 (25.8)	29 (38.2)	0.573
Hypertension, n (%)	25 (78.1)	61 (75.3)	25 (80.6)	52 (68.4)	0.544
Diabetes mellitus, n (%)	12 (37.5)	39 (48.1)	16 (51.6)	32 (42.1)	0.611
Dyslipidemia, n (%)	4 (12.5)	17 (21.0)	6 (19.4)	19 (25.0)	0.565
Atrial fibrillation, n (%)	5 (15.6)	15 (18.5)	6 (19.4)	7 (9.2)	0.304
PAOD, n (%)	3 (9.4)	22 (27.2)	6 (19.4)	12 (15.8)	0.132
Renal dysfunction, n (%)	4 (30.8)	21 (41.2)	4 (20.0)	11 (34.4)	0.417
Concomitant therapy, n (%)
ACE inhibitors	3 (9.4)	13 (16.0)	4 (12.9)	4 (5.3)	0.167
A2RAs	9 (28.1)	30 (37.0)	11 (35.5)	22 (28.9)	0.666
Calcium-channel blockers	21 (65.6)	49 (60.5)	20 (64.5)	42 (55.3)	0.711
Loop diuretics	11 (34.4)	26 (32.1)	14 (45.2)	19 (25.0)	0.234
Antiplatelet	22 (68.8)	51 (63.0)	19 (61.3)	49 (64.5)	0.929
Statins	15 (46.9)	45 (55.6)	12 (38.7)	37 (48.7)	0.439
Digoxin	5 (15.6)	7 (8.6)	4 (12.9)	6 (7.9)	0.538
Nitrates	22 (68.8)	50 (61.7)	20 (64.5)	44 (57.9)	0.758
Spironolactone	4 (12.5)	9 (11.1)	3 (9.7)	5 (6.6)	0.714
Laboratory parameters
NT pro-BNP (pg/mL)	385.7 (142.6–960.1)	226.2 (116.3–718.9)	272.1 (113.1–152.6)	112.6 (71.9–379.1)	0.004
Serum creatinine (μmol/L)	97.5 (70.1–127.7)	93.0 (75.3–126.9)	95.0 (74.0–133.0)	88.9 (75.8–113.3)	0.643
Uric acid (mmol/L)	313.7 (253.5–373.0)	331.4 (266.0–381.1)	353.2 (276.2–453.5)	317.5 (260.7–373.4)	0.282
HS-CRP (mg/dL)	0.84 (0.3–2.9)	0.4 (0.1–0.8)	0.7 (0.3–2.3)	0.6 (0.2–1.9)	0.030
Total cholesterol (mmol/L)	3.9 (3.7–4.8)	3.7 (3.3–4.4)	4.5 (4.0–4.9)	4.3 (3.61–4.87)	0.020
Triglyceride (mmol/L)	1.2 (0.8–1.6)	1.3 (0.9–1.7)	1.6 (1.0–1.9)	1.2 (0.9–1.8)	0.319
HDL-c (mmol/L)	1.3 (1.0–1.4)	1.1 (0.9–1.3)	1.1 (0.9–1.4)	1.1 (0.9–1.4)	0.229
LDL-c (mmol/L)	2.1 (1.8–2.6)	2.1 (1.7–2.7)	2.7 (2.4–3.2)	2.4 (2.0–3.1)	0.006
Serum glucose (mmol/L)	5.7 (4.9–6.2)	5.7 (5.0–6.4)	5.5 (4.7–6.6)	5.6 (5.1–6.1)	0.931
Echocardiographic parameters
LVESV (mL)	39.7 ± 7.5	46.4 ± 12.6	44.3 ± 8.4	43.1 ± 8.7	0.018
LVEDV (mL)	106.6 ± 16.8	115.5 ± 21.8	113.9 ± 14.7	111.9 ± 16.0	0.131
Shortening fraction (%)	34.2 ± 2.2	32.6 ± 3.2	32.7 ± 3.3	33.2 ± 2.5	0.055
LVEF (%)	62.6 ± 3.1	60.1 ± 5.9	60.5 ± 4.6	61.6 ± 3.4	0.108
<50%, n (%)	0 (0.0)	4 (4.9)	1 (3.2)	0 (0.0)
>50%, n (%)	32 (100)	77 (95.1)	30 (96.8)	76 (100.0)

Abbreviations: COPD, chronic obstructive pulmonary disease; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; NYHA, New York Heart Association; BMI, body mass index; BP, blood pressure; bpm, beats per minute; PAOD, peripheral arterial occlusive disease; ACE, angiotensin-converting enzyme; A2RA, angiotensin-II receptor antagonist; HS-CRP, high-sensitivity C-reactive protein; LDL-c, low-density-lipoprotein cholesterol; HDL-c, high-density-lipoprotein cholesterol; NT pro BNP, N-terminal pro-hormone brain natriuretic parameters; LVESV, left ventricular end-systolic volume; LVEDV, left ventricular end-diastolic volume; LVEF, left ventricular ejection fraction.

Table 2 Linear regression analyses of clinical data, echocardiographic data and NT pro-BNP/LVEF

Characteristic	Model 1			Model 2
	NT pro-BNP			LVEF
	β	t	P-value	β	t	P-value
β2-agonists	35.502	0.120	0.905	−0.360	−0.715	0.475
β-blockers	−3.119	−0.013	0.989	−0.411	−1.074	0.284
β-blockers + β2-agonists	298.635	0.986	0.325	−0.397	−0.783	0.435
Heart failure	746.983	3.533	0.001	–	–	–
Serum creatinine	2.954	2.407	0.017	–	–
LDL-c	−312.188	−2.408	0.017	–	–	–
Shortening fraction	–	–	–	1.138	16.148	<0.001
LVESV	–	–	–	−0.106	−5.337	<0.001

Abbreviations: NT pro-BNP, N-terminal pro-hormone brain natriuretic parameters; LVEF, left ventricular ejection fraction; LDL-c, low-density-lipoprotein cholesterol; LVESV, left ventricular end-systolic volume.

Table 3 Associates of all-cause mortality in the total population

Variable	HR (95% CI, P-value)
NT pro-BNP	1.612 (1.265–2.055, <0.001)
Myocardial infarction	4.026 (1.229–13.187, 0.021)
Renal dysfunction	2.363 (1.229–4.544, 0.010)
ACE inhibitors	0.155 (0.035–0.689, 0.014)
A2RAs	0.387 (0.181–0.828, 0.014)
Loop diuretic	3.973 (2.004–7.877, <0.001)
β2-agonists	0.711 (0.287–1.759, 0.460)
β-blockers	0.962 (0.405–2.285, 0.930)
β-blockers + β2-agonists	0.638 (0.241–1.689, 0.366)

Abbreviations: HR, hazard ratio; CI, confidence interval; NT-proBNP, N-terminal pro-hormone brain natriuretic parameters; ACE, angiotensin-converting enzyme; A2RA, angiotensin-II receptor antagonist.

Table 4 Association between β₂-agonist use and all-cause mortality according to β-blocker therapy

Outcome, β-blockers	β2-agonists	No β2-agonists	HR (95% CI)	P-value	P-value interactiona
β-blockers	31	81	1.134 (0.378–3.403)	0.823	0.428
No β-blockers	32	76	1.377 (0.485–3.910)	0.548

Note:

a Interaction between β₂-agonists and β-blockers.

Abbreviations: HR, hazard ratio; CI, confidence interval.