Comorbid Heart Disease in Patients with COPD is Associated with Increased Hospitalization and Mortality – A 15-Year Follow-Up

Figures & data

Figure 1 Kaplan Meier curves for patients with COPD with and without comorbid heart disease for all-cause hospitalization (A) and mortality (B). Solid line: patients with comorbid heart disease, dotted line: patients without comorbid heart disease.

Table 1 Baseline Characteristics for Patients with COPD without and with a Diagnosis of Heart Disease (n = 1071)

	No Heart Disease	Comorbid Heart Disease	p-value
	n=809 (75%)	n=262 (25%)
Sex, n (%)			< 0.001
Men	309 (38)	140 (53)
Women	500 (62)	122 (47)
Mean age, years (SD)	64 (8)	67 (6)	< 0.001
Age-groups, n (%)			< 0.001
≤ 60	238 (29)	34 (13)
61–70	410 (51)	133 (51)
>70	161 (20)	95 (36)
Education level (n=1049), n (%)			0.01
Low	522 (66)	198 (77)
High	271 (34)	58 (23)
Level of care, n (%)			< 0.001
Hospital care	208 (26)	104 (40)
Primary care	601 (74)	158 (60)
Depression, n (%)	98 (12)	29 (11)	0.65
Diabetes, n (%)	66 (8)	36 (14)	0.007
Hypertension, n (%)	201 (25)	93 (36)	0.001
BMI (n=1053), n (%)			0.009
Underweight	93 (12)	22 (9)
Normal weight	287 (37)	78 (31)
Overweight	271 (35)	85 (34)
Obesity	134 (17)	66 (26)
Current daily smoking (n=1069)	239 (30)	67 (26)	0.23
FEV1%pred (n=542), n (%)			0.30
≥ 80%	85 (21)	18 (14)
50–79%	175 (42)	55 (42)
30–49%	111 (27)	42 (32)
<30%	41 (10)	15 (11)
Exacerbation in the previous 6 months, n (%)	288 (36)	112 (44)	0.03
mMRC (n=1031), n (%)			< 0.001
0–1	358 (46)	79 (31)
2	122 (16)	41 (16)
3	112 (15)	42 (16)
4	182 (23)	95 (37)

Note: Exacerbation was defined as an unplanned health care visit or course of oral steroids.

Abbreviations: SD, standard deviation; BMI, body mass index; FEV1%pred, forced expiratory volume in one second as percentage of the predicted value; mMRC, modified Medical Research Council dyspnea score.

Figure 2 Patient flow chart from 2005 through 2019. Heart disease is defined as a doctor’s diagnosis of ischemic heart disease or chronic heart failure.

Table 2 Cause-Specific Hospitalization Days per Year, Hospitalization and Mortality for 2005 Through 2019 for Patients with COPD with and without Comorbid Heart Disease

	No Heart Disease	Comorbid Heart Disease	p-value
	n=809	n=262
Hospitalization days per year
Respiratory, median (IQR)	2.03 (0.68–6.62)	3.39 (0.93–7.66)	0.03
Cardiovascular, median (IQR)	0.69 (0.28–1.72)	1.72 (0.55–4.57)	<0.001
Other, median (IQR)	1.44 (0.54–3.82)	2.79 (1.11–7.63)	<0.001
Hospitalization
Respiratory, n (%)	403 (53)	153 (58)	0.02
Cardiovascular, n (%)	285 (35)	133 (51)	<0.001
Other, n (%)	543 (67)	207 (79)	<0.001
Mortality
Respiratory, n (%)	192 (24)	71 (27)	0.003
Cardiovascular, n (%)	83 (10)	85 (32)	<0.001
Other, n (%)	163 (20)	66 (25)	0.06

Note: For the calculation of hospitalization days per year, non-hospitalized patients have been excluded.

Abbreviation: IQR, inter quartile range.

Table 3 Associations of Comorbid Heart Disease in Patients with COPD with All-Cause and Cause-Specific Hospitalization Days per Year, Hospitalization and Mortality

	Unadjusted Regression Coefficient (95% CI) for Comorbid Heart Disease	p-value	Adjusted Regression Coefficient (95% CI) for Comorbid Heart Disease	p-value
Hospitalization days per year
All-cause	0.70 (0.48–0.92)	<0.001	0.37 (0.15–0.59)	0.001
Respiratory	0.36 (0.07–0.65)	0.02	0.14 (−0.14–0.42)	0.33
Cardiovascular	0.80 (0.52–1.08)	<0.001	0.57 (0.27–0.86)	<0.001
Other	0.61 (0.38–0.84)	<0.001	0.37 (0.12–0.62)	0.004
	Unadjusted Hazard Ratio (95% CI) for Comorbid Heart Disease	p-value	Adjusted Hazard Ratio (95% CI) for Comorbid Heart Disease	p-value
Hospitalization
All-cause	1.76 (1.52–2.04)	<0.001	1.55 (1.32–1.82)	<0.001
Respiratory	1.52 (1.27–1.63)	<0.001	1.18 (0.96–1.45)	0.12
Cardiovascular	2.43 (1.98–3.00)	<0.001	2.14 (1.70–2.70)	<0.001
Other	1.39 (1.19–1.64)	<0.001	1.27 (1.06–1.52)	0.009
Mortality
All-cause	2.37 (2.02–2.79)	<0.001	1,77 (1,48–2,12)	< 0.001
Respiratory	1.71 (1.30–2.24)	<0.001	1.31 (0.97–1.78)	0.08
Cardiovascular	4.69 (3.46–6.37)	<0.001	3.40 (2.41–4.78)	<0.001
Other	1.96 (1.47–2.61)	<0.001	1.50 (1.09–2.06)	0.01

Notes: Results for comorbid heart disease from uni- and multivariate linear regression analysis for all-cause and cause-specific hospitalization days per year and Cox regression analysis for all-cause and cause-specific hospitalization and mortality. Adjusted for age-group, sex, daily smoking, level of education, BMI group, exacerbations in the previous six months, hypertension, diabetes and mMRC at baseline. For the calculation of hospitalization days per year, non-hospitalized patients have been excluded.

Abbreviations: CI, confidence interval; BMI, body mass index; mMRC, medical research council dyspnea score.

Table 4 Sex-Stratification and Interaction Analysis for Associations of Comorbid Heart Disease with Hospitalization Days per Year, Hospitalization and Mortality

	Men		Women		p-value for Interaction Analysis
	Adjusted Regression Coefficient (95% CI)	p-value	Adjusted Regression Coefficient (95% CI)	p-value
Hospitalization days per year
All-cause	0.28 (−0.02–0.59)	0.07	0.47 (0.15–0.80)	0.003	0.30
Respiratory	0.07 (−0.33–0.46)	0.75	0.24 (−0.16–0.65)	0.21	0.58
Cardiovascular	0.31 (−0.10–0.73)	0.14	0.83 (0.39–1.27)	<0.001	0.06
Other	0.33 (−0.03–0.68)	0.07	0.43 (0.06–0.79)	0.02	0.55
	Adjusted HR (95% CI)	p-value	Adjusted HR (95% CI)	p-value	p-value for Interaction Analysis
Hospitalization
All-cause	1.67 (1.33–2.10)	<0.001	1.54 (1.22–1.94)	<0.001	0.60
Respiratory	1.02 (0.76–1.37)	0.89	1.37 (1.03–1.83)	0.03	0.07
Cardiovascular	1.87 (1.36–2.58)	<0.001	2.71 (1.93–3.80)	0.001	0.24
Other	1.21 (0.94–1.59)	0.13	1.36 (1.04–1.76)	0.02	0.27
Mortality
All-cause	1.67 (1.29–2.15)	<0.001	2.11 (1.63–2.72)	<0.001	0.11
Respiratory	1.14 (0.72–1.81)	0.57	1.54 (1.02–2.31)	0.04	0.15
Cardiovascular	3.03 (1.90–4.81)	<0.001	5.09 (3.02–8.57)	<0.001	0.15
Other	1.49 (0.96–2.31)	0.08	1.74 (1.08–2.78)	0.02	0.67

Notes: Sex-stratified results for the association of comorbid heart disease in patient with COPD from multivariate linear regression analysis for all-cause and cause-specific hospitalization days per year and Cox regression analysis for all-cause and cause-specific mortality and hospitalization. Including the p-value of interaction analysis for sex and heart disease. Adjusted for age-group, daily smoking, level of education, BMI group, exacerbations in the previous six months, hypertension, diabetes and mMRC at baseline. For the calculation of hospitalization days per year, non-hospitalized patients have been excluded.

Abbreviations: CI, confidence interval; HR, hazard ratio; BMI, body mass index; mMRC, medical research council dyspnea score.