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Cardiovascular aspects on chronic obstructive pulmonary disease: with focus on ischemic ECG abnormalities, QT prolongation and arterial stiffness
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine. (OLIN-studierna)ORCID iD: 0000-0002-2574-479X
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background

Chronic Obstructive Pulmonary disease (COPD) is an under-diagnosed disease with a prevalence of approximately 10%, highly dependent on age and smoking habits. Comorbidities are common in COPD and of these, cardiovascular diseases (CVD) are the most common. COPD is the fourth leading cause of death globally, and CVD probably contribute to the high mortality. Within CVD, Ischemic Heart Disease (IHD) is the most common. It is highly clinically relevant to identify signs of ischemic heart disease, other cardiac conditions, and risk factors for CVD in COPD. Electrocardiogram (ECG) is a simple but still major diagnostic tool in clinical cardiology, including disturbances in the electric conduction system and ischemia. Due to the under-diagnosis of COPD, there is limited knowledge regarding the prevalence and prognostic impact of ECG abnormalities in COPD. Arterial stiffness is a risk factor for CVD, which has raised an increased interest, however not evaluated in population based studies of COPD.

Aim

The overall aim was to describe cardiovascular aspects on COPD, with a specific focus on arterial stiffness, prevalence and prognostic impact of ischemic ECG abnormalities and prolonged QT interval, by comparing subjects with and without obstructive lung function impairment in a population-based cohort.

Methods

The thesis is based on the Obstructive Lung Disease in Northern Sweden (OLIN) COPD study; a population-based longitudinal cohort study. During the years 2002-2004, all participants in clinical examinations from previously recruited large population-based cohorts were invited to re-examination including spirometry and a structured interview. All subjects with obstructive lung function impairment (n=993) were identified, together with 993 age and sex-matched referents without airway obstruction. The study population (n=1986) has been invited to annual examinations since 2005 including spirometry and structured interview. Papers I-III are based on data from 2005 when electrocardiogram (ECG) was recorded in addition to the basic program. All ECGs were Minnesota coded and QT-time was measured. Paper IV is based data from 2010 when non-invasive measurements of arterial stiffness, assessed as pulse wave velocity (PWV), was added to the program. Spirometric data were classified as normal lung function (NLF), restrictive spirometric pattern (RSP) and airway obstruction (COPD). The following spirometric criteria for COPD were used: post-bronchodilator FEV1/VC<0.70 (papers I-IV, in paper III labelled GOLD-COPD) and lower limit of normal, LLN (LLN-COPD) (paper III). Spirometric classification of COPD severity was based on FEV1 % predicted as a continuous variable or according to the Global Initiative for Obstructive Lung Disease (GOLD), divided into GOLD 1-4.

Results

The prevalence of ischemic heart disease (IHD), both self-reported and assessed as probable and possible ischemic ECG abnormalities (I-ECG) according to the Whitehall criteria, was similar among subjects with NLF and COPD. The prevalence of both self-reported and probable (I-ECG) according to Whitehall increased by GOLD grade.  Among those with COPD, self-reported IHD was associated with disease severity, assessed as FEV1 % predicted also after adjustment for age and sex (paper I).

In both COPD and NLF, those with I-ECG had a higher cumulative mortality over 5 years than those without I-ECG (29.6 vs. 10.6%, p<0.001 and 17.1 vs. 6.3 %, p=0.001). When analysed in a multivariate model, the Mortality Risk Ratio (MRR, 95%CI) was increased for subjects with COPD and I-ECG (2.4, 1.5-3.9), and non-significantly so for NLF with I-ECG (1.65, 0.94-2.90), when compared to NLF without I-ECG.  When analyzed separately among subjects with COPD, the increased risk for death associated with I-ECG persisted independent of age, sex, BMI-class, smoking habits and disease severity assessed as FEV1 % predicted (1.89, 1.20-2.99). The proportion without reported IHD was high among those with I-ECG; 72.4% in NLF and 67.3% in COPD. The pattern was similar also among them; I-ECG was associated with an increased risk for death in COPD and non-significantly so in NLF (paper II).

Mean corrected QT-time (QTc) and prevalence of QTc prolongation was higher in RSP than NLF but similar in NLF and GOLD-COPD. The prevalence of borderline as well as prolonged QTc increased by GOLD grade (test for trend p=0.012 for both groups). Of those with GOLD-COPD, 52% fulfilled the LLN-criterion (LLN-COPD). When comparing LLN-COPD and NLF, the pattern was similar as when comparing NLF and GOLD-COPD. The cumulative mortality over 5 years was higher among subjects with borderline and prolonged QTc than those with normal QTc in subjects with GOLD-COPD and LLN-COPD but not in NLF and RSP (paper III).

Arterial stiffness, assessed as PWV, was higher in GOLD 3-4 compared to non-COPD (10.52 vs. 9.13 m/s, p=0.042). Reported CVD and age >60 were both associated with significantly higher PWV in COPD as well as in non-COPD. In a multivariate model, GOLD 3-4 remained associated with higher PWV when compared with non-COPD, also when adjusted for sex, age group, smoking habits, blood pressure, reported CVD and pulse rate (paper IV).

Conclusion

In this population-based study, the prevalence of ischemic ECG abnormalities was similar among subjects with normal lung function and COPD, but increased by disease severity among subjects with COPD. Ischemic ECG abnormalities were associated with an increased mortality among subjects with COPD, independent of common confounders and disease severity, also among those without known heart disease. Whilst the prevalence of QTc prolongation was similar in NLF, COPD and LLN-COPD, it was associated with an increased mortality only in the COPD-groups. ECG is a simple non-invasive method and seems to identify findings of prognostic importance among subjects with COPD. Central arterial stiffness, a known risk factor for cardiovascular disease, was increased among subjects with severe and very severe COPD when compared to subjects without COPD independent of common confounders.

Place, publisher, year, edition, pages
Umeå: Umeå University , 2017. , p. 65
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1905
Keywords [en]
Epidemiology, COPD, ischemic heart disease, cardiovascular disease, ECG, spirometry
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
URN: urn:nbn:se:umu:diva-138787ISBN: 978-91-7601-756-2 (print)OAI: oai:DiVA.org:umu-138787DiVA, id: diva2:1137369
Public defence
2017-09-22, NUS 1D - Tandläkarhögskolan, Hörsal D, Umeå, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2017-09-01 Created: 2017-08-31 Last updated: 2018-06-09Bibliographically approved
List of papers
1. Ischemic heart disease among subjects with and without chronic obstructive pulmonary disease: ECG-findings in a population-based cohort study
Open this publication in new window or tab >>Ischemic heart disease among subjects with and without chronic obstructive pulmonary disease: ECG-findings in a population-based cohort study
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2015 (English)In: BMC Pulmonary Medicine, ISSN 1471-2466, E-ISSN 1471-2466, Vol. 15, article id 156Article in journal (Refereed) Published
Abstract [en]

Background: Cardiovascular comorbidity in COPD is common and contributes to increased mortality. A few population-based studies indicate that ischemic electrocardiogram (ECG)-changes are more prevalent in COPD, while others do not.

The aim of the present study was to estimate the presence of ischemic heart disease (IHD) in a population-based COPD-cohort in comparison with subjects without COPD.

Methods: All subjects with obstructive lung function (COPD, n = 993) were identified together with age- and sex-matched controls (non-COPD, n = 993) from population-based cohorts examined in 2002–04. In 2005, data from structured interview, spirometry and ECG were collected from 1625 subjects. COPD was classified into GOLD 1–4 after post-bronchodilator spirometry. Ischemic ECG-changes, based on Minnesota-coding, were classified according to the Whitehall criteria into probable and possible IHD.

Results: Self-reported IHD was equally common in COPD and non-COPD, and so were probable and possible ischemic ECG-changes according to Whitehall. After excluding subjects with restrictive spirometric pattern from the non-COPD-group, similar comparison with regard to presence of IHD performed between those with COPD and those with normal lung-function did neither show any differences. There was a significant association between self-reported IHD (p = 0.007) as well as probable ischemic ECG-changes (p = 0.042), and increasing GOLD stage. In COPD there was a significant association between level of FEV1 percent of predicted and self-reported as well as probable ischemic ECG-changes, and this association persisted for self-reported IHD also after adjustment for sex and age.

Conclusion: In this population-based study, self-reported IHD and probable ischemic ECG-changes were associated with COPD disease severity assessed by spirometry.

Place, publisher, year, edition, pages
Umeå: , 2015
Keywords
Comorbidity, Epidemiology, Coronary disease, Respiratory diseases
National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-112463 (URN)10.1186/s12890-015-0149-1 (DOI)000367711700001 ()26637314 (PubMedID)
Available from: 2015-12-08 Created: 2015-12-08 Last updated: 2018-06-07Bibliographically approved
2. Ischemic ECG abnormalities are associated with an increased risk for death among subjects with COPD, also among those without known heart disease
Open this publication in new window or tab >>Ischemic ECG abnormalities are associated with an increased risk for death among subjects with COPD, also among those without known heart disease
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2017 (English)In: The International Journal of Chronic Obstructive Pulmonary Disease, ISSN 1176-9106, E-ISSN 1178-2005, Vol. 12, p. 2507-2514Article in journal, Editorial material (Refereed) Published
Abstract [en]

Background: Cardiovascular comorbidity contributes to increased mortality among subjects with COPD. However, the prognostic value of ECG abnormalities in COPD has rarely been studied in population-based surveys.

Aim: To assess the impact of ischemic ECG abnormalities (I-ECG) on mortality among individuals with COPD, compared to subjects with normal lung function (NLF), in a population-based study.

Methods: During 2002–2004, all subjects with FEV1/VC <0.70 (COPD, n=993) were identified from population-based cohorts, together with age- and sex-matched referents without COPD. Re-examination in 2005 included interview, spirometry, and 12-lead ECG in COPD (n=635) and referents [n=991, whereof 786 had NLF]. All ECGs were Minnesota-coded. Mortality data were collected until December 31, 2010.

Results: I-ECG was equally common in COPD and NLF. The 5-year cumulative mortality was higher among subjects with I-ECG in both groups (29.6% vs 10.6%, P<0.001 and 17.1% vs 6.6%, P<0.001). COPD, but not NLF, with I-ECG had increased risk for death assessed as the mortality risk ratio [95% confidence interval (CI)] when compared with NLF without I-ECG, 2.36 (1.45–3.85) and 1.65 (0.94–2.90) when adjusted for common confounders. When analyzed separately among the COPD cohort, the increased risk for death associated with I-ECG persisted after adjustment for FEV1% predicted, 1.89 (1.20–2.99). A majority of those with I-ECG had no previously reported heart disease (74.2% in NLF and 67.3% in COPD) and the pattern was similar among them.

Conclusion: I-ECG was associated with an increased risk for death in COPD, independent of common confounders and disease severity. I-ECG was of prognostic value also among those without previously known heart disease.

Place, publisher, year, edition, pages
Dove Medical Press, 2017
Keywords
COPD, ECG, ischemic heart disease, epidemiology, mortality
National Category
Cardiac and Cardiovascular Systems Respiratory Medicine and Allergy
Research subject
Cardiology; Lung Medicine
Identifiers
urn:nbn:se:umu:diva-138784 (URN)10.2147/COPD.S136404 (DOI)000408097100002 ()
Available from: 2017-08-31 Created: 2017-08-31 Last updated: 2019-05-20Bibliographically approved
3. The prevalence of prolonged QTc by spirometric classification in a populationbased cohort: normal lung function, restrictive pattern and airway obstruction
Open this publication in new window or tab >>The prevalence of prolonged QTc by spirometric classification in a populationbased cohort: normal lung function, restrictive pattern and airway obstruction
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(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background Prolonged QT (corrected for heart rate, QTc) is associated with malignantarrhythmias. Cardiovascular comorbidity contributes to the increased mortality in COPD, butthe role of QTc is unclear.

Aim The aim of this population-based study was to estimate the prevalence of QTcprolongation among subjects with normal lung function (NLF), airway obstruction (fixedratio, GOLD-COPD and Lower Limit of Normal, LLN-COPD) and restrictive spirometricpattern (RSP). Furthermore, to evaluate the prognostic impact of QTc prolongation.

Method After re-examination of population-based cohorts in 2002-04, all individuals (n=993)with airway obstruction were identified together with age and sex-matched referents withoutairway obstruction. In 2005, the study-population was invited to examination includingspirometry, structured interview and 12-lead ECG, and QTc was calculated. Mortality datawere collected until December 31st, 2010.

Results The study-population included NLF (n=734), RSP (n=175) and GOLD-COPD(n=571) whereof 299 LLN-COPD. RSP had longer mean QTc and higher prevalence ofprolonged QTc than NLF. GOLD-COPD, LLN-COPD and NLF had similar mean QTc andprevalence of prolonged QTc. In GOLD-COPD and LLN-COPD, the prevalence of prolongedQTc increased by GOLD-grade (test for trend p=0.002 and 0.043) and the cumulativemortality was higher in subjects with borderline and prolonged QTc in both groups, comparedto normal QTc. This was not the case in NLF or RSP.

Conclusion The prevalence of prolonged QTc was higher in RSP than NLF, while it wassimilar in COPD and NLF, but increased by GOLD-grade in COPD. QTc prolongation wasassociated with increased mortality in GOLD-COPD and LLN-COPD but not in NLF or RSP.

National Category
Cardiac and Cardiovascular Systems
Research subject
Cardiology
Identifiers
urn:nbn:se:umu:diva-138786 (URN)
Available from: 2017-08-31 Created: 2017-08-31 Last updated: 2018-06-09
4. Central arterial stiffness is increased among subjects with severe and very severe COPD: report from a population-based cohort study
Open this publication in new window or tab >>Central arterial stiffness is increased among subjects with severe and very severe COPD: report from a population-based cohort study
Show others...
2015 (English)In: European Clinical Respiratory Journal, ISSN 2001-8525, Vol. 2, article id 27023Article in journal (Refereed) Published
Abstract [en]

Introduction: Cardiovascular disease (CVD) is common in chronic obstructive pulmonary disease (COPD) and is, as productive cough, related to poorer prognosis in COPD. Central arterial stiffness is a marker of early atherosclerosis, but the association between COPD, productive cough, and arterial stiffness as a possible indicator of CVD is unclear.

Objectives: To compare both arterial stiffness among subjects with and without COPD and the impact of productive cough in a population-based cohort.

Methods: A population-based cohort, including 993 COPD and 993 non-COPD subjects, has been invited to annual examination since 2005. In 2010, 947 subjects, of which 416 had COPD (according to the GOLD spirometric criteria), participated in examinations including structured interview, spirometry, and measurements of central arterial stiffness as pulse wave velocity (PWV).

Results: PWV was higher in GOLD 3–4 compared to non-COPD (10.52 vs. 9.13 m/s, p=0.042). CVD and age ≥60 were both associated with significantly higher PWV in COPD as well as in non-COPD. In COPD, those with productive cough had higher PWV than those without, significantly so in GOLD 1 (9.59 vs. 8.92 m/s, p=0.024). In a multivariate model, GOLD 3–4 but not productive cough was associated with higher PWV, when adjusted for sex, age group, smoking habits, blood pressure, CVD, and pulse rate.

Conclusions: GOLD 3–4, age ≥60, and CVD were associated with increased arterial stiffness, and also increased in COPD subjects with productive cough compared to those without. Of importance, GOLD 3–4 but not productive cough remained associated with increased central arterial stiffness when adjusted for confounders.

Place, publisher, year, edition, pages
Taylor & Francis, 2015
Keywords
COPD, epidemiology, cardiovascular disease, arterial stiffness
National Category
Public Health, Global Health, Social Medicine and Epidemiology Respiratory Medicine and Allergy Cardiac and Cardiovascular Systems
Identifiers
urn:nbn:se:umu:diva-103289 (URN)10.3402/ecrj.v2.27023 (DOI)000215841600012 ()
Available from: 2015-05-19 Created: 2015-05-19 Last updated: 2018-06-07Bibliographically approved

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