COPD: A Modifiable Risk Factor for Cardiovascular Disease?
COPD: A Modifiable Risk Factor for Cardiovascular Disease?
Significant cardiac morbidity and mortality exists in patients with COPD. Shared risk factors include age, smoking history and exposure to air pollution and passive smoke. Although the inappropriate under-prescribing of β-blockers contributes, it is now appreciated that the observed cardiac risk is not only due to smoking and conventional cardiovascular risk factors, but also other independent factors. A number of hypotheses exist for the increased cardiovascular morbidity and mortality seen in COPD including inflammation, pulmonary hypertension, lung hyperinflation and shared genetics models. Mounting evidence from large randomised controlled trials suggests that COPD treatment may be cardio-protective. We review the current evidence supporting the aforementioned hypotheses and how their modulation may prevent cardiovascular morbidity and mortality in COPD. The persisting underdiagnosis of COPD may have significant consequences. Further mechanistic studies identifying the onset and impact of individual interventions will develop our understanding of this emerging and highly relevant clinical field.
Increased Cardiovascular Morbidity and Mortality in COPD Chronic obstructive pulmonary disease (COPD) is predicted to become the sixth leading cause of disability and the third most common cause of death by 2020. COPD is commonly underdiagnosed in the UK and abroad. Its 1% prevalence across all ages rises steeply to 9%–10% for those over 40. A large proportion of morbidity and mortality in COPD is associated with cardiovascular complications.
Reduced pulmonary function, no matter what cause, is associated with increases in all-cause and cardiac mortality, myocardial infarction and arrhythmia. Forced expiratory volume in one second (FEV1) is ranked second to smoking and above blood pressure and cholesterol as a predictor of all-cause and cardiovascular mortality. It has been suggested that a reduction in FEV1 combined with a smoking history better predicts cardiovascular mortality than cholesterol.
In COPD, a large proportion of patients succumb to cardiovascular causes rather than respiratory failure ( Table 1 ). The likelihood of cardiac mortality, ventricular arrhythmias, coronary artery disease (CAD) or congestive cardiac failure increases with worsening FEV1, the rate of FEV1 loss independently predicting CAD mortality. Newer assays, such as the highly sensitive Troponin, have further highlighted the subclinical myocardial damage occurring during COPD exacerbations and are predictive of mortality.
The Impact of Shared Exposures It may be that the relationship between COPD and cardiovascular disease (CVD) is solely due to shared common risk factors.
Smoking It is well accepted that smoking causes both COPD and CVD. Passive smoke inhalation, in a dose–response manner, also increases the likelihood of fatal and non-fatal myocardial infarction with an estimated pooled OR from a meta-analysis of 1.22 (1.04–1.41) and 1.32 (1.04–1.67), respectively. Similarly, increased risks have been observed for COPD mortality with ORs related to spousal smoking of 1.67 in never-smoking male subjects.
Smoke-free Legislation Recently, there has been a significant focus on international public health strategies to combat the adverse effects of smoking, and secondhand smoke in particular. Although the impact of smoke-free legislation (SFL) on respiratory symptoms is well studied in normal individuals data on lung function are less robust since the changes noted were arguably of little clinical relevance, suffered from poor participant compliance and were confounded by seasonal variation in temperature. The impact of SFL on COPD is unclear since the few studies that have assessed the rate of admissions for COPD exacerbations show conflicting results. This is in contrast to the data for CVD. A recent meta-analysis assessing the impact of SFL revealed a reduction of acute coronary syndrome risk in 30 of 35 estimates with a 10% (95% CI 6 to 14, p<0.001) pooled RR reduction, supporting the notion that smoke exposure has a significant independent role in cardiovascular morbidity, although whether those patients with concomitant COPD achieved equivalent improvements in coronary events is unclear.
Air Pollution The development of COPD as a result of damage caused by air pollution is well documented. Day-to-day changes in pollutant levels and longer term exposure also affect CVD risk, and all commonly measured pollutants are positively associated with increased mortality and hospital admissions for CVD. Hypotheses relate to direct pollutant effects of oxidative stress, pulmonary and systemic inflammation or pro-coagulant reactions which, as will be discussed later, have a significant overlap with the postulated effects of COPD. Although observational studies have found associations between cardiac autonomic dysfunction and air pollution, this has not been borne out in controlled conditions and further mechanistic explanations are needed for this discrepancy.
The Impact of Differential Prescribing Practices COPD patients have been excluded from clinical trials involving β-blockers due to historical concerns over bronchoconstriction. Despite database studies persistently demonstrating survival benefit for COPD patients receiving β-blockers in CAD and congestive cardiac failure, and meta-analyses confirming the safety of cardioselective β-blockers in COPD of all severities, underuse still occurs due to lingering concerns over bronchoconstriction in a population which, based on the above evidence, arguably have the most to gain.
Although the underprescribing of key medication contributes to cardiac risk, it is now appreciated that COPD is a multi-system disorder that exerts 'systemic effects'. Despite the aforementioned shared risk, the intriguing finding that increased cardiovascular morbidity and mortality in COPD are independent of smoking as well as other conventional cardiovascular risk factors, age and gender is driving research into understanding the underlying mechanisms of this increased risk and to what extent it is modifiable.
Abstract and Introduction
Abstract
Significant cardiac morbidity and mortality exists in patients with COPD. Shared risk factors include age, smoking history and exposure to air pollution and passive smoke. Although the inappropriate under-prescribing of β-blockers contributes, it is now appreciated that the observed cardiac risk is not only due to smoking and conventional cardiovascular risk factors, but also other independent factors. A number of hypotheses exist for the increased cardiovascular morbidity and mortality seen in COPD including inflammation, pulmonary hypertension, lung hyperinflation and shared genetics models. Mounting evidence from large randomised controlled trials suggests that COPD treatment may be cardio-protective. We review the current evidence supporting the aforementioned hypotheses and how their modulation may prevent cardiovascular morbidity and mortality in COPD. The persisting underdiagnosis of COPD may have significant consequences. Further mechanistic studies identifying the onset and impact of individual interventions will develop our understanding of this emerging and highly relevant clinical field.
Introduction
Increased Cardiovascular Morbidity and Mortality in COPD Chronic obstructive pulmonary disease (COPD) is predicted to become the sixth leading cause of disability and the third most common cause of death by 2020. COPD is commonly underdiagnosed in the UK and abroad. Its 1% prevalence across all ages rises steeply to 9%–10% for those over 40. A large proportion of morbidity and mortality in COPD is associated with cardiovascular complications.
Reduced pulmonary function, no matter what cause, is associated with increases in all-cause and cardiac mortality, myocardial infarction and arrhythmia. Forced expiratory volume in one second (FEV1) is ranked second to smoking and above blood pressure and cholesterol as a predictor of all-cause and cardiovascular mortality. It has been suggested that a reduction in FEV1 combined with a smoking history better predicts cardiovascular mortality than cholesterol.
In COPD, a large proportion of patients succumb to cardiovascular causes rather than respiratory failure ( Table 1 ). The likelihood of cardiac mortality, ventricular arrhythmias, coronary artery disease (CAD) or congestive cardiac failure increases with worsening FEV1, the rate of FEV1 loss independently predicting CAD mortality. Newer assays, such as the highly sensitive Troponin, have further highlighted the subclinical myocardial damage occurring during COPD exacerbations and are predictive of mortality.
The Impact of Shared Exposures It may be that the relationship between COPD and cardiovascular disease (CVD) is solely due to shared common risk factors.
Smoking It is well accepted that smoking causes both COPD and CVD. Passive smoke inhalation, in a dose–response manner, also increases the likelihood of fatal and non-fatal myocardial infarction with an estimated pooled OR from a meta-analysis of 1.22 (1.04–1.41) and 1.32 (1.04–1.67), respectively. Similarly, increased risks have been observed for COPD mortality with ORs related to spousal smoking of 1.67 in never-smoking male subjects.
Smoke-free Legislation Recently, there has been a significant focus on international public health strategies to combat the adverse effects of smoking, and secondhand smoke in particular. Although the impact of smoke-free legislation (SFL) on respiratory symptoms is well studied in normal individuals data on lung function are less robust since the changes noted were arguably of little clinical relevance, suffered from poor participant compliance and were confounded by seasonal variation in temperature. The impact of SFL on COPD is unclear since the few studies that have assessed the rate of admissions for COPD exacerbations show conflicting results. This is in contrast to the data for CVD. A recent meta-analysis assessing the impact of SFL revealed a reduction of acute coronary syndrome risk in 30 of 35 estimates with a 10% (95% CI 6 to 14, p<0.001) pooled RR reduction, supporting the notion that smoke exposure has a significant independent role in cardiovascular morbidity, although whether those patients with concomitant COPD achieved equivalent improvements in coronary events is unclear.
Air Pollution The development of COPD as a result of damage caused by air pollution is well documented. Day-to-day changes in pollutant levels and longer term exposure also affect CVD risk, and all commonly measured pollutants are positively associated with increased mortality and hospital admissions for CVD. Hypotheses relate to direct pollutant effects of oxidative stress, pulmonary and systemic inflammation or pro-coagulant reactions which, as will be discussed later, have a significant overlap with the postulated effects of COPD. Although observational studies have found associations between cardiac autonomic dysfunction and air pollution, this has not been borne out in controlled conditions and further mechanistic explanations are needed for this discrepancy.
The Impact of Differential Prescribing Practices COPD patients have been excluded from clinical trials involving β-blockers due to historical concerns over bronchoconstriction. Despite database studies persistently demonstrating survival benefit for COPD patients receiving β-blockers in CAD and congestive cardiac failure, and meta-analyses confirming the safety of cardioselective β-blockers in COPD of all severities, underuse still occurs due to lingering concerns over bronchoconstriction in a population which, based on the above evidence, arguably have the most to gain.
Although the underprescribing of key medication contributes to cardiac risk, it is now appreciated that COPD is a multi-system disorder that exerts 'systemic effects'. Despite the aforementioned shared risk, the intriguing finding that increased cardiovascular morbidity and mortality in COPD are independent of smoking as well as other conventional cardiovascular risk factors, age and gender is driving research into understanding the underlying mechanisms of this increased risk and to what extent it is modifiable.
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