Rationale: More patients with chronic obstructive pulmonary disease (COPD) die of cardiovascular causes than of respiratory causes, and patients with COPD have increased morbidity and mortality from stroke and coronary heart disease. Arterial stiffness independently predicts cardiovascular risk, is associated with atheromatous plaque burden, and is increased in patients with COPD compared with control subjects matched for cardiovascular risk factors. Elastin fragmentation and changes in collagen are found in the connective tissue of both emphysematous lungs and stiff arteries, but it is not known whether the severity of arterial stiffness in patients with COPD is associated with the severity of emphysema. Objectives: To identify whether the extent of arterial stiffness is associated with emphysema severity. Methods: We performed a cross-sectional study in 157 patients with COPD. Measurements and Main Results: We measured pulse wave velocity (a validated measure of arterial stiffness), blood pressure, smoking pack-years, glucose, cholesterol, and C-reactive protein in 157 patients with COPD. We assessed emphysema using quantitative computed tomography scanning in a subgroup of 73 patients. We found that emphysema severity was associated with arterial stiffness (r 5 0.471, P , 0.001). The association was independent of smoking, age, sex, FEV 1 % predicted, highly sensitive C-reactive protein and glucose concentrations, cholesterol-high-density lipoprotein ratio, and pulse oximetry oxygen saturations. Conclusions: Emphysema severity is associated with arterial stiffness in patients with COPD. Similar pathophysiological processes may be involved in both lung and arterial tissue and further studies are now required to identify the mechanism underlying this newly described association.

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COPD is associated with increased arterial stiffness independent of cigarette smoke exposure. However, this abnormality is not explained by systemic endothelial dysfunction. Increased arterial stiffness may represent the mechanistic link between COPD and the increased risk for cardiovascular disease associated with this condition.

Rationale Chronic obstructive pulmonary disease (COPD) is associated with systemic inflammation and cardiovascular disease. Interaction between inflammatory cells and activated platelets is important in the pathogenesis of atherothrombosis and may contribute to cardiovascular risk in patients with COPD. Objectives To assess platelet-monocyte aggregation in patients with COPD and matched controls, and in patients with an acute exacerbation of COPD. Methods 18 men with COPD and 16 male controls matched for age and cigarette smoke exposure were recruited. A further 12 patients were investigated during and at least 2 weeks after hospitalisation for an acute exacerbation. Platelet-monocyte aggregation and platelet P-selectin expression were determined using flow cytometry. Results Patients with COPD had increased circulating platelet-monocyte aggregates compared with controls (mean (SD) 25.3 (8.3)% vs 19.5 (4.0)%, p¼0.01). Platelet-monocyte aggregation was further increased during an acute exacerbation compared with convalescence (32.0 (11.0)% vs 25.5 (6.4)%, p¼0.03). Platelet P-selectin expression and soluble P-selectin did not differ between groups. Conclusions Patients with stable COPD have increased circulating platelet-monocyte aggregates compared with well-matched controls. Platelet activation is further increased in patients with COPD during an acute exacerbation. These findings identify a novel mechanism to explain the increased cardiovascular risk in COPD and suggest platelet inhibition as a plausible therapeutic target.

Cardiovascular disease (CVD) contributes significantly to morbidity and mortality in COPD. There is a high prevalence of traditional risk factors in this patient group including smoking, sedentary behaviour and low socio-economic class. However, large studies have shown that airflow limitation is an independent risk factor for CVD. Therefore there may be a 'COPD effect' that contributes to CVD in this condition, adding to the body of evidence that COPD has important systemic consequences, as well as being a lung disease. In this article, we review the evidence for CVD in COPD. Next, we examine systemic factors present in COPD, and link these to the pathogenesis of atherosclerosis, including inflammation, oxidative stress and hypoxia. Finally, we review those studies that have investigated therapeutic interventions in COPD that may modify cardiovascular risk.

Cardiovascular disease represents a considerable burden in terms of both morbidity and mortality in patients with chronic obstructive pulmonary disease (COPD). For 20 years, forced expiratory volume in 1 second (FEV 1 ) has been an established predictor of cardiovascular mortality among smokers, never-smokers, and patients with COPD. We review evidence for increased cardiovascular risk in COPD. In addition, we assess the emerging evidence which suggests that hypoxia, systemic inflammation, and oxidative stress in patients with COPD may cause cardiovascular disease. We also discuss alternative hypotheses that the endothelium and connective tissues in the arteries and lungs of patients with COPD and cardiovascular disease have a shared susceptibility to these factors.

Cardiovascular disease is common in chronic obstructive pulmonary disease (COPD) and raised troponin is common in exacerbations. However, the prevalence of myocardial infarction following hospitalisation for exacerbation of COPD is unknown.Patients aged o40 yrs hospitalised with acute exacerbation of COPD (n5242) with o10 packyrs of cigarette smoking were included in a prospective case series conducted in four hospitals. Patients whose primary presenting complaint was chest pain or who had an alternative diagnosis were excluded. Chest pain histories, serial ECGs and troponin levels were obtained.The mean¡SD age was 69¡9 yrs; 108 (45%) patients were male and almost half were current smokers. 124 (51%; 95% CI 48-58%) patients had chest pain, which was exertional in 62 (26%). 24 (10%) had raised troponin, among whom, 20 (8.3%; 95% CI 5.1-12.5%) had chest pain and/or serial ECG changes, fulfilling the 2007 Universal Definition of Myocardial Infarction. Neither chest pain (p50.77) nor serial ECG changes (p50.39) were associated with raised troponin.Raised troponin, chest pain and serial ECG changes are common in patients admitted to hospital with exacerbation of COPD. Overall, one in 12 patients met the criteria for myocardial infarction. Whether these patients would benefit from further cardiac investigation is unknown.KEYWORDS: Chest pain, chronic obstructive pulmonary disease, ECG, myocardial infarction, troponin C oronary heart disease is a major cause of mortality in chronic obstructive pulmonary disease (COPD) [1,2]. Both conditions share common risk factors, such as smoking and socioeconomic status, and reduced forced expiratory volume in 1 s (FEV1), a characteristic feature of COPD, is an independent risk factor for cardiovascular mortality [3].In studies using routine clinical data, diagnosis with myocardial infarction (MI) appears to be more common following exacerbations in patients with COPD [4,5], while raised troponin has been found to be associated with increased mortality in exacerbation of COPD [6][7][8],Coronary events may present without chest pain [9], can be missed even in simple chest pain presentations [10] and may be more likely to be missed in patients presenting with acute exacerbation of COPD who also report acute breathlessness and chest tightness.Raised troponin is common in patients admitted to hospital with exacerbation of COPD [6][7][8]; however, we are unaware of any prospective study that has investigated this group for clinical or electrocardiography features of MI.Therefore, we undertook a prospective case series to identify the prevalence of MI in patients admitted to hospital with acute exacerbation of COPD. The prevalence of MI was calculated along with 95% confidence intervals using the exact binomial test. In exploratory analyses, associations between patient characteristics and raised troponin concentrations were examined using Fisher's exact test, for which we report all associations where the p-value was ,0.10. Analyses were performed using SAS version 9.2 (SAS In...

Background Development of emphysema and vascular stiffness in chronic obstructive pulmonary disease (COPD) may be due to a common mechanism of susceptibility to pulmonary and systemic elastin degradation. Objectives To investigate whether patients with COPD have evidence of systemic elastin degradation in the skin. Methods The authors measured cutaneous elastin degradation using immunohistochemistry (percentage area of elastin fibres) in sun-exposed (exposed) and nonsun-exposed (non-exposed) skin biopsies in 16 men with COPD and 15 controls matched for age and cigarette smoke exposure. Quantitative PCR of matrix metalloproteinase (MMP)-2, -9, -12 and tissue inhibitor of metalloproteinase-1 mRNA and zymography for protein expression of MMP-2 and -9 were performed on homogenised skin. Arterial stiffness and emphysema severity were measured using carotid-femoral pulse wave velocity and quantitative CT scanning. Results Skin elastin degradation was greater in exposed and non-exposed skin of patients with COPD compared with controls (exposed, mean (SD); 43.5 (12.1)% vs 26.3 (6.9)%, p<0.001; non-exposed 22.4 (5.2)% vs 18.1 (4.3)%, p¼0.02). Cutaneous expression of MMP-9 mRNA and proMMP-9 concentrations was increased in exposed skin of COPD patients (p¼0.004 and p¼0.02, respectively) and was also associated with increased skin elastin degradation (r¼0.62, p<0.001 and r¼0.47, p¼0.01, respectively). In the entire cohort of exsmokers, cutaneous elastin degradation was associated with emphysema severity, FEV 1 and pulse wave velocity. Conclusions Patients with COPD have increased skin elastin degradation compared with controls, which is related to emphysema severity and arterial stiffness. Systemic elastin degradation due to increased proteolytic activity may represent a novel shared mechanism for the pulmonary, vascular and cutaneous features of COPD.