Determinants of systemic vascular function in patients with stable chronic obstructive pulmonary disease.

RATIONALE Impaired vascular reactivity is an important factor in the pathogenesis of cardiovascular disease. OBJECTIVES We sought to assess vascular reactivity in patients with chronic obstructive pulmonary disease (COPD) and respective control subjects, and to investigate the relation between vascular function and airflow obstruction and systemic inflammation. METHODS We studied 60 patients with stable COPD; 20 smokers with normal lung function matched for age, sex, and body weight; and 20 similarly matched nonsmokers. Patients with cardiovascular comorbidities were excluded. The endothelium-dependent and endothelium-independent function of the vasculature was measured using flow-mediated and nitrogen-mediated dilation of the brachial artery, respectively. Systemic inflammatory markers, including C-reactive protein, fibrinogen, and interleukin (IL)-6, were determined in serum. MEASUREMENTS AND MAIN RESULTS Both flow-mediated and nitrogen-mediated dilation of the brachial artery were significantly lower in patients with stable COPD than in smoking and nonsmoking control subjects. Levels of inflammatory mediators such as IL-6 and fibrinogen were higher in patients than they were in control subjects. In patients with COPD, stepwise multiple regression analysis showed that age, sex, baseline brachial artery diameter, C-reactive protein level, leukocyte count, blood glucose level, and percentage of predicted forced expiratory volume in 1 s were independent predictors of flow-mediated dilation. There was no relation between flow-mediated dilation and pack-years of smoking. Baseline brachial artery diameter was the only independent predictor of nitrogen-mediated dilation in patients with COPD. CONCLUSIONS Both endothelium-dependent and endothelium-independent vasodilation is significantly impaired in patients with stable COPD. Airflow obstruction and systemic inflammation may increase the risk of cardiovascular disease in patients with COPD.

[1]  David G. Anderson,et al.  Arterial stiffness is independently associated with emphysema severity in patients with chronic obstructive pulmonary disease. , 2007, American journal of respiratory and critical care medicine.

[2]  Anthony P Reeves,et al.  Impaired flow-mediated dilation is associated with low pulmonary function and emphysema in ex-smokers: the Emphysema and Cancer Action Project (EMCAP) Study. , 2007, American journal of respiratory and critical care medicine.

[3]  K. Rabe,et al.  From COPD to chronic systemic inflammatory syndrome? , 2007, The Lancet.

[4]  Peter H Edwards,et al.  Arterial stiffness and osteoporosis in chronic obstructive pulmonary disease. , 2007, American journal of respiratory and critical care medicine.

[5]  P. Ridker C-reactive protein and the prediction of cardiovascular events among those at intermediate risk: moving an inflammatory hypothesis toward consensus. , 2007, Journal of the American College of Cardiology.

[6]  S. Walters,et al.  Prevalence and socioeconomic associations of asthma and allergic rhinitis in northern Africa , 2006, European Respiratory Journal.

[7]  N. Anthonisen,et al.  C-reactive protein and mortality in mild to moderate chronic obstructive pulmonary disease , 2006, Thorax.

[8]  B. Celli,et al.  C-reactive protein levels and clinically important predictive outcomes in stable COPD patients , 2006, European Respiratory Journal.

[9]  J. Soriano,et al.  C-reactive protein in patients with COPD, control smokers and non-smokers , 2005, Thorax.

[10]  Judith K Jones,et al.  Cardiovascular disease in patients with chronic obstructive pulmonary disease, Saskatchewan Canada cardiovascular disease in COPD patients. , 2006, Annals of epidemiology.

[11]  J. Wedzicha,et al.  Systemic and upper and lower airway inflammation at exacerbation of chronic obstructive pulmonary disease. , 2006, American journal of respiratory and critical care medicine.

[12]  T. Seemungal,et al.  Airway and Systemic Inflammation and Decline in Lung Function in Patients With COPD , 2005, Chest.

[13]  J. Hankinson,et al.  Standardisation of spirometry , 2005, European Respiratory Journal.

[14]  D. Sin,et al.  The relationship between reduced lung function and cardiovascular mortality: a population-based study and a systematic review of the literature. , 2005, Chest.

[15]  D. Kass,et al.  Mechanisms, pathophysiology, and therapy of arterial stiffness. , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[16]  John Connett,et al.  The Effects of a Smoking Cessation Intervention on 14.5-Year Mortality , 2005, Annals of Internal Medicine.

[17]  Å. Sjöholm,et al.  Persistent endothelial dysfunction is related to elevated C-reactive protein (CRP) levels in Type II diabetic patients after acute myocardial infarction. , 2005, Clinical science.

[18]  C. Duman,et al.  Endothelial dysfunction in young women with polycystic ovary syndrome: relationship with insulin resistance and low-grade chronic inflammation. , 2004, The Journal of clinical endocrinology and metabolism.

[19]  E. Lonn,et al.  Cross-sectional evaluation of brachial artery flow-mediated vasodilation and C-reactive protein in healthy individuals. , 2004, European heart journal.

[20]  M. Kutryk,et al.  C-Reactive Protein Attenuates Endothelial Progenitor Cell Survival, Differentiation, and Function: Further Evidence of a Mechanistic Link Between C-Reactive Protein and Cardiovascular Disease , 2004, Circulation.

[21]  N. Sattar Inflammation and endothelial dysfunction: intimate companions in the pathogenesis of vascular disease? , 2004, Clinical science.

[22]  E. Benjamin,et al.  Clinical Correlates and Heritability of Flow-Mediated Dilation in the Community: The Framingham Heart Study , 2004, Circulation.

[23]  A. Giordano,et al.  Endothelial dysfunction in young patients with rheumatoid arthritis and low disease activity , 2003, Annals of the rheumatic diseases.

[24]  G. Brevetti,et al.  Endothelial dysfunction in peripheral arterial disease is related to increase in plasma markers of inflammation and severity of peripheral circulatory impairment but not to classic risk factors and atherosclerotic burden. , 2003, Journal of vascular surgery.

[25]  Don D. Sin,et al.  Why Are Patients With Chronic Obstructive Pulmonary Disease at Increased Risk of Cardiovascular Diseases?: The Potential Role of Systemic Inflammation in Chronic Obstructive Pulmonary Disease , 2003 .

[26]  M. Sutton,et al.  Echocardiographic assessment of pulmonary hypertension in patients with advanced lung disease. , 2003, American journal of respiratory and critical care medicine.

[27]  Amir Lerman,et al.  Endothelial Dysfunction: A Marker of Atherosclerotic Risk , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[28]  Ren-Ke Li,et al.  A Self-Fulfilling Prophecy: C-Reactive Protein Attenuates Nitric Oxide Production and Inhibits Angiogenesis , 2002, Circulation.

[29]  G. Kojda,et al.  Vasoprotection by nitric oxide: mechanisms and therapeutic potential. , 2002, Cardiovascular research.

[30]  S. Reis,et al.  Large brachial artery diameter is associated with angiographic coronary artery disease in women. , 2002, American heart journal.

[31]  K. Lam,et al.  Atorvastatin lowers C-reactive protein and improves endothelium-dependent vasodilation in type 2 diabetes mellitus. , 2002, The Journal of clinical endocrinology and metabolism.

[32]  E. Benjamin,et al.  Guidelines for the ultrasound assessment of endothelial-dependent flow-mediated vasodilation of the brachial artery: a report of the International Brachial Artery Reactivity Task Force. , 2002, Journal of the American College of Cardiology.

[33]  V. Hombach,et al.  C-Reactive Protein–Mediated Low Density Lipoprotein Uptake by Macrophages: Implications for Atherosclerosis , 2001, Circulation.

[34]  James T. Willerson,et al.  Direct Proinflammatory Effect of C-Reactive Protein on Human Endothelial Cells , 2000, Circulation.

[35]  T. Seemungal,et al.  Acute Exacerbations of Chronic Obstructive Pulmonary Disease Are Accompanied by Elevations of Plasma Fibrinogen and Serum IL-6 Levels , 2000, Thrombosis and Haemostasis.

[36]  R. Ross,et al.  Atherosclerosis is an inflammatory disease. , 1998, American heart journal.

[37]  J. Deanfield,et al.  Smooth muscle dysfunction occurs independently of impaired endothelium-dependent dilation in adults at risk of atherosclerosis. , 1998, Journal of the American College of Cardiology.

[38]  J. Lekakis,et al.  Effects of acute cigarette smoking on endothelium-dependent arterial dilatation in normal subjects. , 1998, The American journal of cardiology.

[39]  V. Peinado,et al.  Endothelial dysfunction in pulmonary arteries of patients with mild COPD. , 1998, American journal of physiology. Lung cellular and molecular physiology.

[40]  D. Glogar,et al.  Systemic endothelial dysfunction is related to the extent and severity of coronary artery disease. , 1997, Atherosclerosis.

[41]  E. Wouters,et al.  Evidence for a relation between metabolic derangements and increased levels of inflammatory mediators in a subgroup of patients with chronic obstructive pulmonary disease. , 1996, Thorax.

[42]  A. Yeung,et al.  Close relation of endothelial function in the human coronary and peripheral circulations. , 1995, Journal of the American College of Cardiology.

[43]  J. Mege,et al.  Tumor necrosis factor-alpha levels and weight loss in chronic obstructive pulmonary disease. , 1994, American journal of respiratory and critical care medicine.

[44]  D. Spiegelhalter,et al.  Aging is associated with endothelial dysfunction in healthy men years before the age-related decline in women. , 1994, Journal of the American College of Cardiology.

[45]  J. Hodgson,et al.  Evidence that selective endothelial dysfunction may occur in the absence of angiographic or ultrasound atherosclerosis in patients with risk factors for atherosclerosis. , 1994, Journal of the American College of Cardiology.

[46]  D. Celermajer,et al.  Cigarette Smoking Is Associated With Dose‐Related and Potentially Reversible Impairment of Endothelium‐Dependent Dilation in Healthy Young Adults , 1993, Circulation.

[47]  J. K. Lloyd,et al.  Non-invasive detection of endothelial dysfunction in children and adults at risk of atherosclerosis , 1992, The Lancet.