INCREASED RISK OF MYOCARDIAL INFARCTION AND STROKE FOLLOWING EXACERBATION OF COPD Gavin C. Donaldson, PhD ; John R. Hurst, PhD ; Christopher J. Smith, BA ; Richard B. Hubbard, DM ; and Jadwiga A. Wedzicha, MD CHEST 2010; 137(5):1091–1097 R1 이치훈

INTRODUCTION  COPD, third leading cause of death by 2020  increased risk of acute cardiovascular events, about 30% die of cardiovascular disease  Between COPD and cardiovascular disease  shared risk factors, such as smoking  But additional risk factor: systemic inflammation  management of COPD exacerbations  reduce this additional risk

INTRODUCTION  Frequent exacerbations  faster rate of decline in lung function  impaired health-related quality of life  reduced daily activity  increased airway inflammation  greater mortality  Most COPD exacerbations are due to lower respiratory tract infections  systemic inflammatory markers  fibrinogen and interleukin-6  Increased levels of these markers in the blood  associated with an increased risk of thrombus formation and cardiovascular events

INTRODUCTION  Previous self- and case-controlled epidemiologic studies  association between respiratory infection and cardiovascular events in the general population  However, this association may differ in patients with COPD  a self-controlled case series study  To assess the magnitude and timing of the risk of MI and stroke events following an exacerbation of COPD

MATERIALS AND METHODS  Health Improvement Network(THIN) database -primary care practices in England and Wales  Exacerbation Definitions (1) oral steroids (except fludrocortisone) >20mg/d (2) oral antibiotics (3) oral steroids and oral antibiotics

METHODS High risk period Low risk period Fibrinogen IL-6 Fixed-effects conditional poisson regression

RESULTS 1.79 yrs per patient 1.1 per 100pt-yrs 1.4 per 100pt-yrs

RESULTS

DISCUSSION  For the first time, shown that exacerbation of COPD is associated with a small, but statistically significant, 2.27-fold increased relative risk of MI during a short 5-day period and of a stroke during the 1- to 49 day period immediately following an exacerbation.  strengths of our study  a large population of patients with COPD  the prevalence, demographics, smoking habits, and mortality  the self-case-control method  avoids confounding by other cardiovascular risk factors

DISCUSSION  Common risk factors between COPD & MI or stroke  smoking, low socioeconomic status, and early life experiences  Additional risk factor: systemic inflammation  remains increased for a long time after exacerbation  patients with frequent exacerbations  Higher stable airway inflammatory markers  Plasma fibrinogen increases faster over time  Treatments are also needed during stable periods

DISCUSSION  during a COPD exacerbation  both fibrinogen and CRP are increased Fibrinogen  thrombogenic CRP  upregulate other inflammatory cytokines  promote uptake of LDL by macrophages  increase adhesion of leukocytes to arterial endothelium

DISCUSSION  increase mucus production and bronchoconstriction  alveolar hypoxia  increased pulmonary artery pressures  increased burden on the right side of the heart  Increased b2-agonist use or an increase in cardiac afterload due to dynamic hyperinflation  the effects of inflammation, tachycardia, and hypoxia may be synergistic  but the mechanisms underlying our findings require further elucidation

DISCUSSION  limitation  the date of exacerbation onset could not be determined precisely  prophylactically prescribed antibiotics and/or steroids: hard to detect  Oral steroids can affect fibrinolysis, increased the risk of a cardiovascular event  However, no significant increase in MI or stroke post exacerbations treated by oral corticosteroids alone  no subgroups analysis for cardiovascular risk factor  Risk stratification may prove a productive area for future research

DISCUSSION  Coronary arteries are narrow  rapid occlusion at a site of existing stenosis  explain the higher risk of an MI 1 to 5 days postexacerbation  Carotid arteries are relatively larger  Events may take longer to manifest with increased levels of fibrinogen and other clotting factors in the blood

CONCLUSION  Increased risk of MI following an exacerbation of COPD, approximately double in stable disease  MI occurs following one in 2,513 exacerbations  the risk returns to baseline within 5 days of treatment of the exacerbation  Treat both the stable and exacerbation states to reduce cardiovascular events in patients with COPD