CAROTID INTIMA-MEDIA THICKNESS (IMT) COPD EXACERBATIONS & CAROTID INTIMA-MEDIA THICKNESS (IMT) Eda Burcu Boerner 1, Mark Hew 1, Michelle Thompson 1,2, Steve Bozinovski 2, Gary Anderson 2, Louis Irving 1 1Respiratory Medicine, Royal Melbourne Hospital & 2Department of Pharmacology, University of Melbourne, Parkville VIC 3050 Introduction Lung function testing and a 6 minute walk test were performed on the day of carotid ultrasound examination. Statistical analysis was conducted using STATA version IC/10 (stata CORP, College Station TX, USA) and utilised linear and logistic regression facilities. A two tailed p-value of 0.05 was considered statistically significant. Chronic obstructive pulmonary disease (COPD) has been linked to an increased risk of atherosclerosis, as measured by carotid intima-media thickness (IMT) 1, 2. Previous studies demonstrated increased IMT in patients with COPD when compared to smokers with normal lung function 1, 2 . However, within a COPD cohort, no patient factors have been correlated with increased IMT. The mechanisms by which a disease in the respiratory tract such as COPD might lead to a systemic disorder such as atherosclerosis are not fully understood. Potential factors in COPD patients which might influence the risk of atherosclerosis may be classified into those that indicate disease severity (such as the degree of airflow obstruction) or those that reflect ongoing disease activity (such as the frequency of exacerbations). Table 2. Multivariate Logistic regression analysis for dichotomised IMT with ATS 2 as primary variable Figure 1: Carotid Intimal Thickness (IMT) measurement Discussion In our study, there was a significant correlation between elevated IMT and the number of COPD exacerbations requiring hospitalisations in the 12 months preceding carotid sonography. In multivariate analysis, this finding was no longer significant. The only potential confounder to have a significant association with IMT was age. Markers of COPD severity such as FEV1 and the BODE index did not predict increased IMT. While these measurements reflect structural lung damage and ensuing physiological derangements, they may have little effect on systemic inflammation outside the respiratory system. Interestingly, baseline levels of inflammation such as CRP, SAA and IL-6 did not predict elevated IMT. This suggests that only heightened respiratory tract inflammation such as occurs in moderate to severe exacerbations can reach the necessary threshold to impact on systemic inflammation and atherogenesis. Acute pertubations in endothelial function may be another mechanism by which exacerbations may impact on cardiovascular risk. Our study implicates COPD exacerbation frequency and severity as a key pathogenic mechanism in the acceleration of cardiovascular disease. Despite the non-significant result in the multivariate model, we suggest the effects seen in the univariate analysis warrant further investigation on a larger scale. Hypothesis Results Increased COPD activity (exacerbation rate and ensuing systemic inflammation) is more closely associated with abnormal IMT than increased COPD severity [forced expiratory volume in one second (FEV1) and BODE index]. Results 14 subjects (48%) were males, with an average age of 72.7 years. Confounders included hypertension in 15 (52%), diabetes in 4 (14%), total cholesterol greater than 4.0 mmol in 21 (72%) and statin use in 15 (52%). For the univariate analysis of IMT at the common carotid (CCA-IMT), the only significant predictor was the number of moderate acute exacerbations of COPD (ATS Level 2), p= 0.04, (Table 1). However, ATS 2 was not a significant predictor in a multivariate analysis which included age (Table 2). The univariate analysis of IMT at the carotid bifurcation (BIF-IMT) also demonstrated ATS 2 exacerbations as a significant predictor of increased IMT (data not shown, similar as for CCA-IMT). The BODE index and FEV1 did not predict increased IMT within the COPD cohort. Methods 29 COPD patients were recruited through Melbourne Longitudinal COPD cohort and gave informed consent. The study was approved by the Royal Melbourne Hospital Ethics Committee. Carotid Sonography Carotid Ultrasound was undertaken by a single operator (EBB) who had previously performed over 400 general ultrasound examinations. Carotid IMT was examined bilaterally at 2 sites; the common carotid artery (CCA-IMT 20 to 60 mm proximal to the flow division) and the carotid bifurcation (BIF-IMT, 0 to 20 mm proximal to the flow division) using an anterior-oblique approach with a 8 MHz transducer. IMT software by Sonosite was used to calculate IMT, meaned over a distance of approximately 8 mm (Figure 1). An IMT of greater than 0.90 mm was considered elevated. Clinical data All patients had received prospective follow-up in the preceding 12 months which included a weekly phone call by a research nurse, to identify COPD exacerbations which were graded by ATS severity criteria; Level 1 (Mild) AECOPD managed in the community; Level 2 (Moderate) requiring hospital admission; Level 3 (Severe) associated with respiratory failure. Risk factors for atherosclerosis were identified in each patient, including ; age, gender, body mass index, diabetes, hypertension, elevated cholesterol, lipid lowering agents, and cigarette pack years. Blood samples for C-reactive protein (cRP), Serum Amyloid A (SAA) and interleukin-six (IL-6) were taken on the day of ultrasound examination. The lowest documented cRP in the preceding 12 months was also obtained. References Table 1. Characteristic comparisons for dichotomised CCA-IMT Kim SJ, Yoon DW, Lee EJ, Hur GY, Jung KH, Lee SY, Lee SY, Shin C, Shim JJ, In KH, Kang KH, Yoo SH, Kim JH. Carotid atherosclerosis in patients with untreated chronic obstructive pulmonary disease. Int J Tuberc Lung Dis. 2011 Sep;15(9):1265-70. 2. Iwamoto H, Yokoyama A, Kitahara Y, Ishikawa N, Haruta Y, Yamane K, Hattori N, Hara H, Kohno N. Airflow limitation in smokers is associated with subclinical atherosclerosis. Am J Respir Crit Care Med. 2009 Jan 1;179(1):35-40. Epub 2008 Oct 17.