Coronary Artery Disease and Peripheral Artery Disease Etiopathogenic Differences in Coronary Artery Disease and Peripheral Artery Disease: Results From the National Health and Nutrition Examination Survey Shikhar Agarwal, MD, MPH, CPH, FACP 1 , and Sahar Naderi, MD, MHS 1 Abstract Cross-sectional data from the National Health and Nutrition Examination Surveys 1999 to 2004 were pooled for this study. Compared with coronary artery disease (CAD), a greater proportion of individuals with peripheral artery disease (PAD) were female, black, and active smokers. Patients with PAD had significantly higher serum concentrations of low-density lipoprotein cho- lesterol and C-reactive protein than those with CAD alone. The risk of CAD increased with serum cotinine levels >0.02 ng/mL. However, the risk of PAD increased only with serum cotinine levels >138 ng/mL. Despite this association, there was no significant association of secondhand smoke exposure with CAD or PAD. In conclusion, patients with CAD and PAD differed with respect to several demographic and biochemical factors. The relationship between PAD and cotinine demonstrated a threshold phenom- enon (serum cotinine levels >138 ng/mL). Keywords coronary artery disease, peripheral artery disease, cotinine, smoker, low-density lipoprotein cholesterol, C-reactive protein Introduction Coronary artery disease (CAD) and peripheral artery disease (PAD) are manifestations of systemic atherosclerosis. Although both diseases share risk factors, it is not uncommon to encounter CAD without any concomitant PAD or vice versa. 1 This find- ing might suggest differences in the etiopathogenesis of these diseases. In 1992, Fowkes et al demonstrated differences in smoking characteristics and lipid profiles between patients with CAD and patients with PAD. 2 In this study, we aim to examine the differences in demo- graphic characteristics, traditional cardiovascular risk factors, and serum vitamin concentrations between patients with known CAD and those with evidence of PAD in a large nationally rep- resentative database. Methods Study Population This study was based on pooled data from the 1999 to 2000, 2001 to 2002, and 2003 to 2004 National Health and Nutrition Examination Surveys (NHANESs). 3 The NHANES data are collected from on-going cross-sectional surveys from a nation- ally representative group of patients in the United States. We used demographic, laboratory, and physical examination data for our study. Study Variables Ankle brachial index (ABI) was measured in all individuals over the age of 40 years at the time of the survey. PAD was defined as an ABI <0.9 in either leg. Valid information on ABI was obtained from 7571 individuals in the NHANES 1999 to 2004 survey. In all, 21 individuals with ABI values 1.5, pos- sibly related to noncompressible vessels in the legs, were excluded, leaving 7550 individuals in the present study. CAD was defined as self-reported history of CAD, angina pectoris, or heart attack. Cigarette smoking status was determined using serum cotinine measurements along with questionnaire items includ- ing ‘‘Have you smoked at least 100 cigarettes in your entire life?’’ and ‘‘Do you now smoke cigarettes?’’ 3 Active smokers were defined as those who reported active cigarette smoking or had measured serum cotinine levels 10 ng/mL. 4 All those identified as current nonsmokers by self-report were classified as former smokers and never smokers based on survey 1 Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH, USA Corresponding Author: Shikhar Agarwal, Department of Cardiovascular Medicine, Cleveland Clinic, 9500 Euclid Avenue, Desk J3-5, Cleveland, OH 44195, USA. Email: dr.shikhar.agarwal@gmail.com Angiology 2014, Vol. 65(10) 883-890 ª The Author(s) 2013 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/0003319713509303 ang.sagepub.com