Atherosclerosis 176 (2004) 355–360 Potential of free-form TFPI and PAI-1 to be useful markers of early atherosclerosis in a Japanese general population (the Suita Study): association with the intimal-medial thickness of carotid arteries Toshiyuki Sakata a,∗ , Toshifumi Mannami b,1 , Shunroku Baba b,2 , Yoshihiro Kokubo b , Kazuomi Kario c , Akira Okamoto a , Kousuke Kumeda d , Naoki Ohkura e,3 , Yoshiaki Katayama a , Toshiyuki Miyata e , Hitonobu Tomoike b , Hisao Kato e a Laboratory of Clinical Chemistry, National Cardiovascular Center, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan b Department of Preventive Cardiology, National Cardiovascular Center, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan c Department of Cardiology, Jichi Medical School, Tochigi, Japan d Chemo-Sero Therapeutic Research Institute, Kumamoto, Japan e Research Institute, National Cardiovascular Center, Fujishirodai 5-7-1, Suita, Osaka 565-8565, Japan Received 7 May 2003; received in revised form 29 April 2004; accepted 4 May 2004 Available online 14 July 2004 Abstract This study assessed markers of vascular endothelial cell dysfunction associated with early atherosclerosis in carotid arteries. We measured the plasma levels of free-form tissue factor pathway inhibitor (free TFPI), plasminogen activator inhibitor-1 (PAI-1), and von Willebrand factor (vWF) in 522 adults without cardiovascular disease enrolled in the Suita Study. For each sex, we analyzed the association of the degree of intimal-medial thickness (IMT) with hemostatic markers using logistic regression analysis considering potential confounding risk factors, including age, body mass index, lifestyle (current smoking and drinking), illness (diabetes mellitus and hyperlipidemia), systolic blood pressure, and antihypertensive drug use. The age-adjusted levels of free TFPI and PAI-1 were positively and independently associated with the degree of IMT for men. Even after adjustment for all confounding factors, the level of PAI-1 was positively associated with the degree of IMT. These results indicate that measurement of the levels of free TFPI and PAI-1 is a potentially useful tool for the detection of early atherosclerosis in men. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: Atherosclerosis; Endothelium-derived factors; Hypertension 1. Introduction Measurement of the intimal-medial thickness (IMT) of carotid arteries has been used as a non-invasive endpoint ∗ Corresponding author. Tel.: +81 6 6833 5012x2296; fax: +81 6 6835 1176. E-mail address: tsakata@hsp.ncvc.go.jp (T. Sakata). 1 Present address: Department of Hygiene/Public Health, Faculty of Medicine, Kagawa University, Kagawa 761-0701, Japan. 2 Present address: The Second Hanwa Hospital, 3176 Fukaikitamachi, Sakai-City, Osaka 599-8271, Japan. 3 Clinical Molecular Biology, Faculty of Pharmaceutical Science Teikyo University, 1091-1 Suarashi, Sagamiko, Tsukui-gun, Kanagawa 199-0195, Japan. in epidemiological studies and clinical trials to assess the progression and regression of atherosclerosis [1,2]. Fur- thermore, IMT has recently been used not only as a sur- rogate endpoint for atherosclerosis of the coronary artery but also as a good indicator of the presence and extent of coronary artery disease [3–6]. Case-reference studies in a general population have been performed in regard to the association between markers of vascular endothe- lial cell dysfunction and atherosclerosis by measuring IMT of the carotid artery [7–9]. However, to detect early atherosclerosis, it is essential to study the association be- tween these markers and the extent of atherosclerosis, using a general population free from cardiovascular disease (CVD). 0021-9150/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2004.05.017