Atherosclerosis 176 (2004) 173–179 C-Reactive protein is inversely related to physical fitness in middle-aged subjects Doron Aronson a,∗ , Muhammad Sheikh-Ahmad a , Ophir Avizohar b , Arthur Kerner a , Ron Sella a , Peter Bartha c , Walter Markiewicz a , Yishai Levy c , Gerald J. Brook b a Department of Cardiology, Rambam Medical Center and Rappaport Faculty of Medicine, POB 9602, Haifa 31096, Israel b Center for Preventive Medicine, Rambam Medical Center and Rappaport Faculty of Medicine, POB 9602, Haifa 31096, Israel c Department of Internal Medicine D, Rambam Medical Center and Rappaport Faculty of Medicine, POB 9602, Haifa 31096, Israel Received 30 December 2003; received in revised form 30 March 2004; accepted 26 April 2004 Available online 4 July 2004 Abstract Introduction: Physical fitness has a protective effect with regard to the risk of developing coronary disease or diabetes. C-reactive protein (CRP) levels are directly related to increased risk of coronary disease and diabetes. However, data on the association between physical fitness and CRP are sparse. Methods: Physical fitness was assessed in a population-based cross-sectional study (n = 892; age 50 ± 9 years) using the Bruce treadmill protocol. CRP was measured using a high-sensitivity assay. Results: Geometric mean CRP levels were calculated across quartiles of physical fitness after adjustment for age, gender, body mass index, smoking habit, presence of diabetes and hypertension, HDL cholesterol and triglyceride levels, and use of hormone replacement therapy, statins, and aspirin. CRP levels decreased with increasing quartiles of fitness (P for trend <0.0001). When used as a continuous variable in a stepwise linear regression model, the geometric mean of CRP decreased by 0.061 mg/L (95% confidence interval (CI) 0.034–0.089 mg/L) for each 1 unit increase in metabolic equivalents (METs). Multivariate logistic regression models showed that compared to subjects in the lowest fitness quintile, subjects in the highest fitness quintile had significantly lower adjusted odds of having a high-risk (>3 mg/L) CRP level (OR 0.53; 95% CI 0.39–0.71, P = 0.007). Conclusion: CRP concentration decreases continuously with increasing levels of physical fitness. The health-related salutary effects of physical fitness may be mediated, in part, through an antiinflammatory mechanism. © 2004 Elsevier Ireland Ltd. All rights reserved. Keywords: C-reactive protein; Fitness; Obesity; Inflammation; Physical fitness 1. Introduction Chronic, low-level inflammation is an important factor in the initiation and progression of atherosclerosis [1]. Markers of inflammation such as the acute phase reactant C-reactive protein (CRP)—a sensitive marker for systemic inflammation—can identify individuals at high risk of de- veloping coronary events [2]. CRP is strongly associated with various components of the metabolic syndrome and especially with proxy indicators of elevated body fatness such as body mass index (BMI) [3–5]. Although the nature of the relation between adiposity, insulin ∗ Corresponding author. Tel.: +972 48 542790; fax: +972 48 542176. E-mail address: daronson@netvision.net.il (D. Aronson). resistance and CRP has not been clearly established, the importance of this relation is emphasized by studies showing that CRP levels predict incident type-2 diabetes [6,7]. Several studies found that self-reported physical activity is associated with lower CRP levels [8–14]. However, this finding has not been confirmed in all studies, especially after adjusting for BMI [15]. Physical fitness, as assessed with maximal exercise test- ing, is a more accurate and objective measure of regular physical exercise. Physical fitness is associated with lower coronary artery disease and diabetes risk [16–20]. Exer- cise also improves insulin resistance [21] and its associated metabolic abnormalities such as dyslipidemia and hyperten- sion [22,23]. Thus, better physical fitness and elevated CRP have op- posing effects on similar health outcomes. The aim of the 0021-9150/$ – see front matter © 2004 Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.atherosclerosis.2004.04.025