Increased risk of coronary artery diseases in overweight and obese individuals is partially mediated by chronic inflammation: The EPICOR study

Background and aims: It is well known that being overweight or obese is a risk factor for coronary artery disease (CAD). At the same time, belonging to these categories indirectly influences other risk factors like hypertension, diabetes or dyslipidemia also through a chronic inflammation condition. The aim of this study was to establish to which extent the effect of body mass index (BMI) on CAD risk can be explained by the chronic inflammation degree, using a statistical mediation model. Methods and results: The present study used data from EPICOR, the cardiovascular branch of the EPIC Italy (European Investigation into Cancer and Nutrition) study. We employed a case-cohort design including 1416 participants with 622 incident CAD cases (major coronary events, myocardial infarction). Acute phase reactant C-reactive protein (CRP) and Plasminogen Activator Inhibitor-1 (PAI-1), were measured at baseline. A mediation analysis was performed to establish to which extent the effect of BMI on CAD risk can be explained by the inflammation degree expressed by the levels of both CRP and PAI-1. Using a fully adjusted survival model individuals in the second and third BMI categories had increased hazard ratios for CAD compared to the first BMI category. Mediation analysis revealed significant direct and indirect effects of BMI on CAD risk through inflammation, and results were consistent across gender and with waist-to-hip ratio analyses. Conclusion: Chronic inflammation might explain part of the increased risk of CAD due to more or less severe excess weight, in a robust statistical mediation model.