Causal relationship of excess body weight on cardiovascular events through risk factors

Excess body weight is associated with cardiovascular events (CVEs) and premature death. This study aimed to find the causal pathways between excess body weight and CVEs through risk factors in a general adult population. A total of 7921 employees of the Electricity Generating Authority of Thailand were enrolled during 1997-2009. Baseline characteristics and blood test results were collected. A body mass index (BMI) ≥ 23 kg/m², using WHO criteria for Asians was defined as excess body weight. A mediation analysis was applied to assess potential causal pathways. BMI ≥ 23 kg/m² was considered as an independent variable, whereas diabetes mellitus (DM), hypertension (HT), and chronic kidney disease (CKD) were considered as mediators, and CVEs (i.e., fatal and non-fatal coronary artery disease or stroke) were considered as the outcomes. The prevalence of BMI ≥ 23 kg/m², DM, HT, and CKD were 62.7%, 7.8%, 28.1% and 11.8% respectively. During an average of 17.2 ± 5.5 years follow-up, subjects with BMI ≥ 23 kg/m² compared with those with lower BMIs more frequently developed CVEs (9.4 vs 6.2%, P < 0.001). The effects of BMI ≥ 23 kg/m² on CVEs were mediated indirectly through DM and HT with significant ORs of 1.61 (1.34, 2.09) and 1.57 (1.39, 1.80), respectively. The indirect effect of CKD on CVEs was significantly increased if mediated through DM → HT or HT [ORs of 1.17 (1.09, 1.32) and 1.20 (1.10, 1.32), respectively]. Subjects with excess body weight were prone to develop CVEs which were mediated indirectly through DM and HT. The effect of CKD on CVEs was small but enhanced if it occurred as a complication of DM or HT.