Abstract
PURPOSE: We sought to investigate the joint association of systemic inflammation and atherogenic dyslipidemia with cardiometabolic disease (CMD) and whether the temporal relationship between them is associated with risk of CMD. PATIENTS AND METHODS: This prospective cohort study included 78,206 participants without history of cardiovascular disease and diabetes mellitus at study entry in 2006. Systemic inflammation and atherogenic dyslipidemia were evaluated by C-reactive protein (CRP) and atherogenic index of plasma (AIP), respectively. Participants were categorized into six groups according to their CRP level (<1, 1-3, or ≥3 mg/L) and AIP level (<0.1 or ≥0.1). We used Cox proportional hazard regression to calculate the hazard ratios and 95% confidence intervals (CI) for incident CMD. The temporal relationship between increased CRP and elevated AIP and the association of this temporal relationship with subsequent CMD risk were assessed by cross-lagged analysis and mediation analysis in the 53,713 participants who attended the resurvey in 2010. RESULTS: Increased CRP and elevated AIP were additively associated with a higher risk of CMD, where participants with a CRP of ≥3 mg/L and an AIP of ≥0.1 had 64% higher risk compared with those with low CRP and AIP values (adjusted HR: 1.64, 95% CI, 1.55-1.74). In the cross-lagged analysis, the standard regression coefficient from baseline CRP to follow-up AIP was 0.069 (95% CI, 0.061-0.077), which was greater than that from baseline AIP to follow-up CRP 0.014 (95% CI, 0.005-0.023). Furthermore, in the mediation analysis, 21.52% (95% CI 17.71-25.34) of the total association between CRP and incident CMD was mediated through AIP. CONCLUSION: Systemic inflammation and atherogenic dyslipidemia were jointly associated with increased risk of CMD. Systemic inflammation might precede atherogenic dyslipidemia, and atherogenic dyslipidemia partly mediated the association between systemic inflammation and incident CMD.