# Temporal relationship between inflammation and metabolic disorders and its influence on atherosclerotic cardiovascular disease

## TL;DR

The study finds that inflammation and metabolic disorders influence each other over time, with inflammation preceding metabolic issues, and both together increasing heart disease risk, especially in younger and low-risk individuals.

## Contribution

This study reveals a bidirectional but inflammation-leading temporal relationship between inflammation and metabolic disorders, and their combined impact on atherosclerotic cardiovascular disease risk.

## Key findings

- Inflammation (hsCRP) has a stronger influence on future metabolic disorders (cMetS) than vice versa.
- Combined exposure to high inflammation and metabolic disorders significantly increases ASCVD risk, particularly in younger individuals.
- Low-risk individuals showed greater relative increases in ASCVD risk when exposed to both inflammation and metabolic disorders.

## Abstract

Atherosclerotic cardiovascular disease (ASCVD) is one of the conditions driven by imbalances in inflammatory and metabolic regulation. Although the temporal and causal relationships between inflammation and metabolic disorders are complex, the sequence in which they occur remains unclear. This study aimed to explore the temporal relationship between inflammation [high-sensitivity C-reactive protein (hsCRP)) and metabolic disorders (Continuous Metabolic syndrome score (cMets)] and their cumulative joint effects on ASCVD.

This prospective cohort study was conducted in two parts. First, a longitudinal analysis was performed on 62,296 participants over a 4.05-year follow-up period using a cross-lagged panel model to investigate the directional relationship between hsCRP and cMetS. Second, after excluding 3,619 participants with a history of ASCVD, the remaining individuals were categorized into four groups to examine the time-weighted cumulative joint exposure of hsCRP and cMetS on the risk of ASCVD and its subtypes using Cox proportional hazards models.

There was a bidirectional relationship between hsCRP and cMetS, The robustness of the pathway from baseline hsCRP to follow-up cMetS (β2 = 0. 05661, 95% CI: 0. 04827–0. 06496, P < 0.01) exceeded that of the reverse pathway from baseline cMetS to follow-up hsCRP (β1 = 0. 05361, 95% CI: 0. 04511–0. 06212, P < 0.01), and the difference in coefficients was statistically significant (P < 0.01). The results of Cox proportional hazards regression analysis found that after adjusting for a variety of factors such as age and sex, compared with G1, G2, G3, and G4 had a higher risk of ASCVD HR (95% CI) were 1.45 (1.30, 1.62), 1.80 (1.66, 1.95), and 2.17 (1.98, 2.37), respectively. A significant interaction was observed between the exposure groups, 10-year ASCVD risk stratification, and age (Pinteraction < 0.01). Stratified by age, the relative risk of ASCVD was found to be much higher in all groups for those aged <60 years than for those aged ≥60 years. Participants categorized as low-risk had greater relative increases in ASCVD relative risk than those in the intermediate- or high-risk groups.

There is a bidirectional relationship between inflammation and metabolic disorders, with inflammation appearing to precede metabolic disorders. Concurrent exposure to both inflammation and metabolic disorders significantly increases the risk of ASCVD, particularly among individuals under 60 years of age and those classified as having a low risk of developing ASCVD in the next 10 years.