Association between cardiovascular-kidney-metabolic syndrome, inflammatory biomarkers, and cardiovascular outcomes: Insights from the MESA study.

BACKGROUND: This study investigated the association between cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 and atherosclerotic cardiovascular disease (ASCVD) and heart failure (HF), as well as whether this association varies by interleukin-6 and high-sensitivity C-reactive protein (hsCRP). METHODS: 6579 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) were included. Restricted mean survival time (RMST) differences in ASCVD and HF-free survival by CKM syndrome stage, stratified by inflammatory markers, were estimated. RESULTS: Over a median follow-up of 17.5 years (IQR: 10.5-18.4 years), participants with CKM stage 3 demonstrated significantly shorter ASCVD-free survival compared to stage 0 (-1.94 years; 95 % CI: -2.27, -1.61). Subgroup analysis by IL-6 levels demonstrated differential RMST across CKM stages, with participants having above-median IL-6 levels showing greater survival reduction (-2.5 years; 95 % CI: -3.50, -1.85) than those with below-median levels (-1.46 years; 95 % CI: -1.84, -1.07) (interaction p = 0.002). For heart failure outcomes, categorization by IL-6 levels displayed similar patterns by CKM stage (interaction p = 0.006). Among participants with elevated IL-6, both CKM stages 2 and 3 were associated with reduced HF-free survival (-0.40 years [95 % CI: -0.69, -0.01], and -0.87 years [95 % CI: -1.18, -0.55], respectively). Conversely, participants with lower IL-6 levels showed a significant reduction in HF-free survival only at the CKM stage 3 level (-0.36 years: 95 % CI: -0.57, -0.14). hsCRP stratification yielded comparable results but without significant interactions for either cardiovascular outcome. CONCLUSIONS: These findings suggest that systemic inflammation, as measured by IL-6, may modify the risk of ASCVD and HF associated with CKM syndrome. Therefore, IL-6 measurement could potentially refine risk stratification and prognosis of CKM syndrome stages. However, further studies are needed to assess the clinical relevance of this approach.

Duke Scholars

Author Neha Pagidipati Medicine, Cardiology