Muhammad Imtiaz Ahmad, Parag Chevli, Saeid Mirzai, Jared A Spitz, Garima Sharma, Joao Lima, Khurram Nasir, Michael J Blaha, Neha J Pagidipati, Roger S Blumenthal, Michael D Shapiro
{"title":"心血管-肾脏代谢综合征、炎症生物标志物和心血管预后之间的关联：来自MESA研究的见解","authors":"Muhammad Imtiaz Ahmad, Parag Chevli, Saeid Mirzai, Jared A Spitz, Garima Sharma, Joao Lima, Khurram Nasir, Michael J Blaha, Neha J Pagidipati, Roger S Blumenthal, Michael D Shapiro","doi":"10.1016/j.atherosclerosis.2025.120521","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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.</p>","PeriodicalId":8623,"journal":{"name":"Atherosclerosis","volume":"410 ","pages":"120521"},"PeriodicalIF":5.7000,"publicationDate":"2025-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Association between cardiovascular-kidney-metabolic syndrome, inflammatory biomarkers, and cardiovascular outcomes: Insights from the MESA study.\",\"authors\":\"Muhammad Imtiaz Ahmad, Parag Chevli, Saeid Mirzai, Jared A Spitz, Garima Sharma, Joao Lima, Khurram Nasir, Michael J Blaha, Neha J Pagidipati, Roger S Blumenthal, Michael D Shapiro\",\"doi\":\"10.1016/j.atherosclerosis.2025.120521\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>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).</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusions: </strong>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. 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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.
期刊介绍：
Atherosclerosis has an open access mirror journal Atherosclerosis: X, sharing the same aims and scope, editorial team, submission system and rigorous peer review.
Atherosclerosis brings together, from all sources, papers concerned with investigation on atherosclerosis, its risk factors and clinical manifestations. Atherosclerosis covers basic and translational, clinical and population research approaches to arterial and vascular biology and disease, as well as their risk factors including: disturbances of lipid and lipoprotein metabolism, diabetes and hypertension, thrombosis, and inflammation. The Editors are interested in original or review papers dealing with the pathogenesis, environmental, genetic and epigenetic basis, diagnosis or treatment of atherosclerosis and related diseases as well as their risk factors.
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