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. 2025 Apr;4(4):101640.
doi: 10.1016/j.jacadv.2025.101640. Epub 2025 Mar 3.

Chronic Inflammatory-Related Disease and Cardiovascular Disease in MESA

Evan S Manning  1 , Gautam R Shroff  2 , David R Jacobs Jr  3 , Daniel A Duprez  4
Affiliations

Chronic Inflammatory-Related Disease and Cardiovascular Disease in MESA

Evan S Manning et al. JACC Adv. 2025 Apr.

Abstract

Background: Inflammation plays a role in cardiovascular disease (CVD). We defined various noncardiovascular and noncancer conditions, both infectious and noninfectious, with a common basis of inflammation, collectively termed chronic inflammatory-related disease (ChrIRD). We describe ChrIRD and its interplay with CVD during follow-up in the Multi-Ethnic Study of Atherosclerosis.

Objectives: The aim of the study was to describe ChrIRD, its associations with CVD, and its association with mortality.

Methods: Participants were free of overt CVD at baseline with median 17.9 (Q1-Q3: 14.9-18.6) years of follow-up. ChrIRD was determined by review of hospitalization and death records of International Classification of Diseases codes. CVD diagnosis was adjudicated based on medical records. We performed time-dependent proportional hazard regressions to identify risks related to ChrIRD or CVD events.

Results: MESA (Multi-Ethnic Study of Atherosclerosis) participants (n = 6,791) had a mean age of 62 ± 10 years, with 47% (3,201/6,791) men, 39% (2,617/6,791) White, 28% (1,882/6,791) Black, 22% (1,489/6,791) Hispanic, and 12% (803/6,791) Chinese race/ethnicity. ChrIRD was observed in 29% (1,965/6,791) and CVD in 21% (1,420/6,791); including 11% (761/6,791) with both conditions. Mortality after ChrIRD only was 47% (567/1,204; 95% CI: 44%-49%); after CVD only was 45% (300/659; 95% CI: 41%-49%); and after both conditions was 67% (510/761; 95% CI: 63%-70%). CVD was associated with increased risk of ChrIRD (HR: 1.48; 95% CI: 1.23-1.77) and ChrIRD was associated with increased risk of CVD (HR: 2.23; 95% CI: 1.97-2.52). Baseline inflammatory markers predicted both conditions.

Conclusions: ChrIRD is common, present in all organ systems, and is associated with significant mortality, particularly in combination with CVD. The association between CVD and ChrIRD is bidirectional, and baseline inflammatory markers are associated with ChrIRD and CVD.

Keywords: cardiovascular disease; chronic inflammation; chronic inflammatory-related disease; inflammation biomarkers.

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Conflict of interest statement

Funding support and author disclosures This research was supported by contracts 75N92020D00001, HHSN268201500003I, N01-HC-95159, 75N92020D00005, N01-HC-95160, 75N92020D00002, N01-HC-95161, 75N92020D00003, N01-HC-95162, 75N92020D00006, N01-HC-95163, 75N92020D00004, N01-HC-95164, 75N92020D00007, N01-HC-95165, N01-HC-95166, N01-HC-95167, N01-HC-95168, and N01-HC-95169 from the National Heart, Lung, and Blood Institute, and by grants UL1-TR-000040, UL1-TR-001079, and UL1-TR-001420 from the National Center for Advancing Translational Sciences (NCATS). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Figures

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Graphical abstract
Central Illustration
Central Illustration
Chronic Inflammatory-Related Disease Is a Composite of a Wide Variety of Noncardiovascular, Nondiabetes, and Noncancer Pathologies, Both Infectious and Noninfectious, With the Common Basis of Inflammation as the Fundamental Cause ChrIRD was studied among 6,791 participants in the MESA (Multi-Ethnic Study of Atherosclerosis) over 18 years of follow-up. This clinical disease cluster is common, present in all organ systems, and is associated with high mortality, particularly in combination with cardiovascular disease (CVD). Our data suggest that these conditions share an underlying phenotype of inflammatory dysregulation and that the association between ChrIRD and CVD is bidirectional. ChIRD = chronic inflammatory-related disease.
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