The Prognostic Value of Serum Interleukin-6 Concentrations for 9 Cardiovascular and Mortality Outcomes (JACC July 2026-2)-Article: The Prognostic Value of Serum Interleukin-6 Concentrations for 9 Cardiovascular and Mortality Outcomes

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This study examined whether blood interleukin-6 (IL-6), an inflammatory marker, predicts future cardiovascular events and death. Researchers pooled individual-level data from 14 U.S.-based community cohorts in the Cross Cohort Collaboration, including 59,396 adults followed for up to about 16 years. They assessed nine outcomes: myocardial infarction, stroke, atrial fibrillation, heart failure, total coronary heart disease, total cardiovascular disease, all-cause mortality, cardiovascular mortality, and coronary heart disease mortality.<br /><br />Key findings showed that higher IL-6 levels were consistently linked to higher risk for all nine outcomes in a dose-response pattern. The strongest association was for coronary heart disease–specific mortality, while the weakest was for myocardial infarction. Results remained robust after adjusting for traditional cardiovascular risk factors and hsCRP, another common inflammatory biomarker. IL-6 was generally more strongly associated with outcomes than hsCRP, and adding IL-6 to clinical prediction models modestly improved risk discrimination for most outcomes.<br /><br />The associations were consistent across important subgroups, including people with chronic kidney disease, diabetes or prediabetes, elevated hsCRP, obesity, older age, and those with existing cardiovascular disease. Some interactions suggested even stronger associations in certain high-risk groups, especially for mortality outcomes.<br /><br />The authors conclude that IL-6 is a broadly relevant upstream inflammatory biomarker of cardiovascular risk. While it is not ready for routine clinical use, the findings support ongoing efforts to develop IL-6–targeted therapies and suggest IL-6 may help identify people at particularly high inflammatory cardiovascular risk.

Meta Tag

Concept Interleukin-6

Concept Prospective Cohort Study

Concept Myocardial Infarction

Concept Stroke

Concept Heart Failure

Keywords

interleukin-6

IL-6

inflammation

cardiovascular risk

myocardial infarction

stroke

heart failure

atrial fibrillation

mortality

biomarker

Interleukin-6

Prospective Cohort Study

Myocardial Infarction

Stroke

Heart Failure