Chronic inflammation spikes during the earliest phase of cardiovascular-kidney-metabolic syndrome

In a nationally representative sample of more than 4,000 American adults, a common marker of inflammation was nearly doubled in people in the first stage of the syndrome, defined by excess or unhealthy body fat, compared with those with no metabolic risk factors.

A new analysis of US national health data finds that high-sensitivity C-reactive protein (hs-CRP), a blood marker of inflammation, rises across the stages of cardiovascular-kidney-metabolic (CKM) syndrome, with the largest increase at the earliest stage. The study, a collaboration between researchers at the University of Eastern Finland and Rutgers Robert Wood Johnson Medical School, was published open access in the European Journal of Preventive Cardiology and presented at the European Society of Cardiology Congress 2026.

The American Heart Association introduced CKM syndrome in 2023 to describe how heart disease, kidney disease, obesity and type 2 diabetes are linked. It runs from stage 0 (no risk factors) and stage 1 (excess or unhealthy body fat), through stage 2 (conditions such as high blood pressure, diabetes or kidney disease), to stages 3 and 4 (early and established heart disease).

The team analyzed data from 4,315 adults in the 2015 to 2018 National Health and Nutrition Examination Survey (NHANES). Participants' average age was 48 years, and half were women. Average hs-CRP nearly doubled between stage 0 and stage 1, the largest change seen across all stages, and crossed 2 mg/L, the level commonly used to signal increased cardiovascular risk. From stage 1 onward, average levels stayed above this threshold, rising only modestly at stage 2 before levelling off.

The findings suggest that inflammation is already present at the first stage of CKM syndrome. The authors note that hs-CRP is best understood as an easy-to-measure warning sign of underlying inflammation rather than a treatment target in itself. Because the study looked at a single point in time, it shows an association but cannot prove that inflammation drives the syndrome forward. Studies that follow people over time, and trials testing early prevention, are now needed.

"What stood out to us is that inflammation was already elevated at the very first stage, before people had developed diabetes, kidney disease or heart disease, which is where we may have the most room to change the course," said lead author Douglas R. Corsi, MD, a physician at Rutgers Robert Wood Johnson Medical School and a PhD student at the University of Eastern Finland.

This makes a strong case for early prevention, either by treating inflammation directly, or by reducing excess body fat through lifestyle and dietary changes while using an inexpensive blood test like hs-CRP to track the risk."

Andrew Agbaje, MD, MPH, PhD, study's senior author, Associate Professor (Docent) of Clinical Epidemiology and Child Health, University of Eastern Finland