Risk factors for recurrent cardiovascular events in CKD: results from the KNOW-CKD study

Chronic kidney disease (CKD) markedly increases cardiovascular (CV) risk, and some patients experience recurrent CV events over time. Analyses restricted to time-to-first event may therefore underestimate the total CV burden. We evaluated determinants of both first and recurrent non-fatal CV events in CKD.

We analyzed 2099 non-dialysis participants with CKD enrolled in the prospective KNOW-CKD cohort. CV events were adjudicated and included myocardial infarction, stroke, heart failure, coronary or peripheral revascularization, and clinically significant arrhythmias. Predictors of the first event were assessed using Cox proportional hazards models. Recurrent-event risk was evaluated using Andersen-Gill, Prentice-Williams-Peterson total-time and gap-time models, and shared-frailty models, complemented by mean cumulative function analyses.

Over a median follow-up of 8.29 years, 203 participants (9.7%) experienced at least one non-fatal CV event (158 had one event, 39 had two, and 6 had three). Participants with baseline CV disease or diabetes exhibited substantially higher cumulative event burdens. Older age, diabetes, prior CV disease, higher C-reactive protein (CRP), albuminuria, and lower body mass index (BMI) were consistently associated with recurrent events across models; CRP and albuminuria showed relatively stronger associations with recurrence than with the first event.

In CKD, recurrent CV risk is driven not only by traditional factors, particularly diabetes, but also by markers of vascular injury and inflammation. Strategies targeting both metabolic and inflammatory pathways may be critical to reducing recurrent CV burden.