Interleukin–6, but Not Other Inflammatory Biomarkers, Is Associated With Cardiovascular Events Independent of Hypertensive–mediated Organ Damage in a Primary Prevention Population

Background Chronic low–grade inflammation is increasingly recognized as a key determinant of cardiovascular (CV) risk, beyond traditional risk factors. However, the relative role of different inflammatory biomarkers in relation to hypertension–mediated organ damage (HMOD) and long–term CV outcomes in primary prevention remains incompletely defined. Methods We assessed a panel of inflammatory biomarkers, including high–sensitivity C–reactive protein (hs–CRP), interleukin–6 (IL–6), interleukin–18 (IL–18), osteoprotegerin, calprotectin, and tumor necrosis factor–α (TNF–α), in a primary prevention cohort. Subclinical HMOD was evaluated at the vascular (pulse wave velocity, carotid intima–media thickness and carotid plaque), cardiac (left ventricular mass and function), and renal (estimated glomerular filtration rate) levels. Participants were followed for CV events, all–cause mortality, and the relative composite outcome. Results Among 804 participants (mean age 51.1 ± 13.0 years; 62.4% men), none of the inflammatory biomarkers was independently associated with subclinical HMOD after adjustment for age and sex. During a median follow–up of 10.7 years (I–III quartiles 9.7–11.3), 75 CV events and 38 deaths occurred. IL–6 was the only inflammatory biomarker independently associated with CV events (hazard ratio [HR] 1.15; 95% confidence interval [CI] 1.04–1.26), and with the composite outcome of CV events or all–cause mortality (HR 1.13; 95% CI 1.03–1.23), after adjustment for traditional CV risk factors. Conclusions In a primary prevention population, IL–6—but not other inflammatory biomarkers—was independently associated with long–term CV outcomes, while no biomarker showed an independent association with HMOD. These findings highlight the central role of IL–6 in residual inflammatory CV risk beyond structural organ damage.