Elevations of Inflammatory and Procoagulant Biomarkers in Elderly Persons With Renal Insufficiency

TLDR

Renal insufficiency is linked to cardiovascular events and mortality, yet the mechanisms underlying this elevated risk remain unclear. This study examined whether renal insufficiency is associated with higher levels of eight inflammatory and procoagulant biomarkers in a cross‑sectional analysis of 5,888 adults aged 65 and older from the Cardiovascular Health Study. Researchers measured CRP, fibrinogen, factor VIIc, factor VIIIc, IL‑6, ICAM‑1, plasmin‑antiplasmin complex, and D‑dimer, defined renal insufficiency by sex‑specific creatinine thresholds, and compared adjusted biomarker means using multivariate linear regression. After adjustment, individuals with renal insufficiency had significantly higher levels of CRP, fibrinogen, IL‑6, factor VIIc, factor VIIIc, plasmin‑antiplasmin complex, and D‑dimer, and these elevations were consistent across cardiovascular disease status, indicating that inflammatory and procoagulant pathways may mediate the increased cardiovascular risk in kidney disease.

Abstract

Renal insufficiency has been associated with cardiovascular disease events and mortality in several prospective studies, but the mechanisms for the elevated risk are not clear. Little is known about the association of renal insufficiency with inflammatory and procoagulant markers, which are potential mediators for the cardiovascular risk of kidney disease.The cross-sectional association of renal insufficiency with 8 inflammatory and procoagulant factors was evaluated using baseline data from the Cardiovascular Health Study, a population-based cohort study of 5888 subjects aged > or =65 years. C-reactive protein, fibrinogen, factor VIIc, and factor VIIIc levels were measured in nearly all participants; interleukin-6, intercellular adhesion molecule-1, plasmin-antiplasmin complex, and D-dimer levels were measured in nearly half of participants. Renal insufficiency was defined as a serum creatinine level > or =1.3 mg/dL in women and > or =1.5 mg/dL in men. Multivariate linear regression was used to compare adjusted mean levels of each biomarker in persons with and without renal insufficiency after adjustment for other baseline characteristics. Renal insufficiency was present in 647 (11%) of Cardiovascular Health Study participants. After adjustment for baseline differences, levels of C-reactive protein, fibrinogen, interleukin-6, factor VIIc, factor VIIIc, plasmin-antiplasmin complex, and D-dimer were significantly greater among persons with renal insufficiency (P<0.001). In participants with clinical, subclinical, and no cardiovascular disease at baseline, the positive associations of renal insufficiency with these inflammatory and procoagulant markers were similar.Renal insufficiency was independently associated with elevations in inflammatory and procoagulant biomarkers. These pathways may be important mediators leading to the increased cardiovascular risk of persons with kidney disease.