Inflammatory markers and risk of cerebrovascular events in patients initiating dialysis

Abstract

Background and objectives: Stroke remains a leading cause of morbidity and mortality for patients on dialysis; however, its risk factors in this population and measures to prevent it are not well understood.

Design, setting, participants, & measurements: We investigated whether inflammation was associated with cerebrovascular events in a national US cohort of 1041 incident dialysis patients enrolled from October 1995 to June 1998 and followed until January 31, 2004. Incident cerebrovascular events were defined as nonfatal (hospitalized stroke, carotid endarterectomy) and fatal (stroke death) events after dialysis initiation. With Cox proportional hazards regression analysis accounting for the competing risk of nonstroke death, we assessed the independent event risk associated with baseline levels of multiple inflammatory markers (high-sensitivity C-reactive protein [hsCRP], interleukin-6 (IL-6), matrix metalloproteinase-3 [MMP-3], and P-selectin) and hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) use, which may have pleiotropic inflammatory effects.

Results: 165 patients experienced a cerebrovascular event during 3548 person-years of follow-up; overall incidence rate was 4.9/100 person-years. None of the inflammatory markers were associated with cerebrovascular event risk (adjusted hazard ratios [HRs] per log unit [95% confidence interval]: hsCRP, 0.97 [0.85 to 1.11]; IL-6, 1.04 [0.85 to 1.26]; MMP-3, 1.02 [0.70 to 1.48]; P-selectin, 0.98 [0.57 to 1.68]). Statin use was also not associated with significant risk of events in unadjusted (HR 1.07 [0.69 to 1.68]) or propensity-score adjusted analyses (HR 0.98 [0.61 to 1.56]).

Conclusions: In conclusion, neither inflammatory markers nor statin use was associated with risk of cerebrovascular events. Further studies are needed to understand the pathophysiology and prevention of stroke in patients on dialysis.

Figure 1.

Distribution of baseline inflammatory markers in incident dialysis patients. Markers measured a median of 1.22 to 1.35 months after study enrollment. For hsCRP, n = 866. For IL-6, n = 865. For MMP-3, n = 818. For P-selectin, n = 819. *Above the linear range of the assay. IQR, interquartile range.

Figure 2.

Time to first cerebrovascular event in incident dialysis patients, by statin use. *Adjusted hazard ratio (aHR) of cerebrovascular events by statin use from competing risk model accounting for death from causes other than stroke, adjusted for age, gender, race, baseline dialysis modality, and propensity to use statins score.