Association of prior statin therapy with cytokine profiles and outcomes in patients hospitalized with community acquired pneumonia

Introduction

Two small studies found prior statin use was associated with decreased ICU admission and severe sepsis in patients hospitalized with bacterial infection and decreased mortality in bacteremic patients. These effects were postulated to be due to anti-inflammatory effects of statins. We examined prior statin use, plasma cytokine levels, and outcomes in a large cohort of patients hospitalized with community acquired pneumonia (CAP).

Hypothesis

We hypothesized that prior statin use would be associated with: ICU admission, severe sepsis, and hospital mortality; and altered plasma cytokine levels.

Methods

This study was part of Genetic and Inflammatory Markers of Sepsis (GenIMS), a prospective observational cohort study of patients presenting to the Emergency Department with CAP in 28 US hospitals. Demographics, illness severity, and statin use within 7 days of presentation were determined at baseline and patients were followed to determine rates of hospital and ICU admission, severe sepsis, and hospital mortality. Plasma cytokine levels (tumor necrosis factor, IL-6, IL-10) were obtained daily in hospitalized patients. Outcomes were compared for prior statin (S) versus no statin (No S) use in all hospitalized CAP patients and in those who developed severe sepsis. Cytokine levels were assessed using a mixed-model longitudinal analysis.

Results

Of the 2320 patients enrolled, there were 1895 hospitalized with confirmed CAP. Of those, there were 426 (22.5%) S and 1469 (77.5%) No S patients. S patients were older (72.2 vs 66.5 years, P < 0.001) and sicker, with higher comorbidity (2.2 vs 1.9, P = 0.003) and APACHE III (58.2 vs 55.7, P = 0.01) scores. S patients had increased rates of severe sepsis (51.9% vs 45.7%, P = 0.03), but similar ICU admission (18.3% vs 15.2%, P = 0.13) and hospital mortality (3.3% vs 5.0%, P = 0.14). After adjustment for age, gender, PSI, comorbidity, chronic organ dysfunction, SOFA, and APACHE III scores, S patients had greater odds of ICU admission (odds ratio [OR] 1.44, P = 0.02), but not severe sepsis (OR 1.19, P = 0.20) or mortality (OR 0.71, P = 0.28). Among those with severe sepsis, there were 221 (24.7%) S and 672 (75.3%) No S patients, with no baseline difference between groups except for slightly less chronic organ dysfunction in S patients (P = 0.01). S patients trended toward lower mortality (6.3% vs 10.7%, P = 0.056) in univariate analysis, but not after adjusting for baseline covariates (OR 0.68, P = 0.23). Among those with severe sepsis, IL-10 (P = 0.03) and tumor necrosis factor (P = 0.03), but not IL-6 (P = 0.91) were significantly lower in S patients. There were no cytokine differences in the larger hospitalized CAP cohort.

Conclusions

In a large cohort of hospitalized CAP patients, both proinflammatory and anti-inflammatory cytokine levels were lower in S patients with severe sepsis, but we were unable to confirm the protective effect of prior statin use for clinical outcomes seen in smaller studies.