Statistical analysis
non-sepsis, sepsis-induced ARDS, illness, ARDS
REGRESSION, SECONDARY, ARDS
To test our hypothesis that mortality would be higher in subjects with lower cholesterol who received a statin, individuals were assigned to a “low cholesterol” or “not-low cholesterol” group defined by lowest quartile of total cholesterol versus the remaining three quartiles. To our knowledge, there is no universally accepted definition of low total cholesterol. In 2018, the global age-standardized mean total cholesterol was 178 mg/dL (95% confidence interval 174–182 mg/dL) for women and 172 mg/dL (95% confidence interval 168–176 mg/dL) for men [Our primary outcome was mortality at 60 days in subjects with sepsis-induced ARDS (the primary outcome in SAILS). We first compared the lowest cholesterol quartile versus all other quartiles in both trials. Available illness severity indices at enrollment were compared using the Wilcoxon rank-sum test. The illness severity score for SAILS was APACHE III, while HARP-2 reported APACHE II and SOFA scores. Mortality at 60 days for those randomized to a statin was compared using Fisher’s exact test. We also compared mortality for subjects in the lowest quartile randomized to statin versus placebo using Fisher’s exact test. Sixty-day mortality was evaluated using logistic regression which included cholesterol (lowest quartile vs. others), randomization to statin, and their interaction term, controlling for age, gender and body mass index (BMI). These covariates were chosen because of impact on total cholesterol levels in general population data [The secondary outcomes included the same Fisher’s exact tests, survival analysis and logistic regression for mortality at 60 days described above, but applied to the entire HARP-2 cohort (given that HARP-2 enrolled subjects with non-sepsis etiologies of ARDS in contrast to only subjects with sepsis-induced ARDS in both trials for the primary outcome). Additionally, we examined the clinical characteristics of low cholesterol in subjects randomized to receive placebo in both trials. Wilcoxon rank-sum tests and Fisher’s exact tests were used for continuous and categorical variables, respectively. The placebo group was used to remove any effect of statin therapy on survival, instead investigating the impact of cholesterol level alone. We assessed mortality at 60 days for patients in the lowest cholesterol quartile versus the top three quartiles using Fisher’s exact test. To increase statistical power, we also evaluated 60-day mortality for all subjects in both trials with cholesterol levels available.A sensitivity analysis was conducted with several additional thresholds for low cholesterol, and these results are presented in Additional file All data analysis was completed with R Studio, Version 1.2.