Patients with sepsis with a high ratio of visceral adipose tissue (VAT) to subcutaneous adipose tissue (SAT) have increased mortality. Our goal was to investigate the mechanism of this effect, noting that low LDL levels are also associated with increased sepsis mortality. Accordingly we tested for association between VAT/SAT, low-density lipoprotein (LDL) levels, and mortality. Then we examined the effect of statin treatment, which decreases LDL production, and the effect of PCSK9 genotype, which increases LDL clearance. Low LDL levels per se are not simply associated with decreased sepsis survival because lowering LDL levels by inhibiting LDL production (statin treatment) is associated with adverse outcomes, while increased LDL clearance (PCSK9 loss-of-function genotype) is associated with improved outcomes in patients with low VAT/SAT.

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