Survival benefit of a low ratio of visceral to subcutaneous adipose tissue depends on LDL clearance versus production in sepsis

Abstract

BackgroundPatients 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.MethodsWe performed retrospective analysis of a cohort of patients with sepsis from a tertiary care adult intensive care unit in Vancouver, Canada, who underwent abdominal computed tomography (CT) (n = 75) for clinical reasons. We compared LDL levels in patients with sepsis according to high versus low VAT/SAT and 90-day survival. We next examined the effects of statin therapy and PCSK9 loss-of-function genotype on survival.ResultsPatients with a low VAT/SAT had increased 90-day survival and were relatively protected against low LDL levels in sepsis compared to high VAT/SAT. Statin treatment abrogated the beneficial effects of low VAT/SAT; eliminating the difference in LDL levels and survival between patients with low and high VAT/SAT. PSCK9 loss-of-function genotype similarly eliminated the increased LDL levels in low VAT/SAT patients but, in contrast, increased the survival advantage of low VAT/SAT compared to high VAT/SAT.ConclusionsLow 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.Electronic supplementary materialThe online version of this article (10.1186/s13054-018-1985-1) contains supplementary material, which is available to authorized users.

Lipid metabolism impairment in patients with sepsis secondary to hospital acquired pneumonia, a proteomic analysis

“…In this context, our results point to LDL as contributing to inflammation and with impaired scavenger capacity. It is noteworthy, however, that while reduced LDL production is related to a complicated prognosis, LDL clearance can improve survival [51].…”

Clinical significance of dynamic variation of low cholesterol and its prognostic value in patients with pyogenic liver abscesses: a retrospective study

“…Serum lipids have been proven to be closely related to sepsis progression. Several studies have shown that patients with sepsis have decreased plasma total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), and subsequently, patients with low TC, HDL-C and LDL-C levels have higher death risk [6][7][8]. Additionally, patients with sepsis also have increased triglycerides (TG) and decreased lipoprotein(a) (Lp(a)) [9].…”

The authors reply

“…To the Editor: T he network meta-analysis done by Ramadanov et al (1), published in a recent issue of Critical Care Medicine, suggests that in patients treated with targeted temperature management at 32-34°C after cardiac arrest, intravascular cooling is the most beneficial cooling method for neurologic outcome and survival, followed by surface cooling with temperature feedback. In their discussion, they noted several adverse events associated with intravascular cooling, including infection, hemorrhage, and catheter-related thrombosis-which can lead to pulmonary embolism (1). We would like to emphasize the importance and frequency of certain complications linked to intravascular cooling that the authors mentioned very briefly (1).…”