Low PCSK-9 levels Are Associated with Favorable Neurologic Function after Resuscitation from out of Hospital Cardiac Arrest

J Clin Med. 2020 Aug 11;9(8):2606. doi: 10.3390/jcm9082606.

Abstract

Endotoxemia after cardiopulmonary resuscitation (CPR) is associated with unfavorable outcome. Proprotein convertase subtilisin/kexin type-9 (PCSK-9) regulates low-density lipoprotein receptors, which mediate the hepatic uptake of endotoxins. We hypothesized that PCSK-9 concentrations are associated with neurological outcome in patients after CPR. Successfully resuscitated out-of-hospital cardiac arrest patients were included prospectively (n = 79). PCSK-9 levels were measured on admission, 12 h and 24 h thereafter, and after rewarming. The primary outcome was favorable neurologic function at day 30, defined by cerebral performance categories (CPC 1-2 = favorable vs. CPC 3-5 = unfavorable). Receiver operating characteristic curve analysis was used to identify the PCSK-9 level cut-off for optimal discrimination between favorable and unfavorable 30-day neurologic function. Logistic regression models were calculated to estimate the effect of PCSK-9 levels on the primary outcome, given as odds ratio (OR) and 95% confidence interval (95%CI). PCSK-9 levels on admission were significantly lower in patients with favorable 30-day neurologic function (median 158 ng/mL, (quartiles: 124-225) vs. 207 ng/mL (174-259); p = 0.019). The optimally discriminating PCSK-9 level cut-off was 165ng/mL. In patients with PCSK-9 levels ≥ 165 ng/mL, the odds of unfavorable neurological outcome were 4.7-fold higher compared to those with PCSK-9 levels < 165 ng/mL. In conclusion, low PCSK-9 levels were associated with favorable neurologic function.

Keywords: cardiac arrest; cardiopulmonary resuscitation; critical care outcomes; emergency medicine; inflammation mediators; lipid metabolism.