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 165 ng/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.
Highlights
Proprotein convertase subtilisin/kexin type 9 (PCSK–9) regulates the expression of low-density lipoprotein (LDL) receptors (-R) on hepatocytes [1]
Adults (>18 years) with out-of-hospital cardiac arrest of presumed cardiac cause who had achieved the return of spontaneous circulation (ROSC) at admission to the intensive care unit (ICU) of the Department of Emergency Medicine at the Medical University of Vienna, were prospectively included in this study
The adjusted odds ratios were 4.46 (95%CI 1.61–12.38) for PCSK–9 wearnedm1o.0r4ePfCorsacgoer,ewofh3il–e5se(Ox Rw3a.s2e9l;im1.1in2a–t9e.d62f;rpom= 0th.0e3m). oEdxeple. ctedly, patients with mu3l.t3i.-oMrgoartnalfiatiylure (MOF) were more likely to have an unfavorable neurological outcome
Summary
Proprotein convertase subtilisin/kexin type 9 (PCSK–9) regulates the expression of low-density lipoprotein (LDL) receptors (-R) on hepatocytes [1]. PCSK–9 binds to the LDL-R and facilitates the intracellular degradation of the receptor. Thereby, it reduces hepatic LDL-R expression, LDL uptake and increases circulating LDL [2]. Two anti-PCSK–9 antibodies have been marketed: in the pivotal trials, alirocumab and evolocumab both demonstrated potent lipid-lowering effects and both reduced the risk to develop cardiovascular events in risk populations [5,6]. A recent meta-analysis provides evidence that treatment with one of the two marketed monoclonal PCSK–9 antibodies, alirocumab and evolocumab, significantly improves lipid profiles of patients and reduces the risk of non-fatal major adverse cardiovascular events [7]
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