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

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.

SUBMITTER: Merrelaar A

PROVIDER: S-EPMC7465607 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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

Merrelaar Anne A Buchtele Nina N Schriefl Christoph C Clodi Christian C Poppe Michael M Ettl Florian F Herkner Harald H Jilma Bernd B Schwameis Michael M Schoergenhofer Christian C

Journal of clinical medicine 20200811 8

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 (<i>n</i> = 79). PCSK-9 levels were measured on admission ...[more]

PMID: 32796672

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Project description:Little evidence guides the appropriate duration of resuscitation in out-of-hospital cardiac arrest, and case features justifying longer or shorter durations are ill defined. We estimated the impact of resuscitation duration on the probability of favorable functional outcome in out-of-hospital cardiac arrest using a large, multicenter cohort.This was a secondary analysis of a North American, single-blind, multicenter, cluster-randomized, clinical trial (ROC-PRIMED [Resuscitation Outcomes Consortium Prehospital Resuscitation Using an Impedance Valve and Early Versus Delayed]) of consecutive adults with nontraumatic, emergency medical services-treated out-of-hospital cardiac arrest. Primary exposure was duration of resuscitation in minutes (onset of professional resuscitation to return of spontaneous circulation [ROSC] or termination of resuscitation). Primary outcome was survival to hospital discharge with favorable outcome (modified Rankin scale [mRS] score of 0-3). Subjects were additionally classified as survival with unfavorable outcome (mRS score of 4-5), ROSC without survival (mRS score of 6), or without ROSC. Subject accrual was plotted as a function of resuscitation duration, and the dynamic probability of favorable outcome at discharge was estimated for the whole cohort and subgroups. Adjusted logistic regression models tested the association between resuscitation duration and survival with favorable outcome.The primary cohort included 11?368 subjects (median age, 69 years [interquartile range, 56-81 years]; 7121 men [62.6%]). Of these, 4023 (35.4%) achieved ROSC, 1232 (10.8%) survived to hospital discharge, and 905 (8.0%) had an mRS score of 0 to 3 at discharge. Distribution of cardiopulmonary resuscitation duration differed by outcome (P<0.00001). For cardiopulmonary resuscitation duration up to 37.0 minutes (95% confidence interval, 34.9-40.9 minutes), 99% with an eventual mRS score of 0 to 3 at discharge achieved ROSC. The dynamic probability of an mRS score of 0 to 3 at discharge declined over elapsed resuscitation duration, but subjects with initial shockable cardiac rhythm, witnessed cardiac arrest, and bystander cardiopulmonary resuscitation were more likely to survive with favorable outcome after prolonged efforts (30-40 minutes). After adjustment for prehospital (odds ratio, 0.93; 95% confidence interval, 0.92-0.95) and inpatient (odds ratio, 0.97; 95% confidence interval, 0.95-0.99) covariates, resuscitation duration was associated with survival to discharge with an mRS score of 0 to 3.Shorter resuscitation duration was associated with likelihood of favorable outcome at hospital discharge. Subjects with favorable case features were more likely to survive prolonged resuscitation up to 47 minutes.URL: http://clinicaltrials.gov. Unique identifier: NCT00394706.

Project description:Importance:Out-of-hospital cardiac arrest is a common scenario facing prehospital emergency medical services (EMS) professionals and nearly always involves either manual or mechanical cardiopulmonary resuscitation (CPR). Mechanical CPR devices are expensive and prior clinical trials have not provided evidence of benefit for patients when compared with manual CPR. Objectives:To investigate the use of mechanical CPR in the prehospital setting and determine whether patient demographic characteristics or geographical location is associated with its use. Design, Setting, and Participants:A retrospective cross-sectional study was performed using the 2010 through 2016 National Emergency Medical Services Information System data. Participants included all patients identified by EMS professionals as having out-of-hospital cardiac arrest. Main Outcomes and Measures:Use of CPR, categorized as manual or mechanical. Results:From 2010 to 2016, 892?022 patients (38.6% female, 60.4% male, missing for 1%; mean [SD] age, 61.1 [20.5] years) with out-of-hospital cardiac arrest were identified by EMS professionals. Overall, manual CPR was used for 618?171 patients (69.3%) and mechanical CPR was used for 45?493 patients (5.1%). The risk-standardized rate of mechanical CPR use, accounting for patient demographic and geographical characteristics, rose from 1.9% in 2010 to 8.0% in 2016 (P?<?.001). In multivariable analyses, use of mechanical CPR devices was increasingly likely over time among patients identified with out-of-hospital cardiac arrest treated by EMS professionals, increasing from an adjusted odds ratio of 1.58 (95% CI, 1.42-1.77; P?<?.001) when comparing 2011 with 2010, to an adjusted odds ratio of 11.32 (95% CI, 10.22-12.54; P?<?.001) when comparing 2016 with 2010. In addition, several other patient demographic and geographical characteristics were associated with a higher likelihood of receiving mechanical CPR, including being 65 years or older, being male, being Hispanic, as well as receiving treatment in the Northeast Census Region, in a suburban location, or in a zip code with a median annual income greater than $20?000. Conclusions and Relevance:Mechanical CPR device use increased more than 4-fold among patients with out-of-hospital cardiac arrest treated by EMS professionals. Given the high costs of mechanical CPR devices, better evidence is needed to determine whether these devices improve clinically meaningful outcomes for patients treated for out-of-hospital cardiac arrest by prehospital EMS professionals to justify the significant increase in their use.

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

Publications

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

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