In this population-based cohort study, ALP was found to be associated with an elevated risk of the UNO in 3 months, independent of age + gender + Weight + Witnessed.Arrest + Bystander.CPR + time.to. ROSC + Epinephrine.total.dose + Out.of.Hospital + Cardiac.Etiology + Shockable.Rhythm + Corticoids + Chronic.Anticoagulation + Chron.Heart.Failure + Hypertension + Coron.Artery.Dis + Diabetes + COPD.Asthma + Previous.Neurol.Disease + Chronic.Renal.Failur + Liver.Cirrhosis + ICU.stay + TTM + IABP + ECMO + Shock + VSP.used + Dobutamine.used + Mechanical.Ventilation.used + CRRT.used + MAP + Lactate + CRP + Creatinine + ScvO2.SvO2 + AST + ALT + LDH + GGT + Total.bilirubin + APTT + PT + INR + Platelets + Proteins + Glucose + pH + PaO2 + PaCO2.We revealed a linear relationship between serum ALP levels and the risk of the UNO in 3 months. The relationship was characterized as follows: A 7.7% higher risk of UNO in 3 months, associated with a 10 U/L increased in serum ALP. In addition, in the multi-factor analysis (Table 2), we could also find that the relationship between the ALP and the prognostic becomes more obvious as the ALP increases,especially obvious in the T3 group.After adjustment, ALP increased 1 unit, the prognosis risk increased 74.07% (1.7407 (0.7676,3.9472)), while the corresponding T2 groups increased only 10.29% (1.1029 (0.5364,2.2674)).In the stratified analysis, we observed significant associations in patients with non-hypertension, but not in patients with hypertension.Interestingly, we also observed significant associations in the non-Dobutamine.used group, despite no interaction between ALP and the results.We found no interaction in the shock, cardiac.Etiology,shockable.Rhythm groups, indicating that the relationship between ALP and the results was unrelated to the cardiogenic cause, defibrillation rhythm, and shock.
ALP, an enzyme first discovered in the 1920 s, has been evaluated as a potential biomarker for many diseases6.The rise in ALP is a common manifestation of ischemic stroke. It has been made clear that ALP is an independent risk factor for the adverse prognosis of ischemic stroke and has a positive correlation13, 23, 24.Neurodysfunction of ischemic stroke mainly comes from ischemic damage of nerve cells.The injury to brain cells in patients after CA also mainly stems from ischemic and hypoxia injury during cardiac arrest and reperfusion injury after recovery.It shows that the two have some similarities, and our results suggest that the positive correlation of ALP with bad prognosis also agrees with previous studies.
The reasons for ALP rise in CA may be the following:First, some basic studies have shown that ALP activity can be expressed in brain endothelial cells and neurons.8, 9.An association between ALP and minor cerebrovascular disease was found by Lee et al10.When blood supply disorder occurs in the arterial artery, the corresponding brain tissue develops ischemia, damage or even necrosis, and blood ALP increases.The greater the infarct range, the higher the ALP, the more obvious the corresponding nerve function damage. Brichacek et al. also found that ALP caused adverse outcomes by playing a role in the broken blood-brain barrier (BBB), neurological inflammation, and vascular dysfunction in stroke patients6.Because small areas of cerebral infarction are often associated with a neurologic prognosis, this explains why OR increases in ALP > 91 and ALP < 64.Second, serum ALP levels are also associated with inflammation or malnutrition. Similar to the C-reactive protein, ALP also reflects the inflammatory state of the body25.The reperfusion after prolonged cardiac arrest ischemia leads to increased inflammatory cytokines26.Due to the systemic inflammatory response, patients after CA showed a sepsis-like state.In fact, in this study, elevated ALP levels were associated with CRP levels and several nutritional states.However, we found that the elevation of ALP levels and the adverse stroke outcome remained stable after adjusting these indicators.Thus, it is unlikely for the link between ALP and adverse outcomes of stroke to rely solely on malnutrition and inflammation.However, some studies conclude not exactly the same as ours.It was found that ALP was not significantly associated with neurofunctional results from a year later20.The reason may be the grouping of ALP was different.Their study was based on the ALP grouping of the ending, while our research was based on grouping by the ALP value.
In the subgroup analysis,Our subgroup analysis revealed that the association between ALP and risk of UNO in 3 months existed between the layers except hypertension.It showed that ALP concentration was positively associated with UNO in 3 months in nonhypertension (OR 1.018(1.0041,1.032)), P for trend 0.01083)However, the associations were not observed in hypertensions.The reasons for the unclear relationship between ALP and the adverse outcome in the hypertension group were unclear.It has been proposed that there are various complications in patients with hypertension, so TTM is associated with good neurological recovery in patients without hypertension, but not in patients with hypertension27, 28.Eujene Jung suggests that hypertension does not have an adverse effect on the prognosis of patients with cardiac arrest27.This may be associated with hypertension patients with greater awareness of activating emergency medical services (EMS) with ischemic symptoms.And lead to short cardiac arrest to EMS recovery29.Another possibility is that the effects of hypertension drugs can be taken into account.There have been studies that calcium channel blockers can be treated in ischemic pretreatment reserved with cardiac arrest and angiotensin converting enzyme inhibitors to reduce recurrent myocardial infarction and ischemia30, 31.In addition, most patients with hypertension have cerebrovascular sclerosis, which involves too many diseases32.In the future, it is necessary to study the factors related to HTN which improve the favorable neurological outcome of CA patients.
This study has several limitations. First, this is a population-based observational study, not an intervention study. There are likely to be significant potential biases that were not considered.Second,because we studied the population of patients who recovered heart breathing after CA, we excluded the early death (n = 51) to reduce bias. Also, the dependent variable we studied ALP is one of the liver enzymes, so we excluded the absence of data on liver transaminases, coagulation, and/or total bilirubin (n = 10). This leads to a reduced number of studies, but after regression analysis and hierarchical analysis,the results remain robust and reliable. Third, compared to previous studies, we lack variate data like hypertension medication, however, our data have 48 covariates that reduce the bias as possible, and our results all show consistency after adjusting the covariates, which also shows that our results are stable.These limitations should be considered in future studies.