Apolipoprotein E Polymorphism
abstract & commentary
Source: Schiefermeier M, et al. Survival and neurological outcome after cardiopulmonary resuscitation. Stroke 2000; 31:2068-2073.
A number of factors contribute to ultimate neurological outcome following pathological asystole. The time that separates heart stoppage to resumption of circulation is paramount, as is whether the arrest occurred outside hospital walls or within. Normal apolipoprotein E 3/3 (apoE 3/3) functions as a major carrier of reparative cholesterol, cholesterol esters and nervous system lipids. It appears that apoE production continuously acts to the integrity of cell membranes. Variant alleles of the apoE 3/3 have been strongly associated with the advent of early Alzheimer disease as well as in worsening the injuries of brain trauma associated with boxing and road accidents. Schiefermeier and associates now report the comparison of neurological outcomes in patients undergoing cardiac asystole and genetically possessing either normal or abnormal variants of the apoE 3/3 gene.
Sixty-five men and 15 women treated at the University of Vienna Hospital suffered cardiac asystole lasting approximately 5-10 minutes with mean returns of spontaneous circulation at 20 minutes. Outcomes among these patients expressing apoE 3/3 (n = 47) compared to nonapoE 3/3 (n = 33) differed significantly. The following paragraphs list specific factors that 1) affected both groups, and 2) expressed differences between the normal and variant apoE groups.
Nonsignificant differences included: age in years; ratios of men or women; blood pH; plasma lactate; similar proportions of asystole time in hospital and without hospital; cardiac causes; cardiac ventricular fibrillation; asystole at onset; time to return to spontaneous circulation (mins); time to regain low cardiac blood flow; time to regain normal flow; and first meaningful reactivity of patients with apoE 3/3 5 ± 6 days compared to in non 3/3 group compared to 10 ± 10 days in the non 3/3 apoE (P = 0.06).
| Table-Outcome for ApoE 3/3 vs. nonApoE 3/3 | ||
| ApoE 3/3 | nonApoE 3/3 | |
| Good (n =) | 26 | 9 |
| Poor | 21 | 24 (P = 0.013) |
| Survivors | 30 | 11 |
| Deaths | 17 | 22 (P = 0.007) |
The Table numbers above describe patients who experienced less than 20 minutes of cardiac arrest and regained spontaneous circulation within 60 minutes. Patients who experienced asystole within the hospital had 12.9 favorable outcome compared with those who suffered cardiac arrest outside the hospital. The table identifies only patients who recovered arrest in less than 20 minutes, whether in or outside of hospital.
Following the tabular calculations, Schiefermeier et al analyzed outcomes of patients carrying the apoE 3/4 or apoE 4/4 genotypes as well as those having apoE 2/3 or 2/2 genotypes. A total of 28% of the patients with the apoE 3/4 or the epoE 4/4 made a good recovery compared to the apoE 3/3 genotype’s outcome of 55% good. Among patients containing apoE 2/3 or 2/2, only 17% survived compared with the 64% survival of patients with the apoE 3/3 genotype. Numbers were too small to make strong probability of the observations.
Commentary
As Schiefermeier et al comment, homozygosity for apoE 3/3 is the most common apoE isoform. They cite the well known association of abnormal forms of this apolipoprotein in the central nervous system. Alzheimer’s disease, cerebral vascular morbidity, brain trauma, and intracerebral hemorrhage walk in its wake. Despite considerable effort, clear explanations of how and why variant genotypes of apoE 3/3 select their targets of vulnerability with different forms of morphological tissue injury. Accordingly, the specific effects in generating injuries to the brain remain not fully understood. —Fred Plum
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