Preliminary report on the association of apolipoprotein E polymorphisms, with postoperative peak serum creatinine concentrations in cardiac surgical patients

BACKGROUND: Renal dysfunction after cardiac surgery occurs in up to 8% of patients and is associated with major increases in morbidity, mortality, and cost. Genetic polymorphisms have been implicated as a factor in the progression of chronic renal disease, but a genetic basis for the development of acute renal impairment has not been investigated. The authors therefore tested the hypothesis that apolipoprotein E alleles are associated with different postoperative changes in serum creatinine after cardiac surgery. METHODS: The authors performed a prospective observational study with use of data from 564 coronary bypass surgical patients who were enrolled in an ongoing investigation of apolipoprotein E genotypes and organ dysfunction at a university hospital between 1989-1999. Renal function was assessed among apolipoprotein E genotype groups by comparisons of preoperative (CrPre), peak in-hospital postoperative (CrMax) and perioperative change (DCr) in serum creatinine values. RESULTS: The epsilon4 allele grouping (E2 = 2/2,2/3,2/4; E3 = 3/3; E4 = 3/4,4/4) was associated with a smaller increase in postoperative serum creatinine (perioperative change: E4, +0.17; E3, +0.26; E4, +0.27 mg/dl) and a lower peak postoperative creatinine than the epsilon2 and epsilon3 in univariate and multivariate analysis (peak in-hospital postoperative serum creatinine multivariate P = 0.015 vs. epsilon3, P = 0.038 vs. epsilon2). There was no difference in baseline creatinine among allele groups. CONCLUSIONS: Inheritance of the apolipoprotein epsilon4 allele is associated with reduced postoperative increase in serum creatinine after cardiac surgery, compared with the epsilon3 or epsilon2 allele. This is the first report of a possible genetic basis for acute renal impairment. These data may contribute to renal risk stratification for cardiac surgery and raise questions regarding apolipoprotein E and the pathophysiology of acute renal injury.     

Apolipoprotein E Genotype and Cognitive Dysfunction after Noncardiac Surgery

Background: Apolipoprotein E is important in recovery after neuronal damage. The [epsilon]4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the [epsilon]4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery.

Methods: In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the [epsilon]4 allele (yes/no) and other possible risk factors.

Results: The [epsilon]4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the [epsilon]4 allele and 9.9% in patients without the [epsilon]4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the [epsilon]4 allele and in 8.4% of patients without the [epsilon]4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the [epsilon]4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57).     

Preliminary report on the interaction of apolipoprotein E polymorphism with aortic atherosclerosis and acute nephropathy after CABG

Background

Renal dysfunction is a serious complication of cardiac surgery that is highly associated with short- and long-term adverse outcome. While the apolipoprotein E (APOE) ?4 allele has been linked to the occurrence of both postcardiac surgery acute renal injury (?4 favorable) and ascending aortic arteriosclerosis (?4 unfavorable), the role of ?4 in the relationship between these two conditions is unknown. We hypothesized that patients with and without the ?4 allele (E4/non-E4) would have different associations between atheroma burden and postoperative renal dysfunction.

Methods

Ascending, arch, and descending aorta atheromatous burden and APOE status were evaluated for 130 coronary bypass patients. Multivariable analyses were performed for aortic regions to assess the relationship of atheroma burden and APOE ?4 status with peak in-hospital postoperative serum creatinine. All p < 0.05 were considered significant.

Results

We found an interaction between E4 status (E4/non-E4; 24/106) and atheroma burden, with a much greater predicted peak in-hospital postoperative serum creatinine for increases in ascending aorta atheroma load for non-E4 patients versus E4 patients (beta coefficient −0.13; p = 0.002). We also confirmed the association between ascending aorta atheroma and peak creatinine (beta coefficient 0.11; p = 0.0008), after controlling for E4 status, preoperative creatinine, and the E4-atheroma interaction.

Conclusions

Equivalent ascending aortic atheroma burden is associated with a greater susceptibility to postoperative renal injury among patients undergoing cardiac operation who lack the APOE ?4 allele. Findings may be attributable to APOE-related differences in inflammation, susceptibility to atheroma detachment (eg, during operative aortic manipulation), or renal vulnerability to embolic injury.     

Apolipoprotein E epsilon4 allele and neurobehavioral status after on-pump coronary artery bypass grafting

Abstract Background and Aim: The presence of apolipoprotein E epsilon4 allele is being considered as a risk factor for cognitive decline after cardiac surgery. We sought the effect of apolipoprotein E epsilon4 allele on neurobehavioral status after on-pump coronary artery bypass grafting. Methods: Prior to the operation, neurologic examination and neurobehavioral cognitive status test (COGNISTAT) were performed. Both procedures were repeated on the day of discharge and 3 months after surgery. Apolipoprotein E epsilon4 allele positive and apolipoprotein E epsilon4 allele negative patients' performance on COGNISTAT were compared. Results: There was no statistically significant demographic and operative data difference between two groups. No neurological impairment was observed on examinations. There was no statistically significant neurocognitive decline difference between two groups' postoperative performances. Conclusions: It seems that apolipoprotein E epsilon4 allele may not affect neurobehavioral status in the intermediate period after on-pump coronary artery bypass grafting.     

Apolipoprotein E genotype and cognitive dysfunction after noncardiac surgery

BACKGROUND: Apolipoprotein E is important in recovery after neuronal damage. The epsilon4 allele of the apolipoprotein E gene has been shown as a risk factor for Alzheimer disease, poor outcome after cerebral injury, and accelerated cognitive decline with normal aging. The authors hypothesized that patients with the epsilon4 allele would have an increased risk of postoperative cognitive dysfunction (POCD) after noncardiac surgery. METHODS: In a multicenter study, a total of 976 patients aged 40 yr and older undergoing noncardiac surgery were tested preoperatively and 1 week and 3 months after surgery with a neuropsychological test battery comprising seven subtests. POCD was defined as a decline in test performance of more than 2 SD from the expected. Apolipoprotein E genotypes were determined by blood sample analysis at a central laboratory. Multivariate logistic regression analysis with POCD as the dependent variable assessed presence of the epsilon4 allele (yes/no) and other possible risk factors. RESULTS: The epsilon4 allele was found in 272 patients. One week after surgery, the incidence of POCD was 11.7% in patients with the epsilon4 allele and 9.9% in patients without the epsilon4 allele (P = 0.41). Three months later, POCD was found in 10.3% of patients with the epsilon4 allele and in 8.4% of patients without the epsilon4 allele (P = 0.40). Multivariate logistic regression analysis did not identify the epsilon4 allele as a risk factor at 1 week (P = 0.33) or 3 months (P = 0.57). CONCLUSIONS: The authors were unable to show a significant association between apolipoprotein E genotype and POCD, but statistical power was limited because of a lower incidence of POCD than expected.     

Influence of apolipoprotein E polymorphisms on serum creatinine levels and predicted glomerular filtration rate in healthy subjects.

BACKGROUND: There are conflicting results regarding the effect of apolipoprotein (ApoE) polymorphisms on the progression of a variety of renal diseases. However, there are no data on the possible effect of the ApoE alleles on serum creatinine levels and predicted glomerular filtration rate (GFR) in healthy subjects. METHODS: 290 apparently healthy individuals were studied. ApoE genotyping was performed by the polymerase chain reaction; the Modification of Diet in Renal Disease equation (MDRD) predicted the GFR. RESULTS: ApoE2 was associated with lower levels of total cholesterol, low-density lipoprotein cholesterol and non-high-density lipoprotein cholesterol, as well as with higher levels of triglycerides in our population. Furthermore, the ApoE2 allele was associated with increased serum creatinine levels compared with both the E3 and E4 alleles (1.04+/-0.13 vs 0.92+/-0.13 vs 0.88+/- 0.11 mg/dl, respectively, P = 0.0077), while the MDRD-predicted GFR was decreased in ApoE2 carriers compared with both E3 and E4 carriers (80.3+/-10.2 vs 88.1+/-9.6 vs 89.3+/-9.7 ml/min/1.73 m(2), respectively, P = 0.031). These observations remained significant statistically even if the effect of ApoE polymorphisms on age- and body-mass index-adjusted serum creatinine and MDRD-predicted GFR was separately analysed in both men and women. Although, ApoE4 carriers tended to exhibit lower levels of serum creatinine and higher values of predicted GFR compared with the E3 carries, these differences did not reach statistical significance. CONCLUSIONS: ApoE2 allele seems to be associated with increased serum creatinine levels and decreased MDRD-predicted GFR in healthy subjects.     

Apolipoprotein A-IV predicts progression of chronic kidney disease: the mild to moderate kidney disease study

It has not been established firmly whether dyslipidemia contributes independently to the progression of kidney disease. Lipid and lipoprotein parameters, including levels of total, HDL, and LDL cholesterol; triglycerides; lipoprotein(a); apolipoprotein A-IV; and the apolipoprotein E and A-IV polymorphisms, were assessed in 177 patients who had mostly mild to moderate renal insufficiency and were followed prospectively for up to 7 yr. Progression of kidney disease was defined as doubling of baseline serum creatinine and/or terminal renal failure necessitating renal replacement therapy. In univariate analysis, patients who reached a progression end point (n = 65) were significantly older and had higher serum creatinine and proteinuria as well as lower GFR and hemoglobin levels. In addition, baseline apolipoprotein A-IV and triglyceride concentrations were higher and HDL cholesterol levels were lower. Multivariate Cox regression analysis revealed that baseline GFR (hazard ratio 0.714; 95% confidence interval [CI] 0.627 to 0.814 for an increment of 10 ml/min per 1.73 m(2); P < 0.0001) and serum apolipoprotein A-IV concentrations (hazard ratio 1.062; 95% CI 1.018 to 1.108 for an increment of 1 mg/dl; P = 0.006) were significant predictors of disease progression. Patients with apolipoprotein A-IV levels above the median had a significantly faster progression (P < 0.0001), and their mean follow-up time to a progression end point was 53.7 mo (95% CI 47.6 to 59.8) as compared with 70.0 mo (95% CI 64.6 to 75.4) in patients with apolipoprotein A-IV levels below the median. For the apolipoprotein E polymorphism, only the genotype epsilon2/epsilon4 was associated with an increased risk for progression. In summary, this prospective study in patients with nondiabetic primary kidney disease demonstrated that apolipoprotein A-IV concentration is a novel independent predictor of progression.     

Apolipoprotein E polymorphism in 385 patients on renal replacement therapy in Sweden

OBJECTIVE: To examine apolipoprotein (apo) E polymorphism and its possible link to kidney disease in all patients receiving renal replacement therapy in our region. MATERIAL AND METHODS: The apo E genotype, plasma (P) lipids, blood pressure and albumin excretion rate were determined retrospectively in 385 patients. RESULTS: No differences in apo E genotype or the allelic frequencies of epsilon2, epsilon3 or epsilon4 were found between the patient group and a control group of 343 healthy individuals. The apo E3/E4 genotype, however, was found in only 1/24 patients with non-insulin-dependent diabetes mellitus (NIDDM), a significantly lower frequency than that seen in the rest of the patient group (p = 0.041). Similarly, the apo E4/E4 genotype was absent in patients with glomerulonephritis (GN) (p = 0.027). The relative frequency of the epsilon4 allele in patients with GN (0.116) was significantly lower than that in the rest of the patients (0.193; p < 0.05) and that in the control group (0.186; p = 0.027). Furthermore, 19/47 patients (40.4%) with autosomal dominant polycystic kidney disease (ADPKD) had the E3/E4 genotype, as compared to 77/338 (22.8%) in the rest of the patient group (p = 0.035; odds ratio 2.07; CI 1.09-3.92). An increase in the relative frequency of the epsilon4 allele was seen in the same diagnostic group: 0.29 vs 0.16 in the rest of the patient group (p = 0.0023). The mean P-cholesterol level in patients with the epsilon4 allele was 5.9 +/- 1.0 mmol/l, compared to 5.0 +/- 1.1 mmol/l in patients without the epsilon4 allele (p = 0.026). CONCLUSIONS: In this study, variations in the frequencies of the apo epsilon4 allele and the apo E3/E4 and E4/E4 genotypes were found in patients with NIDDM, GN and ADPKD. This result may be a consequence of the effects of the apo epsilon4 and epsilon2 alleles on P-cholesterol and remnant lipoprotein levels. The decreased frequency of apo E3/E4 found in patients with NIDDM may be explained by the fact that the epsilon4 allele gives renoprotection against diabetic nephropathy by lowering plasma remnant lipoprotein levels. Conversely, there may be an association between the apo E3/E4 genotype and the epsilon4 allele in patients with ADPKD, due to the effect of the epsilon4 allele in elevating P-cholesterol levels. The most plausible explanation for the absence of the apo E4/E4 genotype and the lower prevalence of the epsilon4 allele in patients with GN, which is known to result in a higher P-cholesterol compared to the epsilon2 and epsilon3 alleles, ought to be an increase in cardiovascular morbidity, which is known to be associated with a higher P-cholesterol level.     

Apolipoprotein E genotype and neurodevelopmental sequelae of infant cardiac surgery

BACKGROUND: There has been increasing recognition of adverse neurodevelopmental sequelae in some children after repair of congenital heart defects. Even among children with the same cardiac defect, significant interindividual variation exists in developmental outcome. Polymorphisms of apolipoprotein E have been identified as a risk factor for worse neurologic recovery after central nervous system injury. METHODS: A single-institution prospective study of patients 相似文献   

Association between apolipoprotein E polymorphism and macroalbuminuria in patients with non-insulin dependent diabetes mellitus.

OBJECTIVES: Apolipoprotein E (apo E) is known to play an important role in lipoprotein metabolism through its ability to bind to the receptors as a ligand. Three different apo E alleles (epsilon2, epsilon3 and epsilon4) produce six apo E genotypes (epsilon2/2, epsilon2/3, epsilon2/4, epsilon3/3, epsilon3/4 and epsilon4/4). The objective of this study was to investigate an association between apo E gene polymorphism and macroalbuminuria in 167 Korean patients with non-insulin dependent diabetes mellitus (NIDDM). METHODS: The patients in the macroalbuminuria group (n = 74) represent those in whom 24 h urinary albumin excretion was above 300 mg. The patients in the normoalbuminuria group (n = 93) represent those in whom 24 h urinary albumin excretion was below 30 mg and serum creatinine levels were less than 1.2 mg/dl. The duration of diabetes in all patients was at least 8 years. RESULTS: There were no significant differences in terms of age, sex, body mass index, HbA1c, total cholesterol, triglyceride, HDL-cholesterol and LDL-cholesterol between the two groups. In the macroalbuminuria group, the distribution of apo E genotypes revealed epsilon2/2 2 (2.7%), epsilon2/3 14 (18.9%), epsilon2/4 0 (0%), epsilon3/3 47 (63.5%), epsilon3/4 11 (14.9%) and epsilon4/4 0 (0%). In the normoalbuminuria group, the distribution of apo E genotypes revealed epsilon2/2 0 (0%), epsilon2/3 7 (7.5%), epsilon2/4 1 (1.1%), epsilon3/3 72 (77.4%), epsilon3/4 12 (12.9%) and epsilon4/4 1 (1.1%). There was no significant difference in the distribution of apo E genotypes between the two groups. However, there was a significant difference in the allele frequencies, epsilon2 frequency was significantly higher in macroalbuminuria group compared to normoalbuminuria group (12.2% vs 4.3%, P<0.05). Also, we compared apo E carrier frequencies between the two groups. Epsilon2 carrier frequency was significantly higher in macroalbuminuria group compared to normoalbuminuria group (21.6% vs 7.6%, P<0.05). In each group, there was no significant difference in the degree of lipid abnormalities between apo epsilon2 carrier (epsilon2/2, epsilon2/3 genotypes), epsilon3 carrier (epsilon3/3 genotype) and epsilon4 carrier (epsilon3/4, epsilon4/4 genotype). CONCLUSION: Apo epsilon2 allele and epsilon2 carrier frequencies were significantly higher in macroalbuminuria group. These results suggest that epsilon2 allele may be associated with the development of clinical albuminuria in Korean patients with NIDDM.     

Increased prevalence of apolipoprotein E3/E4 genotype among Swedish renal transplant recipients.

There is increasing evidence that lipoproteins are involved in the progression of kidney diseases and in the deterioration of kidney transplant function, although the exact mechanism is still not known. Common polymorphisms of apolipoprotein E genotype associate with the variability of lipoprotein levels and composition. We have, therefore, determined the apolipoprotein E genotype in a group of 112 renal transplant patients, of whom 27 had had an episode of acute vascular rejection, while 85 had not. We found no difference in apolipoprotein E genotype distribution or in relative allele frequency in the vascular rejection group as compared with the group without vascular rejection. The apolipoprotein E genotype distribution in the transplant group was also compared with that in a group of 407 healthy Swedish individuals. The E3/E4 genotype occurred with a significantly increased frequency in the transplant group: 38.3 versus 16% in the control group (p < 0.001). The prevalence of individuals carrying the epsilon4 allele among the transplant group was also significantly higher (44%) as compared with the control group (30%; p < 0.01). This increase was entirely due to the predominant increase of E3/E4, as the E4/E4 genotype was less frequent in transplant recipients than in normal controls (3.5 vs. 10.6%; p < 0.05). The relative frequencies of epsilon2 (0.044), epsilon3 (0.716), and epsilon4 (0.238) alleles in the renal transplant group were not different from those of normal controls (0. 078, 0.718, and 0.202, respectively). With regard to the prevalence of E4/E4 in the two groups, the lack of difference in the relative frequency of the epsilon4 allele must be interpreted with caution. The results thus suggest that the E3/E4 genotype may be associated with the progression of kidney disease leading to renal insufficiency. However, the apolipoprotein E genotype does not seem to influence the risk of vascular rejection among transplant recipients.     

Presence of apolipoprotein E epsilon4 allele in cerebral palsy

The apolipoprotein E gene, which is located on chromosome 19, has three alleles (epsilon2, epsilon3, and epsilon4). Several recent publications associate the presence of the apolipoprotein E epsilon4 allele with the occurrence of neurologic diseases, and consider it a risk factor for the development of central nervous system affections. A group of 40 patients with cerebral palsy was studied and compared to a control group of 40 subjects, and higher occurrence of the allele epsilon4 in the group of subjects with cerebral palsy was observed. A significantly higher risk of developing cerebral palsy was demonstrated among those subjects with the apolipoprotein E epsilon4 allele.     

The association of lowest hematocrit during cardiopulmonary bypass with acute renal injury after coronary artery bypass surgery

BACKGROUND: Acute renal injury is a common serious complication of cardiac surgery. Moderate hemodilution is thought to reduce the risk of kidney injury but the current practice of extreme hemodilution (target hematocrit 22% to 24%) during cardiopulmonary bypass (CPB) has been linked to adverse outcomes after cardiac surgery. Therefore we tested the hypothesis that lowest hematocrit during CPB is independently associated with acute renal injury after cardiac surgery. METHODS: Demographic, perioperative, and laboratory data were gathered for 1,404 primary elective coronary bypass surgery patients. Preoperative and daily postoperative creatinine values were measured until hospital discharge per institutional protocol. Stepwise multivariable linear regression analysis was performed to determine whether lowest hematocrit during CPB was independently associated with peak fractional change in creatinine (defined as the difference between the preoperative and peak postoperative creatinine represented as a percentage of the preoperative value). A p value of less than 0.05 was considered significant. RESULTS: Multivariable analyses including preoperative hematocrit and other perioperative variables revealed that lowest hematocrit during CPB demonstrated a significant interaction with body weight and was highly associated with peak fractional change in serum creatinine (parameter estimate [PE] = 4.5; p = 0.008) and also with highest postoperative creatinine value (PE = 0.06; p = 0.004). Although other renal risk factors were significant covariates in both models, TM50 (an index of hypotension during CPB) was notably absent. CONCLUSIONS: These results add to concerns that current CPB management guidelines accepting extreme hemodilution may contribute to postoperative acute renal and other organ injury after cardiac surgery.     

Renal dysfunction after cardiac surgery with normothermic cardiopulmonary bypass: incidence,risk factors,and effect on clinical outcome

Renal dysfunction is a frequent and severe complication after conventional hypothermic cardiac surgery. Little is known about this complication when cardiopulmonary bypass (CPB) is performed under normothermic conditions (e.g., more than 36 degrees C). Thus, we prospectively studied 649 consecutive patients undergoing coronary artery bypass surgery or valve surgery with normothermic CPB. The association between renal dysfunction (defined as a > or =30% preoperative-to-maximum postoperative increase in serum creatinine level) and perioperative variables was studied by univariate and multivariate analysis. Renal dysfunction occurred in 17% of the patients. Twenty-one (3.2%) patients required dialysis. Independent preoperative predictors of this complication were: advanced age, ASA class >3, active infective endocarditis, radiocontrast agent administration <48 h before surgery, and combined surgery. When all the variables were entered, active infective endocarditis, radiocontrast agent administration, postoperative low cardiac output, and postoperative bleeding were independently associated with renal dysfunction. The in-hospital mortality rate was 27.5% when this complication occurred (versus 1.6%; P < 0.0001). Furthermore, postoperative renal dysfunction was independently associated with in-hospital mortality (odds ratio, 4.1 [95% confidence interval, 1.3-12.8]). We conclude that advanced age, active endocarditis, and recent (within 48 h) radiocontrast agent administration, as well as postoperative hemodynamic dysfunction, are more consistently predictive of postoperative renal dysfunction than CPB factors. IMPLICATIONS: We found that postoperative renal dysfunction was a frequent and severe complication after normothermic cardiac surgery, independently associated with poor outcome. Independent predictors of this complication were advanced age, active endocarditis, and recent (within 48 h) radiocontrast agent administration (the only preoperative modifiable factor), as well as postoperative hemodynamic dysfunction.     

Serum creatinine patterns in coronary bypass surgery patients with and without postoperative cognitive dysfunction

Renal dysfunction is common after coronary artery bypass graft (CABG) surgery. We have previously shown that CABG procedures complicated by stroke have a threefold greater peak serum creatinine level relative to uncomplicated surgery. However, postoperative creatinine patterns for procedures complicated by cognitive dysfunction are unknown. Therefore, we tested the hypothesis that postoperative cognitive dysfunction is associated with acute perioperative renal injury after CABG surgery. Data were prospectively gathered for 282 elective CABG surgery patients. Psychometric tests were performed at baseline and 6 wk after surgery. Cognitive dysfunction was defined both as a dichotomous variable (cognitive deficit [CD]) and as a continuous variable (cognitive index). Forty percent of patients had CD at 6 wk. However, the association between peak percentage change in postoperative creatinine and CD (parameter estimate = -0.41; P = 0.91) or cognitive index (parameter estimate = -1.29; P = 0.46) was not significant. These data indicate that postcardiac surgery cognitive dysfunction, unlike stroke, is not associated with major increases in postoperative renal dysfunction. IMPLICATIONS: We previously noted that patients with postcardiac surgery stroke also have greater acute renal injury than unaffected patients. However, in the same setting, we found no difference in renal injury between patients with and without cognitive dysfunction. Factors responsible for subtle postoperative cognitive dysfunction do not appear to be associated with clinically important renal effects.     

Increased frequency of apolipoprotein epsilon 4 allele in type II diabetes with hypercholesterolemia

The apolipoprotein E (apoE) phenotype and allele frequencies were examined in type II (non-insulin-dependent) diabetic patients with normolipidemia (n = 134) and hypercholesterolemia (type IIa hyperlipoproteinemia, n = 35; type IIb hyperlipoproteinemia, n = 42). The frequencies of apoE4-present phenotypes (apoE4/3, apoE4/4, and apoE4/2) were highest in the type IIa group (51.4%), followed by the type IIb group (38.1%) and the normolipidemic group (16.4%), respectively, whereas the frequency of the most common phenotype, apoE3/3, was lowest in the type IIa group (48.6%), followed by the type IIb group (61.9%) and the normolipidemic group (79.9%), respectively. There were significant differences in the apoE phenotype frequencies between the normolipidemic group and the type IIa and IIb groups. The frequency of the epsilon 4 allele was significantly higher in the type IIa (28.6%) and IIb (20.2%) groups than in the normolipidemic group (8.9%), whereas the frequency of the epsilon 3 allele was significantly lower in the type IIa (71.4%) and IIb (78.6%) groups than in the normolipidemic group (89.2%). The frequency of the epsilon 2 allele tended to be lower in diabetic patients with hypercholesterolemia. In addition, these frequencies were also examined in nondiabetic subjects (n = 59). The frequency of the epsilon 4 allele tended to be higher in hypercholesterolemic diabetic subjects (24.1%) than in hypercholesterolemic nondiabetic subjects (15.3%). These data suggest that diabetic patients with the epsilon 4 allele may be more susceptible to hypercholesterolemia than diabetic patients without the epsilon 4 allele and possibly nondiabetic subjects with the epsilon 4 allele, although the underlying mechanism is unknown.     

Apolipoprotein E epsilon4 allele and outcomes of traumatic spinal cord injury

BACKGROUND/OBJECTIVE: To test the hypothesis that apolipoprotein E (APOE) polymorphisms are associated with outcomes after spinal cord injury (SCI). METHODS: Retrospective cohort study, from rehabilitation admission to discharge. PARTICIPANTS: Convenience sample of 89 persons with cervical SCI (C3-C8) treated from 1995 through 2003. Median age was 30 years (range 14-70); 67 were male (75%) and 83 were white (93%). MAIN OUTCOME MEASURES: American Spinal Injury Association (ASIA) motor and sensory scores, ASIA Impairment Scale (AIS), time from injury to rehabilitation admission, and length of stay (LOS) in rehabilitation. RESULTS: Subjects with an APOE epsilon4 allele (n = 15; 17%) had significantly less motor recovery during rehabilitation than did individuals without an epsilon4 allele (median 3.0 vs 5.5; P < 0.05) and a longer rehabilitation LOS (median 106 vs 89 days; P = 0.04), but better sensory-pinprick recovery (median 5.0 vs 2.0; P= 0.03). There were no significant differences by APOE epsilon4 allele status in sensory-light touch recovery, likelihood of improving AIS Grade, or time from injury to rehabilitation admission. CONCLUSIONS: APOE epsilon4 allele was associated with differences in neurological recovery and longer rehabilitation LOS. Genetic factors may be among the determinants of outcome after SCI and warrant further study.     

Does off‐pump coronary artery bypass grafting beneficially affect renal function?

BACKGROUND: Off-pump coronary artery bypass grafting (CABG) has been reported to beneficially affect renal function, but this remains to be confirmed. The purpose of the present paper was to study the effects of off-pump CABG on renal function and analyse predictors of postoperative renal impairment in patients who received off-pump CABG. METHODS: A total of 451 patients who underwent isolated CABG between January 1999 and August 2003 were retrospectively studied. No patient was receiving dialysis. A total of 300 patients (228 men) underwent off-pump CABG (off-pump group) and 151 patients (104 men) underwent on-pump CABG (on-pump group). Perioperative serum creatinine levels and creatinine ratios (peak postoperative creatinine level/preoperative creatinine level) were compared between the groups. RESULTS: Renal impairment (serum creatinine >1.5 mg/dL) developed postoperatively in 12.7% of the off-pump group and 18.5% of the on-pump group (P = 0.1). The creatinine ratio was significantly lower in the off-pump group (1.2 +/- 0.4) than in the on-pump group (1.4 +/- 0.7, P = 0.003). Logistic regression analysis demonstrated that the strongest predictors of postoperative renal impairment in off-pump CABG were left ventricular dysfunction (odds ratio 10.8) and multivessel grafting (odds ratio 4.3). CONCLUSIONS: Off-pump CABG provides better renal protection than on-pump CABG. However, perioperative renal function should be closely monitored in patients who have left ventricular dysfunction or who undergo multivessel grafting, even when off-pump CABG is performed.     

Changes in Plasma Creatinine Concentration after Cardiac Anesthesia with Isoflurane, Propofol, or Sevoflurane: A Randomized Clinical Trial

Background: Renal impairment often follows cardiac surgery. The authors investigated whether sevoflurane produces greater increases in plasma creatinine concentration than isoflurane or propofol after elective coronary artery surgery.

Methods: As part of maintenance anesthesia, including during cardiopulmonary bypass, patients were randomly allocated to receive one of three agents: isoflurane (n = 118), sevoflurane (n = 118), or propofol (n = 118). Fresh gas flows were 3 l/min. The preoperative plasma creatinine concentration was subtracted from the highest creatinine concentration in the first 3 postoperative days. A median maximum increase greater than 44 [mu]m (0.5 mg/dl) was regarded as clinically important. Data were analyzed on an intention-to-treat basis. Subgroup analyses were performed on per-protocol patients and those with preoperative renal impairment (creatinine concentration > 130 [mu]m [1.47 mg/dl] or urea > 7.7 mm [blood urea nitrogen, 21.6 mg/dl]).

Results: The differences between the groups were small, clinically unimportant, and not statistically significant for the primary analysis and subgroups. The proportions of patients with creatinine increases greater than 44 [mu]m were 15% in the isoflurane group, 17% in the sevoflurane group, and 11% in the propofol group (P = 0.45). The median increases were 8 [mu]m in the isoflurane group, 4 [mu]m in the sevoflurane group, and 6 [mu]m in the propofol group. The differences between the three median maximum increases were 1-4 [mu]m (P > 0.45). In the subgroup with preoperative renal impairment, the median increases were 10 [mu]m in the isoflurane group, 15 [mu]m in the sevoflurane group, and 5 [mu]m in the propofol group (P = 0.72).     

Apolipoprotein E polymorphism in IgA nephropathy.

BACKGROUND/AIM: To clarify the role of the apolipoprotein E (Apo E) phenotype in IgA nephropathy, we investigated its relationship with histological damage and clinical factors. METHODS: The subjects were 104 consecutive patients (41 men and 63 women) with IgA nephropathy. The Apo E phenotype was identified by plasma isoelectric focusing and immunoblotting, and the frequencies of Apo E alleles were calculated. RESULTS: The frequencies of the phenotypes and the alleles were as follows: 2/2 = 0, 2/3 = 0.086, 3/3 = 0.654, 2/4 = 0. 010, 4/3 = 0.211, 4/4 = 0.010, 3/5 = 0.029, epsilon2 = 0.048, epsilon3 = 0.817, epsilon4 = 0.120, and others = 0.015. There were no significant differences between the IgA nephropathy patients and healthy individuals in the frequencies of Apo E phenotypes and the alleles. However, the Apo E2 phenotype was significantly more common among patients with severe histological damage than in those with mild damage. The serum triglyceride levels were significantly elevated, and the Apo E2 phenotype was significantly more prevalent in patients with severe histological damage as compared with those with mild damage. CONCLUSION: The Apo E2 phenotype appears to be associated with the severity of histological damage in IgA nephropathy.