Dataset Information

A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts.

ABSTRACT: Factors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27(Kip1) gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency.This was a retrospective genetic association study nested within a prospective cohort of 204 patients from three referral centers undergoing LEVBG for claudication or critical ischemia. The main outcome measure was primary vein graft patency.All patients were followed up for a minimum of 1 year with duplex graft surveillance (median follow-up, 893 days; interquartile range, 539-1315). Genomic DNA was isolated and SNP analysis for the p27(Kip1)-838C>A variants was performed. Allele frequencies were correlated with graft outcome using survival analysis and Cox proportional hazards modeling. The p27(Kip1)-838C>A allele frequencies observed were CA, 53%; CC, 30%; and AA, 17%, satisfying Hardy-Weinberg equilibrium. Race (P = .025) and history of coronary artery disease (P = .027) were different across the genotypes; all other baseline variables were similar. Primary graft patency was greater among patients with the -838AA genotype (75% AA vs 55% CA/CC at 3 years; P = .029). In a Cox proportional hazards model including age, sex, race, diabetes, critical limb ischemia, redo (vs primary) bypass, vein type, and baseline C-reactive protein level, the p27(Kip1)-838AA genotype was significantly associated with higher graft patency (hazard ratio for failure, 0.4; 95% confidence interval, 0.17-0.93). Genotype was also associated with early (0-1 month) changes in graft lumen diameter by ultrasound imaging.These data suggest that the p27(Kip1)-838C>A SNP is associated with LEVBG patency and, together with previous reports, underscore a central role for p27(Kip1) in the generic response to vascular injury.

SUBMITTER: Conte MS

PROVIDER: S-EPMC3644510 | biostudies-literature | 2013 May

REPOSITORIES: biostudies-literature

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A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts.

Conte Michael S MS Owens Christopher D CD Belkin Michael M Creager Mark A MA Edwards Karen L KL Gasper Warren J WJ Kenagy Richard D RD LeBoeuf Renee C RC Sobel Michael M Clowes Alexander A

Journal of vascular surgery 20130109 5

<h4>Objective</h4>Factors responsible for the variability in outcomes after lower extremity vein bypass grafting (LEVBG) are poorly understood. Recent evidence has suggested that a single nucleotide polymorphism (SNP) in the promoter region of the p27(Kip1) gene, a cell-cycle regulator, is associated with coronary in-stent restenosis. We hypothesized an association with vein graft patency.<h4>Methods</h4>This was a retrospective genetic association study nested within a prospective cohort of 204 ...[more]

PMID: 23312942

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Project description:Despite poor long-term patency, acceptable limb salvage has been reported with cryopreserved saphenous vein bypass (CVB) for various indications. However, utility of CVB in patients with critical limb ischemia (CLI) remains undefined. The purpose of this analysis was to determine the role of CVB in CLI patients and to identify predictors of successful outcomes.A retrospective review of all lower extremity bypass (LEB) procedures at a single institution was completed, and CVB in CLI patients were further analyzed. The primary end point was amputation-free survival. Secondary end points included primary patency and limb salvage. Life tables were used to estimate occurrence of end points. Cox regression analysis was used to determine predictors of limb salvage.From 2000 to 2012, 1059 patients underwent LEB for various indications, of whom 81 received CVB for either ischemic rest pain or tissue loss. Mean age (± standard deviation) was 66 ± 10 years (male, 51%; diabetes, 51%; hemodialysis dependence, 12%), and 73% (n = 59) had history of failed ipsilateral LEB or endovascular intervention. None had sufficient autogenous conduit for even composite vein bypass. Infrainguinal CVB (infrapopliteal target, 96%; n = 78) was completed for multiple indications including Rutherford class 4 (42%; n = 34), class 5 (40%; n = 32), and class 6 (18%; n = 15). Eleven (14%) had CLI and concomitant graft infection (n = 8) or acute on chronic ischemia (n = 3). Intraoperative adjuncts (eg, profundaplasty, suprainguinal stent or bypass) were completed in 49% (n = 40) of cases. Complications occurred in 36% (n = 29), with 30-day mortality of 4% (n = 3). Median follow-up for CLI patients was 11.8 (interquartile range, 0.4-28.4) months with corresponding 1- and 3-year actuarial estimated survival (± standard error mean) of 84% ± 4% and 62% ± 6%. Primary patency of CVB for CLI was 27% ± 6% and 17% ± 6% at 1 and 3 years, respectively. Amputation-free survival was 43% ± 6% and 23% ± 6% at 1 and 3 years, respectively, and significantly higher for rest pain (59% ± 9%, 36% ± 10%) compared with tissue loss (31% ± 7%, 14% ± 7%; log-rank, P = .04). Freedom from major amputation after CVB for CLI was 57% ± 6% and 43% ± 7% at 1 and 3 years. Multivariable predictors of limb salvage for the CVB CLI cohort included postoperative warfarin (hazard ratio [HR], 0.4; 95% confidence interval [CI], 0.2-0.8), dyslipidemia (HR, 0.4; 95% CI, 0.2-0.9), and rest pain (HR, 0.4; 95% CI, 0.2-0.9). Predictors of major amputation included graft infection (HR, 3.1; 95% CI, 1.1-9.0).In CLI patients with no autologous conduit and prior failed infrainguinal bypass, CVB outcomes are disappointing. CVB performs best in patients with rest pain, particularly those who can be anticoagulated with warfarin. However, it may be an acceptable option in patients with minor tissue loss or concurrent graft infection, but consideration should be weighed against the known natural history of nonrevascularized CLI and nonbiologic conduit alternatives, given potential cost implications.

Project description:BACKGROUND:Where each patient has all three conduits of internal mammary artery (IMA), saphenous vein graft (SVG) and radial artery (RA), most confounders affecting comparison between conduits can be mitigated. Additionally, since SVG progressively fails over time, restricting patient angiography to the late period only can mitigate against early SVG patency that may have occluded in the late period. METHODS:Research protocol driven conventional angiography was performed for patients with at least one of each conduit of IMA, RA and SVG and a minimum of 7?years postoperative. The primary analysis was perfect patency and secondary analysis was overall patency including angiographic evidence of conduit lumen irregularity from conduit atheroma. Multivariable generalized linear mixed model (GLMM) was used. Patency excluded occluded or "string sign" conduits. Perfect patency was present in patent grafts if there was no lumen irregularity. RESULTS:Fifty patients underwent coronary angiography at overall duration postoperative 13.1?±?2.9, and age 74.3?±?7.0?years. Of 196 anastomoses, IMA 62, RA 77 and SVG 57. Most IMA were to the left anterior descending territory and most RA and SVG were to the circumflex and right coronary territories. Perfect patency RA 92.2% was not different to IMA 96.8%, P?=?0.309; and both were significantly better than SVG 17.5%, P?<?0.001. Patency RA 93.5% was also not different to IMA 96.8%, P?=?0.169, and both arterial conduits were significantly higher than SVG 82.5%, P?=?0.029. Grafting according to coronary territory was not significant for perfect patency, P?=?0.997 and patency P?=?0.289. Coronary stenosis predicted perfect patency for RA only, P?=?0.030 and for patency, RA, P?=?0.007, and SVG, P?=?0.032. When both arterial conduits were combined, perfect patency, P?<?0.001, and patency, P?=?0.017, were superior to SVG. CONCLUSIONS:All but one patent internal mammary artery or radial artery grafts had perfect patency and had superior perfect patency and overall patency compared to saphenous vein grafts.

Project description:Our aim was to evaluate the effect of gender on early and late procedural and functional outcomes of lower extremity bypass (LEB).We reviewed the records of 2576 patients (828 women; 32%) who underwent LEB for claudication or critical limb ischemia (CLI) in the Vascular Study Group of New England from 2003 to 2010. Logistic regression and proportional hazards models were used to adjust for potential confounding differences between genders. Morbidity, mortality, graft patency, freedom from major amputation, ambulation, and living status were analyzed postoperatively and over 1 year.Women were older (70 vs 68 years; P < .001), had more hypertension (89% vs 85%; P = .006), less coronary artery disease (35% vs 39%; P = .03), smoking (73% vs 88%; P < .001), and preoperative statin use (60% vs 64%; P = .04). Women were more likely to have CLI (76% vs 71%; P = .003), and ambulate with assistance at presentation (19% vs 16%; P = .02). Morbidity was similar except women had higher rates of reoperation for thrombosis (4% vs 2%; P < .001) without differences in major amputation (2% vs 1%; P = .13) or in-hospital mortality (1.7% vs 1.7%; P = .96). Women and men with claudication had similar 1-year graft patency rates. Women with CLI had lower rates of primary (hazard ratio [HR], 1.24; 95% confidence interval [CI], 1.03-1.48; P = .02), assisted primary (HR, 1.42; 95% CI, 1.15-1.76; P = .001) and secondary patency (HR, 1.40; 95% CI, 1.10-1.77; P = .006) during the first year compared with men. Freedom from amputation was similar for men and women with CLI (HR, 1.17; 95% CI, 0.84-1.63; P = .36). There were no differences in late survival between women and men with claudication (HR, 0.89; 95% CI, 0.60-1.31; P = .36) or CLI (HR, 0.94; 95% CI, 0.81-1.09; P = .39). More female claudicants were not independently ambulatory at discharge (30% vs 19%; P = .002) and were discharged to a nursing home (15% vs 5%; P < .001) but these differences did not persist at 1 year. Women with CLI were more likely to be nonambulatory at discharge (13% vs 9%; P = .006) and at 1 year (13% vs 8%; P < .001). More women with CLI were discharged to a nursing home (44% vs 35%; P = .01) and resided there at 1 year (11% vs 7%; P = .02).Women have complication rates similar to men with inferior early and late functional outcomes after LEB. The reduced patency rates in women with CLI did not translate into differences in limb salvage. These findings might help define physician and patient expectations for women before revascularization.

Project description:Infrainguinal bypass (IB) surgery is an effective means of improving arterial circulation to the lower extremity for patients with critical limb ischemia (CLI). However, wound complications (WC) of the surgical incision following IB can impart significant morbidity.A retrospective analysis of WC from the 1404 patients enrolled in a multicenter clinical trial of vein bypass grafting for CLI was performed. Univariate and multivariable regression models were used to determine WC predictors and associated outcomes, including graft patency, limb salvage, quality of life (QoL), resource utilization (RU), and mortality.A total of 543 (39%) patients developed a reported WC within 30 days of surgery, with infections (284, 52%) and hematoma/hemorrhage (121, 22%) being the most common type. Postoperative anticoagulation (odds ratio [OR], 1.554; 95% confidence interval [CI] 1.202 to 2.009; P = .0008) and female gender (OR, 1.376; 95% CI, 1.076 to 1.757; P = .0108) were independent factors associated with WC. Primary, primary-assisted, and secondary graft patency rates were not influenced by the presence of WC; though, patients with WC were at increased risk for limb loss (hazard ratio [HR], 1.511; 95% CI 1.096 to 2.079; P = .0116) and higher mortality (HR, 1.449; 95% CI 1.098 to 1.912; P = .0089). WC was not significantly associated with lower QoL at 3 months (4.67 vs 4.79, P = .1947) and 12 months (5.02 vs 5.13, P = .2806). However, the subset of patients with serious WC (SWC) demonstrated significantly lower QoL at 3 months compared with patients without WC, (4.43 vs 4.79, respectively, P = .0166), though this difference was not seen at 12 months (4.94 vs 5.13, P = .2411). Patients with WC had higher RU than patients who did not have WC. Mean index length of hospital stay (LOS) was 2.3 days longer, mean cumulative 1-year LOS was 8.1 days longer, and mean number of hospitalizations was 0.5 occurrences greater for patients with WC compared with patients without WC (all P < .0001).WC is a frequent complication of IB for CLI, associated with increased risk for major amputation, mortality, and greater RU. Further detailed investigation into the link between female gender and oral anticoagulation use with WC may help identify causes of WC and perhaps prevent or lessen their occurrence.

Dataset Information

A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts.

Publications

A single nucleotide polymorphism in the p27(Kip1) gene is associated with primary patency of lower extremity vein bypass grafts.

Similar Datasets

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