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ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention.

ABSTRACT: Use of drug-eluting stents (DES) has reduced in-stent restenosis after percutaneous coronary intervention (PCI); however, DES are associated with late stent thrombosis. There is no accurate way to predict in-stent restenosis, although risk factors for atherosclerosis overlap those for in-stent restenosis. Therefore, we evaluated atherosclerosis candidate genes for association with in-stent restenosis.We identified 46 consecutive cases that had undergone PCI with bare-metal stents who subsequently developed symptomatic in-stent restenosis of the target lesion (>/=75% luminal narrowing) within 6 months. Forty-six age-, race-, vessel-diameter- and sex-matched controls without in-stent restenosis after PCI with bare-metal stent were also identified. Single-nucleotide polymorphisms (SNPs, N=82) from 39 candidate atherosclerosis genes were genotyped. Multivariable logistic regression models were used to test for association.Five SNPs were associated with in-stent restenosis. Three ALOX5AP SNPs were most strongly associated, two with increased risk (OR 3.74, p=0.01; OR 3.46, p=0.02), and the third with decreased risk of in-stent restenosis (OR 0.09, p=0.004). Two ALOX5AP haplotypes were associated with in-stent restenosis (HapB: OR 3.13, p=0.03); and a haplotype similar to HapA: OR 0.14, p=0.0009).ALOX5AP, a gene within the inflammatory leukotriene pathway linked to and associated with coronary atherosclerosis, is also associated with in-stent restenosis. Genotyping these variants may help identify those at risk for in-stent restenosis who would benefit most from use of DES.

SUBMITTER: Shah SH

PROVIDER: S-EPMC3733458 | biostudies-literature | 2008 Nov

REPOSITORIES: biostudies-literature

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ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention.

Shah Svati H SH Hauser Elizabeth R ER Crosslin David D Wang Liyong L Haynes Carol C Connelly Jessica J Nelson Sarah S Johnson Jessica J Gadson Shera S Nelson Charlotte L CL Seo David D Gregory Simon S Kraus William E WE Granger Christopher B CB Goldschmidt-Clermont Pascal P Newby L Kristin LK

Atherosclerosis 20080212 1

<h4>Background</h4>Use of drug-eluting stents (DES) has reduced in-stent restenosis after percutaneous coronary intervention (PCI); however, DES are associated with late stent thrombosis. There is no accurate way to predict in-stent restenosis, although risk factors for atherosclerosis overlap those for in-stent restenosis. Therefore, we evaluated atherosclerosis candidate genes for association with in-stent restenosis.<h4>Methods</h4>We identified 46 consecutive cases that had undergone PCI wit ...[more]

PMID: 18374923

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Project description:BackgroundThe triglyceride-glucose (TyG) index is an alternative marker of insulin resistance (IR) and is closely associated with the prevalence and prognosis of atherosclerotic cardiovascular disease (ASCVD). However, the association between the TyG index and in-stent restenosis (ISR) after drug-eluting stent (DES) implantation in patients with acute coronary syndrome (ACS) remains unknown.MethodsThe present study retrospectively recruited patients who were admitted for ACS and underwent coronary angiography at 6 to 24 months after successful DES-based percutaneous coronary intervention (PCI). In addition, we calculated the TyG index with the following formula: Ln(fasting triglyceride [mg/dL] × fasting blood glucose [mg/dL]/2) and divided patients into 3 groups according to the tertile of the TyG index. Most importantly, multivariate logistic regression analysis models were also constructed to assess the association between the TyG index and DES-ISR in patients with ACS.ResultsA total of 1574 patients with ACS (58.4 ± 9.4 years, 77.4% male) were included in this study. At the median follow-up time of 12 (9-14) months, the prevalence of DES-ISR increased stepwise with the increasing tertile of the TyG index (11.6% vs 17.3% vs 19.4%, p = 0.002), and the TyG index was also higher in the ISR group than in the non-ISR group (9.00 ± 0.58 vs 8.84 ± 0.61, p < 0.001). In addition, the positive association between the TyG index and the prevalence of DES-ISR was also determined in the fully adjusted model (TyG, per 1-unit increase: OR 1.424, 95% CI 1.116 to 1.818, p = 0.005; tertile of TyG, the OR (95% CI) values for tertile 2 and tertile 3 were 1.454 (1.013 to 2.087) and 1.634 (1.125 to 2.374), respectively, with tertile 1 as a reference). The association was also reflected in most subgroups. Moreover, adding the TyG index to the predictive model for DES-ISR in patients with ACS could contribute to an increase in C-statistics (0.675 vs 0.659, p = 0.010), categorical net reclassification improvement (0.090, p < 0.001), and integrated discrimination improvement (0.004, p = 0.040).ConclusionAn elevated TyG index was independently and positively associated with DES-ISR in patients with ACS who underwent PCI. However, the incremental predictive value of the TyG index for DES-ISR was slight. To further confirm our findings, future studies are needed.

Project description:BackgroundThis study aimed to develop and validate a nomogram to predict probability of in-stent restenosis (ISR) in patients undergoing percutaneous coronary intervention (PCI).MethodsPatients undergoing PCI with drug-eluting stents between July 2009 and August 2011 were retrieved from a cohort study in a high-volume PCI center, and further randomly assigned to training and validation sets. The least absolute shrinkage and selection operator (LASSO) regression model was used to screen out significant features for construction of nomogram. Multivariable logistic regression analysis was applied to build a nomogram-based predicting model incorporating the variables selected in the LASSO regression model. The area under the curve (AUC) of the receiver operating characteristics (ROC), calibration plot and decision curve analysis (DCA) were performed to estimate the discrimination, calibration and utility of the nomogram model respectively.ResultsA total of 463 patients with DES implantation were enrolled and randomized in the development and validation sets. The predication nomogram was constructed with five risk factors including prior PCI, hyperglycemia, stents in left anterior descending artery (LAD), stent type, and absence of clopidogrel, which proved reliable for quantifying risks of ISR for patients with stent implantation. The AUC of development and validation set were 0.706 and 0.662, respectively, indicating that the prediction model displayed moderate discrimination capacity to predict restenosis. The high quality of calibration plots in both datasets demonstrated strong concordance performance of the nomogram model. Moreover, DCA showed that the nomogram was clinically useful when intervention was decided at the possibility threshold of 9%, indicating good utility for clinical decision-making.ConclusionsThe individualized prediction nomogram incorporating 5 commonly clinical and angiographic characteristics for patients undergoing PCI can be conveniently used to facilitate early identification and improved screening of patients at higher risk of ISR.

Project description:BackgroundPatients with type 2 diabetes are under substantially higher risk of in-stent restenosis (ISR) after coronary stent implantation. We sought to investigate whether visit-to-visit HbA1c variability is a potential predictor of ISR in diabetic patients after stent implantation.MethodsWe consecutively enrolled type 2 diabetic patients who underwent successful elective percutaneous coronary intervention and performed follow-up coronary angiography after around 12 months. The incidence of ISR and its relationship with visit-to-visit HbA1c variability, expressed as coefficient of variation (CV), standard deviation (SD) and variability independent of the mean (VIM), were studied. Multivariable Cox proportional hazards models were constructed to analyze the predictive value of HbA1c variability for ISR.ResultsFrom September 2014 to July 2018 in Ruijin Hospital, a total of 420 diabetic patients (688 lesions) after stent implantation were included in the final analysis. During a mean follow-up of 12.8 ± 1.3 months, the incidence of ISR was 8.6%, which was significantly increased in patients with higher CV of HbA1c (P = 0.001). The mean diameter stenosis (DS), net luminal loss and net luminal gain were 22.9 ± 16.8%, 0.42 ± 0.88 mm and 1.66 ± 0.83 mm, respectively. Greater DS was observed in subjects with higher tertiles of CV of HbA1c (P < 0.001), and this trend was more prominent in patients with optimal glycemic control (HbA1c ≤ 7%) in the baseline. In multivariate analysis, HbA1c variability was independently associated with incidence of ISR after adjustment for traditional risk factors and mean HbA1c (HR: 3.00 [95% CI 1.14-7.92] for highest vs. lowest tertile). Inclusion of CV of HbA1c led to a better risk stratification accuracy. Assessing HbA1c variability by SD or VIM yielded similar findings.ConclusionsThis study suggests that visit-to-visit HbA1c variability is an independent predictor of incidence of ISR in patients with type 2 diabetes after stent implantation. Trial registration NCT02089360: NCT.

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ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention.

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ALOX5AP variants are associated with in-stent restenosis after percutaneous coronary intervention.

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