Thrombomodulin Gene Variants Are Associated With Increased Mortality After Coronary Artery Bypass Surgery in Replicated Analyses

Lobato, Robert L.; White, William D.; Mathew, Joseph P.; Newman, Mark F.; Smith, Peter K.; McCants, Charles B.; Alexander, John H.; Podgoreanu, Mihai V.; Team, Safety Outcomes Investigative

doi:10.1161/circulationaha.110.008334

Cited by 34 publications

(30 citation statements)

References 28 publications

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“…Survival information for the secondary outcomes was obtained from Duke Clinical Research Institute Follow-up Services Group, which is responsible for collecting annual follow-up data on death for the Duke Databank for Cardiovascular Diseases. 22 …”

Section: Methodsmentioning

confidence: 99%

Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery

et al. 2016

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Background Cardiac surgery requiring cardiopulmonary bypass is associated with platelet activation. Because platelets are increasingly recognized as important effectors of ischemia and end-organ inflammatory injury, the authors explored whether postoperative nadir platelet counts are associated with acute kidney injury (AKI) and mortality after coronary artery bypass grafting (CABG) surgery. Methods The authors evaluated 4,217 adult patients who underwent CABG surgery. Postoperative nadir platelet counts were defined as the lowest in-hospital values and were used as a continuous predictor of postoperative AKI and mortality. Nadir values in the lowest 10th percentile were also used as a categorical predictor. Multivariable logistic regression and Cox proportional hazard models examined the association between postoperative platelet counts, postoperative AKI, and mortality. Results The median postoperative nadir platelet count was 121 × 109/l. The incidence of postoperative AKI was 54%, including 9.5% (215 patients) and 3.4% (76 patients) who experienced stages II and III AKI, respectively. For every 30 × 109/l decrease in platelet counts, the risk for postoperative AKI increased by 14% (adjusted odds ratio, 1.14; 95% CI, 1.09 to 1.20; P < 0.0001). Patients with platelet counts in the lowest 10th percentile were three times more likely to progress to a higher severity of postoperative AKI (adjusted proportional odds ratio, 3.04; 95% CI, 2.26 to 4.07; P < 0.0001) and had associated increased risk for mortality immediately after surgery (adjusted hazard ratio, 5.46; 95% CI, 3.79 to 7.89; P < 0.0001). Conclusion The authors found a significant association between postoperative nadir platelet counts and AKI and short-term mortality after CABG surgery.

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Section: Methodsmentioning

confidence: 99%

Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery

et al. 2016

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“…12 For patients who had more than one cardiac surgery during that period, only data from the first surgery were included. Patients who received perioperative BB therapy met our eligibility criteria.…”

Section: Study Design and Description Of Study Populationsmentioning

confidence: 99%

“…Each intensity plot was then examined with manual curation of genotype calls. 12 Since single nucleotide polymorphism (SNP) arrays used in both cohorts were different, not all markers identified in the discovery cohort were present on Illumina OMNI1-Quad BeadChip used in the CATHGEN cohort. Therefore, we included imputed SNPs derived from IMPUTE2 17 using 1000 genome as the reference panel in CATHGEN cohort to match selected candidate SNPs between the two datasets.…”

Section: Candidate Gene and Marker Selectionmentioning

confidence: 99%

G Protein–Coupled Receptor Kinase 5 Gene Polymorphisms Are Associated With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting in Patients Receiving β-Blockers

Kertai

et al. 2014

Circ Cardiovasc Genet

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Background We hypothesized that genetic variations in the adrenergic signaling pathway and cytochrome P450 (CYP) 2D6 enzyme are associated with new-onset atrial fibrillation (AF) in patients who underwent coronary artery bypass graft (CABG) surgery and were treated with perioperative beta-blocker (BB). Methods and Results Two cohorts of patients who underwent CABG surgery and received perioperative BBs at Duke University Medical Center were studied. In a discovery cohort of 563 individuals from the Perioperative Genetics and Safety Outcomes Study (PEGASUS), using a covariate adjusted logistic regression analysis, we tested 492 single nucleotide polymorphisms (SNPs) in 10 candidate genes of the adrenergic signaling pathway and CYP2D6 for association with postoperative AF- despite perioperative BB therapy. SNPs meeting a false discovery rate ≤ 0.20 (P<0.002) were then tested in the replication cohort of 245 individuals from the CATHeterization GENetics (CATHGEN) biorepository. Of the 492 SNPs examined, 4 intronic SNPs of the G protein-coupled kinase 5 (GRK5) gene were significantly associated with postoperative AF- despite perioperative BB therapy in the discovery cohort with additive odds ratios between 1.72 and 2.75 (P=4.78×10-5 to 0.0015). Three of these SNPs met nominal significance levels in the replication cohort with odds ratios between 2.07 and 2.60 (P=0.007-0.016). However, meta-analysis of the two datasets cohorts suggested strong association with postoperative AF despite perioperative BB therapy in all 4 SNPs (meta-P-values from 1.66 × 10-6 to 3.39 × 10-5). Conclusions In patients undergoing CABG surgery, genetic variation in GRK5 is associated with postoperative AF despite perioperative BB therapy.

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“…Furthermore, this polymorphism was also associated with increased mortality after coronary artery bypass surgery 37 . However, in our study, THBD rs3176123 polymorphism was not associated with the risk of VTE recurrence.…”

Section: Discussionmentioning

confidence: 97%

Identification of Genetic Aberrations in Thrombomodulin Gene in Patients With Recurrent Venous Thromboembolism

Ahmad

Sundquist

Zöller

et al. 2017

Clin Appl Thromb Hemost

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Thrombomodulin Gene Variants Are Associated With Increased Mortality After Coronary Artery Bypass Surgery in Replicated Analyses

Cited by 34 publications

References 28 publications

Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery

Platelet Counts, Acute Kidney Injury, and Mortality after Coronary Artery Bypass Grafting Surgery

G Protein–Coupled Receptor Kinase 5 Gene Polymorphisms Are Associated With Postoperative Atrial Fibrillation After Coronary Artery Bypass Grafting in Patients Receiving β-Blockers

Identification of Genetic Aberrations in Thrombomodulin Gene in Patients With Recurrent Venous Thromboembolism

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