Thrombotic gene polymorphisms and postoperative outcome after coronary artery bypass graft surgery

Abstract

BackgroundEmerging perioperative genomics may influence the direction of risk assessment and surgical strategies in cardiac surgery. The aim of this study was to investigate whether single nucleotide polymorphisms (SNP) affect the clinical presentation and predispose to increased risk for postoperative adverse events in patients undergoing coronary artery bypass grafting surgery (CABG).MethodsA total of 220 patients undergoing first-time CABG between January 2005 and May 2008 were screened for factor V gene G1691A (FVL), prothrombin/factor II G20210A (PT G20210A), angiotensin I-converting enzyme insertion/deletion (ACE-ins/del) polymorphisms by PCR and Real Time PCR. End points were defined as death, myocardial infarction, stroke, postoperative bleeding, respiratory and renal insufficiency and event-free survival. Patients were compared to assess for any independent association between genotypes for thrombosis and postoperative phenotypes.ResultsAmong 220 patients, the prevalence of the heterozygous FVL mutation was 10.9% (n = 24), and 3.6% (n = 8) were heterozygous carriers of the PT G20210A mutation. Genotype distribution of ACE-ins/del was 16.6%, 51.9%, and 31.5% in genotypes I/I, I/D, and D/D, respectively. FVL and PT G20210A mutations were associated with higher prevalence of totally occluded coronary arteries (p < 0.001). Furthermore the risk of left ventricular aneurysm formation was significantly higher in FVL heterozygote group compared to FVL G1691G (p = 0.002). ACE D/D genotype was associated with hypertension (p = 0.004), peripheral vascular disease (p = 0.006), and previous myocardial infarction (p = 0.007).ConclusionsFVL and PT G20210A genotypes had a higher prevalence of totally occluded vessels potentially as a result of atherothrombotic events. However, none of the genotypes investigated were independently associated with mortality.

Incidence of the genetic mutations in patients with coronary artery disease

“…The incidence of thromboembolic complications during perioperative and postoperative period in cardiac surgical patients was related with heterozygous FVL mutation [16]. In MTHFR C677T MTHFR A1298C PT G20210A FVL HET HET WT WT HET HET WT HET HET HET WT HET HET HET WT HET HET HET WT WT HET HET HET WT HET HET WT WT HET HET WT WT HET HET WT WT HET HET WT HET HET HET WT WT HET HET WT WT HET HET WT WT HET HET HET WT FVL=Factor V Leiden, PT 20210A=Prothrombin gene mutation, MTHFR=Methylenetetrahydrofolate reductase, HET=heterozygous, WT=wild type # contrast, Emiroglu et al [13] did not find a statistically significant difference with postoperative thromboembolic complications, which may be due to routine heparin administration postoperatively. In contrast to the report of Emiroglu et al [13], Donahue et al [15] reported that postoperative bleeding drainage was statistically lower in patients with FVL mutation compared with non-carriers.…”

A single nucleotide polymorphism in the p27Kip1 gene is associated with primary patency of lower extremity vein bypass grafts

“…27,28 The reasons for failure of the test agent in these studies remain unclear; however, variability in clinical outcomes across a range of patient-level factors, including race and sex, was observed in these large multicenter studies. There are few prior reports describing genetic association studies in vein bypass outcomes, 29-31 and none involving peripheral grafting. Importantly, our study was not a broad exploratory investigation of genetic associations but rather a hypothesis-based testing of a single suspected genetic marker based on the recent coronary studies.…”

Biomarkers in Coronary Artery Bypass Surgery: Ready for Prime Time and Outcome Prediction?

“…Gene polymorphisms and/or genetic mutations as new markers of morbidity and mortality in patients after CABG have been intensively studied over the past few years ( 17 ). Numerous studies in this field have been based on the identification of single nucleotide polymorphisms (SNPs) in candidate genes regulating inflammatory response ( 18 , 19 ), thrombotic pathways ( 20 , 21 ), oxidative stress ( 11 ), renin–angiotensin system ( 22 , 23 ), cell damage ( 24 , 25 ), and their association with post-operative results in patients undergoing CABG. The studies published so far and described in Tables S1–S5 in Supplementary Material based on specific pathways, have addressed two main questions: (1) can gene polymorphisms or mutations modulate or affect plasma levels of a dynamic biomarker, both at baseline or after the stimulus resulting from cardiac surgery?…”

“…However, we have reliable data regarding two markers: fibrinogen ( 23 , 27 ), which is between inflammation and hemostasis; and beta-thromboglobulin ( 21 ). Interestingly, only one study has addressed the main issue of graft patency after CABG by assessing the presence of factor V Leiden genetic mutations ( 22 ). This study, limited by the small number of patients enrolled (a total of 100 CABGs), has suggested that the mutation Arg 506 Gln tends to be associated with saphenous graft occlusion [5/11 (45%) carriers vs. 18/89 (20%) non-carriers, p = 0.06] ( 32 ).…”

“…A study conducted by Welsby et al ( 23 ) investigated and showed that ACE insertion/deletion (I/D) polymorphism plays a role in post-operative bleeding. On the contrary, the association of ACE I/D with cardiac mortality or all-cause mortality is controversial ( 22 , 34 ). The large PEGASUS study showed no association with 5-year all-cause mortality ( 20 ), while a smaller study carried out by Völzke et al ( 35 ) showed a strong association with both 2-year all-cause and cardiac mortality.…”