Gene polymorphisms in APOE, NOS3, and LIPC genes may be risk factors for cardiac adverse events after primary CABG

<p>Abstract</p> <p>Introduction</p> <p>Coronary artery disease progression after primary coronary artery bypass grafting may, beside classical atherosclerosis risk factors, be depending on genetic predisposition.</p> <p>Methods</p> <p>We investigated 192 CABG patients (18% female, age: 60.9 ± 7.4 years). Clinically cardiac adverse events were defined as need for reoperation (n = 88; 46%), reintervention (n = 58; 30%), or angina (n = 89; 46%). Mean follow-up time measured 10.1 ± 5.1 years. Gene polymorphisms (<b><it>ApoE, NOS3, LIPC, CETP, SERPINE-1, Prothrombin</it></b>) were investigated separately and combined (gene risk profile).</p> <p>Results</p> <p>Among classical risk factors, arterial hypertension and hypercholesterinemia significantly influenced CAD progression. Single <b><it>ApoE, NOS3 </it></b>and <b><it>LIPC </it></b>polymorphisms provided limited information. Patients missing the most common <b><it>ApoE </it></b>ε3 allele (5,2%), showed recurrent symptoms (p = 0,077) and had more frequently reintervention (p = 0,001). <b><it>NOS3 </it></b>a allele was associated with a significant increase for reintervention (p = 0,041) and recurrent symptoms (p = 0,042).</p> <p>Homozygous <b><it>LIPC </it></b>patients had a higher reoperation rate (p = 0.049).</p> <p>A gene risk profile enabled us to discriminate between faster and slower occurrence of cardiac adverse events (p = 0.0012).</p> <p>Conclusion</p> <p>Single <b><it>APOE, LIPC </it></b>and <b><it>NOS3 </it></b>polymorphisms permitted limited prognosis of cardiac adverse events in patients after CABG. Risk profile, in contrast, allowed for risk stratification.</p

Postoperative Heparin-Mediated Extracorporeal Low-Density Lipoprotein Fibrinogen Precipitation Aphaeresis Prevents Early Graft Occlusion after Coronary Artery Bypass Grafting

Background Early graft occlusion due to thromboembolic events is a well-known complication after coronary artery bypass grafting (CABG). Fibrinogen, the coagulation factor I, is a glycoprotein that is transformed by thrombin into fibrin. It plays amajor role in thrombus formation and is highly elevated after CABG. Our aim was to determine if postoperative lowering of fibrinogen levels by H.E.L.P. (heparin-mediated extracorporeal low-density lipoprotein [LDL] fibrinogen precipitation) aphaeresis could reduce the rate of early graft occlusion in patients with hypercholesterolemia undergoing CABG. Methods Between December 2004 and September 2009, 36 male patients with hypercholesterolemia (mean LDL cholesterol 128 +/- 12 mg/dL), mean age 58 +/- 9 years, underwent CABG. Mean preoperative fibrinogen level was 387 +/- 17 mg/dL. H.E.L.P. aphaeresis was postoperatively performed when fibrinogen levels exceeded 350 mg/dL on day 1 and 250 mg/dL every consecutive day up to day 8. Pre- and postaphaeresis blood samples were obtained and plasma fibrinogen level reduction was calculated. Early graft occlusion was evaluated by means of coronary angiography or multislice computed tomography before discharge. Results A total of 128 distal anastomoses were performed in 36 patients (mean 3.6/patient). Postoperatively, 191 H.E.L.P. aphaeresis sessions were performed (mean 5.3/patient). Fibrinogen levels were lowered from 391 +/- 10 mg/dL (preaphaeresis) to 171 +/- 5 mg/dL (postaphaeresis;p < 0.001). Coronary angiography (multislice computed tomography in 7 patients) revealed graft patency in 125 of 128 grafts (98% patency) with three occluded venous grafts to target vessels of 1.5 mm. H.E.L.P. aphaeresis-related complications were limited to hypotensive episodes in two patients and bacteremia in one patient. Conclusions H.E.L.P. apheresis offers an easy, save, and efficient method to decrease fibrinogen postoperatively in patients having CABG. Showing excellent graft patency rates in comparison to the literature, this method is a promising tool to reduce early graft occlusion after CABG

Postoperative Heparin-Mediated Extracorporeal Low-Density Lipoprotein Fibrinogen Precipitation Aphaeresis Prevents Early Graft Occlusion after Coronary Artery Bypass Grafting

Background Early graft occlusion due to thromboembolic events is a well-known complication after coronary artery bypass grafting (CABG). Fibrinogen, the coagulation factor I, is a glycoprotein that is transformed by thrombin into fibrin. It plays amajor role in thrombus formation and is highly elevated after CABG. Our aim was to determine if postoperative lowering of fibrinogen levels by H.E.L.P. (heparin-mediated extracorporeal low-density lipoprotein [LDL] fibrinogen precipitation) aphaeresis could reduce the rate of early graft occlusion in patients with hypercholesterolemia undergoing CABG. Methods Between December 2004 and September 2009, 36 male patients with hypercholesterolemia (mean LDL cholesterol 128 +/- 12 mg/dL), mean age 58 +/- 9 years, underwent CABG. Mean preoperative fibrinogen level was 387 +/- 17 mg/dL. H.E.L.P. aphaeresis was postoperatively performed when fibrinogen levels exceeded 350 mg/dL on day 1 and 250 mg/dL every consecutive day up to day 8. Pre- and postaphaeresis blood samples were obtained and plasma fibrinogen level reduction was calculated. Early graft occlusion was evaluated by means of coronary angiography or multislice computed tomography before discharge. Results A total of 128 distal anastomoses were performed in 36 patients (mean 3.6/patient). Postoperatively, 191 H.E.L.P. aphaeresis sessions were performed (mean 5.3/patient). Fibrinogen levels were lowered from 391 +/- 10 mg/dL (preaphaeresis) to 171 +/- 5 mg/dL (postaphaeresis;p < 0.001). Coronary angiography (multislice computed tomography in 7 patients) revealed graft patency in 125 of 128 grafts (98% patency) with three occluded venous grafts to target vessels of 1.5 mm. H.E.L.P. aphaeresis-related complications were limited to hypotensive episodes in two patients and bacteremia in one patient. Conclusions H.E.L.P. apheresis offers an easy, save, and efficient method to decrease fibrinogen postoperatively in patients having CABG. Showing excellent graft patency rates in comparison to the literature, this method is a promising tool to reduce early graft occlusion after CABG

Ten-Year Results of a Randomized Trial Comparing Tacrolimus Versus Cyclosporine A in Combination With Mycophenolate Mofetil After Heart Transplantation

Background. Long-term results of prospective randomized trials comparing triple immunosuppressive strategies combining tacrolimus (TAC) or cyclosporine A (CsA) with mycophenolate mofetil (MMF) and steroids after heart transplantation (HTX) are rarely published. Therefore, we collected long-term follow-up data of an intervention cohort 10 years after randomization. Methods. Ten-year follow-up data of 60 patients included in a prospective, randomized trial between 1998 and 2000 were analyzed as intention-to-treat (TAC-MMF n=30; CsA-MMF n=30). Baseline characteristics were well balanced. Cardiac allograft vasculopathy (CAV) was graduated in accordance with the new ISHLT classification. Results. Survival at 1, 5, and 10 years was 96.7%, 80.0%, and 66.7% for TAC-MMF and 90.0%, 83.3%, and 80.0% for CsA-MMF (P=ns). Freedom from acute rejection (AR) was significantly higher in TAC-MMF versus CsA-MMF (65.5% vs. 21.7%, log-rank 8.3, P=0.004). Freedom from ISHLT >= CAV(1) after 5 and 10 years was in TAC-MMF 64.0% and 45.8%, and in CsA-MMF 36.0% (log-rank 3.0, P=0.085) and 8.0% (log-rank 9.0, P=0.003). No difference in long-term results for freedom from coronary angioplasty or stenting, renal dysfunction, diabetes mellitus, CMV infection, or malignancy was detected. Conclusion. Cross-over effects because of treatment switch may result in impairment of significance between the groups. The long-term analysis resulted in a significant difference in manifestation of CAV between the groups after 10 years. Less rejection in the TAC-group might have contributed to the lower incidence of CAV. Superior freedom from AR and CAV in the TAC-MMF group did not result in better long-term survival

Hydrography and food distribution during a tidal cycle above a cold-water coral mound

Cold-water corals (CWCs) are important ecosystem engineers in the deep sea that provide habitat for numerous species and can form large coral mounds. These mounds influence surrounding currents and induce distinct hydrodynamic features, such as internal waves and episodic downwelling events that accelerate transport of organic matter towards the mounds, supplying the corals with food. To date, research on organic matter distribution at coral mounds has focussed either on seasonal timescales or has provided single point snapshots. Data on food distribution at the timescale of a diurnal tidal cycle is currently limited. Here, we integrate physical, biogeochemical, and biological data throughout the water column and along a transect on the south-eastern slope of Rockall Bank, Northeast Atlantic Ocean. This transect consisted of 24-h sampling stations at four locations: Bank, Upper slope, Lower slope, and the Oreo coral mound. We investigated how the organic matter distribution in the water column along the transect is affected by tidal activity. Repeated CTD casts indicated that the water column above Oreo mound was more dynamic than above other stations in multiple ways. First, the bottom water showed high variability in physical parameters and nutrient concentrations, possibly due to the interaction of the tide with the mound topography. Second, in the surface water a diurnal tidal wave replenished nutrients in the photic zone, supporting new primary production. Third, above the coral mound an internal wave (200 m amplitude) was recorded at 400 m depth after the turning of the barotropic tide. After this wave passed, high quality organic matter was recorded in bottom waters on the mound coinciding with shallow water physical characteristics such as high oxygen concentration and high temperature. Trophic markers in the benthic community suggest feeding on a variety of food sources, including phytodetritus and zooplankton. We suggest that there are three transport mechanisms that supply food to the CWC ecosystem. First, small phytodetritus particles are transported downwards to the seafloor by advection from internal waves, supplying high quality organic matter to the CWC reef community. Second, the shoaling of deeper nutrient-rich water into the surface water layer above the coral mound could stimulate diatom growth, which form fast-sinking aggregates. Third, evidence from lipid analysis indicates that zooplankton faecal pellets also enhance supply of organic matter to the reef communities. This study is the first to report organic matter quality and composition over a tidal cycle at a coral mound and provides evidence that fresh high-quality organic matter is transported towards a coral reef during a tidal cycle