Steve Goldman

Starting aspirin therapy after operation. Effects on early graft patency. Department of Veterans Affairs Cooperative Study Group.

BackgroundAlthough aspirin therapy started before operation improves vein graft patency after coronary artery bypass grafting, it also causes bleeding. The objective of this prospective, centrally directed, randomized, double-blind, placebo-controlled trial was to compare the effects of aspirin therapy started before operation with aspirin started 6 hours after operation on early (7–10-day) graft patency. Methods and ResultsPatients were randomized to receive either aspirin 325 mg or placebo the night before surgery; after operation, all patients received aspirin 325 mg daily, with the first dose administered through the nasogastric tube 6 hours after operation. Angiography was performed in 72% of the analyzed patients an average of 8 days after operation, and the primary end point was saphenous vein graft patency in 351 patients. Internal mammary artery graft patency was also assessed in 246 patients because many individuals received both internal mammary artery and vein grafts. In the patients given preoperative aspirin, the vein graft occlusion rate was 7.4 ± 1.3% compared with 7.8 ± 1.5% in those who received preoperative placebo (p =0.871). In the subgroup of patients receiving Y grafts, 0.0% of the grafts were occluded in the preoperative aspirin group compared with 7.0 ± 3.6% in the preoperative placebo group (p =0.066). The internal mammary artery occlusion rate was 0.0% (0 of 131) in the aspirin group compared with 2.4 ± 1.4% (three of 125) in the placebo group (p =0.081). Patients in the aspirin group received more transfusions than those in the placebo group (median, 900 versus 725 ml,p=0.006). The reoperation rate for bleeding in the aspirin group was 6.3% compared with 2.4% in the placebo group (p =0.036). Median chest tube drainage within the first 6 hours after operation was 500 ml in the aspirin group compared with 448 ml in the placebo group (p =0.011). Conclisions. Thus, preoperative aspirin is associated with increased bleeding complications and offers no additional benefit in early vein graft patency compared with starting aspirin therapy 6 hours after operation. There was a trend, although not significant, toward improved early patency for Y grafts and internal mammary artery grafts with preoperative aspirin.

Long-term graft patency (3 years) after coronary artery surgery. Effects of aspirin: results of a VA Cooperative study.

BACKGROUND The long-term success of coronary bypass surgery is dependent on graft patency after surgery. This trial was designed to determine if aspirin improved saphenous vein graft or internal mammary artery (IMA) graft patency between 1 and 3 years after coronary artery bypass grafting (CABG). METHODS AND RESULTS After receiving aspirin 325 mg/d for 1 year after CABG and undergoing a 1-year postoperative cardiac catheterization, patients were randomized to receive either aspirin (325 mg) or placebo for 2 additional years. Angiography was performed 3 years after surgery to determine the primary end point-saphenous vein graft patency in 288 patients and IMA graft patency in 167 patients. At 3 years after CABG, the saphenous vein graft occlusion rate was 17.0% (62 of 365) for patients treated with aspirin compared with 19.7% (74 of 376) for those who received placebo (P = .404). For saphenous vein grafts that were patent at 1 year, the occlusion rate at 3 years was 4.8% (15 of 313) for patients treated with aspirin compared with 4.2% (13 of 310) for patients who received placebo (P = .757). At 3 years, the IMA graft occlusion rate was 10.3% (8 of 78) for patients treated with aspirin compared with 7.9% (7 of 89) for patients who received placebo (P = .594). For IMA grafts that were patent at 1 year, the occlusion rate was 4.3% (3 of 70) for patients treated with aspirin compared with 2.5% (2 of 81) for patients who received placebo (P = .541). CONCLUSIONS These data suggest that aspirin treatment does not improve saphenous vein graft or IMA graft patency between 1 and 3 years after CABG.

Proinflammatory cytokines are increased in type 2 diabetic women with cardiovascular disease

Diabetics have a much greater morbidity and mortality due to cardiovascular disease (CVD) than nondiabetics. Furthermore, diabetic women have a 3.8-fold greater risk for CVD compared to diabetic men. Inflammation is now considered a risk factor for CVD and it has been demonstrated that inflammation also plays a role in diabetes. One component of inflammation that has reported to be increased in patients with diabetes only and CVD only are proinflammatory cytokines, particularly interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha), and interleukin-1 (IL-1beta). This study was performed to test the hypothesis that these proinflammatory cytokines were increased in women with CVD and further increased in diabetic women with CVD compared to nondiabetic women with CVD and healthy age-matched controls. We found that IL-6 was increased in diabetic women with CVD compared to healthy age-matched controls (1.41 = 0.48 to 0.33 +/- 0.06 pg/ml, P < .05). IL-6 was also increased in diabetic women without CVD compared to healthy age-matched controls, but not significantly (0.96 +/- 0.27 to 0.33 +/- 0.06 pg/ml). We found that TNF-alpha was increased in diabetic women with and without CVD compared to healthy age-matched controls, but not significantly (4.53 +/- 1.38 to 3.93 +/ -0.53 to 2.33 +/- 0.89 pg/ml). IL-1beta was not significantly different among any of the four groups of women. These results indicate that both IL-6 and TNF-alpha are chronically increased in diabetic women with and without CVD compared to nondiabetic women. The additive concentration of cytokines in diabetes and CVD suggests a common inflammatory state in both diabetes and CVD.

Chronic inhibition of fatty acid oxidation: New model of diastolic dysfunction

This study was designed to determine the changes in the heart that result from inhibition of long-chain fatty acid oxidation with 2-tetradecylglycidic acid (TDGA). Male Sprague-Dawley rats (n = 64) were treated with TDGA (20 mg.kg-1.day-1) or a comparable volume of vehicle by gavage feeding for 7 or 21 days. In conscious rats TDGA produced no changes in heart rate, left ventricular systolic or end-diastolic pressures, left ventricular pressure development (dP/dt), or the time constant of left ventricular relaxation. Left ventricular developed pressure was not changed at 21 days. TDGA increased left ventricular weight, left ventricular weight-to-body weight ratio, and total heart weight-to-body weight ratio. Left ventricular endocardial and epicardial myocyte volumes were increased by 53 and 65%, respectively. Myocardial triglyceride content was increased threefold. Left ventricular chamber stiffness constants between end-diastolic pressures of 0 and 30 mmHg were increased, and left ventricular end-diastolic volumes at operating end-diastolic pressures were decreased at both 7 and 21 days. The myocardial stiffness constant was also increased at 7 and 21 days. Thus inhibition of long-chain fatty acid oxidation with TDGA increased left ventricular mass and altered left ventricular chamber and muscle stiffness without changing left ventricular relaxation or systolic function. We conclude that inhibition of long-chain fatty acid oxidation produced an unusual model of left ventricular hypertrophy and diastolic dysfunction characterized by abnormalities of passive-elastic properties but preserved relaxation.

Chronic expression of platelet adhesion proteins is associated with severe ischemic heart disease in type 2 diabetic patients: Chronic platelet activation in diabetic heart patients

Cardiac ischemia is a serious complication of type 2 diabetes. However, the pathophysiology underlying the increased severity of myocardial ischemia in diabetes is not clear. This study tested the hypothesis that platelet adhesion protein expression is chronically increased in older type 2 diabetic patients with established ischemic heart disease (IHD) compared to age-matched, nondiabetic patients with IHD. We compared the chronic expression of two platelet adhesion proteins, P-selectin and GPIIb/IIIa, in whole blood and the platelet reactivity to an acute stimulus. We found that the expression of platelet P-selectin was chronically increased in the nondiabetic patients with IHD compared to normal subjects. P-selectin expression was further increased in the diabetic patients with IHD compared to the nondiabetic IHD patients (P<.05). The results were stratified to examine the potential effect of aspirin usage on adhesion protein expression. We found that the expression of the activated GPIIb/IIIa complex was significantly reduced in those diabetic cardiac patients who were taking aspirin (P<.05). These findings indicate that, in patients with IHD, platelet adhesion proteins are chronically expressed and that the level of expression is increased more in IHD patients with type 2 diabetes. This complication of diabetes may exacerbate thrombus formation during a recurrent event, increasing the severity of ischemic injury. The results give further support to the use of aspirin in type 2 diabetics with established cardiac disease.

Multiple giant aneurysms of coronary arteries

Multiple giant aneurysms of the coronary arteries occur extremely rarely and are usually associated with Kawasaki disease in children. A 53-year-old man with multiple giant coronary artery aneurysms was treated successfully by aortocoronary bypass grafting.