N-3 fatty acids and revascularization procedures

Largely initiated by studies among Greenland Eskimos in the early 1970s, great attention has been given to the possible effects of the very long chain n-3 polyunsaturated fatty acids (PUFA) in a variety of cardiovascular disease states. A series of possibly positive effects on pathogenetic mechanisms in cardiovascular disease has evolved from laboratory studies in cell cultures and animals as well as in humans, focusing mainly on eicosanoid metabolism with reduced activities of platelets and leucocytes, reduced plasma triglycerides and, antiarrhythmic effects in the myocardium. A rationale for a positive effect of very long chain n-3 PUFA in the secondary prophylaxis after revascularization procedures obviously also exists. The positive clinical effects based on prospectively randomized trials are summarized as follows. After coronary artery bypass grafting (CABG), the SHOT study showed statistically significant reduction in angiographic vein graft occlusion in 610 patients after 1 yr with supplementation of 3.4 g/d of highly concentrated very long chain n-3 PUFA. The reduction in occlusion rates was significantly related to the change in the n-3 PUFA concentration in serum phospholipids during the study period with the occlusion rate in the upper quartile of such changes at only similar to50% of that in the lower quartile. These results were also clearly related to the presence of angina pectoris and occurrence of myocardial infarction after 1 yr. Several studies were conducted in patients after percutaneous transluminal coronary angioplasty (PTCA). By 1993, two meta-analyses indicated a positive effect on the restenosis rate, a significant problem after otherwise successful PTCA. During the late 1990s, three large prospective randomized placebo-controlled angiographic studies were conducted with very long n-3 PUFA 5.1-8.0 g/d, all with completely negative results. Today, therefore, very long chain n-3 PUFA supplementation cannot be recommended to reduce the incidence of restenosis after PTCA. All studies were performed without stenting of the coronary lesion. In the very special revascularization procedure of heart transplantation, evolving hypertension and accelerated atherosclerosis have been major clinical problems. In other studies, positive effects by supplementation with very long chain n-3 PUFA (3.4-5.7 g/d) were obtained on the surrogate end points coronary vasoreactivity to acetylcholine and hypertension, respectively. On the basis of the presently available literature from clinical studies, recommendations for supplementation with very long chain n-3 PUFA can be given to patients after venous CABG (up to 3.4 g/d), and after heart transplantation (3.4-5.7 g/d) but not to patients after traditional PTCA. In fact, data from substudies suggested the possibility that large doses (5.1 g/d) of very long chain n-3 PUFA might be contraindicated because they induce a proinflammatory state in patients under oxidative stress.