The Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione trial was conceived as a population pragmatic trial on 11,323 patients with recent myocardial infarctions (MI) conducted in the framework of the Italian public health system. The prime aim was to see if omega-3 polyunsaturated fatty acids (n-3 PUFA), vitamin E or the two combined affected mortality and morbidity outcomes.
  Findings of the GISSI-Prevenzione study “strongly suggest” that treatment with n-3 PUFA be integrated with standard treatment and recommended it as a new component of secondary prevention in post-MI patients, reported lead investigator Dr. Roberto Marchioli, Consorzio Mario Negri Sud, Santa Maria Imbaro, Chieti, Italy.
  According to Dr. Marchioli, long-term n-3 PUFA 1.0 g/ day treatment significantly reduced overall risks by 20%, cardiovascular (CV) risks by 30% and sudden death by 45%. A time course analysis showed that the fall in all-cause mortality reached statistical significance after only three months (P=0.037), sudden death after four months (P=0.048) and CV death after nine months. Numbers of deaths due to non-CV causes were similar in the n-3 PUFA group and controls. In patients on a Mediterranean diet who were also receiving standard preventive pharmacological treatments

(ASA, β-blockers, ACE inhibitors and statins), the benefits were additive.

Preliminary subgroup analysis further suggested that the beneficial effects of n-3 PUFAs were similar in diabetic patients, those with different dietary habits and people taking statins.
These findings were “at variance with the cholesterolheart hypothesis,” Dr. Marchioli observed. That is because n-3 PUFAs achieve their effects even though virtually devoid of any cholesterol-lowering properties other than a small but significant reduction in triglycerides. The study showed that up to 5.7 lives/year could be saved for every 1000 previous- MI patients, a finding comparable to the Long-Term Intervention with Pravastatin in Ischemic Disease (LIPID) trial which showed that 5.2 lives/year could be saved per 1000 hypercholesterolemic coronary heart disease (CHD) patients.
A relatively low-dose regimen with a 1.0-g daily capsule is more acceptable in long-term treatment, Dr. Marchioli suggested. The pattern of effects seen in GISSIPrevenzione— the reduction in overall mortality without a fall in the rate of non-fatal MIs—clearly indicated that n-3 PUFA treatment should be a recommended part of secondary prevention. Moreover, there was a direct correlation between the size of the effect and the “correctness” of background diets, Dr. Marchioli noted.

25th Annual Congress of the European Society of Cardiology According to Dr. Andrew Coats, Dean, Faculty of Medicine, University of Sydney, Australia, secondary prevention requires accurate risk stratification, but this is difficult in many cases. Heart rate variability, though a very complex measure, is an effective and economic way of estimating sympatho-vagal balance and powerful in risk stratification.
  “We are only beginning to understand exactly what heart rate variability means and the opportunity it might give us to dissect out the mechanisms of action of effective treatment and to guide new treatments. But it does seem to be one of the most useful, easy and reliable prognostic markers that could be measured in patients needing secondary prevention,” Dr. Coats noted. “Improving heart rate variability seems to mediate protection for opportunistic arrhythmias and may be a useful technique if we could find specific agents to enhance the variability. The mechanisms of certain interventions already known to be beneficial appear to be mediated at least in part via effects on heart rate variability.”
  There are well-developed pharmacological therapies to block the effect of sympathetic nerve endings. It is not known where treatments such as exercise training, weight loss and reduction in anxiety and depression have their effect but all such interventions seem to enhance heart rate variability. That might be the common link to improvement in cardiac outcomes, particularly suppression of opportunistic ventricular arrhythmias summarized by interactions between baroreflex continuation and chemoreflex augmentation. They interact to give tonic and modulated sympathetic control of the whole CV system.
  Whatever therapeutic and preventive progress that has been made, there is still a need for new therapies to prevent sudden cardiac death, reported Dr. Heinz Rupp, Philipps- Universität, Marburg, Germany.
  The major pathophysiological cause of sudden death is seen in the electrical instability of the infarct zone and noninfarcted muscle.

Loss of contractile tissue means that the hypertrophied surviving myocardium is subjected to greater adverse neuroendocrine influences, leading to unfavourable cellular and molecular restructuring of the extra-cellular matrix and the cardiomyocyte. Fibrosis also adversely affects the coronary blood supply and increases the risk of infarction.

Conventional therapies such as ACE inhibitors, β-blockers, antiplatelet agents and probably statins are only partially useful against mechanisms which lead to electrical instability.
  However, according to researchers, this could be affected by specifically altering the body’s fatty acid profile. Fatty acids in membranes and fat stores depend not only on dietary intake but also on adrenergic influences, and fatty acids can influence the function of membrane proteins such as ion channels, pumps, exchangers and receptors. Experimental research has shown that by incorporating n-3 PUFAs into cardiac membranes, an ischemia-induced electrical instability could be reduced. However, although EPA/DHA can be derived from dietary α-linoleic acid, it is not considered to be sufficient.
  With respect to turning to the protective action of EPA/DHA in the ischemic heart after MI, Dr. Rupp pointed out that dilatation often occurs despite the hypertrophy of the non-infarcted myocardium, leading to more arrhythmic events. Cardiac dilatation also amplifies the risk of re-entry in the ischemic myocardium.
  Research findings suggest that EPA/DHA could reduce the activity of various ion channels and thus counter these arrhythmogenic substrates. It appears n-3 PUFA could have a protective action at membrane concentrations which have no effect on channel properties of normal hearts.
  These results, together with the GISSI-Prevenzione findings—that only 1.0 g/day of n-3 PUFA is needed to reduce electrical instability and impact on mortality—demonstrates that n-3 PUFA holds an important place in the secondary prevention and reduction of coronary artery disease mortality and morbidity.