Lyon Heart Study

The Lyon Heart Study was a dietary intervention study in which a modified diet of Crete (the experimental diet) was compared with the prudent diet, or Step I American Heart Association Diet (the control diet). The experimental diet provided a ratio of LA to ALA of 4/1. This ratio was achieved by substituting olive oil and canola (oil) margarine for com oil. Since olive oil is low in LA, whereas com oil is high (8% and 61%, respectively) the ALA incorporation into cell membranes was increased. Cleland et al. have shown that olive oil increases the ineorporation of omega-3 fatty acids, whereas the LA from com oil competes. The ratio of 4/1 of LA/ALA led to a 70% decrease in total mortality at the end of two years. ... 

The results of the Lyon Heart Study and the Indo-Mediterranean Diet Study are compatible with a large observational study, the Greece EPIC cohort, which demonstrates that the reduction in overall mortality is associated with increased adherence to the Mediterranean diet [49],... 

Clinical trials involving mixed nuts have been conducted in six countries Australia, Canada, Israel, India, New Zealand, and the United States [61-67]. In the studies that reported blood lipid values, the nut diets significantly reduced total cholesterol from 7% to 25% and low-density lipoprotein (LDL) cholesterol by 10%-33%. No studies found any significant effect on HDL cholesterol, and two found a significant decrease in triacylglycerols (TAG) [63,66]. Furthermore, both the Lyon Heart Study and the Indo-Mediterranean Diet Study showed a decrease in overall mortality and cardiovascular mortality [45,46]. 

The antiarrhythmic effects of n-3 fatty acids are supported by clinical intervention trials (Diet and Reinfarction Trial (DART), Lyon Heart Study, Gruppo Italiano per lo Studio della Soprawivenza nellTnfarto miocardico (GlSSI)-Prevenzione Trial, Indo-Mediterranean Diet Heart Study). Their results strongly support the role of fish or fish oil in decreasing total mortality and sudden death in patients with one episode of myocardial infarction. Therefore, the addition of 1 g/d of n-3 fatty acids is highly recommended for the primary and secondary prevention of coronary heart disease. 

Nonetheless, the inverse relationship between unsaturated fat and CVD is supported by the results from prospective cohort studies such as the Ireland-Boston Diet Heart Study (Kushi et al., 1985) and the Nurses Health Study (Hu et al., 1997) and long-term intervention studies such as the Los Angeles Veteran Study and the Finnish Mental Hospital Study (Dayton et al., 1965 Turpeinen et al., 1979). In the Indo-Mediterranean Diet Heart Study (Singh et al., 2002) and the Lyon Diet Heart Study (de Lorgeril et al., 1999), a diet high in unsaturated fat and complex carbohydrates were proven to be potent to reduce coronary events. It has been difficult to prove a clear relationship between saturated fat and future cardiovascular events in prospective cohort studies, and this is highlighted by the recent meta-analysis described below. 

In the Lyon Diet Heart Study, survivors of myocardial infarctions on a Mediterranean style diet rich in ALA were less likey to experience a second episode (de Lorgeril et al., 1994). These researchers reported that nonfatal myocardial infarctions and total death in subjects on the experimental and control diets were reduced by 75% and 70%, respectively. Fewer nonfatal myocardial infarctions also were reported in subjects consuming an Indo-Mediterranean diet rich in ALA (Singh et al., 2002). The Nurse s Health Study (Albert et al., 2004) also showed that diets rich in ALA reduce the risk of dying from coronary heart disease. The study was a 16-year followup involving approximately 76,000 women. Women on the highest ALA (1.5 g/day) diet had a 21% and 46%, respectively, lower risk of dying from coronary heart disease or sudden cardiac death compared to women on a 0.7 g ALA/day diet. 

There have been three primary and eight secondary prevention trials in which dietary change was the only variable. Dietary modification included reduction in total fat, substitution of saturated fat by polyunsaturated oils and reduction in cholesterol intake. These changes resulted in a reduction of saturated fat intake by 27 55% and reductions in plasma cholesterol of up to 18%. However, with the exception of one study, the Lyon Diet Heart Study (de Lorgeril et al., 1994), neither total or CHD mortality was lowered significantly by the dietary interventions (Ravnskov, 1998 Parodi, 2004). In the successful Lyon Diet Heart Study, a Mediterranean-type diet was compared with the usual post-infarct prudent diet. Throughout this trial, plasma cholesterol levels were similar in both the treatment and control groups. 

Kris-Etherton, P. et al., Lyon Diet Heart Study Benefits of a Mediterranean-style, National Cholesterol Education Program/American Heart Association Step 1 dietary pattern on cardiovascular disease. Circulation, 103, 1823, 2001. 

The Lyon Diet Heart Study gave us the first solid proof of the benefits of the Mediterranean diet in reducing heart disease. French researchers compared that diet, rich in olive oil, nuts, olives, avocados, and seafood, with the kind of diet typically prescribed by cardiologists in the United States, the United Kingdom, Australia, and elsewhere, which cut way back on fat, while replacing the fat calories with carbohydrates. The subjects were patients who had suffered heart attacks within the past six months. 

As previously discussed under pharmacological predictors, fish oil was shown to be beneficial in the GlSSI-Prevenzione trial in reducing all-cause and cardiovascular mortality. Increased omega-3 fatty acids are one component of the Mediterranean diet, which has the most substantial evidence for benefit in secondary prevention for patients with chronic ischemic heart disease. As reviewed by Parikh et al. (120), several studies have looked at either the addition of omega-3 fatty acids alone, or the institution of the Mediterranean diet in reducing cardiovascular endpoints in patients with established CHD. Perhaps the most impressive from the dietary standpoint was a follow-up of the Lyon Diet Heart study (121) which evaluated 605 post-MI survivors randomized to a Mediterranean-type diet versus a prudent Western-... 

Lyon Diet Heart Study, achieved >70% reduction in CAD events (5), evidence for the existence of other major targets that should be addressed. This short review examines recent paradigm shifts and advances in atherosclerosis research that are likely to influence the future of dietary intervention aimed at preventing CAD. It will consider in turn the shift of emphasis toward unstable plaques, inflammation, oxidative processes, and endothelial dysfunction, as well as the growing interest in gene-diet interactions. 

De Lorgeril, M., Salen, R, Martin, J.L., Monjaud, L, Delaye, J., and Mamelle, N. (1999) Mediterranean Diet, Traditional Risk Factors, and the Rate of Cardiovascular Complications After Myocardial Infarction—Final Report of the Lyon Diet Heart Study, Circulation 99,779-785. 

M. de Lorgeril, P. Salen, J.-L. Martin, I. Monjaud, J. Delaye and N. Mamelle, Mediterranean diet, traditional risk factors, and the rate of cardiovascular complications after myocardial infarction final report of the Lyon Diet Heart Study, Circulation 99, 779-785. 

The Lyon and GISSI-Prevention studies are particularly noteworthy because their subjects already had heart disease severe enough to have caused heart attacks. If those approaches worked for already diseased men and women, think of what they can do for you ... 

Descotes J (1992) Immunotoxicology of cadmium. In Nordberg GF, Herber RFM, Alessio L (eds) Cadmium in the human environment toxicity and carcinogenicity. Inti Agency Res Cancer, Lyon, France, pp 385-390 Donnelly TE (1978) Effects of zinc chloride on the hydrolysis of cyclic GMP and cyclic AMP by the activator-dependent cyclic nucleotide phosphodiesterase from bovine heart. Biochim Biophys Acta 522 151-160 Dorian C, Gattone VH II, Klaassen CD (1992) Renal cadmium disposition and injuries as a result of accumulation of cadmium-metallothionein by the proximal convoluted tubules - a light microscopic autoradiography study with CdMT. Toxicol Appl Pharmacol 114 173-181... 

Cova CARD and Cova ABDO (Biom Up, Lyon, France) are CE marked membranes that are made of purified porcine type I collagen membrane. The membrane is CToss-linked with an oxidized polysaccharide [139]. In a preclinical study, the efficacy of Cova CARD was compared with that of Seprafilm [140]. Sixteen sheep underwent a sternotomy followed by scratching of the heart surface. When the intensity of adhesion was assessed 4 months postoperatively, Cova CARD was found to have been almost totally absorbed, and the adhesion score was significantly lower than that of the Seprafilm group (1 vs. 3 (score from 1, absence to 3, tight)). There was no adverse inflammatory reaction due to Cova CARD , and the extent and density of fibrosis were small. 

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