Patricia Salen

Effect of a mediterranean type of diet on the rate of cardiovascular complications in patients with coronary artery disease insights into the cardioprotective effect of certain nutriments

OBJECTIVES We sought to describe the various cardiovascular complications that occurred in the Lyon Diet Heart Study (a secondary prevention trial testing the protective effects of a Mediterranean type of diet), to analyze their relations with the associated drug treatments and to gain insights into the possible mechanisms underlying the beneficial effects of certain nutriments. BACKGROUND Dietary habits are implicated in coronary heart disease, and the traditional Mediterranean diet is thought to be cardioprotective. However, the exact mechanisms of this protection are unknown. METHODS A total of 605 patients (303 control subjects and 302 study patients) were studied over a mean period of 27 months. Major primary end points (cardiovascular death and nonfatal acute myocardial infarction), secondary end points (including unstable angina, stroke, heart failure and embolisms) and minor end points (stable angina, need for myocardial revascularization, postangioplasty restenosis and thrombophlebitis) were analyzed separately and in combination. RESULTS When major primary and secondary end points were combined, there were 59 events in control subjects and 14 events in the study patients, showing a risk reduction of 76% (p < 0.0001). When these end points were combined with the minor end points, there were 104 events in control subjects and 68 events in the study patients, giving a risk reduction of 37% (p < 0.005). By observational analysis, only aspirin among the medications appeared to be significantly protective (risk ratio after adjustment for prognosis factors 0.45; 95% confidence interval 0.25 to 0.80). CONCLUSIONS These data show a protective effect of the Mediterranean diet. However, the risk reduction varied depending on the type of end point considered. Our hypothesis is that different pathogenetic mechanisms were responsible for the development of the various complications. It is likely that certain nutriments characteristic of the Mediterranean diet (omega-3 fatty acids, oleic acid antioxidant vitamins) have specific cardioprotective effects.

The Mediterranean-style diet for the prevention of cardiovascular diseases

OBJECTIVES To discuss present knowledge about Mediterranean diet and cardiovascular diseases. DESIGN Review of existing literature. SETTING AND RESULTS Epidemiological studies as well as randomised dietary trials suggest that Mediterranean diet may be important in relation to the pathogenesis (and prevention) of CHD. For instance, a striking protective effect of an ALA-rich Mediterranean diet was reported in the Lyon Diet Heart Study with a 50 to 70% reduction of the risk of recurrence after 4 years of follow-up in CHD patients. According to our current knowledge, dietary ALA should represent about 0.6 to 1% of total daily energy or about 2 g per day in patients following a Mediterranean diet, whereas the average intake in linoleic acid should not exceed 7 g per day. Supplementation with very-long-chain omega-3 fatty acids (about 1 g per day) in patients following a Mediterranean type of diet was shown to decrease the risk of cardiac death by 30% and of sudden cardiac death by 45% in the GISSI trial. CONCLUSIONS In the context of a diet rich in oleic acid, poor in saturated fats and low in omega-6 fatty acids (a dietary pattern characterising the traditional Mediterranean diet), even small doses of omega-3 fatty acids (about 1 g EPA+DHA the form of fish oil capsules or 2 g alpha-linolenic acid in canola oil and margarine) might be very protective. These data underline the importance of the accompanying diet in any dietary strategy using fatty acid complements.

Cholesterol lowering, cardiovascular diseases, and the rosuvastatin-JUPITER controversy: a critical reappraisal.

BACKGROUND Among the recently reported cholesterol-lowering drug trials, the JUPITER (Justification for the Use of Statins in Primary Prevention) trial is unique: it reports a substantial decrease in the risk of cardiovascular diseases among patients without coronary heart disease and with normal or low cholesterol levels. METHODS Careful review of both results and methods used in the trial and comparison with expected data. RESULTS The trial was flawed. It was discontinued (according to prespecified rules) after fewer than 2 years of follow-up, with no differences between the 2 groups on the most objective criteria. Clinical data showed a major discrepancy between significant reduction of nonfatal stroke and myocardial infarction but no effect on mortality from stroke and myocardial infarction. Cardiovascular mortality was surprisingly low compared with total mortality-between 5% and 18%-whereas the expected rate would have been close to 40%. Finally, there was a very low case-fatality rate of myocardial infarction, far from the expected number of close to 50%. The possibility that bias entered the trial is particularly concerning because of the strong commercial interest in the study. CONCLUSION The results of the trial do not support the use of statin treatment for primary prevention of cardiovascular diseases and raise troubling questions concerning the role of commercial sponsors.

Mediterranean diet and the French paradox: Two distinct biogeographic concepts for one consolidated scientific theory on the role of nutrition in coronary heart disease

Time for primary review 26 days. Scientists and physicians have long been debating the Mediterranean-style diet and the French paradox for coronary heart disease (CHD). However, folksy they sound, these two biogeographic concepts can still be very useful to explain unexpected or controversial medical and scientific data, such as the low mortality rate from CHD in Mediterranean Southern Europe and in France as compared with other European countries. Understanding these concepts may help improve our ability to treat and prevent CHD. Most of the present confusion probably comes from the consistent underestimation by physicians and scientists of the role of nutrition in CHD. This article is not aimed at giving a comprehensive review of these two complex notions, which have to be analyzed in a broad geographic, climatic, agricultural, historical and socioeconomic context. We will only provide a superficial overview, in relation to the epidemiology of CHD. Finally, we will try to introduce the two concepts as a fundamental premise of a new scientific theory on the role of nutrition in CHD, a theory that remains to be fully formulated. ### 2.1 Definition The definition of the Mediterranean-style diet varies according to the particular Mediterranean area that is considered. For instance, the Greek version of the Mediterranean diet is dominated by the consumption of olive oil and by a high consumption of vegetables and fruits [1]. Since antioxidants are common in these foods, an antioxidant action may provide a plausible explanation for the apparent benefits of that diet [1]. According to another version, however, the Mediterranean diet is a non-strict vegetarian diet rich in oleic acid, omega-3 fatty acids, fiber, vitamins of the B group and various antioxidants, but low in saturated and polyunsaturated fat [2]. With that wider definition, the expected benefits for the prevention of CHD go far … * Corresponding author. Laboratoire du Stress Cardiovasculaire et Pathologies Associees, UFR de Medecine et Pharmacie, Domaine de la Merci, 38706 La Tronche, Grenoble, France. Tel.: +33-4-7663-7471; fax: +33-4-7663-7152

Farmed and wild fish in the prevention of cardiovascular diseases: assessing possible differences in lipid nutritional values.

AIM The consumption of fish and fish-derived products is recommended as a means of preventing cardiovascular and other diseases, and has considerably increased over recent decades. However, as the worlds wild fish stocks are limited, consumers are now being proposed farmed fish as an alternative. The aim of this study was to compare the fat composition of farmed and wild fish in order to estimate whether the expected health effects of the former (especially in relation to cardiovascular diseases) are potentially the same as those of the latter. DATA SUMMARY The data presented in this paper were collected from the recently published literature. The lipid composition of farmed fish is more constant and less affected by seasonal variations than that of wild fish because, as it is largely dependent on the fatty acid composition of their feed, it can be customised by adjusting dietary intakes. Vegetable food is increasingly replacing fishmeal in fish feeds, and may induce a relative decrease in n-3 polyunsaturated fatty acids (PUFAs), expressed as a percentage of total fatty acids. However, as farmed fish generally have higher total lipid levels than wild fish, 100 g of farmed fish fillet can provide a higher amount of n-3 PUFAs (especially EPA and DHA) than 100 g of wild fish. Furthermore, quite high levels of (alpha-tocopherol in farmed fish can theoretically provide better EPA and DHA protection against peroxidation. Sensory analyses by trained consumer panels have not revealed any significant differences between wild and farmed fish. Moreover, fresh fish storage conditions (including the time from slaughtering to consumer sales) are more easily verifiable in the case of farmed fish, in which the content of potentially toxic heavy metals (a major health concern in certain areas) is also theoretically more easily controlled. CONCLUSIONS Provided that they are raised under appropriate conditions, the nutritional content of farmed fish is at least as beneficial as that of wild fish (particularly in terms of the prevention of cardiovascular diseases), and they also have the advantages of freshness and apparent non-toxicity.

New insights into the health effects of dietary saturated and omega-6 and omega-3 polyunsaturated fatty acids

Cardiovascular diseases and cancers are leading causes of morbidity and mortality. Reducing dietary saturated fat and replacing it with polyunsaturated fat is still the main dietary strategy to prevent cardiovascular diseases, although major flaws have been reported in the analyses supporting this approach. Recent studies introducing the concept of myocardial preconditioning have opened new avenues to understand the complex interplay between the various lipids and the risk of cardiovascular diseases. The optimal dietary fat profile includes a low intake of both saturated and omega-6 fatty acids and a moderate intake of omega-3 fatty acids. This profile is quite similar to the Mediterranean diet. On the other hand, recent studies have found a positive association between omega-6 and breast cancer risk. In contrast, omega-3 fatty acids do have anticancer properties. It has been shown that certain (Mediterranean) polyphenols significantly increase the endogenous synthesis of omega-3 whereas high intake of omega-6 decreases it. Finally, epidemiological studies suggest that a high omega-3 to omega-6 ratio may be the optimal strategy to decrease breast cancer risk. Thus, the present high intake of omega-6 in many countries is definitely not the optimal strategy to prevent cardiovascular disease and cancers. A moderate intake of plant and marine omega-3 in the context of the traditional Mediterranean diet (low in saturated and omega-6 fatty acids but high in plant monounsaturated fat) appears to be the best approach to reduce the risk of both cardiovascular diseases and cancers, in particular breast cancer.

Wine Drinking and Risks of Cardiovascular Complications After Recent Acute Myocardial Infarction

Background—Scientific data on the clinical impact of moderate alcohol consumption after a recent acute myocardial infarction (AMI) are limited, and the specific effect of wine ethanol has not been studied. Methods and Results—In survivors of a recent AMI, we analyzed the association between ethanol intake and the risk of recurrence. The patients were classified according to the amount of ethanol that they consumed regularly during follow-up. Major prognostic factors, including the severity of the prior AMI and drug treatment, were recorded and included in the analyses. Only patients with at least 2 reliable assessments of drinking (and dietary) habits were included (n=437). The average ethanol intake was 7.6% of the total energy intake, wherein wine ethanol represented 92% of the total. Among these patients, 104 cardiovascular complications occurred during a mean follow-up period of 4 years. In comparison with abstainers, the adjusted risk of complications was reduced by 59% (95% confidence interval: 17 to 80) in patients whose average ethanol intake was 7.7% of the total energy intake (about 2 drinks/day), and by 52% (95% confidence interval: 4 to 76) in those whose average ethanol intake was of 16% of energy (about 4 drinks/day). Conclusion—Whereas moderate wine drinking was associated with a significant reduction in the risk of complications in this homogenous population of coronary heart disease patients, further studies are required to confirm the data, define the clinical and biological profile of the patients who would most benefit from wine drinking after recent AMI, and examine whether the relations found are due to ethanol or other wine ingredients.

Dietary and blood antioxidants in patients with chronic heart failure. Insights into the potential importance of selenium in heart failure

Chronic heart failure (CHF) seems to be associated with increased oxidative stress. However, the hypothesis that antioxidant nutrients may contribute to the clinical severity of the disease has never been investigated.

Alpha-linolenic acid and coronary heart disease

AIM To summarize our present knowledge about vegetable omega-3 fatty acids. DATA SYNTHESIS Alpha-linolenic acid (ALA) is one of the two essential fatty acids in humans. Epidemiological studies and dietary trials strongly suggest that this fatty acid is important in relation with the pathogenesis (and prevention) of coronary heart disease. Like other n-3 fatty acids from marine origin, it may prevent cardiac arrhythmias and sudden cardiac death. The optimal dietary intake of alpha-linolenic acid seems to be about 2 g per day or 0.6 to 1% of total energy intake. Obtaining an optimal ratio of the two essential fatty acids, linoleic and alpha-linolenic acids--ie a ratio of less than 4 to 1 in the diet--is a major issue. The main sources of alpha-linolenic acid for the European population should be canola oil (and canola-oil based margarine if available), nuts (English walnut), ground linseeds and green leafy vegetables such as purslane. CONCLUSIONS Epidemiological studies and dietary trials in humans suggest that alpha-linolenic acid is a major cardio-protective nutrient.

Selenium and antioxidant defenses as major mediators in the development of chronic heart failure.

Increased oxidative stress is involved in the pathogenesis of chronic heart failure (CHF), the common end result of most cardiac diseases. Selenium is an “essential” trace element, which means that it must be supplied by our daily diet and that its blood and tissue concentrations are extremely low. Selenium has a variety of functions. It is a key component of several functional selenoproteins required for normal health. The best known of these are the antioxidant glutathione peroxidase (GPx) enzymes, which remove hydrogen peroxide and the harmful lipid hydroperoxides generated in vivo by oxygen-derived species. GPx deficiency exacerbates endothelial dysfunction, a major contributing factor in the severity of CHF symptoms, in various conditions such as hyperhomocysteinemia. This suggests that homocysteine may be involved in the CHF associated endothelial dysfunction through a peroxide-dependent oxidative mechanism. Selenium also plays a role in the control of thyroid hormone metabolism and in protection against organic and inorganic mercury. One possible additional mechanism by which low selenium may compromise cardiovascular condition may be through the effect of selenium on the synthesis and activity of deiodinases, enzymes converting thyroxin into the biologically active triiodothyronine. Selenium and iodine actually interact in cardiovascular physiology, and further studies are needed to examine their role, in isolation and in association, in the development of CHF. Thus, selenium (through its role in selenoenzymes, thyroid hormones, and interactions with homocysteine and endothelial function) appears to be a major mediator in several pathways potentially contributing to CHF development.