Blood lipids among young children in Europe: results from the European IDEFICS study.

BACKGROUND: Measurement of cholesterol and triglyceride (TG) fractions in blood has become standard practice in the early detection of atherosclerotic disease pathways. Considerable attention is given nowadays to the presence of these risk factors in children and to start preventive campaigns early in life. In this context, it is imperative to have valid comparative frameworks for interpretation of lipid levels. The aim of this study is to present sex- and age-specific reference values on blood lipid levels in European children aged 2.0-10.9 years. METHODS: Fasting blood was obtained via either venipuncture or capillary sampling. In 13,579 European non-obese children (50.3% boys), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), TG and TC/HDL-C ratio levels were measured with a point-of-care analyser (Cholestech). Sex- and age-specific reference values were computed with the GAMLSS method with the statistical software R. RESULTS: Reference curves and 1st, 3rd, 10th, 25th, 50th, 75th, 90th, 97th and 99th percentile values are presented. HDL-C showed a positive trend with age, from 2 years onwards, but was relatively stable above the age of 7. For LDL-C and TC, linear but small age-related trends were seen. The TC/HDL-C values showed a gradual negative trend from the age of 2 up to 6 and were relatively stable afterwards. For TG, no age trend was found (P=0.285). Boys had higher mean HDL-C values than girls (1.414 vs 1.368 mmol l(-1)), and lower TC, LDL-C, TC/HDL-C and TG values (3.981 vs 4.087 mmol l(-1); 2.297 vs 2.435 mmol l(-1); 2.84 vs 3.01mmol l(-1); and 0.509 vs 0.542 mmol l(-1), respectively). CONCLUSIONS: These new and recent references could serve as a European orientation of blood lipid values in children in the context of standard medical practice and for the purpose of public health screening.

Dietary patterns and fatty acids levels of three European populations. Results from the IMMIDIET study.

BACKGROUND AND AIMS: Differences in blood fatty acids (FAs) profile among populations with different lifestyle have partly been attributed to differences in food intake. A holistic approach in dietary guidance through dietary patterns is essential. This study aimed at evaluating the main plasma and red blood cell (RBC) FAs in three European populations and assessing the role of dietary patterns in explaining variation in their levels. METHODS: In the framework of the IMMIDIET Project, 1604 subjects (802 male-female pairs) aged 26-65 years were enrolled in Italy, Belgium and UK. Plasma and RBC FAs were measured. One year recall food frequency questionnaires were used to evaluate dietary habits of each individual. RESULTS: Italian cohort showed lower plasma and RBC n-3 levels than participants of the other two populations (P<0.001). Both plasma and RBC arachidonic acid were higher in Italian cohort as compared to Belgian and English. Reduced rank regression analysis indicated two dietary patterns explaining 35% and 17% of the total variation of the sum of plasma and RBC n-3, respectively. In a holistic dietary analysis, neither fish nor mollusks intake seemed to contribute to n-3 variation as compared to vegetable oils and polyphenol-rich foods. CONCLUSION: The Italian cohort presented significant lower plasma and RBC n-3 FA levels compared to Belgians and English. A holistic approach in dietary analysis seemed to explain a relatively high proportion of plasma and RBC n-3 FAs variability. Dietary pattern analysis may contribute to the study of the association of human diet with FAs levels.

Gender differences in copper, zinc and selenium status in diabetic-free metabolic syndrome European population - the IMMIDIET study.

BACKGROUND AND AIMS: The European 'IMMIDIET' study was designed to evaluate the effect of genetic and dietary habit interactions on cardiovascular disease risk factors in non-diabetic subjects. Copper, zinc and selenium are involved in redox balance and modifications of their homeostasis could be associated with metabolic syndrome. Because few studies have dealt with trace element status in metabolic syndrome with conflicting results, we aimed at investigating the relationships between plasma copper, zinc and selenium concentrations and metabolic syndrome in the IMMIDIET population. METHODS AND RESULTS: Male-female couples born and living in Abruzzo, Italy (n = 271); Limburg, Belgium (n = 267), southwest part of London, England (n = 263) and 205 Italian-Belgian mixed couples living in Belgium were enrolled. Data on medical history, hypertension and blood lipid profile, medication use, smoking and alcohol habits, physical activity and socioeconomic status were collected using a standardised questionnaire. Anthropometric, blood pressure, glucose, insulin, lipid profile and copper, zinc and selenium measurements were performed. Participants were classified in two groups according to the presence of metabolic syndrome (Yes/No). Comparison between these two groups, performed separately in men and women, indicated no association in men whereas, in women, metabolic syndrome was associated with higher plasma selenium concentrations (odds ratio (OR) = 1.55(1.28-1.89)); this association remained significant after adjustment for age, group, social status, physical activity, energy intake, alcohol consumption, smoking and hormonal status (OR = 1.33 (1.06-1.67)). CONCLUSION: Our results indicate gender differences in the association between plasma selenium concentration and metabolic syndrome without diabetes and may suggest a sub-clinical deleterious effect of high selenium status in women.

C reactive protein and its determinants in healthy men and women from European regions at different risk of coronary disease: the IMMIDIET Project.

AIM: Differences in C-reactive protein (CRP) levels and its determinants in three European populations at different risk of coronary artery disease (CAD) were studied. METHODS: Subjects were recruited randomly in Limburg (Belgium), Abruzzo (Italy) and south-west (SW) London (England). RESULTS: Ten-year risk of fatal coronary events (estimated using risk equations provided by the SCORE Project) was lower both in men and women from Abruzzo, intermediate in people from Limburg and higher in subjects from SW London. Within each country, high sensitivity (hs)-CRP levels were higher in the high-risk class in men but not in women. Men from Abruzzo had higher hs-CRP levels than those from Limburg and SW London. Women always had higher hs-CRP levels than men. The strongest hs-CRP determinant was body mass index (BMI, R(2) = 0.14) in women and waist circumference (WC, R(2) = 0.046) in men. The highest hs-CRP levels were observed in subjects with both high BMI and high WC. Metabolic syndrome was associated with high levels of CRP both in men and women, even after adjustment for confounders. DISCUSSION: Difference in CRP levels cannot explain the European gradient of CVD risk, although CRP levels are associated with the calculated SCORE risk of fatal coronary events within each country.

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.

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 world's 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.

Is alcohol anti-inflammatory in the context of coronary heart disease?

Although the cardioprotective effect of alcohol has been primarily explained by its effect on blood lipids and platelets, could an anti-inflammatory mechanism be involved?

Resveratrol and non-ethanolic components of wine in experimental cardiology.

The mechanisms through which the consumption of alcoholic beverages, in particular wine, protects against cardiac and vascular diseases remain largely unexplored. New methods are needed to investigate that crucial medical and scientific question. Several groups are now beginning to use animal models of myocardial ischemia and reperfusion to explore whether certain nutrients, including ethanol and non-ethanolic components of wine, may have a specific protective effect on the myocardium, independently from the classical risk factors involved in vascular atherosclerosis and thrombosis. Concepts used in experimental cardiology, such as preconditioning and stunning, are now entering the field of nutrition, and this will undoubtedly lead to considerable improvements in the prevention and treatment of cardiovascular diseases.

Insulin resistance modifies plasma fatty acid distribution and decreases cardiac tolerance to in vivo ischaemia/reperfusion in rats.

1. The early stage of insulin resistance, also termed the 'prediabetic state', is characterized by the development of hyperinsulinaemia, which maintains normoglycaemia under fasting conditions. The metabolic disorders induced in myocardial cells during this stage of the disease may constitute a basis for an alteration of the tolerance of the heart to ischaemia and reperfusion. 2. To test this hypothesis, male Wistar rats were fed a 66% fructose diet for 4 weeks, inducing a prediabetic state. Rats were then subjected to in vivo left coronary artery ligation followed by reperfusion. Blood samples were collected for plasma lipid profile determination. 3. The prediabetic state significantly increased the severity of ischaemia-induced arrhythmias (arrhythmia score 1.4 +/- 0.2 vs 2.0 +/- 0.0 in control and fructose-fed rats, respectively; P < 0.05) and the size of infarction (infarct size 41.2 +/- 3.0 vs 56.0 +/- 2.0% in control and fructose-fed rats, respectively; P < 0.01). This alteration of the tolerance to in vivo ischaemia/reperfusion may be the consequence of an increase in mono-unsaturated fatty acids and a decrease in omega3 polyunsaturated fatty acids in fructose-fed-rats. 4. In conclusion, because it is known that the prediabetic state increases the incidence of cardiovascular diseases by promoting coronaropathy, our study suggests that this metabolic disorder may also affect the prognosis of heart disease by decreasing the tolerance of cardiomyocytes to ischaemic insults.

Dietary prevention of post-angioplasty restenosis. From illusion and disillusion to pragmatism.

Prevention of restenosis and major cardiac events after percutaneous coronary intervention (PCI) is of enormous public health importance. Despite the considerable decrease in the restenosis rate in relation to the advent of the drug-eluting stents, it is likely that the complication will still occur in some patients and/or after a certain delay. Thus, dietary or systemic drug prevention will probably have a role in the drama in the future, although the way they can be used is not clear at present. This discussion focuses on the dietary approach of post-PCI restenosis because, among the many drugs that have been tested, none has been consistently shown to be helpful--with the exception of the potent antioxidant drug probucol--, whereas the results of several dietary trials have been encouraging. As discussed in the present issue of NMCD, vitamins of the B group were recently shown to decrease the risk of restenosis, supposedly through an effect on homocysteine metabolization. It seems, however, that homocysteine is a minor risk factor of post-PCI restenosis. On the other hand, 5-methyltetrahydrofolate (the active form of folic acid) was shown to improve endothelial function independently from homocysteine. Thus, folic acid could prevent restenosis not only by reducing homocysteine, but also by promoting nitric oxide formation. Because of their potential to prevent post-PCI restenosis and acute cardiac complications, n-3 fatty acids have been the most widely studied post-PCI medical intervention. Taken together, trial data suggest that if n-3 fatty acids can be useful in certain populations to prevent restenosis, their effects are probably weak. However, according to recent studies on endothelial nitric oxide synthase (eNOS) gene polymorphisms, it is likely that only certain patients could benefit from n-3 fatty acid supplementation. The same reasoning can probably apply to the folic acid and eNOS issue. In conclusion, although none has been concluding, the studies about n-3 fatty acids and folic acid after PCI suggest that certain nutrients (or more probably a combination of nutrients) may be useful for the prevention of post-PCI restenosis. Any future trial involving these nutrients should combine them and take into account some major genetic confounders. In the meantime, it is medically and ethically justified to supplement our CHD patients after PCI. They should receive n-3 fatty acids to prevent sudden cardiac death, and B group vitamins (at the dosages tested in the Swiss Heart Study) to decrease the risk of restenosis. This would be, at least, a low cost intervention, and there is no fear of adverse side effects, contrary to those one can expect from drug treatments.

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

BACKGROUND: 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. AIMS: To examine whether antioxidant nutrients influence the exercise capacity and left ventricular function in patients with CHF. METHODS: Dietary intake and blood levels of major antioxidant nutrients were evaluated in 21 consecutive CHF patients and in healthy age- and sex-matched controls. Two indexes of the severity of CHF, peak exercise oxygen consumption (peak VO2) and left ventricular ejection fraction (LVEF), were measured and their relations with antioxidants were analysed. RESULTS: Whereas plasma alpha-tocopherol and retinol were in the normal range, vitamin C (P=0.005) and beta-carotene (P=0.01) were lower in CHF. However, there was no significant association between vitamins and either peak VO2 or LVEF. Dietary intake (P<0.05) and blood levels of selenium (P<0.0005) were lower in CHF. Peak VO2 (but not LVEF) was strongly correlated with blood selenium: r=0.76 by univariate analysis (polynomial regression) and r=0.87 (P<0.0005) after adjustment for age, sex and LVEF. CONCLUSIONS: Antioxidant defences are altered in patients with CHF. Selenium may play a role in the clinical severity of the disease, rather than in the degree of left ventricular dysfunction. Further studies are warranted to confirm the data in a large sample size and to investigate the mechanisms by which selenium and other antioxidant nutrients are involved in CHF.

Effect of wine ethanol on serum iron and ferritin levels in patients with coronary heart disease.

BACKGROUND AND AIM: The association between high body iron stores and coronary heart disease (CHD) is a subject of intense debate whereas wine consumption is known to be associated with a low CHD rate. It has been suggested that the inhibition of iron absorption is one of the possible mechanisms of the CHD-protective effects of drinking. METHODS AND RESULTS: We analysed the interrelationships of wine ethanol intake and fasting serum ferritin, iron and gamma glutamyl transferase (GGT) in patients enrolled in the Lyon Diet Heart Study, a secondary prevention trial designed to test whether a Mediterranean-type diet may protect against CHD. The intake of wine ethanol was evaluated in the 24 hours preceding blood sampling, and expressed as a percentage of the total daily energy intake. Data were obtained from 437 consecutive patients. There was a positive relationship (Spearman statistics) between wine ethanol and the serum levels of iron (r = 0.21, p < 0.0001), ferritin (r = 0.23, p < 0.0001) and GGT (r = 0.31, p < 0.0001). Uni- and multilinear regression analyses after excluding non-drinkers and log transforming the variables yielded similar results. CONCLUSIONS: The available data showing positive relationships between wine ethanol intake and serum concentrations of both ferritin and iron in patients with CHD tend to disprove the hypothesis that wine ethanol consumption could decrease iron stores and thereby the risk of CHD. Further studies are required to investigate the mechanism(s) by which wine drinking reduces the risk of CHD.

Dietary habit profile in European communities with different risk of myocardial infarction: the impact of migration as a model of gene-environment interaction. The IMMIDIET Study.

The risk of myocardial infarction (MI) is lower in southern than in northern European countries. The lower rate of MI in the Mediterranean regions of Europe suggested a potential role of the traditional Mediterranean diet in the prevention of MI. Unfortunately, in the last 20 years, a tendency to adopt Westernised food habits even in southern regions of Europe is reflected by an increase in the prevalence of obesity. Therefore the impact of diet on MI risk profile among European populations needs to be reconsidered. Genetic risk factors have also been implicated in the development of MI. Genes, indeed, continuously interact with environmental factors in determining the pathogenesis of MI. The aims of the IMMIDIET study are to evaluate: 1. The present dietary habits and the risk profile of three European communities at different risk of MI; 2. The impact of migration on risk factors for MI. Dietary habits and genetic polymorphisms will be evaluated in an Italian, Belgian and British population sample. The historical Italian migration to Belgium and the integration through mixed marriage will be considered as a model of gene-environment interaction. As an index of MI risk profile, factors that are most likely under the combined influence of both dietary and genetic determinants will be investigated.

The dietary prevention and treatment of coronary heart disease in the new millennium.

Dietary changes can reduce the risk of coronary artery disease by 50%-70%. By understanding the mechanism, we can begin explaining why coronary heart disease has been the leading cause of mortality in most industrialized nations over the last century.

Diet as preventive medicine in cardiology.

Because the main cause of death in patients with established coronary heart disease (CHD) is sudden cardiac death (SCD), physicians should develop specific strategy, including dietary changes, to prevent it. In the long term, reduction of the diet-dependent chronic risk factors of CHD, hypercholesterolemia, hypertension, and diabetes, is also important. The association of the cardioprotective effects of the Mediterranean diet (through various mechanisms, likely including the prevention of SCD) with those expected from the reduction of blood lipids and blood pressure and a better control of diabetes (in addition to its gastronomic appeal) renders this dietary pattern extremely attractive for public health purposes. Experimental and epidemiologic studies, as well as randomized trials, clearly demonstrated that n-3 fatty acids reduce the risk of SCD in CHD patients. Their use is now encouraged either as supplements or as part of a Mediterranean-type diet.

Diet and medication for heart protection in secondary prevention of coronary heart disease. New concepts.

BACKGROUND: Sudden cardiac death (SCD) has accounted for about half of total cardiovascular mortality in recent secondary prevention trials. In addition, chronic heart failure (CHF) is becoming the first cause of hospitalisation of cardiac patients and rising to epidemic proportions in most Western countries. Strategies for the secondary prevention of coronary heart disease (CHD) and cardiac rehabilitation programmes should therefore primarily focus on the prevention of these two major clinical complications. OBJECTIVES: To discuss the most effective medication and diet for the prevention of SCD in relation to the current emphasis on essentially two other major goals, namely prevention of thrombosis and modification of blood lipid parameters, and the effects of the Mediterranean type of diet in this context. DATA SYNOPSIS AND CONCLUSIONS: Experimental and clinical studies suggest that anti-platelet agents may have pro-arrhythmic effects and increase the risk of SCD. Warfarin should be thus preferred for patients at high risk of SCD (those with severe left ventricular dysfunction) and in its secondary prevention. Data from secondary prevention trials with statins have revealed differences in their specific effect on the end-point SCD. Simvastatin was significantly protective, whereas pravastatin was ineffective in both CARE and LIPID. The implication of this fact in the clinical practice might be substantial. Lastly, the most effective means of reducing the risk of SCD (apart from the prophylactic implantation of a defibrillator) appears to be dietary prevention in the light of animal experiments, epidemiological studies and four randomised trials showing that (n-3) fatty acids are extremely effective to prevent ischemic ventricular arrhythmias and SCD. However, in the two trials that assessed the actual effect of (n-3) fatty acids in the absence of other dietary changes, non-sudden cardiac death and non-fatal myocardial infarction were not reduced, suggesting that dietary changes in secondary prevention should be more global and not restricted to a single class of nutrient. Adoption of a dietary pattern, for instance a Mediterranean type of diet, seems to be the best way.