[The behavioral goals of the coronary patient: No longer smoke, eat better, move more and better]. / Les objectifs comportementaux du patient coronarien : ne plus fumer, manger mieux, bouger plus et mieux.

The behavioral goals of the coronary patient require active management by the cardiologist. Every smoker must be clearly informed about the cardiovascular consequences of smoking and the major benefits of smoking cessation. The only advice to "quit smoking" is not enough. Validated "treatments" (cognitive-behavioral therapy, nicotine replacement therapy, varenicline, bupropion) must be used, with a precise strategy and prolonged follow-up. All drugs assistance can be prescribed in coronary patients and nicotine replacement therapy can even be used just after a myocardial infarction. Nutrition plays a significant role in cardiovascular prevention. Counseling today is based on solid evidence, although evidence is harder to obtain than with drugs. It should no longer be advisable only to "suppress cooked fats and starches" because these recommendations are unclear and/or false. Today we need positive food-based benchmarks and complex dietary patterns in which fruits and vegetables, fish, whole grains, pulses, nuts, olive oil and a diet closed to the Mediterranean diet. Dairy products have their place. Sugary foods should be limited especially in case of overweight and metabolic syndrome. Physical activity is part of good nutrition. Indeed, the fight against a very sedentary lifestyle and physical inactivity in coronary and heart failure patients is part of the lifelong treatment of these patients. The cardiologist and the general practitioner must be much more involved in their prescription and education to hope for good compliance.

Evaluation of short food-frequency questionnaires to assess the dietary pattern associated with atherosclerotic cardiovascular diseases.

OBJECTIVES: Cardiovascular diseases are strongly related to dietary habits. Diet can be assessed using dedicated questionnaires that can be self-completed by subjects but with the risk of errors. AIM: To compare the completion error rate of two questionnaires designed to assess dietary pattern linked to cardiovascular diseases and to study the correlation between the two questionnaires. MATERIALS AND METHODS: Two questionnaires were used to assess dietary patterns of students: the 14-item Food-Frequency-Questionnaire (FFQ) that was validated against biomarkers, and the Cardiovascular-Dietary-Questionnaire 2 (CDQ2), which is a 19-item-FFQ derived from the previous 14-item FFQ. Both questionnaires assessed the intake of various food groups associated with either favourable or unfavourable effects on cardiovascular risk. A global dietary score was calculated for each questionnaire. RESULTS: FFQ and CDQ2 were completed by 150 sport degree students. In the case of FFQ, 111 questionnaires out of 150 (74.0%) were incomplete compared to only 1 CDQ2 out of 150 (0.7%) (P<0.001). The correlation coefficient between the overall CDQ2 score and the FFQ dietary score was 0.53 (P<0.01). CONCLUSION: The self-completion of CDQ2 compared to FFQ was associated with far less errors. There was a significant correlation between CDQ2 and FFQ. Preference should be given to CDQ2 in clinical practice and in studies where dietary pattern are evaluated without any interviewer.

Genotoxic risk of ethyl-paraben could be related to telomere shortening.

The ability of parabens to promote the appearance of multiple cancer hallmarks in breast epithelium cells provides grounds for regulatory review of the implication of the presence of parabens in human breast tissue. It is well documented that telomere dysfunction plays a significant role in the initiation of genomic instability during carcinogenesis in human breast cancer. In the present study, we evaluated the genotoxic effect of ethyl 4-hydroxybenzoate (ethyl-paraben), with and without metabolic activation (S9), in studies following OECD guidelines. We observed a significant increase in genotoxic damage using the Mouse Lymphoma Assay and in vitro micronucleus (MN) tests in the L5178Y cell line in the presence of S9 only after a short exposure. A high frequency of MN was observed in the TK6 cells after a short exposure (3 h) in the presence of S9 and a long exposure (26 h) without S9. We found significant increases in the MN frequency and induced chromosomal aberrations in the lymphocytes of only one donor after ethyl-paraben exposure in the presence of S9 after a short exposure. Cytogenetic characterization of the paraben-treated cells demonstrated telomere shortening associated with telomere loss and telomere deletions in L5178Y and TK6 cells and lymphocytes of the paraben sensitive-donor. In a control cohort of 68 human lymphocytes, telomere length and telomere aberrations were age-dependent and showed high inter-individual variation. This study is the first to link telomere shortening and the genotoxic effect of ethyl paraben in the presence of S9 and raises the possibility that telomere shortening may be a proxy for underlying inter-individual sensitivity to ethyl-paraben. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of phytosterols/stanols on LDL concentration and other surrogate markers of cardiovascular risk.

Plant sterols and stanols are well-known to reduce LDL-cholesterol (LDL-C) concentrations. It is generally accepted that supplementation with 2g/day of sterols/stanols leads to a 10% reduction in LDL. However, most of the clinical trials supporting this conclusion were of short-term duration, and the results of longer interventions are scanty. In four studies, interventions lasting>6 months were carried out and the LDL-C-lowering effects were maintained over this longer duration, although some results suggest that a reduced effect may be observed with sterols, while stanols maintain their effect. In any case, the data are too limited to be definitive. In a free-living population as well as in multiparametric interventional studies, however, the LDL-C-lowering effect has been confirmed, although to a lesser extent than in clinical studies. In the absence of data on cardiovascular morbidity and mortality, data for surrogate markers of cardiovascular risk could be considered adequate alternatives. Several studies have been conducted on this basis, but their results failed to demonstrate any favourable effects. The present report summarizes the different results obtained in long-term studies, and in those comparing the effects of sterols and stanols on lipids and other surrogate markers of cardiovascular risk.

Cardiovascular risk and lifestyle habits of consumers of a phytosterol-enriched yogurt in a real-life setting.

BACKGROUND: Data on the characteristics of consumers of phytosterol-enriched products and modalities of consumption are rare. An observational study evaluating the lifestyle characteristics and cardiovascular risk (CVR) profile of phytosterol-enriched yogurt consumers was performed in France. METHODS: Subjects were recruited from general practitioners via electronic medical records. Data were obtained from 358 consumers and 422 nonconsumers with 519 subject questionnaires (243 consumers, 276 nonconsumers; 67% response). RESULTS: Consumers had more cardiovascular risk factors than nonconsumers (2.0 ± 1.5 versus 1.6 ± 1.4; P < 0.001) and a higher 10-year SCORE cardiovascular risk (1.8 ± 2.0% versus 1.6 ± 2.2%; P = 0.008); they were older (P = 0.030) and had a higher incidence of hypercholesterolaemia (P < 0.001) and family or personal history of heart disease (P = 0.023/P = 0.026, respectively). Among consumers not on cholesterol-lowering medication, 99% were eligible for lifestyle interventions and 56% were eligible for lipid-lowering drug according to European guidelines. Consumers had a healthier lifestyle, with a higher (fruit/vegetable - saturated fatty acid) score than nonconsumers (P = 0.035), focused more on low-intensity leisure activity (P = 0.023), spent more time travelling by foot or bicycle (P = 0.012) and were more likely to act to reduce CVR. Phytosterol-enriched yogurt intake conformed to recommendations in two-thirds of consumers and was mainly consumed because of concerns over cholesterol levels and CVR. CONCLUSIONS: The higher cardiovascular disease risk profile of phytosterol-enriched yogurt consumers corresponds to a population for whom European guidelines recommend lifestyle changes to manage cholesterol. The coherence of the data in terms of risk factors, adherence to lifestyle recommendations and the consumption of phytosterol-enriched yogurt conforming to recommendations reflects a health-conscious consumer population.

[Use of prolonged-release nicotinic acid in patients treated with statins as a secondary prevention and a persistently low HDL-cholesterol level in France]. / Etude d'utilisation de l'acide nicotinique a libération prolongée en France chez des patients en prévention secondaire sous statine avec persistance d'un taux bas de HDL-c.

UNLABELLED: HDL-c is a potent predictor of cardiovascular risk in all epidemiologic studies, especially as secondary prevention, regardless of LDL-c level obtained on statin treatment. The objective of this longitudinal observational study was to investigate the effects of prolonged-release nicotinic acid in high cardiovascular risk patients on statin treatment and with low HDL-c. METHOD: The selected patients of both genders, aged over 18 years patients showed primary hypercholesterolemia or mixed hyperlipidemia, received statin treatment as secondary prevention and had a HDL-c level

[The best of epidemiology and cardiovascular prevention in 2006]. / L'essentiel de 2006 en épidemiologie et prévention cardiovasculaire.

The recent analysis of the French MONICA registries report a reduction in the incidence of fatal MI related to improvement of care whereas the overall incidence of coronary events remain stable, suggesting the need for a better primary prevention. The extensive review of the death certificates and the analysis of the death classification from the same registries indicate an under estimation of MI-related death in the national death registry. It is also confirmed that instead of 50%, approximately 80% of coronary death are explained by the four major risk factors including smoking, hypercholesterolemia, hypertension and diabetes. The international REACH registry has enrolled more than 67 000 individuals including patients with symptomatic atherothrombotic disease and patients with multiple risk factors. The analysis of baseline characteristics and of the one year FU shows a high residual risk and a lack of efficacy of secondary prevention. The existence of a symptomatic disease and the number of symptomatic localization of atherothrombosis are critical factors to predict recurrence of major vascular events Secondary analysis of the INTERHEART study provide the essence of what should any physician know about the relationship between coronary heart disease and smoking, either active or passive. Prevention with respect to this risk factor remains very insufficient. Varenicline, a new nicotinic receptor partial agonist, should help patients involved in smoking cessation program. The established detrimental effects of perioperative smoking represent a unique opportunity to promote smoking cessation in individuals scheduled for surgery. The major cardiovascular impact of second hand smoking has been recently demonstrated by the short-term effects of banning smoking in public places on the incidence of acute coronary events. The SPARCL study has demonstrated the benefit of high dose of atorvastatine to prevent recurrent acute ischemic cerebrovascular event in patients with a prior history of stroke or TIA. In the open ASTEROID study, high doses of rosuvastatine confirm the possibility of reducing the volume of coronary atheroma analyzed by IVUS. The expected benefit of glitazones to reduce the incidence of death, MI and stroke in diabetes patients with a prior history of vascular event has been confirmed in the PROactive study. Pioglitazone provided a clear reduction of recurrent vascular events in diabetes patient with a prior MI at a cost of a significant increase of the risk of heart failure. In the DREAM study, neither ramipril nor rosiglitazone have reduced the incidence of cardiovascular events significantly. The moderate benefit of the fenofibrate to prevent cardiovascular events in the FIELD study, which was carried out in diabetics mostly in primary prevention, needs to be considered after adjustment on statin use in a higher proportion of patients of the placebo group. Postprandial hyperglycaemia, analyzed by the peak of glycaemia after a load in glucose, has been confirmed as a more powerful independent predictive factor of the risk of cardiovascular event than fasting glycaemia. The systematic screening postprandial hyperglycaemia represents an interesting strategy for primary prevention which warrants further investigation. If obesity is a risk factor whose impact on morbi-mortality is well established, a French study shows that body mass index has an unfavourable influence on the cognitive functions in middle-aged men and women.

[The best of epidemiology and cardiovascular prevention in 2005]. / L'essentiel de 2005 en épidémiologie et prévention cardiovasculaire.

It is difficult to summarize in a few pages the wealth of information appeared during the year 2005 in the field of epidemiology and cardiovascular prevention. The general epidemiological data on the evolutionary tendencies of coronary mortality and morbidity make it possible to underline the effectiveness of the control of the great risk factors within the framework of the primary prevention. Although lipids and diabetes have still this year held the front of the scene through many trials, this analysis is also focused on smoking, subject more and more tackled in the cardiologic journals, and to which a larger attention should be paid in our daily practice. The Paris Prospective Study I brought new data concerning the early identification of the subjects at risk of sudden death, starting from the analysis of the evolution of heart rate profile during and after exercise. Is the concept of metabolic syndrome a phenomenon of mode or does it constitute in itself an autonomous prognostic factor beyond the risk related to the plurality of the factors which define it? The cardiologist will have to be interested more and more in the living conditions of his patients and in particular with the environmental factors such as the air pollution, who seems to have a considerable impact on the incidence of the acute coronary events. Lastly, the ADMA (asymmetric dimethylarginine), seems a possible new marker of cardiovascular risk, but its real prognostic interest remains to be defined.

Blood lipid and lipoprotein levels: relationships with educational level and region of residence in the French SU.VI.MAX study.

BACKGROUND: Blood lipid profile of French men and women obtained from the general population is not well known. Furthermore, the association between these lipids, as a function of other potential risk factors for cardiovascular disease, and sociodemographic factors such as age, educational level, and region of residence is not well studied in large samples in Europe. METHODS: Data on French healthy volunteers, aged between 40 and 65 years for men (n = 5141) and 35 and 65 years for women (n = 7876) were obtained from the "Supplementation en Vitamines et Mineraux Antioxydants" (SU.VI.MAX) study, a primary prevention trial. Baseline blood samples were collected in 1994-1995 and analyzed for cholesterol, triglyceride, apolipoproteins (apo)-B and -A1. The results were analyzed separately for men and women as a function of age, educational level, and area of residence. RESULTS: Overall, blood lipid levels for men and women did not differ significantly from those reported in other Western industrialized countries. Except for triglyceride in men, all blood lipids were statistically different among ages. In women, cholesterol, apo-A1, and apo-B showed a significant decrease with educational level. Statistical differences were found in both genders between blood lipids and lipoproteins among regions of residence. CONCLUSIONS: Even if differences between region of residence were found in blood lipid levels, this cannot explain the North-East to South gradient in the prevalence of cardiovascular disease in France nor differences between France and other industrialized Western countries.

[Nutritional counseling for coronary and hypertensive patients]. / Le conseil nutritionnel chez le coronarien et l'hypertendu.

Nutritional recommendations constitute a major aspect of the long term management of coronary and hypertensive patients, for which the established evidence is more and more solid. The benefits are not limited solely to the impact on weight and lipid parameters. In coronary patients, besides the reduction in saturated fatty acids, which is always indicated, an increase in the intake of omega-3 fatty acids is associated with a significant reduction in morbidity and mortality, notably with sudden death. Intake of folates is also beneficial, as well as fruit and vegetable consumption. These elements are constituents of alimentary models such as the mediterranean diet. In hypertensives, weight reduction, limitation of alcohol and sodium intake, and increasing potassium and magnesium intakes have a demonstrable effect. Evaluation of patient compliance to nutritional recommendations is just as important as that of compliance to treatments and control of classic risk factors.

No evidence for point mutations of the calcium-sensing receptor in familial idiopathic hypercalciuria.

BACKGROUND: Idiopathic hypercalciuria (IH) is frequently associated with nephrolithiasis. As 40% of patients have a positive familial history of IH, an autosomal dominant mode of inheritance has been suggested. Numerous genes have been studied in this regard but none have been found to be linked to IH. Mutation of the calcium-sensing receptor (CaR) has never been studied. Therefore, we conducted a study to detect such mutations. METHODS: Seven families with IH and nephrolithiasis were recruited in a prospective study. Forty-two family members underwent 24-h urine calcium measurement. Twenty-five of them with 24-h hypercalciuria also underwent extensive metabolic evaluation. Blood samples were collected in one or two affected family members in each family and exons 2-7 of the CaR gene were sequenced. RESULTS: In the seven families, at least one parent and more than half of the children had hypercalciuria (21/30), consistent with autosomal dominant inheritance. Among the nine affected family members whose CaR gene has been studied, all nine had absorptive hypercalciuria, three also had fasting hypercalciuria, and one had renal phosphorous leak. No mutation of the CaR gene was detected in these seven families. Two previously reported polymorphisms were detected, each of them in five families: A986S and C-to-T change at -60 in intron 5. CONCLUSION: In these seven families, IH is not related to the CaR gene mutation. Although we cannot exclude that point mutations can be found in other families, familial IH does not seem to be generally associated with CaR mutation.

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.

Clinical evaluation of circulating blood volume in critically ill patients--contribution of a clinical scoring system.

The circulating blood volume (CBV) of critically ill patients may be difficult to estimate on the basis of history and physical examination. The aim of this study was to evaluate the ability of seven clinical signs and central venous pressure (CVP) to predict CBV in critically ill patients; CBV was evaluated with the [125I]human serum albumin technique. A scoring system was constructed using a combination of independence Bayes method and logistic regression. Sixty-eight patients constituted a 'model development' sample and 30 patients a validation sample. Thirty-six patients (53%) in the model development sample were found to have a low CBV (measured CBV at least 10% lower than the predicted mean normal CBV). Neither the haemodynamic variables monitored in ICU, nor the spot urinary sodium concentrations were different between patients with and without a low CBV. Individually, none of the clinical signs tested have a good positive or negative predictive value. For CVP, only extreme values seem to have clinical significance. To construct the score, the signs tested were ranked according to their discriminating efficacy. The probability of a low CBV was obtained by adding the weights of each sign tested and converting the score obtained into a probability. On a validation sample of 30 patients, the predictions are reliable as assessed by Z statistics ranging between -2 and +2. Our results suggest that: (1) individually, no clinical sign presented a clinical useful predictive value; and (2) a clinical scoring system may be helpful for the evaluation of CBV in critically ill patients.

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.

Development of prediction models for three in vitro embryotoxicity tests in an ECVAM validation study.

Since 1997 the National Center for Documentation and Evaluation of Alternative Methods to Animal Experiments, ZEBET, in Berlin, has been coordinating a validation study aimed at prevalidation and validation of three in vitro embryotoxicity tests, funded by the European Center for the Validation of Alternative Methods (ECVAM) at the Joint Research Center (JRC, Ispra, Italy). The tests use the cultivation of postimplantation rat whole embryos (WEC test), cultures of primary limb bud cells of rat embryos (micromass or, MM, test), and cultures of a pluripotent mouse embryonic stem cell line (embryonic stem cell test or EST). Each of the tests was performed in four laboratories under blind conditions. In the preliminary phase of the validation study 6 out of 20 test chemicals comprising different embryotoxic potential (non, weakly, and strongly embryotoxic) were tested. The results were used to define biostatistically based prediction models (PMs) to identify the embryotoxic potential of test chemicals for the WEC test and the MM test. The PMs developed with the results of the preliminary phase of the validation study (training set) will be evaluated with the results of the remaining 14 test chemicals (definitive phase) by the end of the study. In addition, the existing, improved PM (iPM) for the EST, which had been defined previously, was evaluated using the results of the preliminary phase of this study. Applying the iPM of the EST to the results of this study, in 79% of the experiments, chemicals were classified correctly according to the embryotoxic potential defined by in vivo testing. For the MM and the WEC test, the PMs developed during the preliminary phase of this validation study provided 81% (MM test) and 72% (WEC test) correct classifications. Because the PM of the WEC test took into account only parameters of growth and development, but not cytotoxicity data, a second PM (PM2) was developed for the WEC test by incorporating cytotoxicity data of the differentiated mouse fibroblast cell line 3T3, which was derived from the EST. This approach, which has previously never been used, resulted in an increase to 84% correct classifications in the WEC test.