Serge Briançon

A Primary Prevention Trial Using Nutritional Doses of Antioxidant Vitamins and Minerals in Cardiovascular Diseases and Cancers in a General Population: The SU.VI.MAX Study—Design, Methods, and Participant Characteristics

The SUpplementation en VItamines et Minéraux AntioXydants (SU.VI.MAX) Study is a randomized, double-blind, placebo-controlled, primary-prevention trial designed to test the efficacy of daily supplementation with antioxidant vitamins (vitamin C, 120 mg; vitamin E, 30 mg; and beta-carotene, 6 mg) and minerals (selenium, 100 microg; and zinc, 20 mg) at nutrition-level doses (one to three times the daily recommended dietary allowances) in reducing several major health problems in industrialized countries, especially the main causes of premature death, cancers and cardiovascular diseases. The present report describes the design, implementation, and baseline characteristics of participants in this 8-year cohort study, which started in 1994 in France; 12,735 eligible subjects (women aged 35-60, and men aged 45-60) were included in 1994 and will be followed for 8 years. Participants undergo a yearly visit consisting, every other year, of either biological sampling or clinical examination. They also regularly provide information on health events and dietary intake by filling out computerized questionnaires using the Minitel Telematic Network. Data on baseline characteristics of the participants suggest that the present sample is close to the national population in terms of geographic density, socioeconomic status, and the distribution of various major risk factors for the diseases under study. The choice of the study population should allow the results of this trial to apply to adult populations of both sexes in France and other industrialized countries.

Incidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL study ☆

OBJECTIVES Characterize the incidence, clinical and etiologic features and outcomes of advanced congestive heart failure. BACKGROUND This condition is frequent, severe and costly, yet no population-based epidemiological data are available that take into account modern advances in diagnosis and therapy. METHODS The EPICAL (EPidemiologie de l’Insuffisance Cardiaque Avancee en Lorraine) study was based on a comprehensive registration of patients with ACHF (defined as hospital admission for presence of NYHA class III or IV symptoms, radiological and/or clinical signs of pulmonary congestion and/or signs of peripheral edema, left ventricular ejection fraction 60%) in patients aged 20–80 years during year 1994, in the community of the Lorraine region in France (n = 1,592,263). Average follow-up for readmission to hospital and mortality was 18 months (12–24 months). RESULTS From 2,576 registered patients, 499 were enrolled into the study among which, 358 were new presentations. This represents a crude incidence rate of 225 per million. 46.3% had a coronary heart disease. One-year mortality rate was 35.4% and the rate of mortality and/or readmission to hospital was 81%. Patients were admitted to hospital 2.05 times per year (64% of these for worsening heart failure), spending 27.6 days per year in hospital. Twenty received a heart transplant (4%). On discharge, 74.8% were using ACE inhibitors and 49.6% digitalis. CONCLUSIONS Mortality and hospitalization rate of advanced CHF remain very high despite recent therapeutic progress. Major therapeutic and managed-care research is required.

Effects of B vitamins and omega 3 fatty acids on cardiovascular diseases: a randomised placebo controlled trial

Objective To investigate whether dietary supplementation with B vitamins or omega 3 fatty acids, or both, could prevent major cardiovascular events in patients with a history of ischaemic heart disease or stroke. Design Double blind, randomised, placebo controlled trial; factorial design. Setting Recruitment throughout France via a network of 417 cardiologists, neurologists, and other physicians. Participants 2501 patients with a history of myocardial infarction, unstable angina, or ischaemic stroke. Intervention Daily dietary supplement containing 5-methyltetrahydrofolate (560 μg), vitamin B-6 (3 mg), and vitamin B-12 (20 μg) or placebo; and containing omega 3 fatty acids (600 mg of eicosapentanoic acid and docosahexaenoic acid at a ratio of 2:1) or placebo. Median duration of supplementation was 4.7 years. Main outcome measures Major cardiovascular events, defined as a composite of non-fatal myocardial infarction, stroke, or death from cardiovascular disease. Results Allocation to B vitamins lowered plasma homocysteine concentrations by 19% compared with placebo, but had no significant effects on major vascular events (75 v 82 patients, hazard ratio, 0.90 (95% confidence interval 0.66 to 1.23, P=0.50)). Allocation to omega 3 fatty acids increased plasma concentrations of omega 3 fatty acids by 37% compared with placebo, but also had no significant effect on major vascular events (81 v 76 patients, hazard ratio 1.08 (0.79 to 1.47, P=0.64)). Conclusion This study does not support the routine use of dietary supplements containing B vitamins or omega 3 fatty acids for prevention of cardiovascular disease in people with a history of ischaemic heart disease or ischaemic stroke, at least when supplementation is introduced after the acute phase of the initial event. Trial registration Current Controlled Trials ISRCTN41926726.

Clinical StudiesIncidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL study☆

OBJECTIVES Characterize the incidence, clinical and etiologic features and outcomes of advanced congestive heart failure. BACKGROUND This condition is frequent, severe and costly, yet no population-based epidemiological data are available that take into account modern advances in diagnosis and therapy. METHODS The EPICAL (EPidemiologie de l’Insuffisance Cardiaque Avancee en Lorraine) study was based on a comprehensive registration of patients with ACHF (defined as hospital admission for presence of NYHA class III or IV symptoms, radiological and/or clinical signs of pulmonary congestion and/or signs of peripheral edema, left ventricular ejection fraction 60%) in patients aged 20–80 years during year 1994, in the community of the Lorraine region in France (n = 1,592,263). Average follow-up for readmission to hospital and mortality was 18 months (12–24 months). RESULTS From 2,576 registered patients, 499 were enrolled into the study among which, 358 were new presentations. This represents a crude incidence rate of 225 per million. 46.3% had a coronary heart disease. One-year mortality rate was 35.4% and the rate of mortality and/or readmission to hospital was 81%. Patients were admitted to hospital 2.05 times per year (64% of these for worsening heart failure), spending 27.6 days per year in hospital. Twenty received a heart transplant (4%). On discharge, 74.8% were using ACE inhibitors and 49.6% digitalis. CONCLUSIONS Mortality and hospitalization rate of advanced CHF remain very high despite recent therapeutic progress. Major therapeutic and managed-care research is required.

Impact of nephrology referral on early and midterm outcomes in ESRD: EPidémiologie de l'Insuffisance REnale chronique terminale en Lorraine (EPIREL): results of a 2-year, prospective, community-based study.

BACKGROUND Most studies looking at how the outcome of end-stage renal disease (ESRD) is affected by the timing and quality of the care received before initiation of renal replacement therapy (RRT) are inconclusive. METHODS Five hundred and two adult French patients (age, 62.8 +/- 16 years) receiving their first RRT were enrolled in a 2-year, community-based, prospective study. Subjects were assigned to 1 of 5 groups depending on the time between their first serum creatinine reading above 2 mg/dL (177 micromol/L): chronic renal failure (CRF) and nephrology referral (NR) and RRT. Multivariate logistic regression was used to analyze 90-day survival data, and data concerning long-term survival and inclusion on the waiting list for renal transplantation were analyzed using Cox proportional hazards regression. RESULTS Overall survival rates were 88% at 90 days, 77.2% at 1 year, 65.2% at 2 years, and 54.2% at 3 years. The nephrology referral pattern was associated with age and systolic blood pressure, and independently predicted early death. Compared with group 1 (NR > 12 months), odds ratios (confidence interval 95%) were 2.7 (1.2 to 6.3) for group 2 (NR < or = 12 months or >4 months), 2.8 (1.0 to 8.0) for group 3 (NR < or = 4 months or >1 month), 4.9 (2.2 to 11.0) for group 4 (NR < or = 1 month; CRF > 1 month), and 5.2 (2.2 to 12.3) for group 5 (NR < or = 1 month; CRF < or = 1 month). Independent predictors of death in 90-day survivors were age, cardiac disease with previous episodes of heart failure, vascular disease, low diastolic blood pressure, and group 3 referral pattern. Not being entered on the waiting list for renal transplantation was predicted by age, diabetes, vascular disease, and nonelective first dialysis. CONCLUSION Late nephrology referral is strongly associated with early death. Emergency first dialysis is an independent risk factor for not being placed on the waiting list for transplantation. Among 90-day survivors, referral pattern has little influence on mortality, which is mainly determined by cardiovascular complications at initiation of RRT.

The Groningen activity restriction scale for measuring disability: its utility in international comparisons

OBJECTIVES The Groningen Activity Restriction Scale (GARS) is a non-disease-specific instrument to measure disability in activities of daily living (ADL) and instrumental activities of daily living (IADL). It was developed in studies of Dutch samples consisting of elderly or chronically ill people. The psychometric properties of the GARS demonstrated in these studies were highly satisfactory. This paper addresses the psychometric properties of the GARS across countries. METHODS Data of 623 patients with recently diagnosed rheumatoid arthritis from four European countries were analyzed by means of a principal components analysis and a Mokken scale analysis for polychotomous items. RESULTS The results of the analyses were highly satisfactory: there was one strong and reliable general factor representing one underlying dimension of disability in ADL and IADL, and there was a clear hierarchical ordering of the items included in the GARS. The validity of the GARS was strongly suggested by the pattern of associations of the GARS with age, sex, and other existing health status measures. CONCLUSIONS The psychometric characteristics of the GARS, which measures disability in ADL and IADL simultaneously, make this instrument very useful for comparative research across countries.

Right ventricular overload and induced sustained ventricular tachycardia in operatively “repaired” tetralogy of Fallot

The aim of the study was to evaluate the main predictors of the inducibility of sustained ventricular tachycardia (VT) in patients with repaired tetralogy of Fallot. Thirty-five patients (age 12 +/- 6 years) underwent right-sided cardiac catheterization, echocardiography, radionuclide angiography and ventricular stimulation; 10 had (group 1) and 25 had no (group 2) sustained VT. Group 1 patients were significantly older at the time of surgery and had longer follow-up periods (7 +/- 3 vs 4 +/- 4 years, p less than 0.02; and 12 +/- 4 vs 5 +/- 2 years, p less than 0.001, respectively). Right ventricular (RV) systolic pressure, end-systolic and end-diastolic normalized RV volumes were higher in group 1 (48 +/- 14 vs 38 +/- 11 mm Hg, p less than 0.05; 1.23 +/- 0.2 vs 0.86 +/- 0.17, p less than 0.001; and 2.35 +/- 0.37 vs 1.70 +/- 0.22, p less than 0.001, respectively). RV end-diastolic pressure, left ventricular and RV ejection fractions were similar in the 2 groups. A stepwise discriminant analysis was made to predict patients with inducible sustained VT (group 1): Time period from surgery to follow-up (p less than 0.001), normalized RV end-systolic volume (p less than 0.002) and RV systolic pressure (p = 0.01) were higher in group 1 and allowed classification of 90% of patients in group 1 and 96% in group 2.(ABSTRACT TRUNCATED AT 250 WORDS)

Determining factors in the iron status of adult women in the SU.VI.MAX study

The iron status of a national sample of adults living in France and participating in the SU.VI.MAX cohort, was assessed using serum ferritin and hemoglobin concentrations. Complete data were obtained for 6648 women 35–60 y old and for 3283 men 45–60 y old. Assessment of iron dietary intakes was realized on a subsample of 3111 women and 2337 men who reported six 24 h dietary records during a one-year period; 22.7% of menstruating women and 5.3% of post-menopausal women presented a total depletion of iron stores (serum ferritin <15 μg/l). Iron-deficient anemias were found in, respectively, 4.4% and less than 1% of these women. Three-quarters of the anemias were related to iron deficiency in menstruating women. In men, iron depletion and iron deficiency anemia were very rare. Post-menopausal women had much higher serum ferritin levels than menstruating women. In menstruating women, those using intrauterine devices had significantly lower serum ferritin levels than those without contraception, and much lower than those using oral contraception. The frequency of iron depletion reached 28.1% in women using intrauterine devices, but only 13.6% in those using oral contraceptives.The mean iron intake was 16.7±5.7 mg/d in men and 12.3±3.4 mg/d in women. Heme iron represented respectively, 11.1 and 10.4% of iron intake. Ninety-three percent of menstruating women had dietary iron intakes lower than recommended dietary allowances (RDA); 52.6% consumed less than two thirds of these RDA. In post-menopausal women and men, respectively 27.7% and 3.6% had dietary intakes lower than RDA. Serum ferritin was positively correlated with meat, fish and total iron intake, and negatively correlated with dietary products consumption, calcium and fiber intake.

Self-rating of quality of life provides additional prognostic information in heart failure. Insights into the EPICAL study.

The relationship between quality of life (QoL) and survival have been poorly investigated. The aim of this study was to determine the value of QoL score as a prognostic factor in a prospective cohort of patients with advanced chronic heart failure (CHF).

An international study on measuring social support: Interactions and satisfaction

Recently, a new instrument was developed to measure social support. It consists of two parts; the Social Support Questionnaire for Transactions (SSQT) and the Social Support Questionnaire for Satisfaction with the supportive transactions (SSQS). The SSQT measures the number of supportive interactions and has proved to have good psychometric properties. From the taxonomy that was used for the present study, it results that social support in general consists of two aspects. There are, on the one hand, actual supportive transactions and, on the other hand, the perception of being supported or the satisfaction with the social support provided. In the present study, two research questions were addressed. The first concerned the psychometric properties of the SSQS, measuring the individuals satisfaction with the supportive interactions provided. Secondly, the relative contribution of both supportive interactions (the SSQT) and the satisfaction with the support provided (the SSQS) were assessed, in explaining the level of health related quality of life outcome. The data of 744 rheumatoid arthritis (RA) patients from four different countries (116 French, 238 Norwegian, 98 Swedish and 292 Dutch patients) were used in the present study. At the entry of the study, all patients fulfilled four out of seven American Rheumatism Association (ARA) criteria and had a disease duration of 4 years or less. The results of the study indicate that the SSQS has good psychometric properties across countries. Cronbachs alpha for the emotional support scales was 0.80 or more, and for the instrumental support subscales around 0.60. The standardized regression coefficients demonstrated that, compared to supportive interactions, support satisfaction was more relevant in explaining health related quality of life measures, although it is recommended that the SSQT and SSQS be used to complement each other.