An audit of dementia education and training in UK health and social care: a comparison with national benchmark standards.

BACKGROUND: Despite people living with dementia representing a significant proportion of health and social care users, until recently in the United Kingdom (UK) there were no prescribed standards for dementia education and training. This audit sought to review the extent and nature of dementia education and training offered to health and social care staff in the UK against the standards described in the 2015 Dementia Training Standards Framework, which describes the knowledge and skills required of the UK dementia workforce. METHODS: This audit presents national data concerning the design, delivery, target audience, length, level, content, format of training, number of staff trained and frequency of delivery within existing dementia training programmes offered to health and social care staff. The Dementia Training Standards Framework was used as a reference for respondents to describe the subjects and learning outcomes associated with their training. RESULTS: The findings are presented from 614 respondents offering 386 training packages, which indicated variations in the extent and quality of training. Many training packages addressed the subjects of 'person-centred care', 'communication', 'interaction and behaviour in dementia care', and 'dementia awareness'. Few training packages addressed subjects concerning 'pharmacological interventions in dementia care', 'leadership' and 'end of life care'. Fewer than 40% of The Dementia Training Standards Framework learning outcomes targeted to staff with regular contact with people with dementia or in leadership roles were covered by the reported packages. However, for training targeted at increasing dementia awareness more than 70% of the learning outcomes identified in The Dementia Training Standards Framework were addressed. Many training packages are not of sufficient duration to derive impact; although the majority employed delivery methods likely to be effective. CONCLUSIONS: The development of new and existing training and education should take account of subjects that are currently underrepresented and ensure that training reflects the Training Standard Framework and evidence regarding best practice for delivery. Lessons regarding the limitations of training in the UK serve as a useful illustration of the challenge of implementing national dementia training standards; particularly for countries who are developing or have recently implemented national dementia strategies.

Completion task to uncover consumer's perception: a case study using distinct types of hen's eggs.

The choice and consumption of eggs are made considering a consumers' multidimensional perception, and their understanding becomes essential to the production targeting and the products' success in the market. In this context, this work aimed to verify the consumers' perception about the distinct types of hens' eggs, using a projective technique of completion task combined with presentation of images. A hundred consumers (n = 100) evaluated the main factors, both positive and negative, involved at the purchase time of eggs besides estimating their price. Between the positive factors that guide the eggs' consumption and purchase, the category with highest mention of terms was "Health," whereas negatively it was highlighted the category "Price." Concerning the perception of price, the results showed that the factory farm white eggs' value was the one that least differed from the average market price, possibly due to the nearness and familiarity with this variety. The methodology of completion task combined with presentation of images proved as being a practical and efficient tool to capture the consumers' perception of eggs, capable of providing valuable information to the ones involved in the production chain and commercialization of these products.

[Therapeutic plasma exchange for the treatment of hypertriglyceridemia-induced pancreatitis : A case report]. / Plasmapherese zur Behandlung einer hypertriglyzeridämiebedingten Pankreatitis : Ein Fallbericht.

A rare but serious form of pancreatitis is caused by severe hypertriglyceridemia. It accounts for up to 10 % of all acute pancreatitis episodes. Despite a pathophysiology that differs distinctly from other forms of pancreatitis, there are no accepted guidelines for the treatment of hypertriglyceridemia-induced pancreatitis. We report a morbidly obese (BMI 45 kg/m²) 36-year-old Caucasian woman with a history of schizophrenic psychosis who was transferred to our tertiary care hospital for further diagnosis and treatment of increasing abdominal pain and hypertryglyceridemia of 2757 mg/dl. Due to rapid clinical deterioration, requiring invasive mechanical ventilation we performed therapeutic plasma exchange (TPE). About 1.5 times of the patient's calculated plasma volume was exchanged using fresh frozen plasma as substitution fluid. After a single TPE the triglyceride levels decreased by 86 % to 387 mg/dl. Concomitantly C­reactive protein decreased from 303 to 179 mg/dl. Despite the paucity of data, TPE may be a beneficial means to lower triglycerides in patients with hypertriglyceridemia-induced pancreatitis, due to the rapid removal of the causative agent leading to pancreatic injury.

Performance of cognitive tests, individually and combined, for the detection of cognitive disorders amongst community-dwelling elderly people with memory complaints: the EVATEM study.

BACKGROUND AND PURPOSE: Dementia is a leading cause of dependence amongst the aged population. Early identification of cognitive impairment could help to delay advanced stages of dependence. This study aimed at assessing the performance of three neuropsychological tests to detect cognitive disorders in elderly subjects with memory complaints. METHODS: The EVATEM study is a prospective multicentre cohort with a 1-year follow-up. Subjects with memory complaints were selected during preventive health examinations, and three neuropsychological tests (five-word, cognitive disorders examination, verbal fluency) were administered. Two groups were identified in memory clinics: (i) cognitively healthy individuals (CHI) and (ii) mild cognitive impairment or demented individuals (MCI-DI). Cross-sectional analyses were performed on data at inclusion. The relationship between the diagnosis of MCI-DI/CHI and the neuropsychological tests was assessed using logistic regressions. The performance of the neuropsychological tests, individually and combined, to detect cognitive disorders was calculated. RESULTS: Of 585 subjects, 31.11% had cognitive disorders (MCI, 176 subjects; DI, six subjects). Amongst the three tests studied, the odds ratio for MCI-DI was higher for the five-word test <10 [odds ratio 3.2 (1.81; 5.63)]. The best performance was observed when the three tests were combined: specificity 90.5% and sensitivity 42.4% compared to respectively 89.2% and 28.3% for the five-word test. CONCLUSIONS: Despite the poor sensitivity of the five-word test, it seems to be the most adapted for the diagnosis of MCI-DI in older adults with a memory complaint, in prevention centres, taking into account its high specificity and its rapid administration compared to the other tests.

Assessment of Health Inequalities Among Older People Using the EPICES Score: A Composite Index of Social Deprivation.

BACKGROUND: Most of the indicators commonly used to assess social deprivation are poorly suited to study health inequalities in older people. The EPICES (Evaluation of Deprivation and Inequalities in Health Examination Centres) score is a new composite index commonly used to measure individual deprivation. OBJECTIVE: To assess the relationships between health indicators and the EPICES score in older people. Design, Setting, and participants: We performed a cross-sectional study using the data from the 2008 ESPS Survey (Health, HealthCare and Insurance Survey). Of the 4235 survey respondents aged 60 and over in 2008, 2754 completed the 11 items of the EPICES score and were included in the study. MAIN OUTCOMES AND MEASURES: Deprivation was measured using the EPICES score. Health indicators were: Disability, physical performance, cognitive decline, self-perceived health status, and health-care use and participation in prevention programs (missing teeth not replaced, healthcare renunciation, no hemoccult test [60-75 years] and no mammography [60-75 years]). RESULTS: Of the 4235 survey respondents aged 60 and over in 2008, 2754 completed the 11 items of the EPICES score and were included in the study. The mean age was 70.5± 8.2 years. 52.8% were women. 25.8% were living in poor households. According to the EPICES score, 35.1% were deprived. The EPICES score is linked to all the health indicators assessed in this study: Physical disability, cognitive decline; lifestyle and health care accessibility. These relationships increase steadily with the level of social deprivation. For example, the risk of having difficulties in walking 500m without help or an assistive device is multiplied by 13 (RR=13.5 [7.9-20.8]) in the elderly of quintile 5 (maximum precariousness). Limitations: The observational nature limits inferences about causality.CONCLUSION: The EPICES score is linked to health indicators. It could be a useful instrument to assess health inequalities in older people living in the community.

[Qualitative and quantitative comparisons of three individual deprivation scores for outpatients attending a free hospital care clinic in Paris]. / Caractéristiques métrologiques et comparaison de trois outils de repérage de la précarité sociale dans une permanence d'accès aux soins de santé hospitalière à Paris.

BACKGROUND: Inequality in health care is a growing problem, leading to the development of different tools for the assessment of individual deprivation. In France, three tools are mainly used: Epices (which stands for "score for the evaluation of social deprivation and health inequities among the centers for medical examination"), a score called "Handicap social" and a screening tool built for medical consultations by Pascal et al. at Nantes' hospital. The purpose of this study was to make a metrological assessment of those tools and a quantitative comparison by using them on a single deprived population. METHODS: In order to assess the metrological properties of the three scores, we used the quality criteria published by Terwee et al. which are: content validity, internal consistency, criterion validity, construct validity, reproducibility (agreement and reliability), responsiveness, floor and ceiling effects and interpretability. For the comparison, we used data from the patients who had attended a free hospital outpatient clinic dedicated to socially deprived people in Paris, during one month in 2010. The "Handicap social" survey was first filled in by the 721 outpatients before being recoded to allow the comparison with the other scores. RESULTS: While the population of interest was quite well defined by all three scores, other quality criteria were less satisfactory. For this outpatient population, the "Handicap social" score classed 3.2% as non-deprived (class 1), 32.7% as socially deprived (class 2) and 64.7% as very deprived (class 3). With the Epices score, the rates of deprivation varied from 97.9% to 100% depending on the way the score was estimated. For the Pascal score, rates ranged from 83.4% to 88.1%. On a subgroup level, only the Pascal score showed statistically significant associations with gender, occupation, education and origin. CONCLUSION: These three scores have very different goal and meanings. They are not interchangeable. Users should be aware of their advantages and disadvantages in order to use them wisely. Much remains to be done to fully assess their metrological performances.

[Is the socioeconomic deprivation EPICES score useful in obstetrics?]. / Intérêt de l'échelle d'évaluation de la précarité EPICES en obstétrique.

OBJECTIVES: To describe a validated and multifactorial deprivation score to study the relationship between socioeconomic deprivation and perinatal risks. PATIENTS AND METHODS: The index of deprivation EPICES (Evaluation of Precarity and Inequalities in Health Examination Centers) was used to characterize the deprivation status of 234 women in post-partum in comparison with perinatal morbidity. The cutoff value of 30.7 was the threshold to define deprivation. RESULTS: Two hundred and eight patients were included in this retrospective study from whom 48 (23%) had a score of deprivation higher than 30.7. Maternofetal morbidity was more severe in deprived patients. DISCUSSION AND CONCLUSION: The current results show that the EPICES score could be a useful obstetrical tool for the identification of deprived women during pregnancy.

[Job insecurity, unemployment and health: results from the health examination centers of the French General Health Insurance]. / Santé et instabilité professionnelle : résultats issus des centres d'examens de santé de l'assurance-maladie.

BACKGROUND: Job insecurity has increased over the last 30 years. Socioeconomic changes have led to various insecure employment categories, including fixed term employment, part time employment and government sponsored jobs. This study was aimed at investigating relationships between employment status and health. METHODS: The study population was composed of 767,184 people, aged 26 to 59 years, examined between 2003 and 2005 in the Health Examination Centers of the French General Health Insurance. Employment status was defined using insecure employment (combining permanent/fixed-term contracts and part-time/full time), government sponsored jobs and duration of unemployment (from <6 months to > or =3 years). Health indicators were poor perceived health, smoking, lack of gynecological follow-up, obesity, untreated caries and high blood pressure. Data were analysed by logistic regression (odds ratios [OR]) adjusted on age, occupational social class and education level, the reference category being permanent full time contracts (OR=1). RESULTS: Significant level-dependent relations with health were observed between non permanent versus permanent employments, part time versus full time. Most OR of unemployed people were higher than those of having employment and increased with duration of unemployment. For example, for poor perceived health in men, OR ranged between 1.00 and 1.68 (95%CI 1.57-1.78) according to job insecurity categories, and between 1.75 (95%CI 1.67-1.83) and 2.80 (95%CI 2.72-2.89) according to duration of unemployment. For obesity in women, OR increased from 1.00 to 1.48 (95%CI 1.37-1.60) in active women and from 1.35 (95%CI 1.27-1.44) to 1.77 (95%CI 1.70-1.84) in unemployed. CONCLUSIONS: This study showed quantitative relationships between job insecurity, unemployment and health. In particular, workers having government-sponsored jobs and long-time unemployed people were at high risk of health problems.

[Comparison of the individual deprivation index of the French Health Examination Centres and the administrative definition of deprivation]. / Comparaison du score individuel de précarité des centres d'examens de santé, EPICES, à la définition socio- administrative de la précarité.

In French Health Examination Centres, populations in deprived situation were usually defined by administrative criteria The aim of the study was to investigate whether EPICES, a new individual index of deprivation, was more strongly related to health status than an administrative classification. The EPICES score was calculated on the basis of 11 weighted questions related to material and social deprivation. Participants were 197, 389 men and women, aged over 18, encountered in 2002 in French Health Examination Centres. Relationships between health status, health-related behaviours, access to health care, EPICES and the administrative classification of deprivation were analyzed by logistic regression. The associations between EPICES and the study variables were stronger than those observed for the administrative definition. The comparison also showed socially disadvantaged people with poor health identified by the EPICES score who were not by the administrative classification. These results showed that the EPICES score can be a useful tool to improve the identification of deprived people having health problems associated to deprivation.

Genetic influences on lipid metabolism trait variability within the Stanislas Cohort.

The contribution of 17 polymorphisms within 13 candidate genes on lipid trait variability was investigated by a multiplex assay in 772 men and 780 women coming for a health checkup examination. The studied genes were APOE, APOB, APOC3, CETP, LPL, PON, MTHFR, FGB, GpIIIa, SELE, ACE, and AGT. We found that APOB-Thr71Ile, APOE-(112/158), APOC3-1100C/T, and SELE-98G/T polymorphisms had a significant effect on lipid traits (P < or = 0.001 to P < or = 0.01). Genetic effects accounted for 3.5-5.7% of variation in apolipoprotein B (apoB)-related traits among men, and for 5.7-9.0% among women. The contribution of APOE polymorphism on apoB-related traits variability was two to three times more important in women than in men. We found suggestive evidence for interactive effects between genetics and age, smoking status, and oral contraceptives. Increase of LDL-cholesterol and apoB concentrations with age was stronger among the epsilon4 carriers in women, and apolipoprotein A-I (apoA-I) concentration decreased with age in epsilon4 male carriers. The effect of epsilon2 allele on LDL-cholesterol was more important in the oral contraceptive users. In nonsmokers only, the APOC3-1100C allele in women was related to lower apoB-related traits concentrations, and in men to higher apoA-I and HDL-cholesterol concentrations. In conclusion, this work, in addition to the reinforcement of the already known associations between APOB, APOE, and APOC3 genes and lipids, leads to new perspectives in the complex relationships among genes and environmental factors. The newly observed relationships between E-selectine gene and lipid concentrations support the hypotheses of multiple metabolic pathways contributing to the complexity of lipids variability.

[APOC3, CETP, beta-fibrinogen and MTHFR are genetic determinants of carotid intim-media thickness (Stanislas cohort)]. / L'APOC3, la CETP, le beta-fibrinogène et la MTHFR sont des déterminants génétiques de l'épaisseur intima-média de la carotide (cohorte Stanislas).

The purpose of this study was to examine the relationship between carotid intima-media thickness (CIMT) interindividual variability and 16 polymorphisms of 11 genes associated with cardiovascular risk factors (genes among lipid and homocysteine metabolisms, blood viscosity, platelet aggregation, leukocyte adhesion and renin-angiotensin system). CIMT was measured by high resolution B mode ultrasonography in an healthy population of 77 men and 84 women, aged 35-54 years and selected from a French cohort: the Stanislas cohort. The polymorphisms studied were genotyped by a multilocus approach. Statistical analysis were done by ANOVA after adjustment of CIMT for age, BMI and smoking and by multiple regression analyses. No association was found with APOB Thr71 Ile, APOC3 -482C/T, -455T/C, GpIIIa P1A, AT1R 1166A/C, AGT Met235Thr, CBS Ile278Thr, SELE 98G/T and SELE Ser128Arg, polymorphism neither in men nor in women. Although, in women we found always no association for the APOC3 3206T/G, 3175C/G, 1100C/T, the CETP Ile405Val, the MTHFR 677C/T and the fibrinogen -455G/A polymorphism's, in men these polymorphism's were associated with CIMT variability (0.01 < or = p < or = 0.05). The most interesting finding was that altogether these genes in men were able to explain a considerable part, 20.6%, of CIMT variability. Therefore, our study gives a new opportunity to understand CIMT variability.

[Association between E-selectin Leu554Phe polymorphism and blood pressure in the Stanislas cohort]. / Association entre le polymorphisme Leu554Phe de la E-sélectine et la pression artérielle au sein de la cohorte Stanislas.

We investigated the relationship between polymorphisms of the E-selectin gene, SELE (L/F554, S/R128 and 98G/T), a cell adhesion molecule, and interindividual variability in blood pressure and changes over time. The study population was extracted from the Stanislas Cohort (1006 families), a cohort of nuclear families volunteering for a free health check-up and recruited by the Centre of Preventive Medicine in Nancy (CMP) between 1993 and 1994. For this specific study, 359 men and 337 women were selected from families that had already visited the CMP 11 years before the recruitment of the Stanislas Cohort. Measurements of blood pressure at the time -11 years (t-11) and at the time of recruitment (t0), and all other measurements necessary for the analysis (BMI, lipids, SELE genotypes) were available. Pregnant women or subjects taking antihypertensive, lipid lowering or anti-inflammatory medications were excluded from the study. During the follow-up period, systolic and diastolic blood pressure (SBP and DBP) were lower in SELE F554 allele carriers than in those with the L/L554 genotype (p < or = 0.05), whereas longitudinal changes were not related to any SELE polymorphism. Multiple regression analysis showed that at t-11 SELE L/F554 polymorphism was associated with both SBP and DBP levels (p < or = 0.01 and p < or = 0.05, respectively). However, these associations were no longer present at t0. Our results suggest an age-specific effect of the SELE L/F554 polymorphism on blood pressure levels. If confirmed in other studies, these findings would suggest that assessment of common variation in an adhesion molecule could be useful in predicting blood pressure.

Sample size calculations for classical association and TDT-type methods using family data.

Transmission Disequilibrium Test (TDT)-based methods have been advocated by several authors for testing that a marker-phenotype association is actually due to linkage and not to uncontrolled stratification. As a pre-requisite of TDT-type methods is the presence of an association between marker and phenotype, one may wish to first investigate the association using a classical association study, and then to check by a TDT approach whether this association is actually due to linkage. We propose an estimating equation (EE) procedure, to compute analytically the minimum sample size of sibship data required to detect the association between a marker and a quantitative phenotype, and that required to confirm it by two TDT methods. We show that, when the marker allele frequency is low or high, the number of informative sibs needed in TDT-type methods can be lower than the number required in an association analysis, and even more so when the familial clustering is strong. However, in all cases, the number of sibs that need to be sampled to get the appropriate number of informative sibs for analysis is always larger for TDT methods than for an association study. In a phenotype-first strategy, this number may be critical when investigating costly phenotypes.

APOC3, CETP, fibrinogen, and MTHFR are genetic determinants of carotid intima-media thickness in healthy men (the Stanislas cohort).

The purpose of this study was to examine the relationship between carotid intima-media thickness (CIMT) inter-individual variability and 16 polymorphisms of 11 genes associated with cardiovascular risk factors (genes among lipid and homocysteine metabolisms, blood viscosity, platelet aggregation, leukocyte adhesion and renin-angiotensin system). CIMT was measured by high resolution B-mode ultrasonography in an healthy population of 77 men and 84 women, aged 35-54 years and selected from a French Cohort: the Stanislas Cohort. The polymorphisms studied were genotyped by a multilocus approach. Statistical analyses were carried out by ANOVA, after adjustment of CIMT for age, body mass index, and smoking, and by multiple regression analyses. No association was found with APOB Thr71Ile, APOC3 -482C/T, -455T/C, GpIIIa P1A, AT1R 1166A/C, AGT Met235Thr, CBS Ile278Thr, SELE 98G/T, and SELE Ser128Arg, polymorphisms neither in men nor in women. Although, in women we did not find any association for APOC3 3206T/G, 3175C/G, 1100C/T, CETP Ile405Val, MTHFR 677C/T and fibrinogen -455G/A polymorphisms; in men these polymorphisms were associated with CIMT variability (p< or =0.01; p< or =0.05). The most interesting finding was that altogether these genes in men were able to explain a considerable part, 20.6%, of CIMT variability. Therefore, our study gives a new opportunity to understand CIMT variability.

Candidate gene polymorphisms in cardiovascular disease: a comparative study of frequencies between a French and an Italian population.

A multilocus assay was used to genotype up to 27 variable sites in 15 genes in French and Italian, presumed to be healthy populations (n=1480, n=162, respectively). These genes are involved in lipid metabolism (APOE, APOB, APOC3, CETP, LPL, PON), homocysteine metabolism (CBS, MTHFR), blood viscosity (Fibrinogen, FV), platelet aggregation (GpIIIa), leukocyte adhesion (SELE), and renin-angiotensin system (AT1R, ACE, AGT). Allele frequencies for all the markers were compared between the two populations. Five allele frequencies differed between the two European countries: APOB 71Ile (p < 0.001), SELE 98T (p < 0.001), SELE 128Arg (p < or = 0.01), APOE E4 (p < or = 0.01) and MTHFR 677T (p < or = 0.01), suggesting the existence of a north-south gradient in European allele frequencies. The other allele frequencies : APOC3 -482T, -455C, 1100T, 3175G, 3206G; LPL -93G, 9Asn, 291Ser; CETP 405Val; PON 192Arg; ACE Del; AGT 235Thr; AT1R 1166C; CBS 278Thr, GpIIIa P1A2; Fibrinogen -455A, FV 506Gln and SELE 554Phe, were similar between the two populations. They were also similar to those observed in other European countries.

Serum myeloperoxidase concentration in a healthy population: biological variations, familial resemblance and new genetic polymorphisms.

Myeloperoxidase (MPO) has been involved in the pathogenesis of several diseases through excessive production of reactive oxygen species (ROS) as well as through its genetic polymorphism. The aims of this study were to identify the factors affecting MPO serum concentration, to study the familial resemblance of MPO levels and to investigate the association between newly described MPO polymorphisms as well as the G-463A one and MPO levels in a healthy population. MPO serum concentrations were measured by an enzymatic immuno-assay (EIA) in 82 healthy families of the STANISLAS Cohort and MPO genotype, determination was performed using PCR-restriction fragment length polymorphism or allele specific oligonucleotide assay. MPO concentrations were significantly higher in parents than in offspring. The factors affecting MPO levels were age, the number of white cells, smoking in fathers and oral contraceptive intake in mothers. They explain from 12.4% up to 35.9% of MPO variability in men and women, respectively. Family correlations of MPO concentrations were of similar magnitude. The -129A allele of a newly described G-129A substitution was significantly associated with decreased MPO levels, whereas the -463A allele was suggested to be associated with increased levels of lipid variables. In this study, we identified factors affecting MPO serum concentrations and showed that molecular variations of the gene have only a weak influence on MPO variability. In contrast, the association between the G-463A polymorphism and lipid levels would suggest a possible implication of MPO in the risk of cardiovascular diseases. These results have to be confirmed and further investigations will be conducted in that way.

Environmental and genetic determinants of intima-media thickness of the carotid artery.

1. The aim of the present study was to investigate carotid intima-media thickness (CIMT) in relation to anthropometric, environmental and genetic factors, as well as cholesterol and blood pressure levels. 2. The study sample was composed of 89 families, with no documented cardiovascular disease, consisting of 369 subjects (aged from 10 to 54 years) from the Stanislas cohort. 3. Carotid intima-media thickness was measured by B-mode ultrasonography. Fifteen genetic markers, including genes involved in lipid metabolism, the regulation of blood pressure, thrombosis, platelet function and endothelial cell adhesion, were studied by multiplex assay. 4. The effects of gender, age, smoking, alcohol, body mass index, cholesterol, blood pressure and genetic factors were studied using ANOVA and bivariate and regression analyses. 5. Segregation analysis was also performed to estimate the contribution of genetic and environmental factors to CIMT variability. 6. Carotid intima-media thickness values were not affected by age or by gender up to 18 years of age. Thereafter, CIMT values increased sharply in men and remained significantly higher than in women. 7. Approximately 30% of CIMT variability was attributable to genetic factors. Associations between CIMT and polymorphisms in the apolipoprotein CIII, cholesteryl ester transfer protein, methylene tetrahydrofolate reductase and fibrinogen genes were observed and explained approximately 20% of CIMT variation in men. 8. In women, none of the studied polymorphisms was associated with CIMT variation. 9. Our study gives new perspectives for understanding CIMT variability in healthy middle-aged subjects.

Familial studies on the genetics of cardiovascular diseases: the Stanislas cohort.

In a given individual, the level of cardiovascular risk results from the combination of and interactions between genetic and environmental components. We choose to investigate segregation analysis of intermediate phenotypes in healthy nuclear families, belonging to the Stanislas cohort, a large familial cohort composed of 1006 families, which will be followed for 10 years. We developed a panel of 35 genetic markers including genes involved in lipid metabolism, regulation of blood pressure, thrombosis, platelet function, and endothelial cell adhesion. The allele frequencies of the studied polymorphisms were in agreement with those reported in other Caucasian populations. As an example of segregation analysis, we investigated carotid intima-media thickness (CIMT) variability in a subset sample of the Stanislas cohort. We found that about 30% of CIMT variability was attributable to genetic factors. Associations between CIMT and polymorphisms in apo CIII, cholesteryl ester transfer protein, methylene tetrahydrofolate reductase, and fibrinogen genes were observed and explained about 20% of CIMT variability in men. Furthermore, as another example of association studies, we investigated the relations between E-selectin polymorphisms and blood pressure interindividual variability and longitudinal changes in unrelated adults of this familial population. The E-selectin Phe554 allele was found associated with lower systolic blood pressure and diastolic blood pressure.

Apolipoprotein E polymorphisms and concentration in chronic diseases and drug responses.

Apolipoprotein (apo) E is an important circulating and tissue protein involved in cholesterol homeostasis and many other functions. The common polymorphism in the coding region of the gene, four polymorphisms in the promoter region, other additional single nucleotide polymorphisms, as well as several apo E variants have been identified. The common coding polymorphism strongly influences the lipid metabolism and the circulating concentration of apo E itself. This polymorphism is at the origin of the implication of apo E in cardiovascular and neurodegenerative diseases, but also of the relation of apo E with longevity. Probably due to its many metabolic and functional consequences, apo E polymorphism has been shown to influence the responses of patients to several drugs (fibrates, statins, hormone replacement therapy, anti-Alzheimer drugs) or environmental interventions (black tea, alcohol, diet). Apo E genotyping may be clinically helpful in defining the risk of patients and their responses to therapeutics. Finally, circulating apo E concentration appears to be altered in diseases and can be modulated by some of the drugs cited above. This parameter can thus also give interesting clinical information and could be a therapeutic target, providing it is validated. At the present time, we cannot exclude that apo E concentration may be the most prominent apo E parameter to be considered in health and disease, while apo E polymorphisms would represent only secondary parameters influencing apo E concentration.