The lupus impact tracker is responsive to changes in clinical activity measured by the systemic lupus erythematosus responder index.

Objective The lupus impact tracker (LIT) is a 10-item patient reported outcome tool to measure the impact of systemic lupus erythematosus or its treatment on patients' daily lives. Herein, we describe the responsiveness of the LIT and LupusQoL to changes in disease activity, using the systemic lupus erythematosus responder index (SRI). Methods A total of 325 adult systemic lupus erythematosus patients were enrolled in an observational, longitudinal, multicentre study, conducted across the USA and Canada. Data (demographics, LIT, LupusQoL, BILAG, SELENA-SLEDAI) were obtained three months apart. Modified SRI was defined as: a decrease in SELENA-SLEDAI (4 points); no new BILAG A, and no greater than one new BILAG B; and no increase in the physician global assessment. Standardised response mean and effect size for LIT and LupusQoL domains were calculated among SRI responders and non-responders. Wilcoxon's test was used to compare the LIT and LupusQoL variation by SRI responder status. Results Of the participants 90% were women, 53% were white, 33% were of African descendant and 17% were Hispanic. Mean (SD) age and SELENA-SLEDAI at baseline were 42.3 (16.2) years and 4.3 (3.8), respectively. Mean (SD) LIT score at baseline was 39.4 (22.9). LIT standardised response mean (effect size) among SRI responders and non-responders were -0.69 (-0.36) and -0.20 (-0.12), respectively ( P = 0.02). For LupusQoL, two domains were responsive to SRI: standardised response mean (effect size) for physical health and pain domains were 0.42 (0.23) and 0.65 (0.44), respectively. Conclusions LIT is moderately responsive to SRI in patients with systemic lupus erythematosus. Inclusion of this tool in clinical care and clinical trials may provide further insights into its responsiveness. This is the first systemic lupus erythematosus patient reported outcome tool to be evaluated against composite responder index (SRI) used in clinical trials.

Social deprivation and stroke severity on admission: a French cohort study in Burgundy and the West Indies - Guyana region.

BACKGROUND AND PURPOSE: Although there is growing and convincing evidence that socially deprived patients are at higher risk of stroke and worse outcomes, it remains controversial whether or not they suffer more severe stroke. This study aimed to evaluate the influence of social deprivation on initial clinical severity in patients with stroke. METHODS: A total of 1536 consecutive patients with an acute first-ever stroke (both ischaemic stroke and intracerebral hemorrhage) were prospectively enrolled from six French study centers. Stroke severity on admission was measured by the National Institutes of Health Stroke Scale score. Social deprivation was assessed at the individual level by the Evaluation de la Précarité et des Inégalités de santé dans les Centres d'Examen de Santé (EPICES) score, a validated multidimensional questionnaire, and several additional single socioeconomic indicators. Polytomous logistic regression analyses were performed to evaluate the association between social deprivation and stroke severity. RESULTS: In univariate analysis, the EPICES score (P = 0.039) and level of education (P = 0.018) were the only two socioeconomic variables associated with stroke severity. Multivariate analysis of the association between EPICES and National Institutes of Health Stroke Scale scores showed that more deprived patients presented a significantly higher risk of both mild and moderate/severe stroke (odds ratio for mild versus minor stroke, 1.39; 95% confidence interval, 1.06-1.84; odds ratio for moderate/severe versus minor stroke, 1.44; 95% confidence interval, 1.09-1.92). A non-significant trend towards a higher risk of both mild and moderate/severe stroke in less educated patients was observed. CONCLUSIONS: Social deprivation was associated with a more severe clinical presentation in patients with stroke. These findings may contribute to the worse outcome after stroke in deprived patients, and underline the need for strategies to reduce social inequalities for stroke.

[Cost of multiple sclerosis in France]. / Coûts de la sclérose en plaques en France.

Multiple sclerosis (MS) is one of the 30 chronic conditions specifically listed by the French healthcare system as a long-term disease (affections de longue durée [ALD]) for which the main health insurance fund (Caisse nationale d'assurance maladie des travailleurs salariés [CNAMTS]) provides full (100%) coverage of healthcare costs. The CNAMTS insures 87% of the French population (52,359,912 of the 60,028,292 inhabitants). The objectives of this study were to evaluate the direct and indirect medical costs of MS among the entire population insured by the CNAMTS in France in 2004. The CNAMTS provided us with access to the ALD database of patients with MS that contains different MS-related expenditures made in 2004. We calculated the overall direct and indirect cost of MS and the cost per patient and per item of expenditure. In 2004, 49,413 patients were registered on the ALD list for MS. Direct cost for MS patients was 469,719,967 €. The direct cost per patient and per year was 9,506 € with variations between regions (French administrative divisions) ranging from 10,800 € in northeastern France (Champagne-Ardenne) to 8,217 € in western France (Pays de la Loire). The different items of expenditure were treatments (44.5%), hospitalization (27.9%), nursing care (5.8%), physiotherapy (5.7%), transport (4%), biology (1.1%), and other (1.5%). During the course of the disease, the overall cost of MS increased slowly during the first 15 years (from 8,000 to 11,000 €), but dramatically the last year of life (23,410 €). The costs of immunomodulator treatments were higher during the first six years after registration on the ALD list. Conversely, physiotherapy costs increased linearly with time during the course of MS. Indirect costs were an estimated 116 million euros in 2004. A disability pension (8,918 € per patient) was perceived by 9,430 patients (19.1%) and a daily allowance (3,317 € per patient) by 9,894 patients (20%). In France, MS has an important economic impact, comparable to human immunodeficiency virus infection.

The new Ghent criteria for Marfan syndrome: what do they change?

The diagnosis of Marfan syndrome (MFS) is challenging and international criteria have been proposed. The 1996 Ghent criteria were adopted worldwide, but new diagnostic criteria for MFS were released in 2010, giving more weight to aortic root aneurysm and ectopia lentis. We aimed to compare the diagnosis reached by applying this new nosology vs the Ghent nosology in a well-known series of 1009 probands defined by the presence of an FBN1 mutation. A total of 842 patients could be classified as MFS according to the new nosology (83%) as compared to 894 (89%) according to the 1996 Ghent criteria. The remaining 17% would be classified as ectopia lentis syndrome (ELS), mitral valve prolapse syndrome or mitral valve, aorta, skeleton and skin (MASS) syndrome, or potential MFS in patients aged less than 20 years. Taking into account the median age at last follow-up (29 years), the possibility has to be considered that these patients would go on to develop classic MFS with time. Although the number of patients for a given diagnosis differed only slightly, the new nosology led to a different diagnosis in 15% of cases. Indeed, 10% of MFS patients were reclassified as ELS or MASS in the absence of aortic dilatation; conversely, 5% were reclassified as MFS in the presence of aortic dilatation. The nosology is easier to apply because the systemic score is helpful to reach the diagnosis of MFS only in a minority of patients. Diagnostic criteria should be a flexible and dynamic tool so that reclassification of patients with alternative diagnosis is possible, requiring regular clinical and aortic follow-up.

National estimate of multiple sclerosis incidence in France (2001-2007).

BACKGROUND: In France, the incidence of multiple sclerosis (MS) is not well known, and MS is one of the 30 long-term illnesses for which patients are covered for 100% of their health care costs. OBJECTIVE: To estimate the incidence of MS in France and its geographic variations. METHODS: We estimated the national rate for notification of MS to the main French health insurance system, and its confidence interval (CI), between November 2000 and October 2007, which covers 87% of the population. We analysed geographic variations using a Bayesian approach. RESULTS: Between November 2000 and October 2007, among a covered population of 52,449,871, some 28,682 individuals were registered as having MS. After age standardization according to the European population, the notification rate for MS was 6.8 per 100,000 (6.7-6.9), 9.8 (9.7-10.0) in women and 3.7 (3.6-3.8) in men. When the under-notification rate (11.5% and 29%) was taken into account, the notification rate per 100,000 inhabitants was estimated between 7.6 and 8.8. The notification rate was higher in north-eastern France, and lower on the Atlantic coast and in the Alps as well as on both sides of the Rhône River. CONCLUSIONS: This study, conducted on a representative French population, provides for the first time national estimates of MS incidence between November 2000 and October 2007.

Abdominal and pelvic injuries caused by road traffic accidents: characteristics and outcomes in a French cohort of 2,009 casualties.

BACKGROUND: The frequency, characteristics, and effect on outcome of abdominal and pelvic injuries (API) caused by road traffic accidents are not well known. We studied them in a well-defined geographical area in France. METHODS: The medical data of all hospitalized victims of road traffic accidents that occurred over a 3-year period were recorded. Injuries were coded according to the Abbreviated Injury Scale (AIS). The Injury Severity Score (ISS) was calculated. Continuous and qualitative variables were described by means and standard deviations or medians and percentages, respectively. Proportions and means were compared using the χ2 and Student tests, respectively. RESULTS: Of 6,977 victims of road traffic accidents, 2,009 were hospitalized (mean ISS=7.9). API were present in 9.3% (n=186) of all hospitalized victims and in 32.2% (n=82) of the most severely injured (ISS≥16, n=255) hospitalized victims. The most frequently seriously injured abdominopelvic organs (AIS≥3) were the spleen, the retroperitoneal organs, and the liver. The mean ISS and the mortality rate were significantly higher for victims with API than those without API (17.5 vs. 6.9, P<0.001; 9.7% vs. 1.9%, P<0.001). In multivariate analysis, the presence of severe API increased the mortality rate by a factor of 2.5. CONCLUSIONS: In this study, API were present in one third of the most severely injured victims of road traffic accidents and were a significant factor of gravity and mortality. This study, conducted in France where there is no National Trauma Registry, underlined the need for establishing such registry.

The very low penetrance of cystic fibrosis for the R117H mutation: a reappraisal for genetic counselling and newborn screening.

BACKGROUND: Cystic fibrosis (CF) is caused by compound heterozygosity or homozygosity of CF transmembrane conductance regulator gene (CFTR) mutations. Phenotypic variability associated with certain mutations makes genetic counselling difficult, notably for R117H, whose disease phenotype varies from asymptomatic to classical CF. The high frequency of R117H observed in CF newborn screening has also introduced diagnostic dilemmas. The aim of this study was to evaluate the disease penetrance for R117H in order to improve clinical practice. METHODS: The phenotypes in all individuals identified in France as compound heterozygous for R117H and F508del, the most frequent CF mutation, were described. The allelic prevalences of R117H (p(R117H)), on either intron 8 T5 or T7 background, and F508del (p(F508del)) were determined in the French population, to permit an evaluation of the penetrance of CF for the [R117H]+[F508del] genotype. RESULTS: Clinical details were documented for 184 [R117H]+[F508del] individuals, including 72 newborns. The disease phenotype was predominantly mild; one child had classical CF, and three adults' severe pulmonary symptoms. In 5245 healthy adults, p(F508del) was 1.06%, p(R117H;T7) 0.27% and p(R117H;T5)<0.01%. The theoretical number of [R117H;T7]+[F508del] individuals in the French population was estimated at 3650, whereas only 112 were known with CF related symptoms (3.1%). The penetrance of classical CF for [R117H;T7]+[F508del] was estimated at 0.03% and that of severe CF in adulthood at 0.06%. CONCLUSIONS: These results suggest that R117H should be withdrawn from CF mutation panels used for screening programmes. The real impact of so-called disease mutations should be assessed before including them in newborn or preconceptional carrier screening programmes.

Pathogenic FBN1 mutations in 146 adults not meeting clinical diagnostic criteria for Marfan syndrome: further delineation of type 1 fibrillinopathies and focus on patients with an isolated major criterion.

Mutations in the FBN1 gene cause Marfan syndrome (MFS) and have been associated with a wide range of milder overlapping phenotypes. A proportion of patients carrying a FBN1 mutation does not meet diagnostic criteria for MFS, and are diagnosed with "other type I fibrillinopathy." In order to better describe this entity, we analyzed a subgroup of 146 out of 689 adult propositi with incomplete "clinical" international criteria (Ghent nosology) from a large collaborative international study including 1,009 propositi with a pathogenic FBN1 mutation. We focused on patients with only one major clinical criterion, [including isolated ectopia lentis (EL; 12 patients), isolated ascending aortic dilatation (17 patients), and isolated major skeletal manifestations (1 patient)] or with no major criterion but only minor criteria in 1 or more organ systems (16 patients). At least one component of the Ghent nosology, insufficient alone to make a minor criterion, was found in the majority of patients with isolated ascending aortic dilatation and isolated EL. In patients with isolated EL, missense mutations involving a cysteine were predominant, mutations in exons 24-32 were underrepresented, and no mutations leading to a premature truncation were found. Studies of recurrent mutations and affected family members of propositi with only one major clinical criterion argue for a clinical continuum between such phenotypes and classical MFS. Using strict definitions, we conclude that patients with FBN1 mutation and only one major clinical criterion or with only minor clinical criteria of one or more organ system do exist but represent only 5% of the adult cohort.

Contribution of molecular analyses in diagnosing Marfan syndrome and type I fibrillinopathies: an international study of 1009 probands.

BACKGROUND: The diagnosis of Marfan syndrome (MFS) is usually initially based on clinical criteria according to the number of major and minor systems affected following international nosology. The number of FBN1 mutation carriers, at risk of aortic complications who would not be properly diagnosed based only on clinical grounds, is of growing importance owing to the increased availability of molecular screening. The aim of the study was to identify patients who should be considered for FBN1 mutation screening. METHODS: Our international series included 1009 probands with a known FBN1 mutation. Patients were classified as either fulfilling or not fulfilling "clinical" criteria. In patients with unfulfilled "clinical" criteria, we evaluated the percentage of additional patients who became positive for international criteria when the FBN1 mutation was considered. The aortic risk was evaluated and compared in patients fulfilling or not fulfilling the "clinical" international criteria. RESULTS: Diagnosis of MFS was possible on clinical grounds in 79% of the adults, whereas 90% fulfilled the international criteria when including the FBN1 mutation. Corresponding figures for children were 56% and 85%, respectively. Aortic dilatation occurred later in adults with unfulfilled "clinical criteria" when compared to the Marfan syndrome group (44% vs 73% at 40 years, p<0.001), but the lifelong risk for ascending aortic dissection or surgery was not significantly different in both groups. CONCLUSIONS: Because of its implications for aortic follow-up, FBN1 molecular analysis is recommended in newly suspected MFS when two systems are involved with at least one major system affected. This is of utmost importance in patients without aortic dilatation and in children.

Low compliance with colonoscopic screening in first-degree relatives of patients with large adenomas.

BACKGROUND: Little is known about compliance with colonoscopy as a screening method in first-degree relatives of patients with large adenomas. Aims To evaluate the compliance with screening colonoscopy among this population, and its determinants. METHODS: Data were obtained from the family part of the GEADE study, a study on genetic factors of colorectal adenomas. Index cases were 306 patients with adenomas > or = 10 mm. All living first-degree relatives aged 40-75 who could be contacted by the index case were asked to undergo a colonoscopy, unless they had had one in the previous 5 years. RESULTS: Among 674 eligible relatives, 56 had had a colonoscopy within the preceding 5 years and 114 underwent a screening colonoscopy resulting in a compliance with screening colonoscopy of 18%. This was not related to most characteristics of index cases. Compliance was significantly lower when the index case lived in the Greater Paris area than when he/she lived in other areas (12% vs. 21%). It was higher in siblings (18%) and offspring (23%) than in parents (9%) and in relatives under 55 years old (22%) than in relatives aged 55 and over (15%). CONCLUSIONS: Compliance with colonoscopy was low in first-degree relatives of patients with large adenomas. The reasons for this should be determined and appropriate strategies developed to increase compliance.

Increased risk of acute leukemia after adjuvant chemotherapy for breast cancer: a population-based study.

PURPOSE: To quantify the risk of acute leukemia after adjuvant therapy, especially chemotherapy with topoisomerase II inhibitors. PATIENTS AND METHODS: We performed a population-based study in a cohort of 3,093 women younger than 85 years who resided in the French administrative area of the Côte d'Or, who were given a first diagnosis of primary breast cancer between 1982 and 1996, and who received a curative treatment. Information about therapy and follow-up events was obtained from records of cancer registries that covered this area. RESULTS: Until December 1998, 10 cases of acute leukemia, including nonlymphoid acute leukemia and refractory anemia with excess of blasts, occurred in patients before any local or distant recurrence. All cases developed in the first 4 years of follow-up. Compared with the general female population, the incidence rate of leukemia was significantly increased in women who received radiotherapy and chemotherapy (standardized incidence ratio, 28.5; P <.0001). A dose-dependent increase in the risk of leukemia was observed in women treated with mitoxantrone. Cox regression analysis showed that the risk of leukemia was significantly lower in patients treated with anthracyclines than in those treated with mitoxantrone at cumulative doses >/= 13 mg/m(2). CONCLUSION: The combination of adjuvant radiotherapy and chemotherapy with mitoxantrone induces a high risk of acute leukemia in patients with breast cancer. A leukemogenic effect of chemotherapy with anthracyclines cannot be ruled out with certainty. However, there are some suggestions that these topoisomerase II inhibitors might be less leukemogenic than mitoxantrone and could be preferred in an adjuvant setting.

Is the management of hepatitis C patients appropriate? A population-based study.

BACKGROUND: In order for hepatitis C patients to receive antiviral treatment, they must reach medical care. AIM: To assess the proportion of patients reaching medical care after hepatitis C diagnosis in a general population (1 006 171 inhabitants) in France. METHODS: Between 1994 and 1999, 1508 cases were diagnosed, of which 1251 were eligible for the study. RESULTS: Two-hundred and two patients did not have any medical care; among them, 55.4% had normal alanine transferase, 58.4% had risk factors related to lifestyle and 22.8% were alcoholics. Amongst the 1049 other patients, 41.6% had a liver biopsy, 25.0% were treated. Treatment was more often carried out in males than in females (OR: 1.59; P = 0.001), and in patients under 65 than in older patients (OR: 2.22; P < 0.008). Among non-treatment reasons, alcoholism (P = 0.001), drug-addiction (P = 0.04) and escaping monitoring (P = 0.04) were more frequent in males than in females, whereas normal alanine transferase was more frequent in females than in males (P = 0.004). Amongst 278 patients with a Metavir score >A1F1, 71 (25.5%) did not undergo treatment. CONCLUSION: In a general population, one patient in six did not receive on-going health care; a quarter of patients with a Metavir score >A1F1 did not receive any treatment. These results showed insufficient clinical management, which could compromise the effectiveness of treatment in general population.

Dietary patterns and the risk of colorectal adenoma recurrence in a European intervention trial.

The relations between individual foods and nutrients to colorectal tumours are conflicting. Few studies have taken into account the interdependence between individual components of diet and their possible interactions. The aim of the study was to examine the associations between dietary patterns and the risk of colorectal adenoma recurrence in the European fibre-calcium intervention trial. Among the 640 patients with confirmed adenomas at the index colonoscopy, 592 had an initial dietary assessment using a diet history questionnaire. The present analysis was restricted to 277 men and 165 women without history of adenoma prior to the index colonoscopy and who completed the study. The main end point was the 3-year recurrence of adenomas. Principal component analysis was used to identify dietary patterns from 50 food groups. Ninety-two patients presented new colorectal adenomas at the 3-year colonoscopy (65 men and 27 women). In men, three meaningful dietary patterns emerged from analysis, explaining 21.3% of variability. They were called 'Mediterranean', 'Sweets and snacks' and 'High fat and proteins' patterns. None of them were significantly related to the overall recurrence of colorectal adenomas either in univariate or multivariate analyses. Among women, the 'Mediterranean', the 'Western' and the 'Snacks' patterns explained 21.9% of variability. The 'Mediterranean' pattern characterized by a high consumption of olive oil, vegetables, fruit, fish and lean meat significantly reduced adenoma recurrence [second tertile: adjusted odds ratio (OR)=0.50, 95% confidence interval (CI)=0.18-1.42; third tertile: adjusted OR=0.30, 95% CI=0.09-0.98; P for linear trend=0.04]. The 'Western' and 'Snacks' patterns were not associated with recurrence among women. In conclusion, this study suggests that the Mediterranean dietary pattern may reduce the recurrence of colorectal adenomas, at least in women. These exploratory results need to be confirmed by larger studies.

Weights at birth and in early infancy, systolic pressure, and left ventricular structure in subjects aged 8 to 24 years.

The objective of this study was to determine whether systolic pressure and left ventricular mass in children, adolescents, and young adults are related to fetal and infant growth. Blood pressure measurements and M-mode echocardiography were performed in 210 subjects aged 8 to 24 years whose information on weights at birth and in early infancy, written by physicians, was obtained from the children's health record booklets. Systolic pressure, adjusted for sex and current height or for sex, current age, weight, and height, was the highest in subjects with low birth weight. No association was observed between systolic pressure and weight at either 9 months or 2 years. Left ventricular mass, adjusted for sex and current height or for sex, current age, weight, and height, increased with decreasing weight at 9 months or 2 years, independent of systolic pressure. Increased ventricular mass associated with reduced infant growth was concentric, resulting from a proportionate thickening of the posterior wall and interventricular septum. Left ventricular mass was not related to birth weight. These findings were observed in both sexes and in all age subgroups and were independent of gestational age, birth order, and parental risk factors. This study supports the hypothesis that systolic pressure and left ventricular mass might be partly determined during fetal life and early infancy. The mechanisms that underlie the associations of blood pressure and left ventricular structure with weights at birth and in early infancy should be studied thoroughly.

Systemic oxidative stress and cognitive performance in the population-based EVA study. Etude du Vieillissement Artériel.

The aim of this study was to examine the relationships between cognitive functioning and blood levels of antioxidants and lipoperoxidation products in an elderly population. In 1991-1992, 1389 volunteers (574 men and 815 women aged 59 to 71 years) were recruited from the general population. Levels of selenium, carotenoids, and thiobarbituric-reactive substances in plasma and of vitamin E, glutathione peroxidase, and Cu-Zn superoxide dismutase in red blood cells were measured. Cognitive functioning was assessed with various psychometric tests. We used logistic regression to estimate the risk of poor cognitive functioning (< 25th percentile of the score distribution) associated with low values of each antioxidants (< 25th percentile) including potential confounding factors. A low level of total carotenoids (< 1.86 mumol/l) was associated with poor cognitive performance in two tests assessing visual attention and logical reasoning: the Trail-Making Test part B [OR = 1.34 IC95% (0.99-1.81), p = .055] and the Digit Symbol Substitution from the WAIS-R [OR = 1.38 IC95% (1.02-1.89), p = .04]. Low levels of other antioxidants and high levels of thiobarbituric-reactive substances were not related to poor cognitive functioning. Results observed with plasma carotenoids are in accordance with previous data obtained mostly from dietary records.

Relationships between 3-y longitudinal changes in body mass index, waist-to-hip ratio, and metabolic variables in an active French female population.

Three-year longitudinal changes in body mass index (BMI), waist-to-hip ratio (WHR), and metabolic variables were examined in 209 active French women. For the entire group, a weak but significant positive association was found between change in BMI and change in WHR. However, analysis of covariance according to the degree of abdominal fat distribution showed a heterogeneity of this association that was confined to women with abdominal fat distribution. Changes in BMI were positively associated with changes in total cholesterol (P less than 0.05), triglycerides (P less than 0.10), and blood pressure (P less than 0.001), whereas changes in WHR were associated with changes in triglycerides (P less than 0.05) and diastolic blood pressure (P less than 0.10). These longitudinal results suggest that a more favorable body-fat pattern and metabolic profile might be achieved by reducing weight, or at least by preventing weight gain, particularly in women with high abdominal-fat distribution.

Combined effects of lipid peroxidation and antioxidant status on carotid atherosclerosis in a population aged 59-71 y: The EVA Study. Etude sur le Vieillisement Artériel.

There are few epidemiologic studies of the effects of lipid peroxidation and antioxidant status on atherosclerosis. The relation of lipid peroxidation evaluated by thiobarbituric acid-reactive substances (TBARS) and biological markers of antioxidant status to ultrasonographically assessed carotid atherosclerosis was examined from baseline data of a longitudinal study on cognitive and vascular aging (Etude sur le Vieillisement Artériel, the EVA Study). The study sample was composed of 1187 mean and women aged 59-71 y without any history of coronary artery disease or stroke. Ultrasound examination included measurements of intima-media thickness (IMT) on the common carotid arteries (CCAs) and at the site of plaques. After adjustment for conventional cardiovascular risk factors, erythrocyte vitamin E was significantly and negatively associated with CCA-IMT in both men and women whereas plasma selenium and carotenoids were not. No association was found between TBARS and CCA-IMT in either sex. However, TBARS were significantly higher in men with carotid plaques than in those without. This association was strengthened in men with concentrations of erythrocyte vitamin E, plasma selenium, and carotenoids below the lowest quartile. Our findings give some epidemiologic support to the hypothesis that lipid peroxidation and low antioxidant status are involved in the early phases of atherosclerosis.

Relationship between sex hormones and haemostatic factors in healthy middle-aged men.

Associations of plasma testosterone and estradiol with some haemostatic factors (factor VII activity, fibrinogen, antithrombin III and alpha 2-antiplasmin) were cross-sectionally examined in 251 healthy, middle-aged men participating in the Paris Prospective Study II on risk factors for ischaemic heart disease. Testosterone levels were negatively correlated to factor VII activity and alpha 2-antiplasmin, the main inhibitor of fibrinolysis. No association was found either between testosterone levels and both fibrinogen and antithrombin III, or between estradiol levels and the set of haemostatic variables. The associations between testosterone and both factor VIIc and alpha 2-antiplasmin were independent of HDL-cholesterol, LDL-cholesterol, triglycerides, smoking, alcohol, body mass index and blood pressure. These results suggest that low circulating testosterone levels might be associated with a hypercoagulability state and therefore could contribute to an increased risk of IHD.

Relation of serum elastase activity to ultrasonographically assessed carotid artery wall lesions and cardiovascular risk factors. The EVA study.

The potential interest of serum elastase activity (SEA) as a marker of vascular aging and atherosclerosis was studied as part of an epidemiological study on vascular and cognitive aging (EVA Study). SEA was measured in 555 men and 774 women aged 59-71 years with a synthetic substrate, suc(ala)3pNA, according to a modified enzyme-linked immunosorbant assay (ELISA)-type procedure. The distribution of SEA-values was skewed to the right in men and women, the mean value was 0.52 +/- 0.55 U/ml in males and 0.43 +/- 0.52 U/ml for females. This difference could be entirely explained by alcohol consumption. SEA increased strongly with alcohol consumption in males and females. It was also positively and significantly correlated with body mass index (BMI) and systolic blood pressure (SBP). SEA significantly decreased with age in men and was not influenced by smoking in either sex. SEA was significantly increased in diabetic men compared with non-diabetics and a similar trend, although not significant, was observed in women. When both sexes were combined, the association between diabetes and SEA was independent of other clinical risk factors. No significant associations were observed with intima-media thickness or atherosclerotic plaques assessed by B-mode carotid ultrasonography. Among biological risk factors, triglycerides (in both sexes) and glucose (in men) appeared the strongest correlates of increase in SEA. In multivariate analysis, independent determinants of an increased SEA were age, alcohol consumption, triglycerides and glucose in men, and alcohol consumption and triglycerides in women.

Hormonal influences on the relationships between body fatness, body fat distribution, lipids, lipoproteins, glucose and blood pressure in French working women.

The independent associations between overall obesity, body fat distribution, lipids, lipoproteins, glucose, blood pressure and some hormonal factors (sex hormone-binding globulin (SHBG), corticosteroid binding globulin (CBG) and fasting insulin) were cross-sectionally examined in 205 French working women. After adjustment for age, overall adiposity assessed by body mass index (BMI) was significantly associated with most metabolic parameters, whereas regional adiposity assessed by the waist-hip ratio (WHR) was significantly associated only with triglyceride, systolic and diastolic blood pressure. Blood pressure, glucose but not triglyceride, were also negatively and significantly correlated with SHBG and positively with fasting insulin. Negative independent associations were found between SHBG and both BMI and WHR, whereas CBG was positively associated only with WHR. Fasting insulin was no longer related to WHR after adjustment for BMI. After controlling for the effect of SHBG or insulin, the associations between triglyceride, blood pressure and both BMI and WHR were not substantially modified. After adjustment for BMI and WHR, fasting insulin was independently associated with both HDL cholesterol and diastolic blood pressure. In conclusion, in these French women, hormonal factors under study appeared to have little influence on the relationships between body fatness, body fat distribution, metabolic variables and blood pressure.