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Biomedical subjects

P Y Scarabin

Publications and source records attributed to P Y Scarabin.

At least 19 recordsLinked to original sources
PubMed2006

Obesity and risk of venous thromboembolism among postmenopausal women: differential impact of hormone therapy by route of estrogen administration. The ESTHER Study.

BACKGROUND: Oral estrogen use and elevated body mass index (BMI) increase the risk of venous thromboembolism (VTE). Recent data suggest that transdermal estrogen might be safe with respect to thrombotic risk. However, the impact of transdermal estrogen on the association between overweight (25 kg m(-2) < BMI < or = 30 kg m(-2)) or obesity (BMI >30 kg m(-2)) and VTE risk has not been investigated. METHODS: We carried a multicenter case-control study of VTE among postmenopausal women aged 45-70 years, between 1999 and 2005, in France. Case population consisted of women with a first documented idiopathic VTE. We recruited 191 hospital cases matched with 416 hospital controls and 62 outpatient cases matched with 181 community controls. RESULTS: The odds ratio (OR) for VTE was 2.5 [95% confidence interval (CI):1.7-3.7] for overweight and 3.9 (95% CI: 2.2-6.9) for obesity. Oral, not transdermal, estrogen was associated with an increased VTE risk (OR = 4.5; 95% CI: 2.6-7.7 and OR = 1.1; 95% CI: 0.7-1.7, respectively). Compared with non-users with normal weight, the combination of oral estrogen use and overweight or obesity further enhanced VTE risk (OR = 10.2; 95% CI: 3.5-30.2 and OR = 20.6; 95% CI: 4.8-88.1, respectively). However, transdermal users with increased BMI had similar risk as non-users with increased BMI (OR = 2.9; 95% CI: 1.5-5.8 and OR = 2.7; 95% CI: 1.7-4.5 respectively for overweight; OR = 5.4; 95% CI: 2.1-14.1 and OR = 4.0; 95% CI: 2.1-7.8 respectively for obesity). CONCLUSIONS: In contrast to oral estrogen, transdermal estrogen does not confer an additional risk of idiopathic VTE in women with increased BMI. The safety of transdermal estrogen on thrombotic risk has to be confirmed.

Administration, Cutaneous↗
PubMed2002

[Deep venous thrombosis: epidemiology, acquired risk factors].

Deep vein thrombosis is a frequent disease with an annual incidence reaching 5 per thousand among subjects over 75 years. Major acquired risk factors for venous thrombosis include surgery, neoplasm, reduced mobility or paresis, and a previous episode of deep vein thrombosis. Among women, hormonal status (pregnancy, oral contraceptive, hormone replacement therapy) is responsible for the majority of all venous thrombotic events. The impact of other factors is controversial: obesity, tobacco use and varicose veins. Venous thrombosis is a multifactorial disease and analysis of the interactions between acquired and inherited risk factors is an extremely interesting field of investigation.

Adult↗
PubMed2001

Haemostasis in relation to dietary fat as estimated by erythrocyte fatty acid composition: the prime study.

We investigated whether haemostatic variables were related with dietary fatty acid composition as estimated by the fatty acid content of erythrocytes. Subjects were a subsample (n=283) of the participants in the Prospective Epidemiological Study of Myocardial Infarction (PRIME) Study. Factor VII, fibrinogen, tissue-type plasminogen activator antigen (tPA-ag), plasminogen activator inhibitor type 1 (PAI-1), D-dimer and von Willebrand factor (vWf) were measured and the fatty acid composition was determined in the phospholipids of total erythrocytes by gas chromatography. Statistical analyses were performed using multiple linear regression analyses with adjustment for age, center and body mass index. tPA-ag was significantly related to the n-3 fatty acids derived from fish. This was reflected in an inverse association of all n-3 fatty acids combined with tPA-ag (beta=-0.37 ng/ml/%, 95% confidence intervals: -0.45, -0.29, P<.01). Positive and significant associations of D-dimer with arachidic and eicosamonoenoic acid were observed (P<.01). No relationships were found between fatty acids and fibrinogen, vWf, PAI-1 or factor VII. The results of this study suggest that consumption of n-3 fatty acids derived from fish may favourably influence tPA-ag.

Body Mass Index↗
PubMed2001

Relationships between alcoholic beverages and cardiovascular risk factor levels in middle-aged men, the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction Study.

The relationships between alcoholic beverages and cardiovascular risk factors were assessed in 6730 men living in France or Northern Ireland. In France, all alcoholic beverages were significantly correlated with body mass index (BMI), systolic (SBP) and diastolic blood pressure (DBP), high density lipoprotein (HDL) parameters, PAI-1 and Factor VII, whereas only wine was negatively related with fibrinogen levels. After adjusting for center, age, BMI, educational level, smoking and marital status, wine had a lesser effect on blood pressure, triglyceride, apo B and LpE:B levels than beer. Wine was associated with lower fibrinogen levels and beer with higher PAI-1 activity levels independent of the amount of alcohol consumed. In Northern Ireland, wine was negatively correlated with BMI, triglycerides, LpE:B and fibrinogen, whereas beer was positively correlated with SBP and DBP, triglycerides, HDL, apoprotein A-I and fibrinogen. Multivariate analysis showed wine to be positively associated with HDL parameters, and negatively with fibrinogen levels. Wine was also associated with higher LpA-I levels and lower fibrinogen levels independent of the amount of alcohol consumed. We conclude that alcohol consumption is related to lipid, lipoprotein and haemostatic variables, but the magnitude of the relationships depends on the type of alcoholic beverage. Also, some effects might be related to non-alcoholic components.

Alcohol Drinking↗
PubMed2001

Thrombomodulin promoter mutations, venous thrombosis, and varicose veins.

We analyzed the distal promoter region of the thrombomodulin (TM) gene (nucleotides -300 to -2052) in subjects from the Paris Thrombosis Study (PATHROS), a French case-control study of venous thrombosis, to identify polymorphisms that might modify TM gene expression. Eight novel mutations were found in the 40 DNA samples initially screened. Two of these mutations (-1748G/C and -1208/-1209 del TT) were frequent. One rare transition (-1166G/A) might have functional consequences owing to its position. These 3 mutations were screened for in the entire study population of 327 patients and 398 controls. None of the 3 was significantly associated with thrombosis. Interestingly, the -1208/-1209 TT deletion was associated with varicose veins in the patients. This mutation was in tight linkage disequilibrium with the +1418 C/T change in the coding sequence, a known polymorphism that predicts an Ala 455 Val substitution in the sixth epidermal growth factor-like TM module, a domain previously implicated in the proliferative functions of TM. This linkage suggests that the Ala 455 Val mutation may promote changes in these functions and thus be involved in varicose vein formation.

Adult↗
PubMed2001

Diagnostic accuracy of compression ultrasonography for the detection of asymptomatic deep venous thrombosis in medical patients--the TADEUS project.

We assessed the accuracy of venous compression ultrasonography (CUS) for the detection of asymptomatic deep vein thrombosis in 122 consecutive patients, with a mean age of 69 years, who were hospitalised in an internal medicine unit. All included patients had CUS within 48 h of admission. Twelve out of 17 patients with a positive CUS underwent phlebography, as the others withdrew their consent, whereas the remaining 105 patients with a negative serial CUS testing were clinically followed-up at 3 months. We found that CUS had a sensitivity and a specificity of respectively 1 (95% CI, 0.73 to 1) and 1 (95% CI, 0.96 to 1) for the detection of asymptomatic deep vein thrombosis. Kappa-coefficients for intra-observer and inter-observer agreements were respectively 0.88 and 0.56. We concluded that venous compression ultrasonography, performed as described, fulfils requirements of a screening test that could be available for prophylactic clinical trials or epidemiological researches.

Aged↗
PubMed2000

Association of hypertensive status and its drug treatment with lipid and haemostatic factors in middle-aged men: the PRIME study.

AIMS: To assess the association of hypertensive status and antihypertensive drug treatment with lipid and haemostatic levels in middle-aged men. METHODS AND RESULTS: Hypertensive status, antihypertensive drug treatment, total and high-density lipoprotein (HDL) cholesterol, triglyceride, apoproteins A-I and B, lipoparticles LpA-I, LpE:B and Lp(a), fibrinogen, plasminogen activator inhibitor-1 (PAI-1) activity and factor VII were assessed in a sample of men 50-59 years living in France (n = 7050) and Northern Ireland (n = 2374). After adjustment for age, body mass index, smoking status, educational level, country, alcohol drinking and hypolipidaemic drug treatment, untreated hypertensive subjects had higher levels of total cholesterol, triglyceride, apoproteins A-I and B and PAI-I activity than normotensive subjects. On univariate analysis, diuretics decreased total and HDL-cholesterol and apoproteins A-I and B; those differences remained after multivariate adjustment. Treatment with beta-blockers decreased total and HDL-cholesterol, apoprotein A-I and LpA-I, and this effect remained after multivariate adjustment. Calcium channel blockers decreased total cholesterol and apoproteins A-I and B; those differences remained significant after multivariate adjustment. ACE inhibitors decreased total cholesterol, triglycerides, apoprotein B and LpE:B; and this effect remained after multivariate adjustment. Analysis of the subjects on monotherapy showed beta-blockers to decrease total cholesterol and HDL parameters and angiotensin-converting enzyme (ACE) inhibitors to decrease low-density lipoprotein (LDL)-related parameters, while no effect was found for the other antihypertensive drugs. CONCLUSIONS: Hypertensive status is associated with an unfavourable lipid and haemostatic profile in middle-aged men. Antihypertensive treatment with beta-blockers decreases HDL parameters, whereas treatment with ACE inhibitors appears to decrease total cholesterol and LDL-related parameters.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1999

Assessment of the risk for venous thromboembolism among users of hormone replacement therapy.

Although hormone replacement therapy (HRT) provides health benefits, concerns about harmful effects have been raised, including an increased risk of venous thromboembolism. The purpose of this review is to assess the risk for venous thromboembolism associated with HRT. Data searches involved the MEDLINE database from January 1982 to December 1997, and bibliographies of retrieved articles. Seven case-control studies and 1 prospective cohort study considering venous thromboembolism as the outcome of interest were selected and rated according to methodological criteria. Results of case-controls studies were pooled to determine an overall estimate. The pooled risk ratio (95% confidence interval) for venous thromboembolism among current users of HRT compared with non-users (never-users and past-users combined) was 2.1 (1.4 to 3.0) in the case-control studies (n = 7). Based on one prospective cohort study, the risk of primary pulmonary embolism associated with HRT was 2.1 (1.2 to 3.8). No association was found with past use of HRT. The risk of venous thromboembolism was higher within the first year of treatment. There was no strong evidence for a dose-response relationship with estrogen. No striking difference in risk of venous thromboembolism was observed between unopposed and opposed regimens. The small number of women using transdermal estrogen therapy precluded any firm conclusions about the impact of the route of estrogen administration. Current use of oral estrogen as HRT is associated with a 2- to 3-fold increased risk of venous thromboembolism. However, the absolute risk remains low, and these findings need to be weighed against the potential benefits of treatment. Whether transdermal estrogen therapy is safe with respect to venous thromboembolism has yet to be adequately investigated.

Dose-Response Relationship, Drug↗
PubMed1999

Hormone replacement therapy and circulating ICAM-1 in postmenopausal women--a randomised controlled trial.

Hormone replacement therapy may reduce the risk of coronary heart disease but underlying mechanism has not been adequately explained. Recent data suggest that intercellular adhesion molecule 1 (ICAM-1) plays a critical role in early stage of atherosclerosis and may serve as a molecular marker for the development of arterial disease. We investigated the effects of oral and transdermal cyclic oestradiol combined with progesterone on plasma concentration of soluble ICAM-1 (sICAM-1). Thirty-seven healthy postmenopausal women were randomly assigned to receive either oral estradiol valerate or transdermal estradiol both combined with micronized progesterone or no hormonal treatment. Plasma sICAM-1 was assayed at baseline and after a 6-month period. Oral but not transdermal estradiol regimen significantly decreased mean value of sICAM-1 compared with no treatment. Differences in sICAM-1 levels between active treatments were significant. There were no significant changes in mean values of fibrinogen between the three groups. Our results show a favorable effect of oral estrogen plus progesterone on a soluble marker of vascular inflammation and may provide plausible explanation for a cardioprotective effect of hormone replacement therapy among healthy postmenopausal women.

Administration, Oral↗
PubMed1999

Elevated plasma fibrinogen and increased fibrin turnover among healthy women who both smoke and use low-dose oral contraceptives--a preliminary report.

Among users of low-dose oral contraceptives (OC), cardiovascular diseases occur mainly in smokers. The mechanisms by which OC and smoking increase the risk for arterial thrombotic risk have not been adequately explained. Epidemiological evidence suggests that changes in blood coagulation and fibrinolysis may play an important role as determinants of thrombotic events. Therefore, we have investigated the associations of OC and smoking with haemostatic variables among 194 premenopausal healthy women. Fourty women were current users of low-dose OC and 62 women were smokers. After adjustment for age and body mass index, mean values of factor XIIa, factor VII activity and antigen, fibrinogen, D-dimer, global fibrinolytic capacity were significantly higher in OC users than in non-users. Mean levels of PAI activity and t-PA antigen were significantly lower in OC users than in non-users. Smokers had significantly higher mean values of fibrinogen than non-smokers. Two-way analysis of variance showed that the differences in mean levels of fibrinogen and D-dimer between OC users and non users were restricted to smokers. The positive and significant interactions between OC use and smoking in their effects on haemostatic variables were consistent with respect to age and type of OC. These preliminary data suggest that elevated plasma levels of fibrinogen and intravascular fibrin deposition may play a role in the pathogenesis of arterial thrombotic disease among women who are both low-dose OC users and smokers.

Adult↗
PubMed1999

[Hormone replacement therapy in menopause and the risk of cerebrovascular accident].

BACKGROUND AND PURPOSE: Hormone replacement therapy relieves climacteric symptom and prevents postmenopausal osteoporosis. A protective effect of estrogen against coronary heart disease remains debatable and inconclusive results have been reported with respect to the risk of stroke. We have therefore performed an updated quantitative assessment of the risk for stroke associated with hormone replacement therapy. METHODS: MEDLINE database was used. Studies analyzing postmenopausal women and considering any subtypes of stroke--i.e. fatal or non-fatal, ischaemic or haemorrhagic--as the outcome of interest were selected. An overall estimate was calculated as a weighted average of the odds ratios or relative risks, with the weights being the reciprocal of their variance. Random effects models were used to take into account the heterogeneity of data. RESULTS: Six case-control studies, seventeen cohort studies and one randomized trial were selected between 1978 and 1998. Seven studies assessed the risk of ischaemic stroke associated with hormone replacement therapy and the pooled estimate of the risk was 1.12 (95% confidence interval, 1.01 to 1.25). The random effects model showed an increased risk of 18% (relative risk 1.18, 95% confidence interval, 0.98 to 1.43). Regarding haemorrhagic stroke, the analysis based on two case-control studies and one cohort study showed a significantly reduced risk of 35%. Lastly, based on five studies, no significant change in the risk of subarachnoidal hemorrhage was found. CONCLUSION: This updated analysis suggests an increased risk for ischaemic stroke among postmenopausal women who use oral estrogen replacement therapy. No data regarding transdermal estrogen are available.

Clinical Trials as Topic↗
PubMed1998

Associations of fibrinogen, factor VII and PAI-1 with baseline findings among 10,500 male participants in a prospective study of myocardial infarction--the PRIME Study. Prospective Epidemiological Study of Myocardial Infarction.

The contribution of coagulation factors and fibrinolytic variables to the development of ischaemic arterial disease is still not clearly established. The PRIME study is a prospective cohort study of myocardial infarction in men aged 50-59 years and recruited from three MONICA field centers in France (Lille, Strasbourg and Toulouse) and the center in Northern Ireland (Belfast). Baseline examination included measurement of plasma fibrinogen, factor VII, and PAI-1 activity in over 10,500 participants. We investigated the associations of these haemostatic variables with cardiovascular risk factors, prevalent atherosclerotic disease and geographical area. Fibrinogen level increased with age, smoking, waist-to-hip ratio, LDL-cholesterol, and it decreased with educational level, leisure physical activity, alcohol intake and HDL-cholesterol. Factor VII activity increased with body mass index, waist-to-hip ratio, triglycerides. HDL- and LDL-cholesterol. PAI-1 activity increased with body mass index, waist-to-hip ratio, triglycerides, alcohol intake, smoking, and decreased with leisure physical activity. PAI-1 level was higher in diabetic subjects than in subjects without diabetes. Cardiovascular risk factors explained 8%, 9%, and 26% of the total variance in fibrinogen, factor VII, and PAI-1, respectively. Compared with participants without prevalent cardiovascular disease, those with previous myocardial infarction (n = 280), angina pectoris (n = 230), or peripheral vascular disease (n = 19) had significantly higher levels of fibrinogen. but those with stroke (n = 67) had not. PAI-1 activity showed a similar pattern of association. The odds ratio for cardiovascular disease associated with a rise of a one standard deviation in fibrinogen and PAI-1 was 1.31 (95% confidence interval: 1.20 to 1.42, p <0.001) and 1.38 (95% confidence interval: 1.27 to 1.49, p<0.001), respectively. After adjustment for cardiovascular risk factors, these associations were attenuated but remained highly significant. There was no significant association between factor VII activity and prevalent cardiovascular disease. Fibrinogen level and, to a lesser extent, factor VII and PAI-1 activity were higher in Northern Ireland than France after adjustment for the main cardiovascular risk factors. These geographical variations are consistent with the 2 to 3-fold higher incidence of myocardial infarction in Northern Ireland than France. Our results provide further epidemiological evidence for a possible role of fibrinogen and PAI-1 in the pathogenesis of coronary heart disease.

Alcohol Drinking↗
PubMed1997

Effects of oral and transdermal estrogen/progesterone regimens on blood coagulation and fibrinolysis in postmenopausal women. A randomized controlled trial.

Postmenopausal hormone replacement therapy is associated with a reduction in the incidence of coronary heart disease. However, inconclusive results have been reported with respect to the risk of stroke, and recent studies consistently showed an increased risk of venous thromboembolism in postmenopausal women using oral estrogen. There are surprisingly few interventional studies to assess the true effects of estrogen-progestin regimens on blood coagulation and fibrinolysis, and the impact of the route of estrogen administration on hemostasis has not been well documented. Therefore, we investigated the effects of oral and transdermal estradiol/progesterone replacement therapy on hemostatic variables. Forty-five healthy postmenopausal women, aged 45 to 64 years, were assigned randomly to one of the three following groups: cyclic oral or transdermal estradiol, both combined with progesterone, or no hormonal treatment. Hemostatic variables were assayed at baseline and after a 6-month period. Pairwise differences in the mean change between the three groups were compared using nonparametric tests. Oral but not transdermal estradiol regimen significantly increased the mean value of prothrombin activation peptide (F1 + 2) and decreased mean antithrombin activity compared with no treatment. Differences in fragment F1 + 2 levels between active treatments were significant. The oral estrogen group was associated with a significant decrease in both mean tissue-type plasminogen (t-PA) concentration and plasminogen activator inhibitor (PAI-1) activity and a significant rise in global fibrinolytic capacity (GFC) compared with the two other groups. A transdermal estrogen regimen had no significant effect on PAI-1, t-PA, and GFC levels. There were no significant changes in mean values of fibrinogen, factor VII, von Willebrand factor, protein C, fibrin D-dimer, and plasminogen between and within the three groups. We conclude that oral estrogen/progesterone replacement therapy may result in coagulation activation and increased fibrinolytic potential, whereas opposed transdermal estrogen appears without any substantial effects on hemostasis. Whereas these results may account for an increased risk of venous thromboembolism in users of oral postmenopausal estrogen, they emphasize the potential importance of the route of estrogen administration in prescribing hormone replacement therapy to postmenopausal women, especially to those at high risk of thrombotic disease.

Administration, Cutaneous↗