Valérie Olié

Postmenopausal Hormone Therapy and Risk of Idiopathic Venous Thromboembolism. Results From the E3N Cohort Study

Objective—Oral estrogen therapy increases venous thromboembolism risk among postmenopausal women. Although recent data showed transdermal estrogens may be safe with respect to thrombotic risk, the impact of the route of estrogen administration and concomitant progestogens is not fully established. Methods and Results—We used data from the E3N French prospective cohort of women born between 1925 and 1950 and biennially followed by questionnaires from 1990. Study population consisted of 80308 postmenopausal women (average follow-up: 10.1 years) including 549 documented idiopathic first venous thromboembolism. Hazard ratios (HR) and 95% confidence intervals (CI) were estimated using Cox proportional models. Compared to never-users, past-users of hormone therapy had no increased thrombotic risk (HR=1.1; 95% CI: 0.8 to 1.5). Oral not transdermal estrogens were associated with increased thrombotic risk (HR=1.7; 95% CI: 1.1 to 2.8 and HR=1.1; 95% CI: 0.8 to 1.8; homogeneity: P=0.01). The thrombotic risk significantly differed by concomitant progestogens type (homogeneity: P<0.01): there was no significant association with progesterone, pregnanes, and nortestosterones (HR=0.9; 95% CI: 0.6 to 1.5, HR=1.3; 95% CI: 0.9 to 2.0 and HR=1.4; 95% CI: 0.7 to 2.4). However, norpregnanes were associated with increased thrombotic risk (HR=1.8; 95% CI: 1.2 to 2.7). Conclusions—In this large study, we found that route of estrogen administration and concomitant progestogens type are 2 important determinants of thrombotic risk among postmenopausal women using hormone therapy. Transdermal estrogens alone or combined with progesterone might be safe with respect to thrombotic risk.

Risk of venous thrombosis with oral versus transdermal estrogen therapy among postmenopausal women.

Purpose of reviewVenous thromboembolism (VTE) is a main harmful effect of oral estrogen therapy among postmenopausal women. Transdermal estrogens may be safer but early results need to be confirmed. This review provides a summary of the most recent findings regarding the VTE risk among oral versus transdermal estrogens users. Recent findingsSince 2008, we identified five relevant observational studies. Among them, two large cohort studies confirmed that oral but not transdermal estrogens were associated with VTE risk among postmenopausal women. In an updated meta-analysis of current data, pooled risk ratios for VTE were 1.9 [95% confidence interval (CI) 1.3–2.3] and 1.0 (95% CI 0.9–1.1) among oral and transdermal estrogens users, respectively. In addition, one recent cohort study showed that transdermal estrogens did not confer an excess risk of recurrent VTE among postmenopausal women with a history of VTE. The difference in VTE risk between oral and transdermal estrogen users is supported by biological data. Whereas oral estrogens can increase thrombin generation and induce a resistance to activated protein C, transdermal estrogens have minimal effects on hemostatic variables. SummaryTransdermal estrogens may improve substantially the benefit/risk ratio of postmenopausal hormone therapy and should be considered as a safer option, especially for women at high risk for VTE.

Activated protein C resistance among postmenopausal women using transdermal estrogens: importance of progestogen

Objective: Although the route of estrogen administration is known to be an important determinant of the thrombotic risk among postmenopausal women using hormone therapy, recent data have shown that norpregnane derivatives but not micronized progesterone increase venous thromboembolism risk among transdermal estrogens users. However, the differential effects of progesterone and norpregnanes on hemostasis have not yet been investigated. Methods: We set up a cross-sectional study among healthy postmenopausal women aged 45 to 70 years. The impact of activated protein C (APC) on endogenous thrombin potential was investigated in the plasma samples of 108 women who did not use any hormone therapy (n = 40) or who were treated with transdermal estrogens combined with micronized progesterone (n = 30) or norpregnane derivatives (n = 38). Results: After exclusion of women with factor V Leiden and/or G20210A prothrombin gene mutations, there was no significant change in APC sensitivity among women who used transdermal estrogens combined with micronized progesterone compared with nonusers. Women using transdermal estrogens combined with norpregnanes were less sensitive to APC than were nonusers (P = 0.003) or users of transdermal estrogens combined with micronized progesterone (P = 0.004). In addition, prothrombin fragment 1 + 2 concentration was higher in users of transdermal estrogens plus norpregnanes than in nonusers (P = 0.004). Other hemostatic parameters did not vary significantly across the different subgroups. Conclusions: Transdermal estrogens combined with norpregnanes may induce APC resistance and activate blood coagulation. These results provide a biological support to epidemiological data regarding the potential thrombogenic effects of norpregnanes. However, these findings need to be confirmed in a randomized trial.

Synergism between non-O blood group and oral estrogen in the risk of venous thromboembolism among postmenopausal women: The ESTHER Study

Synergism between non-O blood group and oral estrogen in the risk of venous thromboembolism among postmenopausal women: The ESTHER Study -

National Trends in Patients Hospitalized for Stroke and Stroke Mortality in France, 2008 to 2014

Background and Purpose— Stroke is the leading cause of death in women and the third leading cause in men in France. In young adults (ie, <65 years old), an increase in the incidence of ischemic stroke was observed at a local scale between 1985 and 2011. After the implementation of the 2010 to 2014 National Stroke Action Plan, this study investigates national trends in patients hospitalized by stroke subtypes, in-hospital mortality, and stroke mortality between 2008 and 2014. Methods— Hospitalization data were extracted from the French national hospital discharge databases and mortality data from the French national medical causes of death database. Time trends were tested using a Poisson regression model. Results— From 2008 to 2014, the age-standardized rates of patients hospitalized for ischemic stroke increased by 14.3% in patients <65 years old and decreased by 1.5% in those aged ≥65 years. The rate of patients hospitalized for hemorrhagic stroke was stable (+2.0%), irrespective of age and sex. The proportion of patients hospitalized in stroke units substantially increased. In-hospital mortality decreased by 17.1% in patients with ischemic stroke. From 2008 to 2013, stroke mortality decreased, except for women between 45 and 64 years old and for people aged ≥85 years. Conclusions— An increase in cardiovascular risk factors and improved stroke management may explain the increase in the rates of patients hospitalized for ischemic stroke. The decrease observed for in-hospital stroke mortality may be because of recent improvements in acute-phase management.

Time trends in pulmonary embolism mortality in France, 2000-2010

BACKGROUND Pulmonary Embolism (PE) is a potentially fatal complication of venous thrombosis. Recent and comprehensive estimates of PE incidence and mortality are scarce. Moreover, while contemporary mortality trends of PE would enable the evaluation of prevention and quality of care, such data are lacking. The aim of this study was to provide nationwide estimations of PE mortality and time trends in France between 2000 and 2010. METHODS Mortality data were obtained from the French Epidemiology Center on medical causes of death. Mortality rates were calculated with PE as an underlying or one of multiple causes of death. The annual percentage changes were assessed using a Poisson regression model. Age-standardized PE mortality rates were also assessed. RESULTS In 2010, the overall age-adjusted PE mortality rate was 21.0 per 100000. This rate was 30% higher in men than in women and decreased by 3% per year between 2000 and 2010. Over this period, PE mortality declined in men and women over 55 years but only slightly decreased in patients younger than 55. Cancer, obesity, osteopathies and complications of surgery were often coded as the underlying causes of death when PE was an associated cause of death recorded on certificate. DISCUSSION This study is the first to provide a contemporary and exhaustive nationwide estimation of PE mortality and time trends in France. The observed decrease in PE mortality between 2000 and 2010 is encouraging, but further efforts in prevention are needed to ensure that this reduction is widespread in all age groups.

Regional disparities in acute and post-acute care of stroke patients in France, 2015

OBJECTIVE The aim of this study was to assess regional variations of the hospital management of stroke patients during acute and post-acute phases in France in 2015. MATERIAL AND METHODS Hospitalized patients coded with stroke as their main diagnosis or, if hospitalized in several different wards, any main ward diagnosis were identified in the 2015 French national hospital discharge database for acute care. Rates of hospitalization in stroke units (SUs) were assessed at a national level and in all metropolitan and overseas regions. All stroke survivors discharged at the end of the acute phase were subsequently identified in the national database for post-acute rehabilitation hospitalization (PARH) within 3 months. RESULTS In the acute phase, half the stroke patients hospitalized for intracerebral hemorrhage, cerebral infarction or unspecified stroke were admitted to SUs. However, there were variations across metropolitan regions (from 30% to 69%) and in overseas regions (from 1% to 59%); these rates correlated with regional ratios of SU beds/100,000 inhabitants. There were also regional differences in PARH rates-in hemiplegic stroke patients, 62% were admitted for PARH (range: 58% to 67%) in metropolitan regions and, overseas, from 8% to 67%-as well as geographical discrepancies in PARH rates to specialized rehabilitation units. Hospitalization rates of hemiplegic stroke patients in neurological rehabilitation centers were 30% for the whole country, but ranged from 23% to 36% in metropolitan regions and from 2% to 45% in overseas regions. CONCLUSION This study focused on hospital-based management of stroke patients. In spite of the creation of new SUs over the past decade in France, there are persistent regional differences in the number of SU beds/100,000 inhabitants and, consequently, in the rate of stroke patients managed in SUs. However, rates continue to improve with the creation of new SUs and the expansion of existing ones. Regional variations were also noted for post-acute hospitalization rates and PARH beds/places.

Admission in Neurorehabilitation and Association with Functional Outcomes after Stroke in France: A Nation-Wide Study, 2010-2014

GOAL We studied time trends of admission in neurological rehabilitation units (NRU) among patients hospitalised for stroke from 2010 to 2014 and compared prognostic factors of functional gain, home return and inpatient survival. METHODS Patients hospitalized for Stroke from 2010 to 2014 were selected from the French national hospital databases. Admission in rehabilitation was searched till 3 months. Predictive factors of functional gain, home return, in-patient survival, and the corresponding trends were studied using logistic regression. RESULTS In 2014, global rehabilitation rate was 36.3% with 15.8 discharged in a NRU. The rate of patients managed in NRU rose between 2010 and 2014. An increase in the proportion of home return (+4%) and inpatient survival rate (+7%) were observed between 2010 and 2014. Almost 40% of patients with severe functional deficits benefited of a partial or complete recovery after their rehabilitation stay. NRU admission was associated with higher probability of functional gain (OR [odds ratio] =1.76 [confidence interval {CI} 95% 1.67-1.85]), home return (OR = 1.38 [CI 95% 1.29-1.47]) and inpatient survival (OR = 3.15 [CI 95% 2.83-3.52]). CONCLUSIONS A greater proportion of patients were admitted in NRU along with an increase of home return and in-patient survival, but too many patients remained excluded.

The 2015 and 2016 terrorist attacks in France: was there a short-term impact on hospitalizations for cardiovascular disease?

Background The terrorist attacks in Paris and Nice in 2015 and 2016 generated widespread emotional stress in France. Given that acute emotional stress is a well-known trigger for cardiovascular disease, we investigated whether these attacks had any short-term impact on hospitalizations for acute cardiovascular disease in France. Methods Annual hospital discharge data from 2009 to 2016 were extracted from the French Hospital Discharge Database. All hospitalizations with a primary diagnosis of acute coronary syndrome, heart failure, or stroke were selected. Generalized additive Poisson models were used to differentiate “unusual” variations in daily hospitalization numbers in the 15 days following the attacks from the expected background hospitalization rate. Results The average daily number of hospitalizations was 396.4 for acute coronary syndrome, 598.6 for heart failure, and 334.6 for stroke. The daily mean number of hospitalizations for heart failure and stroke was higher in the 15 days following each attack compared with the reference periods. However, multivariate analysis showed no significant variation in the risk of hospitalization in the days following the attacks. Interpretation Watching events unfold on television, no matter how dramatic, was not a sufficiently potent trigger for cardiovascular disease, although it may have led to an increase in hospitalizations for stress or anxiety. The 2015 and 2016 terrorist attacks do not seem to have had any measurable short-term impact on hospitalizations for cardiovascular disease either in the Paris and Nice regions or in the rest of France.

What is the evolution of stroke unit’s accessibility in metropolitan France from 2009 to 2014? A trend analysis of over 600 000 patients using national hospital databases.

Objectives We aimed to study trends in stroke unit (SU) admission during a period of their deployment in France and to assess whether this led to better and more equitable access to this specialised care. Design Analysis of records from the national hospital database. Setting All acute care hospitals in metropolitan France for the period 2009–2014. Participants Over 600 000 patients admitted in acute care with a main diagnosis of stroke. Main outcome measures Admission to a SU. Results Between 2009 and 2014, the number of stroke admissions rose from 93 728 to 109 456, and the proportion of SU admission from 23% to 44%. Overall, characteristics associated with higher probability of SU admission were: male gender, younger age, ischaemic stroke type, medium level of comorbidity and larger size of town of residence. Although likelihood of SU admission increased in all patients’ categories during the study period, we identified steeper positive temporal trends among older patients, those with more comorbidities and those residing in medium or small towns (all p values <0.001), suggesting a ‘catching up’ phenomena. Temporal trends of men and women did not differ however. Conclusions Admission to SU nearly doubled in France between 2009 and 2014. Faster trends observed for patients with lower admission to SU suggest that equity in access has improved over the period.