Association of the PHACTR1/EDN1 genetic locus with spontaneous coronary artery dissection

Background: Spontaneous coronary artery dissection (SCAD) is an increasingly recognized cause of acute coronary syndromes (ACS) afflicting predominantly younger to middle-aged women. Observational studies have reported a high prevalence of extracoronary vascular anomalies, especially fibromuscular dysplasia (FMD) and a low prevalence of coincidental cases of atherosclerosis. PHACTR1/EDN1 is a genetic risk locus for several vascular diseases, including FMD and coronary artery disease, with the putative causal noncoding variant at the rs9349379 locus acting as a potential enhancer for the endothelin-1 (EDN1) gene. Objectives: This study sought to test the association between the rs9349379 genotype and SCAD. Methods: Results from case control studies from France, United Kingdom, United States, and Australia were analyzed to test the association with SCAD risk, including age at first event, pregnancy-associated SCAD (P-SCAD), and recurrent SCAD. Results: The previously reported risk allele for FMD (rs9349379-A) was associated with a higher risk of SCAD in all studies. In a meta-analysis of 1,055 SCAD patients and 7,190 controls, the odds ratio (OR) was 1.67 (95% confidence interval [CI]: 1.50 to 1.86) per copy of rs9349379-A. In a subset of 491 SCAD patients, the OR estimate was found to be higher for the association with SCAD in patients without FMD (OR: 1.89; 95% CI: 1.53 to 2.33) than in SCAD cases with FMD (OR: 1.60; 95% CI: 1.28 to 1.99). There was no effect of genotype on age at first event, P-SCAD, or recurrence. Conclusions: The first genetic risk factor for SCAD was identified in the largest study conducted to date for this condition. This genetic link may contribute to the clinical overlap between SCAD and FMD

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Contribution de l'électrophysiologie cardiaque à l'étude étiopathogénique des accidents ischémiques cérébraux indéterminés de l'adulte jeune

Non disponible / Not availabl

Contribution de l'électrophysiologie cardiaque à l'étude étiopathogénique des accidents ischémiques cérébraux indéterminés de l'adulte jeune

NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Thrombolyse précoce dans l'infarctus cérébral au CHU de Nancy (évaluation de l'efficacité et de la tolérance sur une période de 28 mois)

L'étude du NINDS précise l'intérêt de la thrombolyse dans le traitement des AVC ischémiques. L'AMM pour le Rt-PA en 2003 est assortie d'indications et de précautions strictes suivantes : un délai d'administration de 3 heures, une expertise neurovasculaire, la proximité d'une structure de soins intensifs et la possibilité de recours à un avis neurochirurgical. Le Ri-PA n'est pas indiqué en cas d'infarctus cérébral étendu ou de transformation hémorragique. Ce travail est une étude rétrospective de l'efficacité et la tolérance de 19 thrombolyses IV conformes à l'AMM, 5 IA et 8 autres ECASS3 réalisées du 1/9/2003 au 31/12/2004 dans l'UNV du CHU de Nancy. L'âge moyen des thrombolysés de 62 ans indique un risque élevé d'AVC en Lorraine. L'éligibilité à l'un des groupes est largement déterminée par les délais d'accès à l'hôpital. Leur comparaison indique que les pertes de temps se produisent avant prise en charge par la filière AVC. Il n'apparaît pas de différence d'efficacité ou de sécurité entre les groupes. Sur l'effectif total, l'efficacité est conforme aux résultats internationaux. A 90 jours le pourcentage de décès est inférieur aux observations épidémiologiques ou aux résultats du' NINDS. Ces résultats démontrent la qualité de la filière AVC en Région Lorraine. La réalisation d'un registre informatisé des AVC lorrains permettrait de faire progresser les traitements des AVC du plus grand nombre.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Hypotension intracrânienne spontanée (analyse de 19 observations et revue de la littérature)

Cette thèse rapporte une série rétrospective consécutive de 19 observations d'hypotension intracrânienne spontanée recensées entre 1992 et 2005 dans les services de neurologie et de neurochirurgie du CHU de Nancy et dans le CH J. Monnet d'Epinal. Le nombre considérable de cas ainsi répertoriés confère aux données obtenues un certain intérêt. D'autre part, bien que cette pathologie soit habituellement rare et bénigne, il faut noter parmi ces 19 patients la présence de formes compliquées chez deux d'entre eux (thromboses veineuses cérébrales et hématomes sous-duraux) dont une à l'évolution fatale.NANCY1-SCD Medecine (545472101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Tourisme d’observation et éléphants de forêt (Loxodonta cyclotis) au Campement de Nyonié, Gabon

Central African ecosystems are home to a rich biodiversity, including the endangered forest elephant (Loxodonta cyclotis). Ecotourism is a growing industry in the region, but it can have a negative impact on elephant populations. This study investigates the relationship between ecotourism and forest elephants at the "Campement de Nyonié" in Gabon, a tourist site located outside of protected areas. Data was collected through direct observations of elephants on foot and in off-road vehicle. Results showed that elephants are present in a large and continuous area around the camp. Their activity is concentrated in the south, near the Wonga-Wongué Presidential Reserve, and in the west, near the coast. Elephants live in matriarchal groups, led by older females. The results suggest that tourist activity at the "Campement de Nyonié" does not drive elephants away. On the contrary, it could even contribute to their conservation by raising public awareness and generating revenue for environmental protection. The study highlights the importance of cooperation between tourism stakeholders and authorities to balance biodiversity conservation and economic development. Keywords: Sighting tourism, Loxodonta cyclotis, spatial distribution, social structuring, Campement de NyoniéLes écosystèmes d'Afrique centrale abritent une importante biodiversité, dont l'éléphant de forêt (Loxodonta cyclotis), une espèce menacée. Le tourisme d'observation de la faune est une activité en plein essor dans la sous-région, mais il peut avoir un impact négatif sur les populations d'éléphants. Une étude a été menée au Campement de Nyonié, au Gabon, un site touristique situé en dehors des aires protégées. Les données ont été collectées par observations directes des éléphants à pied et en voiture tout-terrain. Les résultats montrent que les éléphants sont présents dans une zone large et continue autour du Campement de Nyonié. Leur activité se concentre au sud, près de la Réserve présidentielle de Wonga-Wongué et à l'ouest, près de la côte. Les éléphants vivent en groupes matriarcaux, dirigés par des femelles âgées. Les résultats suggèrent que l'activité touristique du Campement de Nyonié n'éloigne pas les éléphants. Au contraire, elle pourrait même contribuer à leur conservation en favorisant la sensibilisation du public et en générant des revenus pour la protection de l'environnement. Les résultats de cette étude soulignent l'importance de la coopération entre les acteurs du tourisme et les autorités pour concilier la conservation de la biodiversité et le développement économique. Mots clés: Tourisme d’observation, Loxodonta cyclotis, distribution spatiale, structuration sociale, Campement de Nyoni