Home blood pressure measurement self-reporting in real-life practices using the Hy-Result app: self-monitoring and digital pathway.

Background: Little real-life information is available on the clinical characteristics of information and communication technologies (ICTs) users, particularly in the context of hypertension and home blood pressure measurement (HBPM). This retrospective observational study describes HBPM practices obtained through the Hy-Result® system, a validated app designed to help patients perform HBPM and understand their results through an automatic interpretation of the readings using web interface. Methods: We analyzed 19,176 HBPM reports (sequence of 1 to 7 days of measurements; 3 in the morning, 3 in the evening) collected in real life circumstances from two groups of users: primary care (Prim) and hypertension center (Hosp). Results: Population: among the 19,176 reports, 63.2% declared receiving antihypertensive medication, having diabetes (15.2%), chronic kidney disease (9.7%) or history of stroke (7.6%). Treated users were older than normotensives [mean ± standard deviation (SD) age 64±12 vs. 58±14 years] with higher prevalence of comorbidities. Compliance with the HBPM schedule: the majority of reports (90.2%) totaled 15 systolic blood pressure (SBP) and diastolic blood pressure (DBP) readings or more, of which 96.1% were Hosp users and 89.3% Prim users, with a significant difference between both groups (P<0.001). The compliance rate for 7 days of measurement was higher in the Hosp group (57.6% vs. 30.5%; P<0.001). Blood pressure (BP) levels: in the 17,289 reports with a minimum of 15 readings, 42.7% had an average SBP and/or DBP above the recommended thresholds (below 135 and/or 85 mmHg), among whom, 36.8% were untreated subjects. Hosp users had better BP control than Prim (P<0.001). Users that are followed in the European Society of Hypertension (ESH) excellence center (Hosp) had better BP control than those in a Prim setting (P<0.001). HBPM oscillometric devices: in both groups, treated patients and untreated users, used the arm cuff devices more frequently than the wrist device. Conclusions: Our real-life study shows that 90% of the HBPM reports include the required minimum number of BP readings to allow the calculation of a reliable average among whom 40% have uncontrolled BP levels. The self-management Hy-Result web app demonstrates significant potential for inclusion in the patient care process and reinforces the patient's engagement to independently monitor and self-reported their BP. When the mean BP is not within the recommended range, the users were automatically prompted by text messages to seek medical advice by the software. Further research should determine the extent to which users adhere to text messages advice.

Inhibition of thrombin-activatable fibrinolysis inhibitor via DS-1040 to accelerate clot lysis in patients with acute pulmonary embolism: a randomized phase 1b study.

BACKGROUND: The optimal treatment of intermediate-risk pulmonary embolism (PE) in hemodynamically stable patients remains unknown. Fibrinolytics reduce the risk of hemodynamic deterioration but increase bleeding risk. DS-1040, an inhibitor of thrombin-activatable fibrinolysis inhibitor, enhanced endogenous fibrinolytic activity without increasing bleeding risk in preclinical studies. OBJECTIVES: To evaluate the tolerability and explore the efficacy of DS-1040 in patients with acute PE. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, ascending doses of intravenous DS-1040 (20-80 mg) or placebo were added to enoxaparin (1 mg/kg twice daily) in patients with intermediate-risk PE. The primary endpoint was the number of patients with major or clinically relevant nonmajor bleeding. The percentage change in thrombus volume and right-to-left ventricular dimensions, assessed using quantitative computed tomography pulmonary angiography, at baseline and after 12 to 72 hours were used to explore the efficacy of DS-1040. RESULTS: Of 125 patients with all available data, 38 were randomized to placebo and 87 to DS-1040. The primary endpoint occurred in 1 patient in the placebo group (2.6%) and 4 patients who received DS-1040 (4.6%). One subject experienced major bleeding (DS-1040 80 mg group); no fatal or intracranial bleeding occurred. Thrombus volume was 25% to 45% lower after infusion, with no differences between the DS-1040 and placebo groups. There was no difference in the change from baseline right-to-left ventricular dimensions between the DS-1040 and placebo groups. CONCLUSION: In patients with acute PE, adding DS-1040 to standard anticoagulation was not associated with an increase in bleeding but did not improve thrombus resolution or right ventricular dilation.

Primary Non-Aortic Lesions Are Not Rare in Marfan Syndrome and Are Associated with Aortic Dissection Independently of Age.

PURPOSE: The study sought to estimate the prevalence of primary non-aortic lesions (PNAL) unrelated to extension of aortic dissection (AD) in a cohort of patients with Marfan syndrome (MFS). METHODS: Adult patients presenting with pathogenic FBN1 mutations and an available pan-aortic contrast-enhanced CTA in eight French MFS clinics from April to October 2018 were included. Clinical and radiological data, particularly the presence of aortic lesions and PNAL (including aneurysm and ectasia), were retrospectively analyzed. RESULTS: Out of 138 patients, 28 (20.3%) had PNAL. In total, 27 aneurysms in 13 patients and 41 ectasias in 19 patients were reported mainly in the subclavian, iliac, and vertebral segments. Four patients (31%) with aneurysms and none with ectasia required prophylactic intervention during follow-up (median: 46 months). In multivariate analysis, factors associated with PNAL were history of AD (OR = 3.9, 95%CI: 1.3-12.1, p = 0.018), history of previous descending aortic surgery (OR = 10.3, 95%CI: 2.2-48.3, p = 0.003) and age (per 10 years OR = 1.6, 95%CI: 1.1-2.4, p = 0.008). CONCLUSION: PNAL is not rare in MFS patients with evolutive aortic disease. Natural history may differ between aneurysms and ectasia, emphasizing the need for standardized definitions and systematic screening for PNAL.

The Complexity of Two Colouring Games.

We consider two variants of orthogonal colouring games on graphs. In these games, two players alternate colouring uncoloured vertices (from a choice of m ∈ N colours) of a pair of isomorphic graphs while respecting the properness and the orthogonality of the partial colourings. In the normal play variant, the first player unable to move loses. In the scoring variant, each player aims to maximise their score, which is the number of coloured vertices in their copy of the graph. We prove that, given an instance with partial colourings, both the normal play and the scoring variant of the game are PSPACE-complete. An involution σ of a graph G is strictly matched if its fixed point set induces a clique and v σ ( v ) ∈ E ( G ) for any non-fixed point v ∈ V ( G ) . Andres et al. (Theor Comput Sci 795:312-325, 2019) gave a solution of the normal play variant played on graphs that admit a strictly matched involution. We prove that recognising graphs that admit a strictly matched involution is NP-complete.

Management of arterial hypertension: home blood pressure measurement is a cornerstone for telemonitoring and self-management.

The development of mobile telephones has made it possible to design blood pressure (BP) monitors with data transmission via cellular lines, contributing to the emergence of "e-health". Today, the direct-to-consumer marketing of devices create a new context allowing an algorithmic processing of information for remote decision-making either by the patient or by a healthcare professional. The home BP telemonitoring (HBPT) is the remote transmission of BP values, measured at home and transmitted to the doctor's office or hospital, by means of telehealth strategies. In this context, randomized controlled trials (RCTs) studies have demonstrated HBPT ability in improving patients' compliance and adherence to treatment and in accomplishing better hypertension control rates. The level of evidence for the drop in BP is "moderate" and the place of HBPT is not clearly established in current practice. Digital interventions have the potential to support patient in self-management. This approach presupposes the prior acquisition of skills, the level of which must be adapted to the level of health literacy of each patient. Few of medical applications (mobile apps or web-apps) for hypertension can be regarded as accurate and safe for clinical use and to date, we do not have high quality evidence to determine the overall effect of the use smartphone apps on BP control.

A Real-World Cost-Effectiveness Analysis of Rivaroxaban versus Vitamin K Antagonists for the Treatment of Symptomatic Venous Thromboembolism: Lessons from the REMOTEV Registry.

Background and objectives: Venous thromboembolism (VTE) represents a health and economic burden with consequent healthcare resource utilization. Direct oral anticoagulants (DOACs) have emerged as the mainstay option for VTE treatment but few data exist on their cost-effectiveness as compared to the standard therapy (vitamin K antagonists (VKAs)). This study aimed to assess the cost-effectiveness of rivaroxaban compared to VKAs in VTE treatment by calculating the incremental cost effectiveness ratio (ICER). Materials and methods: We conducted a prospective observational study based on the REMOTEV registry, including patients hospitalized for VTE from 23 October 2013 to 31 July 2015, to evaluate the impact of the anticoagulant treatment (DOACs versus VKAs) on 6-month complications: major or clinically relevant non-major bleeding, VTE recurrence and all-cause death. Rivaroxaban was the only DOAC prescribed in this study. The ICER was calculated as the difference in costs divided by the difference in effectiveness. Results: Among the 373 patients included, 279 were treated with rivaroxaban (63.1 ± 17.9 years old; 49% men) and 94 with VKAs (71.3 ± 16.6 years old; 46% men). The mean cost was EUR 5662 [95% CI 6606; 9060] for rivaroxaban and EUR 7721 [95% CI 5130; 6304] for VKAs, while effectiveness was 0.0586 95% CI [0.0114; 0.126] for DOACs and 0.0638 [95% CI 0.0208; 0.109] for VKAs. The rivaroxaban treatment strategy was dominant with costs per patient EUR 2059 lower [95% CI -3582; -817] and a higher effectiveness of 0.00527 [95% CI -0.0606; 0.0761] compared to VKAs. Conclusions: This study provides real-world evidence that rivaroxaban is not only an efficient and safe alternative to VKAs for eligible VTE patients, but also cost-saving.

Postthrombotic syndrome and quality of life after deep vein thrombosis in patients treated with edoxaban versus warfarin.

Background: Postthrombotic syndrome (PTS) is a long-term complication after deep vein thrombosis (DVT) and can affect quality of life (QoL). Pathogenesis is not fully understood but inadequate anticoagulant therapy with vitamin K antagonists is a known risk factor for the development of PTS. Objectives: To compare the prevalence of PTS after acute DVT and the long-term QoL following DVT between patients treated with edoxaban or warfarin. Methods: We performed a long-term follow-up study in a subset of patients with DVT who participated in the Hokusai-VTE trial between 2010 and 2012 (NCT00986154). Primary outcome was the prevalence of PTS, defined by the Villalta score. The secondary outcome was QoL, assessed by validated disease-specific (VEINES-QOL) and generic health-related (SF-36) questionnaires. Results: Between 2017 and 2020, 316 patients were enrolled in 26 centers in eight countries, of which 168 (53%) patients had been assigned to edoxaban and 148 (47%) to warfarin during the Hokusai-VTE trial. Clinical, demographic, and thrombus-specific characteristics were comparable for both groups. Mean (SD) time since randomization in the Hokusai-VTE trial was 7.0 (1.0) years. PTS was diagnosed in 85 (51%) patients treated with edoxaban and 62 (42%) patients treated with warfarin (adjusted odds ratio 1.6, 95% CI 1.0-2.6). Mean differences in QoL scores between treatment groups were not clinically relevant. Conclusion: Contrary to our hypothesis, the prevalence of PTS tended to be higher in patients treated with edoxaban compared with warfarin. No differences in QoL were observed. Further research is warranted to unravel the role of anticoagulant therapy on development of PTS.

The Conundrum of Occult Cancer Screening in Venous Thromboembolism: Lessons from the REMOTEV Registry.

(1) Background and Objectives: Venous thromboembolism (VTE) is strongly associated with cancer, and may be the first event revealing occult neoplasia. Nonetheless, the reasonable extent of the etiological assessment after an unprovoked VTE event remains debated. The main objective of this study was to evaluate the incidence of occult neoplasia one year after an episode of VTE, in consecutively hospitalized patients for VTE from the REMOTEV registry. The secondary objectives were to assess the performance of the various tests used for occult cancer screening in a real-life setting and analyze the risk factors associated with the discovery of cancer and the 1-year prognosis. (2) Methods: REMOTEV is a prospective, non-interventional cohort study of patients with acute VTE. Patients included in the registry from 23 October 2013 to 28 July 2018 were analyzed after a follow-up of 12 months. Cancer detection was performed according to local practices and consisted of a limited strategy to which an abdominal ultrasound was added. In the presence of suggestive clinical manifestations, further examinations were performed on an individual basis. (3) Results: A total of 993 patients were included in the study. At 1 year, the incidence of newly diagnosed cancer was low (5.3%). Half of the detected cancers were metastatic at discovery (51%) and had a poor global prognosis (32% of mortality at 1 year). Admission pulmonary CT scans as well as (thoracic)-abdomino-pelvic CT scans (when performed) were responsible for the majority of detected cancers. Age over 65 years and the concomitant presence of an unusual site and lower-limb deep vein thrombosis were the only factors associated with occult neoplasia in this cohort. After 1-year FU, mortality was higher in cancer patients (HR 6.0 (CI 95% 3.5−10.3, p < 0.0001)), and cancer evolution was the leading cause of death in the cancer group. (4) Conclusions: In REMOTEV, VTE-revealed occult cancer prevalence was low, but similar to recent reports and associated with higher age, multiple thrombotic sites and worse prognosis.

SPARTE Study: Normalization of Arterial Stiffness and Cardiovascular Events in Patients With Hypertension at Medium to Very High Risk.

[Figure: see text].

Withdrawal Notice: Is There a Link between Lung Parenchyma Lesions, BMI, CRP and D-dimer in COVID-19 Patients Who Had Acute Pulmonary Embolism?

The article has been withdrawn at the request of the editor of the journal Cardiovascular & Hematological Disorders-Drug Targets due to incoherent content.Bentham Science apologizes to the readers of the journal for any inconvenience this may have caused.The Bentham Editorial Policy on Article Withdrawal can be found at https://benthamscience.com/editorial-policies-main.php. BENTHAM SCIENCE DISCLAIMER: It is a condition of publication that manuscripts submitted to this journal have not been published and will not be simultaneously submitted or published elsewhere. Furthermore, any data, illustration, structure or table that has been published elsewhere must be reported, and copyright permission for reproduction must be obtained. Plagiarism is strictly forbidden, and by submitting the article for publication the authors agree that the publishers have the legal right to take appropriate action against the authors, if plagiarism or fabricated information is discovered. By submitting a manuscript the authors agree that the copyright of their article is transferred to the publishers if and when the article is accepted for publication.

Quality of life in patients with pulmonary embolism treated with edoxaban versus warfarin.

BACKGROUND: Long-term sequelae of acute pulmonary embolism (PE) include decreased quality of life (QoL). Evidence suggests that adequacy of initial anticoagulant treatment in the acute phase of venous thrombosis has a key impact on late postthrombotic complications. We hypothesize that patients with acute PE treated with edoxaban for acute PE experience have improved QoL compared to those treated with warfarin. METHODS: Patients with PE who participated in the Hokusai-VTE trial were contacted between June 2017 and September 2020 for a single long-term follow-up visit. Main outcomes were the generic and disease-specific QoL measured by the 36-Item Short Form Health Survey (SF-36) and Pulmonary Embolism Quality of Life questionnaire. RESULTS: We included 251 patients from 26 centers in eight countries, of which 129 (51%) had been assigned to edoxaban and 122 (49%) to warfarin. Patient- and thrombus-specific characteristics were similar in both groups. Mean time since randomization in the Hokusai-VTE trial was 7.0 years (standard deviation, 1.0). No relevant or statistical differences were observed in the QoL for patients treated with edoxaban compared to patients treated with warfarin. The mean difference between patients treated with edoxaban and patients with PE treated with warfarin was 0.8 (95% confidence interval [CI]. -1.6 to 3.2) for the SF-36 summary mental score and 1.6 (95% CI, -0.9 to 4.1) for summary physical score. CONCLUSION: Our findings indicate that patients with an index PE treated with edoxaban or warfarin have a similar long-term QoL. Since our study was a follow-up study from a well-controlled clinical trial setting, future studies should be designed in a daily clinical practice setting. We suggest a longitudinal design for investigation of changes in QoL over time.

Systematic duplex ultrasound screening in conventional units for COVID-19 patients with follow-up of 5 days.

OBJECTIVE: COVID-19 patients may develop coagulopathy, which is associated with poor prognosis and high risk of thrombosis. The main objective of this work was to evaluate the prevalence of deep venous thrombosis of lower limbs (DVT) through ultrasonography in patients infected with COVID-19 admitted to conventional units at our hospital with 5 days of monitoring. The secondary objective was to determine if D-dimer levels, body mass index, and C-reactive protein were associated with DVT. METHODS: A total of 72 patients, with a mean age of 65 ± 12.3 years, infected with COVID-19 were admitted to three conventional units at our institution; 28 patients were women. A COVID-19 diagnosis was made by a transcriptase polymerase chain reaction by means of nasopharyngeal swab or by chest computer tomography without iodine contrast media. Demographics, comorbidities, and laboratory parameters were collected. A preventive anticoagulation treatment was established on admission with low-molecular-weight heparin. A complete venous duplex ultrasound (DU) test of lower limbs was performed on day (D) 0 and D5. A pulmonary computer tomography angiogram with iodine contrast media was required when pulmonary embolism was suspected. RESULTS: On D0, the DU showed acute DVT in seven patients (9.75%). A pulmonary computer tomography angiogram was performed in 12 patients (16.65%), 3 (25%) of whom had an acute pulmonary embolism. On D0, acute DVT was not significantly associated with C-reactive protein (mean 101 ± 98.6 in the group without DVT vs 67.6 ± 58.4 mg/L, P = .43) or body mass index (27.7 ± 5.04 vs 28.1 ± 2.65 kg/m2, P = .54). However, we found a significant association between acute DVT and D-dimer levels (1536 ± 2347 vs 9652 ± 10,205 ng/mL, P < .01). Among the patients included on D0, only 32 had a DU on D5. Forty of them (55.55%) were not examined for the following reasons: 7 (9.7%) were previously diagnosed with venous thromboembolism on D0 and therefore were excluded on D5, 8 (11%) were transferred to the intensive care unit, 10 (14%) were discharged from the hospital, 5 (7%) died, and 10 (13.9%) were excluded because of technical issues. On D5, five (15.6%) patients had acute DVT in addition to those found on D0; three were distal and two proximal despite preventive anticoagulation with low-molecular-weight heparin. CONCLUSIONS: Hospitalized non-intensive care unit patients with COVID-19 pneumonia have a high frequency of venous thrombotic events justifying screening with DU.

Aminotransferases disorders associated with venous thromboembolic events in patients infected with COVID-19.

INTRODUCTION AND OBJECTIVES: Since the outbreak of the COVID-19 pandemic, increasing evidence suggests that infected patients present a high incidence of venous thromboembolic (VTE) events and elevated aminotransferases (AT).The objective of this work was to evaluate the incidence of aminotransferases disorders in patients infected with COVID-19 and to manage the VTE events associated with elevated AT. PATIENTS OR MATERIALS AND METHODS: We report a retrospective study of 46 patients admitted for COVID-19 infection. Venous duplex ultrasound of lower limbs was performed in all patients at Day 0 and Day 5. All patients had antithrombotic-prophylaxis upon admission using low molecular weight heparin with Enoxaparin. Demographics, comorbidities and laboratory parameters were collected and analyzed. RESULTS: Elevated AT were reported in 28 patients (61%). 10 had acute VTE events of which eight (17.4%) had aminotransferases disorders. They had been treated with curative Enoxaparin. After a follow-up of 15 and/or 30 days, six of them were controlled, and treated with direct oral anticoagulant (DOACs) after normalization of aminotransferases. CONCLUSIONS: The incidence of aminotransferases disorders associated with acute VTE events in patients infected with COVID-19 is significant. The use of DOACs appear pertinent in these patients. Monitoring of the liver balance should therefore be considered at a distance from the acute episode in the perspective of DOACs relay.

Prognostic Value of Troponin Elevation in COVID-19 Hospitalized Patients.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates the respiratory epithelium through angiotensin-converting enzyme-2 (ACE2) binding. Myocardial and endothelial expression of ACE2 could account for the growing body of reported evidence of myocardial injury in severe forms of Human Coronavirus Disease 2019 (COVID-19). We aimed to provide insight into the impact of troponin (hsTnI) elevation on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with the SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 772 adult, symptomatic COVID-19 patients were hospitalized for more than 24 h in our institution, of whom 375 had a hsTnI measurement and were included in this analysis. The median age was 66 (55-74) years, and there were 67% of men. Overall, 205 (55%) patients were placed under mechanical ventilation and 90 (24%) died. A rise in hsTnI was noted in 34% of the cohort, whereas only three patients had acute coronary syndrome (ACS) and one case of myocarditis. Death occurred more frequently in patients with hsTnI elevation (HR 3.95, 95% CI 2.69-5.71). In the multivariate regression model, a rise in hsTnI was independently associated with mortality (OR 3.12, 95% CI 1.49-6.65) as well as age ≥ 65 years old (OR 3.17, 95% CI 1.45-7.18) and CRP ≥ 100 mg/L (OR 3.62, 95% CI 1.12-13.98). After performing a sensitivity analysis for the missing values of hsTnI, troponin elevation remained independently and significantly associated with death (OR 3.84, 95% CI 1.78-8.28). (4) Conclusion: Our study showed a four-fold increased risk of death in the case of a rise in hsTnI, underlining the prognostic value of troponin assessment in the COVID-19 context.

Outcomes of COVID-19 Hospitalized Patients Previously Treated with Renin-Angiotensin System Inhibitors.

(1) Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) penetrates respiratory epithelium through angiotensin-converting enzyme-2 binding, raising concerns about the potentially harmful effects of renin-angiotensin system inhibitors (RASi) on Human Coronavirus Disease 2019 (COVID-19) evolution. This study aimed to provide insight into the impact of RASi on SARS-CoV-2 outcomes in patients hospitalized for COVID-19. (2) Methods: This was a retrospective analysis of hospitalized adult patients with SARS-CoV-2 infection admitted to a university hospital in France. The observation period ended at hospital discharge. (3) Results: During the study period, 943 COVID-19 patients were admitted to our institution, of whom 772 were included in this analysis. Among them, 431 (55.8%) had previously known hypertension. The median age was 68 (56-79) years. Overall, 220 (28.5%) patients were placed under mechanical ventilation and 173 (22.4%) died. According to previous exposure to RASi, we defined two groups, namely, "RASi" (n = 282) and "RASi-free" (n = 490). Severe pneumonia (defined as leading to death and/or requiring intubation, high-flow nasal oxygen, noninvasive ventilation, and/or oxygen flow at a rate of ≥5 L/min) and death occurred more frequently in RASi-treated patients (64% versus 53% and 29% versus 19%, respectively). However, in a propensity score-matched cohort derived from the overall population, neither death (hazard ratio (HR) 0.93 (95% confidence interval (CI) 0.57-1.50), p = 0.76) nor severe pneumonia (HR 1.03 (95%CI 0.73-1.44), p = 0.85) were associated with RASi therapy. (4) Conclusion: Our study showed no correlation between previous RASi treatment and death or severe COVID-19 pneumonia after adjustment for confounders.

Empagliflozin improved systolic blood pressure, endothelial dysfunction and heart remodeling in the metabolic syndrome ZSF1 rat.

BACKGROUND: Empagliflozin (empa), a selective sodium-glucose cotransporter (SGLT)2 inhibitor, reduced cardiovascular mortality and hospitalization for heart failure in patients with type 2 diabetes at high cardiovascular risk independent of glycemic control. The cardiovascular protective effect of empa was evaluated in an experimental model of metabolic syndrome, the obese ZSF1 rat, and its' lean control. METHODS: Lean and obese ZSF1 rats were either non-treated or treated with empa (30 mg/kg/day) for 6 weeks. Vascular reactivity was assessed using mesenteric artery rings, systolic blood pressure by tail-cuff sphygmomanometry, heart function and structural changes by echocardiography, and protein expression levels by Western blot analysis. RESULTS: Empa treatment reduced blood glucose levels from 275 to 196 mg/dl in obese ZSF1 rats whereas normoglycemia (134 mg/dl) was present in control lean ZSF1 rats and was unaffected by empa. Obese ZSF1 rats showed increased systolic blood pressure, and blunted endothelium-dependent relaxations associated with the appearance of endothelium-dependent contractile responses (EDCFs) compared to control lean rats. These effects were prevented by the empa treatment. Obese ZSF1 rats showed increased weight of the heart and of the left ventricle volume without the presence of diastolic or systolic dysfunction, which were improved by the empa treatment. An increased expression level of senescence markers (p53, p21, p16), tissue factor, VCAM-1, SGLT1 and SGLT2 and a down-regulation of eNOS were observed in the aortic inner curvature compared to the outer one in the control lean rats, which were prevented by the empa treatment. In the obese ZSF1 rats, no such effects were observed. The empa treatment reduced the increased body weight and weight of lungs, spleen, liver and perirenal fat, hyperglycemia and the increased levels of total cholesterol and triglycerides in obese ZSF1 rats, and increased blood ketone levels and urinary glucose excretion in control lean and obese ZSF1 rats. CONCLUSION: Empa reduced glucose levels by 28% and improved both endothelial function and cardiac remodeling in the obese ZSF1 rat. Empa also reduced the increased expression level of senescence, and atherothrombotic markers at arterial sites at risk in the control lean, but not obese, ZSF1 rat.

Oral Intake of EPA:DHA 6:1 by Middle-Aged Rats for One Week Improves Age-Related Endothelial Dysfunction in Both the Femoral Artery and Vein: Role of Cyclooxygenases.

In humans, aging is associated with endothelial dysfunction and an increased risk of venous thromboembolism. Although intake of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) at a ratio of 6:1 by old rats improved the endothelial dysfunction in arteries, the impact on veins remains unclear. Eight-month-old male Wistar rats were either untreated or orally administered corn oil, EPA:DHA 1:1, or EPA:DHA 6:1 (500 mg/kg/d) for seven days. Vascular reactivity was studied by myography. In middle-aged femoral artery rings, acetylcholine caused a partial relaxation at low concentrations and a contractile response at high concentrations, whereas in the old femoral vein only a partial relaxation was observed. The EPA:DHA 6:1 treatment blunted the contractile response to acetylcholine in the middle-aged femoral artery and both EPA:DHA 6:1 and 1:1 increased the relaxation to acetylcholine in the old femoral vein. No such effects were observed with corn oil. Both the non-selective cyclooxygenase inhibitor indomethacin and the COX-1 inhibitor SC-560 increased the relaxation to acetylcholine in the middle-aged femoral artery whereas the COX-2 inhibitor NS-398 increased that in the middle-aged femoral vein. In conclusion, our results indicate that aging is associated with an endothelial dysfunction in the femoral artery and vein, which can be improved by EPA:DHA 6:1 treatment-most likely via a cyclooxygenase-dependent mechanism.

Pulmonary Embolism and Coexisting Deep Vein Thrombosis: A Detrimental Association?

BACKGROUND: The prognostic significance of coexisting deep vein thrombosis (DVT) in acute pulmonary embolism (PE) is controversial. This study aimed to provide routine patient care data on the impact of this association on PE severity and 3-month outcomes in a population presenting with symptomatic venous thromboembolism (VTE) from the REMOTEV registry. METHODS AND RESULTS: REMOTEV is a prospective, non-interventional study of patients with acute symptomatic VTE, treated with direct oral anticoagulants (DOACs) or standard anticoagulation (vitamin K antagonists (VKA) or parenteral heparin/fondaparinux alone) for at least 3 months. From 1 November 2013 to 28 February 2018, among 1241 consecutive patients included, 1192 had a follow-up of at least 3 months and, among them, 1037 had PE with (727) or without DVT (310). The median age was 69 (55-80, 25th-75th percentiles). Patients with PE-associated DVT had more severe forms of PE (p < 0.0001) and, when DVT was present, proximal location was significantly correlated to PE severity (p < 0.01). However, no difference in all-cause mortality rate (hazard ratio (HR) 1.36 (CI 95% 0.69-2.92)), nor in the composite criterion of all-cause mortality and recurrence rate (HR 1.56 (CI 95% 0.83-3.10)) was noted at 3 months of follow-up. CONCLUSION: In REMOTEV, coexisting DVT was associated with a higher severity of PE, with no impact on short-term prognosis.