Vascular Diseases in Women: Do Women Suffer from Them Differently?

According to the World Health Organization, cardiovascular disease (CVD) is the leading cause of death among women worldwide, yet its magnitude is often underestimated. Biological and gender differences affect health, diagnosis, and healthcare in numerous ways. The lack of sex and gender awareness in health research and healthcare is an ongoing issue that affects not only research but also treatment and outcomes. The importance of recognizing the impacts of both sex and gender on health and of knowing the differences between the two in healthcare is beginning to gain ground. There is more appreciation of the roles that biological differences (sex) and sociocultural power structures (gender) have, and both sex and gender affect health behavior, the development of diseases, their diagnosis, management, and the long-term effects of an illness. An important issue is the knowledge and awareness of women about vascular diseases. The risk of cardiovascular events is drastically underestimated by women themselves, as well as by those around them. The purpose of this review is to draw attention to improving the medical care and treatment of women with vascular diseases.

Diagnostic criteria for Buerger's disease: International Consensus of VAS - European Independent Foundation in Angiology/Vascular Medicine.

Buerger's disease (BD) remains a debilitating condition and early diagnosis is paramount for its effective management. Despite many published diagnostic criteria for BD, selective criteria have been utilized in different vascular centers to manage patients with BD worldwide. A recent international Delphi Consensus Study on the diagnostic criteria of BD showed that none of these published diagnostic criteria have been universally accepted as a gold standard. Apart from the presence of smoking, these published diagnostic criteria have distinct differences between them, rendering the direct comparison of patient outcomes difficult. Hence, the expert committees from the Working Group of the VAS-European Independent Foundation in Angiology/Vascular Medicine critically reviewed the findings from the Delphi study and provided practical recommendations on the diagnostic criteria for BD, facilitating its universal use. We recommend that the 'definitive' diagnosis of BD must require the presence of three features (history of smoking, typical angiographic features and typical histopathological features) and the use of a combination of major and minor criteria for the 'suspected' diagnosis of BD. The major criterion is the history of active tobacco smoking. The five minor criteria are disease onset at age less than 45 years, ischemic involvement of the lower limbs, ischemic involvement of one or both of the upper limbs, thrombophlebitis migrans and red-blue shade of purple discoloration on edematous toes or fingers. We recommend that a 'suspected' diagnosis of BD is confirmed in the presence of a major criterion plus four or more minor criteria. In the absence of the major criterion or in cases of fewer than four minor criteria, imaging and laboratory data could facilitate the diagnosis. Validation studies on the use of these major and minor criteria are underway.

An International Delphi Consensus on Diagnostic Criteria for Buerger's Disease.

BACKGROUND: Buerger's disease (BD) remains a debilitating condition. Despite multiple published diagnostic criteria for BD, none is universally accepted as a gold standard. METHODS: We conducted a 2-round modified Delphi consensus study to establish a consensus on the diagnostic. The questionnaire included statements from several commonly used diagnostic criteria for BD. Qualitative and quantitative analysis methods were performed. An agreement level of 70% was applied. RESULTS: Twenty nine experts from 18 countries participated in this study. Overall, 75 statements were circulated in Round 1. Of these, 28% of statements were accepted. Following comments, 21 statements were recirculated in Round 2 and 90% were accepted. Although more than 90% of the experts did not agree that the diagnosis of BD can be based only on clinical manifestation, none of the nonclinical manifestations of BD were agreed as a part of the diagnostic criteria. There was an agreement that a history of tobacco consumption in any form, not necessarily confined to the current use, should be a part of the diagnostic criteria of BD. The history of thrombophlebitis migrans, even if not present at presentation, was accepted as a clue for BD diagnosis. It was also agreed that discoloration of the toes or fingers could be included in the diagnostic criteria of BD. Experts agreed that histology results could differentiate BD from atherosclerosis obliterans and other types of vasculitis. The presence of corkscrew collaterals on imaging and burning pain reached the agreement at the first round but not at the second. There was no consensus regarding age cut-off, the requirement of normal lipid profile, and normal blood glucose for BD diagnosis. CONCLUSIONS: The present study demonstrated discrepancies in the various published diagnostic criteria for BD and their selective utilization in routine clinical practice worldwide. We propose that all published diagnostic criteria for BD be re-evaluated for harmonization and universal use.

Milestones in thromboangiitis obliterans: a position paper of the VAS-European independent foundation in angiology/vascular medicine.

Even today thromboangiitis obliterans has disease features that remain misunderstood or underappreciated. The epidemiology, etiology and pathophysiology of the disease are still unclear. Biomarkers and disease activity markers are lacking, thus clinical assessment is difficult. We are still struggling to establish unique diagnostic, staging and treatment criteria. This is an academic-collaborative effort to describe the pathophysiology, the clinical manifestations, the diagnostic approach, and the challenges of management of patients with TAO. A systematic search for relevant studies dating from 1900 to the end of 2020 was performed on the PubMed, SCOPUS, and Science Direct databases. Given the intriguing nature of presentation of TAO, its management, to some extent is not only different in different regions of the world but also varies within the same region. Following this project, we discovered ambiguity, overlap and lack of clear-cut criteria for management of TAO. An international group of experts however came to one conclusion. They all agree that management of TAO needs a call for action for a renewed global look with multi-center studies, to update the geographical distribution of the disease and to establish a unique set of diagnostic criteria and a consensus-based guideline for best treatment based on current evidence.

National guidelines on the management of venous thromboembolism: Joint guideline of the Turkish Society of Cardiovascular Surgery, National Society of Vascular and Endovascular Surgery, and Phlebology Society.

These evidence-based guidelines from the Turkish Society of Cardiovascular Surgery, National Society of Vascular and Endovascular Surgery, and Phlebology Society intend to support clinicians in best decisions regarding the treatment of venous thromboembolism (VTE). The Editor was selected by the three national societies and was tasked with the recruitment of the recognized panel. All financial support was solely derived from the sponsoring societies without the direct involvement of industry or other external stakeholders. The panel prioritized clinical questions and outcomes according to their importance for clinicians in terms of VTE. The panel agreed on 42 recommendations under 15 headings for the diagnosis, initial management, secondary prevention of VTE, and treatment of recurrent VTE events. Important recommendations included the use of ultrasonography, preference for home treatment over hospital treatment for uncomplicated VTE, preference for direct oral anticoagulants (DOACs) over vitamin K antagonists for primary treatment of cancer and non-cancer-related VTE, extended or indefinite anticoagulation with DOACs in selected high-risk patients. Early catheter-directed thrombectomy was recommended in only young symptomatic patients with a diagnosis of fresh iliofemoral deep vein thrombosis.

Guidance for the Management of Patients with Vascular Disease or Cardiovascular Risk Factors and COVID-19: Position Paper from VAS-European Independent Foundation in Angiology/Vascular Medicine.

COVID-19 is also manifested with hypercoagulability, pulmonary intravascular coagulation, microangiopathy, and venous thromboembolism (VTE) or arterial thrombosis. Predisposing risk factors to severe COVID-19 are male sex, underlying cardiovascular disease, or cardiovascular risk factors including noncontrolled diabetes mellitus or arterial hypertension, obesity, and advanced age. The VAS-European Independent Foundation in Angiology/Vascular Medicine draws attention to patients with vascular disease (VD) and presents an integral strategy for the management of patients with VD or cardiovascular risk factors (VD-CVR) and COVID-19. VAS recommends (1) a COVID-19-oriented primary health care network for patients with VD-CVR for identification of patients with VD-CVR in the community and patients' education for disease symptoms, use of eHealth technology, adherence to the antithrombotic and vascular regulating treatments, and (2) close medical follow-up for efficacious control of VD progression and prompt application of physical and social distancing measures in case of new epidemic waves. For patients with VD-CVR who receive home treatment for COVID-19, VAS recommends assessment for (1) disease worsening risk and prioritized hospitalization of those at high risk and (2) VTE risk assessment and thromboprophylaxis with rivaroxaban, betrixaban, or low-molecular-weight heparin (LMWH) for those at high risk. For hospitalized patients with VD-CVR and COVID-19, VAS recommends (1) routine thromboprophylaxis with weight-adjusted intermediate doses of LMWH (unless contraindication); (2) LMWH as the drug of choice over unfractionated heparin or direct oral anticoagulants for the treatment of VTE or hypercoagulability; (3) careful evaluation of the risk for disease worsening and prompt application of targeted antiviral or convalescence treatments; (4) monitoring of D-dimer for optimization of the antithrombotic treatment; and (5) evaluation of the risk of VTE before hospital discharge using the IMPROVE-D-dimer score and prolonged post-discharge thromboprophylaxis with rivaroxaban, betrixaban, or LMWH.

Differences in pain, fatigue, and quality of life in patients with chronic venous insufficiency based on physical activity level.

BACKGROUND: This study aims to compare the effect of different physical activity levels on pain, fatigue, and quality of life in patients with chronic venous insufficiency. METHODS: Between October 2018 and February 2019, a total of 69 patients (4 males, 65 females; mean age 50 years; range, 19 to 73 years) who were diagnosed with chronic venous insufficiency and consulted for physiotherapy were included in the study. The physical activity level of the patients was determined using the International Physical Activity Questionnaire in three groups as light, moderate, or vigorous. Fatigue, pain, and QoL were assessed using the Fatigue Severity Scale, visual analog scale (during the night, activity, and rest), and Venous Insufficiency Epidemiological and Economic Study Quality/Symptom Scale, respectively. RESULTS: Of a total of 69 patients, 17 were in the light-intensity physical activity group, 32 in the moderate-intensity physical activity group, and 20 in the vigorous-intensity physical activity group. Perceived pain during activity and fatigue were significantly different between the light- and moderate-intensity physical activity groups (p<0.05). There was no significant difference in pain, fatigue, and quality of life scores between the vigorous-intensity physical activity group and the other two groups (p>0.05). CONCLUSION: Our study results suggest that a moderate level of physical activity may be helpful to overcome symptoms such as pain and fatigue in patients with chronic venous insufficiency and to improve quality of life.

Acute Cardiovascular Responses to the Application of Manual Lymphatic Drainage in Different Body Regions.

Background: The purpose of this study was to investigate acute cardiovascular responses to manual lymphatic drainage (MLD) on different parts of the body. Materials and Methods: Thirty healthy individuals (10 women and 20 men) participated in the study voluntarily. Heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), respiration frequency, and oxygen saturation were measured before and after MLD was applied to different regions of the body (neck, abdomen, anastomosis, arm, and leg). HR, SBP, and DBP were measured with a sphygmomanometer (OMRON, USA) and oxygen saturation was measured with a pulse oximeter. Results: Increase in DBP was seen after abdominal drainage (p = 0.038); reduction in SBP (p = 0.002) and DBP (p = 0.004) after neck drainage; reduction in SBP (p < 0.001) and HR (p = 0.004) after arm drainage; and reduction in SBP and DBP after leg drainage. There was no change in the oxygen saturation levels of participants after MLD (p > 0.05). Conclusions: In healthy subjects, the effects of MLD were found to vary according to the region of application. This study signals that the cardiovascular effects of MLD treatment vary in different regions of the body.

Protective effect of erdosteine on erythrocyte deformability in a rat model of lower limb ischemia/reperfusion injury

Background/aim: The protective effect of erdosteine on local and distant organ injury due to ischemia/reperfusion has been well documented but its effect on erythrocyte deformability needs further investigation. Our aim was to investigate the effect of erdosteine on erythrocyte deformability in the infrarenal aorta of rats undergoing ischemia/reperfusion. Materials and methods: Our study was conducted with 18 Wistar albino rats. Rats were divided into 3 groups: a randomized control group (group 'control', n = 6), an ischemia/reperfusion group without erdosteine (group 'ischemia/reperfusion', n = 6), and an ischemia/reperfusion group with erdosteine at 150 mg kg−1, intraperitoneally (group 'ischemia/reperfusion - erdosteine', n = 6). Packs of erythrocytes were prepared from heparinized blood samples and deformability measurements were conducted. Results: Comparisons of the control and ischemia/reperfusion - erdosteine groups revealed similar results (P = 0.051). The values of the ischemia/reperfusion group were significantly higher than those of the control and ischemia/reperfusion - erdosteine groups (P < 0.0001 and P = 0.024, respectively). Relative resistance, a marker of erythrocyte deformability, was increased significantly by ischemia/reperfusion compared to the control and ischemia/reperfusion - erdosteine groups (P < 0.05). Conclusion: We detected unfavorable effects of ischemia/reperfusion on erythrocyte deformability, which may lead to disturbance in blood flow and hence tissue perfusion in the infrarenal rat aorta. We also found that erdosteine had beneficial effects by reversing undesirable effects of ischemia/reperfusion. However, these promising results should be further supported by more detailed studies with larger volumes.

Effects of alprostadil and iloprost on renal, lung, and skeletal muscle injury following hindlimb ischemia-reperfusion injury in rats.

OBJECTIVES: To evaluate the effects of alprostadil (prostaglandin [PGE1] analog) and iloprost (prostacyclin [PGI2] analog) on renal, lung, and skeletal muscle tissues after ischemia reperfusion (I/R) injury in an experimental rat model. MATERIALS AND METHODS: Wistar albino rats underwent 2 hours of ischemia via infrarenal aorta clamping with subsequent 2 hours of reperfusion. Alprostadil and iloprost were given starting simultaneously with the reperfusion period. Effects of agents on renal, lung, and skeletal muscle (gastrocnemius) tissue specimens were examined. RESULTS: Renal medullary congestion, cytoplasmic swelling, and mean tubular dilatation scores were significantly lower in the alprostadil-treated group than those found in the I/R-only group (P<0.0001, P=0.015, and P<0.01, respectively). Polymorphonuclear leukocyte infiltration, pulmonary partial destruction, consolidation, alveolar edema, and hemorrhage scores were significantly lower in alprostadil- and iloprost-treated groups (P=0.017 and P=0.001; P<0.01 and P<0.0001). Polymorphonuclear leukocyte infiltration scores in skeletal muscle tissue were significantly lower in the iloprost-treated group than the scores found in the nontreated I/R group (P<0.0001). CONCLUSION: Alprostadil and iloprost significantly reduce lung tissue I/R injury. Alprostadil has more prominent protective effects against renal I/R injury, while iloprost is superior in terms of protecting the skeletal muscle tissue against I/R injury.

The effects of iloprost on ischemia-reperfusion injury in skeletal muscles in a rodent model.

PURPOSE: The aim of this study was to investigate the effects of iloprost (IL) on ischemia-reperfusion injury in a rodent model. MATERIALS AND METHODS: Twenty-four Wistar Albino rats were randomized into four groups (n = 6). Laparotomy was performed in all groups under general anesthesia. Only laparotomy was applied in group S (Sham). Ischemia-reperfusion group (group I/R) underwent ischemia and reperfusion performed by clamping and declamping of the infrarenal abdominal aorta for 120 min. The iloprost group (group IL) received intravenous infusion of IL 0.5 ng/kg/min, without I/R. Group I/R + IL received intravenous infusion of IL 0.5 ng/kg/min immediately after 2 h period of ischemia. At the end of the reperfusion period, all rats were killed under anesthesia and skeletal muscle samples of lower extremity were harvested for biochemical and histopathologic analyses. RESULTS: Tissue levels of endothelial nitric oxide were significantly higher in I/R groups than those in groups S and IL. The heat shock protein 60 levels were higher in group I/R than the other groups. But the heat shock protein 60 levels in group I/R + IL were found to be similar with the groups S and IL. Malondialdehyde levels were significantly higher in group I/R. On the other hand, in group I/R + IL, malondialdehyde levels were higher than those in groups S and IL but lower than those in group I/R. Superoxide dismutase (SOD) enzyme activities were found to be significantly lower in group I/R than the other groups. Also in group I/R/I, the SOD enzyme activities were higher than those in group I/R. But, in group I/R + IL, SOD levels were found to be higher than those in group I/R but lower than those in groups S and IL. CONCLUSIONS: These results indicate that IL has protective effects on I/R injury in skeletal muscle in a rodent model.

Glutamine enhances the heat shock protein 70 expression as a cardioprotective mechanism in left heart tissues in the presence of diabetes mellitus.

OBJECTIVE: Effects of diabetes mellitus on myocardium were investigated, by assessing levels of heat shock protein (HSP) 70, and efficacy of glutamine was tested. MATERIALS AND METHODS: Thirty male rats were divided into three groups: control group (Group 1), diabetic group (Group 2) and glutamine-induced diabetic group (Group 3). Diabetes was created by intravenous streptozocin injection. Rats were examined one month later for cardiac complications of diabetes. Serum and tissue samples were obtained to measure HSP 70 levels. RESULTS: Following streptozocin administration, glucose levels increased markedly. This resulted in a significant increase in HSP 70 in serum and tissues. When Group 3 was compared with other groups, HSP 70 was more increased in serum and tissues. When Groups 2 and 3 were compared, more increased HSP 70 values were observed in Group 3, statistical significance was obtained for left atrial and left ventricular HSP 70 levels. Elevated blood glucose was correlated with elevated HSP 70 levels. Increased serum HSP 70 levels were correlated with tissue HSP 70 values. CONCLUSIONS: HSP 70 levels increase in the myocardium of rats in diabetes mellitus as a protective mechanism. Levels of HSP 70 may further be increased with parenteral administration of glutamine. Efficacy of glutamine is more pronounced in left heart structures.

Peripheric stem cell transplantation in children with dilated cardiomyopathy: preliminary report of first two cases.

We report two pediatric patients with IDC who underwent autologous PSCT. Both cases were referred to our clinic for cardiac transplantation because of end-stage heart failure resistant to conventional therapy with digoxin, diuretics, ACE inhibitors, and sympathomimetics. They had ejection fractions below 35%. In each case, autologous stem cell transplantation was performed via the coronary arteries, and five wk after the procedure transthoracic echocardiography showed a striking gain in their ejection fractions and an improvement in the left ventricular dimensions compared with the initial measurements. Although heart transplantation is the only option for children with IDC, stem cell transplantation can lessen the waiting list mortality and prolong the time for a patient to wait for a suitable donor.

Aortic stiffness in diabetes mellitus--association with glutamine and heat shock protein 70 expression: a pilot study based on an experimental rodent model.

BACKGROUND: Diabetes mellitus (DM) alters arterial wall compliance and causes aortic stiffness, which is a predictor of vascular mortality. Heat shock proteins (HSPs) are involved in the protection of cells under stress. We evaluated aortic stiffness in DM and the effects of glutamine (which induces HSP 70) on HSP 70 levels in experimental DM. MATERIALS AND METHODS: Male Sprague-Dawley rats (n = 30) were divided into three groups: Control (Group 1), DM (Group 2) and glutamine-treated DM (Group 3). DM was induced using streptozocin injection. Group 3 rats received two doses of glutamine during the fourth week. Blood and infrarenal aortic tissue samples were obtained for analysis at the end of the fourth week. RESULTS: Compared with Group 1, serum HSP 70 levels were significantly increased in Groups 2 and 3. Aortic HSP 70 was increased in DM. There was a significant difference in aortic HSP 70 with glutamine injection (Group 1 versus Group 3). DM also interfered with the elastin content of the aorta. There was a significant correlation between the serum glucose and serum and aortic HSP 70 levels and between serum and aortic HSP 70 levels; as well as between severity of DM and aortic elastin levels. CONCLUSIONS: DM causes aortic stiffness and this may contribute to the increase in mortality and morbidity associated with DM. The expression of HSP 70 may become a therapeutic target.

Anaesthesia for caesarean section in the presence of multivalvular heart disease and severe pulmonary hypertension: a case report.

INTRODUCTION: Pulmonary hypertension is a rare condition and in combination with pregnancy, it can result in high maternal mortality. Mitral stenosis is one of the complicated cardiac diseases that may occur during pregnancy. In this report, we describe our management of such a case, which was even more difficult in combination with pulmonary hypertension, mitral stenosis, and aortic and tricuspid valve insufficiency requiring emergency caesarean section under general anaesthesia. CASE PRESENTATION: A 29-year-old primiparae was presented to the anaesthetic department for an urgent caesarean section with a diagnosis of severe pulmonary hypertension in combination with mitral stenosis. The patient was hospitalized prepartum and received oxygen therapy and anticoagulation with heparin. The patient was monitored during labour and delivery with oximetry and arterial and central venous pressure line. Pulmonary arterial lines were not used due to an increased risk and questionable usefulness. Echocardiography revealed a systolic pulmonary arterial pressure of 75 mmHg, and mitral stenosis, aortic and tricuspid valve insufficiency. We decided to proceed under general anaesthesia. Anaesthesia was induced with etomidate, and succinylcholine. Dopamine and nitroglycerin infusion was preoperatively started and infusion was also preoperatively continued. Hemodynamic parameters were stable during delivery. Neonatal weight and apgar score were satisfactory. After the delivery of a healthy baby, oxytocin was administered. Surgery was completed uneventfully. During the postoperative period, the patient received furosemide and morphine. As the arterial blood gas analyses were stable and the chest-ray was normal, the patient was extubated postoperatively in the second hour in ICU. CONCLUSION: Patients with significant multivalvular heart disease require careful preoperative, multidisciplinary assessment and anesthetic planning before delivery in order to optimize cardiac function during the peripartum period and make informed decisions regarding the mode of delivery and anaesthetic technique.

Traditional single patch versus the "Australian" technique for repair of complete atrioventricular canal defects.

PURPOSE: A variety of operative techniques has been used to repair complete atrioventricular (AV) canal defects and satisfactory outcomes after single patch repairs have been reported. We report our comparative results of repairing complete AV canal defects between 1998 and 2006 using the traditional single patch and the "Australian" techniques. METHODS: Fourteen patients underwent traditional AV canal repair with the single patch technique (Group 1) and 11 patients underwent repair with the "Australian" technique (Group 2). All patients were examined with preoperative echocardiography and cardiac catheterization, and were followed up with echocardiography to evaluate AV valve and ventricular function. RESULTS: There were two early postoperative deaths in Group 1 and one in Group 2. One patient from each group had moderate left AV valve regurgitation postoperatively, but none from either group had left ventricular outflow obstruction. CONCLUSIONS: The "Australian" technique is a simpler method requiring shorter aortic cross-clamping and total bypass times with good clinical and functional results. The early postoperative results are as encouraging as those achieved by the traditional single patch technique; however, long-term follow-up results are required to establish the efficacy of this simplified technique.

Detection of Helicobacter pylori DNA in aortic and left internal mammary artery biopsies.

We investigated the relationship between acute coronary ischemia and the presence of Helicobacter pylori DNA in aortic regions that were absent macroscopic atheromatous plaques. The study group (Group 1) consisted of 42 patients who underwent coronary artery bypass grafting. Biopsy samples were obtained from 2 different locations: from regions of the aorta that were free (macroscopically) of atheromatous plaque (Group 1A), and from the internal mammary artery (Group 1B). The control group (Group 2) of 10 patients who had no atherosclerotic vascular disease provided aortic tissue samples for comparison. The real-time polymerase chain reaction method was used to detect H. pylori DNA in all biopsy samples. Eleven of 42 aortic tissue samples (26%) in Group 1A were positive for H. pylori DNA. Neither biopsies from the left internal mammary arteries of those patients nor biopsies from the aortas of the control group (Group 2) were positive for H. pylori DNA. There was a statistically significant difference between 1A and 1B in terms of H. pylori positivity (P=0.001). In Group 1 as a whole, acute coronary ischemia was more prevalent in the H. pylori-positive patients than in the H. pylori-negative patients (P=0.001). To our knowledge, this is the 1st study to investigate the detection of H. pylori DNA in aortic biopsy samples that are macroscopically free of atheromatous plaque. Such detection in patients who have atherosclerotic coronary artery disease could be an important indication of the role of microorganisms in the pathogenesis of atherosclerosis.