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.

Impact of chronic kidney disease on hemoglobin among patients with peripheral artery disease treated with P2Y12 inhibitors: Insights from the EUCLID trial.

Patients with chronic kidney disease may develop new or more severe anemia when treated with antiplatelet agents due to blood loss in conjunction with impaired erythropoiesis. Because anemia independently predicts limb amputation and mortality among patients with peripheral artery disease (PAD), we evaluated the relationship between estimated glomerular filtration rate (eGFR) and hemoglobin (Hb) levels in the EUCLID trial in which patients with symptomatic PAD were randomized to ticagrelor or clopidogrel. At baseline, 9025, 1870, and 1000 patients had eGFR ⩾ 60, 45-59, and < 45 mL/min/1.73 m2, respectively. The mean fall in Hb during the trial was 0.46 ± 1.68 g/dL and did not differ by baseline eGFR category, although Hb fall ⩾ 10% was more frequent among patients with lower eGFR (p for trend < 0.0001). On-study treatment with iron, erythropoiesis-stimulating agents, and/or red blood cell transfusion was reported for 479 (5.3%), 165 (8.8%), and 129 (12.9%) patients in the three eGFR categories, respectively (p for trend < 0.0001). After adjustment for baseline and post-randomization effects, those not receiving anemia treatment had a smaller reduction in Hb from baseline than those receiving anemia treatment (p < 0.0001). Other determinants of Hb reduction included absence of on-study myocardial infarction, coronary or peripheral revascularization, residence outside North America, male sex, and baseline eGFR. We conclude that among patients with PAD treated with P2Y12 inhibitors, lower baseline eGFR was associated with a greater reduction in Hb. ClinicalTrials.gov Identifier: NCT01732822.

The COVID-19 Pandemic and the Need for an Integrated and Equitable Approach: An International Expert Consensus Paper.

BACKGROUND: One year after the declaration of the coronavirus disease 2019 (COVID-19) pandemic by the World Health Organization (WHO) and despite the implementation of mandatory physical barriers and social distancing, humanity remains challenged by a long-lasting and devastating public health crisis. MANAGEMENT: Non-pharmacological interventions (NPIs) are efficient mitigation strategies. The success of these NPIs is dependent on the approval and commitment of the population. The launch of a mass vaccination program in many countries in late December 2020 with mRNA vaccines, adenovirus-based vaccines, and inactivated virus vaccines has generated hope for the end of the pandemic. CURRENT ISSUES: The continuous appearance of new pathogenic viral strains and the ability of vaccines to prevent infection and transmission raise important concerns as we try to achieve community immunity against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) and its variants. The need of a second and even third generation of vaccines has already been acknowledged by the WHO and governments. PERSPECTIVES: There is a critical and urgent need for a balanced and integrated strategy for the management of the COVID-19 outbreaks organized on three axes: (1) Prevention of the SARS-CoV-2 infection, (2) Detection and early diagnosis of patients at risk of disease worsening, and (3) Anticipation of medical care (PDA). CONCLUSION: The "PDA strategy" integrated into state policy for the support and expansion of health systems and introduction of digital organizations (i.e., telemedicine, e-Health, artificial intelligence, and machine-learning technology) is of major importance for the preservation of citizens' health and life world-wide.

Global Burden of Cardiovascular Diseases and Risk Factors, 1990-2019: Update From the GBD 2019 Study.

Cardiovascular diseases (CVDs), principally ischemic heart disease (IHD) and stroke, are the leading cause of global mortality and a major contributor to disability. This paper reviews the magnitude of total CVD burden, including 13 underlying causes of cardiovascular death and 9 related risk factors, using estimates from the Global Burden of Disease (GBD) Study 2019. GBD, an ongoing multinational collaboration to provide comparable and consistent estimates of population health over time, used all available population-level data sources on incidence, prevalence, case fatality, mortality, and health risks to produce estimates for 204 countries and territories from 1990 to 2019. Prevalent cases of total CVD nearly doubled from 271 million (95% uncertainty interval [UI]: 257 to 285 million) in 1990 to 523 million (95% UI: 497 to 550 million) in 2019, and the number of CVD deaths steadily increased from 12.1 million (95% UI:11.4 to 12.6 million) in 1990, reaching 18.6 million (95% UI: 17.1 to 19.7 million) in 2019. The global trends for disability-adjusted life years (DALYs) and years of life lost also increased significantly, and years lived with disability doubled from 17.7 million (95% UI: 12.9 to 22.5 million) to 34.4 million (95% UI:24.9 to 43.6 million) over that period. The total number of DALYs due to IHD has risen steadily since 1990, reaching 182 million (95% UI: 170 to 194 million) DALYs, 9.14 million (95% UI: 8.40 to 9.74 million) deaths in the year 2019, and 197 million (95% UI: 178 to 220 million) prevalent cases of IHD in 2019. The total number of DALYs due to stroke has risen steadily since 1990, reaching 143 million (95% UI: 133 to 153 million) DALYs, 6.55 million (95% UI: 6.00 to 7.02 million) deaths in the year 2019, and 101 million (95% UI: 93.2 to 111 million) prevalent cases of stroke in 2019. Cardiovascular diseases remain the leading cause of disease burden in the world. CVD burden continues its decades-long rise for almost all countries outside high-income countries, and alarmingly, the age-standardized rate of CVD has begun to rise in some locations where it was previously declining in high-income countries. There is an urgent need to focus on implementing existing cost-effective policies and interventions if the world is to meet the targets for Sustainable Development Goal 3 and achieve a 30% reduction in premature mortality due to noncommunicable diseases.

Positive and negative well-being of older adults with symptomatic peripheral artery disease: A population-based investigation.

OBJECTIVE: We investigated positive and negative subjective well-being in relation to lower-extremity peripheral artery disease (PAD) in a sample of older adults. METHOD: 4760 participants in the English Longitudinal Study of Ageing (ELSA) provided baseline data on symptomatic PAD, sociodemographic characteristics, lifestyle risk factors, and co-morbid conditions. Baseline and two-year follow-up data were available for life satisfaction, quality of life, and depressive symptoms. RESULTS: Participants with PAD symptoms had lower baseline levels of life satisfaction (ß = -0.03, p < .05) and quality of life (ß = -0.04, p < .01), and more depressive symptoms (ß = 0.03, p < .05). These associations remained statistically significant in multivariate analyses. Baseline PAD did not, however, influence well-being levels at two-year follow-up. DISCUSSION: Greater awareness of the potential for chronic vascular morbidity to disrupt the lives of older adults is needed to inform effective multidisciplinary support and interventions that help maintain the quality of life of those affected.

Epidemiology of peripheral artery disease in Europe: VAS Educational Paper.

This paper reviews the current epidemiological data on peripheral artery disease (PAD) in Europe. Cardiovascular disease (CVD) burden is presented and PAD prevalence is discussed, as compared to coronary (CAD) and cerebrovascular (CeVD) diseases, in European Union (EU) countries and European continent countries. The article reviews PAD clinical manifestations, PAD diagnosis, risk factors for PAD incidence and progression, PAD prognosis and financial implications. CVD mortality is higher in women than in men and in European continent countries, as compared to EU countries. While CAD and CeVD have a lower prevalence in EU countries, as compared to the whole continent, PAD and other CVDs still have a higher prevalence in EU countries. PAD prevalence vary widely between countries, increases sharply with aging and has a relation with ethnicity. CVD comorbidities are high in PAD subjects and particularly high in those with critical limb ischemia. PAD prognosis is related to CAD and CeVD mortality, that are particularly high in critical limb ischemia. This review promotes the need for global awareness on PAD burden, stimulates PAD screening and emphasizes the importance of early diagnosis and treatment of PAD and associated cardiovascular comorbidities.

WITHDRAWN: Angioplasty (versus non surgical management) for intermittent claudication.

BACKGROUND: Intermittent claudication is pain in the legs due to muscle ischaemia associated with arterial stenosis or occlusion. Angioplasty is a technique that involves dilatation and recanalisation of a stenosed or occluded artery. OBJECTIVES: The objective of this review was to determine the effects of angioplasty of arteries in the leg when compared with non surgical therapy, or no therapy, for people with mild to moderate intermittent claudication. SEARCH METHODS: Sources searched include the Cochrane Peripheral Vascular Diseases Group's Specialized Trials Register (August 2006), the Cochrane Central Register of Controlled Trials (CENTRAL, Issue 3, 2006) and reference lists of relevant articles. The review authors also contacted investigators in the field and handsearched relevant conference proceedings (August 2006). SELECTION CRITERIA: Randomised trials of angioplasty for mild or moderate intermittent claudication. DATA COLLECTION AND ANALYSIS: The contact author selected suitable trials and this was checked by the other review author. Both review authors assessed trial quality independently. The contact author extracted data and this was cross checked by the other review author. MAIN RESULTS: Two trials with a total of 98 participants were included. The average age was 62 years old with 20 women and 78 men. Participants were followed for two years in one trial and six years in the other.At six months follow up, mean ankle brachial pressure indices were higher in the angioplasty groups than control groups (mean difference 0.17; 95% confidence interval (CI) 0.11 to 0.24). In one trial, walking distances were greater in the angioplasty group, but in the other trial, in which controls underwent an exercise programme, walking distances did not show a greater improvement in the angioplasty group. At two years follow up in one trial, the angioplasty group were more likely to have a patent artery (odds ratio 5.5; 95% CI 1.8 to 17.0) but not a significantly better walking distance or quality of life. In the other trial, long term follow up at six years demonstrated no significant differences in outcome between the angioplasty and control groups. AUTHORS' CONCLUSIONS: These limited results suggest that angioplasty may have had a short term benefit, but this may not have been sustained.

[Epidemiology of lower extremity artery disease]. / Épidémiologie de l'artériopathie des membres inférieurs.

It is estimated that more than 200 million individuals are affected by lower extremity artery disease (LEAD) worldwide. This prevalence has increased between 2000 and 2010 by 25%, especially in low/middle income countries. In France, about one million people are affected by this condition. Almost two-thirds of patients with LEAD are asymptomatic. This explains the interest of the measurement of the ankle-brachial index (ABI), an objective and harmless diagnostic tool. An ABI≤0.90 is considered as diagnostic for LEAD. The detection of symptomatic LEAD requires standardized questionnaires identifying intermittent claudication. Epidemiological studies on chronic limb-threatening ischemia (CLTI) - the most severe presentation of the disease - are scarce: the prevalence is estimated around 0.5-2.0% after the age of 40, mostly affecting elderly people. Similar to other atherosclerotic diseases, the risk factors are multiple (genetic factors, traditional risk factors, metabolic and inflammatory factors, socioeconomic factors), with different weighs of association as compared to coronary artery diseases. Due to their high prevalence and strength of association, cigarette smoking and hypertension are the most frequent purveyors of this disease in population. Diabetes mellitus is a strong risk factor, and its increasing prevalence contributes to the global epidemics of LEAD. In claudicants, the 5-year amputation risk is estimated at 5%, increasing to 25% at one year in case of CLTI. However, the main risk is related to general cardiovascular events. It is estimated that patients with LEAD present concomitantly coronary and cerebrovascular disease in respectively 50% and 20% of cases. The non-cardiovascular mortality, especially related to cancer, is also higher than in general population. Overall, the control of traditional risk factors has a beneficial effect both for the limb and general prognosis.

An Update on Methods for Revascularization and Expansion of the TASC Lesion Classification to Include Below-the-Knee Arteries: A Supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II).

The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today.

An update on methods for revascularization and expansion of the TASC lesion classification to include below-the-knee arteries: A supplement to the inter-society consensus for the management of peripheral arterial disease (TASC II): The TASC steering committee.

The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today.

An Update on Methods for Revascularization and Expansion of the TASC Lesion Classification to Include Below-the-Knee Arteries: A Supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II).

The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today.

An Update on Methods for Revascularization and Expansion of the TASC Lesion Classification to Include Below-the-Knee Arteries: A Supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II): The TASC Steering Comittee(.).

The Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC) guidelines were last updated in 2007 (TASC II) and represented the collaboration of international vascular specialties involved in the management of patients with peripheral arterial disease (PAD). Since the publication of TASC II, there have been innovations in endovascular revascularization strategies for patients with PAD. The intent of this publication is to provide a complete anatomic lower limb TASC lesion classification, including the infrapopliteal segment, and an updated literature review of new endovascular techniques and practice patterns employed by vascular specialists today.

A gene-centric study of common carotid artery remodelling.

BACKGROUND: Expansive remodelling is the process of compensatory arterial enlargement in response to atherosclerotic stimuli. The genetic determinants of this process are poorly characterized. METHODS: Genetic association analyses of inter-adventitial common carotid artery diameter (ICCAD) in the IMPROVE study (n = 3427) using the Illumina 200k Metabochip was performed. Single nucleotide polymorphisms (SNPs) that met array-wide significance were taken forward for analysis in three further studies (n = 5704), and tested for association with Abdominal Aortic Aneurysm (AAA). RESULTS: rs3768445 on Chromosome 1q24.3, in a cluster of protein coding genes (DNM3, PIGC, C1orf105) was associated with larger ICCAD in the IMPROVE study. For each copy of the rare allele carried, ICCAD was on average 0.13 mm greater (95% CI 0.08-0.18 mm, P = 8.2 × 10(-8)). A proxy SNP (rs4916251, R(2) = 0.99) did not, however, show association with ICCAD in three follow-up studies (P for replication = 0.29). There was evidence of interaction between carotid intima-media thickness (CIMT) and rs4916251 on ICCAD in two of the cohorts studies suggesting that it plays a role in the remodelling response to atherosclerosis. In meta-analysis of 5 case-control studies pooling data from 5007 cases and 43,630 controls, rs4916251 was associated with presence of AAA 1.10, 95% CI 1.03-1.17, p = 2.8 × 10(-3), I(2) = 18.8, Q = 0.30). A proxy SNP, rs4916251 was also associated with increased expression of PIGC in aortic tissue, suggesting that this may the mechanism by which this locus affects vascular remodelling. CONCLUSIONS: Common variation at 1q24.3 is associated with expansive vascular remodelling and risk of AAA. These findings support a hypothesis that pathways involved in systemic vascular remodelling play a role in AAA development.

Intravenous naftidrofuryl for critical limb ischaemia.

BACKGROUND: Peripheral arterial disease affects five per cent of men and women by late middle age. Approximately 25% of those affected will develop critical limb ischaemia (rest pain, ulceration and gangrene) within five years. Naftidrofuryl is a vasoactive drug which may be beneficial in the treatment of critical limb ischaemia. OBJECTIVES: To determine whether naftidrofuryl, when administered intravenously, is effective in alleviating symptoms and reducing progression of disease in patients with critical limb ischaemia. SEARCH METHODS: The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2012) and CENTRAL (2012, Issue 4). We searched the reference lists of articles. We also contacted pharmaceutical companies for any unpublished trials. SELECTION CRITERIA: All randomised controlled trials of critical limb ischaemia in which participants were randomly allocated to intravenous naftidrofuryl or control (either pharmacological, inert placebo or conservative therapy) were included. People with intermittent claudication were not included. DATA COLLECTION AND ANALYSIS: Sixteen trials were identified, but eight were excluded because of poor methodology. The eight included trials involved a total of 269 participants from five different countries. The following outcomes were reported: pain reduction, rest pain/necrosis, progression of disease in terms of incidence of surgical reconstruction/amputation, mortality and side effects. On extraction of the data, odds ratios and mean differences were estimated where appropriate. MAIN RESULTS: Treatment with naftidrofuryl tended to show reduction of pain evaluated by both analogue score and analgesic consumption, but the effect was statistically non-significant (mean difference (MD): 0.42; 95% confidence interval (CI)1.19 to 0.35). Similarly, improvement in rest pain or skin necrosis occurred, but these effects were also non-significant. The effect on mean ankle systolic pressure was inconclusive. AUTHORS' CONCLUSIONS: Based on the results of these trials, it cannot be confirmed that intravenous naftidrofuryl is effective in the treatment of people with critical limb ischaemia. However, these results were based on trials of generally low methodological quality which had only a small number of participants, the duration of treatment was extremely short, and the methods varied between the trials. The wide range of endpoints effectively precluded any meaningful pooling of the results. Intravenous naftidrofuryl was withdrawn as a treatment for severe peripheral arterial disease in 1995 because of reported side effects.

Meta analysis of candidate gene variants outside the LPA locus with Lp(a) plasma levels in 14,500 participants of six White European cohorts.

BACKGROUND: Both genome-wide association studies and candidate gene studies have reported that the major determinant of plasma levels of the Lipoprotein (a) [Lp(a)] reside within the LPA locus on chromosome 6. We have used data from the HumanCVD BeadChip to explore the contribution of other candidate genes determining Lp(a) levels. METHODS: 48,032 single nucleotide polymorphisms (SNPs) from the Illumina HumanCVD BeadChip were genotyped in 5059 participants of the Whitehall II study (WHII) of randomly ascertained healthy men and women. SNPs showing association with Lp(a) levels of p<10(-4) outside the LPA locus were selected for replication in a total of an additional 9463 participants of five European based studies (EAS, EPIC-Norfolk, NPHSII, PROCARDIS, and SAPHIR). RESULTS: In Whitehall II, apart from the LPA locus (where p values for several SNPs were <10(-30)) there was significant association at four loci GALNT2, FABP1, PPARGC1A and TNFRSFF11A. However, a meta-analysis of the six studies did not confirm any of these findings. CONCLUSION: Results from this meta analysis of 14,522 participants revealed no candidate genes from the HumanCVD BeadChip outside the LPA locus to have an effect on Lp(a) levels. Further studies with genome-wide and denser SNP coverage are required to confirm or refute this finding.

High risk of peripheral arterial disease in the United Kingdom: 2-year results of a prospective registry.

We report a prospective 2-year, multicenter study of patients presenting with intermittent claudication (IC; ankle brachial blood pressure index, ABPI ≤ 0.9). Mean age of the 473 patients enrolled was 68 years, 20% were diabetics, 30% had prior symptomatic coronary heart disease (CHD), 7% had prior stroke, and 39% were current smokers. At baseline, 26.2% of patients had BP ≤ 140/85 mm Hg or lower and at 2 years this figure was 32.5% (P = .01). Current smokers had fallen to 27% (from 39%) at 2 years (P < .001). Use of antiplatelet agents, statins, and angiotensin converting enzyme inhibitors increased significantly during the course of the study as did claudication distance. Death and the composite of death, stroke or myocardial infarction (MI), occurred in 8.4% and 11.6% of patients, respectively. Prognosis was worse in patients with prior history of CHD, older age, those with diabetes and a lower ABPI.