Samantha Huo

Yung Kai

Jean Ferrières

Camille Carles

Marion Turpin

François-Xavier Lapébie

Frédéric Dutheil

Alessandra Bura-Rivière

Yolande Esquirol

Frederic Dutheil

Alessandra Bura-Riviere

Lower limb venous and arterial peripheral diseases and work conditions: Systematic review

Keywords: varicose vein, venous thromboembolism, aortic dissection, aortic aneurysm, standing, work CRD42019127652 varicose vein, venous thromboembolism, aortic dissection, aortic aneurysm, standing, sitting, carrying, work

à la diffusion de documents scientifiques de niveau recherche, publiés ou non, émanant des établissements d'enseignement et de recherche français ou étrangers, des laboratoires publics ou privés.

INTRODUCTION

In Europe, the incidence rate of venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary embolism (PE), is estimated between 104 and 183/100,000 person-years with a recurrence of 30% within 10 years [START_REF] Heit | Epidemiology of venous thromboembolism[END_REF] . The prevalence of lower limb varicose veins (LLVV) is about 25% of women and 15% of men [START_REF] Depopas | Varicose Veins and Lower Extremity Venous Insufficiency[END_REF] .

The annual incidence of intermittent claudication is evaluated between 0.4 and 6/1000 men [START_REF] Aboyans | Epidemiology of lower extremity artery disease[END_REF] and the prevalence of abdominal aortic aneurysm ranges between 1.3-12.5% in men, and up to 5.2% in women [START_REF] Altobelli | Risk Factors for Abdominal Aortic Aneurysm in Population-Based Studies: A Systematic Review and Meta-Analysis[END_REF] . The incidence of aortic dissection is evaluated at 3.5 and 2.53/100,000 person-year, respectively in the USA and Iceland.

Although some vascular disease risk factors are well-known (age, gender, smoking, immobilisation, etc. 1 4 ) occupational aetiologies remain little explored. Thus, the links between some occupational exposures and upper-extremity vascular diseases are well described (such as hand-arm vibration and Raynaud's phenomenon [START_REF] Nilsson | Hand-arm vibration and the risk of vascular and neurological diseases-A systematic review and meta-analysis[END_REF] ), but the role of occupational exposures on peripheral vascular disease remains unclear and still debated. D'Souza and Al. proposed in 2005 [START_REF] Souza | Review of epidemiologic studies on occupational factors and lower extremity musculoskeletal and vascular disorders and symptoms[END_REF] a short non exhaustive overview about occupational constraints and vein varicose, without conclusive result. This current systematic review was performed to evaluate the potential link between lower limb peripheral venous (LLVV and VTE) and arterial diseases (intermittent claudication, aortic dissection, and aortic aneurysm) and work conditions, and to summarize the current knowledge on this topic. Given that a lot of time is spent working, we hypotheses that the occupational constraints can be related to these vascular diseases. Some of occupational constraints are probably common for all these vascular diseases, while others are more specific. Determining this potential role, could be helpful to implement preventive strategies in companies.

METHODS

Search strategy

Systematic Reviews guidelines [START_REF] Moher | Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement[END_REF] were used to define the protocol of this systematic review of published studies which does not require approval by institutional and ethics committees.

A literature research in several databases including MEDLINE-PubMed, Web of Science, and ClinicalTrial.gov was conducted to identify the studies published until February the 28 th 2019 and focused on the associations between the diseases of interest (LLVV, VTE, intermittent claudication, aortic dissection, aortic aneurysm) and working conditions. Moreover, added researches were performed to find unpublished articles from the System for Information on Grey Literature in Europe ('OpenGrey.eu'). The keywords and MESH terms used are specific for each vascular disease and listed in Supplementary table 1.

Study eligibility criteria

Retrospective, prospective, cross-sectional studies, controlled trials and case reports reporting data on the potential link between each vascular event and working conditions were included. To analyse the potential role of occupational factors, only studies enrolling adult people ≥18 years old were included.

Studies written in English and in French were retained. No date selection was applied.

We excluded oral presentations, posters, opinion articles, books and when only the abstracts were available. Studies with no results concerning the potential link between occupational exposure and the studied vascular events were excluded (no assessment of risk was provided in observational studies.). Vascular diseases of the upper limbs were excluded. Flow charts, using PRISMA method [START_REF] Moher | Preferred reporting items for systematic reviews and meta-analyses: the PRISMA statement[END_REF] , summarize the different steps of the article selection for each investigated vascular diseases.

Study selection

Article selection was conducted independently by three reviewers (MT, SHYK, YE) using defined search terms. The results of the search were imported in Endnote software which was useful to delete duplicate articles. The next step consisted in selecting studies based on the screening of titles and then on abstracts independently by two reviewers (SHYK, YE) who also conducted a further selection after reading the full articles. In case of disagreement, a discussion with a third reviewer (JF) resolved it. The references listed in the included articles were compared and checked to those obtained after our selection, to ensure that we did not omit important articles.

Data extraction

A table was created for each vascular disease (LLVV, VTE, arterial diseases) to synthetize the main findings and the characteristics of each study: publication references, authors, study design, country, origin and number of participants, gender, age, study size, type of vascular events, diagnosis methods, type and methods to assess occupational constraints, confounders taken into account and the main results reported by authors.

Protocol

This systematic review was registered in the prospective register of systematic reviews (PROSPERO) (registration number CRD42019127652).

Study quality assessment -Risk of bias

To understand and assess the quality of these studies, two additional methods were applied.

Firstly, criteria of Strobe 8 and CARE 9 checklists were screened to evaluate the reporting of observational studies and case reports respectively. The studies were scored to reach a maximum value of 22 and 29 points, respectively. Secondly the quality of the studies and risk of bias were evaluated using several specific tools according to the study design.

For case reports, we applied the CARE checklist to assess their quality.

For the observational studies (prospective, retrospective, and cross-sectional studies) the Newcastle-Ottawa Scale (NOS) was used [START_REF] Wells | The Newcastle-Ottawa Scale (NOS) for assessing the quality of nonrandomised studies in meta-analyses[END_REF] . Three dimensions were evaluated: selection (representativeness of the population, ascertainment of the exposure or of case definition), comparability (control for confounding factors), and outcome (blind assessment of the outcome, adequacy of follow up etc.). Stars were assigned according to the study quality and bias risk. The total number of stars for cross-sectional studies is 10 while for case-controls and prospective studies a total of 9 could be reached. The higher the number of stars, the lower the bias risk is.

The predefinition of inclusion and exclusion criteria, the independent implication of two reviewers and a third in case of disagreement, and the several detailed tables were helpful to reduce the selection bias.

RESULTS

Characteristics of Eligible Studies

For LLVV: 457 articles were initially reported from which 138 not in English or French or on humans and 94 duplicates were excluded. Thus 225 were checked on titles and abstracts and 52 full texts were examined. Three overviews conducted in 1994 (Callam MJ.), 1997 [START_REF] Hobson | Venous insufficiency at work[END_REF] , and 2005 [START_REF] Beebe-Dimmer | The epidemiology of chronic venous insufficiency and varicose veins[END_REF] which provided only prevalence and incidence data were excluded. An article [START_REF] Tuchsen | Occupation, morbidity, and hospital admission[END_REF] did not fulfil the eligibility criteria because the authors did not propose results but discussed the interest of the use of their hospitalization register to explore the link between some diseases and occupational environment (Supplementary figure 1). Finally, 21 studies were included in the qualitative synthesis.

For VTE, the research yielded 535 articles, and 13 articles met all the eligibility criteria (Supplementary figure 2).

For aortic dissection and aneurysm respectively, 44 and 167 articles were retrieved, 1 and 2 articles suited the eligibility criteria, respectively (Supplementary figures 3 and 4).

For intermittent claudication, no articles explored the link between occupational environment and the disease (Supplementary figure 5).

No clinical trials were found on this topic. odds ratio with 95% confidence interval SRR, standardized risk ratio with 95% confidence interval RR, relative risk with 95% confidence interval HR, hazard ratio with 95% confidence interval Twenty one studies have explored the link between OC and LLVV: 16 cross-sectional studies, enrolling from 53 to 4,802 participants [START_REF] Chen | Varicose veins in hairdressers and associated risk factors: a crosssectional study[END_REF][START_REF] Basic | Orthostatics and chronic venous insufficiency in Croatian doctors of dental medicine[END_REF][START_REF] Labropoulos | Venous reflux in symptom-free vascular surgeons[END_REF][START_REF] Nia | Varicose veins of the legs among nurses: Occupational and demographic characteristics[END_REF][START_REF] Yun | A Study on Prevalence and Risk Factors for Varicose Veins in Nurses at a University Hospital[END_REF][START_REF] Ziegler | High prevalence of chronic venous disease in hospital employees[END_REF][START_REF] Stewart | Social medicine studies based on civilian medical board records. II. Physical and occupational characteristics of men with varicose conditions[END_REF][START_REF] Ebrahimi | Prevalence and risk factors of varicose veins among female hairdressers: a cross sectional study in north-east of Iran[END_REF][START_REF] Kohno | Standing posture at work and overweight exacerbate varicose veins: Shimane CoHRE Study[END_REF][START_REF] Criqui | Risk factors for chronic venous disease: the San Diego Population Study[END_REF][START_REF] Kontosic | Work conditions as risk factors for varicose veins of the lower extremities in certain professions of the working population of Rijeka[END_REF][START_REF] Tomei | Chronic venous disorders and occupation[END_REF][START_REF] Mekky | Varicose veins in women cotton workers. An epidemiological study in England and Egypt[END_REF][START_REF] Abramson | The epidemiology of varicose veins. A survey in western Jerusalem[END_REF][START_REF] Fowkes | Lifestyle risk factors for lower limb venous reflux in the general population: Edinburgh Vein Study[END_REF][START_REF] Lee | Lifestyle factors and the risk of varicose veins: Edinburgh Vein Study[END_REF] , 1 retrospective study [START_REF] Huang | Standing Posture at Work Does Not Increase the Risk of Varicose Veins among Health Care Providers in Taiwan[END_REF] , with 54,943 physicians and non-physicians, and 4 prospective studies including two conducted in the same population [START_REF] Tuchsen | Prolonged standing at work and hospitalisation due to varicose veins: a 12 year prospective study of the Danish population[END_REF][START_REF] Tuchsen | Standing at work and varicose veins[END_REF][START_REF] Tabatabaeifar | Varicose veins in the lower extremities in relation to occupational mechanical exposures: a longitudinal study[END_REF][START_REF] Robertson | Incidence and risk factors for venous reflux in the general population: Edinburgh Vein Study[END_REF] , ranging from 5,447 to more than 1,600,000 participants from hospital registries in Denmark, and with a follow-up varying from 3 to 31 years.

Lower limb varicose veins (Table 1 and Supplementary

Mean values and ranges obtained after the quality evaluations by NOS for the crosssectional and prospective studies were respectively: 5.1 [2 -8] (maximum 10), and 7 [5 -8] (maximum 9) stars.

The mean score calculated from Strobe checklist was 15.5 and varied between 7 and 22.

The LLVV diagnosis was established with several methods: the international disease classification was used in retrospective and prospective studies, while the cross-sectional studies exploited the medical data from Doppler ultrasound, medical records or selfadministered questionnaires.

Most of these studies proposed analyses adjusted on age and gender. Other well-known confounders (such as smoking status, body mass index, education level, physical activity etc.) were heterogeneously considered.

To analyse the occupational environment, two methods were used, on one hand using professional categories 15 19 20 23 25 30 such as hairdressers, dentists, nurses, physicians, secretary, scientific staff, cleaners, utility workers, and labourers, and on the other hand, using the types of constraint (standing, lifting, sitting, walking) to which the worker was exposed during the working period 16-18 21 22 24 26-29 31-35 . Regarding standing constraint, several measures of exposure duration were used such as hours/month, hours/day (with different thresholds according to the study).

Several studies exploring the link between time spent standing, expressed in hours/day or month, and LLVV found a significant dose-response effect 17 21 33 35 but not for Yun et al.

study [START_REF] Yun | A Study on Prevalence and Risk Factors for Varicose Veins in Nurses at a University Hospital[END_REF] and Edinburgh studies 28 29 34 . Thus, standing more than 3-4 hours/day seemed to increase the risk of LLVV in men as well as in women, compared to those less exposed (about 2.5-fold higher), and the degree of severity of the LLVV which is also associated to the number of years of service [START_REF] Nia | Varicose veins of the legs among nurses: Occupational and demographic characteristics[END_REF] .

In population in age to be employed, Tuchsen 2000 at al. [START_REF] Tuchsen | Standing at work and varicose veins[END_REF] showed that standing at work more than 75% of the time was associated with increased risk of LLVV (analyses adjusted for age, social group and smoking, respectively for men and women, RR=1.85 [95% CI 1.33-2.36] and RR=2.63 [95% CI 2.25-3.02]).

Moreover, some authors were interested by the effect of carrying or lifting heavy loads on LLVV during working period with contrasted findings. However in the most recent study conducted in a large sample involving men and women aged 18-65 years old, lifting more than 1 ton a day increase significantly the risk of LLVV [START_REF] Tabatabaeifar | Varicose veins in the lower extremities in relation to occupational mechanical exposures: a longitudinal study[END_REF] , but only for women in Edinburgh Study.

Sitting and walking were scarcely explored, and the few results were in favour of a nonsignificant link with LLVV 17 18 and from the Edinburgh study, sitting time at work appeared to be protective on vein reflux only in women 28 29 Only one study investigated the exposition to high temperatures at work with no significant association [START_REF] Kontosic | Work conditions as risk factors for varicose veins of the lower extremities in certain professions of the working population of Rijeka[END_REF] .

Concerning the occupational categories, compared to general population, the risk of LLVV was not increased among dentists [START_REF] Basic | Orthostatics and chronic venous insufficiency in Croatian doctors of dental medicine[END_REF] , physician and non-physician [START_REF] Huang | Standing Posture at Work Does Not Increase the Risk of Varicose Veins among Health Care Providers in Taiwan[END_REF] .

Venous thromboembolism (deep vein thrombosis and pulmonary embolism)

Thirteen articles were included in the current review (Table 2 and Supplementary table 2), including four prospective studies [START_REF] Kuipers | The absolute risk of venous thrombosis after air travel: a cohort study of 8,755 employees of international organisations[END_REF][START_REF] Rosengren | Psychosocial factors and venous thromboembolism: a long-term follow-up study of Swedish men[END_REF][START_REF] Suadicani | Jobs encompassing prolonged sitting in cramped positions and risk of venous thromboembolism: cohort study[END_REF][START_REF] Zoller | Socioeconomic and occupational risk factors for venous thromboembolism in Sweden: a nationwide epidemiological study[END_REF] with large study size (up to 389,530 participants) and about 20 years of follow-up, four case-control studies, two conducted in the same initial population 40 41 including respectively 97 and 192 cases, one among insured bank staff [START_REF] Dimberg | Deep venous thrombosis associated with corporate air travel[END_REF] , and one from clinic services [START_REF] Braithwaite | Venous thromboembolism risk associated with protracted work-and computer-related seated immobility: A case-control study[END_REF] and five case-reports [START_REF] Aldington | Prolonged seated immobility at work is a common risk factor for venous thromboembolism leading to hospital admission[END_REF][START_REF] Patel | Work ergonomics and e-thrombosis: a grievous yet preventable combination[END_REF][START_REF] Van Beeck | Deep vein thrombosis following prolonged kneeling: a case report[END_REF][START_REF] Beasley | eThrombosis: the 21st century variant of venous thromboembolism associated with immobility[END_REF][START_REF] Doctor | When Computers Can Kill-Two Unusual Cases of "E-Thrombosis[END_REF] . The vascular events were diagnosed using the International Classification Diseases (ICD8-10), imaging (Doppler ultrasound, pulmonary angiography and scan) or filed medical insurance claims.

All the studies adjusted their analyses on gender and age while other confounders, known as causal risk factors of VTE, were heterogeneously considered.

Among the eight observational studies, five of them recruited participants from hospital registers.

Prolonged sitting was the most studied occupational exposure in observational studies 38 40 41 43 and case reports 44 45 47 48 with contrasted results. Only the studies undertaken from the Wellington Hospital register 40 41 and clinical services [START_REF] Braithwaite | Venous thromboembolism risk associated with protracted work-and computer-related seated immobility: A case-control study[END_REF] Regarding social class, Rosengren et al. [START_REF] Rosengren | Psychosocial factors and venous thromboembolism: a long-term follow-up study of Swedish men[END_REF] found that the risk of PE was halved for whitecollars (HR=0.57 [95% CI 0.39-0.83]), which was also corroborated by Zöller study [START_REF] Zoller | Socioeconomic and occupational risk factors for venous thromboembolism in Sweden: a nationwide epidemiological study[END_REF] .

Air travel is a known risk factor of DVT (2 to 4 fold risk increase) [START_REF] Kuipers | Travel and venous thrombosis: a systematic review[END_REF] for passengers but the consequences for air travel professionals has been scarcely specifically explored.

Two studies focussed on determining incidence rate of VTE among business air travellers, its relationship with duration of travel, number of long-haul flights, and with the time passed after air travel.

Kuipers et al. [START_REF] Kuipers | The absolute risk of venous thrombosis after air travel: a cohort study of 8,755 employees of international organisations[END_REF] conducted a cohort study among more than 8,000 respondents (32% response rate) and VTE was confirmed for 53 employees. Overall incidence rate was 1.4/1,000 person-years (PY) compared to 1.0/1,000 PY in individuals unexposed to air travel.

Incidence rates were higher in women, with the number of flights, and with the travel time.

In Dimberg et al. case-control study [START_REF] Dimberg | Deep venous thrombosis associated with corporate air travel[END_REF] , incidence rate (phlebitis, thrombophlebitis or thromboembolism) was 2.5/1,000 employees. DVT incidence rate was 0.9/1,000 employees.

No statistically significant associations were found between VTE and number of missions, number of travel days, or number of days since last mission. aortic enlargement and should initially and periodically be examined using echocardiography.

Aortic dissection (

In 1960, Cohn [START_REF] Cohn | Rupture of dissecting aneurysm of the aorta. The relationship of effort to onset[END_REF] reported two cases of aortic aneurysm: one after an intense physical effort at work in a metal worker and a second exposed to chronic stress (bus mechanic).

DISCUSSION

The peripheral vascular disease can affect young workers, but there is still no study summarising the occupational factors that could participate in peripheral vascular diseases development.

The current systematic review of the literature aims to resume the relationship between lower limb peripheral venous diseases (LLVV, VTE [DVT and PE]), peripheral arterial disease (intermittent claudication, aortic dissection, and aortic aneurysm) and exposition to occupational constraints.

The link between vascular disease and work was assessed in two ways: by estimating the exposure duration to occupational constraints during a typical working period (expressed by day or month), or by using occupational social categories which allow an empirical evaluation of the exposure, usually facing the workers.

Lower limb varicose veins

The most explored potential occupational risk of varicose are prolonged standing 14 18 19 21 22 24 28 31-34 , walking 18 28 33 34 , sitting 17 18 26 28 , working overtime [START_REF] Nia | Varicose veins of the legs among nurses: Occupational and demographic characteristics[END_REF] , and heavy lifting 24 28 29 31 .

While some evidence provided further weight to the hypothesis concerning the link between prolonged standing posture and varicose, the obtained results need to be considered carefully. Indeed, if the working hours/day spent standing-up act on the risk of varicose in most of the studies, the threshold which can have an adverse effect, is difficult to determine:

>4 hours/day for patients recruited from hospital register [START_REF] Tabatabaeifar | Varicose veins in the lower extremities in relation to occupational mechanical exposures: a longitudinal study[END_REF] and for nurses [START_REF] Nia | Varicose veins of the legs among nurses: Occupational and demographic characteristics[END_REF] studies, >3 hours for hairdressers [START_REF] Ebrahimi | Prevalence and risk factors of varicose veins among female hairdressers: a cross sectional study in north-east of Iran[END_REF] , 5 hours only for people who have upright standing posture without some movements in the same time for Kohno study [START_REF] Kohno | Standing posture at work and overweight exacerbate varicose veins: Shimane CoHRE Study[END_REF] . Moreover, this link was not confirmed by Yun [START_REF] Yun | A Study on Prevalence and Risk Factors for Varicose Veins in Nurses at a University Hospital[END_REF] , Kontosic [START_REF] Kontosic | Work conditions as risk factors for varicose veins of the lower extremities in certain professions of the working population of Rijeka[END_REF] and Edinburgh 34 studies, using dichotomized variables: > 4hours/day vs <4 hours/day or exposed vs unexposed people. Chen et al. [START_REF] Chen | Varicose veins in hairdressers and associated risk factors: a crosssectional study[END_REF] found only significant results in hairdressers aged more than 45 years old (with large confidence intervals) and Tuchsen et al. [START_REF] Tuchsen | Prolonged standing at work and hospitalisation due to varicose veins: a 12 year prospective study of the Danish population[END_REF] only among women (population recruited from hospital register). Moreover, two explanations can be put forward. Firstly, none of the studies have considered the number of years of exposure to this occupational constraint, which can explain the inconstancy of these findings. Secondly, only two prospective studies were undertaken, both with patients from hospital registers which can lead to some bias by omitting people with no or mild symptoms and who do not need hospital care. The link between the degree of severity of varicose (assessed by the CEAP classification) and occupational constraints was considered in only one study [START_REF] Nia | Varicose veins of the legs among nurses: Occupational and demographic characteristics[END_REF] which demonstrated that being exposed to a standing-up posture more than 4 hours/day increased by two the degree of severity of varicose.

Some strong pathophysiological mechanisms can explain these links. Indeed, prolonged standing-up posture provokes an increased hydrostatic venous pressure that, combined to the incapacity to reduce venous pressure with regular stimulation of peripheral muscle pump [START_REF] Meissner | The hemodynamics and diagnosis of venous disease[END_REF] leads to venous stasis inducing a high risk of varicose veins and thrombosis. Using ultrasound Doppler, Labropoulos et al. [START_REF] Labropoulos | Venous reflux in symptom-free vascular surgeons[END_REF] were the to demonstrate that people with occupations involving prolonged standing position (as vascular surgeons) without symptoms of venous insufficiency, had a higher risk of venous reflux in lower limbs compared to unexposed people, suggesting that prolonged standing leads to superficial venous incompetence.

Consequences of time spent sitting, walking, carrying heavy loads at work were little explored, and were not found to significantly increase the risk of varicose veins.

Walking is supposed to favour venous return due to the calf muscular contraction. Only one study considered standing and walking in the same variable. People working more than 4 hours/day were at high risk of varicose. In this study, stamping on feet rather than walking was probably considered [START_REF] Tabatabaeifar | Varicose veins in the lower extremities in relation to occupational mechanical exposures: a longitudinal study[END_REF] . Only one study dealing with heat exposure and varicose was retrieved, without any significant risk. It could be of interest to investigated potential occupations at risk such as cooks, bakers, dry-cleaner's or foundry employees.

Overall, these results need to be confirmed by future prospective studies.

Venous thromboembolism

Several occupational constraints have been studied in link with DVT and PE, but the types of occupational constraints and the results differ substantially from those studied for LLVV.

While cases of VTE following immobility due to playing computer games (designated as 'ethrombosis') is documented by several case reports [START_REF] Lippi | e-thrombosis: epidemiology, physiopathology and rationale for preventing computer-related thrombosis[END_REF] , the studies specifically focused on the link between DVT/PE and working conditions imposing a prolonged sitting time are more scarce: three case-control studies 40 41 43 found an increased risk with extended sitting-time, while the only prospective study [START_REF] Suadicani | Jobs encompassing prolonged sitting in cramped positions and risk of venous thromboembolism: cohort study[END_REF] did not confirm it. However, strong and complex pathophysiological mechanisms support this link. According to Virchow's triad, venous stasis is one of the main components of the thrombotic risk.

As exposure durations to prolonged sitting while playing computer (12-48 hours as described in several case-reports) are not comparable to exposure durations of prolonged sitting during working day periods (8-10 hours/day), results regarding playing computer are hard to transpose to general working population. More researches are needed to reinforce the hypothesis that sitting time at work could be considered as an occupational risk of DVT, notably by distinguishing in detail time spent sitting at work and out of work (including leisure such as gaming, reading, watching TV, eating…) and also the number of years of exposure.

If the risk of DVT in air travel for passengers in long distance flights is well documented [START_REF] Gavish | Air travel and the risk of thromboembolism[END_REF] , the consequences for airline cabin crew and pilots are less investigated.

Lower limb DVT and PE also appear to be related to persistent stress and low socioeconomic level 37 39 . The 2014 literature review of Austin et al. [START_REF] Austin | Stress and hemostasis: an update[END_REF] on stress and hemostasis suggested that stress at work could be associated to elevated levels of fibrinogen and clotting factor VII and to decreased fibrinolysis capacity. Low socioeconomic status (before instance determined with education attainment and social class) can induce chronic stress. Low socioeconomic status has been found to be associated to elevated levels of fibrinogen, factor VII, and von Willebrand factor. Moreover, men with high job strain exposed to acute stress had higher von Willebrand factor levels. On the contrary, those who felt happy during the day at work had lower levels of fibrinogen after adjusting for sociodemographic factors and cardiovascular risk factors.

Prevention measures have been described in the literature and some recommendations for people suffering lower limb DVT or PE have been suggested: take breaks regularly in order to move the legs, and develop reminder systems to encourage to get up every 30-60 minutes [START_REF] Patel | Work ergonomics and e-thrombosis: a grievous yet preventable combination[END_REF] .

Mitsuya et al. [START_REF] Mitsuya | Prevention of deep vein thrombosis in VDU work[END_REF] have suggested to sit in a reclining posture and occasionally use a footrest, stretch the legs, and walk 10 min during breaks. However, studies to assess the effectiveness of such recommendations are still needed.

Consequences of the occupational exposure to chemical toxics on DVT or PE have been scarcely explored. However, it would be interesting to investigate this topic in future research. Indeed even if mechanisms are not fully similar with DVT or PE, occupational exposure to organic solvents has been pointed out as a potential novel risk factor for pulmonary veno-occlusive disease [START_REF] Montani | Occupational exposure to organic solvents: a risk factor for pulmonary veno-occlusive disease[END_REF] .

Arterial diseases

Few studies have explored the link between arterial disease and occupational constraints. It is surprising given that these arterial diseases are, among others, related to hypertension and that some occupational factors are suspected to increase blood pressure, notably by occupational stress.

Regarding lower limbs intermittent claudication, workers who seem to be the most affected are the manual workers. These observations are probably linked to the fact that manual worker usually have more physical activity during their job revealing by the effort ischemia, a peripheral arterial disease that can be completely asymptomatic in subjects not practicing physical efforts. Contrary to upper limbs arteritis [START_REF] Nilsson | Hand-arm vibration and the risk of vascular and neurological diseases-A systematic review and meta-analysis[END_REF] , no link with vibrations has been demonstrated.

Endothelial vascular dysfunction induced by noise exposure is suspected by assuming the role of the adrenergic system 59 which can explain an increased incidence of arterial hypertension, myocardial infarction, heart failure, and stroke. However, no study has specifically explored the relation between noise exposure and peripheral arterial diseases and aneurism.

Strengths and limitation at study and outcome level

PRISMA guideline was used to select all the studies, giving transparency and homogeneity in method used, and reproducibility of searches.

Depending on the type of vascular disease or on the type of occupational exposures, the number of studies retrieved is quite different. Thirty-four studies were retained on lower limb peripheral venous diseases while there were only three studies on peripheral arterial diseases for which the potential role of occupational constraints was little explored.

No interventional trials, allowing to provide a better level of evidence than the observational studies included in this review (17 cross-sectional, 8 prospective and 6 retrospective studies, and 6 case reports), were found.

The case-control studies can induce difficulties to describe the working conditions accurately (memory bias). Moreover, the outcomes were measured differently for some vascular disease, such as varicose measured by ultrasound Doppler (which constitutes Gold standard method), or by self-questionnaires, or by phone interviews.

Given the numerous exposure assessment methods (occupational status, number of hours exposed), the few studies available for each vascular disease, the different thresholds of exposure used, and the differences in the recruitment of the studied populations, carrying out meta-analyses did not seem adapted to the included studies. But it could be conducted and be more informative if new studies, particularly prospective ones, are undertaken. Thus, the evidence of the potential associations between vascular diseases and occupational constraints were assessed based on the number and quality of the studies, and on the consistency of the results.

Strengths and limitation at review level

Only the articles written in English and French were included in this review which can induce a weak selection bias.

Publication bias cannot be excluded. Indeed, positive studies are more likely to be published, possibly explaining the small number of articles retrieved on arterial diseases. Also, the bias of multiple publications from the same study population must be considered (e.g. Danish population register 31 32 ).

The quality of the studies evaluated with the most recent quality scales (NOS, CARE) and by the latest publication guidelines (Strobe checklist) often varied according to the year of publication. Indeed, we choose to include all studies whatever the date of publication, which can lead to a low-quality assessment score considering the guidelines used at this time.

The NOS is very often used in systematic review to evaluate quality of observational studies.

However, there are some limits to use this scale [START_REF] Stang | Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses[END_REF] . Indeed, most of retained studies in this review are case-control studies, often undertaken in specific population with no possibility to extend to general population, leading to a lower quality score even when the results are interesting.

Moreover, quality assessment of the studies relied only the information reported in the articles which can be subject to selective presentation (e.g., omission of non-significant results evaluated as not relevant by the authors). This current review is concerned by this limitation as are most of the reviews undertaken.

CONCLUSION

In regard to the results, it seems that there are some associations between occupational exposures and peripheral vascular diseases, with more data on venous vascular diseases than arterial diseases.

Although some links between occupational conditions (as prolonged standing time and varicose or sitting time and DVT) have been suggested, there is no sufficient evidence to determine a precise threshold of exposure due to the heterogeneity of the studies. Thus, none of the concerned vascular diseases are sufficiently documented to be considered as official occupational diseases.

Some little explored occupational constraints, such as carrying heavy loads, stress at work, and exposure to high temperatures have emerged more recently notably in relation to LLVV but need to be better explored. Finally, more prospective studies on the topic are still needed, especially multidisciplinary studies encompassing vascular surgeons, vascular clinicians, occupational physicians, and general practitioners, to complete and to update the knowledge on the relationship between occupational exposures and vascular diseases.

Lower limb varicose veins

Deep vein thrombosis and pulmonary embolism

Table 2 )Table 1 : Varicose veins study characteristics.

 21

	Authors, year	Study design,	Participants	Vascular Events Occupational	Confounders	Results	Quality
	of publication	country,	(gender, age)		constraints and			assessme
		follow-up or			environmental			nt
		recruitment			exposures
		period
	Stewart et al.	Cross-	Three English	Varicose veins	Occupational status	standardized	Standardized prevalence ratios in occupational groups:	Strobe:
	1955	sectional	regions	(Civilian		on age and	Boot and Shoe: 116 (p<0.001)	13/22
		England	♂3,582	Medical Board		region	Clerical: 69 (p<0.001)
		Recruitment:	<45 yo	records)			Professional and administrative: 81 (p<0.01)	NOS: 4/10
		1941-1944
	Mekky et al.	Cross-	7 cotton mills	Varicose veins	Position at work	none	Prevalence: 32% England, 6% Egypt	Strobe:
	1969	sectional	♀971	(clinical			Prevalence, according to working condition:	13/22
		England and		examination)			English mills: Sitting: 18.2%, Walking: 28.7%, Mixed
		Egypt					job: 35.4%, Standing: 56.6% (p<0.001)	NOS: 2/10
		Recruitment:					Egyptian mills: NS
		1964-1966

Lee et al 2003

	Ziegler et al Tuchsen et al. Huang et al.	Cross-Prospective Retrospectiv	mean age: 36-39 Vienna's general Central National Health	Chronic venous Varicose veins Varicose veins	Group 1: medical Prolonged standing Occupation:	none cardiovascular age, smoking, age, gender,	Occurrence of CVD according to groups, p<0.02: People standing more than 75% of working hours (ref: Ref: general population	Strobe: Strobe: Strobe:
	2003 2000 2017	sectional Denmark e cohort	yo hospital, population Insurance	disease (CEAP (ICD-8: 454) (ICD-9)	doctors and nurses at work and/or physician, non-	diseases social group deep venous	Group 1: 31% <75%): Being a physician:	OR=0.86 (0.53, 1.40)	13/22 21/22 18/22
		Austria Follow-up: Taiwan	employees register Research	classification) from hospital	Group 2: medical walking physician health care	Stratified on thrombosis	Group 2: 22% ♀ SRR=2.63 (2.25, 3.02) Being a non-physician: OR=1.43 (0.82, 2.50)
		1991-1993 Period: 2007-	♂58 ♂727 145 Database:	register	technician assistants, (questionnaire, providers	gender	Group 3: 46% ♂ SRR=1.85 (1.33, 2.36)	NOS: 2/10 NOS: 8/9 NOS: 6/9
		2011	♀161 ♀878 756 Physician		secretaries and interview by phone)		Mean period of standing at work (h/day), occurrence of
	Abramson 1981 Labropoulos 1995 Tomei et al. 1999 Kontosic et al. 2000 Fowkes et al 2001 Criqui et al 2007 Basic et al. 2014 Chen et al. 2014 Kohno et al 2014 Yun et al. 2018 2015 et al. Tabatabaeifar Ebrahimi et al 2015 Tuchsen et al. 2005 Table 1 footnote: Cross-sectional Israel Recruitment: 1969-1971 Cross-sectional Recruitment: 1991-1994 Cross-sectional Italy Cross-sectional Croatia Cross-sectional Scotland (Edinburgh Vein Study) Recruitment: 1994-1996 Cross-sectional Scotland (Edinburgh Vein Study) Recruitment: 1994-1996 Cross-sectional USA Recruitment: 1994-1998 Cross-sectional Croatia Cross-sectional Southern Taiwan Cross-sectional Japan Recruitment: Cross-sectional Korea 2014 1980-2011 Follow-up: Denmark Prospective Cross-sectional Iran Recruitment: 2012 Prospective Denmark Follow-up: 1991-2002 ♂, men Sharif et al. 2015 Cross-sectional Iran Recruitment: 2010 ♀, women yo, years old Robertson et al. 2014 Prospective Scotland (Edinburgh Vein Study) Follow-up: 13 years NOS, Newcastle-Ottawa scale NS, not significant BMI, body mass index CVD, cardiovascular disease CEAP classification, Comprehensive Classification System for Chronic Venous Disorders Western Jerusalem ♂2,245 ♀2,557 Varicose veins (clinical examination) Time spent sitting, standing, and walking during working hours; lifting or carrying of heavy weights, physical exertion (interview at home) 28 vascular surgeons 25 normal volunteers men, 29-45 yo Venous reflux in the lower extremities (colour-flow duplex imaging) Prolonged standing Industrial workers, stoneworkers, office workers Chronic venous disorders (clinical examination by Standing, sitting, walking during working time (questionnaire) Rijeka Community ♂530 ♀794 Varicose veins (clinical examination by trained physicians) Occupational status, standing, moving, lifting, high temperature 19-60 yo scientific staff 20-59 yo ♂24,802/♀4,042 Registers of 12 general practices ♂609 ♀739 18-64 yo Varicose vein (clinical examination), Venous reflux (Duplex scan) Visual analogue scales of time spent sitting, standing, walking, and heavy lifting (never to all the time) (self-administered questionnaire) Registers of 12 general practices ♂699 ♀867 18-64 yo Varicose vein (clinical examination, Basle Study classification), Venous reflux (Duplex scan) Visual analogue scales of time spent sitting, standing, walking, and heavy lifting (never to all the time) (self-administered questionnaire) Group 3: cleaners and utility workers (self-questionnaire) Current and retired employees of the University of California, San Diego: ♂854 ♀1,580 40-79 yo Varicose veins (doppler examination, CEAP classification) Occupational status (laborers, no laborers) 60 dentists (median 42 yo) 60 other occupation (median 38 yo) ♂15 ♀166 average age 45.8 yo Lower limb varicose veins (self-administered questionnaire) Hairdressers Prolonged standing at work (self-administered questionnaire) ♂113 ♀205 ≥45 yo Varicose veins (doppler examination, CEAP Occupation, duration of standing per day mean 42-45 yo (questionnaire) 18-65 yo years ♀21,777 Nurses in a university hospital ♂7 ♀407 mean age 30 yo Varicose veins (doppler ultrasound) Number of daily working hours in a static standing, walking, and sitting position number of consecutive service Ramazzini Centre ♂16,259 hospital register Exposure Matrix) at the Danish 10:183) (Lower Body Job Database (MRD) 454, ICD-total load lifted Research surgery (ICD-8: standing/walking and Musculoskeletal Varicose veins Time spent questionnaire) Gender unknown Lower limb varicose veins (questionnaire, ultrasonograph (Duplex scan) (self-administered y) Being a dentist ♀197 (hairdresser) 18-68 yo Varicose veins (questionnaire + standard physical examination, severity score) Duration of standing per day (random sample Non-physician of 5,940 ♂7,984/♀18,115 participants) General Central Varicose veins Prolonged standing population population (ICD-8: 454, at work and/or (matched 1:1) register ICD-10:183) walking; time spent ♂2,939 from hospital carrying and Hospital nurses ♂58; ♀145 < 30 yo (n=81); 30-40 yo (n=77); > 40 yo (n=45) Varicose veins (CEAP classification: clinical degrees, C0 to C6) Time sitting, standing, walking posture, and overtime (self-questionnaire) ♀2,708 20-59 yo register lifting>20 kg (questionnaire, interview by phone) Registers of 12 general practices ♂390 ♀490 18-64 yo Varicose vein (clinical examination, Basle Study classification), Venous reflux Visual analogue scales of >50% of time spent sitting, standing, walking, and heavy lifting (never to all the time) ICD, International Classification of Diseases OR,	age, gender age job classification gender, age, BMI, flat feet, duration of fertile period/ pregnancies/d eliveries, family history of varicose veins stratified on gender; age, gastrointestina l habits, smoking, BMI stratified on gender; age, diet intake, BMI, smoking age, ethnicity stratified on age (≤45 yo, >45 yo) BMI, gender, age, family history, physical age, pregnancy, compression stocking period smoking activity, physical age, BMI, none age, BMI, pregnancy, family history, high blood age, smoking, social group pressure, oral Stratified on contraceptive, gender constipation gender, age, BMI, education level, family history age, gender	Much standing (ref: Little standing): OR= 1.6 (p<0.01) Lifting or carrying of heavy weights, physical exertion at work: no significant associations No venous hemodynamic abnormalities: 68% of the control group / 48% of the vascular surgeons (p=NS) Venous reflux: 32% of the control group / 52% of the vascular surgeons (p = 0.039) Prevalence: industrial workers (39.28%), stoneworkers (24.16%) and office workers (22.11%) Standing for 50% of the work shift (ref: <50%): OR= 1.07, p<0.001 At workplace (ref: no) Standing: ♂ OR= 2.53 (0.96, 6.73) ♀ OR= 0.67 (0.33, 1.36) Moving: ♂ OR= 1.12 (0.57, 2.17) ♀ OR= 0.63 (0.33, 1.18) Carrying heavy loads: ♂ OR= 0.82 (0.52, 1.29) ♀ OR= 0.79 (0.55, 1.13) High temperature: ♂ OR= 0.96 (0.57, 1.62) ♀ OR= 1.22 (0.79, 1.91) CVD vs absence of CVD, p<0.02: Mobility at work (ref: visual analogue scale<5) Sitting: ♂ OR= 1.09 (0.83, 1.43) ♀ OR= 0.75 (0.57, 0.99) Standing: ♂ OR= 1.04 (0.77, 1.40) ♀ OR= 1.01 (0.76, 1.34) Walking: ♂ OR= 0.93 (0.68, 1.27) ♀ OR= 0.88 (0.65, 1.18) Heavy lifting: ♂ OR= 0.96 (0.68, 1.38) ♀ OR= 1.02 (1.45, 1.54) Mobility at work (ref: visual analogue scale<5) Sitting: ♂ OR= 1.34 (0.86, 2.11) ♀ OR= 0.53 (0.32, 0.87) Standing: ♂ OR= 1.12 (0.70, 1.80) ♀ OR= 1.28 (0.79, 2.08) Walking: ♂ OR= 1.16 (0.70, 1.91) ♀ OR= 0.96 (0.57, 1.60) Heavy lifting: ♂ OR= 0.90 (0.50, 1.61) ♀ OR= 1.32 (0.66, 2.62) ♂ 4.4 / 2.7 ♀3.9 / 3.2 Laborers, men (ref: no laborer): OR= 3.24 (1.21, 8.67) Standing at work (ref: No or <5 h a day): With substantial movement: OR= 0.89 (0.40, 1.98) Upright posture: OR= 1.98 (1.04, 3.77) OR=3.40 (1.27, 9.09) Up (stand + walk, ref: ≤4h): 3.31) Work posture (ref: <2h/day): Stand: 2-4h OR=1.03 (0.53, 2.0) Walk: 2-4h OR=0.92 (0.27, 3.14) Sit: 2-4h OR=0.64 (0.33, 1.25) ≥4h OR=0.58 (0.27, 1.21) ≥1000-≤4900: HR= ♂ 3.95 (2.32, 6.73) / ♀ 2.54 (1.95, >0-<1000: HR= ♂ 2.65 (1.63, 4.32) / ♀ 2.1 (1.6, 2.76) ≥4h OR=1.70 (0.55, 5.25) Lifting (kg/day, ref: 0): ≥6-≤7.3: HR=♂ 3.17 (2.06, 4.89) /♀ 2.34 (1.72, 3.19) ≥4h OR=1.53 (0.75, 3.14) ≥4-<6: HR= ♂ 2.65 (1.52, 4.62) / ♀ 2.42 (1.91, 3.06) Standing/walking (hours/day, ref: <4): No statistically significant difference between-group according to the presence of varicose leg veins (p=0.835) Duration of Standing per day (ref: ≤3 hours): > 3 hours: OR= 2.34 (1.05, 5.22) Standing more than 75% of working hours: ♀ RR=1.82 (1.12, 2.95) ♂ RR=1.75 (0.92, 3.34) Heavy lifting (>20 kg): ♀ RR=1.16 (0.59, 2.31) ♂ RR=0.81 (0.35, 1.90) Link between incidence of varicose veins and mobility at work Sitting: OR= 1.0 Standing: OR= 1.0 (0.3, 3.2) Walking: OR= 1.5 (0.6, 3.8) Heavy lifting: OR= 1.5 (0.6, 3.9)	Strobe: 17/22 NOS: 7/10 Strobe: 10/22 NOS: 4/10 Strobe: 13/22 NOS: 5/10 Strobe: 17/22 NOS: 7/10 Strobe: 15/22 NOS: 7/10 Strobe: 16/22 NOS: 7/10 Strobe: 15/22 NOS: 6/10 Strobe: 14/22 NOS: 6/10 NOS: 6/10 16/22 Strobe: NOS: 8/9 NOS: 5/10 22/22 14/22 Strobe: Strobe: Strobe: 7/22 NOS: 2/10 Strobe: 17/22 Strobe: NOS: 4/10 21/22 NOS: 5/9 Strobe: 18/22 NOS: 6/10 Strobe: 16/22 NOS: 8/9
		2012	♂308	a trained classification)		activity,
				physician)		lumber corset,
						history of

Monthly standing work hours (ref <120 hours; OR for ≤ 45 yo and > 45 yo respectively): 121-168H: OR: 2.4 (0.1, 55.6) / OR: 9.7 (0.7, 132.5) 169-208H: OR: 2.0 (0.2, 24.2) / OR: 7.4 (0.6, 89.9) 209-260H: OR: 0.5 (0.0, 11.3) / OR: 6.4 (0.5, 86.2) 261-360H: OR: 5.2 (0.4, 75.8) / OR: 31.8 (1.8, 566.5) Leg varicose intensity (C0-C6) and standing (ref: <2 h): 2-4 h: OR= 0.9 (0.4, 2.2) >4 h: OR= 2.3 (1.01, 5.4) Leg varicose prevalence and standing (ref: <2 h): 2-4 h: OR= 1.3 (0.4, 3.7) >4 h: OR= 3.8 (1.2, 11.9) No significant link with time spent sitting or walking Overtime (hours) (ref: no) OR= 1.02 (1.01, 1.03) Leg varicose intensity (C0-C6) and years of service: OR= 1.07 (1.03, 1.12)

Table 2 : Venous thromboembolism study characteristics.

 2 Case-control studies obtained 5 to 6/9 stars at NOS evaluation, while prospective studies reached 8/9 with an average of 7 stars. The scores obtained with the STROBE checklist varied between 14 and 21/22. The quality of the case reports evaluated by the CARE checklist varied between 9 and 20/29 fulfilled items.

	Authors, year	Study design,	Participants	Vascular Events Occupational	Confounders Results
	of publication	country,	(gender, age)	constraints and
		follow-up or		environmental
		recruitment		exposures
		period

  at work during the previous 6 weeks was suspected. Two of the three components of Virchow's triad may have been present: venous stasis (prolonged immobility) and vascular endothelial microtrauma (tight straps). The third component, hypercoagulability, could not be confirmed.Rosengren et al. aimed to determine the effect of psychosocial factors on VTE[START_REF] Rosengren | Psychosocial factors and venous thromboembolism: a long-term follow-up study of Swedish men[END_REF] . The study consisted in a mean 23-year follow-up of about 7,000 men and evaluated stress comprising stress at work, stress at home, sleeping difficulties, anxiety, and irritability. Men with persistent stress had higher risk of developing PE (HR=1.66 [95% CI 1.12-2.48]) compared to men with none or little stress. No link was found for DVT.

	analysed the number of hours spent
	sitting at work with around 10% increase of the risk of VTE per hour seated. Moreover,
	eating lunch at their desk and having their own desk at work significantly increased the risk
	of VTE (respectively, OR= 2.2 [95%IC 1.1-4.1] and OR= 2.1 [95%IC 1.3-3.3]), with no
	protective effect of adjustable chair use and stretching legs 40 .
	The other occupational exposures were less documented.
	No link between prolonged kneeling and VTE has been clearly identified yet. But a case

report was presented by van Beeck et al. in 2014

[START_REF] Van Beeck | Deep vein thrombosis following prolonged kneeling: a case report[END_REF]

. A 41-year-old man presented with DVT in the left lower limb without no thrombosis risk factors. The involvement of kneeling 8 hours/day

Table 3 and supplementary table 2)Table 3 : Arterial diseases study characteristics

 3

	Authors,	Study design,	Participants	Vascular Events	Occupational	Confounders	Results	Quality
	year of	country,	(gender, age)		constraints and			assessment
	publication	follow-up or			environmental
		recruitment			exposures
		period
	Cohn	Case reports	Case 1: ♂ 56 yo	Aortic aneurysm	Case 1: metal	NA	Case 1: pain after heavy lifting	Care: 10/29
	1960	(2) USA	Case 2: ♂ 59 yo		Case 2: bus worker		Case 2: pain after chronic stress
		1958			mechanic
	Owada et al.	Case-control	91 sudden	Aortic dissection	Duration of global	age, sex,	All sudden deaths	Strobe:
	1999	Japan	deaths		stress	occupations,	Short-term stress: OR= 1.78 (0.90, 3.5)	18/22
		Recruitment:	(including 4		(telephone	cardiovascular	Long-term stress: OR= 2.63 (1.30, 5.35)
		1994-1998	acute aortic		interviews from	risk factors		NOS: 5/9
			dissections),		family members)
			♂77/♀14 from
			Segamihara
			city
			958 controls
			(health check)
			from Niigata
			city
			20-59 yo
	Aparci et al.	Cross-sectional	Etimesgut	Aortic	Physical activity	none	Aortic diameters (millimetres), respectively for OAT and	Strobe:
	2013	Turkey	Military	echocardiographic	during work:		SAT	9/22
		2011	Hospital,	parameters	Ordinary activity		Aortic root: 33.5±1.9 / 35.6±3.0, p=0.001
			military		trainers (OAT,		Aortic root index: 16.7±1.0 / 17.6±1.5, p=0.004	NOS: 7/10
			personnel		exercise duration		Ascending aorta: 34.4±1.9 / 36.8±3.0, p=0.001
			♂60		<2h, <2		Ascending aorta index: 17.2±1.1 / 18.2±1.5, p=0.002
			mean age ~38		times/week)
			yo		Strenuous activity
					trainers (SAT, daily
					exercise leading
					4000 kcal/day
					energy
					consumption)

Table 3

 3

	footnote:
	♂, men

table 2 : Newcastle Ottawa Score

 2

	Varicose AND occupation OR	-Deep vein thrombosis AND occupation OR
	occupational	occupational
	-Chronic venous insufficiency AND	-Phlebitis AND occupation OR occupational
	occupation OR occupational	-Pulmonary embolism AND occupation OR
	-Varicose AND job	occupational
	-Chronic venous insufficiency AND job	-Venous thromboembolism AND occupation
	-Varicose AND employment	OR occupational
	-Chronic venous insufficiency AND	-Deep vein thrombosis AND job
	employment	-Phlebitis AND job
		-Pulmonary embolism AND job
		-Venous thromboembolism AND job
		-Deep vein thrombosis AND employment
		-Phlebitis AND employment
		-Pulmonary embolism AND employment
		-Venous thromboembolism AND
		employment
	Intermittent claudication	Aortic dissection
	-Claudication of the lower limb AND	-Aortic dissection AND occupation OR
	occupation OR occupational	occupational
	-Arteriopathy of the lower limb AND	-Aortic dissection AND job
	occupation OR occupational	-Aortic dissection AND employment
	-Obliterating arteriopathy of the lower
	limb AND employment
	-Obliterating arteriopathy of the lower	Aortic aneurysm
	limb AND occupation OR occupational
	-Claudication of the lower limb AND job	-Aortic aneurysm AND occupation OR
	-Arteriopathy of the lower limb AND job	occupational
	-Intermittent claudication AND job	-Aortic aneurysm AND job
	-Obliterating arteriopathy of the lower	-Aortic aneurysm AND employment
	limb AND job

ACKNOWLEDGMENTS

Pr Vanina Bongard for her advice.

DATA SHARING

Data and material will be made available by the authors upon reasonable request (contact: corresponding author).

Very few studies explored the link between aortic dissection and occupational exposure.

In 1999, Owada et al. [START_REF] Owada | Risk factors and triggers of sudden death in the working generation: an autopsy proven case-control study[END_REF] aimed to determine the risk factors of sudden death among a working population with a case-control study (NOS: 5/9 stars). Among the 91 cases of sudden death, 4 (4.4%) were caused by acute aortic dissection (three men and one woman).

Occupations were only compared between all sudden deaths and controls. There was a significant difference in terms of occupations (p<0.001): proportion of office workers was lower in the sudden death group than in controls, while proportion of workers in manufacture, construction, transportation and telecommunication industries, manual workers, unemployed people and housewives were higher than in controls.

Aortic aneurysm (Tables 3 and supplementary table 2)

The search yielded only two references.

In a cross-sectional study (NOS evaluation: 7/10 stars), Aparci et al. [START_REF] Aparci | Enlargement of the aorta: An occupational disease?[END_REF] compared two groups: participants with daily high intensity physical activity (isometric-type strenuous training, weight lifting, benching, jumping, squatting and hanging up) necessitating at least a 4000 kcal/day energy consumption versus people who participated in physical activity no more than twice per week. They found that echocardiographic measurements of the aorta and intensity of physical activity at work were related. Patients of the first group had larger aortic root and ascending aorta diameters than those of the second group. The diameter of the ascending aorta was significantly correlated to the type of occupation. They finally suggested that some occupations (for example, members of the military or of the army, security, professional weightlifters, endurance athletes, etc.) were at a risk for the development of

DISCLOSURE

The authors have no conflict of interest.

SOURCES OF FUNDING

None.

AUTHOR CONTRIBUTIONS

MT, YE, SHYK, and JF: Conducted the article selection, and screening. YE, and SHYK: Prepared the material and methods and results, and the discussion sections. FXL, CC, FD, JF, and ABR: Contributed substantially to the discussion and reviewed all the manuscript.

All authors read and approve the final manuscript.

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