Assessment of Subclinical Atherosclerosis in Asymptomatic People In Vivo: Measurements Suitable for Biomarker and Mendelian Randomization Studies.

BACKGROUND: One strategy to reduce the burden of cardiovascular disease is the early detection and treatment of atherosclerosis. This has led to significant interest in studies of subclinical atherosclerosis, using different phenotypes, not all of which are accurate reflections of the presence of asymptomatic atherosclerotic plaques. The aim of part 2 of this series is to provide a review of the existing literature on purported measures of subclinical disease and recommendations concerning which tests may be appropriate in the prevention of incident cardiovascular disease. METHODS: We conducted a critical review of measurements used to infer the presence of subclinical atherosclerosis in the major conduit arteries and focused on the predictive value of these tests for future cardiovascular events, independent of conventional cardiovascular risk factors, in asymptomatic people. The emphasis was on studies with >10 000 person-years of follow-up, with meta-analysis of results reporting adjusted hazard ratios (HRs) with 95% CIs. The arterial territories were limited to carotid, coronary, aorta, and lower limb arteries. RESULTS: In the carotid arteries, the presence of plaque (8 studies) was independently associated with future stroke (pooled HR, 1.89 [1.04-3.44]) and cardiac events (7 studies), with a pooled HR, 1.77 (1.19-2.62). Increased coronary artery calcium (5 studies) was associated with the risk of coronary heart disease events, pooled HR, 1.54 (1.07-2.07) and increasing severity of calcification (by Agaston score) was associated with escalation of risk (13 studies). An ankle/brachial index (ABI) of <0.9, the pooled HR for cardiovascular death from 7 studies was 2.01 (1.43-2.81). There were insufficient studies of either, thoracic or aortic calcium, aortic diameter, or femoral plaque to synthesize the data based on consistent reporting of these measures. CONCLUSIONS: The presence of carotid plaque, coronary artery calcium, or abnormal ankle pressures seems to be a valid indicator of the presence of subclinical atherosclerosis and may be considered for use in biomarker, Mendelian randomization and similar studies.

Use of Artificial Intelligence With Deep Learning Approaches for the Follow-up of Infrarenal Endovascular Aortic Repair.

INTRODUCTION: Endoleaks represent one of the main complications after endovascular aortic repair (EVAR) and can lead to increased re-intervention rates and secondary rupture. Serial lifelong surveillance is required and traditionally involves cross-sectional imaging with manual axial measurements. Artificial intelligence (AI)-based imaging analysis has been developed and may provide a more precise and faster assessment. This study aims to evaluate the ability of an AI-based software to assess post-EVAR morphological changes over time, detect endoleaks, and associate them with EVAR-related adverse events. METHODS: Patients who underwent EVAR at a tertiary hospital from January 2017 to March 2020 with at least 2 follow-up computed tomography angiography (CTA) were analyzed using PRAEVAorta 2 (Nurea). The software was compared to the ground truth provided by human experts using Sensitivity (Se), Specificity (Sp), Negative Predictive Value (NPV), and Positive Predictive Value (PPV). Endovascular aortic repair-related adverse events were defined as aneurysm-related death, rupture, endoleak, limb occlusion, and EVAR-related re-interventions. RESULTS: Fifty-six patients were included with a median imaging follow-up of 27 months (interquartile range [IQR]: 20-40). There were no significant differences overtime in the evolution of maximum aneurysm diameters (55.62 mm [IQR: 52.33-59.25] vs 54.34 mm [IQR: 46.13-59.47]; p=0.2162) or volumes (130.4 cm3 [IQR: 113.8-171.7] vs 125.4 cm3 [IQR: 96.3-169.1]; p=0.1131) despite a -13.47% decrease in the volume of thrombus (p=0.0216). PRAEVAorta achieved a Se of 89.47% (95% confidence interval [CI]: 80.58 to 94.57), a Sp of 91.25% (95% CI: 83.02 to 95.70), a PPV of 90.67% (95% CI: 81.97 to 95.41), and an NPV of 90.12% (95% CI: 81.70 to 94.91) in detecting endoleaks. Endovascular aortic repair-related adverse events were associated with global volume modifications with an area under the curve (AUC) of 0.7806 vs 0.7277 for maximum diameter. The same trend was observed for endoleaks (AUC of 0.7086 vs 0.6711). CONCLUSIONS: The AI-based software PRAEVAorta enabled a detailed anatomic characterization of aortic remodeling post-EVAR and showed its potential interest for automatic detection of endoleaks during follow-up. The association of aortic aneurysmal volume with EVAR-related adverse events and endoleaks was more robust compared with maximum diameter. CLINICAL IMPACT: The integration of PRAEVAorta AI software into clinical practice promises a transformative shift in post-EVAR surveillance. By offering precise and rapid detection of endoleaks and comprehensive anatomic assessments, clinicians can expect enhanced diagnostic accuracy and streamlined patient management. This innovation reduces reliance on manual measurements, potentially reducing interpretation errors and shortening evaluation times. Ultimately, PRAEVAorta's capabilities hold the potential to optimize patient care, leading to more timely interventions and improved outcomes in endovascular aortic repair.

Cost Effectiveness of Early Endovenous Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis in the United Kingdom.

OBJECTIVE: Early clot removal using endovascular intervention aims to reduce post-thrombotic syndrome (PTS) following iliofemoral deep venous thrombosis (DVT). This may reduce long term morbidity but incurs a higher initial cost. This study examined the cost effectiveness of catheter directed thrombolysis (CDT) and pharmacochemical thrombectomy (PMT) compared with oral anticoagulation (OAC) alone for treatment of acute iliofemoral DVT in the United Kingdom. METHODS: A combined decision tree (acute DVT complications) and Markov model (long term complications [PTS]) was used for decision analytic modelling with five states: no PTS, mild PTS, moderate PTS, severe PTS, and dead. All patients started with acute DVT. Patients who survived acute complications transitioned into the Markov model. Cycle time was six months. A healthcare payer perspective and lifetime horizon was used, adjusting for excess mortality due to history of thrombosis. Data for probabilities, transition probabilities, mortality, and utilities were obtained from the published literature. Cost data were obtained from UK NHS tariffs and published literature. Outcomes were mean lifetime cost, quality adjusted life years (QALYs), and cost effectiveness. RESULTS: Over a patient's lifetime, OAC was more costly (£37 206) than CDT (£32 043) and PMT (£36 288). Mean lifetime QALYs for OAC (12.9) were lower than CDT (13.5) and PMT (13.3). Therefore, in the incremental cost effectiveness analysis, both CDT and PMT were dominant: CDT was less costly (-£5 163) and more effective (+0.6 QALYs) than OAC, and PMT was also less costly (-£917) and more effective (+0.3 QALYs) than OAC. Results were robust to univariable sensitivity analyses, but probabilistic sensitivity analyses suggested considerable parameter uncertainty. CONCLUSION: Early interventional treatment of iliofemoral DVT is cost effective in the UK. Future clinical and epidemiological studies are needed to characterise parameter uncertainty. Further analysis of modern practice, alternative treatments, and optimised care models is warranted.

Vascular Registries Contributing to VASCUNET Collaborative Abdominal Aortic Aneurysm Outcome Projects: A Scoping Review.

OBJECTIVE: Vascular surgery registries report on procedures and outcomes to promote patient safety and drive quality improvement. International registries have contributed significantly to the VASCUNET collaborative abdominal aortic aneurysm (AAA) outcome projects. This scoping review aimed to outline the national registries in vascular surgery that currently participate in the VASCUNET collaborative AAA projects. METHODS: A scoping review of all published VASCUNET AAA studies and validation reports between 1997 and 2024 was undertaken. A survey was conducted among representatives of the international vascular registries contributing to VASCUNET collaborative AAA projects. RESULTS: Currently, vascular registries from 10 countries (Australia, Denmark, Finland, Hungary, Iceland, New Zealand, Norway, Sweden, Switzerland, and the UK) contribute to the current VASCUNET collaborative AAA project, of which eight have national coverage. In the past, three countries (Germany, Malta, and Italy) have participated in previous VASCUNET AAA projects, and a further three countries (Serbia, Greece, and Portugal) have planned participation in future projects. External validity is high for all current registries, with most reporting rates of > 90%. The majority have internal validation processes to assess data accuracy. VASCUNET mediated validation has also been performed by the consortium for five countries to date (Hungary, Sweden, Denmark, Malta, and Switzerland), for which a high degree of external and internal validity was identified. Most registries have established mechanisms for data linkage with national administrative datasets or insurance claims datasets and contribute to quality improvement through regular reporting to participating centres. CONCLUSION: National vascular registries from nations participating in the VASCUNET collaborative AAA projects are largely comprehensive, with high case ascertainment rates and good quality data with internal quality assurance. This provides a template for new registries wishing to join the VASCUNET collaboration and a benchmark for future research.

Halo sign on temporal artery ultrasound versus temporal artery biopsy for giant cell arteritis.

BACKGROUND: Giant cell arteritis (GCA) is a systemic, inflammatory vasculitis primarily affecting people over the age of 50 years. GCA is treated as a medical emergency due to the potential for sudden, irreversible visual loss. Temporal artery biopsy (TAB) is one of the five criteria of the American College of Rheumatology (ACR) 1990 classification, which is used to aid the diagnosis of GCA. TAB is an invasive test, and it can be slow to obtain a result due to delays in performing the procedure and the time taken for histopathologic assessment. Temporal artery ultrasonography (US) has been demonstrated to show findings in people with GCA such as the halo sign (a hypoechoic circumferential wall thickening due to oedema), stenosis or occlusion that can help to confirm a diagnosis more swiftly and less invasively, but requiring more subjective interpretation. This review will help to determine the role of these investigations in clinical practice. OBJECTIVES: To evaluate the sensitivity and specificity of the halo sign on temporal artery US, using the ACR 1990 classification as a reference standard, to investigate whether US could be used as triage for TAB. To compare the accuracy of US with TAB in the subset of paired studies that have obtained both tests on the same patients, to investigate whether it could replace TAB as one of the criteria in the ACR 1990 classification. SEARCH METHODS: We used standard Cochrane search methods for diagnostic accuracy. The date of the search was 13 September 2022. SELECTION CRITERIA: We included all participants with clinically suspected GCA who were investigated for the presence of the halo sign on temporal artery US, using the ACR 1990 criteria as a reference standard. We included studies with participants with a prior diagnosis of polymyalgia rheumatica. We excluded studies if participants had had two or more weeks of steroid treatment prior to the investigations. We also included any comparative test accuracy studies of the halo sign on temporal artery US versus TAB, with use of the 1990 ACR diagnostic criteria as a reference standard. Although we have chosen to use this classification for the purpose of the meta-analysis, we accept that it incorporates unavoidable incorporation bias, as TAB is itself one of the five criteria. This increases the specificity of TAB, making it difficult to compare with US. We excluded case-control studies, as they overestimate accuracy, as well as case series in which all participants had a prior diagnosis of GCA, as they can only address sensitivity and not specificity. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed the studies for inclusion in the review. They extracted data using a standardised data collection form and employed the QUADAS-2 tool to assess methodological quality. As not enough studies reported data at our prespecified halo threshold of 0.3 mm, we fitted hierarchical summary receiver operating characteristic (ROC) models to estimate US sensitivity and also to compare US with TAB. We graded the certainty of the evidence using the GRADE approach. MAIN RESULTS: Temporal artery ultrasound was investigated in 15 studies (617 participants with GCA out of 1479, 41.7%), with sample sizes ranging from 20 to 381 participants (median 69). There was wide variation in sensitivity with a median value of 0.78 (interquartile range (IQR) 0.45 to 0.83; range 0.03 to 1.00), while specificity was fair to good in most studies with a median value of 0.91 (IQR 0.78 to 1.00; range 0.40 to 1.00) and four studies with a specificity of 1.00. The hierarchical summary receiver operating characteristic (HSROC) estimate of sensitivity (95% confidence interval (CI)) at the high specificity of 0.95 was 0.51 (0.21 to 0.81), and 0.84 (0.58 to 0.95) at 0.80 specificity. We considered the evidence on sensitivity and specificity as of very low certainty due to risk of bias (-1), imprecision (-1), and inconsistency (-1). Only four studies reported data at a halo cut-off > 0.3 mm, finding the following sensitivities and specificities (95% CI): 0.80 (0.56 to 0.94) and 0.94 (0.81 to 0.99) in 55 participants; 0.10 (0.00 to 0.45) and 1.00 (0.84 to 1.00) in 31 participants; 0.73 (0.54 to 0.88) and 1.00 (0.93 to 1.00) in 82 participants; 0.83 (0.63 to 0.95) and 0.72 (0.64 to 0.79) in 182 participants. Data on a direct comparison of temporal artery US with biopsy were obtained from 11 studies (808 participants; 460 with GCA, 56.9%). The sensitivity of US ranged between 0.03 and 1.00 with a median of 0.75, while that of TAB ranged between 0.33 and 0.92 with a median of 0.73. The specificity was 1.00 in four studies for US and in seven for TAB. At high specificity (0.95), the sensitivity of US and TAB were 0.50 (95% CI 0.24 to 0.76) versus 0.80 (95% CI 0.57 to 0.93), respectively, and at low specificity (0.80) they were 0.73 (95% CI 0.49 to 0.88) versus 0.92 (95% CI 0.69 to 0.98). We considered the comparative evidence on the sensitivity of US versus TAB to be of very low certainty because specificity was overestimated for TAB since it is one of the criteria used in the reference standard (-1), together with downgrade due to risk of bias (-1), imprecision (-1), and inconsistency (-1) for both sensitivity and specificity. AUTHORS' CONCLUSIONS: There is limited published evidence on the accuracy of temporal artery US for detecting GCA. Ultrasound seems to be moderately sensitive when the specificity is good, but data were heterogeneous across studies and either did not use the same halo thickness threshold or did not report it. We can draw no conclusions from accuracy studies on whether US can replace TAB for diagnosing GCA given the very low certainty of the evidence. Future research could consider using the 2016 revision of the ACR criteria as a reference standard, which will limit incorporation bias of TAB into the reference standard.

Sex-specific differences in the standard of care for infrarenal abdominal aortic aneurysm repair, and risk of major adverse cardiovascular events and death.

BACKGROUND: This study investigated whether sex-specific differences in preoperative/perioperative standard of care (SOC) account for disparity in outcomes after elective infrarenal abdominal aortic aneurysm repair. METHODS: This was a retrospective cohort study of elective infrarenal abdominal aortic aneurysm repairs (2013-2020) using depersonalized patient-level National Vascular Registry data. SOC was defined for waiting times, preoperative assessment (multidisciplinary/anaesthetic review), cardiovascular risk prevention, and perioperative medication. The primary outcome was major cardiovascular event and/or death (MACED). RESULTS: Some 21 810 patients with an infrarenal abdominal aortic aneurysm were included, 2380 women and 19 430 men. Women less often underwent aneurysm repair within SOC waiting times (51.5 versus 59.3 per cent; P < 0.001), but were equally likely to receive preoperative assessment (72.1 versus 72.5 per cent; P = 0.742). Women were less likely to receive secondary prevention for known cardiac disease (34.9 versus 39.6 per cent; P = 0.015), but more often met overall cardiovascular risk prevention standards (52.1 versus 47.3 per cent; P < 0.001). Women were at greater risk of MACED (open: 12.0 versus 8.9 per cent, P < 0.001; endovascular: 4.9 versus 2.9 per cent, P < 0.001; risk-adjusted OR 1.33, 95 per cent c.i. 1.12 to 1.59). A significant reduction in the odds of MACED was associated with preoperative assessment (OR 0.86, 0.75 to 0.98) and SOC waiting times (OR 0.78, 0.69 to 0.87). There was insufficient evidence to confirm a significant sex-specific difference in the effect of SOC preoperative assessment (women: OR 0.69, 0.50 to 0.97; men: OR 0.89, 0.77 to 1.03; interaction P = 0.170) or SOC waiting times (women: OR 0.84, 0.62 to 1.16; men: OR 0.76, 0.67 to 0.87; interaction P = 0.570) on the risk of MACED. CONCLUSION: SOC waiting times and preoperative assessment were not met for both sexes, which was associated with an increased risk of MACED. Sex-specific differences in SOC attenuated but did not fully account for the increased risk of MACED in women.

Fully automatic volume segmentation using deep learning approaches to assess aneurysmal sac evolution after infrarenal endovascular aortic repair.

OBJECTIVE: Endovascular aortic repair (EVAR) surveillance relies on serial measurements of the maximal diameter despite significant inter- and intraobserver variability. Volumetric measurements are more sensitive; however, their general use has been hampered by the time required for their implementation. An innovative, fully automated software (PRAEVAorta; Nurea, Bordeaux, France), using artificial intelligence, had previously demonstrated fast and robust detection of the characteristics of infrarenal abdominal aortic aneurysms on preoperative imaging studies. In the present study, we assessed the robustness of these data on post-EVAR computed tomography (CT) scans. METHODS: We compared fully automatic and semiautomatic segmentation manually corrected by a senior surgeon (E.D.) using a dataset of 48 patients (48 early post-EVAR CT scans with 6466 slices and 101 follow-up CT scans with 13,708 slices). RESULTS: The analyses confirmed the excellent correlation of the post-EVAR volumes and surfaces and the proximal neck and maximum aneurysm diameters measured using the fully automatic and manually corrected segmentation methods (Pearson's coefficient correlation, >0.99; P < .0001). A comparison between the fully automatic and manually corrected segmentation methods revealed a mean Dice similarity coefficient of 0.950 ± 0.015, Jaccard index of 0.906 ± 0.028, sensitivity of 0.929 ± 0.028, specificity of 0.965 ± 0.016, volumetric similarity of 0.973 ± 0.018, and mean Hausdorff distance/slice of 8.7 ± 10.8 mm. The mean volumetric similarity reached 0.873 ± 0.100 for the lumen and 0.903 ± 0.091 for the thrombus. The segmentation time was nine times faster with the fully automatic method (2.5 minutes vs 22 minutes per patient with the manually corrected method; P < .0001). A preliminary analysis also demonstrated that a diameter increase of 2 mm can actually represent a >5% volume increase. CONCLUSIONS: PRAEVAorta enabled a fast, reproducible, and fully automated analysis of post-EVAR abdominal aortic aneurysm sac and neck characteristics, with a comparison between different time points. It could become a crucial adjunct for EVAR follow-up through the early detection of sac evolution, which might reduce the risk of secondary rupture.

Editor's Choice - Systematic Review and Meta-Analysis of Sex Specific Differences in Adverse Events After Open and Endovascular Intact Abdominal Aortic Aneurysm Repair: Consistently Worse Outcomes for Women.

OBJECTIVE: Previously, reports have shown that women experience a higher mortality rate than men after elective open (OAR) and endovascular (EVAR) repair of abdominal aortic aneurysm (AAA). With recent improvements in overall AAA repair outcomes, this study aimed to identify whether sex specific disparity has been ameliorated by modern practice, and to define sex specific differences in peri- and post-operative complications and pre-operative status; factors which may contribute to poor outcome. METHODS: This was a systematic review, meta-analysis, and meta-regression of sex specific differences in 30 day mortality and complications conducted according to PRISMA guidance (Prospero registration CRD42020176398). Papers with ≥ 50 women, reporting sex specific outcomes, following intact primary AAA repair, from 2000 to 2020 worldwide were included; with separate analyses for EVAR and OAR. Data sources were Medline, Embase, and CENTRAL databases 2005 - 2020 searched using ProQuest Dialog. RESULTS: Twenty-six studies (371 215 men, 65 465 women) were included. Meta-analysis and meta-regression indicated that sex specific odds ratios (ORs) for 30 day mortality were unchanged from 2000 to 2020. Mortality risk was higher in women for OAR and more so for EVAR (OR [95% CI] 1.49 [1.37 - 1.61]; 1.86 [1.59 - 2.17], respectively) and this remained following multivariable risk adjustment. Transfusion, pulmonary complications, and bowel ischaemia were more common in women after OAR and EVAR (OAR: ORs 1.81 [1.60 - 2.04], 1.40 [1.28 - 1.53], 1.54 [1.36 - 1.75]; EVAR: ORs 2.18 [2.08 - 2.29] 1.44 [1.17 - 1.77], 1.99 [1.51 - 2.62], respectively). Arterial injury, limb ischaemia, renal and cardiac complications were more common in women after EVAR (ORs 3.02 [1.62 - 5.65], 2.13 [1.48 - 3.06], 1.46 [1.22 - 1.72] and 1.19 [1.03 - 1.37], respectively); the latter was associated with greater mortality risk on meta-regression. CONCLUSION: Increased mortality risk for women following AAA repair remains. Women had a higher incidence of transfusion, pulmonary and bowel complications after EVAR and OAR. Higher mortality risk ratios for EVAR may result from cardiac complications, additional arterial injury, and embolisation, leading to renal and limb ischaemia. These findings indicate possible causes for observed outcome disparities and targets for quality improvement.

AngioJet Pharmacomechanical Thrombectomy and Catheter Directed Thrombolysis vs. Catheter Directed Thrombolysis Alone for the Treatment of Iliofemoral Deep Vein Thrombosis: A Single Centre Retrospective Cohort Study.

OBJECTIVE: Percutaneous thrombus removal is used for the treatment of iliofemoral deep vein thrombosis (DVT), but the efficacy of different treatment modalities has not yet been determined. The aim of this study was to compare the outcomes of patients treated with additional AngioJet pharmacomechanical thrombectomy (PCDT) vs. catheter directed lysis (CDT) alone. METHODS: A retrospective review of all patients who received thrombolysis for the treatment of symptomatic acute iliofemoral DVT between 2011 and 2017 was carried out. Outcome measures included the incidence of post-thrombotic syndrome (PTS), procedural outcomes (lytic exposure), the incidence of complications, and vessel patency. All patients were followed up for a minimum of one year. RESULTS: A total of 151 limbs were treated, 70 limbs with PCDT and 81 limbs with CDT alone. Demographic data and prevalence of risk factors were comparable. Incidence of PTS (Villalta score at one year) showed no significant difference (22.2% PCDT vs. 24.7% CDT alone, p = .74). Use of PCDT resulted in a non-statistically significant trend for fewer bleeds (n = 4/63 [6.3%] vs. 13/76 [17.1%]; relative risk 0.37, 95% confidence interval [CI] 0.13-1.08; p = .07), a statistically significant reduction in lysis duration (40 h [95% CI 34-46] vs. 53 h [95% CI 49-58]; p < .001) and a reduction in lytic dose (49 mg [95% CI 42-55] vs. 57 mg [95% CI 52-61]; p = .011) compared with CDT. This reduction was accentuated in 24 cases primarily treated with AngioJet PowerPulse mode (27 h, 95% CI 20-34 [p < .001] and 42 mg, 95% CI 34-50 [p = .009]). Incidences of complications were comparable between groups, with one death due to an intracranial haemorrhage following CDT. Although the incidence of haemoglobinuria was increased following PCDT (12/63 [19.0%] vs. 3/76 [3.9%]; p = .006), no significant difference in acute kidney injury was observed (3/63 [4.8%] vs. 1/76 [1.3%]; p = .33). No significant difference in vessel patency over two years was observed (p = .73). CONCLUSION: The use of PCDT for the treatment of iliofemoral DVT was observed to provide comparable patient outcomes, comparable vessel patency, an acceptable safety profile, and reduced overall lytic dose.

Smoking as a risk factor for lower extremity peripheral artery disease in women compared to men: A systematic review and meta-analysis.

BACKGROUND: To investigate whether the relationship between smoking and peripheral artery disease (PAD) differs by sex (PROSPERO CRD42022352318). METHODS: PubMed, EMBASE, and CINAHL were searched (3 March 2024) for studies reporting associations between smoking and PAD in both sexes, at least adjusted for age. Data were pooled using random effects. Between-study heterogeneity was examined using I2 statistic and Cochran's Q test. Newcastle-Ottowa Scale was adopted for quality assessment. RESULTS: Four cohort studies (n = 2,117,860, 54.4% women) and thirteen cross-sectional studies (n = 230,436, 59.9% women) were included. In cohort studies, former and current smokers had higher risk of PAD than never smokers. Compared to those who never or previously smoked, women current smokers (relative risk (RR) 5.30 (95% confidence interval 3.17, 8.87)) had higher excess risk of PAD than men (RR 3.30 (2.46, 4.42)), women-to-men ratio of RR 1.45 (1.30, 1.62)(I2 = 0%, p = 0.328). In cross-sectional studies, risk of PAD was higher among former and current compared to never smokers, more so in men, women-to-men ratios of odds ratio: 0.64 (0.46, 0.90)(I2 = 30%, p = 0.192), 0.63 (0.50, 0.79)(I2 = 0%, p = 0.594), respectively. For both sexes, risk of PAD was higher among current smokers compared to those who were not currently smoking. Cohort studies and five cross-sectional studies were of good quality, scoring 6 to 8 of a possible maximum 9 points. Eight cross-sectional studies scored 2 to 5. DISCUSSIONS: Further research is required to elucidate sex differences in the relationships between smoking and PAD, as the current evidence is limited and mixed. Tobacco-control programs should consider both sexes.

Sex differences in risk factors for incident peripheral artery disease hospitalisation or death: Cohort study of UK Biobank participants.

BACKGROUND: Women with peripheral artery disease (PAD) often have atypical symptoms, late hospital presentations, and worse prognosis. Risk factor identification and management are important. We assessed sex differences in associations of risk factors with PAD. METHODS: 500,207 UK Biobank participants (54.5% women, mean age 56.5 years) without prior hospitalisation of PAD at baseline were included. Examined risk factors included blood pressure, smoking, diabetes, lipids, adiposity, history of stroke or myocardial infarction (MI), socioeconomic status, kidney function, C-reactive protein, and alcohol consumption. Poisson and Cox regressions were used to estimate sex-specific incidence of PAD hospitalisation or death, hazard ratios (HRs), and women-to-men ratios of HRs (RHR) with confidence intervals (CIs). RESULTS: Over a median of 12.6 years, 2658 women and 5002 men had a documented PAD. Age-adjusted incidence rates were higher in men. Most risk factors were associated with a higher risk of PAD in both sexes. Compared with men, women who were smokers or had a history of stroke or MI had a greater excess risk of PAD (relative to those who never smoked or had no history of stroke or MI): RHR 1.18 (95%CI 1.04, 1.34), 1.26 (1.02, 1.55), and 1.50 (1.25, 1.81), respectively. Higher high-density lipoprotein cholesterol (HDL-C) was more strongly associated with a lower risk of PAD in women than men, RHR 0.81 (0.68, 0.96). Compared to HDL-C at 40 to 60 mg/dL, the lowest level of HDL-C (≤40 mg/dL) was related to greater excess risk in women, RHR 1.20 (1.02, 1.41), whereas the highest level of HDL-C (>80 mg/dL) was associated with lower risk of PAD in women, but higher risk in men, RHR 0.50 (0.38, 0.65). CONCLUSIONS: While the incidence of PAD was higher in men, smoking and a history of stroke or MI were more strongly associated with a higher risk of PAD in women than men. HDL-C was more strongly associated with a lower risk of PAD in women than men.

Sex-Specific Differences in Cardiovascular Risk, Risk Factors and Risk Management in the Peripheral Arterial Disease Population.

Cardiovascular disease (CVD) is the leading cause of mortality in women worldwide but has been primarily recognised as a man's disease. The major components of CVD are ischaemic heart disease (IHD), stroke and peripheral arterial disease (PAD). Compared with IHD or stroke, individuals with PAD are at significantly greater risk of major cardiovascular events. Despite this, they are less likely to receive preventative treatment than those with IHD. Women are at least as affected by PAD as men, but major sex-specific knowledge gaps exist in the understanding of relevant CVD risk factors and efficacy of treatment. This prompted the American Heart Association to issue a "call to action" for PAD in women, in 2012. Despite this, PAD and CVD risk in women continues to be under-recognised, leading to a loss of opportunity to moderate and prevent CVD morbidity. This review outlines current evidence regarding cardiovascular risk in women and men with PAD, the relative significance of traditional and non-traditional risk factors and sex differences in cardiovascular risk management.