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Epidemiological evidence has highlighted a strong relationship between cardiorespiratory fitness and surgical outcomes; specifically, fitter patients possess heightened resilience to withstand the surgical stress response. This narrative review draws on exercise and surgical physiology research to discuss and hypothesise the potential mechanisms by which higher fitness affords perioperative benefit. A higher fitness, as indicated by higher peak rate of oxygen consumption and ability to sustain metabolic homeostasis (i.e. higher anaerobic threshold) is beneficial postoperatively when metabolic demands are increased. However, the associated adaptations with higher fitness, and the related participation in regular exercise or physical activity, might also underpin the observed perioperative benefit through a process of hormesis, a protective adaptive response to the moderate and intermittent stress of exercise. Potential mediators discussed include greater antioxidant capacity, metabolic flexibility, glycaemic control, lean body mass, and improved mood.

The authors regret there was a mistake in Figure 6 and 13. In Figure 6, it should read ‘Compression’ for oedema, to include inelastic compression as well (green box); in Figure 13, the pressure at the ankle should read ‘≤ 40 mm Hg’, for small and recent onset ulcer (yellow box):[Formula presented][Formula presented] The authors would like to apologise for any inconvenience caused. publishersversion published

Teaching traditionally asserts that the arterial pressure pulse is dampened across the capillary bed to the extent that pulsatility is nonexistent in the venous circulation of the lower limbs. Herein, we present evidence of transmission of arterial pulsations across the capillary network into perforator veins in the lower limbs of healthy, heat-stressed humans. Perforator veins are connections from the superficial veins that drain into the deep veins. When assessed using ultrasound at rest, they infrequently demonstrate flow, and a pulsatile flow waveform is not described. We investigated perforator vein pulsatility in 10 young, healthy volunteers who underwent passive heating by +2°C core body temperature via a hot-water-perfused suit, and 5 who also underwent active heating by +2°C via low-intensity cycling while wearing the hot-water-perfused suit. At +0.5°C increments in temperature, blood velocity in an ankle perforator vein was measured using duplex ultrasound. In all perforators with heating, sustained flow was demonstrated, with a pulsatile waveform that was synchronous with the cardiac cycle. The maximum velocity was 30 ± 13 cm/s with passive heating and approximately half with active heating ( P = 0.04). The small veins of the skin at the ankle also demonstrated increased perfusion with pulsatility, seen with low-velocity microvascular imaging technology. We consider explanations for this pulsatility and conclude that it is propagated from the arterial inflow through the skin microcirculation as a result of increased dilatation and flow volume and that this is a normal response to increased skin blood flow.

New findings What is the central question of this study? How does resistance exercise affect peripheral haemodynamics in the active and inactive limb? What is the main finding and its importance? Preliminary data indicate that resistance exercise increases flow and shear rate in the active limb transiently. The same exercise has minimal, short-lasting influence on peripheral haemodynamics in the inactive limb, but further research is required to elaborate on resistance exercise-mediated changes in vascular function in active and inactive limbs. Abstract Current evidence indicates that to achieve maximum health benefits, regular resistance exercise should be a key component of structured physical activity. Several studies have revealed that regular resistance exercise may be associated with impaired vascular function, although this finding is inconsistent. Proposed explanations for impairment include substantial increases in blood pressure and increased retrograde blood flow in active limbs promoted by resistance exercise. However, few studies have examined the acute haemodynamics of resistance exercise in active - and even fewer in inactive - limbs. The purpose of this study was to characterise the haemodynamic responses in peripheral arteries in active and inactive limbs in response to resistance exercise using upper and lower limbs. Ten participants (five male, five female) familiar with resistance training performed three sets of 10 isotonic repetitions of right-sided bicep curls or knee extensions on separate days. Blood flow, shear rate and muscle oxygenation in the active and inactive limb, and blood pressure were measured before and for 3 min after each set. Blood flow increased in response to resistance exercise in the active limb (∼8-fold and ∼6-fold for the upper and lower limb respectively), with concurrent significant increases in mean and antegrade shear rate. In the inactive limb, blood flow more than doubled for both upper and lower limb exercise, transiently, with no significant change in retrograde shear rate. These acute blood flow profiles following resistance exercise are not indicative of long-term vessel impairment based on current understanding of blood flow and shear stress patterns.

Objective Past studies have suggested a potential “J shaped” relationship between infrarenal aortic diameter and both cardiovascular disease (CVD) prevalence and all cause mortality. However, screening programmes have focused primarily on large (aneurysmal) aortas. In addition, aortic diameter is rarely adjusted for body size, which is particularly important for women. This study aimed to investigate specifically the relationship between body size adjusted infrarenal aortic diameter and baseline prevalence of CVD. Methods A retrospective analysis was performed on a total of 4882 elderly (>50 years) participants (mean age 69.4 ± 8.9 years) for whom duplex ultrasound to assess infrarenal abdominal aortic diameters had been performed. History of CVDs, including ischaemic heart disease (IHD), and associated risk factors were collected at the time of assessment. A derivation cohort of 1668 participants was used to select cut offs at the lower and upper 12.5% tails of the aortic size distributions (aortic size index of 1.2, respectively), which was then tested in a separate cohort. Results A significantly elevated prevalence of CVD, and specifically IHD, was observed in participants with both small and large aortas. These associations remained significant following adjustment for age, sex, diabetes, hypertension, dyslipidaemia, obesity (body mass index), and smoking. Conclusion The largest and smallest infrarenal aortic sizes were both associated with prevalence of IHD. In addition to identifying those with aneurysmal disease, it is hypothesised that screening programmes examining infrarenal aortic size may also have the potential to improve global CVD risk prediction by identifying those with small aortas.

The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30-90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6-12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.

Corrigendum: Volume 64, Issues 2–3, 2022, 284-285

Objective Recently, the prevalence of abdominal aortic aneurysm (AAA) using screening strategies based on elevated cardiovascular disease (CVD) risk was reported. AAA was defined as a diameter ≥30 mm, with prevalence of 6.1% and 1.8% in men and women respectively, consistent with the widely reported AAA predominant prevalence in males. Given the obvious differences in body size between sexes this study aimed to re-evaluate the expanded CVD risk based AAA screening dataset to determine the effect of body size on sex specific AAA prevalence. Methods Absolute (26 and 30 mm) and relative (aortic size index [ASI] equals the maximum infrarenal aorta diameter (cm) divided by body surface area (m2), ASI ≥ 1.5) thresholds were used to assess targeted AAA screening groups (n = 4115) and compared with a self reported healthy elderly control group (n = 800). Results Male AAA prevalence was the same using either the 30 mm or ASI ≥1.5 aneurysm definitions (5.7%). In females, AAA prevalence was significantly different between the 30 mm (2.4%) and ASI ≥ 1.5 (4.5%) or the 26 mm (4.4%) thresholds. Conclusion The results suggest the purported male predominance in AAA prevalence is primarily an artefact of body size differences. When aortic size is adjusted for body surface area there is only a modest sex difference in AAA prevalence. This observation has potential implications in the context of the ongoing discussion regarding AAA screening in women.

Retrievable inferior vena cava filters carry a risk of penetrating into adjacent structures, which may necessitate open retrieval. We report a unique case of a retrievable inferior vena cava filter penetrating into an overlying horseshoe kidney, leading to clinical hematuria. After repeated failed endovascular retrieval, an open approach with associated access challenges was required.

Background Obesity is a known risk factor for the development of chronic venous disease (CVD). However, some obese patients with lower limb skin changes suggestive of venous disease do not demonstrate venous reflux or obstruction. Popliteal vein compression (PVC) caused by knee hyperextension during standing has been postulated by others to be more common in the obese due to the increased adipose content of the popliteal fossa. This compression may contribute to the development of venous disease. The objective was to examine the prevalence of PVC in obese and nonobese subjects, with and without venous disease. Methods Participants were recruited across the range of Clinical-Etiology-Anatomy-Pathophysiology (CEAP) clinical classifications and body mass. Those referred for venous studies had full venous ultrasound assessments. To assess for PVC, the popliteal vein was assessed via B-mode ultrasound whilst the subject stood and performed two maneuvers: knee hyperextension and a bilateral toe stand. Video clips of each maneuver were analyzed offline. Results There were 309 limbs (158 subjects), of which 131 were nonobese (body mass index [BMI]: 26 ± 3 kg/m2) and 178 obese (BMI: 43 ± 8 kg/m2). PVC with toe stand (PVC(toe stand)) was more common in obese limbs (89% vs 64%, P Conclusions PVC(toe stand) and PVC(lock) are both functional effects and more common in obese limbs. PVC(toe stand) is likely associated with normal functioning of the calf muscle pump. Although PVC(lock) may contribute to CVD in some obese limbs, the demonstration of PVC(lock) alone is insufficient evidence for direct intervention.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Type 2 diabetes is a prominent risk factor for peripheral artery disease (PAD). Yet, the mechanistic link between diabetes and PAD remains unclear. This study proposes that dysregulation of the endogenous hormone ghrelin, a potent modulator of vascular function, underpins the causal link between diabetes and PAD. Moreover, this study aimed to demonstrate the therapeutic potential of exogenous ghrelin in a diabetic mouse model of PAD. Standard ELISA analysis was used to quantify and compare circulating levels of ghrelin between (i) human diabetic patients with or without PAD (clinic) and (ii) db/db diabetic and non-diabetic mice (lab). Db/db mice underwent unilateral hindlimb ischaemia (HLI) for 14 days and treated with or without exogenous ghrelin (150 µg/kg/day.) Subsequently vascular reparation, angiogenesis, hindlimb perfusion, structure and function were assessed using laser Doppler imaging, micro-CT, microangiography, and protein and micro-RNA (miRNA) analysis. We further examined hindlimb perfusion recovery of ghrelin KO mice to determine whether an impaired vascular response to HLI is linked to ghrelin dysregulation in diabetes. Patients with PAD, with or without diabetes, had significantly lower circulating levels of endogenous ghrelin, compared to healthy individuals. Diabetic db/db mice had ghrelin levels that were only 7% of non-diabetic mice. The vascular reparative capacity of diabetic db/db mice in response to HLI was impaired compared to non-diabetic mice and, importantly, comparable to ghrelin KO mice. Daily therapeutic treatment of db/db mice with ghrelin for 14 days post HLI, stimulated angiogenesis, and improved skeletal muscle architecture and cell survival, which was associated with an increase in pro-angiogenic miRNAs-126 and -132. These findings unmask an important role for endogenous ghrelin in vascular repair following limb ischemia, which appears to be downregulated in diabetic patients. Moreover, these results implicate exogenous ghrelin as a potential novel therapy to enhance perfusion in patients with lower limb PAD, especially in diabetics.

Changes in whole blood DNA methylation levels at several CpG sites have been associated with circulating blood lipids, specifically high-density lipoprotein and triglycerides. This study performs a discovery and validation epigenome-wide association study (EWAS) for circulating lipoprotein(a) [Lp(a)], an independent risk factor for cardiovascular diseases. Whole-blood DNA methylation profiles were assessed in a cohort of 1020 elderly individuals using the Illumina EPIC array and independent validation in 359 elderly males using the Illumina 450 k array. Plasma Lp(a) was measured using an apolipoprotein(a)-size-independent ELISA. Epigenome-wide rank regression analysis identified and validated a single CpG site, cg17028067 located in intron 1 of the LPA gene, that was significantly associated with plasma Lp(a) levels after correction for multiple testing. Genotyping of the site identified a relatively uncommon SNP (rs76735376, MAF

The coronavirus disease 2019 (COVID-19) global pandemic has resulted in diversion of healthcare resources to the management of patients infected with SARS-CoV-2 virus. Elective interventions and surgical procedures in most countries have been postponed and operating room resources have been diverted to manage the pandemic. The Venous and Lymphatic Triage and Acuity Scale was developed to provide an international standard to rationalise and harmonise the management of patients with venous and lymphatic disorders or vascular anomalies. Triage urgency was determined based on clinical assessment of urgency with which a patient would require medical treatment or surgical intervention. Clinical conditions were classified into six categories of: (1) venous thromboembolism (VTE), (2) chronic venous disease, (3) vascular anomalies, (4) venous trauma, (5) venous compression and (6) lymphatic disease. Triage urgency was categorised into four groups and individual conditions were allocated to each class of triage. These included (1) medical emergencies (requiring immediate attendance), example massive pulmonary embolism; (2) urgent (to be seen as soon as possible), example deep vein thrombosis; (3) semi-urgent (to be attended to within 30–90 days), example highly symptomatic chronic venous disease, and (4) discretionary/non-urgent- (to be seen within 6–12 months), example chronic lymphoedema. Venous and Lymphatic Triage and Acuity Scale aims to standardise the triage of patients with venous and lymphatic disease or vascular anomalies by providing an international consensus-based classification of clinical categories and triage urgency. The scale may be used during pandemics such as the current COVID-19 crisis but may also be used as a general framework to classify urgency of the listed conditions.

This study investigated whether microvenous reflux can be detected in limbs with chronic venous disease using superb microvascular imaging (SMI) and colour Doppler imaging. Participants with venous disease (limbs, n = 26) and without venous disease (limbs, n = 10) were studied. The skin in the medial gaiter region was imaged using both SMI and colour Doppler to identify reflux in the small vessels in response to distal augmentation. The diameters and depths of responsive vessels were measured. In limbs with venous disease, reflux in response to provocation was visualised with SMI in a greater number of vessels (12/26 versus 4/26) and smaller vessels than with colour Doppler. Reflux in the superficial skin veins was demonstrated in one control participant (1/10) using SMI and in none using colour Doppler (0/10). Our study indicates that microvenous reflux is demonstrable in limbs with venous disease and that SMI is more sensitive than colour Doppler.

Passive heat induces beneficial perfusion profiles, provides substantive cardiovascular strain, and reduces blood pressure, thereby holding potential for healthy and cardiovascular disease populations. The aim of this study was to assess acute responses to passive heat via lower-limb, hot-water immersion in patients with peripheral arterial disease (PAD) and healthy, elderly controls. Eleven patients with PAD (age 71 ± 6 yr, 7 male, 4 female) and 10 controls (age 72 ± 7 yr, 8 male, 2 female) underwent hot-water immersion (30-min waist-level immersion in 42.1 ± 0.6°C water). Before, during, and following immersion, brachial and popliteal artery diameter, blood flow, and shear stress were assessed using duplex ultrasound. Lower-limb perfusion was measured also using venous occlusion plethysmography and near-infrared spectroscopy. During immersion, shear rate increased ( P < 0.0001) comparably between groups in the popliteal artery (controls: +183 ± 26%; PAD: +258 ± 54%) and brachial artery (controls: +117 ± 24%; PAD: +107 ± 32%). Lower-limb blood flow increased significantly in both groups, as measured from duplex ultrasound (>200%), plethysmography (>100%), and spectroscopy, while central and peripheral pulse-wave velocity decreased in both groups. Mean arterial blood pressure was reduced by 22 ± 9 mmHg (main effect P < 0.0001, interaction P = 0.60) during immersion, and remained 7 ± 7 mmHg lower 3 h afterward. In PAD, popliteal shear profiles and claudication both compared favorably with those measured immediately following symptom-limited walking. A 30-min hot-water immersion is a practical means of delivering heat therapy to PAD patients and healthy, elderly individuals to induce appreciable systemic (chronotropic and blood pressure lowering) and hemodynamic (upper and lower-limb perfusion and shear rate increases) responses.

The CEAP (Clinical-Etiology-Anatomy-Pathophysiology) classification is an internationally accepted standard for describing patients with chronic venous disorders and it has been used for reporting clinical research findings in scientific journals. Developed in 1993, updated in 1996, and revised in 2004, CEAP is a classification system based on clinical manifestations of chronic venous disorders, on current understanding of the etiology, the involved anatomy, and the underlying venous pathology. As the evidence related to these aspects of venous disorders, and specifically of chronic venous diseases (CVD, C2-C6) continue to develop, the CEAP classification needs periodic analysis and revisions. In May of 2017, the American Venous Forum created a CEAP Task Force and charged it to critically analyze the current classification system and recommend revisions, where needed. Guided by four basic principles (preservation of the reproducibility of CEAP, compatibility with prior versions, evidence-based, and practical for clinical use), the Task Force has adopted the revised Delphi process and made several changes. These changes include adding Corona phlebectatica as the C4c clinical subclass, introducing the modifier "r" for recurrent varicose veins and recurrent venous ulcers, and replacing numeric descriptions of the venous segments by their common abbreviations. This report describes all these revisions and the rationale for making these changes.

Background Cyanoacrylates are fast-acting adhesives used in procedural medicine including closure of superficial wounds, embolization of truncal vessels pre-operatively, vascular anomalies, visceral false aneurysms, endoleaks, gastrointestinal varices and gastrointestinal bleeding. More recently, catheter-directed cyanoacrylate adhesive closure was introduced as an alternative to endovenous thermal ablation (ETA) to occlude superficial veins of the lower limbs. Objectives To formulate policies for the safe and effective delivery of cyanoacrylate adhesive closure procedures in Australasia, based on current experience and evidence. Methods A panel of phlebologists including vascular surgeons, interventional radiologists, dermatologists and research scientists systematically reviewed the available data on cyanoacrylate products used in medicine and shared personal experience with the procedure. The reviewed material included bibliographic and biomedical data, material safety data sheets and data requested and received from manufacturers. Results and recommendations: Cyanoacrylate adhesive closure appears to be an effective treatment for saphenous reflux with occlusion rates at 36 months of 90–95%. We recommend a maximum dose of 10 mL of cyanoacrylate per treatment session. Serious complications are rare, but significant. Hypersensitivity to acrylates is reported in 2.4% of the population and is an important absolute contraindication to cyanoacrylate adhesive closure. 1 Post-procedural inflammatory reactions, including hypersensitivity-type phlebitis, occur in 10–20% of patients. 2 In the long term, cyanoacrylate adhesive closure results in foreign-body granuloma formation within 2–12 months of the procedure. We recommend against the use of cyanoacrylate adhesive closure in patients with uncontrolled inflammatory, autoimmune or granulomatous disorders (e.g. sarcoidosis). Caution should be exercised in patients with significant active systemic disease or infection and alternative therapies such as thermal ablation and foam sclerotherapy should be considered. Conclusions Cyanoacrylate adhesive closure appears to be an effective endovenous procedure, with short-term closure rates comparable to ETA and therefore greater efficacy than traditional surgery for treating superficial veins of the lower limbs. Ongoing data collection is required to establish the long-term safety.

ObjectivesTo identify the frequency of postoperative complications, including problems identified by patients and complications occurring after discharge from hospital. To identify how these impact on quality of life (QoL) and the patient’s perception of the success of their treatment.DesignData from three prospective sources: surgical audit, a telephone interview (2 weeks after discharge) and a patient-focused questionnaire (2 months after surgery) were retrospectively analysed.SettingDunedin Hospital, Dunedin, New Zealand.ParticipantsOf the 500 patients, 100 undergoing each of the following types of surgeries: anorectal, biliary, colorectal, hernia and skin.Primary and secondary outcome measuresThe primary outcomes were complications and the 36-item Short Form Health Survey (SF-36). Secondary outcomes included the patient’s ratings of their treatment and a questionnaire-derived patient satisfaction score.Results226 patients reported a complication; there were 344 separate complications and 411 reports of complications (16% of complications were reported on more than one occasion). The audit, telephone interview and questionnaire captured 12.6%, 36.3% and 51% of the 411 reports, respectively. Patients with complications had a lower SF-36 Physical Composite Summary (PCS) score (48.5 vs 43.9, p=0.021) and a lower Patient Satisfaction Score (85.6 vs 74.6, pConclusionsFollowing surgery, over 40% of patients experienced complications. The QoL and satisfaction score were significantly less than for those without complications. The majority of complications were diagnosed after discharge from hospital. Taking more notice of the patient perspective helps us to identify problems, to understand what is important to them and may suggest ways to improve perioperative care.

Peripheral arterial disease (PAD) is characterized by lower limb atherosclerosis impairing blood supply and causing walking-induced leg pain or claudication. Adherence to traditional exercise training programs is poor due to these symptoms despite exercise being a mainstay of conservative treatment. Heat therapy improves many cardiovascular health outcomes, so this study tested if this was a viable alternative cardiovascular therapy for PAD patients. Volunteers with PAD were randomized to 12 wk of heat ( n = 11; mean age 76 ± 8 yr, BMI 28.7 ± 3.5 kg/m2, 4 females) or exercise ( n = 11; 74 ± 10 yr, 28.5 ± 6.8 kg/m2, 3 females). Heat involved spa bathing at ∼39°C, 3–5 days/wk for ≤30 min, followed by ≤30 min of callisthenics. Exercise involved ≤90 min of supervised walking and gym-based exercise, 1–2 days/wk. Following the interventions, total walking distance during a 6-min walk test increased (from ∼350 m) by 41 m (95% CI: [13, 69], P = 0.006) regardless of group, and pain-free walking distance increased (from ∼170 m) by 43 m ([22, 63], P < 0.001). Systolic blood pressure was reduced more following heat (−7 mmHg, [−4, −10], P < 0.001) than following exercise (−3 mmHg, [0, −6], P = 0.078), and diastolic and mean arterial pressure decreased by 4 mmHg in both groups ( P = 0.002). There were no significant changes in blood volume, ankle-brachial index, or measures of vascular health. There were no differences in the improvement in functional or blood pressure outcomes between heat and exercise in individuals with PAD. NEW & NOTEWORTHY Heat therapy via hot-water immersion and supervised exercise both improved walking distance and resting blood pressure in peripheral arterial disease (PAD) patients over 12 wk. Adherence to heat therapy was excellent, and the heat intervention was well tolerated. The results of the current study indicate that heat therapy can improve functional ability and has potential as an effective cardiovascular conditioning tool for individuals with PAD. Listen to this article's corresponding podcast at https://ajpheart.podbean.com/e/heat-therapy-vs-exercise-in-peripheral-arterial-disease/ .

Recent reports have suggested a reproducible association between the rs11121615 SNP, located within an intron of the castor zinc finger 1 (CASZ1) gene, and varicose veins. This study aimed to determine if this variant is also differentially associated with the various clinical classifications of chronic venous disease (CVD). The rs11121615 SNP was genotyped in two independent cohorts from New Zealand (n = 1876 controls /1606 CVD cases) and the Netherlands (n = 1626/2966). Participants were clinically assessed using well-established CVD criteria. The association between the rs11121615 C-allele and varicose veins was validated in both cohorts. This was strongest in those with higher clinical severity classes and was not significant in those with non-varicose vein CVD. Functional analysis of the rs11121615 variant demonstrated that the risk allele was associated with increased enhancer activity. This study demonstrates that the CASZ1 gene associated C-allele of rs11121615 has a significant, reproducible, association with CVD (CEAP C ≥ 2 meta-odds ratio 1.31, 95% CI 1.27–1.34, P = 1 × 10−98, PHet = 0.25), but not with non-varicose vein (CEAP C1, telangiectasia or reticular veins) forms of venous disease. The effect size of this association therefore appears to be susceptible to influence by phenotypic heterogeneity, particularly if a cohort includes a large number of cases with lower severity CVD.

Exercise induces arterial flow patterns that promote functional and structural adaptations, improving functional capacity and reducing cardiovascular risk. While heat is produced by exercise, local and whole-body passive heating have recently been shown to generate favorable flow profiles and associated vascular adaptations in the upper limb. Flow responses to acute heating in the lower limbs have not yet been assessed, or directly compared to exercise, and other cardiovascular effects of lower-limb heating have not been fully characterized. Lower-limb heating by hot-water immersion (30 min at 42°C, to the waist) was compared to matched-duration treadmill running (65-75% age-predicted heart rate maximum) in 10 healthy, young adult volunteers. Superficial femoral artery shear rate assessed immediately upon completion was increased to a greater extent following immersion (mean ± SD: immersion +252 ± 137% vs. exercise +155 ± 69%, interaction: p = 0.032), while superficial femoral artery flow-mediated dilation was unchanged in either intervention. Immersion increased heart rate to a lower peak than during exercise (immersion +38 ± 3 beats·min-1 vs. exercise +87 ± 3 beats·min-1, interaction: p < 0.001), whereas only immersion reduced mean arterial pressure after exposure (−8 ± 3 mmHg, p = 0.012). Core temperature increased twice as much during immersion as exercise (+1.3 ± 0.4°C vs. +0.6 ± 0.4°C, p < 0.001). These data indicate that acute lower-limb hot-water immersion has potential to induce favorable shear stress patterns and cardiovascular responses within vessels prone to atherosclerosis. Whether repetition of lower-limb heating has long-term beneficial effects in such vasculature remains unexplored.

Ankle-brachial index (ABI) and pulse volume recordings (PVR) are non-invasive tests used in diagnosis of peripheral arterial disease (PAD). The Dopplex Ability is an automated ABI/PVR device utilising air plethysmography, offering easy and rapid PAD diagnosis. The accuracy and repeatability of the Dopplex were assessed in comparison to the Doppler/air plethysmography-based Parks Flo-Lab system.Sixty-six patients (n = 129 lower limbs) were assessed with both Dopplex and Parks systems. For Dopplex ABI and PVR to be deemed accurate, it had to be within ±10% of the Parks ABI, and the PVR grade (1-4) had to be equal. The coefficient of variation (CV) was calculated from three repeat ABI/PVR readings to assess repeatability.The Dopplex and Parks devices correlated poorly for ABI (R2 = 0.17) with only 43% of ABIs and 69% of PVRs meeting the accuracy criteria compared to the Parks values. The specificity and sensitivity were 56% and 82%, respectively for ABI, and 91% and 89%, respectively for PVRs. The Dopplex showed a significantly higher CV for both ABIs and PVRs compared to the Parks.We found the Dopplex device to demonstrate suboptimal accuracy and repeatability in assessing ABI/PVR, and it was deemed unsuitable for use in our community.

Background: Up to 20% of patients with inflammatory bowel disease (IBD) who are refractory to thiopurine therapy preferentially produce 6-methylmercaptopurine (6-MMP) at the expense of 6-thioguanine nucleotides (6-TGN), resulting in a high 6-MMP:6-TGN ratio (>20). The objective of this study was to evaluate whether genetic variability in guanine monophosphate synthetase (GMPS) contributes to preferential 6-MMP metabolizer phenotype. Methods: Exome sequencing was performed in a cohort of IBD patients with 6-MMP:6-TGN ratios of >100 to identify nonsynonymous single nucleotide polymorphisms (nsSNPs). In vitro assays were performed to measure GMPS activity associated with these nsSNPs. Frequency of the nsSNPs was measured in a cohort of 530 Caucasian IBD patients. Results: Two nsSNPs in GMPS (rs747629729, rs61750370) were detected in 11 patients with very high 6-MMP:6-TGN ratios. The 2 nsSNPs were predicted to be damaging by in silico analysis. In vitro assays demonstrated that both nsSNPs resulted in a significant reduction in GMPS activity (P < 0.05). The SNP rs61750370 was significantly associated with 6-MMP:6-TGN ratios ≥100 (odds ratio, 5.64; 95% confidence interval, 1.01-25.12; P < 0.031) in a subset of 264 Caucasian IBD patients. Conclusions: The GMPS SNP rs61750370 may be a reliable risk factor for extreme 6MMP preferential metabolism.

We investigated the reliability of contrast-enhanced ultrasound (CEUS) in assessing calf muscle microvascular perfusion in health and disease. Response to a post-occlusive reactive hyperaemia test was repeated on two occasions >48 h apart in healthy young (28 ± 7 y) and elderly controls (70 ± 5 y), and in peripheral arterial disease patients (PAD, 69 ± 7 y; n = 10, 9 and 8 respectively). Overall, within-individual reliability was poor (coefficient of variation [CV] range: 15-87%); the most reliable parameter was time to peak (TTP, 15-48% CV). Nevertheless, TTP was twice as long in elderly controls and PAD compared to young (19.3 ± 10.4 and 22.0 ± 8.6 vs. 8.9 ± 6.2 s respectively; p < 0.01), and area under the curve for contrast intensity post-occlusion (a reflection of blood volume) was ∼50% lower in elderly controls (p < 0.01 versus PAD and young). Thus, CEUS assessment of muscle perfusion during reactive hyperaemia demonstrated poor reliability, yet still distinguished differences between PAD patients, elderly and young controls.

A proportion of patients with deep vein thrombosis (DVT) will develop postthrombotic syndrome (PTS). Currently, the only clearly identified risk factors for developing PTS are recurrent ipsilateral DVT and extensive proximal disease. The aim of the study was to assess the natural history of DVT and identify early predictors of poor clinical outcome at 5 years.Patients with suspected acute DVT in the lower limb were assessed prospectively. All patients with a confirmed DVT were asked to participate in this study. Within 7-10 days after diagnosis of DVT, patients underwent a further review, involving clinical, ultrasound, and air plethysmography assessment of both lower limbs. Patients were reassessed at regular intervals for 5 years.One hundred twenty-two limbs in 114 patients were included in this study. Thrombus regression occurred in two phases, with a rapid regression between 10 days and 3 months, and a more gradual regression thereafter. Reflux developed as thrombus regression occurred. Segmental reflux progressed to axial deep reflux and continued to deteriorate in a significant proportion of patients with iliofemoral-popliteal-calf DVT throughout the 5-year study period. Similarly, venous filling index became progressively more abnormal, in this group, over the course of the study. Four risk factors for PTS were identified as best predictors: extensive clot load on presentation;50% clot regression at 6 months; venous filling index2.5 mL/sec; and abnormal outflow rate (0.6). Patients with three or more of these risk factors had a significant risk of developing PTS with sensitivity 100%, specificity 83%, and positive predictive value 67%. Patients scoring 2 or less did not have PTS at 5 years with a negative predictive value of 100%.This is the first study to show that venous assessment at 6 months post-DVT can predict PTS at 5 years. Those who will not develop PTS can be reassured of this at 6 months.

Objective This study aimed to determine the prevalence and relevance of incidental abdominal aortic aneurysm (AAA) on routine abdominal computed tomography (CT) and to audit the performance of radiologists to identify and report AAA. Methods A retrospective audit of all abdominal CT scans performed on men and women ≥50 years at Dunedin Public Hospital between January 2013 and September 2014 was carried out. All CT scans for planning of AAA treatment or follow-up were excluded. The maximal anterior-posterior diameter of the infrarenal abdominal aorta was measured in both the sagittal and transverse planes on the picture archiving and communication system. The radiologist reports were analyzed. All detected AAAs were reviewed for clinical relevance. Results A total of 3332 scans were performed, of which 86 scans were excluded, resulting in a total cohort of 3246. There were 187 incidental AAAs detected with a prevalence of 5.8%. The prevalence was 8.7% in men and 3.1% in women. Whereas the prevalence increased with age, a significant number were detected in those younger than 65 years, with a prevalence of 1.5%. Of the 187 AAAs, 122 (65%) were reported by radiologists: 100% reporting rate in AAAs ≥50 mm, 87% in AAAs ≥40 to 49 mm, and 52% in AAAs ≥30 to 39 mm. Of these, 15% were specifically recommended for referral to a vascular service. Of the incidentally detected AAAs, 72% were considered to be clinically relevant, which is an overall 4.1% prevalence of AAAs with an ability to benefit. In addition, all 3246 subjects avoided the need for further AAA screening. Conclusions There is a high prevalence of AAAs (5.8%) and clinically relevant AAAs (4.1%) detected on routine abdominal CT. As an opportunistic approach, it is a simple and effective way to detect AAAs and to broaden traditional screening criteria to include women and those younger than 65 years in our region. Furthermore, large numbers of subjects with normal aortic diameters are identified who will not need to be screened. Consequently, we consider routine diagnostic abdominal CT to be an important adjunct to national and community AAA screening strategies.

Contains fulltext : 171388.pdf (Publisher’s version ) (Closed access) OBJECTIVE: Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout. METHODS: We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Maori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C). RESULTS: In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 x 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P 0.10). CONCLUSION: Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.

Background Inflammation of the aortic wall is recognised as a key pathogenesis of abdominal aortic aneurysm ( AAA ). This study was undertaken to determine whether inflammatory cytokines could be used as biomarkers for the presence of AAA . Methods and Results Tissue profiles of 27 inflammatory cytokine were examined in AAA (n=14) and nonaneurysmal (n=14) aortic tissues. Three cytokines, regulated upon activation normally T‐cell expressed and secreted ( RANTES ), eotaxin, and macrophage inflammatory protein 1 beta ( MIP‐ 1b), had increased expression in AAA , particularly within the adventitial layer of the aortic wall. Basic fibroblast growth factor ( bFGF ) had reduced expression in all layers of the AAA wall. Examination of the circulating plasma profiles of AAA (n=442) and AAA ‐free controls (n=970) suggested a (risk factor adjusted) AAA ‐association with eotaxin, RANTES , and high sensitivity C‐reactive protein (hs CRP ). A plasma inflammatory cytokine score, calculated using these three markers, suggested a strong risk association with AAA (odds ratio, 4.8; 95% CI , 3.5–6.7; P Conclusions Contrary to reports suggesting a distinct T helper 2–associated inflammatory profile in AAA , this current study suggests a more‐generalized pattern of inflammation, albeit with some potentially distinct features, including elevated plasma eotaxin and decreased plasma RANTES . In combination with hs CRP , these markers may have potential utility as AAA biomarkers.

Introduction: Routine measurement of cardiac biomarkers such as troponin T (TnT) is recommended perioperatively, especially in high-risk vascular surgery. Long-term prognosis is worse even in those with nonspecific perioperative myocardial injury. However, a clear understanding of these biomarker profiles and how they should affect patient management is lacking. Methods: We examined the perioperative profile of high-sensitivity TnT (hsTnT) release in 85 patients undergoing elective major vascular surgery. Plasma hsTnT was measured preoperatively, at 6, 12, and 24 hours postoperatively, and then every 24 hours for a maximum of 5 days. Significant elevations in hsTnT with/without clinical indicators of ischemia were used to diagnose myocardial infarction or injury. Results: A high incidence of myocardial injury was evident (46% had elevated hsTnT); only 5% were associated with myocardial infarction, and 41% were due to myocardial injury. Conclusions: This study emphasizes the high incidence of perioperative myocardial injury and stress in vascular surgery as revealed by the use of the robust and very sensitive biomarker of myocardial damage, hsTnT. The high availability and swift development of increasingly sensitive assays allow detection of abnormal elevated hsTnT levels in a higher proportion of the population. Consequent challenges are the reduced specificity to separate acute events as well as to deduce the prognostic value of elevations due to confusing criteria; this is especially the case in a patient group with multiple comorbidities that affect hsTnT levels chronically.

BACKGROUNDSeveral sequence variants are known to have effects on serum levels of non-high-density lipoprotein (HDL) cholesterol that alter the risk of coronary artery disease.METHODSWe sequenced the genomes of 2636 Icelanders and found variants that we then imputed into the genomes of approximately 398,000 Icelanders. We tested for association between these imputed variants and non-HDL cholesterol levels in 119,146 samples. We then performed replication testing in two populations of European descent. We assessed the effects of an implicated loss-of-function variant on the risk of coronary artery disease in 42,524 case patients and 249,414 controls from five European ancestry populations. An augmented set of genomes was screened for additional loss-of-function variants in a target gene. We evaluated the effect of an implicated variant on protein stability.RESULTSWe found a rare noncoding 12-base-pair (bp) deletion (del12) in intron 4 of ASGR1, which encodes a subunit of the asialoglycoprotein receptor, a lectin that plays a role in the homeostasis of circulating glycoproteins. The del12 mutation activates a cryptic splice site, leading to a frameshift mutation and a premature stop codon that renders a truncated protein prone to degradation. Heterozygous carriers of the mutation (1 in 120 persons in our study population) had a lower level of non-HDL cholesterol than noncarriers, a difference of 15.3 mg per deciliter (0.40 mmol per liter) (P = 1.0x10(-16)), and a lower risk of coronary artery disease (by 34%; 95% confidence interval, 21 to 45; P = 4.0x10(-6)). In a larger set of sequenced samples from Icelanders, we found another loss-of-function ASGR1 variant (p.W158X, carried by 1 in 1850 persons) that was also associated with lower levels of non-HDL cholesterol (P = 1.8x10(-3)).CONCLUSIONSASGR1 haploinsufficiency was associated with reduced levels of non-HDL cholesterol and a reduced risk of coronary artery disease. (Funded by the National Institutes of Health and others.)

Objective Cholesterol crystals have been shown to cause inflammation, and ultimately atherosclerotic lesions through the activation of the NLRP3 inflammasome. As cholesterol crystals have also been found in the walls of patients with abdominal aortic aneurysms (AAA), it is possible that the NLRP3 inflammasome is involved in AAA and genetic variability within this protein complex could alter disease risk. The primary objective of this study was to assess whether there is genetic evidence for a role of the NLRP3 inflammasome in AAA by testing for association of AAA with functional single nucleotide polymorphisms (SNPs) in the CARD8 and NLRP3 genes. Methods AAA patients ( n =1151) and controls ( n =727) were genotyped for CARD8 SNP rs2043211 and NLRP3 SNP rs35829419 using TaqMan SNP assays. IL1-β, C-reactive protein (CRP), and lipoprotein (a) [Lp(a)] were measured in the plasma of a subset of study participants. The Kruskal–Wallis Rank test was conducted to test for differences in mean concentration of IL1-β, CRP and Lp(a). Logistic regression was used to test for interaction between CARD8 and NLRP3. Results Significantly higher mean concentration of plasma IL1-β was observed in study participants who were homozygous for the common C allele of NLRP3 rs35829419 ( p =0.010). Interaction between rs2043211 and rs35829419 was observed in this dataset ( χ 2 =6.22; p =0.044), which strengthened when adjusted for age, gender, smoking, diabetes, hypertension, and dyslipidemia ( χ 2 =14.75; p =0.012); and separately for NOD2 genotype ( χ 2 =14.06; p =0.015). Conclusion Our finding suggests genetic variability within the NLRP3 inflammasome may be important in the pathophysiology of AAA.

Decision making is a key competency of surgeons; however, how best to assess decisions and decision makers is not clearly established. The aim of the present study was to identify criteria that inform judgments about surgical trainees’ decision-making skills. A qualitative free text web-based survey was distributed to recognized international experts in Surgery, Medical Education, and Cognitive Research. Half the participants were asked to identify features of good decisions, characteristics of good decision makers, and essential factors for developing good decision-making skills. The other half were asked to consider these areas in relation to poor decision making. Template analysis of free text responses was performed. Twenty-nine (52%) experts responded to the survey, identifying 13 categories for judging a decision and 14 for judging a decision maker. Twelve features/characteristics overlapped (considered, informed, well timed, aware of limitations, communicated, knowledgeable, collaborative, patient-focused, flexible, able to act on the decision, evidence-based, and coherent). Fifteen categories were generated for essential factors leading to development of decision-making skills that fall into three major themes (personal qualities, training, and culture). The categories compiled from the perspectives of good/poor were predominantly the inverse of each other; however, the weighting given to some categories varied. This study provides criteria described by experts when considering surgical decisions, decision makers, and development of decision-making skills. It proposes a working definition of a good decision maker. Understanding these criteria will enable clinical teachers to better recognize and encourage good decision-making skills and identify poor decision-making skills for remediation.

Background: Abdominal aortic aneurysm (AAA) is an important cause of mortality for the aged, a group that has been denied surgery in the past for fear of peri-operative mortality. Is this attitude still justified? Methods: Analysis of prospectively gathered data from a vascular database. Results: 10.9% of all open AAA operations were in patients older than 79 years with an 8% mortality cate compared to 3% for younger patients. For fit elderly patients with ASA scores less than 3, mortality was just under 4%. Renal failure and wound dehiscence were more common in the elderly. Conclusion: When endovascular repair is not possible in a fit elderly patient, open surgery can be performed with acceptable results.

Background: New Zealand, like Australia, has a widely dispersed population in towns at long distances from the main centres. We set out to estimate the in-hospital mortality rate for ruptured abdominal aortic aneurysms in New Zealand and identify factors associated with mortality. Methods: Data were gathered prospectively as part of the Vascular Society of New Zealand’s continuous audit programme of all member surgeons. Data collection was validated by random record audit. In-hospital mortality of ruptured abdominal aortic aneurysms, defined as death during hospital admission irrespective of cause, was determined for the period 1993–2005. Along with other performance indicators, differences in outcomes were assessed to take into account the trend over the time period, hospital size and number of non-operative admissions. Results: Of the 740 patients admitted with a mean age of 73.9 ± 8.5 years, 78% were men and 17.8% were declined an operation. The in-hospital mortality was 48.3% and the operative mortality was 37.8%. With univariate analysis increasing patient age, American Society of Anesthesiology score, hospital size and female sex were predictors of in-hospital mortality. Only age and American Society of Anesthesiology score were independent predictors of operative mortality. Women were less likely to have surgery. Conclusion: Over the past 13 years in-hospital mortality of ruptured abdominal aortic aneurysms in New Zealand remained unchanged. In provincial hospitals the operative outcomes were satisfactory, but the reported number not offered surgery was higher.

Background— Saphenofemoral junction (SFJ) ligation has been a major component of surgical intervention for varicose veins; however, recurrence occurs in as many as 40%. Neovascularization with reconnection of the venous channels at the transected SFJ has been identified as the major cause of this recurrence. This randomized controlled study sought to evaluate mechanical suppression of neovascularization at the SFJ, with the use of a synthetic patch, to prevent recurrence after ligation surgery. Methods and Results— A total of 389 limbs (from 292 patients) were randomized into either control (SFJ ligation surgery) or patch (SFJ ligation with polytetrafluoroethylene patch of the transected SFJ) groups. All patients underwent clinical assessment, duplex imaging, and air plethysmography studies preoperatively and at 1, 6, 12, and 36 months postoperatively. The patch consistently halved the recurrence rate to 3 years postoperatively in all clinical subgroups. In those patched SFJs that still developed recurrence, evidence of neovascularization circumventing the polytetrafluoroethylene patch was observed by both ultrasound and histology. Conclusions— This study demonstrates that use of a polytetrafluoroethylene patch is an effective mechanical suppressant of neovasculogenesis at the SFJ and can be safely used as a strategy to improve long-term outcome of varicose vein surgery.

Objectives— Although polymorphic variations in genes of the RAS system have previously been associated with susceptibility to AAA, such studies have been significantly limited by small sample sizes. This study was undertaken, using the largest case series yet reported, to determine whether common genetic variants of the RAS are associated with either susceptibility or severity of AAA. Methods and Results— The frequencies of 4 common genetic variants of genes related to the renin-angiotensin system were investigated in 3 geographically distinct, but ethnically similar, case-control cohorts, resulting in comparison of 1226 AAA cases with 1723 controls. In all 3 the AGTR1 1166C allele was significantly more common in AAA patients than controls (overall adjusted OR 1.60, 95% CI 1.32 to 1.93, P =1.1×10 −6 ). Overall, the ACE ID genotype was associated with AAA (OR 1.33, 95% CI 1.06 to 1.67, P AGT 268T allele appeared to have an epistatic effect on large aneurysm size. Conclusion— This study has identified a strong and repeated association between the AGTR1 1166C allele and susceptibility to AAA, and a weaker effect associated with the ACE deletion allele, in 3 geographically distinct, but ethnically similar, case-control cohorts. This study highlights the key role of the RAS in AAA and emphasizes the need for replication and validation of results in suitable independent cohorts.

Contains fulltext : 70663.pdf (Publisher’s version ) (Closed access) Recently, two common sequence variants on 9p21, tagged by rs10757278-G and rs10811661-T, were reported to be associated with coronary artery disease (CAD) and type 2 diabetes (T2D), respectively. We proceeded to further investigate the contributions of these variants to arterial diseases and T2D. Here we report that rs10757278-G is associated with, in addition to CAD, abdominal aortic aneurysm (AAA; odds ratio (OR) = 1.31, P = 1.2 x 10(-12)) and intracranial aneurysm (OR = 1.29, P = 2.5 x 10(-6)), but not with T2D. This variant is the first to be described that affects the risk of AAA and intracranial aneurysm in many populations. The association of rs10811661-T to T2D replicates in our samples, but the variant does not associate with any of the five arterial diseases examined. These findings extend our insight into the role of the sequence variant tagged by rs10757278-G and show that it is not confined to atherosclerotic diseases.

Background Iatrogenic trauma is the most common cause of pseudoaneurysm. Several treatment methods are now available, including surgical repair, direct compression with the assistance of ultrasound, and ultrasound-guided thrombin injection. Each of these treatments has its own risks and advantages. Objective We sought to retrospectively assess the causes of pseudoaneurysm and the evolution of treatments and outcomes. Results Ninety-three pseudoaneurysms were diagnosed at Dunedin Public Hospital between September 1994 and December 2005, the majority resulting from cardiac catheterization. Fifteen patients were treated with ultrasound-guided compression, with a success rate of 66%. Sixty-three patients were treated with ultrasound-guided thrombin injection, with a success rate of 95%. No major or lasting complications were observed with either compression or thrombin injection; however, delayed diagnosis and treatment may have serious consequences requiring surgical salvage. Conclusions Ultrasound-guided thrombin injection is safe, effective, quick, and well tolerated by patients. It has become preferable to compression treatment and it is less invasive than surgical repair. Treatment should be given promptly upon diagnosis of the pseudoaneurysm rather than delaying with watchful expectation.

Background Wound infection occurs when bacterial contamination overcomes the hosts' defences against bacterial growth. Wound categories are a measurement of wound contamination. The American Society of Anesthesiologists (ASA) classification of physical status may be an effective indirect measurement of the hosts' defence against infection. This study examines the association between the ASA score of physical status and wound infection. Methods A retrospective review of a prospective study of antibiotic prophylaxis was carried out. Patients with a documented ASA score who received optimal prophylactic antibiotics were included. The anaesthetist scored the ASA classification of physical status in theatre. Other risk factors for wound infection were also documented. Patients were assessed up to 30 days postoperatively. Results Of 1013 patients there were 483 with a documented ASA score. One hundred and one may not have received optimal prophylaxis, leaving a database of 382 patients. There were 36 wound infections (9.4%). Both the ASA classification of physical status (P = 0.002) and the wound categories (P = 0.034) significantly predicted wound infection. The duration of surgery, patient's age, acuteness of surgery and the organ system being operated on did not predict wound infection. On logistic regression analysis the ASA score was the strongest predictor of wound infection. Conclusion When effective prophylactic antibiotics were used the ASA classification of physical status was the most significant predictor of wound infection.

Background: Increased lipoprotein(a) [Lp(a)] concentrations are predictive for coronary artery disease (CAD). The risk conferred by Lp(a) for other types of vascular disease compared with CAD has not been investigated within a single population. This study aimed to investigate Lp(a) risk association for 4 different types of vascular disease (including CAD) within a predominantly white population.Methods: We used an Lp(a) ELISA that measures Lp(a) independently of apolipoprotein(a) size to measure plasma Lp(a) in patients [384 CAD, 262 peripheral vascular disease, 184 ischemic stroke (stroke), 425 abdominal aortic aneurysm] and 230 disease-free controls. We then conducted association studies with logistic regression, integrating the potential confounding effects of age, sex, diabetes, plasma lipids, and a history of previous hypertension, hypercholesterolemia, and smoking.Results: Multivariate analyses with Lp(a) concentrations of >45 nmol/L (the 75th percentile value for controls) as the clinical cutoff showed increased Lp(a) concentrations to be a risk factor for all disease groups, with adjusted odds ratios ranging from 1.96 [95% confidence interval (CI) 1.24–3.08] for CAD to 2.33 (95% CI 1.39–3.89) for PVD. The risk conferred by Lp(a) appeared to be independent of other confounders, including exposure to statin/fibrate therapies. Similar odds ratios and CIs between disease groups indicated that increased Lp(a) conferred a similar risk for all groups studied.Conclusions: Lp(a) constitutes a stable risk factor of similar magnitude for 4 major forms of vascular disease. This association was not altered by exposure to standard lipid-lowering therapy.