A low socioeconomic status (SES) is associated with higher cardiovascular mortality and morbidity. It has remained unclear whether such a social gradient is evident in peripheral artery disease (PAD) because both diseases show different clinical courses. We looked at the association between education and income with PAD within the population of the Heinz Nixdorf Recall Study (HNRS) including 4738 individuals. In both men and women, the ankle–brachial index (ABI) decreased and the prevalence of PAD (ABI < 0.9) increased with decreasing education and income. Looking only at participants without cardiovascular disease, doctor-diagnosed PAD and media calcinosis participants with low (odds ratio 2.58, 95% confidence interval 1.53–4.34) and median education (1.90, 1.27–2.85) had higher odds for suffering from PAD compared to participants with high education. Additional adjustment for classical arteriosclerosis risk factors reduced the strength of the association while the odds ratios remained elevated. Current smoking, diabetes and BMI seem to be the most relevant mediators. Income does not significantly correlate with events when adjustments for all other risk factors are made. In conclusion, our study demonstrates that PAD is more pronounced in men and women with lower socioeconomic status. Diabetes prevention and smoking prevention and cessation programs need to specifically target individuals of lower income and education. According to our findings, prevention of PAD would benefit extraordinarily.

Patients with peripheral arterial disease (PAD) report diverse clinical manifestations that are not always consistent with classic intermittent claudication. We examined the degree to which atypical exertional leg symptoms, intermittent claudication, and exertional leg symptoms that begin at rest were associated with mood states such as anxiety, depressive symptoms, and anhedonia (i.e. lack of positive affect). A cohort of consecutive PAD patients (n = 628) from the Erasmus Medical Center, Rotterdam, The Netherlands, completed the Hospital Anxiety and Depression Scale and the San Diego Claudication questionnaire. The ankle–brachial index and clinical factors were assessed in all patients at baseline. Anxiety was present in 29%, depressive symptoms in 30%, and anhedonia in 28% of patients. Pain at rest was independently associated with anxiety, depressive symptoms, and anhedonia (ORs between 2.5 and 4.0, p ≤ 0.001), while there was no relationship between intermittent claudication and mood states. Patients with atypical leg symptoms had a twofold risk of anxiety (OR = 1.9, 95% CI 1.1–3.5, p < 0.05). Adjusting for sex, age, ankle–brachial index, cardiovascular history, time since ankle–brachial index screening, clinical factors, and medication use, both pain at rest (OR = 3.4, 95% CI 1.6–7.0, p = 0.001) and atypical leg symptoms (OR = 2.3, 95% CI 1.1–4.9, p < 0.05) were associated with comorbid mood problems. In conclusion, PAD patients with atypical leg symptoms or pain at rest reported more impaired mood than patients without those symptoms. These patients should be monitored closely in clinical practice, as previous research in cardiovascular patients has shown that mood disorders and sub-threshold symptoms predict poor prognosis.

This study aimed to evaluate the efficacy of high-resolution 3D contrast-enhanced magnetic resonance angiography (3D CE MRA) with parallel imaging techniques for the diagnosis of various arterial stenoses and its value for planning endovascular interventional treatment. Thirty-five patients underwent 3D CE MRA before endovascular interventional treatment. Numbers of patients were as follows: clinically documented renal artery stenosis (n = 10), renal transplant artery stenosis (n = 1), carotid artery stenosis (n = 12), iliac artery stenosis (n = 11) and femoro-popliteal artery stenosis (n = 1). A total of 39 arterial segments were treated. The depiction of various arterial stenoses was evaluated. The degree and length of the stenoses were compared and analyzed between 3D CE MRA and digital subtraction angiography (DSA). The accuracy of MRA in depicting lesion characteristics (ulceration, eccentricity, post-stenotic dilatation) was reviewed. The overall value of 3D CE MRA in planning interventional treatment was determined. The quality of 3D CE MRA in the demonstration of various arterial stenoses was judged excellent or good. A strong correlation was noted between 3D CE MRA and DSA regarding severity and length of stenosis. The accuracy of 3D CE MRA in depicting lesion characteristics was good. 3D CE MRA overestimated three severe iliac artery stenoses. Except in these three segments, the value of 3D CE MRA analysis was judged high. 3D CE MRA was found to be better than DSA in revealing the distal reconstitution and occluded segment in cases of iliac artery stenosis. 3D CE MRA is accurate in demonstrating the relevant anatomy necessary to plan endovascular interventional treatment for patients with arterial stenosis.

The CLaudication: Exercise Vs Endoluminal Revascularization (CLEVER) study is the first randomized, controlled, clinical, multicenter trial that is evaluating a supervised exercise program compared with revascularization procedures to treat claudication. In this report, the methods and dissemination techniques of the supervised exercise training intervention are described. A total of 217 participants are being recruited and randomized to one of three arms: (1) optimal medical care; (2) aortoiliac revascularization with stent; or (3) supervised exercise training. Of the enrolled patients, 84 will receive supervised exercise therapy. Supervised exercise will be administered according to a protocol designed by a central CLEVER exercise training committee based on validated methods previously used in single center randomized control trials. The protocol will be implemented at each site by an exercise committee member using training methods developed and standardized by the exercise training committee. The exercise training committee reviews progress and compliance with the protocol of each participant weekly. In conclusion, a multicenter approach to disseminate the supervised exercise training technique and to evaluate its efficacy, safety and cost-effectiveness for patients with claudication due to peripheral arterial disease (PAD) is being evaluated for the first time in CLEVER. The CLEVER study will further establish the role of supervised exercise training in the treatment of claudication resulting from PAD and provide standardized methods for use of supervised exercise training in future PAD clinical trials as well as in clinical practice.

The objective of this study was to examine the association of alcohol drinking and lipid profile with infrarenal aortic dimension. The diameter of the infrarenal aorta was measured using ultrasound in 395 individuals (mean 66.6 ± 10.3 years) with atherosclerotic diseases or risk factors. The associations between heavy drinking, serum lipoprotein (a) levels, lipid profile and infrarenal aorta diameters were examined. Heavy drinking and lipoprotein (a) were positively related with infrarenal aortic dimension, while low-density lipoprotein cholesterol (LDL-C)/high-density lipoprotein cholesterol (HDL-C), LDL-C and total cholesterol (TC)/HDL-C were negatively associated with infrarenal aortic diameter (p < 0.05). In addition, there were negative associations of LDL-C/HDL-C, TC/HDL-C and positive associations of HDL-C and apolipoprotein AI (Apo AI) with heavy drinking (p < 0.05). In conclusion, there was a positive association between infrarenal aortic diameters and heavy drinking, as well as lipoprotein (a) levels. Furthermore, the novel and unexpected inverse association between LDL-C/HDL-C, LDL-C, TC/HDL-C and abdominal aortic diameter may suggest a possible role for anti-atherogenic lipid profile (characterized by a higher level of HDL-C and lower level of LDL-C) in aortic dilatation processes, which need to be clarified by further studies.

Proximal claudication remains a difficult diagnosis. The ankle to brachial index may be insensitive in the case of isolated hypogastric lesions. Penile pressure represents an alternative method for proximal arteries. Surprisingly, the accuracy of penile pressure measurement in detecting lesions on the arteries supplying pelvic circulation in patients suffering claudication has rarely been studied. We aimed to evaluate the diagnostic accuracy of the penile brachial index < 0.60 (penile over brachial systolic pressure ratio) to non-invasively investigate arteriographic lesions on arteries supplying the hypogastric circulation in 88 male patients referred for Fontaine stage II. The receiver operating characteristic (ROC) curve was used to define the diagnostic performance of the penile brachial index and search for a specific cut-off point in this population. Accuracy was 69.3% (95% confidence interval: 58.6–78.7) for the detection of an arterial stenosis or occlusion on at least one side. The penile brachial index ≤ 0.45 was 74% sensitive and 68% specific to discriminate the 19 patients with bilateral arterial occlusion from the other 66 patients. In conclusion, the penile brachial index is relatively insensitive for the detection of proximal abnormal blood flow impairment except in the case of bilateral occlusion of arteries supplying the hypogastric circulation in patients with claudication. A normal penile pressure is probably not efficient enough to rule out the presence of lesions on the arteries towards the hypogastric circulation in patients with arterial claudication.

Venous stasis syndrome may complicate deep vein thrombosis (DVT; i.e. post-phlebitic syndrome), but, in most cases, venous stasis syndrome is not post-phlebitic. The objective of this study was to determine the risk factors (including prior DVT) for venous stasis syndrome, and to assess venous outflow obstruction and venous valvular incompetence as possible mechanisms for venous stasis syndrome. This was a case–control study nested within a population-based inception cohort. The study population consisted of 232 Olmsted County, MN residents with a first lifetime venous thromboembolism (VTE) and 133 residents without VTE. Measurements included a questionnaire and physical examination for venous stasis syndrome; strain gauge outflow plethysmography, venous continuous wave Doppler ultrasonography and passive venous drainage and refill testing for venous outflow obstruction and venous valvular incompetence. Altogether, 161 (44%), 43 (12%), and 136 (38%) subjects respectively, had venous stasis syndrome, venous outflow obstruction and venous valvular incompetence. Independent risk factors for venous stasis syndrome included increasing patient age and body mass index (BMI), prior DVT, longer time interval since DVT, and varicose veins. Both venous outflow obstruction (p = 0.003) and venous valvular incompetence (p < 0.0001) were strongly associated with venous stasis syndrome. Increasing age and prior DVT were significantly associated with venous outflow obstruction, while prior DVT, varicose veins and venous stasis syndrome diagnosed prior to the incident DVT were significantly associated with venous valvular incompetence. The risks of venous outflow obstruction, venous valvular incompetence and venous stasis syndrome were higher with left leg DVT. In conclusion, increasing patient age and BMI, prior DVT (particularly left leg DVT), longer time interval since DVT and varicose veins are independent risk factors for venous stasis syndrome. Venous stasis syndrome related to DVT is due to venous outflow obstruction and venous valvular incompetence, while venous stasis syndrome related to older age and to varicose veins is due to venous outflow obstruction and to venous valvular incompetence, respectively.

Clinic-based, case-control studies linked sleep-disordered breathing (SDB) to markers of endothelial dysfunction. We attempted to validate this association in a large community-based sample, and evaluate the relation of SDB to arterial diameter and peripheral blood flow. This community-based, cross-sectional observational study included 327 men and 355 women, aged 42–83 years, from the Framingham Heart Study site of the Sleep Heart Health Study. The polysomnographically derived apnea-hypopnea index and the hypoxemia index (percent sleep time with oxyhemoglobin saturation below 90%) were used to quantify the severity of SDB. Brachial artery ultrasound measurements included baseline diameter, percent flow-mediated dilation, and baseline and hyperemic flow velocity and volume. The baseline brachial artery diameter was significantly associated with both the apnea-hypopnea index and the hypoxemia index. The association was diminished by adjustment for body mass index, but remained significant for the apnea-hypopnea index. Age-, sex-, race- and body mass index-adjusted mean diameters were 4.32, 4.33, 4.33, 4.56, 4.53 mm for those with apnea-hypopnea index < 1.5, 1.5–4.9, 5–14.9, 15–29.9, ≥ 30, respectively; p = 0.03. Baseline flow measures were associated with the apnea-hypopnea index but this association was non-significant after adjusting for body mass index. No significant association was observed between measures of SDB and percent flow-mediated dilation or hyperemic flow in any model. In conclusion, this study supports a moderate association of SDB and larger baseline brachial artery diameter, which may reflect SDB-induced vascular remodeling. This study does not support a link between SDB and endothelial dysfunction as measured by brachial artery flow-mediated dilation.

Renal artery stenosis may cause or exacerbate hypertension and renal failure. Percutaneous transluminal renal artery stent placement, increasingly the first-line therapy for ostial atherosclerotic renal artery stenosis, can be complicated by in-stent restenosis weeks to months after the procedure. There is currently no consensus for the treatment of in-stent restenosis. Sirolimus-eluting stents have been shown to be effective to treat in-stent restenosis in the coronary circulation. We report a case of sustained 24-month patency after repair of recurrent renal artery in-stent restenosis with use of a sirolimus-eluting stent.

We report the case of a 60-year-old patient with acute renal failure and occluded bilateral renal arteries presenting with acute pulmonary edema and non-ST segment elevation myocardial infarction. The patient required renal replacement therapy with hemodialysis and was subsequently successfully treated with bilateral renal artery stent placement. Marked improvement in renal function was noted within 1 week with freedom from the need for renal replacement therapy at 4 months of follow-up.

Arteriovenous fistulae in the arm are commonly used for hemodialysis in end-stage renal disease. Although physiological steal with reverse flow in the artery distal to the fistula is common, hand ischemia or infarction are rare. The ischemic steal syndrome (hand or forearm ischemia) is usually a result of arterial disease proximal or distal to the fistula and/or poor collateral supply to the hand. The diagnosis is primarily clinical; however, markedly reduced digital pressures and pulse volume recordings support the diagnosis. Management requires imaging for focal stenoses or disease in arteries proximal and distal to the fistula from the aorta to the hand. We present a case caused by subclavian artery occlusion that was initially missed due to focusing investigation only on the fistula. We describe the percutaneous treatments and surgical revisions that attempt to restore flow to the hand without compromising the fistula.

A 22-year-old woman presented with a 3-month history of a pulsatile swelling in the right supraclavicular region. A CT angiogram revealed an aneurysm arising from the distal right subclavian artery. At surgery, the subclavian artery was almost entirely replaced by a well-vascularized tumor mass. The vascular tumor along with the native vessel was excised and replaced with a vascular prosthesis. Biopsy was suggestive of an epithelioid hemangioma (EH). In conclusion, an EH is a rare vascular tumor. The presence of vascular hyperplasia with plump endothelial cells protruding into the lumen is the most important discriminator in establishing the diagnosis of EH. Vascular neoplasms presenting as aneurysms should be considered, especially if other etiologies can be excluded.

Peripheral arterial disease (PAD), a relatively common manifestation of atherosclerotic vascular disease, is associated with significant morbidity and mortality. Although conventional risk factors contribute to the onset and progression of PAD, the role of ‘novel’ biomarkers in pathways of inflammation, thrombosis, lipoprotein metabolism, and oxidative stress in determining susceptibility to PAD is being increasingly recognized. Validation of novel risk factors for PAD may allow earlier detection, an improved understanding of disease etiology and progression, and the development of new therapies. In this review, we discuss available evidence for associations between novel circulating markers and several aspects of PAD including disease susceptibility, progression, functional limitation, and adverse outcomes.

The primary objective of this study was to examine in a post hoc secondary analysis, the interaction of race and gender as they affect graft patency, limb salvage and mortality among patients enrolled in the Project of Ex Vivo Vein Graft Engineering via Transfection III (PREVENT III). PREVENT III was a randomized controlled trial, designed to test the efficacy of edifoligide versus placebo in patients undergoing vein bypass for critical limb ischemia (CLI).

Population

PREVENT III enrolled 1404 patients, > 18 years of age with CLI (defined as arterial insufficiency with gangrene, a non-healing ischemic ulcer or rest pain) undergoing vein bypass graft surgery, across 83 North American centres.

Design and methods

The primary outcome measure for PREVENT III was time to occurrence of non-technical graft failure resulting in either graft revision or major amputation at 12 months post enrolment. Graft failure was assessed with angiographic or ultrasound surveillance and clinical follow-up at multiple intervals for up to 1 year. For this post hoc study, data from the PREVENT III trial were analysed as an observational cohort for the effect of race and gender on vascular endpoints and patient outcomes. For this analysis, race was dichotomized (‘black’ versus ‘non-black’) and race and gender were analysed in individual (dichotomized) and combined groups (black men, black women, non-black men, non-black women). Graft and limb-related endpoints consisted of primary patency (graft patency without intervention), primary assisted patency (graft patency after preventive intervention of a stenosis), secondary patency (graft patency after intervention on a thrombosed graft), major amputation (transtibial or higher) and composite outcomes including amputation-free survival and amputation/revision-free survival. Univariate analysis (using ANOVA and Fisher’s exact test) examined the association of race/gender groups with patient demographic characteristics and co-morbidities. Univariate logistic regression models examined the relationship of patient characteristics and 30-day peri-operative variables to clinical endpoints. Cox proportional-hazard models were used for 1-year outcomes for graft patency, limb salvage and patient mortality. Propensity score modelling was used to control for 16 covariates (including demographic variables, technical factors, selected co-morbidities and medications) to allow multivariable analysis of the associations and interactions between race and gender with outcomes. Propensity score adjustments nested covariates into the primary outcomes models to analyse the effects of the four combinations of race and gender.

Results

Of the 1404 patients enrolled in PREVENT III, 249 black patients (118 women and 131 men) were included. The overall peri-operative (30-day) mortality was 2.7% and no differences were observed between race and gender groups. Although black race and gender were not individually associated with primary patency at 30 days, the subgroup of black men were at increased risk of graft failure at 30 days compared to non-black men (hazard ratio [HR] = 2.96, 95% CI: 1.72–6.06, p < 0.01) and this difference persisted even after adjustments for high-risk grafts (odds ratio [OR] = 3.03, 95% CI: 1.29–7.12, p = 0.01). At 1 year, no significant differences were observed in mortality or primary patency rates among race and gender groups; however, black patients experienced reduced secondary patency compared to non-black patients (HR = 1.49, 95% CI: 1.08–2.06, p = 0.02) and limb salvage (HR = 2.02, 95% CI: 1.27–3.20, p < 0.01). Propensity score models indicated that this disparity was more pronounced among black women (secondary patency HR = 2.02, 95% CI: 1.27–3.20, p < 0.01; major amputation HR = 2.38, 95% CI: 1.18–4.83, p < 0.02). No significant differences were seen between race and gender subgroups in patient survival, amputation-free survival or amputation/revision-free survival.

Conclusions

No differences were observed in mortality or primary patency at 30 days or at 1 year among individual and combined race/gender groups. Black patients, especially black women, were found to have worse secondary patency and limb salvage outcomes after vein bypass surgery for CLI.

We determined whether higher levels of physical activity in daily life are associated with better brachial artery flow-mediated dilation (FMD) among individuals with lower extremity peripheral arterial disease (PAD). Participants were 111 men and women with PAD (ankle–brachial index (ABI) ≤ 0.95) who completed baseline testing in the Study to Improve Leg Circulation (SILC). We evaluated FMD of the brachial artery at baseline and at 60 seconds following 4 minutes of suprasystolic blood pressure cuff inflation. Physical activity was measured continuously over 7 days using a vertical accelerometer (Caltrac) and a pedometer (Digiwalker). Adjusting for age, sex, race, ABI, cardiovascular risk factors and other potential confounders, higher levels of physical activity were associated with a greater percent change in brachial artery FMD at 60 seconds post cuff deflation for both Caltrac (1st tertile of activity +4.81% change; 2nd tertile +4.60% change; 3rd tertile +7.23% change; p-trend = 0.018) and the Digiwalker (1st tertile of activity +3.76% change; 2nd tertile +6.25% change; 3rd tertile +7.25% change; p-trend = 0.001). Similar findings were observed for absolute change in brachial artery FMD 60 seconds after cuff deflation. In conclusion, higher levels of physical activity during daily life are associated significantly and independently with better brachial artery FMD among individuals with PAD, even after adjusting for confounders. ClinicalTrials.gov Identifier: NCT00106327.

The efficacy of treadmill walking training to improve pain-free (PFWD) and maximal (MWD) walking distance in patients with claudication is well documented. The effects of aerobic arm-ergometry to improve PFWD and MWD compared to treadmill walking or usual care are not known. Forty-one participants (29 male, 12 female, mean age 67.7 years, 92.7% smoking history, 36.6% with diabetes) with lifestyle-limiting claudication were randomized to 12 weeks of 3 hours/week of supervised exercise training using either arm-ergometry, treadmill walking, or a combination, versus control. PFWD and MWD were assessed before and after training, and after 12 weeks of follow-up. The 12-week MWD increased significantly in the arm-ergometry (+53%), treadmill (+69%), and combination (+68%) groups (p < 0.002 versus control). The 24-week MWD was maintained in the arm-ergometry (p = 0.009) and treadmill (p = 0.019) groups, whereas the combination group declined (p = 0.751) versus control. The 12-week PFWD increased significantly in the arm-ergometry group (+82%; p = 0.025 versus control). Change in PFWD in treadmill (+54%; p = 0.196 versus control) and combination (+60%; p = 0.107 versus control) groups did not reach statistical significance. PFWD improvement was maintained in the arm-ergometry group after a 12-week follow-up (+123%; p = 0.011 versus control). In conclusion, these pilot data demonstrate for the first time that dynamic arm exercise training can improve walking capability in people with peripheral arterial disease (PAD)-induced claudication compared to participants receiving usual care and that improvement was not different from that seen with treadmill walking exercise training. Dynamic arm exercise may be a therapeutic exercise option for patients with PAD.

Myeloperoxidase (MPO) is an enzymatic mediator of several inflammatory cascades and higher serum levels have been associated with increased risk of adverse cardiovascular events. We investigated the association of serum MPO with the ankle–brachial index (ABI) and peripheral arterial disease (PAD) in a bi-ethnic cohort of African-Americans and non-Hispanic white individuals. Participants included 1324 African-Americans (mean age 64 years, 71% women) and 1237 non-Hispanic white individuals (mean age 59 years, 57% women) belonging to hypertensive sibships. Serum levels of MPO were measured by solid phase sandwich immunoassay. ABI was measured using a standard protocol and PAD was defined as an ABI < 0.90. Multivariable regression analysis using generalized estimating equations were performed to assess whether serum MPO levels were associated with ABI and the presence of PAD. After adjustment for age and sex, higher MPO levels were significantly associated with lower ABI and the presence of PAD in African-Americans (p = 0.004 and p = 0.005, respectively) and in non-Hispanic white individuals (p = 0.001 and p = 0.016, respectively). After additional adjustment for conventional risk factors (diabetes, smoking status, total and high-density lipoprotein cholesterol, waist circumference, hypertension), prior history of myocardial infarction or stroke, and medication use (statins, aspirin, estrogen), higher MPO levels remained significantly associated with lower ABI and the presence of PAD in both African-Americans (p = 0.008 and p = 0.010, respectively) and non-Hispanic white individuals (p = 0.001 and p = 0.018, respectively). We conclude that higher MPO levels are associated with lower ABI and the presence of PAD in African-Americans and non-Hispanic white individuals.

The ankle–brachial index (ABI) post exercise is claimed to play a complementary role in the diagnosis or exclusion of intermittent claudication (IC). The interobserver variability of ABI measurements at rest and post exercise in patients with typical symptoms of IC is the subject of this study with emphasis on ABI post exercise. ABI at rest and post exercise were measured in both legs of 20 patients with typical symptoms of IC. After 15 minutes of rest these measurements were repeated by another observer. Analysis according to Bland–Altman was performed on 40 paired leg measurements at rest and 40 paired leg measurements post exercise. The average ABI at rest for the first observer was 0.84 (standard deviation ±0.18) and for the second was 0.84 (±0.17). Post-exercise averages were 0.73 (±0.25) and 0.74 (±0.27), respectively. The standard deviation of the ABI difference between observers was 0.08 at rest and 0.15 post exercise. The interobserver variability of the ABI was 10% at rest and 21% post exercise. The interobserver variability post exercise is an important given when rules are defined about how the ABI post exercise translates into a more reliable and objective diagnosis of IC.

The Cyprus Study is a prospective cohort study of cardiovascular disease (CVD). Its aim is to determine the relationship of intima–media thickness (IMT) of the common carotid (IMTcc), maximum thickness of IMT in the carotid bifurcation (IMTmax), number of carotid and femoral bifurcations with plaque and total plaque thickness (TPT) (sum of the maximum plaque measurements taken from the four bifurcations scanned) with the prevalence of clinical CVD. A total of 767 individuals (46% male) over the age of 40 years were recruited from a mountain village and a town outside the capital Nicosia. In addition to clinical examination, carotid and common femoral bifurcations were scanned with ultrasound. After controlling for conventional risk factors, there was little evidence of an association of IMTcc with CVD prevalence. However, IMTmax and TPT were associated with 2.9-fold (1.22 to 7.07) and 6.87-fold (2.42 to 19.43) increased odds of CVD prevalence, respectively. In conclusion, the TPT and number of bifurcations with plaque are more strongly associated with the prevalence of CVD. These findings warrant investigation in prospective studies to document associations with incident CVD events.

Carotid duplex ultrasonography (DUS) is routinely performed prior to coronary artery bypass graft surgery (CABG) on all patients > 65 years old because of the reported associated risk of finding concomitant carotid artery stenosis. Identifying risk factors that correlate with severe carotid stenosis may result in more cost-effective screening for patients with asymptomatic carotid artery disease prior to CABG. We performed a retrospective study to identify risk factors for significant carotid artery disease in patients scheduled to undergo CABG between March 2005 and March 2008 at the Massachusetts General Hospital. Patients with carotid stenosis ≥ 70% identified by DUS (n = 50) were matched by age and sex to control patients who had < 50% stenosis (n = 50). Data were analyzed using the chi-squared test or analysis of variance as appropriate. Logistic regression was used to examine multivariate correlates of carotid stenosis. A total of 643 patients were screened to arrive at the patient cohorts described below. This produced a prevalence of 7.7% for significant (> 70%) carotid disease. The patient cohorts were predominantly male with no significant difference in the incidence of diabetes, hypertension, extent of coronary artery disease (CAD) (i.e. left main coronary artery disease (LMCA) and one, two-, or three-vessel CAD) or lipid abnormalities in the two groups. Univariate analysis identified the presence of peripheral arterial disease (PAD, p = 0.001), a cervical bruit (p < 0.0001), a prior neurological event (p = 0.020), and the presence of an abdominal aortic aneurysm (AAA; p = 0.046) as significant predictors of ≥ 70% internal carotid artery stenosis. Logistic regression analysis revealed that the presence of a carotid bruit (p = 0.0068) and PAD (p = 0.0194) were associated with an increased risk of significant carotid artery disease. In conclusion, the presence of a carotid bruit or PAD predicts an increased likelihood of significant carotid artery disease in patients undergoing CABG. Unlike previous studies, LMCA or extent of CAD did not correlate with significant carotid artery disease. Using these predictive models, a prospective outcomes trial is required to validate these criteria.

Studies with l-arginine supplementation have shown inconsistent effects on endothelial function. The generation of guanidinoacetate (GAA) from l-arginine with subsequent formation of creatine and homocysteine and consumption of methionine may reduce the pool of l-arginine available for nitric oxide generation. Experimental studies suggest that creatine supplementation might block this pathway. We sought to determine the effects of l-arginine, creatine, or the combination on endothelium-dependent vasodilation and homocysteine metabolism in patients with coronary artery disease. Patients with coronary artery disease were randomized to l-arginine (9 g/day), creatine (21 g/day), l-arginine plus creatine, or placebo for 4 days (n = 26–29/group). Brachial artery flow-mediated dilation and plasma levels of l-arginine, creatine, homocysteine, methionine, and GAA were measured at baseline and follow-up. l-Arginine and creatine supplementation had no effects on vascular function. l-Arginine alone increased GAA (p < 0.01) and the ratio of homocysteine to methionine (p < 0.01), suggesting increased methylation demand. The combination of creatinine and l-arginine did not suppress GAA production or prevent the increase in homocysteine-to-methionine ratio. Unexpectedly, creatine supplementation (alone or in combination with l-arginine) was associated with an 11–20% increase in homocysteine concentration (p < 0.05), which was not attributable to worsened renal function, providing evidence against an effect of creatine on decreasing methylation demand. In conclusion, the present study provides no evidence that l-arginine supplementation improves endothelial function and suggests that l-arginine may increase methylation demand. Creatine supplementation failed to alter the actions of l-arginine on vascular function or suppress methylation demand. The unexpected increase in homocysteine levels following creatine supplementation could have adverse effects and merits further study, since creatine is a commonly used dietary supplement.

We previously reported an attenuation of both exercise hyperemia and measures of aerobic capacity in hypercholesterolemic mice. In this study, we expanded upon the previous findings by examining the temporal and quantitative relationship of hypercholesterolemia to aerobic and anaerobic capacity and by exploring several potential mechanisms of dysfunction. Eight-week-old wild type (n = 123) and apoE knockout (n = 79) C57BL/6J mice were divided into groups with distinct cholesterol levels by feeding with regular or high-fat diets. At various ages, the mice underwent treadmill ergospirometry. To explore mechanisms, aortic ring vasodilator function and nitrate (NO_x) activity, urinary excretion of NO_x, running muscle microvascular density and citrate synthase activity, as well as myocardial mass and histologic evidence of ischemia were measured. At 8 weeks of age, all mice had similar measures of exercise capacity. All indices of aerobic exercise capacity progressively declined at 12 and 20 weeks of age in the hypercholesterolemic mice as cholesterol levels increased while indices of anaerobic capacity remained unaffected. Across the four cholesterol groups, the degree of aerobic dysfunction was related to serum cholesterol levels; a relationship that was maintained after correcting for confounding factors. Associated with the deterioration in exercise capacity was a decline in measures of nitric oxide-mediated vascular function while there was no evidence of aberrations in functional or oxidative capacities or in other components of transport capacity. In conclusion, aerobic exercise dysfunction is observed in murine models of genetic and diet-induced hypercholesterolemia and is associated with a reduction in vascular nitric oxide production.

Percutaneous renal artery stenting is a common means of treating atherosclerotic renal artery stenosis. However, renal artery restenosis remains a frequent problem. The optimal treatment of restenosis has not been established and may involve percutaneous renal artery angioplasty or deployment of a second stent. Other modalities include cutting balloon angioplasty, repeat stenting with drug-eluting stents or endovascular brachytherapy. Most recently, use of polytetrafluoroethylene (PTFE)-covered stents may offer a new and innovative way to treat recurrent renal artery stenosis. We describe a case in a patient who initially presented with renal insufficiency and multi-drug hypertension in the setting of severe bilateral renal artery stenosis. Her renal artery stenosis was initially successfully treated by percutaneous deployment of bilateral bare metal renal artery stents. After initial improvement of her hypertension and renal insufficiency, both parameters declined and follow-up duplex evaluation confirmed renal artery in-stent restenosis. Owing to other medical co-morbidities she was felt to be a poor surgical candidate and was subsequently treated first with bilateral cutting balloon angioplasty and second with drug-eluting stent deployment. Each procedure was associated with initial improvement of renal function and blood pressure control, which then later deteriorated with the development of further significant in-stent restenosis. It was then decided to treat the restenosis using PTFE-covered stents. At 12 months of follow-up, the blood pressure had remained stable and renal function had normalized. The covered stents remained free of any significant neointimal tissue or obstruction.

We describe a patient with rotational vertebrobasilar ischemia (RVBI) due to vertebral artery (VA) compressive stenoses during neck rotation, complicated by an ostial atherosclerotic stenosis (OAS). Referred for ‘near-syncopal spells’, inquiry revealed a symptom-complex consistent with vertebrobasilar transient ischemic attacks (TIAs) provoked by head rotation. VA dynamic angiography with imaging via prevertebral subclavian injections in neck-rotated positions while reproducing symptoms, demonstrated two compressive stenoses not present in the neck-neutral position, establishing the diagnosis of RVBI due to CT-demonstrated cervical spondylosis. There was an occluded contralateral VA, isolated posterior circulation, and absent vertebral collateral flow. Disabling symptoms persisted despite using a cervical collar. Surgical decompression of the dynamic stenoses would not address the OAS, was considered high risk, and absence of a suitable donor artery precluded distal VA reconstruction. RVBI resolved with ostial stent placement by improving perfusion pressure across the compressive stenoses. To our knowledge, this is the first report of RVBI in which the affected VA had an obstructive atherosclerotic stenosis in addition to the characteristic rotation-induced dynamic stenoses, and the first report of stent placement in the culprit artery to treat this disorder. Diagnosis depends on recognizing the association of symptoms with positional neck changes and VA dynamic angiography demonstrating the compressive stenosis while reproducing symptoms. This case illustrates the management complexities when there are coexisting abnormalities, emphasizing the need to individualize treatment. RVBI is a potentially correctable cause of TIAs and particularly relevant due to the aging population which has a significant incidence of both degenerative cervical and atherosclerotic cerebrovascular disease.

Peripheral arterial disease (PAD) is a common disease, and intermittent claudication (IC) is a life-changing symptom. Exercise therapy has been demonstrated to be an effective treatment for IC in a supervised setting; however, most insurance carriers do not reimburse for exercise therapy. As a result, non-supervised programs have largely replaced supervised programs, despite limited evidence of their benefit. In this retrospective study of the results of our routine care, we analyzed the outcomes of a structured 6-month home-based exercise program for IC. A total of 120 patients with PAD and IC were enrolled in a home-based exercise program. Forty-one patients fulfilled program requirements, for a 34.2% completion rate. Those who completed the program demonstrated an 86.4% improvement in their initial claudication distance and a 19.8% improvement in their absolute claudication distance. No patient factors identified those who did not complete the program versus those who completed the program and thus attained the observed benefit. We did observe that 47% of those who did not complete the program dropped-out by not keeping their follow-up appointment. Although patients who completed our program improved from baseline, it was less dramatic than reported in studies of supervised programs. The design of home-based programs should include mechanisms that maximize compliance in returning for follow-up appointments.

In a (negative) multicenter randomized trial on management for inoperable critical lower limb ischemia, comparing spinal cord stimulation and best medical treatment, a number of pre-defined factors were analyzed for prognostic value. We included a radiological arterial disease score, modified from the SVS/ISCVS runoff score. The purpose of this analysis was to evaluate clinical factors and commonly used circulatory measurements for prognostic modeling in patients with critical lower limb ischemia. We determined the incidence of amputation and its relation to various pre-defined risk factors. A total of 120 patients with critical limb ischemia were included in the study. The integrity of circulation in the affected limb was evaluated on five levels: suprainguinal, infrainguinal, popliteal, infrapopliteal and pedal. A total radiological arterial disease score was calculated from 1 (full integrity of circulation) to 20 (maximally compromised state). We used Cox regression analysis to quantify prognostic effects and differential treatment (predictive) effects. Major amputation occurred in 33% of the patients at 6 months and in 51% at 2 years. The presence of ischemic skin lesions and the radiological arterial disease score were independent prognostic factors for amputation. Patients with ulcerations or gangrene had a higher amputation risk (hazard ratio 2.38, p = 0.018 and 2.30, p = 0.036 respectively) as well as patients with a higher radiological arterial disease score (hazard ratio 1.17 per increment, p = 0.003). We did not observe significant interactions between prognostic factors and the effect of spinal cord stimulation. In conclusion, in patients with critical lower limb ischemia, the presence of ischemic skin lesions and the described radiological arterial disease score can be used to estimate amputation risk.

The objective of this study was to perform a cultural adaptation and define the validity of the Turkish version of the Intermittent Claudication Questionnaire (ICQ) in order to provide a practical instrument for the evaluation of the impact of intermittent claudication (IC) on patients’ quality of life and response to therapy. A standard ‘forward–backward’ translation method was used to translate the questionnaire into Turkish. Reliability was assessed by internal consistency of the questionnaire reporting Cronbach’s coefficient, test–retest reliability that was assessed with the intraclass correlation between instrument scores over time and with the Spearman–Brown coefficient as a variant of split-half reliability. Validity was examined by correlation of the ICQ with the scores of the SF-36 and its eight domains. Eighty-four patients (mean age, 60.7 ± 7.3 years; male, 57%) were given the ICQ and a final completion rate of 98.8% (83 patients) was reached. The mean total ICQ score was 39.1 ± 21.8 (SD) (0–100) for the first application of the questionnaire. Thirty patients out of the eligible 83 completed the questionnaire at two time points with a 1-day interval. For the retest, the total ICQ score was 40.6 ± 26.1 (4.7–97.2). The total SF-36 score of all the study patients was 33.8 ± 20.7 (3.0–81.0). Cronbach’s was 0.95; the Spearman–Brown coefficient was 0.92; and the intraclass correlation coefficient for the two measurements was 0.91. For the total score and for the scores of domains except the emotional role domain, the correlations were high and all the correlations were statistically significant. In conclusion, the Turkish version of the ICQ, which is a disease-specific, self-administered, and practical instrument, is reliable and valid. We recommend its use to assess the effect of IC on the quality of life of patients in clinical trials and in daily clinical practice.

Acute penetrating thoracic aortic ulcers (PTAU) are associated with vessel rupture, particularly when intramural haematoma (IMH) is present. Although surgical repair is the treatment of choice for PTAU in the aortic arch, definitive treatment of PTAU in other locations of the thoracic aorta remains controversial, particularly in this frail cohort of patients. Recent series of elective and semi-elective endovascular stent-graft repair of PTAU of the descending thoracic aorta show comparable results with the previously advocated best medical management. We report our results from a retrospective, observational study of acute stent-graft repair of symptomatic PTAU. Between 2000 and 2005, 11 patients (seven male, four female; median age 71 years) presented with acute PTAU. CT scans demonstrated an associated IMH in six, a contained leak in three or rupture in four unstable patients. All were covered by a single endovascular stent [Gore (5), Talent (5), Zenith (1); 10 inserted via the groin and one via iliac conduit within 1 week of presentation (five < 24 h). Technical success was 90.90% (10/11) and 3/11 (27%) died within 30 days (two ARDS, one a persistent leak and rupture at 48 h). One patient developed transient paraplegia; three haemothoraces required chest drains, one of which subsequently required empyema drainage. In survivors, CT scans were satisfactory, with no further intervention required at 32.5 (6–66) months of median follow-up. In conclusion, endovascular management of acute PTAU appears effective and durable with mortality rates that are likely to be better than for open surgery. However, haemodynamic compromise at presentation remains a robust denominator of over-all survival.

Bilirubin may have a major role in the prevention of cardiovascular disease based on recent data regarding its anti-oxidant properties. We determined the relationship between total serum bilirubin and vascular reactivity in a large cohort of individuals with diabetes, a disease associated with known oxidant stress. We studied 302 individuals: 52 controls, 37 with type 1 diabetes, 213 with type 2 diabetes. High-resolution ultrasound was used to measure flow-mediated dilation (FMD; endothelium-dependent) and nitroglycerin-induced dilation (NID, endothelium-independent) of the brachial artery. Laser Doppler perfusion imaging was used to measure microvascular reactivity in the forearm skin before and after iontophoresis of acetylcholine (endothelium-dependent) and sodium nitroprusside (endothelium-independent). Bilirubin levels were higher in the type 2 diabetes group (0.71 ± 0.34 mg/dl) compared to controls (0.56 ± 0.26 mg/dl, p < 0.0001). A weak inverse correlation was observed between bilirubin and FMD (r = –0.125, p = 0.032) and skin endothelium-dependent vasodilation (r = –0.157, p = 0.019). In multivariate analyses, however, these correlations were not statistically significant. There is no association between bilirubin levels and vascular reactivity in the macro- and microcirculation of individuals with diabetes. Bilirubin, therefore, does not correlate with predictors of cardiovascular risk in the diabetic population.

Infant feeding practices have an impact on health in later life, although the evidence for its effects on cardiovascular health is not so clear. The aim of this study was to investigate the relationship between breastfeeding in infancy and vascular function in later childhood. Infant feeding data, together with demographic and clinical information, were obtained prospectively from a cohort of children from birth until 2 years of age. Vascular function was assessed in 159 children, now aged 11–14 years, by measuring their skin microvascular responses to iontophoretic administration of the endothelium-dependent vasodilator acetylcholine. Endothelial function was significantly better in children who had been breastfed than in those who had received infant milk formula (p = 0.001), after adjustment for potential confounding factors. Linear regression showed that acetylcholine responses were significantly related to the duration of breastfeeding (r = 0.30, p = 0.006). The risk of later cardiovascular disease may be reduced by exclusively breastfeeding during infancy. These findings have potential public health implications, and support policies aimed at promoting breastfeeding.

Digital thermal monitoring (DTM) of vascular function during cuff-occlusive reactive hyperemia relies on the premise that changes in fingertip temperature during and after an ischemic stimulus reflect changes in blood flow. To determine its utility in individuals with and without known coronary heart disease (CHD), 133 consecutive individuals (age 54 ± 10 years, 50% male, 19 with known CHD) underwent DTM during and after 2 minutes of supra-systolic arm cuff inflation. Fingertip temperatures of the occluded and non-occluded fingertips were measured simultaneously. Post-cuff deflation temperature rebound (TR) was lower in the CHD patients and in those with an increased Framingham risk score (FRS) compared to the normal group. After adjustment for age, sex, and cardiac risk factors, TR was significantly lower in those with CHD compared to those without CHD (p < 0.05). This study demonstrates that vascular dysfunction measured by DTM is associated with CHD and an increased FRS, and could potentially be used to identify high-risk patients.

Primary vascular tumours are very rare. Most cases are leiomyosarcomas usually arising from large veins such as the inferior vena cava. Involvement of major veins in the limbs is uncommon and of small veins or tributaries extremely uncommon. We report a case of leiomyosarcoma originating from a tributary of the femoral vein in a 55-year-old woman.

The discovery, over a decade ago, of endothelial progenitor cells that are able to participate in neovascularization of adult tissue has been greeted enthusiastically because of the potential for new cell-based therapies for therapeutic angiogenesis. Since that time, an ever-growing list of candidate cells has been proposed for cardiovascular regeneration. However, to date, pre-clinical and clinical studies evaluating the therapeutic potential of various cell therapies have reported conflicting results, generating controversy. Key issues within the field of cell therapy research include a lack of uniform cellular definitions, as well as inadequate functional characterization of the role of putative stem/progenitor cells in angiogenesis. Given the mixed results of initial clinical studies, there is now a scientific imperative to understand better the vascular biology of candidate cells in order to better translate cell therapy to the bedside. This review will provide a translationally relevant overview of the biology of candidate stem/progenitor cells for therapeutic angiogenesis.

The purpose of this study was to evaluate the utility of 16-slice multidetector computed tomographic (MDCT) angiography for identifying anatomic features of aberrant subclavian arteries. Seventeen patients with aberrant subclavian arteries were assessed by MDCT angiography. The aortic arch position, the presence of a Kommerell’s diverticulum, aneurysm, vascular compression of trachea and oesophagus and associated cardiovascular abnormalities were evaluated. MDCT findings were confirmed by surgery in eight patients but in the other nine patients no further evaluation or management was warranted as the aberrant subclavian artery had no significant clinical consequence. Eleven patients had an aberrant right subclavian artery arising from the left aortic arch and six patients had an aberrant left subclavian artery arising from the right aortic arch. Kommerell’s diverticulum was identified in three patients with an aberrant right subclavian artery and in five patients with an aberrant left subclavian artery. In two patients it was aneurysmal. Oesophageal compression was detected in eight patients, and tracheal compression was identified in only one paediatric patient. An aberrant subclavian artery was associated with complex congenital heart disease in one patient, intracardiac defects in two patients, aortic coarctation in two patients, patent ductus arteriosus in two patients and an aberrant vertebral artery in one patient. In conclusion, MDCT angiography is superior to digital subtraction angiography for the assessment of aberrant subclavian arteries since digital subtraction angiography has only a poor ability to visualize adjacent structures completely and is invasive in nature. MDCT angiography or magnetic resonance angiography are the current standard in the initial evaluation of thoracic vascular anomalies.

In coronary artery disease (CAD), a concomitant peripheral arterial disease (PAD) entails a more severe coronary atherosclerosis. We hypothesized that the severity of carotid artery disease is greater in CAD+PAD than in CAD alone. In 90 CAD and 79 CAD+PAD patients, carotid plaque echolucency was measured by gray-scale median (GSM), and the degree of carotid stenosis by routine Doppler criteria. Plaques were absent in 20 (22.2%) CAD and 8 (10.1%) CAD+PAD patients (p = 0.035), while the prevalence of carotid stenosis ≥ 50% was 16.7% and 25.3%, respectively (p = 0.166). The GSM score was 45.1 [21.7–67.7] in CAD+PAD vs 60.1 [44.9–83.1] in CAD alone (p < 0.001). Consistently, hypoechoic plaques (GSM < 25th percentile) were more common in CAD+PAD than in CAD patients (38.0% vs 11.4%, p < 0.001). On multivariate analysis, CAD+PAD was the only variable significantly associated with hypoechoic plaques (OR = 4.16, 95% CI 1.68–10.28). However, when the leukocyte count was added to the model, it showed the strongest association with hypoechoic plaques (OR = 6.70, 95% CI 2.13–21.10). In conclusion, compared with CAD alone patients, those with concomitant PAD showed a greater prevalence of plaques with characteristics of instability. Thus, our data suggest that in CAD+PAD, evaluation of carotid plaque echogenicity could contribute to improve clinical decision-making and differentiate treatments for individual patients.

Secondary prevention of cardiovascular disease after carotid endarterectomy should include management of low-density lipoprotein (LDL) levels, but increased LDL levels are undertreated in these patients. We examined trends in statin use and LDL goal achievement in veterans undergoing carotid endarterectomy (CEA), a medically high-risk group with high rates of cardiovascular morbidity and mortality. The records of all CEA performed between 1995 and 2005 in the Connecticut Veterans’ Affairs (VA) hospital were reviewed. Kaplan-Meier analysis was used to analyze long-term outcomes. ANOVA was used for comparisons between groups. A total of 309 CEA procedures were performed in 298 patients. The mean follow-up was 4.1 years. Statin use increased over time (12% in 1995, 84% in 2005) and mean LDL levels decreased (105 mg/dl in 1997, 90 mg/dl in 2007). The number of patients achieving LDL goals of 100 mg/dl or 70 mg/dl increased. Mean HDL levels decreased (53 mg/dl in 1997 and 38 mg/dl in 2007). Patients with three or more comorbid medical conditions were more likely to achieve LDL goals. At 12 years, freedom from stroke was 91%, freedom from myocardial infarction was 46% and survival was 12%. In conclusion, over the last decade, among patients who have undergone CEA, statin use has increased and LDL levels have improved.

We investigated whether administration of estradiol to male mice augments mobilization of bone marrow-derived endothelial progenitor cells (EPC) and incorporation into foci of neovascularization after hind-limb ischemia, thereby contributing to blood flow restoration. Mice were randomized and implanted with placebo pellets or pellets containing low-dose estradiol (0.39 mg) or high-dose estradiol (1.7 mg). Hind-limb ischemia was induced by unilateral resection of the left femoral artery 1 week after pellet implantation, then EPC mobilization and functional recovery was evaluated. EPC recruitment was assessed in mice transplanted with bone marrow from transgenic donors expressing β-galactosidase driven by the Tie-2 promoter. EPC culture assay performed 2 weeks after pellet implantation revealed a significantly greater (p < 0.05) number of circulating EPCs in the high-dose estradiol group than in the low-dose estradiol and placebo groups. At 3 and 4 weeks after induction of hind-limb ischemia, perfusion was significantly greater (p < 0.05) in high-dose estradiol mice than in mice implanted with the low-dose estradiol or placebo pellets. At 1 and 4 weeks after hind-limb ischemia surgery, more bone marrow-derived EPCs, identified as β-galactosidase-positive cells, were observed in ischemic regions from high-dose estradiol animals than in low-dose (p < 0.05) or placebo groups (p < 0.05). These results indicate that estradiol dose-dependently increases the levels of EPCs in peripheral blood in male animals, improves the recovery of blood flow, and decreases limb necrosis after hind-limb ischemia, and that this enhancement occurs, in part, through augmentation of EPC mobilization and greater incorporation of bone marrow-derived EPCs into foci of neovascularization.

Signals in the tumor necrosis factor (TNF-) pathway are upregulated after ischemia, yet its role in peripheral ischemia remains unclear. We investigated the effect of TNF- receptor 1 (TNFR-1) in acute limb ischemia of TNFR-1 knockout (TNFR-1^–/–) and wild type (WT, TNFR-1^+/+) mice. Laser Doppler scanning showed that although pre-ischemia blood flow levels were similar in these mice, the limb reperfusion after ischemia was significantly higher in TNFR-1^–/– mice 1–7 days after injury. Consistently, fewer TUNEL-positive cells, less DNA fragmentation, and a lower ischemic score were detected in the TNFR-1^–/– group when compared to WT controls. Western blot analysis revealed less expression of pro-apoptotic markers Bax and cleaved caspase-3 in TNFR-1^–/– mice 1 day after ischemia, supporting the hypothesis that the absence of TNFR-1 results in a reduction of apoptosis. The rate of post-ischemia amputation was 50% in WT mice versus 0% in TNFR-1^–/– mice. However, immunohistochemical co-staining of microvessel marker CD31 and cellular proliferation marker BrdU 21 days after ischemia showed an impaired angiogenic activity in the TNFR-1^–/– mice. These data were supported by Western blot analysis, which indicated a decreased expression of angiopoietin-1 (Ang-1) and its receptor Tie-2 in TNFR-1^–/– mice. Our results suggest that a deficiency in TNFR-1 prevents the activation of death-related proteins downstream to TNF- and attenuates apoptosis in acute limb ischemia, but the lack of TNFR-1 signaling hinders the belated angiogenesis mediated by the Ang-1/Tie-2 pathway.

We report a case of severe deep venous thrombosis (DVT) treated with multimodality therapy that was complicated by sepsis due to thrombus likely infected by Salmonella virchow. We review the current therapeutic options in the therapy of severe DVT and cardiovascular pathology associated with non-typhoid Salmonella.

As a marker of generalized atherosclerosis, peripheral arterial disease (PAD) has implications not only for the affected lower extremity but also to overall cardiovascular health. It confers an increased risk of non-fatal and fatal vascular events which increases with the severity of the disease. Patient-based studies have shown that individuals with advanced PAD tend to perform poorly on cognitive tests compared to controls. In population studies, PAD is associated with an increased cognitive decline independently of previous cerebrovascular disease and cardiovascular risk factors. A low ankle–brachial index (ABI) may be an early predictor of cognitive decline and of potential value in identifying individuals at increased risk of cognitive impairment. In patients with PAD, secondary preventive measures directed at decreasing the long-term systemic vascular complications may also be important to the preservation of cognitive health. However, evidence suggests that PAD patients may be undertreated with regard to atherosclerotic risk factors, as demonstrated by an undue emphasis on symptom relief rather than essential risk factor reduction. More research needs to be carried out to determine the predictors of cognitive function in PAD patients, whether subtle cognitive disturbances are related to activities of daily living, including medical treatment compliance, and whether neuroprotective strategies and atherosclerotic risk factor control positively influence cognitive function in these high-risk patients.

Optical coherence tomography (OCT) is an emerging imaging modality that provides high-resolution, microstructural information on atherosclerotic plaques in biological systems. Intracoronary OCT can identify thin-cap fibroatheroma and other vulnerable plaques that may be responsible for acute coronary events. These characteristics make OCT helpful in guiding coronary management and interventions, including stent apposition and early identification of procedure-related complications. OCT is being assessed for its potential role in carotid plaque characterization and in the diagnosis of peripheral arterial atherosclerosis. Its current use in studying carotid and cerebral vasculature and in the diagnosis of peripheral arterial diseases is limited and ill defined, but it is finding increasing application in these areas. Its performance can be further improved by increasing the signal to noise ratio and by using dynamic focus tracking techniques. It can potentially be used to monitor the progression and regression of atherosclerosis in the coronary, cerebral and peripheral vasculature. New indications for its use in vascular medicine are emerging as its technology continues to improve over time.

Collagens constitute a major portion of the extracellular matrix in the atherosclerotic plaque, where they contribute to the strength and integrity of the fibrous cap, and also modulate cellular responses via specific receptors and signaling pathways. This review focuses on the diverse roles that collagens play in atherosclerosis; regulating the infiltration and differentiation of smooth muscle cells and macrophages; controlling matrix remodeling through feedback signaling to proteinases; and influencing the development of atherosclerotic complications such as plaque rupture, aneurysm formation and calcification. Expanding our understanding of the pathways involved in cell–matrix interactions will provide new therapeutic targets and strategies for the diagnosis and treatment of atherosclerosis.