Vascular Medicine

Abstract

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.

Abstract

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.

Abstract

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.

Abstract

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.

Abstract

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.

Abstract

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.

Abstract

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.

Abstract

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.

Abstract

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.

Abstract

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.