Severity Of Peripheral Arterial Disease Research Articles

Increased levels of symmetric dimethyl-arginine are associated with all-cause mortality in patients with symptomatic peripheral arterial disease

Recent interest has focused on the role of the methyl-arginines, endogenous inhibitors of nitric oxide, as adverse prognostic indicators. To date, few studies have assessed the role of symmetric dimethyl-arginine (SDMA) in patients with peripheral arterial disease. We aimed to determine the relationship, if any, of SDMA to all-cause mortality and disease severity as assessed by the ankle-brachial index (ABI) in patients with symptomatic peripheral arterial disease (PAD). In 238 patients with symptomatic PAD and an ABI of <0.8, l-arginine, asymmetric dimethyl-arginine (ADMA) and SDMA levels were measured by hydrophilic-interaction liquid chromatography-electrospray tandem mass spectrometry. The median follow-up was 6 years 11 months (interquartile range [IQR], 4 years 5 months-7 years 10 months). SDMA and ADMA levels were higher in those who died compared with those who survived (0.51 [IQR, 0.44-0.66] μmol/L vs 0.46 [IQR, 0.39-0.55] μmol/L, P ≤ .001; and 0.48 [IQR, 0.41-0.55] μmol/L vs 0.45 [IQR, 0.39-0.50] μmol/L, P = .007, respectively). l-arginine levels were similar in the two groups. On multivariate analysis, SDMA and ADMA as continuous variable were significantly associated with mortality (P = .001). For SDMA and ADMA, the highest compared with the lowest quartile levels were significantly associated with mortality (SDMA: hazard ratio, 3.855; 95% confidence interval, 1.625-9.143; P = .002; ADMA: hazard ratio, 2.277; 95% confidence interval, 1.114-4.654; P = .024). ADMA and SDMA showed a negative correlation with severity of PAD as assessed by ABI (r = -0.236, N = 216, P < .001; r = -0.209, N = 208, P = .002, respectively). The novel finding of this study is that SDMA levels were predictive of all cause-mortality and correlated with disease severity. Further studies should assess the role of nitric oxide donors in patients with high levels of SDMA.

Racial Disparities in Outcomes of Endovascular Procedures for Peripheral Arterial Disease: An Evaluation of California Hospitals, 2005–2009

Racial/ethnic disparities in treatment outcomes of peripheral arterial disease (PAD) are well documented. Compared with non-Hispanic (NH) whites, blacks and Hispanics are more likely to undergo amputation and less likely to undergo bypass surgery for limb salvage. Endovascular procedures are being increasingly performed as first line of therapy for PAD. In this study, we examined the outcomes of endovascular PAD treatments based on race/ethnicity in a contemporary large population-based study. We used Patient Discharge Data from California's Office of Statewide Health Planning and Development to identify all patients over the age of 35 who underwent a lower extremity arterial intervention from 2005 to 2009. A look-back period of 5 years was used to exclude all patients with prior lower extremity arterial revascularization procedures or major amputation. Cox proportional hazards regression was used to compare amputation-free survival and time to death within 365 days. Logistic regression was used for comparison of 1-month myocardial infarction, 1-month major amputation, 1-month all-cause mortality, 12-month major amputation, 12-month reintervention, and 12-month all-cause mortality rates among NH white, black, and Hispanic patients. These analyses were adjusted for age, gender, insurance status, severity of PAD, comorbidities, history of coronary artery angioplasty or bypass surgery, or history of carotid endarterectomy. Between 2005 and 2009, a total of 41,507 individuals underwent PAD interventions, 25,635 (61.7%) of whom underwent endovascular procedures. There were 17,433 (68%) NH whites, 4,417 (17.2%) Hispanics, 1,979 (7.7%) blacks, 1,163 (4.5%) Asian/Native Hawaiians, and 643 (2.5%) others in this group. There was a statistically significant difference in the amputation-free survival within 365 days among the NH white, Hispanic, and black groups (P < 0.0001); the hazard ratio for amputation within 365 days was 1.69 in Hispanics (95% confidence interval [CI] 1.51-1.90, P < 0.0001) and 1.68 in blacks (95% CI 1.44-1.96, P < 0.001) compared with NH whites following endovascular procedures after adjusting for age, gender, insurance status, comorbidities, severity of PAD, history of coronary artery angioplasty or bypass surgery, or history of carotid endarterectomy. After adjusting for the aforementioned confounders, the first reintervention within 12 months was also significantly associated with race/ethnicity (P = 0.002). Odds ratio for reintervention was 1.17 in blacks (95% CI 1.06-1.30, P = 0.002) and 1.084 in Hispanics (95% CI 1.00-1.16, P = 0.04) compared with NH whites. In this contemporary large population-based study, we demonstrated that even among matched cohorts Hispanics and blacks have worse amputation-free survival than NH whites following endovascular therapy. Our study also found that Hispanics and blacks are more likely to undergo lower extremity arterial reinterventions than NH whites. Further research is crucial in understanding if higher reintervention rates in Hispanics and blacks are because of more severe disease and/or poor access to proper follow-up care and optimal medical management.

Scientific Prize Papers

Objective Recent interest has focused on the role of the methyl-arginines, endogenous inhibitors of nitric oxide, as adverse prognostic indicators. To date, few studies have assessed the role of symmetric dimethyl-arginine (SDMA) in patients with peripheral arterial disease. We aimed to determine the relationship, if any, of SDMA to all-cause mortality and disease severity as assessed by the ankle-brachial index (ABI) in patients with symptomatic peripheral arterial disease (PAD). Methods In 238 patients with symptomatic PAD and an ABI of Results The median follow-up was 6 years 11 months (interquartile range [IQR], 4 years 5 months-7 years 10 months). SDMA and ADMA levels were higher in those who died compared with those who survived (0.51 [IQR, 0.44-0.66] μmol/L vs 0.46 [IQR, 0.39-0.55] μmol/L, P ≤ .001; and 0.48 [IQR, 0.41-0.55] μmol/L vs 0.45 [IQR, 0.39-0.50] μmol/L, P = .007, respectively). l-arginine levels were similar in the two groups. On multivariate analysis, SDMA and ADMA as continuous variable were significantly associated with mortality ( P = .001). For SDMA and ADMA, the highest compared with the lowest quartile levels were significantly associated with mortality (SDMA: hazard ratio, 3.855; 95% confidence interval, 1.625-9.143; P = .002; ADMA: hazard ratio, 2.277; 95% confidence interval, 1.114-4.654; P = .024). ADMA and SDMA showed a negative correlation with severity of PAD as assessed by ABI ( r = −0.236, N = 216, P r = −0.209, N = 208, P = .002, respectively). Conclusions The novel finding of this study is that SDMA levels were predictive of all cause-mortality and correlated with disease severity. Further studies should assess the role of nitric oxide donors in patients with high levels of SDMA.

Serum nesfatin-1 is reduced in type 2 diabetes mellitus patients with peripheral arterial disease.

BackgroundNesfatin-1, recently identified as a satiety regulator, elicits an anti-atherosclerosis effect. Our study was designed to determine whether there is an association between serum nesfatin-1 and the development and severity of peripheral arterial disease (PAD) in patients with type 2 diabetes mellitus (T2DM).Material/MethodsThis cross-sectional study included 355 T2DM patients (200 without PAD and 155 with PAD).ResultsT2DM patients with PAD exhibited marked lower serum nesfatin-1 concentrations than those without PAD. Multivariable logistic regression analysis indicated an inverse association of serum nesfatin-1 concentrations with the development of PAD in T2DM patients (OR 0.008, 95% CI 0.002 to 0.028; P<0.001). Simple linear regression analysis showed a marked correlation between serum nesfatin-1 concentrations and body mass index (BMI), homeostasis model assessment of insulin resistance (HOMA-IR), C-reactive protein (CRP), and ankle-brachial index (ABI) in T2DM patients. By contrast, multivariable analysis showed only BMI and ABI as independent correlates of serum nesfatin-1.ConclusionsOur study shows an association of serum nesfatin-1 concentrations and the development and severity of PAD in T2DM patients.

Site-specific association between distal aortic pulse wave velocity and peripheral arterial stenosis severity: a prospective cardiovascular magnetic resonance study.

BackgroundVascular disease expression in one location may not be representative for disease severity in other vascular territories, however, strong correlation between disease expression and severity within the same vascular segment may be expected. Therefore, we hypothesized that aortic stiffening is more strongly associated with disease expression in a vascular territory directly linked to that aortic segment rather than in a more remote segment. We prospectively compared the association between aortic wall stiffness, expressed by pulse wave velocity (PWV), sampled in the distal aorta, with the severity of peripheral arterial occlusive disease (PAOD) as compared to atherosclerotic markers sampled in remote vascular territories such as PWV in the proximal aorta and the normalized wall index (NWI), representing the vessel wall thickness, of the left common carotid artery.MethodsForty-two patients (23 men; mean age 64±10 years) underwent velocity-encoded cardiovascular magnetic resonance (CMR) in the proximal and distal aorta, whole-body contrast-enhanced MR angiography (CE-MRA) and carotid vessel wall imaging with black-blood CMR in the work-up for PAOD. Strength of associations between aortic stiffness, carotid NWI and peripheral vascular stenosis grade were assessed and evaluated with multiple linear regression.ResultsStenosis severity correlated well with PWV in the distal aorta (Pearson rP=0.64, p<0.001, Spearman rS=0.65, p<0.001) but to a lesser extent with PWV in the proximal aorta (rP=0.48, p=0.002, rS=0.22, p=0.18). Carotid NWI was not associated with peripheral stenosis severity (rP=0.17, p=0.28, rS=0.14, p=0.37) nor with PWV in the proximal aorta (rP=0.22, p=0.17) nor in the distal aorta (rP=0.21, p=0.18). Correlation between stenosis severity and distal aortic PWV remained statistically significant after correction for age and gender.ConclusionsDistal aortic wall stiffness is more directly related to peripheral arterial stenosis severity than markers from more remote vascular territories such as proximal aortic wall stiffness or carotid arterial wall thickness. Site-specific evaluation of vascular disease may be required for full vascular risk estimation.

The Correlation between the Psoas Muscle/Vertebral Body Ratio and the Severity of Peripheral Artery Disease

The measurement of psoas muscle area is a new and potentially useful tool for assessing the frailty of patients in the context of various disease states ranging from cancer to abdominal aortic aneurysms (AAAs). Considering the similarity of risk factors for frailty and atherosclerosis, we sought to investigate whether patients with peripheral artery disease (PAD) have smaller psoas muscle areas in general. Furthermore, we investigated whether PAD symptom severity correlates with psoas muscle size. A chart review was conducted on 146 patients with PAD. Of these patients, 85 (58%) had a computed tomography scan within the last 5 years and were included in the study. Fifty-five patients with AAA and no occlusive disease were included as controls. Cross-sectional areas of the psoas muscles and L4 vertebral body were collected at the mid-L4 level for all patients. Total psoas muscle area was calculated and divided by L4 area to correct for body habitus. Ankle-brachial indices and Rutherford classification were collected as measures of PAD severity. Logistic and multiple regressions were run to assess the difference in psoas muscle/vertebral body ratio between patients with PAD and AAA and within PAD patients, respectively. PAD patients have a lower psoas muscle/vertebral body ratio controlled for sex and age than patients with AAA (P<0.05). However, among patients with PAD, psoas muscle/vertebral body ratio does not correlate with severity of symptoms. Using psoas muscle area as a measure of frailty, patients with PAD may be frail as a group. However, the severity of each patient's symptoms does not appear to correlate with the patient's degree of frailty. Prospective studies with larger populations are needed to clarify whether the psoas muscle area has any prognostic value in PAD.

Clinical assessment of patients with peripheral arterial disease.

Peripheral arterial disease (PAD) describes the clinical manifestations of atherosclerosis affecting the circulation in the legs. The severity of PAD is classified according to symptom severity, time course, and anatomical distribution. The signs and symptoms of PAD reflect the degree of circulatory compromise and whether there has been a gradual reduction in the circulation or an abrupt, uncompensated decrease. Accurate clinical assessment underpins decisions on management strategy and should objectively assess the severity of the ischemia and need for revascularization. Clinical history should discriminate symptoms of PAD from other conditions presenting with leg pain, elucidate cardiovascular risk factors and the effect of symptoms on the patient's quality of life. Clinical examination includes signs of general cardiovascular disease and associated conditions before assessing the circulation and viability of the limb. Palpation of peripheral pulses must be augmented by determination of the ankle brachial pressure index using hand held Doppler. A whole patient approach to management is required and must include modification of cardiovascular risk status as well as dealing with the local circulatory manifestation of PAD.

Matrix metalloproteinase 10 is associated with disease severity and mortality in patients with peripheral arterial disease

Peripheral arterial disease (PAD) is associated with poor prognosis in terms of cardiovascular (CV) morbidity and mortality. Matrix metalloproteinases (MMPs) contribute to vascular remodeling by degrading extracellular matrix components and play a role in atherosclerosis as demonstrated for MMP-10 (stromelysin-2). This study analyzed MMP-10 levels in PAD patients according to disease severity and CV risk factors and evaluated the prognostic value of MMP-10 for CV events and mortality in lower limb arterial disease after a follow-up period of 2 years. MMP-10 was measured by enzyme-linked immunosorbent assay in 187 PAD patients and 200 sex-matched controls. PAD patients presented with increased levels of MMP-10 (702 ± 326 pg/mL control vs 946 ± 473 pg/mL PAD; P < .001) and decreased levels of tissue inhibitor of matrix metalloproteinase 1 (312 ± 117 ng/mL control vs 235 ± 110 ng/mL PAD; P < .001) compared with controls. Among PAD patients, those with critical limb ischemia (n = 88) showed higher levels of MMP-10 (1086 ± 478 pg/mL vs 822 ± 436 pg/mL; P < .001) compared with those with intermittent claudication (n = 99), whereas the MMP-10/tissue inhibitor of matrix metalloproteinase 1 ratio remained similar. The univariate analysis showed an association between MMP-10, age (P = .015), hypertension (P = .021), and ankle-brachial index (P = .006) in PAD patients that remained significantly associated with PAD severity after adjustment for other CV risk factors. Patients with the highest MMP-10 tertile had an increased incidence of all-cause mortality and CV mortality (P < .03). Our results suggest that MMP-10 is associated with severity and poor outcome in PAD.

Vascular Reactivity is Impaired and Associated With Walking Ability in Patients With Intermittent Claudication.

We verified whether vascular reactivity is impaired and whether there is any association between vascular reactivity, walking ability, and peripheral artery disease (PAD) severity in patients with intermittent claudication (IC). We studied 63 patients and 17 age- and sex-matched volunteers without PAD. Vascular reactivity was evaluated in the brachial artery during reactive hyperemia (flow-mediated dilation [FMD]) and after a sublingual single dose of nitroglycerin (nitroglycerin-induced vasodilation [NID]). Walking ability was verified by a 6-minute walk test. Vascular reactivity and walking ability were significantly worse in patients with IC compared with control participants. The ankle-brachial index correlated with FMD, NID, as well as total and pain-free distances. The NID and walking ability progressively decreased as PAD severity increased. Walking ability correlated with NID but not with FMD. In patients with IC, vascular reactivity is impaired and is related to the severity of PAD and to walking ability.

Comparison of Accuracy of Two Different Methods to Determine Ankle-Brachial Index to Predict Peripheral Arterial Disease Severity Confirmed by Angiography

Ankle-brachial index (ABI) is conventionally derived as the ratio of higher of the 2 systolic ankle blood pressures to the higher brachial pressure (HABI method). Alternatively, ABI may be derived using the lower of the 2 systolic ankle pressures (LABI method). The objective of this study was to assess the utility and difference between 2 techniques in predicting peripheral artery disease (PAD). Participants who underwent both ABI measurement and arteriography from July 2005 to June 2010 were reviewed. Angiographic disease burden was scored semiquantitatively (0=<50%, 1=50% to 75%, and 2=>75% stenosis of any lower extremity arterial segment), and PAD by angiography was defined as >50% stenosis of any 1 lower extremity arterial segment. A combined PAD disease score was calculated for each leg. A total of 130 patients were enrolled (260 limbs). The ABI was <0.9 (abnormal) in 68% of patients by HABI method and in 84% by LABI. LABI method had higher sensitivity and overall accuracy to detect PAD compared with the HABI method. Regression analysis showed that an abnormal ABI detected by LABI method is more likely to predict angiographic PAD and total PAD burden compared with HABI. Moreover, abnormal ABI by LABI method had higher sensitivity and accuracy to detect PAD in patients with diabetes and below knee PAD compared with the HABI method. In conclusion, ABI determined by the LABI method has higher sensitivity and is a better predictor of PAD compared with the conventional (HABI) method.

Clot strength is negatively associated with ambulatory function in patients with peripheral artery disease and intermittent claudication.

Peripheral artery disease (PAD) is associated with exercise impairment and greater thrombotic risk. We investigated whether clot formation and platelet aggregation assessed by thromboelastography and light-transmission aggregometry correlate with the severity of symptomatic PAD assessed by ambulatory function measures. We studied 40 symptomatic patients with PAD in whom severity of disease was assessed using ankle-brachial index, peak walking time (PWT), claudication onset time, peak oxygen uptake, daily ambulatory activity, and walking impairment questionnaire (WIQ) scores. Clot strength correlated negatively with peak oxygen uptake, PWT, WIQ distance, and stair-climbing scores. Time to clot formation did not correlate with exercise parameters. Platelet aggregation was negatively correlated with WIQ distance score and was positively correlated with PWT and peak oxygen uptake. In conclusion, clot strength and platelet aggregation correlated with objective and self-perceived ambulatory measures. Patients with PAD having more severe walking impairment may be likely to form stronger clots.

Relationship between nitroglycerine-induced vasodilation and clinical severity of peripheral artery disease

ObjectiveNitroglycerine-induced vasodilation is usually used as a control test for flow-mediated vasodilation (FMD). However, nitroglycerine-induced vasodilation per se has also been reported to be impaired in patients with atherosclerosis. The purpose of this study was to determine the relationship between nitroglycerine-induced vasodilation and the clinical severity of peripheral artery disease (PAD). Methods and resultsWe measured nitroglycerine-induced vasodilation and FMD in 144 subjects (mean age: 63.8 ± 15.1 years), including 32 PAD patients with critical limb ischemia (CLI group), 28 PAD patients without CLI (non-CLI group), 60 age- and sex-matched patients without established cardiovascular disease (at-risk group), and 24 healthy subjects (healthy group). Nitroglycerine-induced vasodilation was significantly impaired in the CLI group compared to that in the other three groups (healthy group, 16.0 ± 5.3%; at-risk group, 12.9 ± 3.8%; non-CLI group, 10.3 ± 5.1%; CLI group, 6.7 ± 3.9%; P < 0.05, respectively). Even after multivariate adjustment, the differences remained significant. On the other hand, FMD was significantly impaired in the at-risk, non-CLI, and CLI group compared with that in the healthy group (healthy group, 7.1 ± 2.9%; at-risk group, 3.4 ± 2.3%; non-CLI group, 3.5 ± 2.7%; CLI group, 3.0 ± 2.8%; P < 0.001, respectively), but the differences among the at-risk, non-CLI, and CLI groups were not significant. Multivariate analysis revealed that nitroglycerine-induced vasodilation (odds ratio: 0.77, 95% confidence interval [CI]: 0.61–0.97) and diabetes mellitus (odds ratio: 8.75, 95% CI: 1.74–44.2) were independent variables for CLI in PAD patients. ConclusionsThere was no significant difference in FMD between PAD patients with and those without CLI, but nitroglycerine-induced vasodilation was significantly smaller in PAD patients with CLI compared with those without CLI.

Risk Factors for Protracted Postoperative Length of Stay after Lower Extremity Bypass for Critical Limb Ischemia

Compared with other common chronic conditions, admissions for management of peripheral arterial disease (PAD) are associated with prolonged hospitalizations. Length of stay (LOS) is one of many metrics receiving increased attention in the current focus on efficient healthcare delivery. Our objective was to characterize LOS among patients with severe PAD, those undergoing surgical bypass for critical limb ischemia (CLI), and identify risk factors for protracted postoperative LOS. Patient data from the 2007 to 2009 American College of Surgeons National Surgical Quality Improvement Program were used to develop a database consisting of patients undergoing bypass surgery for CLI (n = 4,894). Protracted postoperative LOS was defined as the top quartile of days hospitalized from surgery to discharge. Preoperative risk factors with significant association (Pearson chi-squared test; P < 0.05) were used to develop a logistic regression model for protracted postoperative LOS. Average postoperative LOS was 7.5 days (median 6 days). The top quartile of postoperative LOS, >8 days, was used to define protracted LOS. Independent preoperative risk factors for protracted postoperative LOS included demographic characteristics (advanced age and non-Caucasian race), comorbidities, and medical history (e.g., obesity, dialysis dependence, severe cardiac and pulmonary disease, and bleeding disorders). Indicators of PAD severity (e.g., distal target sites, open wounds or gangrene, and prior arterial surgery) were also independent predictors of protracted LOS after surgery. The greatest predictors of extended postoperative LOS were prolonged preoperative hospitalization (OR 2.2 [95% CI: 1.8-2.6], P < 0.001) and preoperative dependent functional status (OR 2.0 [95% CI: 1.7-2.3], P < 0.001 for partial dependence; OR 2.8 [95% CI: 1.8-4.3], P < 0.001 for totally dependent status), where OR and CI stand for odds ratio and confidence interval. Here, we identify preoperative risk factors for protracted postoperative LOS after infrainguinal bypass for CLI. These findings provide an important evidence basis for ongoing efforts to reduce healthcare spending and facilitate provision of efficient health care. Future efforts will include prospective identification of patients at high risk for protracted postoperative LOS and targeted multidisciplinary efforts to reduce associated costs without sacrificing healthcare quality.

Functional MRI in Peripheral Arterial Disease: Arterial Peak Flow versus Ankle-Brachial Index

ObjectivesThe purpose of this study was to compare the success rate of successful arterial peak flow (APF) and ankle-brachial index (ABI) measurements in patients with suspected or known peripheral arterial disease (PAD).Materials and Methods183 patients with varying degrees of PAD were included. All subjects underwent ABI measurements and MR imaging of the popliteal artery to determine APF. Proportions of patients with successful APF and ABI measurements were compared and the discriminative capability was evaluated.ResultsAPF was successfully measured in 91% of the patients, whereas the ABI could be determined in 71% of the patients (p<0.01). Success rates of APF and ABI were significantly higher in patients with intermittent claudication (95% and 80%, respectively) than in patients with critical ischemia (87% and 62%, respectively).ConclusionsCompared to the assessment of PAD severity with ABI, the success rate of MRI-based APF measurements in patients with a clinical indication for MRA is 20% higher, with similar discriminatory capacity for disease severity. Therefore, APF is an especially convenient and valuable measure to assess severity in PAD patients scheduled to undergo MR angiography to obtain additional functional information concerning the vascular status.

What is the clinical benefit of neutrophil-lymphocyte ratio in cardiovascular patients?

Dear Editor, Neutrophil-lymphocyte ratio (NLR) has gained a significant interest in the recent years, especially in cardiovascular research area. NLR is an easy to use parameter with not requiring an extreme effort to obtain. It can be obtained easily from the complete blood count (CBC) test, which is the most performed test in hospitals. NLR is used to predict cognitive dysfunction after carotid endarterectomy1, peripheral arterial disease prognostication2, presence, severity and extent of coronary artery disease3,4, and calcific aortic stenosis5. NLR has also been used for prediction of coronary heart disease mortality6, left atrial trombus7, impaired myocardial perfusion8, outcomes of cryoballoon-based atrial fibrillation ablation9, and prognostication of ST-elevation myocardial infarction (STEMI).10 In almost all of these studies, higher NLR was associated with worse clinical outcomes in patients with coronary artery disease, STEMI, peripheral arterial disease, calcific aortic stenosis and atrial fibrillation. However, there is no a universally accepted cut-off value of NLR that dictates a negative outcome as normal or abnormal. All of the above-mentioned studies have used different cutt-off values as normal or acceptable. Arbel et al. state >3 as an abnormally high value, other authors vary between <1.4 and <6 being normal.1-10 In a recent study, Ghaffari et al.11 evaluated the predictive value of peripheral neutrophil count and NLR in determining the prognosis of MI and the risk of major post-MI adverse events. In view of previous studies, it was not surprising to find an association between NLR and the frequency of heart failure and development of ventricular arrhythmias within the first day. The NLR was not associated with mortality but higher neutrophil count was the best predictive value for both mortality and heart failure. In STEMI, peripheral leukocyte count usually increases within 2 hours after the onset of chest pain, that peaks 2 to 4 days after infarction, returning to normal in one week.12 Ghaffari et al.11 measured CBC within 12-24 hours of onset of sypmtoms. The shorter lifespan with a rapid turn-over of neutrophils may have also affected the results of the study. Thus, serial neutrophil count may potentially be advantageous over its single measurement at the time of admission. This could easily be examined from the blood samples that are routinely obtained for monitoring cardiac enzymes. Also the measurement of NLR can be potentially affected by conditions such as metabolic syndrome, valvular heart disease, abnormal thyroid function tests, renal or hepatic dysfunction, local or systemic infection and ingestion of anti-inflammatory drugs.13 Park et al.10 evaluated the prognostic value of leukocyte profiles (neutrophil, lymphocyte, and monocyte absolute counts) in patients with STEMI treated with primary percutaneous intervention (PCI) and found that patients with 24-hour NLRs ≥5.44 were at increased risk for mortality and not admission leukocyte profile but the leukocyte profile at 24 hours after admission was associated with clinical outcomes (all-cause death). Indeed, Chia et al. showed that total leukocyte and neutrophil counts at 24 hours after primary PCI was an independent predictor of adverse cardiac events in patients with STEMI, but not the baseline hematologic indexes.14 After bare metal stent implantation hypersensitivity-mediated inflammation by eosinophilic cationic protein may be responsible for major cardiac events.15 Furthermore, hypersensitivity reactions against the drug eluting stent polymer material or the eluted drug have been associated with thrombotic complications probably mediated by persistent inflammation and incomplete apposed stent struts.16 Ghaffari et al. did not give any information about their revascularisation strategies. Therefore, it is not clear what type of stents were generally used and how long was their door to needle time. Also there was no any information about the patients’ medication. In conclusion, should the presence of a higher NLR without a universally accepted cutt-off value alert the physician to a higher hospital mortality? If so, how can we manipulate the NLR to improve the outcome? The NLR may be useful when combined with standardized clinical mortality risk prediction scores and other inflammatory markers. More importantly, further epidemiological studies will be required to consider NLR as a useful marker in these clinical settings.

Impaired Peripheral Circulation in Veterans with Claudication is Associated with Smoking

We compared the peripheral vascular function of veterans and non-veterans with peripheral artery disease (PAD) and claudication. The circulation of the lower extremities was assessed under rest and reactive hyperemia conditions in 413 veterans and in 83 non-veterans. Veterans had more severe PAD as measured by a lower ankle/ brachial index (p<0.001). Following the occlusive test, veterans had a greater relative percentage decrease in ankle systolic blood pressure (p=0.015), a greater percentage decrease in calf transcutaneous oxygen tension (p=0.035), and a blunted percentage increase in calf blood flow (p=0.031). After adjustment for current smoking status, these measures were no longer statistically different between the veterans and non-veterans. We conclude that veterans with PAD and claudication have greater impairments in macrovascular and microvascular function of the lower extremities, and greater severity of PAD than compared to non-veterans, and that these factors were primarily associated with their higher prevalence of smoking. The greater compromise in peripheral vascular measures in veterans is particularly noteworthy given that the prevalence of diabetes, hypertension, and dyslipidemia were not higher.

Index de pression systolique et médecine de ville : motivation, formation, mesure et valorisation de l’acte. Enquête auprès d’un échantillon de 165 médecins généralistes d’Île-de-France

Peripheral arterial disease (PAD) is under-diagnosed despite its predictive value for cardiovascular mortality. The ankle brachial index (ABI), a simple reliable measure recommended by the French health authorities to detect and evaluate the severity of PAD, is used by too few general practitioners (GPs). This study aimed at identifying motivations and barriers for using ABI in general practice. A representative, descriptive, cross-sectional survey was conducted amongst 165GPs practicing in Île-de-France who were interviewed using stratified quotas. Although 1out of 5GPs considered ABI to be an irrelevant indicator, most had a favorable opinion about its use (OR: 4.9 [CI 95%: 4.2-5.7]). Only 42% (CI 95%: 34%-49%) of GPs knew ABI was recommended by the health authorities. This information had a critical impact on the acceptance of ABI relevancy (OR: 3.7 [CI 95%: 3.2-4.2]). Training reinforced acceptance (OR: 5.0 [CI 95%: 4.4-5.6]) and pre-residency education provided a better understanding of ABI (OR: 2.8 [CI 95%: 2.3-3.4]). Time needed to measure ABI was the main barrier (OR: 0.6 [CI 95%: 0.6-0.7]). A Doppler-calculation kit (OR: 11.8 [CI 95%: 8.9-15.6]), equipment cost≤300Euros (OR: 3.4 [CI 99%: 3.0-3.9]), a specific fee in addition to the regular consultation fee (OR: 2.6 [CI 95%: 2.3-3.0]) and inclusion of ABI in the GP's evaluation scheme (OR: 2.6 [CI 95%: 2.3-2.9]) would motivate more GPs. Seven out of 10GPs agreed that ABI has a positive impact on patient adherence to treatment and follow-up, but ABI remained underexploited for symptomatic patients (OR: 0.4 [CI 95%: 0.3-0.4]). Better communication and training together with an upgraded status for ABI would provide motivation for GPs to measure ABI.

Abstract 15492: ADAM12 Modifies Severity of Peripheral Arterial Disease; Evidence from Preclinical and Human studies

Ayotunde Dokun, 2013 Finalist and Presenting Author

A 3-D Ultrasound Imaging Robotic System to Detect and Quantify Lower Limb Arterial Stenoses: In Vivo Feasibility

The degree of stenosis is the most common criterion used to assess the severity of lower limb peripheral arterial disease. Two-dimensional ultrasound (US) imaging is the first-line diagnostic method for investigating lesions, but it cannot render a 3-D map of the entire lower limb vascular tree required for therapy planning. We propose a prototype 3-D US imaging robotic system that can potentially reconstruct arteries from the iliac in the lower abdomen down to the popliteal behind the knee. A realistic multi-modal vascular phantom was first conceptualized to evaluate the system's performance. Geometric accuracies were assessed in surface reconstruction and cross-sectional area in comparison to computed tomography angiography (CTA). A mean surface map error of 0.55 mm was recorded for 3-D US vessel representations, and cross-sectional lumen areas were congruent with CTA geometry. In the phantom study, stenotic lesions were properly localized and severe stenoses up to 98.3% were evaluated with –3.6 to 11.8% errors. The feasibility of the in vivo system in reconstructing the normal femoral artery segment of a volunteer and detecting stenoses on a femoral segment of a patient was also investigated and compared with that of CTA. Together, these results encourage future developments to increase the robot's potential to adequately represent lower limb vessels and clinically evaluate stenotic lesions for therapy planning and recurrent non-invasive and non-ionizing follow-up examinations.

Co-Existence of Carotid Artery Disease, Renal Artery Stenosis, and Lower Extremity Peripheral Arterial Disease in Patients With Coronary Artery Disease

In atherosclerosis, carotid artery stenosis (CAS), renal artery stenosis (RAS), lower extremity peripheral arterial disease (PAD), and coronary artery disease (CAD) are common pathologic lesions; their interrelationship is, however, unclear. We studied concomitant multiple atherosclerotic lesions in patients with CAD to understand their prevalence and relations. A cross-sectional analysis was performed on data from consecutive patients who underwent nonemergent coronary angiography. Simultaneous carotid and renal artery Doppler studies and ankle-brachial systolic pressure measurements were reviewed to diagnose concomitant lesions and their severity. The study included 1,734 patients (aged 71 ± 9 years; 70% men), with prevalences of CAS, RAS, lower extremity PAD, and CAD of 6%, 7%, 13%, and 72%, respectively. In patients with CAD (n = 1,253), the prevalences of CAS, RAS, and lower extremity PAD were 7%, 9%, and 16%, respectively; 24% CAD patients had ≥1 additional atherosclerotic lesion. Significant interactions among the prevalences of these lesions were found. In addition, the extent of CAD and the prevalences of CAS, RAS, and lower extremity PAD were significantly correlated. Multivariate analysis supported these relationships. In conclusion, the prevalences of CAS, RAS, lower extremity PAD, and CAD were strongly interrelated in the study population; CAD severity was related to that of other atherosclerotic lesions. Additional systematic screening of other concomitant atherosclerotic lesions is recommended, especially in CAD patients having multivessel disease, left main disease, and/or already diagnosed with other concomitant atherosclerotic lesions.