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Proatherogenic Oxidized Low-Density Lipoprotein/beta2-Glycoprotein I Complexes in Arterial and Venous Disease

Berger, Jeffrey S; Rockman, Caron B; Guyer, Kirk E; Lopez, Luis R
OxLDL/beta2GPI complexes have been implicated in the initiation and progression of atherosclerosis and associated with disease severity and adverse outcomes. We investigate the significance of anti-oxLDL/beta2GPI antibodies and oxLDL/beta2GPI complexes in patients with arterial and idiopathic venous disease. A cohort of 61 arterial disease patients, 32 idiopathic venous disease patients, and 53 healthy controls was studied. Because statins influence oxLDL/beta2GPI, these complexes were analyzed on subjects not taking statins. Arterial and venous groups expressed higher levels of IgG anti-oxLDL/beta2GPI antibodies than controls without any other significant clinical association. OxLDL/beta2GPI complexes were significantly elevated in arterial (0.69 U/mL, P = 0.004) and venous disease (0.54 U/mL, P = 0.025) than controls (0.39 U/mL). Among arterial diseases, oxLDL/beta2GPI was 0.85 U/mL for carotid artery disease, 0.72 U/mL for peripheral artery disease, and 0.52 U/mL for abdominal aortic aneurysm. There was a significant association with male gender, age, hypertension, and history of thrombosis. Subjects with oxLDL/beta2GPI above the median (0.25 U/mL) were more likely to have arterial (OR 4.5, P = 0.004) or venous disease (OR 4.1, P = 0.008). Multivariate regression indicated that males (P = 0.021), high cholesterol (P = 0.011), and carotid disease (P = 0.023) were significant predictors of oxLDL/beta2GPI. The coexistence of oxLDL/beta2GPI in arterial and venous disease may suggest a common oxidative mechanism that independently predicts carotid artery disease.
PMCID:4227323
PMID: 25405208
ISSN: 2314-7156
CID: 1355772

Platelet activation increases in patients undergoing vascular surgery

Schneider, Gabriel S; Rockman, Caron B; Berger, Jeffrey S
BACKGROUND: Platelets are a major contributor to atherothrombosis and may contribute to the heightened risk of perioperative cardiovascular events. We sought to examine changes in platelet activity in subjects undergoing vascular surgery. METHODS: Platelet activity in 18 patients (median age 74, 45% female) undergoing non-emergent open vascular surgery was assessed by light transmission aggregometry in response to saline, epinephrine and adenosine-5 diphosphate (ADP), and by flow cytometric analysis of monocyte-platelet aggregation (MPA). Platelet activity was assessed preoperatively (T1), 1-hour into the operation (T2), 1-hour (T3), 24-hours (T4) and 48-hours post-operatively (T5). Data were compared using the Wilcoxon Signed Ranks Test. Continuous variables are summarized as medians and (interquartile, IQR) ranges. RESULTS: Spontaneous platelet aggregation increased transiently during the surgical period (T1-5.8% [2.4, 10.8], T2-13.5% [9.3, 26.5], T3-7.5% [3.3, 17], T4-10.0% [7.3, 16.3], T5-7.25% [4.5, 29.9], P=0.002). Similar trends in perioperative platelet activity were noted for platelet aggregation in response to epinephrine (P=0.035) and ADP (P=0.036). Using flow cytometry, we found an increase in MPA during the perioperative period (P=0.047), which was most significant between T1 and T3 (P=0.005). CONCLUSIONS: Platelet activity increases significantly during and following open vascular surgery. This data may help explain the pathophysiology of increased thrombotic risk during the perioperative period of vascular surgery.
PMCID:4533998
PMID: 25208456
ISSN: 0049-3848
CID: 1258212

Bovine arch and carotid artery atherosclerosis: are they related?

Baadh, Amanjit S; Rockman, Caron B; Mitnick, Robin J; Lim, Ruth P
OBJECTIVES: The prevalence of the "bovine" arch in the population is known (8-25%). However, its prevalence in patients with significant carotid atherosclerosis has never been investigated. Altered flow patterns or turbulence that may occur in these patients may play a causative role in the development of atherosclerotic lesions. The primary purpose of this study was to retrospectively compare the prevalence of aortic arch variants in patients with and without significant carotid artery atherosclerosis, as we hypothesize that carotid atherosclerosis may be more prevalent in patients with a bovine arch due to hemodynamic alterations. A secondary objective was to review radiologist reporting of arch anatomy. METHODS: Single-center, retrospective, case-control study in which 79 patients with hemodynamically significant carotid artery atherosclerosis who underwent computed tomography angiography, magnetic resonance angiography, or unenhanced computed tomography (CT) imaging including the aortic arch were identified. These patients were then compared with 95 randomly selected controls without carotid atherosclerosis that underwent similar imaging during the same time period. Images were independently reviewed by two blinded radiologists, who assessed arch anatomy as normal, bovine, or other variant. The original radiology reports were reviewed for reporting of arch anatomy. RESULTS: In controls, 70% had normal arch anatomy, and 24% had a bovine arch. Among patients with significant carotid disease, these numbers were 70% and 20%, respectively. There was no statistically significant difference between incidence of arch variants in subjects with and without carotid artery atherosclerosis (P=.97). There was good interreader agreement. Among patients with aortic arch anomalies, 20% of the original radiology reports did not mention arch anatomy. CONCLUSIONS: In our experience, percentage of bovine arch anomalies in patients with significant carotid atherosclerosis is not significantly different from those without disease. Clinicians should be aware of the high prevalence of arch anomalies, which can impact endovascular approach and management, and radiologists should be aware of the clinical importance of reporting such variants.
PMID: 24993641
ISSN: 0899-7071
CID: 1065972

Association of the ankle-brachial index with history of myocardial infarction and stroke

Jones, W Schuyler; Patel, Manesh R; Rockman, Caron B; Guo, Yu; Adelman, Mark; Riles, Thomas; Berger, Jeffrey S
BACKGROUND: Ankle-brachial index (ABI) testing is a simple, noninvasive method to diagnose peripheral artery disease (PAD) and is associated with all-cause mortality. The association of ABI levels and myocardial infarction (MI) and stroke is less certain. We sought to further characterize the association between ABI levels and history of MI and stroke. METHODS: Using data from the Life Line Screening program, 3.6 million self-referred participants from 2003 to 2008 completed a medical questionnaire and had bilateral ABIs performed. Logistic regression was used to estimate the association between ABI cutoff points (ABI <0.90 and ABI >1.40) and ABI levels with history of MI, stroke, and MI or stroke (MI/stroke). Models were adjusted for age, sex, race/ethnicity, smoking, diabetes, hypertension, hypercholesterolemia, physical activity, and family history of cardiovascular disease. Separate sex-specific models were performed. RESULTS: Overall, 155,552 (4.5%) had an ABI <0.90, and 42,890 (1.2%) had an ABI >1.40. An ABI <0.90 was associated with higher odds of MI (adjusted odds ratio [OR] 1.67, 95% CI 1.63-1.71), stroke (OR 1.77, 95% CI 1.72-1.82), and MI/stroke (OR 1.71, 95% CI 1.67-1.74), all P < .001. An ABI >1.40 was also associated with higher odds of MI (OR 1.19, 95% CI 1.14-1.24), stroke (OR 1.30, 95% CI 1.22-1.38), and MI/stroke (OR 1.22, 95% CI 1.17-1.27), all P < .001. The ORs for MI/stroke for different ABI levels formed a reverse J-shaped curve in both women and men. CONCLUSIONS: In a large national screening database, there is a strong, consistent relationship between ABI levels and a history of prevalent MI, stroke, and MI/stroke.
PMID: 24655698
ISSN: 0002-8703
CID: 932322

Diabetes and Vascular Disease in Different Arterial Territories

Shah, Binita; Rockman, Caron B; Guo, Yu; Chesner, Jaclyn; Schwartzbard, Arthur Z; Weintraub, Howard S; Adelman, Mark A; Riles, Thomas S; Berger, Jeffrey S
OBJECTIVEThe aim of this study was to investigate the relationship between diabetes and different phenotypes of peripheral vascular disease (lower extremity peripheral artery disease [PAD], carotid artery stenosis [CAS], and abdominal aortic aneurysm [AAA]).RESEARCH DESIGN AND METHODSPrevalence of vascular disease was evaluated in 3,696,778 participants of the Life Line Screening survey between 2003 and 2008. PAD was defined as ankle-brachial pressure index <0.90 or prior revascularization, CAS as >/=50% stenosis or prior revascularization, and AAA as infrarenal aortic diameter >/=3 cm or prior repair. Odds ratios (ORs) and 95% CIs were assessed using logistic regression modeling.RESULTSDiabetes mellitus was present in 10.8% of participants (n = 399,884). Prevalence of PAD, CAS, and AAA were significantly higher (P < 0.0001) in participants with compared with those without diabetes. After multivariate adjustment for baseline demographics and clinical risk factors, a significant interaction existed between diabetes and vascular disease phenotype (P < 0.0001). Diabetes was associated with increased odds of PAD (OR 1.42 [95% CI 1.41-1.4]; P < 0.0001) and CAS (1.45 [1.43-1.47]; P < 0.0001) but decreased odds of AAA (0.86 [0.84-0.88]; P < 0.0001). The strength of association increased with increasing severity of disease in each vascular phenotype, and this association persisted in the population with asymptomatic vascular disease.CONCLUSIONSIn a large population-based study, the association between diabetes and vascular disease differed according to vascular phenotype. Future studies exploring the mechanism for these vascular-specific differences are needed.
PMCID:4030086
PMID: 24705616
ISSN: 0149-5992
CID: 902312

Increasing frequency of fruit and vegetable consumption is associated with lower prevalence of peripheral arterial disease in a very large community cohort [Meeting Abstract]

Heffron, S; Rockman, C; Guo, Y; Adelman, M; Berger, J
Background: While fruit and vegetable (F&V) consumption is associated with reduced risk of stroke and coronary heart disease, there is little data on peripheral artery disease (PAD). We sought to study the association between F&V intake and prevalence of PAD in a large community cohort. Methods: From 2003 - 2008, over 3.5 million self-referred participants at >20,000 US sites completed a medical and lifestyle questionnaire and were evaluated by screening ankle-brachial index <0.9 for PAD. Subjects were queried for frequency of consumption of >3 servings of F&V (<1x/mo, 1x/mo- 1x/wk, 2-3x/wk, 4- 5x/wk, daily). Multivariate logistic regression analysis was used to estimate odds of PAD by F&V intake. Results: Among 3,523,545 individuals, mean age was 63.4 + 10.6 years and 63% were female. F&V intake ranged from 7% (<1x/month) to 29% (daily consumption of >3 servings). After adjustment for age, sex, race, smoking, physical activity, diabetes, hypertension, hyperlipidemia and family history of vascular disease, there was a step-wise inverse association of F&V intake with PAD (P for trend <0.0001; Figure). Compared to subjects with <1x/month consumption of >3 servings of F&V, daily intake was associated with 20% lower odds of PAD (OR 0.800, 95% CI 0.784 - 0.816). Conclusion: We present data from a large community cohort, in which F&V intake exhibited an inverse step-wise relationship with PAD prevalence after correction for multiple established risk factors, suggestive of protective effects in this vascular territory. (Figure Presented)
EMBASE:71408072
ISSN: 0735-1097
CID: 884482

Nationwide Comparative Impact of Thoracic Endovascular Aortic Repair of Acute Uncomplicated Type B Aortic Dissections

Shah, Tejas R; Rockman, Caron B; Adelman, Mark A; Maldonado, Thomas S; Veith, Frank J; Mussa, Firas F
Objective: Thoracic endovascular aortic repair (TEVAR) for acute uncomplicated type B aortic dissection (TBAD) remains controversial. This study aims to evaluate the impact of TEVAR on mortality, morbidity, length of stay (LOS), and discharge status in patients with acute uncomplicated TBAD.Methods: We analyzed the National Inpatient Sample from 2009 and 2010. Patients were categorized according to the type of treatment: TEVAR or medical management. Outcomes, including mortality, stroke, myocardial infarction (MI), acute renal failure, discharge disposition, and LOS, were compared between the treatment groups.Results: We identified 4706 patients with TBAD. Mean age was 67 years and 55% were male. Treatment options included TEVAR in 504 and medical management in 4202. The overall adjusted in-hospital mortality was similar for both the groups (8.5% for TEVAR vs 10.3% for medical management, P = .224). The TEVAR carried higher risk of stroke (odds ratio [OR] = 1.61, 95% confidence interval [CI] = [1.14-2.27]; P = .0073). The TEVAR was associated with prolonged LOS (12 vs 5.6 days, P < .0001) and patients were less likely to be discharged home (OR 0.73, 95% CI 0.54-0.99; P = .013). When stratified by age, all outcomes were similar between the 2 groups, with the exception of longer LOS with TEVAR.Conclusions: Thoracic endovascular aortic repair for acute uncomplicated TBAD was associated with similar in-hospital mortality, MI, and renal failure as compared to medical management. The TEVAR had higher rate of stroke up to the age 70 years and longer LOS. Because extending TEVAR to less complicated patients could only decrease TEVAR mortality rates, these findings support the more widespread use of TEVAR to treat patients with uncomplicated TBAD.
PMID: 24399132
ISSN: 1538-5744
CID: 737912

Endovascular-first approach is not associated with worse amputation-free survival in appropriately selected patients with critical limb ischemia

Garg, Karan; Kaszubski, Patrick A; Moridzadeh, Rameen; Rockman, Caron B; Adelman, Mark A; Maldonado, Thomas S; Veith, Frank J; Mussa, Firas F
OBJECTIVE: Endovascular interventions for critical limb ischemia are associated with inferior limb salvage (LS) rates in most randomized trials and large series. This study examined the long-term outcomes of selective use of endovascular-first (endo-first) and open-first strategies in 302 patients from March 2007 to December 2010. METHODS: Endo-first was selected if (1) the patient had short (5-cm to 7-cm occlusions or stenoses in crural vessels); (2) the disease in the superficial femoral artery was limited to TransAtlantic Inter-Society Consensus II A, B, or C; and (3) no impending limb loss. Endo-first was performed in 187 (62%), open-first in 105 (35%), and 10 (3%) had hybrid procedures. RESULTS: The endo-first group was older, with more diabetes and tissue loss. Bypass was used more to infrapopliteal targets (70% vs 50%, P = .031). The 5-year mortality was similar (open, 48%; endo, 42%; P = .107). Secondary procedures (endo or open) were more common after open-first (open, 71 of 105 [68%] vs endo, 102 of 187 [55%]; P = .029). Compared with open-first, the 5-year LS rate for endo-first was 85% vs 83% (P = .586), and amputation-free survival (AFS) was 45% vs 50% (P = .785). Predictors of death were age >75 years (hazard ratio [HR], 3.3; 95% confidence interval [CI], 1.7-6.6; P = .0007), end-stage renal disease (ESRD) (HR, 3.4; 95% CI, 2.1-5.6; P < .0001), and prior stroke (HR, 1.6; 95% CI, 1.03-2.3; P = .036). Predictors of limb loss were ESRD (HR, 2.5; 95% CI, 1.2-5.4; P = .015) and below-the-knee intervention (P = .041). Predictors of worse AFS were older age (HR, 2.03; 95% CI, 1.13-3.7; P = .018), ESRD (HR, 3.2; 95% CI, 2.1-5.11; P < .0001), prior stroke (P = .0054), and gangrene (P = .024). CONCLUSIONS: At 5 years, endo-first and open-first revascularization strategies had equivalent LS rates and AFS in patients with critical limb ischemia when properly selected. A patient-centered approach with close surveillance improves long-term outcomes for both open and endo approaches.
PMID: 24184092
ISSN: 0741-5214
CID: 653412

Use of Preoperative Magnetic Resonance Angiography and the Artis zeego Fusion Program to Minimize Contrast During Endovascular Repair of an Iliac Artery Aneurysm

Sadek, Mikel; Berland, Todd L; Maldonado, Thomas S; Rockman, Caron B; Mussa, Firas F; Adelman, Mark A; Veith, Frank J; Cayne, Neal S
BACKGROUND: A 61-year-old man with a previous endovascular repair and stage 5 chronic kidney disease presented with a symptomatic 4.5-cm left internal iliac artery aneurysm. The decision was made to proceed with endovascular repair. METHODS: The preoperative magnetic resonance angiography (MRA) scan was linked to on-table rotational imaging using the Artis zeego Fusion program (Siemens AG, Forchheim, Germany). Using the fused image as a road map, we undertook coil embolization of the left internal iliac artery, and a tapered stent graft was extended from the previous graft into the external iliac artery. RESULTS: Completion angiography revealed exclusion of the aneurysm sac. Three milliliters of contrast were used throughout the procedure. A follow-up magnetic resonance angiography scan at 1 month and duplex ultrasonography at 1 year revealed continued exclusion of the aneurysm sac. The patient's renal function remained unchanged. CONCLUSIONS: This case shows that in a patient with severe chronic kidney disease, fusion of preoperative imaging with intraoperative rotational imaging is feasible and can limit significantly the amount of contrast used during a complex endovascular procedure.
PMID: 24075152
ISSN: 0890-5096
CID: 612962

Concomitant Unruptured Intracranial Aneurysms and Carotid Artery Stenosis: An Institutional Review of Patients Undergoing Carotid Revascularization

Borkon, Matthew J; Hoang, Han; Rockman, Caron; Mussa, Firas; Cayne, Neal S; Riles, Thomas; Jafar, Jafar J; Veith, Frank J; Adelman, Mark A; Maldonado, Thomas S
BACKGROUND: The incidence of concomitant carotid artery stenosis and unruptured intracranial aneurysms (UIAs) has been reported at between 0.5% and 5%. In these patients, treatment strategies must balance the risk of ischemic stroke with the risk of aneurysmal rupture. Several studies have addressed the natural course of UIAs in the setting of carotid revascularization; however, the final recommendations are not uniform. The purpose of this study was to review our institutional experience with concomitant UIAs and carotid artery stenosis. METHODS: We performed a retrospective review of all patients with carotid artery stenosis who underwent carotid artery endarterectomy (CEA) or carotid artery stenting (CAS) at our institution between 2003 and 2010. Only patients with preoperative imaging demonstrating intracranial circulation were included. Charts were reviewed for patients' demographic and clinical data, duration of follow-up, and aneurysm size and location. Patients were stratified into 2 groups: carotid artery stenosis with unruptured intracranial aneurysm (CS/UIA) and carotid artery stenosis without intracranial aneurysm (CS). RESULTS: Three hundred five patients met the inclusion criteria and had a total of 316 carotid procedures (CAS or CEA) performed. Eleven patients were found to have UIAs (3.61%) prior to carotid revascularization. Male and female prevalence was 2.59% and 5.26% (P = 0.22), respectively. Patients' demographics did not differ significantly between the 2 groups. The average aneurysm size was 3.25 +/- 2.13 mm, and the most common location was the cavernous segment of the internal carotid artery. No patient in the study had aneurysm rupture, and the mean follow-up time was 26.5 months for the CS/UIA group. CONCLUSIONS: Concomitant carotid artery stenosis and UIAs is a rare entity. Carotid revascularization does not appear to increase the risk of rupture for small aneurysms (<10 mm) in the midterm. Although not statistically significant, there was a higher incidence of aneurysms found in females in our patient population.
PMID: 24189005
ISSN: 0890-5096
CID: 612952