Loss of the hyaluronan receptor RHAMM prevents constrictive artery wall remodeling.

OBJECTIVE: Constrictive extracellular matrix (ECM) remodeling contributes significantly to restenosis after arterial reconstruction, but its molecular regulation is poorly defined. Hyaluronan (HA) accumulates within ECM at sites of injury where it is thought to facilitate smooth muscle cell (SMC) trafficking and collagen remodeling analogous to its role in cutaneous wound healing. SMC receptors for HA include receptor for hyaluronan-mediated motility (RHAMM), which mediates HA-induced migration. We hypothesized RHAMM would also mediate SMC-matrix interactions to alter the extent of constrictive remodeling. METHODS: We studied the role of RHAMM in SMC attachment to collagen, migration, and contraction of collagen gels using blocking antibodies and SMC from RHAMM -/- knockout mice. We then determined the role of RHAMM in constrictive artery wall remodeling by comparing changes in wall geometry in RHAMM -/- vs wild-type (WT) RHAMM +/+ controls 1 month after carotid ligation. RESULTS: HA increased SMC attachment to collagen-coated plates, but blocking RHAMM reduced adhesion (P = .025). RHAMM -/- SMC also demonstrated reduced adhesion (% adherent: 36.1 ± 2.2 vs 76.3 ± 1.9; P < .05). SMC contraction of collagen gels was enhanced by HA and further increased by RHAMM blockade (P < .01) or knockout (gel diameter, mm: RHAMM -/-, 6.7 ± 0.1 vs WT 9.8 ± 0.1; P < .01). RHAMM promoted constrictive remodeling in vivo as carotid artery size was significantly larger in knockout mice 1 month after ligation. Neointimal thickening, however, was not affected in RHAMM -/- (P = NS vs WT), but lumen size was significantly larger (lumen area, µm(2): 52.4 ± 1.4 × 10(3) vs 10.4 ± 1.8 × 10(3); P = .01) because artery size constricted less (external elastic lamina area, µm(2): RHAMM -/-, 92.4 ± 4.7 × 10(3) vs WT, 51.3 ± 5.9 × 10(3); P = .015). Adventitial thickening and collagen deposition were also more extensive in ligated RHAMM -/- carotids (adventitial thickness, µm: 218 ± 12.2 vs 109 ± 7.9; P = .01). CONCLUSIONS: HA activation of RHAMM significantly impacts SMC-ECM adhesive interactions and contributes to constrictive artery wall remodeling in mice. Strategies to block RHAMM at sites of vessel injury may prove useful in the prevention of clinical restenosis.

Associations between renal duplex parameters and adverse cardiovascular events in the elderly: a prospective cohort study.

BACKGROUND: Atherosclerotic renovascular disease is associated with an increased risk of cardiovascular disease (CVD) events. This study examines associations between Doppler-derived parameters from the renal artery and renal parenchyma and all-cause mortality and fatal and nonfatal CVD events in a cohort of elderly Americans. STUDY DESIGN: Cohort study. SETTING: A subset of participants from the Cardiovascular Health Study (CHS). Through an ancillary study, 870 (70% recruitment) Forsyth County, NC, CHS participants consented to undergo renal duplex sonography to define the prevalence of renovascular disease in the elderly, resulting in 726 (36% men; mean age, 77 years) technically adequate complete studies included in this investigation. PREDICTOR: Renal duplex sonography-derived Doppler signals from the main renal arteries and renal parenchyma. Spectral analysis from Doppler-shifted frequencies and angle of insonation were used to estimate renal artery peak systolic and end diastolic velocity (both in meters per second). Color Doppler was used to identify the corticomedullary junction. Using a 3-mm Doppler sample, the parenchymal peak systolic and end diastolic frequency shift (both in kilohertz) were obtained. Resistive index was calculated as (1 - [end diastolic frequency shift/peak systolic frequency shift]) using Doppler samples from the hilar arteries of the left or right kidney with the higher main renal artery peak systolic velocity. OUTCOMES & MEASUREMENTS: Proportional hazard regression analysis was used to determine associations between renal duplex sonography-derived Doppler signals and CVD events and all-cause mortality adjusted for accepted cardiovascular risk factors. Index CVD outcomes were defined as coronary events (angina, myocardial infarction, and coronary artery bypass grafting/percutaneous coronary intervention), cerebrovascular events (stroke or transient ischemic attack), and any CVD event (angina, congestive heart failure, myocardial infarction, stroke, transient ischemic attack, and coronary artery bypass grafting [CABG]/percutaneous transluminal coronary intervention [PTCI]). RESULTS: During follow-up, 221 deaths (31%), 229 CVD events (32%), 122 coronary events (17%), and 92 cerebrovascular events (13%) were observed. Renal duplex sonography-derived Doppler signals from the renal parenchyma were associated independently with all-cause mortality and CVD outcomes. In particular, increased parenchymal end diastolic frequency shift was associated significantly with any CVD event (HR, 0.73; 95% CI, 0.62-0.87; P < 0.001). Marginally significant associations were observed between increases in parenchymal end diastolic frequency shift and decreased risk of death (HR, 0.86; 95% CI, 0.73-1.00; P = 0.06) and decreased risk of cerebrovascular events (HR, 0.78; 95% CI, 0.61-1.01; P = 0.06). Parenchymal end diastolic frequency shift was not significantly predictive of coronary events (HR, 0.84; 95% CI, 0.67-1.06; P = 0.1). LIMITATIONS: CHS participants showed a "healthy cohort" effect that may underestimate the rate of CVD events in the general population. CONCLUSION: Renal duplex sonographic Doppler signals from the renal parenchyma showed significant associations with subsequent CVD events after controlling for other significant risk factors. In particular, a standard deviation increase in parenchymal end diastolic frequency shift was associated with 27% risk reduction in any CVD event.

Atherosclerotic renovascular disease among hypertensive adults.

PURPOSE: This report describes the change in atherosclerotic renovascular disease (AS-RVD) among hypertensive adults referred for renal duplex sonography (RDS) scan. METHODS: From Oct 1993 through July 2008, 20,994 patients had RDS at our center. A total of 434 hypertensive patients with two or more RDS exams without intervention comprised the study cohort. Patient demographics (blood pressures, medications, serum creatinine levels, and data from RDS) were collected. Analyses of longitudinal changes in Doppler scan parameters, blood pressures, and renal function were performed by fitting linear growth-curve models. After confirming the linearity of change in Doppler scan parameters among patients with variable number of studies, estimates of mean slopes were calculated using maximum likelihood techniques. For changes in renal function, quadratic growth curves were required to describe longitudinal change. RESULTS: A total of 434 subjects (212 men [49%] and 222 women [51%]; mean age, 64.6 +/- 12.2 years) provided 1351 studies (mean, 3.2 +/- 2.4; range, 2 to 18) for 863 kidneys over a mean follow-up of 34.4 +/- 25.1 months. At baseline, 20.6% of kidneys demonstrated hemodynamically significant stenosis. On follow-up, 72 kidneys (9.1%) demonstrated anatomic progression of disease. A total of 54 kidneys (6.9%) progressed to significant stenosis and 18 (2.3%) progressed to occlusion. Controlling for progression of disease, baseline renal artery status demonstrated a strong association with baseline kidney length (P = .0006). Significant annualized change in renal length was observed (cm change/year +/- standard error of the mean [SEM]: 0.042 +/- 0.011; P = .0002) among both kidneys with and without critical disease at baseline, however, decline in length was significantly greater among kidneys exhibiting progression of renovascular disease (-0.152 +/- 0.028 cm/year; comparison of slopes between groups P = .0005). In the absence of progression, the presence or absence of critical renal artery stenosis at baseline did not affect the rate of decline in renal length. Fitted models for the natural log transform of serum creatinine demonstrated a significant increase during follow-up (P < .0001). No association was observed between change in serum creatinine and baseline renovascular disease status, or its progression. CONCLUSION: A total of 32% of hypertensive adults referred for RDS demonstrated hemodynamically significant renal artery stenosis. Regardless of the presence or absence of baseline disease, a small percentage of patients demonstrated anatomic progression of AS-RVD. A total of 9.1% demonstrated anatomic progression and 2.3% progressed to occlusion. Although anatomic progression of AS-RVD was associated with an increased rate of decline in renal length, progression did not predict a decline in excretory renal function. Intervention for AS-RVD should be selective and reserved for strict indications.

Restenosis after renal artery angioplasty and stenting: incidence and risk factors.

BACKGROUND: Management of renal artery stenosis (RAS) with primary renal artery percutaneous angioplasty and stenting (RA-PTAS) is associated with a low risk of periprocedural death and major complications; however, restenosis develops in a subset of patients and repeat intervention may be required. We examined the incidence of restenosis after RA-PTAS and associations with clinical factors. METHODS: Consecutive patients undergoing RA-PTAS for hemodynamically significant atherosclerotic RAS associated with hypertension or ischemic nephropathy, or both, between October 2003 and September 2007 were identified from a registry. Restenosis was defined using duplex ultrasound (DUS) imaging as a renal artery postintervention peak systolic velocity (PSV) >or=180 cm/s. The incidence and temporal distribution of restenosis was analyzed using survival analysis based on treated kidneys. Associations between clinical factors and recurrent stenosis were examined using proportional hazards regression. RESULTS: RA-PTAS was performed on 112 kidneys for atherosclerotic RAS during the study period. Initial postintervention renal artery DUS imaging confirming PSV <180 cm/s in 101 kidneys, which formed the basis of this analysis. Estimated restenosis-free survival was 50% at 12 months and 40% at 18 months. Decreased risk of restenosis was associated with preoperative statin use (hazard ratio [HR], 0.35; 95% confidence interval [CI], 0.16-0.74; P = .006) and increased preoperative diastolic blood pressure (DBP; HR, 0.70 per 10-mm Hg increase in preoperative DBP; 95% CI, 0.49-0.99; P = .049). No other factors assessed were associated with restenosis. CONCLUSION: Restenosis occurs in a substantial number of patients treated with RA-PTAS. Preoperative statin medication use and increased preoperative DBP are associated with reduced risk of restenosis. In the absence of contraindications, statins should be considered standard therapy for patients with atherosclerotic renal artery stenosis.

Clinical utility of the resistive index in atherosclerotic renovascular disease.

OBJECTIVE: This retrospective study examines the relationship between the renal resistive index (RI) and blood pressure and renal function response after open and percutaneous intervention for atherosclerotic renovascular disease (AS-RVD). METHODS: From March 1997 to December 2005, 86 patients (46 women, 40 men; mean age, 68 +/- 10 years) underwent renal duplex sonography (RDS), including main renal artery and hilar vessel Doppler interrogation, before treatment of AS-RVD. Of these, 56 patients had open operative repair, and 30 had percutaneous intervention. The RI (1-[EDV/PSV]) was calculated from the kidney with the highest peak systolic velocity (PSV). Hypertension response was graded from preprocedural and postprocedural blood pressure measurements and medication requirements. Renal function response was graded by a >or=20% change in estimated glomerular filtration rate (eGFR) calculated from the serum creatinine concentration. RESULTS: Comorbid conditions, baseline blood pressure, and preoperative renal function were not significantly different between open and percutaneous groups. Baseline characteristics that differed between the percutaneous vs open group were higher mean age (71 +/- 11 years vs 67 +/- 9 years; P = .05), kidney length (11.3 +/- 1.3 cm vs 10.7 +/- 1.2 cm; P = .02), proportion of patients with RI >or=0.8 (50% vs 21%; P = .01), and proportion of bilateral AS-RVD (37% vs 80%; P < .01). After controlling for preintervention blood pressure and extent of repair, postoperative eGFR differed significantly for RI <0.8 or >or=0.8 when all patients (P = .003) and percutaneous intervention (P = .008) were considered. Specifically, eGFR declined from preprocedure to postprocedure in the patients with RI >or=0.8 after percutaneous repair and in the group analyzed as a whole. Neither systolic nor diastolic pressure after intervention demonstrated an association with RI. Considering all patients and both groups, multivariable proportional hazards regression models demonstrated that RI was predictive of all-cause mortality. RI was the most powerful predictor of death during follow-up (hazard ratio, 6.7; 95% confidence interval, 2.6-17.2; P < .001). CONCLUSION: After intervention for AS-RVD, RI was associated with renal function, but not blood pressure response. A strong, independent relationship between RI and mortality was observed for all patients and both treatment groups.

Endovascular management of atherosclerotic renovascular disease: early results following primary intervention.

OBJECTIVE: This retrospective review examines periprocedural morbidity and early functional responses to primary renal artery angioplasty and stenting (RA-PTAS) for patients with atherosclerotic renovascular disease (RVD). METHODS: Consecutive patients undergoing primary RA-PTAS for hemodynamically significant atherosclerotic RVD with hypertension and/or ischemic nephropathy were identified from a prospectively maintained registry. Hypertension responses were determined based on pre- and post-intervention blood pressure measurements and medication requirements. Estimated glomerular filtration rate (eGFR) was used to determine renal function responses. Both hypertension and renal function responses were assessed at least three weeks after RA-PTAS. Stepwise multivariable regression analysis was used to examine associations between blood pressure and renal function responses to RA-PTAS and select clinical variables. RESULTS: One-hundred ten primary RA-PTAS were performed on 99 patients with atherosclerotic RVD with a mean angiographic diameter-reducing stenosis of 79.2 +/- 12.9%. All patients had hypertension (mean of 3.4 +/- 1.3 antihypertensive agents). Mean pre-intervention eGFR was 49.9 +/- 22.7 mL/min/1.73 m(2), and 74 patients had a pre-intervention eGFR < 60 mL/min/1.73 m(2). The technical success rate for RA-PTAS was 94.5%. The periprocedural complication rate was 5.5%; there were no periprocedural deaths. Statistically significant decreases in mean systolic blood pressure (161.3 +/- 25.2 vs. 148.5 +/- 25.2 post-intervention, P < .0001), diastolic blood pressure (78.6 +/- 13.3 versus 72.5 +/- 13.5 post-intervention, P < .0001), and number of antihypertensive agents (3.3 +/- 1.2 versus 3.1+/- 1.3 post-intervention, P = .009) were observed. Assessed categorically, hypertension response to RA-PTAS was cured in 1.1%, improved in 20.5%, and unchanged in 78.4%. Categorical eGFR response to RA-PTAS was improved in 27.7%, unchanged in 65.1%, and worsened in 7.2%. Multivariable stepwise regression revealed associations between pre- and post-intervention systolic blood pressure (P < .0001), diastolic blood pressure (P < .0001), and eGFR (P < .0001), as well as a trend toward improved diastolic blood pressure response among patients managed with staged bilateral intervention (P = .0589). CONCLUSION: Primary RA-PTAS for atherosclerotic RVD was associated with low peri-procedural morbidity and mortality but only modest early improvements in blood pressure and renal function. Results from ongoing prospective trials are needed to assess the long term outcomes associated with RA-PTAS and clarify its role in the management of atherosclerotic RVD.

Open repair of aortic aneurysms involving the renal vessels.

This retrospective review examines the open surgical repair of intact juxtarenal (JRAAs) and suprarenal (SRAAs) aortic aneurysms to estimate effects on survival and renal function. Patients undergoing open repair of JRAA and SRAA were identified. Preoperative medical comorbidities and perioperative and late outcomes were recorded. Primary end points were survival (perioperative and long-term survival) and changes in renal function (acute tubular necrosis [ATN], acute dialysis, and late functional decline). Associations between outcomes and clinical variables were examined using univariate and multivariate techniques. Between December 1996 and September 2006, 678 patients underwent open repair of aortic aneurysms, including 150 aneurysms involving the renal vessels (134 JRAAs, 16 SRAAs). Perioperative mortality was 3% and long-term survival was 69% at 5 years. Fourteen percent of patients experienced ATN, and 7% required acute in-hospital dialysis. Late renal function remained unchanged or improved in 75%. These results demonstrate a perioperative mortality and renal complication rate in keeping with previous reports of open abdominal aortic aneurysm repairs involving the renal vessels. Future implementation of branch and fenestrated aortic endografts to treat similar aneurysms should approximate these results prior to widespread acceptance.

Branch renal artery repair with cold perfusion protection.

PURPOSE: This retrospective review describes the use and clinical outcome of cold perfusion protection during branch renal artery (RA) repair in 77 consecutive patients. METHODS: From July 1987 through November 2006, 874 patients had open operative RA repair to 1312 kidneys. Seventy-seven patients (62 women, 15 men; mean age, 44 +/- 17 years) had branch RA reconstruction using ex vivo or in situ cold perfusion protection for 78 kidneys. Demographic data and surgical technique were examined. Blood pressure response and renal function were estimated. Patency of repair was determined by angiography and renal duplex ultrasound (RDUS) imaging. Primary RA patency was estimated by life-table methods. RESULTS: Seventy-eight RAs were repaired using ex vivo (49 kidneys) or in situ (29 kidneys) cold perfusion protection. Bilateral RA repair was performed in eight patients, with 13 repairs to solitary kidneys. RA disease included aneurysm (RAA) in 50, fibromuscular dysplasia (FMD) in 37, atherosclerosis in 5, and arteritis in 2; 16 patients had both FMD and RAA. Hypertension was present in 93.5% (mean blood pressure, 184 +/- 35/107 +/- 19 mm Hg; mean of 1.9 +/- 1.1 drugs). RA repair included bypass using saphenous vein in 69, hypogastric artery in 3, polytetrafluoroethylene (PTFE) in 2, composite vein/PTFE in 2, cephalic vein in 1, or aneurysmorrhaphy in 1. The eight bilateral RA repairs were staged. One patient required bilateral cold perfusion protection. One planned nephrectomy was performed at the time of contralateral ex vivo reconstruction. No primary nephrectomies were required for intended reconstruction. Each RA reconstruction required branch dissection and reconstruction (mean of 2.8 +/- 1.6 branches were repaired). Mean cold ischemia time was 125 +/- 40 minutes. Each kidney was reconstructed in an orthotopic fashion. Five early failures of repair required three nephrectomies and one operative revision. Based on postoperative angiography or RDUS, or both, primary patency of RA repair at 12 months was 85% +/- 5%; assisted primary patency was 93% +/- 4%. Among patients with preoperative hypertension, 15% were cured, 65% were improved, and 20% were considered failed. Early renal function was improved in 35%, unchanged in 48%, and worse in 17%. Four patients had perioperative acute tubular necrosis. No patient progressed to dialysis-dependence. CONCLUSION: Both ex vivo and in situ cold perfusion protection extend the safe renal ischemia time for complex branch RA repair and avoid the need for nephrectomy.

Atheroembolism during percutaneous renal artery revascularization.

INTRODUCTION: Atheroembolization during renal artery angioplasty and stenting (RA-PTAS) has been postulated as a cause for the inferior renal function results observed when compared with those with surgical revascularization. To further characterize procedure-associated atheroembolism, we analyzed recovered atheroembolic debris and clinical data from patients undergoing RA-PTAS with distal embolic protection (DEP). METHODS: RA-PTAS procedures were performed with DEP using a commercially available temporary balloon occlusion and aspiration catheter system between July 2005 and December 2006. Following RA-PTAS but prior to deflation of the distal occlusion balloon, the static column of blood proximal to the balloon was aspirated and submitted for embolic particle analysis. Angiograms, demographics, and laboratory data were reviewed. Glomerular filtration rate (eGFR) was estimated before RA-PTAS and at 4 to 8 weeks postintervention using the abbreviated Modification of Diet in Renal Disease formula. Associations between clinical factors, captured particle counts, and changes in renal function were examined using univariate techniques and multiple linear regression. RESULTS: Twenty-eight RA-PTAS procedures were performed with DEP. Mean total number of embolic particles counted per procedure was 2033 +/- 1553 for particles 20-60 microm and 265 +/- 132 for particles >60 microm. Significant positive associations with quantity of captured particles 20 to 60 microm were observed for African American race (P = .002), predilation (P = .005), and stent diameter (P < .001); a significant negative association was observed for preoperative aspirin use (P =.016). Quantity of captured particles >60 microm was positively associated with ratio of stent to renal artery diameter (P =.009). Change in eGFR was positively associated with preoperative aspirin use (P = .006) and preoperative eGFR (P < .001), while a negative association was observed for captured particle counts >60 microm (P = .015). CONCLUSION: These results demonstrate the liberation of thousands of atheroembolic particles during RA-PTAS. Clinical, anatomic, and device-related factors may be predictive of procedural embolization, and increasing captured particle counts >60 microm were associated with inferior renal function results. Further investigation is warranted to establish relationships between atheroembolism, end organ functional impairment, and clinical responses.

Progression of atherosclerotic renovascular disease: A prospective population-based study.

OBJECTIVE: Previous reports from select hypertensive patients suggest that atherosclerotic renovascular disease (RVD) is rapidly progressive and associated with a decline in kidney size and kidney function. This prospective, population-based study estimates the incidence of new RVD and progression of established RVD among elderly, free-living participants in the Cardiovascular Health Study (CHS). METHOD: The CHS is a multicenter, longitudinal cohort study of cardiovascular risk factors, morbidity, and mortality among men and women aged >65 years old. From 1995 through 1996, 834 participants underwent renal duplex sonography (RDS) to define the presence or absence of significant RVD. Between 2002 and 2005, a second RDS study was performed in 119 participants (mean study interval, 8.0 +/- 0.8 years). Significant RVD was defined as hemodynamically significant stenosis (renal artery peak systolic velocity [RA-PSV] exceeding 1.8 m/s) or renal artery occlusion. Prevalent RVD was significant RVD at the first RDS, and incident disease was defined as new significant RVD at the second RDS. Significant change of RVD was defined as a change in RA-PSV of greater than two times the standard deviation of expected change over time, regardless of hemodynamic significance or progression to renal artery occlusion. RESULTS: The second RDS study cohort included 119 CHS participants with 235 kidneys (35% men; mean age, 82.8 +/- 3.4). On follow-up, no prevalent RVD (n = 13 kidneys; 6.0%) progressed to occlusion. Twenty-nine kidneys without RVD at the first RDS demonstrated significant change in PSV at the second RDS; including nine kidneys with new significant RVD (8 new stenoses; 1 new occlusion). Controlling for within-subject correlation, the overall estimated change in RVD among all 235 kidneys was 14.0% (95% confidence interval [CI], 9.2% to 21.4%), with progression to significant RVD in 4.0% (95% CI, 1.9% to 8.2%). Longitudinal increase in diastolic blood pressure and decrease in renal length were significantly associated with progression to new (ie, incident) significant RVD but not prevalent RVD. CONCLUSIONS: This is the first prospective, population-based estimate of incident RVD and progression of prevalent RVD among free-living elderly Americans. In contrast to previous reports among select hypertensive patients, CHS participants with a low rate of clinical hypertension demonstrated a significant change of RVD in only 14.0% of kidneys on follow-up of 8 years (annualized rate, 1.3% per year). Progression to significant RVD was observed in only 4.0% (annualized rate, 0.5% per year), and no prevalent RVD progressed to occlusion.

Renal duplex parameters, blood pressure, and renal function in elderly people.

BACKGROUND: Changes in renal artery and renal parenchyma perfusion are believed to correlate with severity of hypertension and worsened renal function, but population-based studies of these associations are not available. This study examines relationships between parameters derived from renal duplex sonography (RDS), blood pressure (BP), and excretory renal function in a population-based cohort of elderly Americans. METHODS: Through an ancillary study to the Cardiovascular Health Study, 758 participants (37% men; mean age, 77 years) underwent RDS in which flow velocities and frequency shifts were determined from spectral analysis of Doppler-shifted signals obtained from the renal artery and parenchyma. Associations of these duplex parameters with BP and inverse serum creatinine were examined by using multivariate regression techniques. RESULTS: Main renal artery peak systolic flow velocity (PSV) showed independent associations with BP, with an SD increase in PSV (0.53 m/s) associated with a 3.3-mm Hg increase in systolic BP (SBP) and a 2.4-mm Hg decrease in diastolic BP (DBP). An SD decrease in end-diastolic frequency shift (EDF; 131 kHz) was associated with a 6.0-mm Hg increase in SBP, a 4.2-mm Hg decrease in DBP, and a significant 3.7% decrease in inverse serum creatinine. CONCLUSION: Increases in renal artery PSV and decreases in parenchymal EDF are associated with increased SBP and decreased DBP. Moreover, decreased parenchymal EDF showed significant associations with impaired excretory renal function. These results suggest that renal duplex parameters are associated with renal parenchymal changes caused by hypertension and progressive renal dysfunction in elderly people.

Chronic visceral ischemia: symptom-free survival after open surgical repair.

A retrospective review of patients treated with a history of chronic visceral ischemia (CVI) was made to determine primary patency of open surgical repair and estimated symptom-free survival. Patients with CVI between 1990 and 2003 were reviewed. Included were those with chronic symptoms alone (C-CVI) and acute-on-chronic symptoms (A-CVI). Data were obtained from a vascular database. Symptom-free survival and graft patency were estimated by using product limit estimates. Fifty-eight patients (13 men, 45 women; mean age: 63 years) were treated surgically for C-CVI (34 patients) and A-CVI (24 patients). All patients had postprandial abdominal pain and weight loss (mean: 17 kg). One fourth reported food fear. Preoperative imaging demonstrated disease of the superior mesenteric artery (SMA) (100%; 64% occluded), celiac axis (89%; 37% occluded), and inferior mesenteric artery (IMA) (54%; 60% occluded). Multiple vessels were involved in 95% of patients (mean: 2.3 vessels/patient). Operative management included antegrade revascularization of 80 vessels. Combined aortic and/or renal procedures were performed in 7 patients. Patient demographics and visceral disease did not differ for C-CVI and A-CVI; however, perioperative mortality differed significantly (10% for C-CVI vs 54% for A-CVI [p < 0.001]). Intestinal gangrene at presentation was associated with perioperative (hazard ratio [HR]: 7.6; 95% CI: 2.7-21.6; p=0.0002) and follow-up death (HR: 7.8; CI 2.8-21.9; p <0.0001). Follow-up (mean: 34 months) was complete for 54/68 vessels (79%). Estimated primary and primary assisted patency at 5 years were 81% and 89% respectively. Estimated symptom-free survival for hospital survivors was 57% at 70 months. Open antegrade methods of visceral artery repair for CVI were durable and associated with 57% symptom-free survival at 70 months. Patient demographics and distribution of visceral artery anatomy were similar; however, perioperative mortality for C-CVI and A-CVI differed dramatically. Improved outcomes for A-CVI require recognition and treatment of CVI before onset of intestinal gangrene.

Mesenteric artery disease in the elderly.

PURPOSE: The purpose of this study was to estimate the population-based prevalence of mesenteric artery stenosis (MAS) and occlusion among independent elderly Americans. METHOD: As part of an ancillary investigation to the Cardiovascular Health Study (CHS), participants in the Forsyth County, NC cohort had visceral duplex sonography of the celiac arteries and superior mesenteric arteries (SMAs). Critical MAS was defined by celiac peak systolic velocity >or=2.0 m/s and/or SMA peak systolic velocity >or=2.7 m/s. Occlusion of either vessel was defined by lack of a Doppler-shifted signal within the imaged artery. Demographic data, blood pressures, and blood lipid levels were collected as part of the baseline CHS examination. Participants' weights were measured at baseline and before the duplex exam. Univariate tests of association were performed with two-way contingency tables, Student t tests, and Fisher exact tests. Multivariate associations were examined with logistic regression analysis. RESULTS: A total of 553 CHS participants had visceral duplex sonography technically adequate to define the presence or absence of MAS. The study group had a mean age of 77.2 +/- 4.9 years and comprised 63% women and 37% men. Participant race was 76% white and 23% African-American. Ninety-seven participants (17.5%) had MAS. There was no significant difference in age, race, gender, body mass index, blood pressure, cholesterol, or low-density lipoproteins for participants with or without MAS. Forward stepwise variable selection found renal artery stenosis (P =.008; odds ratio [OR], 2.85; 95% confidence interval [CI], 1.31, 6.21) and high-density lipoprotein >40 (P =.02; OR, 3.03; 95% CI, 1.17, 7.81) significantly associated with MAS in a multivariate logistic regression model. Eighty-three of the 97 participants with MAS (15.0% of the cohort) had isolated celiac stenosis. Seven participants (1.3% of the cohort) had combined celiac and SMA stenosis. Five participants (0.9% of the cohort) had isolated SMA stenosis. Two participants (0.4% of the cohort) had celiac occlusion. Considering all participants with MAS, there was no association with weight change. However, SMA stenosis and celiac occlusion demonstrated an independent association with annualized weight loss (P =.028; OR, 1.54; 95% CI, 1.05, 2.26) and with renal artery stenosis (P =.001; OR, 9.48; 95% CI, 2.62, 34.47). CONCLUSION: This investigation provides the first population-based estimate of the prevalence of MAS among independent elderly Americans. MAS existed in 17.5% of the study cohort. The majority had isolated celiac disease. SMA stenosis and celiac artery occlusion demonstrated a significant and independent association with weight loss and concurrent renal artery disease.

Surgical management of renal artery aneurysms.

PURPOSE: This retrospective review describes the surgical management and clinical outcome for renal artery aneurysms (RAAs) in 62 consecutive patients. METHODS: From January 1987 through July 2003, 804 patients had operative renal artery (RA) repair involving 1206 kidneys at our center. A subgroup of 62 patients (42 women, 20 men; mean age 46 +/- 18 years) received repair of 72 RAAs. Demographic data, comorbidity, and surgical technique were examined. Blood pressure and renal function response were determined. Patency of repair was evaluated by renal duplex sonography. Primary patency and patient survival were estimated by life-table methods. Tests of association were performed using chi(2) and the Student t tests. RESULTS: Seventy-two RAs were repaired for RAA with a mean diameter of 2.6 cm (range, 1.3 to 5.5 cm). Bilateral RAAs were present in 21 patients. Associated conditions included fibromuscular dysplasia, atherosclerosis, and arteritis in 54%, 35%, and 7%, respectively. Hypertension was present in 89% (mean blood pressure, 171 +/- 35/95 +/- 19 mm Hg; mean medications, 2.2 +/- 1.2 drugs) and renal insufficiency was present in 8% (mean serum creatinine, 1.9 +/- 0.6 mg/dL). RAA repair included bypass (67%), aneurysmorrhaphy (15%), or a combination (17%). One planned nephrectomy (1%) was performed for un-reconstructable disease. Branch RA reconstruction in 78% used ex vivo cold perfusion in 50%, in situ cold perfusion in 29%, and warm in situ repair in 21%. Of 9 bilateral RAA repairs, 7 (78%) were staged and 2 (22%) were simultaneous. Combined aortic reconstruction was required in 6 (10%) patients. Perioperative death occurred in 1 patient (1.6%), and significant morbidity was observed in 8 patients (12%). Hypertension was considered improved in 54%, cured in 21%, and unchanged in 25% at mean follow-up of 48 months (range, 1-156 months). Among patients with renal insufficiency, renal function was improved in 3 (60%), unchanged in 1 (20%), and declined in 1 (20%). Follow-up patency (mean, 33 months; range, 1-118 months) was determined for 64 (91%) RA reconstructions. Product-limit estimate of primary patency at 48 months was 96%. Product-limit estimate of survival was 91% at 120 months. CONCLUSION: RAAs were repaired with low morbidity and mortality. Complex branch RAA repair using cold perfusion preservation and ex vivo techniques resulted in no unplanned nephrectomy, with an estimated primary patency of 96% at 48 months. Beneficial blood pressure response was observed in the majority of hypertensive patients. These results support selective surgical management of RAA.

Differential effects of Rho-kinase inhibition on artery wall mass and remodeling.

PURPOSE: Constrictive remodeling and new artery wall mass contribute to lumen narrowing in atherosclerosis and following injury. Rho-kinase, an important regulator of myosin phosphorylation and cytoskeletal reorganization, is critical to smooth muscle cell (SMC) growth and vasoconstriction, but its role in artery wall remodeling is poorly defined. We hypothesized that constrictive artery wall remodeling is dependent on Rho signaling so that blocking Rho-kinase would promote outward artery wall remodeling in response to intimal hyperplasia and thus limit lumen narrowing. METHODS: To test this hypothesis, we first studied the effects of the Rho-kinase inhibitor fasudil on SMC remodeling of collagen matrix in vitro. Mouse aortic SMCs were seeded into three-dimensional collagen gels with and without fasudil, and extent of contraction was measured at 24 hours. We then used the mouse carotid ligation model to study the effects of Rho-kinase inhibition on remodeling and intimal hyperplasia in vivo. C57B6/J mice were randomly assigned to fasudil (100 mg/kg per day) or vehicle and underwent unilateral carotid artery ligation or sham ligation. Remodeling and wall mass were measured after 28 days. RESULTS: Fasudil blocked SMC contraction of collagen gels in a dose-dependent manner. Complete inhibition of collagen gel remodeling was achieved between 10 and 30 micromol/L fasudil. In control mice, carotid ligation caused significant thickening of the adventitia, media, and intima (P <.01) and outward remodeling of the carotid wall. The external elastic lamina (EEL) area increased by 14% versus sham (P <.05), but this increase was insufficient to prevent lumen narrowing (-42% vs sham, P <.05). Fasudil treatment had favorable effects on wall mass, inhibiting neointimal (P =.04), medial (P =.03), and adventitial thickening (P =.07) versus controls. Opposite our hypothesis, however, fasudil did not enhance outward artery wall remodeling or improve lumen caliber. Rather, inhibiting Rho-kinase blocked outward remodeling in response to ligation. EEL area was significantly smaller in treated versus control animals (P =.04) and slightly smaller versus shams (P = NS). These data suggest that Rho activation contributes significantly to both hyperplasia and outward remodeling of the injured artery wall. Rho-kinase may prove an important target to limit intimal hyperplasia and prevent restenosis when remodeling is improved by other means (eg, stents).

Multiple aneurysms in childhood.

Arterial aneurysms in children are rare. When present, they are often associated with connective tissue disorders or arteritidies. Idiopathic aneurysms occurring at multiple sites throughout the arterial tree are rare, with only ten cases reported. This report describes a case of multiple arterial aneurysms of uncertain origin involving upper-extremity, extracranial cerebrovascular, aortoiliac, and renal arteries in a 14-year-old boy. The clinical presentation, vascular reconstruction, pathologic findings, and a brief review of the literature are described.

Analysis of medical risk factors and outcomes in patients undergoing open versus endovascular abdominal aortic aneurysm repair.

OBJECTIVE: The emergence of endovascular repair (ER) for infrarenal abdominal aortic aneurysm (AAA) has provided surgeons with a new technique that should ideally improve patient outcomes. To more accurately characterize the advantages of ER versus traditional/open AAA repair (TOR), we compared the preoperative medical risk factors (PMRFs) and perioperative outcomes (PO) of those patients undergoing elective treatment of infrarenal AAA with ER and TOR over a recent 18-month period at our center. METHODS: Through our institutional vascular surgery patient registry, all patients undergoing aortic aneurysm repair of any type between December 1999 and June 2001 were identified. Only those patients undergoing elective infrarenal AAA repair were analyzed. Hospital records were examined for all patients, and PMRF and PO were assessed via Society for Vascular Surgery/International Society for Cardiovascular Surgery reporting guidelines. Student t, chi(2), Fisher exact, or Wilcoxon rank sum tests were applied where appropriate to determine differences among PMRF and PO according to method of aneurysm repair. RESULTS: During the 18-month study period, a total of 199 aortic aneurysms were repaired at our institution. Ninety-nine elective infrarenal AAA repairs made up the study cohort (ER, n = 33; TOR, n = 66). When examined by method of aneurysm repair, no differences existed in demographics or AAA size. Patients undergoing ER had a significantly greater degree of preoperative pulmonary comorbidity than patients undergoing TOR (P <.001). However, no differences existed in terms of American Society of Anesthesiologists classification or cardiac (P =.52), cerebrovascular (P =.44), diabetic (P =.51), hypertensive (P =.90), hyperlipidemia (P =.91) or renal (P =.23) comorbidities between the two groups. Perioperative morbidity and mortality rates were also not significantly different by method of repair. ER was associated with shorter operative time, intensive care unit stay, and overall hospital length of stay (P <.0001). However, subsequent operative procedures related to the AAA repair were performed more frequently after ER (TOR = 1.5% versus ER = 15.2%; P = 0.015). CONCLUSION: These results suggest that ER offers improvements in hospital convalescent and operating room times but no beneficial impact on overall morbidity and mortality rates when similar PMRFs exist, especially when used at medical centers where low morbidity and mortality rates are already established for TOR. Other centers performing ER should undertake such an analysis to assess its impact on their patients.