Early carotid endarterectomy in symptomatic patients is associated with poorer perioperative outcomes

ObjectiveThe optimal timing of carotid endarterectomy (CEA) after ipsilateral hemispheric stroke is controversial. Although early studies suggested that an interval of about 6 weeks after a completed stroke was preferred, more recent data have suggested that delaying CEA for this period of time is not necessary. With these issues in mind, we reviewed our experience to examine perioperative outcome with respect to the timing of CEA in previously symptomatic patients.MethodsA retrospective review of a prospectively maintained database of all CEAs performed at our institution from 1992 to 2003 showed that 2537 CEA were performed, of which 1158 (45.6%) were in symptomatic patients. Patients who were operated on emergently ≤48 hours of symptoms for crescendo transient ischemic attacks (TIAs) or stroke-in-evolution were excluded from analysis (n = 25). CEA was considered “early” if performed ≤4 weeks of symptoms, and “delayed” if performed after a minimum of a 4-week interval following the most recent symptom.ResultsOf nonurgent CEAs in symptomatic patients, in 87 instances the exact time interval from symptoms to surgery could not be precisely determined secondary to the remoteness of the symptoms (>18 months), and these were excluded from further analysis. Of the remaining 1046 cases, 62.7% had TIAs and 37.3% had completed strokes as their indication for surgery. Among the entire cohort, patients who underwent early CEA were significantly more likely to experience a perioperative stroke than patients who underwent delayed CEA (5.1% vs 1.6%, P = .002). Patients with TIAs alone were more likely to be operated on early rather than in a delayed fashion (64.3% vs 46.7%, P < .0001), likely reflecting institutional bias in selecting delayed CEA for stroke patients. However, even when examined as two separate groups, both TIA patients (n = 656) and CVA patients (n = 390) were significantly more likely to experience a perioperative stroke when operated upon early rather than in a delayed fashion (TIA patients, 3.3% vs 0.9%, P = .05; CVA patients, 9.4% vs 2.4%, P = .003). There were no significant differences in demographics or other meaningful variables between patients who underwent early CEA and those who underwent delayed CEA.ConclusionsIn a large institutional experience, patients who underwent CEA ≤4 weeks of ipsilateral TIA or stroke experienced a significantly increased rate of perioperative stroke compared with patients who underwent CEA in a more delayed fashion. This was true for both TIA and stroke patients, although the results were more impressive among stroke patients. On the basis of these results, we continue to recommend that waiting period of 4 weeks be considered in stroke patients who are candidates for CEA

Association Between Advanced Age and Vascular Disease in Different Arterial Territories A Population Database of Over 3.6 Million Subjects

ObjectivesThis study sought to determine the relationship between vascular disease in different arterial territories and advanced age.BackgroundVascular disease in the peripheral circulation is associated with significant morbidity and mortality. There is little data to assess the prevalence of different phenotypes of vascular disease in the very elderly.MethodsOver 3.6 million self-referred participants from 2003 to 2008 who completed a medical and lifestyle questionnaire in the United States were evaluated by screening ankle brachial indices <0.9 for peripheral artery disease (PAD), and ultrasound imaging for carotid artery stenosis (CAS) >50% and abdominal aortic aneurysm (AAA) >3 cm. Participants were stratified by decade of life. Multivariate logistic regression analysis was used to estimate odds of disease in different age categories.ResultsOverall, the prevalence of PAD, CAS, and AAA, was 3.7%, 3.9%, and 0.9%, respectively. Prevalence of any vascular disease increased with age (40 to 50 years: 2%, 51 to 60 years: 3.5%, 61 to 70 years: 7.1%, 71 to 80 years: 13.0%, 81 to 90 years: 22.3%, 91 to 100 years: 32.5%; p < 0.0001). Prevalence of disease in each vascular territory increased with age. After adjustment for sex, race/ethnicity, body mass index, family history of cardiovascular disease, smoking, diabetes, hypertension, hypercholesterolemia, and exercise, the odds of PAD (odds ratio [OR]: 2.14; 95% confidence interval [CI]: 2.12 to 2.15), CAS (OR: 1.80; 95% CI: 1.79 to 1.81), and AAA (OR: 2.33; 95% CI: 2.30 to 2.36) increased with every decade of life.ConclusionsThere is a dramatic increase in the prevalence of PAD, CAS, and AAA with advanced age. More than 20% and 30% of octogenarians and nonagenarians, respectively, have vascular disease in at least 1 arterial territory

Clinical and operative predictors of outcomes of carotid endarterectomy

ObjectiveThe net benefit for patients undergoing carotid endarterectomy is critically dependent on the risk of perioperative stroke and death. Information about risk factors can aid appropriate selection of patients and inform efforts to reduce complication rates. This study identifies the clinical, radiographic, surgical, and anesthesia variables that are independent predictors of deaths and stroke following carotid endarterectomy.MethodsA retrospective cohort study of patients undergoing carotid endarterectomy in 1997 and 1998 by 64 surgeons in 6 hospitals was performed (N = 1972). Detailed information on clinical, radiographic, surgical, anesthesia, and medical management variables and deaths or strokes within 30 days of surgery were abstracted from inpatient and outpatient records. Multivariate logistic regression models identified independent clinical characteristics and operative techniques associated with risk-adjusted rates of combined death and nonfatal stroke as well as all strokes.ResultsDeath or stroke occurred in 2.28% of patients without carotid symptoms, 2.93% of those with carotid transient ischemic attacks, and 7.11% of those with strokes (P < .0001). Three clinical factors increased the risk-adjusted odds of complications: stroke as the indication for surgery (odds ratio [OR], 2.84; 95% confidence interval [CI] = 1.55-5.20), presence of active coronary artery disease (OR, 3.58; 95% CI = 1.53-8.36), and contralateral carotid stenosis ≥50% (OR, 2.32; 95% CI = 1.33-4.02). Two surgical techniques reduced the risk-adjusted odds of death or stroke: use of local anesthesia (OR, 0.30; 95% CI = 0.16-0.58) and patch closure (OR, 0.43; 95% CI = 0.24-0.76).ConclusionsInformation about these risk factors may help physicians weigh the risks and benefits of carotid endarterectomy in individual patients. Two operative techniques (use of local anesthesia and patch closure) may lower the risk of death or stroke

Five-year efficacy and safety of asfotase alfa therapy for adults and adolescents with hypophosphatasia

Hypophosphatasia (HPP) features low tissue-nonspecific alkaline phosphatase (TNSALP) isoenzyme activity resulting in extracellular accumulation of its substrates including pyridoxal 5\u27-phosphate (PLP), the principal circulating form of vitamin B6, and inorganic pyrophosphate (PPi), a potent inhibitor of mineralization. Asfotase alfa is an enzyme replacement therapy developed to treat HPP. This multinational, randomized, open-label study (NCT01163149; EudraCT 2010-019850-42) evaluated the efficacy and safety of asfotase alfa in adults and adolescents 13-66 years of age with HPP. The study comprised a 6-month primary treatment period and a 4.5-year extension phase. In the primary treatment period, 19 patients were randomized to receive asfotase alfa 0.3 mg/kg/d subcutaneously (SC; n = 7), asfotase alfa 0.5 mg/kg/d SC (n = 6), or no treatment (control; n = 6) for 6 months. In the extension phase, patients received asfotase alfa (0.5 mg/kg/d for 6 mo-1 y, then 1 mg/kg/d 6 d/wk). During the primary treatment period, changes from Baseline to Month 6 in plasma PLP and PPi concentrations (coprimary efficacy measure) were greater in the combined asfotase alfa group compared with the control group, reaching statistical significance for PLP (P = 0.0285) but not for PPi (P = 0.0715). However, for the total cohort, the within subject changes in both PLP and PPi after 6 months and over 5 years of treatment with asfotase alfa were significant (P \u3c 0.05). Secondary efficacy measures included transiliac crest histomorphometry, dual-energy X-ray absorptiometry (DXA), and the 6-Minute Walk Test (6MWT). A significant decrease from Baseline in mineralization lag time was observed in the combined asfotase alfa group at Year 1. There were no significant differences between treated and control patients in DXA mean bone mineral density results at 6 months; Z-scores and T-scores were within the expected range for age at Baseline and remained so over 5 years of treatment. On the 6MWT, median (min, max) distance walked increased from 355 (10, 620; n = 19) meters before treatment to 450 (280, 707; n = 13) meters at 5 years (P \u3c 0.05). Results for the exploratory outcome measures suggested improvements in gross motor function, muscle strength, and patient-reported functional disability over 5 years of treatment. There were no deaths during this study. Asfotase alfa was generally well tolerated; the most common adverse events were mild to moderate injection site reactions. This study suggests that in adults and adolescents with pediatric-onset HPP, treatment with asfotase alfa is associated with normalization of circulating TNSALP substrate levels and improved functional abilities

A comparison of regional and general anesthesia in patients undergoing carotid endarterectomy

AbstractPurpose: The optimal anesthetic for use during carotid endarterectomy is controversial. Advocates of regional anesthesia suggest that it may reduce the incidence of perioperative complications in addition to decreasing operative time and hospital costs. To determine whether the anesthetic method correlated with the outcome of the operation, a retrospective review of 3975 carotid operations performed over a 32-year period was performed.Methods: The records of all patients who underwent carotid endarterectomy at our institution from 1962 to 1994 were retrospectively reviewed. Operations performed with the patient under regional anesthesia were compared with those performed with the patient under general anesthesia with respect to preoperative risk factors and perioperative complications.Results: Regional anesthesia was used in 3382 operations (85.1%). There were no significant differences in the age, gender ratio, or the rates of concomitant medical illnesses between the two patient populations. The frequency of perioperative stroke in the series was 2.2%; that of myocardial infarction, 1.7%; and that of perioperative death, 1.5%. There were no statistically significant differences in the frequency of perioperative stroke, myocardial infarction, or death on the basis of anesthetic technique. A trend toward higher frequencies of perioperative stroke (3.2% vs 2.0%) and perioperative death (2.0% vs 1.4%) in the general anesthesia group was noted. In examining operative indications, however, there was a significant increase in the percentage of patients receiving general anesthesia who had sustained preoperative strokes when compared with the regional anesthesia patients (36.1% vs 26.4%; p < 0.01). There was also a statistically significant higher frequency of contralateral total occlusion in the general anesthesia group (21.8% vs 15.4%; p = 0.001). The trend toward increased perioperative strokes in the general anesthesia group may be explicable either by the above differences in the patient populations or by actual differences based on anesthetic technique that favor regional anesthesia.Conclusions: In a retrospective review of a large series of carotid operations, regional anesthesia was shown to be applicable to the vast majority of patients with good clinical outcome. Although the advantages over general anesthesia are perhaps small, the versatility and safety of the technique is sufficient reason for vascular surgeons to include it in their armamentarium of surgical skills. Considering that carotid endarterectomy is a procedure in which complication rates are exceedingly low, a rigidly controlled, prospective randomized trial may be required to accurately assess these differences. (J Vasc Surg 1996;24;946-56.

Carotid endarterectomy in female patients: Are the concerns of the Asymptomatic Carotid Atherosclerosis Study valid?

AbstractObjectives: Although the results of the Asymptomatic Carotid Atherosclerosis Study clearly demonstrated the benefit of surgical over medical management of severe carotid artery stenosis, the results for women in particular were less certain. This was to some extent because of the higher perioperative complication rate observed in the 281 women (3.6% vs 1.7% in men). The objective of this study was to review a large experience with carotid endarterectomy in female patients and to determine whether the perioperative results differed from those of male patients. Methods: A review was conducted of a prospectively compiled database on all carotid endarterectomies performed between 1982 and 1997. Operations performed in 991 female patients were compared with those performed in 1485 male patients. Results: Female patients had a significantly lower incidence of diabetes, coronary artery disease, and contralateral carotid artery occlusion than did male patients. Female patients had a significantly higher incidence of hypertension. There were no significant differences in the age, smoking history, anesthetic route, shunt use, or clamp tolerance between the two groups. Of 991 female patients, 659 (66.5%) had preoperative symptoms, whereas 332 (33.5%) cases were performed for asymptomatic stenosis. Among 1485 male patients, 1041 (70.1%) had symptoms, and 444 (29.9%) were symptom free before surgery. There were no significant differences noted in the perioperative stroke rates between men and women overall (2.3% vs 2.4%, P =.92), or when divided into symptomatic (2.5% vs 3.0%, P =.52) and asymptomatic (2.0% vs 1.2%, P =.55) cases. Conclusions: Carotid endarterectomy can be performed with equally low perioperative stroke rates in men and women in both symptomatic and asymptomatic cases. In this series, symptom-free female patients had the lowest overall stroke rate. The concerns of the Asymptomatic Carotid Atherosclerosis Study regarding the benefit of carotid endarterectomy in female patients should therefore not prevent clinicians from recommending and performing carotid endarterectomy in appropriately selected symptom-free female patients. (J Vasc Surg 2001;33:236-41.

Left subclavian artery coverage during thoracic endovascular aortic aneurysm repair does not mandate revascularization

ObjectiveThis study assessed the risk of left subclavian artery (LSA) coverage and the role of revascularization in a large population of patients undergoing thoracic endovascular aortic aneurysm repair.MethodsA retrospective multicenter review of 1189 patient records from 2000 to 2010 was performed. Major adverse events evaluated included cerebrovascular accident (CVA) and spinal cord ischemia (SCI). Subgroup analysis was performed for noncovered LSA (group A), covered LSA (group B), and covered/revascularized LSA (group C).ResultsOf 1189 patients, 394 had LSA coverage (33.1%), and 180 of these patients (46%) underwent LSA revascularization. In all patients, emergency operations (9.5% vs 4.3%; P = .001), renal failure (12.7% vs 5.3%; P = .001), hypertension (7% vs 2.3%; P = .01), and number of stents placed (1 = 3.7%, 2 = 7.4%, ≥3 = 10%; P = .005) were predictors of SCI. History of cerebrovascular disease (9.6% vs 3.5%; P = .002), chronic obstructive pulmonary disease (9.5% vs 5.4%; P = .01), coronary artery disease (8.5% vs 5.3%; P = .03), smoking (8.9% vs 4.2%) and female gender (5.3% men vs 8.2% women; P = .05) were predictors of CVA. Subgroup analysis showed no significant difference between groups B and C (SCI, 6.3% vs 6.1%; CVA, 6.7% vs 6.1%). LSA revascularization was not protective for SCI (7.5% vs 4.1%; P = .3) or CVA (6.1% vs 6.4%; P = .9). Women who underwent revascularization had an increased incidence of CVA event compared with all other subgroups (group A: 5.6% men, 8.4% women, P = .16; group B: 6.6% men, 5.3% women, P = .9; group C: 2.8% men, 11.9% women, P = .03).ConclusionsLSA coverage does not appear to result in an increased incidence of SCI or CVA event when a strategy of selective revascularization is adopted. Selective LSA revascularization results in similar outcomes among the three cohorts studied. Revascularization in women carries an increased risk of a CVA event and should be reserved for select cases

Growth and disease burden in children with hypophosphatasia

Hypophosphatasia, an inborn error of metabolism characterized by impaired bone mineralization, can affect growth. This study evaluated relationships between anthropometric parameters (height, weight, and body mass index) and clinical manifestations of hypophosphatasia in children. Design: Data from children (aged < third percentile) and those with normal stature. Methods: Anthropometric parameters were evaluated by age group (< third percentile) and those with normal stature. Results: This analysis included 215 children (54.4% girls). Short stature presented in 16.1% of children aged<2 years and 20.4% of those aged≥2 years at assessment. Among those with available data (n = 62), height was below the target height (mean: −0.66 standard deviations). Substantial worsening of growth (mean delta height z score: −1.45; delta weight z score: −0.68) occurred before 2 years of age, while in those aged≥2 years, anthropometric trajectories were maintained (delta height z score: 0.08; delta weight z score: 0.13). Broad-ranging hypophosphatasia manifestations (beyond dental) were observed in most children. Conclusions: Short stature was not a consistent characteristic of children with hypophosphatasia, but growth impairment was observed in those aged<2 years, indicating that hypophosphatasia might affect growth plate activity during infancy. In addition, a broad range of clinical manifestations occurred in those above and below the third percentile for height, suggesting that height alone may not accurately reflect hypophosphatasia disease burden and that weight is less affected than longitudinal growt