Long-Term Prognostic Risk in Lower Extremity Peripheral Arterial Disease as a Function of the Number of Peripheral Arterial Lesions.

BACKGROUND: Although patients with peripheral artery disease (PAD) are known to have an increased risk of adverse prognosis, simple techniques to further risk-stratify PAD patients would be clinically useful. A plausible but unexplored factor to predict such risk would be greater disease burden, manifested as multiple lower extremity lesions. The aim of this study was to examine the association between having multiple versus isolated lower extremity PAD lesions and long-term prognosis. METHODS AND RESULTS: A prospective cohort of 756 newly diagnosed PAD patients underwent duplex ultrasound testing to determine the number of lower extremity lesions. Cox regression models examined the independent association of lesion number (≥3 and 2 versus 1) and adverse prognosis (defined as a composite end point comprising first occurrence of either lower extremity amputation, admission for heart failure, nonfatal stroke, myocardial infarction, or unstable angina or mortality), adjusting for demographic and clinical risk factors. Analyses were replicated using an advanced Cox-based model for multiple events. A total of 173 patients (23%) had ≥3 lesions, 197 (26%) had 2 lesions, and 386 (51%) had 1 lesion. After a median follow-up of 3.2 years, patients with ≥3 lesions had an increased risk of experiencing a first adverse event (adjusted hazard ratio 1.60, 95% CI 1.08-2.38, P=0.020) and an increased risk of having multiple events (adjusted hazard ratio 1.53, 95% CI 1.08-2.18, P=0.018). Patients with 2 lesions had a prognosis similar to those with 1 lesion. CONCLUSIONS: Among PAD patients, a greater number of lesions is associated with an increased risk of an adverse prognosis over 3 years of follow-up. Assessing the number of lower extremity lesions might serve as a simple risk-stratification tool at initial PAD diagnosis.

Gender differences in health status and adverse outcomes among patients with peripheral arterial disease.

BACKGROUND: Few studies have examined gender differences in health status and cardiovascular outcomes in patients with peripheral artery disease (PAD). This study assessed (1) self-reported health status at PAD diagnosis and 12-months later, and explored (2) whether outcomes in women with PAD differ with regard to long-term major adverse events. METHODS AND RESULTS: A total of 816 patients (285 women) with PAD were enrolled from 2 vascular clinics in the Netherlands. Baseline clinical data and subsequent adverse events were recorded and patients completed the Short Form-12 (SF-12, Physical Component Score [PCS] and Mental Component Score [MCS]) upon PAD diagnosis and 12-months later. Women had similar ages and clinical characteristics, but poorer socio-economic status and more depressive symptoms at initial diagnosis, as compared with men. Women also had poorer physical (PCS: 37±10 versus 40±10, P=0.004) and mental ( MCS: 47±12 versus 49±11, P=0.005) health status at the time of presentation. At 12-months, women still reported a poorer overall PCS score (41±12 versus 46±11, P=0.006) and MCS score (42±14 versus 49±12, P=0.002). Female gender was an independent determinant of a poorer baseline and 12-month PCS and MCS scores. However, there were no significant differences by gender on either mortality (unadjusted hazard ratio [HR]=0.93, 95% CI 0.60;1.44, P=0.74) or major adverse events (unadjusted HR=0.90, 95% CI 0.63;1.29, P=0.57), after a median follow-up of 3.2 years. CONCLUSIONS: Women's physical and mental health status is compromised both at initial PAD diagnosis and at 12-month follow-up, despite experiencing a similar magnitude of change in their health scores throughout the first 12-months after diagnosis.

Determinants of invasive treatment in lower extremity peripheral arterial disease.

OBJECTIVE: Since it is unknown what factors are weighed in a clinician's decision to refer patients with symptomatic lower extremity peripheral arterial disease (PAD) for invasive treatment, we examined the relationship between health status, lesion location, and site variations and invasive treatment referral ≤1 year following diagnosis in patients with PAD. METHODS: This was a prospective observational cohort study on ambulatory patients that presented themselves at two vascular surgery outpatient clinics. A total of 970 patients with new symptoms of PAD or with an exacerbation of existing PAD symptoms that required clinical evaluation and treatment (Rutherford Grade I) were eligible, 884 consented and were included between March 2006 and November 2010. We report on 505 patients in the current study. Prior to patients' initial PAD evaluation, the Short Form-12, Physical Component Scale (PCS) was administered to measure health status. Anatomical lesion location (proximal vs distal) was derived from duplex ultrasounds. PCS scores, lesion location, and site were evaluated as determinants of receiving invasive (endovascular, surgery) vs noninvasive treatment ≤1 year following diagnosis in Poisson regression analyses, adjusting for demographics, ankle-brachial index, and risk factors. RESULTS: Invasive treatment as a first-choice was offered to 167 (33%) patients. While an association between poorer health status and invasive therapy was found in unadjusted analyses (relative risk [RR], 0.98; 95% confidence interval [CI], 0.97-1.00; P = .011), proximal lesion location (RR, 3.66; 95% CI, 2.70-4.96; P < .0001) and site (RR, 1.69; 95% CI, 1.11-2.58; P = .014) were independent predictors of invasive treatment referral in the final model. CONCLUSIONS: One-third of patients were treated invasively following PAD diagnosis. Patients' health status was considered in providers' decision to refer patients for invasive treatment, but having a proximal lesion was the strongest predictor. This study also found some important first indications of site variations in offering invasive treatment among patients with PAD. Future work is needed to further document these variations in care.

A shift toward endovascular repair for vascular complications in lumbar disc surgery during the last decade.

BACKGROUND: The purpose of this study is to evaluate 2 patients who underwent endovascular repair directly after acute life-threatening vascular injury complicating lumbar disc surgery, and to update an overview of the literature from 2002 to gain insights into characteristics, diagnosis, treatment, and outcomes of this rare, life-threatening complication. METHODS: PubMed was searched for English language studies on vascular injury (lacerations, arteriovenous fistulas, and pseudoaneurysms) complicating lumbar disc surgery by a posterior approach published from 2002. Two cases from the authors' institute were added to the review. Information on patient characteristics, diagnosis, treatment strategies, and outcomes were extracted by 2 independent reviewers. CASE REPORTS: The first case describes a 54-year-old man who underwent lumbar disc surgery through a posterior approach (L5-S1) and became hypotensive intraoperatively. Angiography revealed an injury of the right internal iliac artery. Bleeding was successfully repaired by endovascular repair (acute balloon occlusion followed by coiling). The second case describes a 51-year-old women who suddenly became hypotensive during L4 through L5 discectomy caused by bleeding from a laceration in the right common iliac artery. Angiography confirmed the diagnosis, and the bleeding was successfully treated through endovascular repair with a covered stent. RESULTS: A total of 56 cases from 34 articles were found in the literature since 2002, including lacerations, arteriovenous fistulas, and pseudoaneurysms. Two cases from the authors' institute were added to the review. Vascular injury was recognized intraoperatively in 36%, and within 24 hours postsurgery in 28%. The common iliac artery was most frequently affected (51%), followed by the iliac vein (23%). All lacerations were detected during surgery, whereas most arteriovenous fistulas and pseudoaneurysms were detected in the long term. Treatment consisted of open surgical repair (57%) or endovascular repair (43%). All patients survived surgery. CONCLUSIONS: Publication bias might play a role in the literature of this area because all cases survived surgery, whereas mortality rates for this condition are high. However, early recognition, diagnosis, and prompt surgical repair are essential to prevent fatal outcomes in vascular injuries complicating lumbar disc surgery. Endovascular repair is a minimally invasive, fast, and efficient treatment modality that is increasingly and preferably used because of its low morbidity and mortality.

Report of two in situ reconstructions with a saphenous spiral vein graft of Coxiella burnetii-infected aneurysms of the abdominal aorta.

Coxiella burnetii is a rare cause of vascular infections. Yet, Q fever is endemic in the southern part of The Netherlands. This report describes two patients--from the southern part of The Netherlands--with infected aneurysms of the abdominal aorta caused by Coxiella burnetii. Both patients underwent surgical debridement, in situ reconstruction with a great saphenous vein spiral graft, and a transmesenteric omentumplasty. One patient fully recovered, while the other died due to ischemic complications. A multidisciplinary work-up approach to treat infected abdominal aneurysms is proposed, including adequate surgical treatment and long-term antibiotic administration.

Infected abdominal aneurysm due to Salmonella sepsis: report of a unique case treated using the superficial femoral vein.

We describe a 61-year-old patient with an infected aneurysm of the abdominal aorta due to Salmonella sepsis. Treatment was successful and included aneurysm resection, extensive debridement, and reconstruction of the abdominal aorta using the superficial femoral vein, combined with long-term antibiotic therapy.

Self-reported symptoms on questionnaires and anatomic lesions on duplex ultrasound examinations in patients with peripheral arterial disease.

OBJECTIVE: Whether a typical patient and symptom profile is associated with proximal or distal lesions in lower extremity peripheral arterial disease (PAD) is unknown. Knowing which patient characteristics, exertional leg symptoms, and cardiovascular risk profile accompany the anatomic lesion location may facilitate a more tailor-made management of PAD. METHODS: This cross-sectional study comprised 701 patients from two vascular surgery outpatient clinics with new-onset symptoms of PAD (Fontaine 2) who underwent duplex ultrasound (DUS) examinations from March 2006 to March 2011. The main outcome measures were patient characteristics, self-reported leg symptoms, and cardiovascular risk factors as documented from questionnaires and medical records. Peripheral lesion information, categorized by proximal and distal lesions, was obtained from DUS examinations. Multivariable logistic regression analyses were performed of proximal vs nonproximal lesions, distal vs nondistal lesions, and proximal and distal vs absence of having both lesions to assess relationships between patient characteristics, leg symptom categories (typical vs atypical leg symptoms), cardiovascular risk factors, and anatomic lesion location. RESULTS: Lesions were proximal in 270 (38.5%), distal in 441 (62.9%), and proximal and distal in 94 (13.4%). Patients with proximal lesions were younger (odds ratio [OR], 0.94; P < .0001) and less likely to be obese (OR, 0.34; P < .0001) than those without proximal lesions. Older age (OR, 1.07; P < .0001), male sex (OR, 1.96; P = .003), being without a partner (OR, 2.24; P = .004), and lower anxiety scores (OR, 0.42; P = .003) were associated with distal lesions. Patients with both lesions were more likely to be single (OR, 2.30; P = .010) and less likely to be obese (OR, 0.24; P = .009). No distinguishing leg symptom pattern was observed for patients with proximal lesions. Intermittent claudication was more frequently reported in those with distal lesions (P = .011). Although buttock and thigh pain seemed to be somewhat more present in proximal lesions (P < .01) and calf pain more in distal lesions (P < .001), patients still reported pain at a variety of levels throughout their legs, regardless of the anatomic lesion location. CONCLUSIONS: Two distinctive PAD phenotypes-each with its own characteristics and risk factors-emerged by anatomic lesion location; however, PAD-specific leg symptoms did not always reflect the anatomic lesion location. These findings may open new opportunities to better tailor PAD management to these two PAD subgroups and may raise awareness about not relying on self-reported symptoms to guide further diagnostic imaging and peripheral lesion management.

Genome-based prediction of breast cancer risk in the general population: a modeling study based on meta-analyses of genetic associations.

BACKGROUND: Genome-wide association studies identified novel breast cancer susceptibility variants that could be used to predict breast cancer in asymptomatic women. This review and modeling study aimed to investigate the current and potential predictive performance of genetic risk models. METHODS: Genotypes and disease status were simulated for a population of 10,000 women. Genetic risk models were constructed from polymorphisms from meta-analysis including, in separate scenarios, all polymorphisms or statistically significant polymorphisms only. We additionally investigated the magnitude of the odds ratios (OR) for 1 to 100 hypothetical polymorphisms that would be needed to achieve similar discriminative accuracy as available prediction models [modeled range of area under the receiver operating characteristic curve (AUC) 0.70-0.80]. RESULTS: Of the 96 polymorphisms that had been investigated in meta-analyses, 41 showed significant associations. AUC was 0.68 for the genetic risk model based on all 96 polymorphisms and 0.67 for the 41 significant polymorphisms. Addition of 50 additional variants, each with risk allele frequencies of 0.30, requires per-allele ORs of 1.2 to increase this AUC to 0.70, 1.3 to increase AUC to 0.75, and 1.5 to increase AUC to 0.80. To achieve AUC of 0.80, even 100 additional variants would need per-allele ORs of 1.3 to 1.7, depending on risk allele frequencies. CONCLUSION: The predictive ability of genetic risk models in breast cancer has the potential to become comparable to that of current breast cancer risk models. IMPACT: Risk prediction based on low susceptibility variants becomes a realistic tool in prevention of nonfamilial breast cancer.

Improvement of risk prediction by genomic profiling: reclassification measures versus the area under the receiver operating characteristic curve.

Reclassification is observed even when there is no or minimal improvement in the area under the receiver operating characteristic curve (AUC), and it is unclear whether it indicates improved clinical utility. The authors investigated total reclassification, net reclassification improvement, and integrated discrimination improvement for different DeltaAUC using empirical and simulated data. Empirical analyses compared prediction of type 2 diabetes risk based on age, sex, and body mass index with prediction updated with 18 established genetic risk factors. Simulated data were used to investigate measures of reclassification against DeltaAUCs of 0.005, 0.05, and 0.10. Total reclassification and net reclassification improvement were calculated for all possible cutoff values. The AUC of type 2 diabetes risk prediction improved from 0.63 to 0.66 when 18 polymorphisms were added, whereas total reclassification ranged from 0% to 22.5% depending on the cutoff value chosen. In the simulation study, total reclassification, net reclassification improvement, and integrated discrimination improvement increased with higher DeltaAUC. When DeltaAUC was low (0.005), net reclassification improvement values were close to zero, integrated discrimination improvement was 0.08% (P > 0.05), but total reclassification ranged from 0 to 6.7%. Reclassification increases with increasing AUC but predominantly varies with the cutoff values chosen. Reclassification observed in the absence of AUC increase is unlikely to improve clinical utility.