Computational fluid dynamics of a novel perfusion strategy during hybrid thoracic aortic repair.

BACKGROUND AND AIM: To mitigate the risk of perioperative neurological complications during frozen elephant trunk procedures, we aimed to computationally evaluate the effects of direct cerebral perfusion strategy through a left carotid-subclavian bypass on hemodynamics in a patient-specific thoracic aorta model. METHODS: Between July 2016 and March 2019, 11 consecutive patients underwent frozen elephant trunk operation using the left carotid-subclavian bypass with a side graft anastomosis and right-axillary cannulation for systemic and brain perfusion. A multiscale model realized coupling three-dimensional computational fluid dynamics was developed and validated with in vivo data. Model comparison with direct antegrade cannulation of all epiaortic vessels was performed. Wall shear stress, wall shear stress spatial gradient, and localized normalized helicity were selected as hemodynamic indicators. Four cerebral perfusion flows were tested (6 to 15 mL/kg/min). RESULTS: Direct cerebral perfusion of the left subclavian bypass resulted in higher flow rates with augmented speeds in all epiaortic vessels in comparison with traditional perfusion model. At the level of the left vertebral artery (LVA), a speed of 22.5 vs 21 mL/min and mean velocity of 3.07 vs 2.93 cm/s were registered, respectively. With a cerebral perfusion flow of 15 mL/kg, lower LVA wall shear stress (1.596 vs 2.030 N/m2 ), and wall shear stress gradient (1445 vs 5882 N/m3 ) were observed. A less disturbed flow considering the localized normalized helicity was documented. No patients experienced neurological/spinal cord damages. CONCLUSIONS: Direct perfusion of a left carotid bypass proved to be cerebroprotective, resulting in a more physiological and stable anterior and posterior cerebral perfusion.

Editor's Choice - Spinal Cord Ischaemia in Endovascular Thoracic and Thoraco-abdominal Aortic Repair: Review of Preventive Strategies.

INTRODUCTION: The incidence of spinal cord ischaemia (SCI) and subsequent paraplegia after thoracic endovascular aneurysm repair (TEVAR) and thoraco-abdominal endovascular aneurysm repair is estimated to be between 2.5% and 8%. The aim of this review is to provide an overview of SCI preventive strategies in TEVAR and thoraco-abdominal repair and recommend an optimal strategy. METHODS: Medline, Embase, and the Cochrane Library were searched for studies on TEVAR, thoraco-abdominal endovascular repair, and the use of SCI preventive measures. The review was reported according to the PRISMA statement. RESULTS: The final analysis included 43 studies (7168 patients). All studies are cohort studies (non-comparative cohorts n = 37, comparative cohorts n = 6) and largely performed retrospectively (n = 27). The included studies had an average MINORS score of 9 (range 6-13) for non-comparative studies and 15.5 (range 12-18) for comparative studies. Transient SCI occurred in 5.7% (450/7,168, 95% CI 4.5-6.9%), permanent SCI in 2.2% (232/7,168, 95% CI 1.6-2.8%). There was a trend towards increased SCI incidence for more "high risk" cohorts. Avoidance of hypotension resulted in a slightly lower permanent SCI rate 1.8% (102/4216, 95% CI 1.2-2.3%) than the overall cohort. A very low SCI estimate (transient and permanent) was found in the subgroup of studies (2 studies, n = 248) using (mild) peri-operative hypothermia (transient SCI 0.8%, permanent SCI 0.4%). In the subgroup using temporary permissive endoleak, there was a transient SCI estimate (15.4%), with a permanent SCI estimate of 4.8%. The remaining preventive measures did not significantly impact transient or permanent SCI estimates. CONCLUSION: Low overall transient and permanent SCI rates are achieved during endovascular thoracic and thoraco-abdominal aortic repair. Based on the presented data, the use of selective spinal fluid drainage in high risk patients seems justified. Peri-operative hypotension should be avoided and treated where possible. The use of mild hypothermia is promising in small cohorts, but requires further evaluation. Further high quality data are essential to establish a definitive preventive strategy.

Accuracy of Routine Endoscopy Diagnosing Colonic Ischaemia After Abdominal Aortic Aneurysm Repair: A Meta-analysis.

BACKGROUND: Colonic ischaemia (CI) is a devastating complication after abdominal aortic aneurysm (AAA) surgery. The aim of this review was to evaluate the diagnostic test accuracy of routine endoscopy in diagnosing CI after treatment for elective and acute AAA. PATIENTS AND METHODS: The Pubmed and Embase database searches resulted in 1188 articles. Prospective studies describing routine post-operative colonoscopy or sigmoidoscopy after elective or emergency AAA repair were included. The study quality was assessed with the QUADAS-2 tool. Sensitivity and specificity forest plots were drawn. Diagnostic odds ratios were calculated by a random effect model. RESULTS: Twelve articles were included consisting of 718 AAA patients of whom 44% were treated electively, 56% ruptured and, 6% by endovascular repair. Of all patients, 20.8% were identified with CI (all grades), and 6.5% of patients had Grade 3 CI. The pooled diagnostic odds ratio for all grades of CI on endoscopy was 26.60 (95% CI 8.86-79.88). The sensitivity and specificity of endoscopy for detection of Grade 3 CI after AAA repair was 0.52 (95% CI, 0.31-0.73) and 0.97 (95% CI 0.95-0.99) respectively. The positive post-test probability is up to 60% in all kinds of AAA patients and 68% in ruptured AAA patients. CONCLUSION: Routine endoscopy is highly accurate for ruling out CI after AAA repair. Clinicians should be aware that endoscopy is less accurate in diagnosing the presence of the clinically relevant transmural CI. Endoscopy is a safe diagnostic test to use routinely as none of the studies reported adverse events.

Endovascular treatment of a hepatic artery pseudoaneurysm associated with gastrointestinal tract bleeding.

Hemosuccus pancreaticus is a rare cause of gastrointestinal bleeding from the pancreatic duct originating from aneurysms or pseudoaneurysms of peripancreatic arteries. It is a life-threatening cause of gastrointestinal bleeding that should always be considered in patients with prolonged or intermittent obscure gastrointestinal blood loss, or both, especially in patients with pancreatic disorders or prior pancreatic surgery. We demonstrate an endovascular treatment strategy in a patient with a common hepatic pseudoaneurysm and upper gastrointestinal tract bleeding, with preserved flow in the hepatic artery. This treatment consisted of a covered stent placement in the hepatic artery, followed by transcatheter coil embolization of collateral feeding arteries.

Single-Stage Off-Pump Hybrid Repair of Kommerell's Diverticulum with Right-Sided Aortic Arch Using a Surgeon-Customized Vascular Prosthesis.

We report the successful single-stage hybrid management of Kommerell's diverticulum associated with a right-sided aortic arch in a 63-year-old woman. She underwent total aortic arch debranching utilizing a surgeon-customized vascular prosthesis, without cardiopulmonary bypass or deep hypothermic circulatory arrest, and concomitant zone-0 endovascular stent-graft deployment.

Endovascular treatment of traumatic thoracic aortic lesions: a systematic review and meta-analysis.

INTRODUCTION: To provide an overview of the experience of endovascular treatment for traumatic thoracic aortic lesions (TTAL). Thoracic aortic injury secondary to high-energy chest trauma constitutes an emergency situation with potentially devastating outcome. In the present time, the majority of patients are treated with thoracic endovascular aortic repair. The aim of this study was to provide a systematic overview of endovascular aortic repair in patients with TTAL with special attention to perioperative mortality, paraplegia, stroke, influence of left subclavian artery (LSA) coverage herein, and long-term stent-related complications. EVIDENCE ACQUISITION: PubMed and Embase were searched for studies describing endovascular treatment of TTAL in the period between January 1st, 2000 and January 30th, 2016. The methodological quality of articles was assessed using the MINORS score and PRISMA guidelines. Data on early mortality, perioperative complications, and long-term stent-related complications were extracted. EVIDENCE SYNTHESIS: A total of 2005 reports were screened, and 74 publications were finally included in the analysis describing treatment of 1882 patients. Early mortality rate, paraplegia rate, and stroke rate were 7.5%, 0.4%, and 1.5%, respectively. LSA coverage did not increase the risk of stroke. The severity of injuries had a positive association on early mortality. Late stent related mortality and morbidity were uncommon. CONCLUSIONS: TTAL can be treated endovascularly with low mortality and (neurological) morbidity. LSA coverage does not increase the risk of neurological complications but is associated with a moderate risk of left arm ischemia. Long-term stent-related complications are rare, but the available data is limited.

Infection and atherosclerosis. An alternative view on an outdated hypothesis.

Already at the beginning of the 20th century, a potential role for microbes in vascular diseases was suggested. However, until the late '70 of that century, not much attention has been paid to this infection hypothesis. Then, predominantly based on the pioneering work of Fabricant et al., evidence for a contributing or even initiating role for microbes in atherosclerosis, as well as other vascular diseases, was accumulating. Also, the seminal paper by Saikku and co-workers, demonstrating serological evidence of an association of Chlamydia pneumoniae, an obligate intracellular respiratory gram-negative bacterium, with chronic coronary heart disease and acute myocardial infarction, significantly boosted the research on the infection hypothesis. Since then, numerous papers have been published demonstrating associations between a large variety of pathogens and atherosclerotic disease. Furthermore, many molecular mechanisms have been suggested by which microbes may affect atherogenesis. Nevertheless, in recent large randomised prospective trials, evaluating the efficacy of antibiotic treatment for the secondary prevention of coronary events, no reduction in the rate of cardiovascular events was observed, thereby seriously challenging the validity of the infection hypothesis. Nevertheless, the large body of supporting evidence, which has accumulate over the past decades, should not be ignored and maybe we should look at the hypothesis, and in particular the mechanisms by which microbes affect the disease, from a different angle.

Endograft Sizing for Endovascular Aortic Repair and Incidence of Endoleak Type 1A.

OBJECTIVE: In endovascular aortic aneurysm repair (EVAR), proximal type 1A endoleaks can occur as a result of hostile neck anatomy or over- or undersizing of the endograft. As the current standard is based on the diameter or average of the short and long axes in a central lumen reconstruction image, it can falter in irregularly shaped aortic necks. An alternative method is circumference-based, therefore minimizing the measurement error. In this study we aimed to assess the degree of discrepancy between both methods and the association of this discrepancy with the occurrence of endoleak type 1A. METHODS: All patients with early (<30 days post-operative) endoleak type 1A after elective EVAR at our center between 2004 and 2016 were identified for a retrospective case-control study. Control patients were matched based on hostile neck anatomy, such as calcification, thrombus, reverse taper, and ß-angulation. The aortic neck diameter was measured using the traditional, diameter-based method as well as an alternative method, based on the circumference of the aortic neck. RESULTS: In 482 EVAR patients, 18 early endoleak type 1A cases were found (3.9%). After exclusion, 12 cases remained and 48 matching controls were found. No significant differences were found between the two measuring methods at any level below the renal arteries. The inter-observer variability was significant for the D(mean) (0.4 ± 1.69 mm, P = .02) and was larger than the D(circ) method (-0.1 ± 1.03 mm, P = .35). In only four out of 12 cases the endograft size was 10-20% larger than the D(mean) and D(circ) measurements. The differences between the diameter of the D(mean) and D(circ) and the chosen endograft were smaller for the case group (-8 ± 25.6% and -7 ± 24%) than for the control group. (-12.4 ± 12.4% and -11 ± 10.7%). CONCLUSION: The difference between the D(mean) and D(circ) methods for aortic neck measurement was not large enough to play a significant role in the incidence of endoleak type 1A. Inadequate oversizing and considerable ß-angulation of the aortic neck may have been the cause of endoleak type 1A in this population. Robust and well-investigated sizing methods are paramount for accurate endograft sizing and prevention of endoleak type 1A. Therefore the lack of studies in this field and a sizeable inter-observer variability do not justify the widespread reliance on the traditional diameter-based methods for endograft sizing.

Serum C-reactive protein level is associated with abdominal aortic aneurysm size and may be produced by aneurysmal tissue.

BACKGROUND: Abdominal aortic aneurysms (AAA) are characterized by extensive transmural inflammation and C-reactive protein (CRP) has emerged as an independent risk factor for the development of cardiovascular disease. Therefore, we evaluated a possible association between serum CRP and aneurysm dimension in patients with asymptomatic AAA. Furthermore, the possibility of CRP production by aneurysmal tissue has been examined. METHODS AND RESULTS: Serum CRP was determined highly sensitive (hsCRP) and aneurysmal size was measured in 39 patients with AAA. The presence of CRP mRNA was assessed in the aneurysmal tissue of 16 patients. Mean (SD) hsCRP was 3.23 (2.96) mg/L. After log-transformation, hsCRP correlated significantly with aneurysmal size (r=0.477, P=0.002). When the patients were divided into 3 equally sized groups according to hsCRP level, aortic diameter increased from lowest to upper hsCRP-tertile (49 mm, 61 mm, and 67 mm, respectively; P<0.05 for 3rd versus 1st tertile). This association persisted after correction for risk factors. CRP mRNA was found in 25% of aneurysmal aortic tissues. CONCLUSIONS: This is the first report showing that serum hsCRP is associated with aneurysmal size and that-in at least some patients-CRP may be produced by aneurysmal tissue. These data underscore the inflammatory nature of AAA formation, suggesting that serum hsCRP may serve as a marker of AAA disease and that CRP produced in vascular tissue might contribute to aneurysm formation.

Circumference as an alternative for diameter measurement in endovascular aneurysm repair.

Appropriate sizing of endografts for endovascular aneurysm repair has traditionally been performed by one standardized method. By measuring the average of the minor and major axes in the sealing zone, the endograft size is traditionally calculated. However, no adequate scientific evaluation has been performed to validate this method. The guidelines that were published are based on theories and experience, more than scientific evidence. In case the central lumen line artery cross-section is a circular disk, the vessel diameter is a reliable estimation. Yet the aortic neck cross-section may not always be geometrically a perfect circular disk. Application of the standardized method might therefore lead to inaccurate endograft sizing, potentially leading to endoleaks. We hypothesize that in these cases the circumference of the vessel is a mathematically correct reference to deduct the appropriate endograft diameter. The following formula was applied in this study: diameter of the corresponding circle (d) equals circumference (C) divided by πd=Cπ. This study provides a theoretical analysis of the mathematical implications of this method. Only in case of highly irregularly shaped cylinders, the circumference-based method was more accurate than the standardized method. Nonetheless, the circumferential method was a practical reference in case the aortic neck was irregularly shaped. Also, the circumference method was accurate in all cases in deducting the diameter of a matching circle. Therefore, the hypothesis that was raised in this study has a strong theoretical base. We predict that in case this hypothesis holds true in the clinical practice, application of the circumference method might lead to less endoleaks than the standardized method.

Chlamydia pneumoniae serology is associated with thrombosis-related but not with plaque-related microembolization during carotid endarterectomy.

BACKGROUND AND PURPOSE: Chlamydia pneumoniae has repeatedly been associated with atherosclerotic disease. Our study was designed to clarify whether this association is based on C pneumoniae-induced transformation of a stable into an unstable atherosclerotic plaque or on stimulation of hypercoagulability leading to increased thrombotic arterial occlusions by C pneumoniae infection. Transcranial Doppler ultrasonographic monitoring of the middle cerebral artery during carotid endarterectomy offers the opportunity to study, before removal of the plaque, atherothrombotic emboli dislodging from an unstable carotid plaque (plaque-related emboli) and emboli related to (excessive) thrombus formation at the endarterectomy site after removal of the plaque and restoration of flow (thrombosis-related emboli). METHODS: C pneumoniae IgA (> or =1/16) and IgG (> or =1/64) seropositivity was assessed in 53 patients with symptomatic carotid artery disease undergoing carotid endarterectomy. The removed carotid plaques were studied histologically to assess plaque instability. RESULTS: Plaque- and thrombosis-related emboli were registered in 43 patients with an adequate transtemporal window. IgA seropositivity (58%) was associated significantly with thrombosis-related embolization (P=0.030) but not with plaque-related embolization or with histological plaque instability. CONCLUSIONS: C pneumoniae serology is associated with microembolization after endarterectomy and restoration of flow. Since these microemboli represent platelet aggregations and are related to cerebrovascular complications, our data suggest that C pneumoniae infection contributes to cerebrovascular events in patients with carotid artery disease through stimulation of thrombosis.

Chlamydia pneumoniae serology: comparing a commercial enzyme immunoassay and microimmunofluorescence test in patients with cardiovascular disease.

Chlamydia pneumoniae has been associated with cardiovascular disease and the detection of C. pneumoniae antibodies has subsequently challenged many cardiovascular investigators. The micro-immunofluoresence (MIF) test is considered the gold standard for detection of C. pneumoniae antibodies, but requires a high-level of expertise for adequate interpretation. We compared an enzyme immunoassay (EIA) with a microimmunofluorescence test for the detection of C. pneumoniae IgG- and IgA antibodies in sera of 141 patients with atherosclerosis. The MIF test was read by two independent observers. The interobserver agreement of the MIF test for detection of seropositivity at various cut-off levels was good for IgG and for IgA. The intra-test agreement of the EIA was excellent for IgG and IgA. The agreement between EIA and MIF in detection of IgG- and IgA antibodies was adequate at low but not at high titer levels. At low titer levels, the sensitivity, specificity, positive and negative predictive value of EIA compared to the MIF test was sufficient. The sensitivity of the EIA increased, improving the agreement with the MIF at high titer levels by retesting sera with elevated titers at higher pre-dilutions. In conclusion, the EIA shows sufficient agreement with the MIF test in the detection of C. pneumoniae seropositivity. Therefore, the EIA is a practical alternative to the MIF in the detection of C. pneumoniae antibodies in patients with cardiovascular disease, bearing in mind that the sensitivity of the EIA depends on the antibody titer.

Does glutamine-enriched parenteral nutrition really affect intestinal morphology and gut permeability?

BACKGROUND: Nutritional depletion has been related to low glutamine levels in plasma and gut mucosa. This study was set up to investigate the effects of glutamine-enriched total parenteral nutrition on intestinal morphology and permeability. METHODS: Twenty-three depleted patients were randomized and after stabilization baseline measurements were performed. Plasma glutamine concentrations, gut morphology (including proliferation and lymphocyte markers) and intestinal permeability were measured. After administration during 8-10 days of a glutamine enriched total parenteral nutrition or an isonitrogenous control solution the measurements were repeated. RESULTS: No significant changes in glutamine concentrations, intestinal permeability, mucosal morphology or gut mucosal inflammation were observed between groups. CONCLUSIONS: Glutamine enriched total parenteral nutrition in a depleted patient population does not result in improvements in gut morphology and gut barrier function.

Pressure Ulcers and Prolonged Hospital Stay in Hip Fracture Patients Affected by Time-to-Surgery.

BACKGROUND: Hip fractures are associated with high morbidity. Pressure ulcer formation after hip surgery is often related to delayed patient mobilization. The objectives of this study were to determine whether time-to-surgery affects development of pressure ulcers postoperatively and, thus, length of hospital stay. PATIENTS AND METHODS: We performed a retrospective analysis of consecutive hip fracture patients, aged 60 years and above, who underwent surgery between 1995 and 2001. The primary outcome was in-hospital development of pressure ulcers. The secondary outcome measure was the overall length of hospital stay. Analyses were adjusted for relevant confounders. RESULTS: Of the 722 patients enrolled, 488 patients (68%) received surgery at 12 h after admission. Approximately 30% (n = 214) developed pressure ulcers during admission, whilst 19% of patients operated within 12 h of admission developed pressure ulcers. Time-to-surgery was an independent predictor of both development of pressure ulcers (OR = 1.7, 95% confidence interval [CI] = 1.2-2.6; p = 0.008) and length of hospital stay (11.3 vs 13.3 days in the early and the late surgery group, respectively, p = 0.050). Furthermore, development of pressure ulcers was associated with prolonged postoperative hospital stay (19.5 vs 11.1 days for patients with and without pressure ulcers, respectively, p = 0.001) INTERPRETATION: : In hip fracture patients, time-to-surgery was an independent predictor of both postoperative pressure ulcer development and prolonged hospital stay. These data suggest that the implementation of an early surgery protocol following admission for hip fractures may reduce both the postoperative complications and overall hospital stay.

State-of-the-art treatment of chronic leg ulcers: A randomized controlled trial comparing vacuum-assisted closure (V.A.C.) with modern wound dressings.

BACKGROUND: Current treatment modalities for chronic leg ulcers are time consuming, expensive, and only moderately successful. Recent data suggest that creating a subatmospheric pressure by vacuum-assisted closure (V.A.C., KCI Concepts, San Antonio, Texas) therapy supports the wound healing process. METHODS: The efficacy of vacuum-assisted closure in the treatment of chronic leg ulcers was prospectively studied in a randomized controlled trial in which 60 hospitalized patients with chronic leg ulcers were randomly assigned to either treatment by V.A.C. or therapy with conventional wound care techniques. The primary outcome measure was the time to complete healing (days). Statistical analysis was performed on the intention-to-treat basis. RESULTS: The median time to complete healing was 29 days (95% confidence interval [CI], 25.5 to 32.5) in the V.A.C. group compared with 45 days (95% CI, 36.2 to 53.8) in the control group (P = .0001). Further, wound bed preparation during V.A.C. therapy was also significantly shorter at 7 days (95% CI 5.7 to 8.3) than during conventional wound care at 17 days (95% CI, 10 to 24, P = .005). The costs of conventional wound care were higher than those of V.A.C. Both groups showed a significant increase in quality of life at the end of therapy and a significant decrease in pain scores at the end of follow-up. CONCLUSIONS: V.A.C. therapy should be considered as the treatment of choice for chronic leg ulcers owing to its significant advantages in the time to complete healing and wound bed preparation time compared with conventional wound care. Particularly during the preparation stage, V.A.C. therapy appears to be superior to conventional wound care techniques.

Synergistic effect of Toll-like receptor 4 and CD14 polymorphisms on the total atherosclerosis burden in patients with peripheral arterial disease.

BACKGROUND: Genes involved in the regulation of immune responses, such as Toll-like receptor 4 (TLR4) and CD14, show genetic variations with potential functional implications. Because atherosclerosis is an inflammatory process apparently modulated by chronic infections, we studied the effect of single nucleotide polymorphisms (SNPs) in TLR4 and CD14 on the extent of clinically relevant atherosclerosis in patients with peripheral arterial disease (PAD). METHODS: Using an in-house-developed polymerase chain reaction-based restriction length polymorphism assay, we determined the genotype, allele frequency, and carrier traits of the TLR4 +896 A>G and the CD14 -260 C>T SNPs in 607 white Dutch patients with PAD. The extent of clinically relevant atherosclerosis was determined on the basis of the number of vascular territories involved, ie, coronary, cerebral, aortic, and peripheral. RESULTS: A total of 55% of the patients had PAD only. Approximately one third of the patients had two and 11% had three vascular territories affected by clinically relevant atherosclerosis. The TLR4 +866 G allele frequency was 11%, and the CD14 -260 T allele frequency was approximately 74%. Among PAD patients, TLR4 +896 G allele carriership was univariantly associated with extensive (more than two vascular territories affected) atherosclerotic disease (odds ratio, 2.22; P = .020; chi(2) test), whereas CD14 -260 C>T carriership/homozygosity was not. Trend analysis showed that the TLR4 +866 G allele frequency increased with the number of vascular territories affected by clinically relevant atherosclerosis (P trend, .0074). In a multivariate logistic regression analysis including cardiovascular risk factors and TLR4 and CD14 SNPs, only the interaction variable "TLR4 +896 G allele carriership/CD14 -260 TT genotype" survived as an independent predictor of extensive atherosclerotic disease (P = .031; odds ratio, 4.2; 95% confidence interval, 1.1-15.4). CONCLUSIONS: The carrier trait TLR4 G allele/CD14 TT genotype, rather than each SNP individually, is associated with the extent of clinically relevant atherosclerotic disease. Considering the importance of immune responses in atherogenesis and the genetic variation of immune regulatory genes, our data provide an explanation for interindividual differences in susceptibility to atherosclerosis and demonstrate the need to take a wider approach in analyzing relevant carrier traits instead of individual polymorphisms in relation to atherosclerosis.

C-reactive protein in peripheral arterial disease: relation to severity of the disease and to future cardiovascular events.

BACKGROUND: Serum C-reactive protein (CRP) has proven to be an independent marker of the extent of atherosclerosis in patients with coronary, cerebrovascular, and peripheral arterial disease. In this prospective observational study, we wanted to assess the relationship between serum CRP and extent of disease transversely and longitudinally in time, as well as future cardiovascular complications in patients with peripheral arterial disease (PAD). Hypothesizing that CRP not only is a marker of but also actively participates in atherogenesis, we explored the possibility of CRP production by femoral atherosclerotic plaques. METHODS: Serum CRP was measured as highly sensitive (hsCRP) in 387 patients with PAD attending the vascular clinic of a university and 2 affiliated teaching hospitals. Serum hsCRP was related to the ankle-brachial pressure index (ABPI) as an indication of severity of disease at inclusion and at 12 months' follow-up and to future events (death and coronary, cerebral, and peripheral arterial events). In femoral plaques, the production of CRP was analyzed with reverse transcription-polymerase chain reaction, and CRP plaque localization was assessed with immunostaining on serial tissue sections with antibodies toward CRP, smooth muscle cells, T cells, and macrophages. RESULTS: The hsCRP (average +/- SD) was 3.26 +/- 2.41 mg/L. Serum hsCRP showed a correlation with baseline and 12-month follow-up ABPI (Spearman rank correlation; P < .05 for both correlations). When the patients were divided into three equally sized groups according to baseline serum hsCRP, the ABPI at baseline and at 12 months decreased significantly from the low- to the high-hsCRP group (baseline ABPI: 0.70, 0.65, and 0.57, P < .01; 12-month follow-up ABPI: 0.78, 0.70, and 0.65, P < .01). These associations persisted after correction for conventional risk factors. Furthermore, serum hsCRP was related to the combined end point "death and/or any cardiovascular event" (log-rank test; P = .04) during a median 24-month follow-up period. Reverse transcription-polymerase chain reaction analysis showed CRP production in 4 of 14 femoral plaques. CRP was detected in all femoral plaques, but not in healthy brachial arteries. Immunoreactivity for CRP was observed in smooth muscle cells, macrophages, and T cells. CONCLUSIONS: Serum hsCRP was related to the severity of PAD, showing a relation to future hemodynamic function and cardiovascular events in PAD patients. In addition to coronary plaques, aneurysmal aortas, and failed venous coronary bypasses, femoral plaques also produce CRP, thus illustrating that the production of CRP may represent a universal response to vascular injury and suggesting that vascular CRP may contribute to plaque development.