Advanced Peripheral Vascular Disease Research Articles

Experience of Intravenous infusion of prostaglandin E1 for cessation of rest pain and further ischemic changes in patients with PVD

Prostaglandins are potent vasoactive agents with wide variety of other actions - vasodilatation, fibrinolysis and inhibition of platelet aggregation. Prostaglandin E1( PGE1) was the agent used since 1973 for cardiovascular diseases, mainly in patients with advanced peripheral vascular disease. PGE1 intra venous infusion has shown to be beneficial in limb threatening ischemia, especially when reconstructive procedures are not feasible. The original research of benefitted 28 cases in last 5 years is presented here.

Werner Syndrome

A 36-year-old male presented with young-onset diabetes and advanced peripheral vascular disease. He had a history of bilateral juvenile cataracts and premature aged appearance. Closer scrutiny unraveled multiple endocrine and nonendocrine abnormalities. Genetic studies revealed a novel pathogenic variant (homozygous c.3233+2T>c) confirming and expanding the mutation spectrum of Werner syndrome. This report highlights the need for precise diagnosis, which has important implications for prognosis and genetic counseling.

Abstract 16856: Mathematical Modeling of Blood Flow to Evaluate the Hemodynamic Significance of Peripheral Vascular Lesions

Introduction: Evaluating the severity of lesions in peripheral arteries is challenging. Image-based blood flow modeling from peripheral computed tomographic angiography (pCTA) may provide a non-invasive method to determine the hemodynamic significance of lesions. The objective of this study was to evaluate the diagnostic performance of a trans-lesion pressure drop computed from pCTA-based blood flow modeling in the peripheral arteries. Methods: Ten patients undergoing digital subtraction angiography (DSA) and pCTA were included. The peripheral arteries were divided into 8 segments per extremity and stenosis severity was visually graded by DSA as non-stenosed (grade 0), mild (grade I), moderate (grade II), severe (grade III), occluded (grade IV) or non-evaluable. A functionally significant lesion was defined as grade III or IV by DSA. Independent from the DSA review, a resting pressure gradient (rPG) and exercise PG (ExPG) for each segment was calculated from pCTA-based blood flow modeling (Figure), and a functionally significant lesion was defined as having an rPG > 5 mm Hg or an ExPG > 20 mm Hg. Results: Mean age was 52±16 years, 4 patients (40%) were male, 8 patients (80%) presented with critical limb ischemia, mean ankle brachial index was 0.60±0.29 and 66 arterial segments were available for both assessment methods. Twenty-two segments had functionally significant lesions by DSA. For rPG, sensitivity was 80%, specificity was 85% and accuracy was 79% with DSA as the standard; for ExPG, sensitivity was 84%, specificity was 89% and accuracy was 88%. Conclusions: Use of a resting pressure gradient > 5 mm Hg and an exercise pressure gradient > 20 mm Hg measured by peripheral computed tomography-based blood flow modeling accurately identifies functionally significant stenosis in patients with advanced peripheral vascular disease. These results support a prospective imaging trial to further validate this novel approach.

The Value of Using a Dedicated Vascular Lab in Managing and Treating Diabetic Critical Limb Ischemia Patients

Critical limb ischemia (CLI) is a debilitating end stage of advanced peripheral vascular disease. Treating CLI, particularly in the diabetic patient, is a multifaceted process that requires an experienced team of providers. The CLI model employs practitioners from interventional cardiology, vascular surgery, wound care, endocrinology, nephrology, internal medicine, and podiatry. The main treatment goal is to improve quality of life and reduce the number of limb amputations and the subsequent complications. Often, multiple endovascular procedures are needed to restore perfusion to the lower leg and foot to prevent limb loss. The overall health care savings are significant if limb loss is avoided despite requiring multiple procedures. The number of patients, particularly diabetics, who will need this advanced level of care is only expected to rise.

Socioeconomically Distressed Communities Index independently Predicts Major Adverse Limb Events After Infrainguinal Bypass in a National Cohort

Socioeconomically Distressed Communities Index independently Predicts Major Adverse Limb Events After Infrainguinal Bypass in a National Cohort

Treatment of central pain syndrome with spinal cord stimulation

Central pain syndrome (CPS) is a neurological disorder caused by damage or dysfunction of the central nervous system. Both conservative and operative methods of treatment are used in its treatment, but in most cases their effectiveness is rather low. We are presenting the clinical observation of a 60-year-old patient with spinal cord injury at the level of Th10 due to a car accident that occurred 44 years before the treatment in our clinic, who suffered from phantom pain that occurred after bilateral above the knee amputation because of advanced peripheral vascular disease. Due to the ineffectiveness of the conservative treatment, it was decided to proceed with spinal cord stimulation. The presence of pronounced postoperative changes in the area of spinal cord injury has complicated the transcutaneous placement of trial leads at the L1-L2 and Th12-L1 level. We managed to introduce leads at the level of Th7-Th8 and position them at the level of Th5-Th7. During continuous neurostimulation the pain in the sacrum, in the area of the hip joints, the phantom pain was relieved. The patient stopped using all pain medications. Spinal cord stimulation can be utilized as an alternative treatment for patients with intractable CPS.

A systematic review describing incidence rate and prevalence of dysvascular partial foot amputation; how both have changed over time and compare to transtibial amputation

BackgroundPartial foot amputation (PFA) is a common consequence of advanced peripheral vascular disease. Given the different ways incidence rate and prevalence data have been measured and reported, it is difficult to synthesize data and reconcile variation between studies. As such, there is uncertainty in whether the incidence rates and prevalence of PFA have increased over time compared to the decline in transtibial amputation (TTA). The aims of this systematic review were to describe the incidence rate and prevalence of dysvascular PFA over time, and how these compare to TTA.MethodDatabases (i.e., MEDLINE, EMBASE, psychINFO, AMED, CINAHL, ProQuest Nursing and Allied Health) were searched using MeSH terms and keywords related to amputation level and incidence rate or prevalence. Original research published in English from 1 January 2000 to 31 December 2015 were independently appraised, and data extracted, by two reviewers. The McMaster Critical Review Forms were used to assess methodological quality and bias. Results were reported as narrative summaries given heterogeneity of the literature and included the weighted mean annual incidence rate and 95% confidence interval.ResultsTwenty two cohort studies met the inclusion criteria. Twenty one reported incidence rate data for some level of PFA; four also included a TTA cohort. One study reported prevalence data for a cohort with toe(s) amputation. Samples were typically older, male and included people with diabetes among other comorbidities. Incidence rates were reported using a myriad of denominators and strata such as diabetes type or initial/recurrent amputation.ConclusionWhen appropriately grouped by denominator and strata, incidence rates were more homogenous than might be expected. Variation between studies did not necessarily reduce confidence in the conclusion; for example, incidence rate of PFA were many times larger in cohorts with diabetes (94.24 per 100,000 people with diabetes; 95% CI 55.50 to 133.00) compared to those without (3.80 per 100,000 people without diabetes; 95% CI 1.43 to 6.16). It is unclear whether the incidence rates of PFA have changed over time or how they have changed relative to TTA. Further research requires datasets that include a large number of amputations each year and lengthy time periods to determine whether small annual changes in incidence rates have a cumulative and statistically significant effect over time.Systematic review registrationPROSPERO CRD42015029186.

Outcomes of dysvascular partial foot amputation and how these compare to transtibial amputation: a systematic review for the development of shared decision-making resources

BackgroundDysvascular partial foot amputation (PFA) is a common sequel to advanced peripheral vascular disease. Helping inform difficult discussions between patients and practitioners about the level of PFA, or the decision to have a transtibial amputation (TTA) as an alternative, requires an understanding of the current research evidence on a wide range of topics including wound healing, reamputation, quality of life, mobility, functional ability, participation, pain and psychosocial outcomes, and mortality. The aim of this review was to describe a comprehensive range of outcomes of dysvascular PFA and compare these between levels of PFA and TTA.MethodsThe review protocol was registered in PROSPERO (CRD42015029186). A systematic search of the literature was conducted using MEDLINE, EMBASE, psychINFO, AMED, CINAHL, ProQuest Nursing and Allied Health, and Web of Science. These databases were searched using MeSH terms and keywords relating to different amputation levels and outcomes of interest. Peer reviewed studies of original research—irrespective of the study design—were included if published in English between 1 January 2000, and 31 December 2015, and included discrete cohort(s) with dysvascular PFA or PFA and TTA. Outcomes of interest were rate of wound healing and complications, rate of ipsilateral reamputation, quality of life, functional ability, mobility, pain (i.e., residual limb or phantom pain), psychosocial outcomes (i.e., depression, anxiety, body image and self-esteem), participation, and mortality rate. Included studies were independently appraised by two reviewers. The McMaster Critical Review Forms were used to assess methodological quality and identify sources of bias. Data were extracted based on the Cochrane Consumers and Communication Review Group’s data extraction template by a primary reviewer and checked for accuracy and clarity by a second reviewer. Findings are reported as narrative summaries given the heterogeneity of the literature, except for mortality and ipsilateral reamputation where data allowed for proportional meta-analyses.ResultsTwenty-nine unique articles were included in the review, acknowledging that some studies reported multiple outcomes. Eighteen studies reported all-cause proportionate mortality. A smaller number of studies reported outcomes related to functional ability (two), mobility (four), quality of life (three), ipsilateral reamputation (six) as well as wound healing and complications (four). No studies related to pain, participation or psychosocial outcomes met the inclusion criteria. Subjects were typically older and male and had diabetes among other comorbidities. More detailed information about the cohorts such as race or sociodemographic factors were reported in an ad hoc manner. Common sources of bias included contamination, co-intervention, or lack of operational definition for some outcomes (e.g., wound healing) as illustrative examples.ConclusionsAside from mortality, there was limited evidence regarding outcomes of dysvascular PFA, particularly how outcomes differ between levels of PFA and TTA. Acknowledging that there is considerable uncertainty given the small body of literature on many topics where the risk of bias is high, the available evidence suggests that a large proportion of people with PFA experience delayed wound healing and ipsilateral reamputation. People with TTA have increased risk of mortality compared to those with PFA, which may reflect that those considered suitable candidates for TTA have more advanced systemic disease that also increases the risk of dying. Mobility and quality of life may be similar in people with PFA and TTA.Systematic review registrationCRD42015029186

Pathophysiology and burden of infection in patients with diabetes mellitus and peripheral vascular disease: focus on skin and soft-tissue infections

Diabetes mellitus affects 284 million adults worldwide and is increasing in prevalence. Accelerated atherosclerosis in patients with diabetes mellitus contributes an increased risk of developing cardiovascular diseases including peripheral vascular disease (PVD). Immune dysfunction, diabetic neuropathy and poor circulation in patients with diabetes mellitus, especially those with PVD, place these patients at high risk for many types of typical and atypical infections. Complicated skin and soft-tissue infections (cSSTIs) are of particular concern because skin breakdown in patients with advanced diabetes mellitus and PVD provides a portal of entry for bacteria. Patients with diabetes mellitus are more likely to be hospitalized with cSSTIs and to experience related complications than patients without diabetes mellitus. Patients with PVD requiring lower extremity bypass are also at high risk of surgical site and graft infections. Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent causative pathogen in cSSTIs, and may be a significant contributor to surgical site infections, especially in patients who are colonized with MRSA on hospital admission. Patients with cSSTIs and diabetes mellitus or PVD experience lower clinical success rates than patients without these comorbidities, and may also have a longer length of hospital stay and higher risk of adverse drug events. Clinicians should be vigilant in recognizing the potential for infection with multi-drug-resistant organisms, especially MRSA, in these populations and initiating therapy with appropriate antibiotics.

Tibio‐pedal arterial minimally invasive retrograde revascularization in patients with advanced peripheral vascular disease: The TAMI technique, original case series

A tibial-pedal access method is needed for patients with advanced peripheral artery disease (PAD) unable to tolerate common femoral artery (CFA) access and intervention due to body habitus or comorbidities. This is the first case series reporting an alternative technique to revascularize such patients. Using ultrasound (US) and the tibio-pedal arterial minimally invasive retrograde revascularization (TAMI) technique, operators accessed, and revascularized the lower extremity completely via tibial-pedal arterial access. This retrospective, single-center, case series recorded on 23 patients who underwent TAMI revascularization during a seven-month period in 2012, demonstrating the feasibility and safety of the TAMI technique. Eighty-three percent had Rutherford Classification IV-VI. Ultrasound guidance aided all tibial access. Demographics, vascular symptoms, disease characteristics, success, procedure length, time to discharge, immediate and 30-day complications were collected. Comparison was sought with 201 unmatched patients treated via traditional CFA access over a similar period. Arterial access was successful in all patients. Thirty-six lesions were treated. Lesion success (ability to cross lesion and achieve post treatment stenosis <30%) was achieved in 95% of patients. 25% of lesions were above the knee. Average prestenosis was 92.5%; average poststenosis 12%. No major complications were noted. Two patients presented within 30 days with access site pain. Access site peroneal artery pseudo-aneurysms were diagnosed and treated percutaneously with covered stents. Both recovered with no sequelae. Retrograde tibio-pedal intervention appears to be safe and effective. The TAMI technique offers an alternate revascularization method for critically ill advanced PAD patients.

Abstract No. 309 - Percutaneous lumbar sympathectomy: technique and clinical outcome review

Purpose Percutaneous sympathectomy has been used for treatment of complex regional pain syndromes (1), plantar hyperhydrosis (2,3), and peripheral vascular disease (PVD) with critical limb ischenia (CLI). We report technique of CT guided percutaneous sympathectomy using anhydrous ethanol in patients with CLI. Materials and Methods CT guided percutaneous lumbar sympathetic ablations were performed in a group of 5 patients (avg. age 68, range 61-82) with advanced PVD (Fontaine Stage IV). All had rest pain, clinical CLI and impending amputation. Patients were assessed for preprocedure and post procedure pain, color and warmth after the procedure, 4 hrs later and 2-3 months later. Results All patients showed a positive response of increased warmth, color, flushing and lessening of pain at the end of the procedure. Over three months follow-up, none underwent amputation, and 4 of the 5 (80%) maintained residual improvement in color and warmth. One returned to baseline appearance, but without amputation. No procedural complications were encountered. Conclusion CT guided lumbar sympathectomy with anhydrous ethanol is safe and effective in advanced PVD to stave off impending amputation. CT guidance increases accuracy of needle placement, decreases the volume of ablative chemical needed and may be able to reduce the incidence of complications reported in the literature (5).

Utility and feasibility of ultrasound‐guided access in patients with critical limb ischemia

Patients with advanced peripheral vascular disease (PVD) and critical limb ischemia (CLI) require immediate revascularization to improve blood flow and prevent amputation. Vascular, and especially tibial, access is arguably a very important part of the procedure. Utilization of ultrasound (US) guidance to access the peripheral vessels will maximize success and decrease the risk of complications. This is a retrospective analysis of patients admitted to our institution between 2010 and 2011. Eighty-six patients with 191 lesions underwent revascularization for advanced PVD and CLI. US guidance was utilized to access the vascular bed in an antegrade or retrograde fashion in 100% of these patients. Data collected included success rate and time to access using US. Immediate in hospital and 30 day outcomes were also documented. The average age of patients was 69.8 years, with 69.7% male patients. All tibial access (33.7%) was obtained under US guidance. Obtaining vascular access using US was achieved in 95.3% of patients. At discharge, access site complications were limited to one patient (1.1%) with a pseudoaneurysm; no access complications related to the tibial vessels. At 30 days, there was one major amputation (1.1%) and one vascular access complication (1.1%). US guided access is a feasible and safe procedure that can aid in accessing vascular conduits in patients with CLI. Applying this technique across the board in CLI patients decreases the risk of immediate complications and facilitates accessing tibial arteries.

Effect of a chronic disease management service for patients with diabetes on hospitalisation and acute care costs

To evaluate the effect of a diabetes-management program for patients with type 2 diabetes and related comorbidities on acute healthcare utilisation and costs. This was a retrospective administrative dataset analysis using data for patients enrolled from 2007 to 2008. Inpatient admissions for diabetes-related conditions were compared before, during and following enrolment. Costs per episode were estimated from Weighted Inlier Equivalent Separations (WIES) funding. A cost model was then developed based on admission rates per 100 patients. Data were retrieved for 357 patients; 49% males, mean age 62 years. The mean per-patient cost of the program was AU$524 (s.d. $213). The mean cost of an inpatient admission was $4357(95% CI 2743-5971) pre-enrolment and $4396 (95% CI 2888-5904) post-enrolment. Following program completion the annual costs (per 100 patients) for managing 'diabetes with multiple complications' and hypoglycaemia decreased from $10181 to $1710 and $9947 to $7800. In contrast, the annual cost of cardiovascular disorders increased from $14485 to $40071 per 100 patients. In the short-term diabetes-management programs for patients with comorbid vascular disease may reduce hospital utilisation for diabetes but not for cardiovascular disease. Longer-term follow-up is needed to determine whether intensive management of vascular complications can reduce costs.

Preprocedural hemoglobin predicts outcome in peripheral vascular disease patients undergoing percutaneous transluminal angioplasty

Anemia is a risk factor for adverse outcome in patients with symptomatic cardiovascular disease. This study assessed the association of preprocedural hemoglobin with adverse outcome in patients with advanced peripheral vascular disease (PVD) undergoing percutaneous transluminal angioplasty (PTA). Consecutive first-time procedures for patients with Rutherford category 4 or 5 PVD who underwent successful nonemergency PTA were analyzed in a retrospective cohort study. Cardiovascular risk factors, preprocedural hemoglobin, and angiographic data were recorded. Preprocedural (<or=24 hours) hemoglobin was divided into tertiles (first tertile: 10.5 +/- 0.7 g/dL; second tertile: 12.0 +/- 0.4 g/dL; third tertile: 13.9 +/- 0.9 g/dL). Study end points were a composite of adverse peripheral vascular events consisting of target lesion revascularization (repeat PTA or vascular bypass operation), limb amputation, or death. Cox regression analysis was used to identify independent predictors of adverse peripheral vascular outcome. A total of 101 patients (mean age, 76 +/- 10 years) were studied, of which 54 (53%) were men, and 62 (65%) were anemic. We observed 42 events during a median of 14 months (interquartile range, 4-26 months follow-up). Cox regression analysis found preprocedural hemoglobin in the first tertile vs third tertile (odds ratio, 4.17; 95% confidence interval, 1.56-11.16, P = .004), diabetes, renal failure, Rutherford category 5, and tibial vessels runoff score were independent predictors of adverse peripheral vascular outcome. Anemia is a common comorbid condition in patients with advanced PVD. Preprocedural hemoglobin could be used in clinical practice to risk stratify patients with advanced PVD who are being considered for PTA. Correction of anemia before PTA in patients with Rutherford category 4 and 5 PVD may improve long-term outcome. Further investigation is needed regarding the optimization of preprocedural hemoglobin.

Preprocedural neutrophil count predicts outcome in patients with advanced peripheral vascular disease undergoing percutaneous transluminal angioplasty

The neutrophil count has been associated with adverse cardiovascular events after percutaneous coronary intervention. There are limited data on risk stratification of patients with advanced peripheral vascular disease (PVD) using white blood cell (WBC) subtypes. This study assessed the association of total and differential WBC counts with adverse outcome in patients with advanced PVD undergoing percutaneous transluminal angioplasty (PTA). In a retrospective cohort study, consecutive de novo procedures were analyzed for patients with Rutherford category 4 or 5 PVD who underwent successful nonemergency PTA. Cardiovascular risk factors, baseline total and differential WBC counts, and angiographic data were recorded. Primary outcome was a composite of events of target vessel revascularization (repeat PTA or vascular bypass operation) or lower limb amputation. A total of 101 patients were studied. Their mean age was 76 +/- 10 years, 54% had diabetes mellitus, 68% were hypertensive, and 12% had had previous myocardial infarction. We observed 29 events during a median period of 14 months (interquartile range, 4-26). Cox regression analysis found diabetes mellitus (odds ratio [OR], 4.67; 95% confidence interval [CI], 1.35-16.14; P = .02), Rutherford category 5 (OR, 4.18; 95% CI, 1.06-16.51; P = .04), poor tibial runoff (OR, 4.42; 95% CI, 1.16-16.82; P = .03), and preprocedural neutrophil count in the third tertile (OR, 10.77; 95% CI, 2.19-52.91; P = .003) were independent predictors of outcome. The results suggest that the preprocedural neutrophil count could be used in global risk factor assessment of patients with advanced PVD who are being considered for PTA. The neutrophil count may reflect the burden of atherosclerosis and tissue damage, and so could identify patients who need more aggressive intervention for advanced PVD.

Prevalence of Metabolic Syndrome in Patients With Clinically Advanced Peripheral Vascular Disease

The aim of this cross-sectional study was to determine the prevalence of metabolic syndrome (MetS) and its components among 100 patients with progressive peripheral arterial disease (PAD) referred for diagnostic angiography in preparation for a revascularization procedure. The prevalence of MetS was more than 95%. Diabetes mellitus was the most prevalent component followed by hypertension and low high-density lipoprotein. Almost half the patients aggregated in the highest metabolic score category. A direct relationship was identified between the number of MetS components and serum uric acid (P = .001) and C-reactive protein (P = .826), whereas an inverse relationship was seen between the clustering of components and androgen levels in men (P < .001). For PAD, which could have a benign clinical course, early screening for MetS might identify those at greater risk of failing conservative therapy and progressing to a more aggressive atherosclerotic disease typically associated with high morbidity and mortality.

Low-dose aspirin fails to inhibit increased platelet reactivity in patients with peripheral vascular disease.

A study was performed to evaluate the effect of low-dose aspirin (75 mg/day) on platelet reactivity in patients with peripheral vascular disease. Platelet function was measured in 31 patients with advanced peripheral vascular disease requiring surgery. Shear-induced haemostasis and collagen-induced thrombus formation were used as indicators of platelet reactivity. They were measured in non-anticoagulated fresh whole blood samples ex vivo using a haemostatometer. Results were compared with those from 30 age- and sex-matched controls. Shear-induced haemostasis and collagen-induced thrombus formation were also measured in 18 of the 31 patients before the start of aspirin administration (before operation) and 1 week after surgery. Patients with advanced peripheral vascular disease were found to have increased platelet reactivity with a mean(s.e.m.) shear-induced haemostasis index of 1977(180) mmHg s compared with a control value of 3161(234) mmHg s (P < 0.001) and a mean(s.e.m.) collagen-induced thrombus formation index of 3980(460) mmHg s compared with a control value of 5350(420) mmHg s (P = 0.02). Perioperative low-dose aspirin failed to inhibit platelet function in patients with peripheral vascular disease.

Selective Use of Off-Pump Coronary Bypass Surgery Reduces Mortality and Neurologic Morbidity Associated with High-Risk Coronary Bypass Surgery: A 400-Case Comparative Experience

The frequency of use of off-pump coronary artery bypass (CAB) surgery to surgically treat coronary artery disease has varied greatly from center to center and from surgeon to surgeon because of preference, training, and experience. We report an experience with 400 consecutive isolated CAB procedures selectively managed with on-pump or off-pump surgery, according to the perceived potential for aortic embolization or stroke as determined by clinical and imaging determinations. The off-pump CAB group (46 patients) was 7.1 years older (P < .05) and had an 11% lower ejection fraction (P < .03) than the on-pump group. There was no difference in gender, urgency of surgery, hemodynamic stability, angina class, or incidence of prior myocardial infarction. All 400 patients underwent intraoperative transesophageal echocardiography, and many underwent an epiaortic study to supplement image quality. Patients without palpable or imaged advanced aortic disease or deemed to be at clinically high risk for stroke (advanced age, prior strokes, or advanced cerebrovascular or peripheral vascular disease) underwent on-pump procedures requiring 55 minutes of aortic ischemia and 97 minutes of high-flow, high-pressure bypass on average. All others underwent off-pump procedures. The numbers of grafts per patient were similar (3.2 on-pump, 2.8 off-pump; = ns). There was no in-hospital or 30-day mortality in either group. Using the New York State risk-adjustment algorithm, we found the predicted mortality rate for the off-pump group was higher (2.24% on-pump versus 5.54% off-pump, P = .008). The postoperative length of stay was longer in the off-bypass group (3.67 days versus 4.31 days, P = .003). The frequencies of hospital readmission and perioperative complications (renal, pulmonary, infection, bleeding, cardiac, neurologic) were similar, and there were no postoperative strokes in either group. The selective use of off-pump surgery safely managed patients at higher risk for perioperative stroke and associated embolic multisystem organ failure and death. Individual surgeon and center-wide use of a selective approach is recommended as an alternative to a single-procedure nonselective approaches.

Implementation of an iron reduction protocol in patients with peripheral vascular disease: VA cooperative study no. 410: The Iron (FE) and Atherosclerosis Study (FEAST)

Background Iron accumulates imperceptibly over time in adults because intake exceeds loss and because no physiologic mechanism exists for excreting levels that may be toxic. Levels of stored iron represented by the serum ferritin concentration have been implicated in the pathogenesis of vascular (and other) diseases, but the role of such stored iron remains controversial. Our hypothesis was that reduction in body iron stores to levels typical of children and premenopausal women (corresponding to ferritin levels of approximately 25 ng/mL) would alter morbidity and mortality rates in patients with advanced peripheral vascular disease. Methods and results A randomized, single-blinded, clinical trial of graded reduction of iron stores by controlled phlebotomy was undertaken in patients with advanced peripheral vascular disease. Details of implementation of the protocol for testing this unusual experimental intervention are reported. Conclusions A methodology is described for testing the concept that reduction of body iron stores (while avoiding iron deficiency) may alter disease outcomes. This methodology appears to be suitable for further testing to determine whether levels of iron stores presumed to be pathologic contribute to disease initiation or progression.

C-reactive protein as a novel biomarker

PREVIEWC-reactive protein (CRP) is a relatively nonspecific marker of inflammation. However, it can be used to monitor the severity and progression of some well-defined cardiovascular diseases. For example, it can predict serious events in patients with coronary artery disease (CAD) who are hospitalized with acute coronary syndrome, myocardial infarction (MI), or advanced peripheral vascular disease. In this article, the authors review the role of CRP in the diagnosis, monitoring, and treatment of various forms of ischemic and inflammatory cardiovascular disease.