Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011.

Intima-media thickness (IMT) provides a surrogate end point of cardiovascular outcomes in clinical trials evaluating the efficacy of cardiovascular risk factor modification. Carotid artery plaque further adds to the cardiovascular risk assessment. It is defined as a focal structure that encroaches into the arterial lumen of at least 0.5 mm or 50% of the surrounding IMT value or demonstrates a thickness >1.5 mm as measured from the media-adventitia interface to the intima-lumen interface. The scientific basis for use of IMT in clinical trials and practice includes ultrasound physics, technical and disease-related principles as well as best practice on the performance, interpretation and documentation of study results. Comparison of IMT results obtained from epidemiological and interventional studies around the world relies on harmonization on approaches to carotid image acquisition and analysis. This updated consensus document delineates further criteria to distinguish early atherosclerotic plaque formation from thickening of IMT. Standardized methods will foster homogenous data collection and analysis, improve the power of randomized clinical trials incorporating IMT and plaque measurements and facilitate the merging of large databases for meta-analyses. IMT results are applied to individual patients as an integrated assessment of cardiovascular risk factors. However, this document recommends against serial monitoring in individual patients.

The next 10 years in the management of peripheral artery disease: perspectives from the 'PAD 2009' Conference.

OBJECTIVES: To briefly inform on the conclusions from a conference on the next 10 years in the management of peripheral artery disease (PAD). DESIGN OF THE CONFERENCE: International participation, invited presentations and open discussion were based on the following issues: Why is PAD under-recognised? Health economic impact of PAD; funding of PAD research; changes of treatment options? Aspects on clinical trials and regulatory views; and the role of guidelines. RESULTS AND CONCLUSIONS: A relative lack of knowledge about cardiovascular risk and optimal management of PAD patients exists not only among the public, but also in parts of the health-care system. Specialists are required to act for improved information. More specific PAD research is needed for risk management and to apply the best possible evaluation of evidence for treatment strategies. Better strategies for funding are required based on, for example, public/private initiatives. The proportion of endovascular treatments is steadily increasing, more frequently based on observational studies than on randomised controlled trials. The role of guidelines is therefore important to guide the profession in the assessment of most relevant treatment.

"The challenge facing renal artery revascularization: what have we not proven and why we must"?

Endovascular renal artery stent therapy for atherosclerotic renal artery stenosis (RAS) is associated with excellent acute technical success, low complication rates and acceptable long-term patency. However, the clinical benefits to patients of renal artery stenting remain uncertain. To facilitate debate regarding the treatment of RAS, we need to understand the epidemiology, basic physiology and clinical consequences of renal artery stenosis. We must attempt to determine which patients are likely to benefit from renal artery stenting, assess the nuances of the percutaneous procedure and review the current literature pertaining to renal artery stenting.

Clinical endpoints in peripheral endovascular revascularization trials: a case for standardized definitions.

BACKGROUND: Endovascular therapy is a rapidly expanding option for the treatment of patients with peripheral arterial disease (PAD), leading to a myriad of published studies reporting on various revascularization strategies. However, these reports are often difficult to interpret and compare because they do not utilize uniform clinical endpoint definitions. Moreover, few of these studies describe clinical outcomes from a patients' perspective. METHODS AND RESULTS: The DEFINE Group is a collaborative effort of an ad-hoc multidisciplinary team from various specialties involved in peripheral arterial disease therapy in Europe and the United States. DEFINE's goal was to arrive at a broad based consensus for baseline and endpoint definitions in peripheral endovascular revascularization trials for chronic lower limb ischemia. In this project, which started in 2006, the individual team members reviewed the existing pertinent literature. Following this, a series of telephone conferences and face-to-face meetings were held to agree upon definitions. Input was also obtained from regulatory (United States Food and Drug Administration) and industry (device manufacturers with an interest in peripheral endovascular revascularization) stakeholders, respectively. The efforts resulted in the current document containing proposed baseline and endpoint definitions in chronic lower limb PAD. Although the consensus has inevitably included certain arbitrary choices and compromises, adherence to these proposed standard definitions would provide consistency across future trials, thereby facilitating evaluation of clinical effectiveness and safety of various endovascular revascularization techniques. CONCLUSION: This current document is based on a broad based consensus involving relevant stakeholders from the medical community, industry and regulatory bodies. It is proposed that the consensus document may have value for study design of future clinical trials in chronic lower limb ischemia as well as for regulatory purposes.

Tibioperoneal (outflow lesion) angioplasty can be used as primary treatment in 235 patients with critical limb ischemia: five-year follow-up.

BACKGROUND: In a prospective, nonrandomized, consecutive series of tibioperoneal vessel angioplasty (TPVA), critical limb ischemia (CLI) patients' data were analyzed with regard to immediate and follow-up success. METHODS AND RESULTS: TPVA was successful in 270 of 284 critically ischemic limbs (95%), with 167 limbs (59%) requiring dilatation of 333 ipsilateral inflow obstructions to access and successfully dilate 486 of 529 (92%) tibioperoneal lesions. A clinical success (relief of rest pain or improvement of lower-extremity blood flow) was attained in 270 limbs at risk (95%). Clinical 5-year follow-up of 215 of 221 successful CLI patients (97%) with 266 successfully revascularized limbs revealed that bypass surgery occurred in 8% and significant amputations in 9% of limbs; 91% of the limbs were salvaged. The cohort's probability of survival was 56%: 58% for Fontaine class III and 33% for class IV patients. Class III compared with class IV patients had significantly (P<0.05) fewer surgical bypasses (3% versus 16%) and amputations: above-knee, 1% versus 4%; below-knee, 3% versus 12%; and transmetatarsal, <1% versus 21%. CONCLUSIONS: TPVA, often in combination with inflow lesions, is an effective primary treatment for critical limb ischemia. The poor cumulative survival reflects the existence of severe comorbidities, which could potentially be affected by aggressive and effective cardiovascular diagnostic and therapeutic strategies.

Follow-up of primary Palmaz-Schatz stent placement for atherosclerotic renal artery stenosis.

A Palmaz-Schatz stent was successfully placed in 92 stenotic renal arteries (76 patients) for (1) hypertension in 62 (82%), and/or (2) chronic renal failure (serum creatinine > or = 1.5 mg/dl) and preservation of renal function in 39 (51%). Patients were followed to assess clinical and angiographic 6-month outcome. Angiography, performed in 45 of 62 eligible patients (73%) and in 56 of 74 treated arteries (76%), showed restenosis occurring in 14 renal arteries (25%). Serum creatinine improved or remained stable in 78% of patients. In patients with chronic renal failure, improvement or stability was observed in 55%. Blood pressure recordings significantly decreased for the entire cohort (systolic: 168 +/- 25 to 156 +/- 22 mm Hg, p < 0.0001; diastolic: 87 +/- 11 to 81 +/- 11 mm Hg, p < 0.005), and for hypertensive patients with normal creatinine (systolic: 179 +/- 20 to 155 +/- 23 mm Hg, p < 0.0001; diastolic: 92 +/- 9 to 83 +/- 12 mm Hg, p < 0.002). These follow-up data of a prospective, nonrandomized, observational study showed that stent recanalization of atherosclerotic renal artery stenoses was beneficial with regard to renal function and blood pressure response, and had a restenosis incidence of 25%.

Carotid artery disease: natural history, diagnosis, and therapy.

Stroke remains a major complication of atherosclerotic cerebrovascular disease, with extracranial carotid occlusive disease accounting for nearly one-third of all events. Although historical symptoms and physical examination findings are important, objective testing with carotid duplex ultrasonography and magnetic resonance arteriography represent the foundation for therapeutic decision making. Contrast arteriography is playing a decreasing role in the evaluation of patients with carotid artery disease. Options for therapy, based on the presence or absence of symptoms and degree of stenosis, include antiplatelet therapy with cardiovascular risk factor modification, carotid endarterectomy, and more recently, endovascular therapy.

Intra-arterial reteplase for the treatment of acute limb ischemia.

The removal of urokinase from the market has created a dilemma for interventionists and vascular surgeons treating patients with acute limb threatening ischemia due to arterial thrombosis or embolization. Reteplase is a newer, fibrin-specific thrombolytic agent with properties that make it an attractive alternative to urokinase. We report two cases of successful treatment of acute, limb threatening ischemia with intra-arterial Reteplase therapy.

Intramural hematoma of the aorta caused by a penetrating atheromatous ulcer.

Aortic dissection is a life-threatening condition which is difficult to diagnose because of its variable clinical presentation and diverse pathophysiologic manifestations. We present a case in which intramural hematoma of the thoracic aorta occurred in the absence of an intimal flap. Computed tomography and magnetic resonance imaging both showed hemorrhage in the wall of the aorta. Transesophageal echocardiography also revealed a penetrating atherosclerotic ulcer in the transverse aorta as a cause of the hematoma. A high index of clinical suspicion and a combination of diagnostic procedures resulted in proper diagnosis and successful surgical treatment.

Medical aspects of pregnancy.

BACKGROUND: Physiologic changes during pregnancy can precipitate or exacerbate potentially serious maternal illnesses that may adversely affect the outcome for both mother and fetus. OBJECTIVE: To review the common medical conditions that may complicate pregnancy. SUMMARY: Venous thromboembolic disease is the most common medical disorder complicating pregnancy; heparin is the safest and most effective treatment and prophylactic agent in high-risk patients. Systemic lupus erythematosus may flare during pregnancy and may require therapy with corticosteroids, which may also be needed to treat immune thrombocytopenic purpura. Hypertension should be monitored closely throughout the pregnancy and puerperium; certain antihypertensive agents control blood pressure without affecting the fetus. Asthma may worsen or improve during pregnancy; therapy is similar to that for nonpregnant women. Diabetes mellitus may antedate pregnancy or become manifest during pregnancy; detection and strict glycemic control are the keys to a successful outcome. Approximately 30% of infants born to mothers with established HIV infection acquire the syndrome of immunodeficiency; testing must continue until 15 months of life. Mothers with epilepsy should use the lowest effective dose of a single antiepileptic agent to prevent congenital birth defects. CONCLUSIONS: When the internist, obstetrician, anesthesiologist, and perinatologist use a team approach, most patients can expect a successful outcome.

Lambda light chain myeloma with pleural involvement.

A case is reported of lambda light chain multiple myeloma complicated by a myelomatous pleural effusion. Pleural effusions are uncommon in multiple myeloma, and most are secondary to nonmalignant causes. The clinical characteristics, natural history and pathophysiology of myelomatous pleural effusions are reviewed.

Meeting the challenge of geriatric UTIs.

Urinary tract infections (UTIs) are common, and the geriatric population, because of multiple risk factors, is particularly susceptible. The diagnosis may be difficult and requires consideration in the appropriate clinical settings. Many antimicrobial agents provide effective initial therapy for UTIs. Recurrence is a problem that mandates urine culture and antibiotic sensitivity studies; urologic evaluation may also be necessary. The patient with a chronic indwelling bladder catheter and bacteriuria presents a unique challenge to the practicing physician.

Atherosclerotic stenosis of the renal arteries. Indications for intervention.

Advances in the ability to diagnose atherosclerotic stenosis of the renal arteries have increased awareness of this disorder over the past decade, and several medical specialties have become interested in its pathophysiology, diagnosis, and therapy. Improved surgical and anesthetic techniques and the development of endovascular technology have paved the way for more aggressive management of atherosclerotic renal artery stenosis. However, there is a lack of prospective data supporting this aggressive approach, and there is little agreement among physician groups concerning the appropriateness of revascularization in many patient scenarios. We will examine the available data and make recommendations about which patient groups might benefit most from renal artery revascularization (surgical or endovascular).

Stent revascularization for atherosclerotic renal artery stenosis. 1-year clinical follow-up.

Patients who had undergone stent revascularization of renal artery stenosis for poorly controlled hypertension, preservation of renal function, or both were monitored to assess the procedure's effect upon subsequent renal function and blood pressure control. At 1-year follow-up, systolic and diastolic blood pressures had significantly decreased (166 +/- 26 to 156 +/- 25 mmHg and 86 +/- 14 to 80 +/- 13 mmHg, respectively; P < 0.05), and creatinine levels decreased or remained stable in approximately two thirds of the patients. Renal artery stent revascularization appears to have a beneficial effect upon blood pressure control and a nondeleterious effect upon renal function in the majority of patients.

Hypertension and renal artery stenosis: a complex clinical scenario.

Hypertension remains the most common reason for patients to visit physicians in the United States. Although awareness of hypertension among patients continues to increase, adequate control of hypertension remains poor. In addition, as the population of patients with hypertension ages, atherosclerosis becomes increasingly prevalent. Atherosclerotic renal artery stenosis is the most common secondary cause of hypertension and can cause hypertension to be difficult to control. Atherosclerotic renal artery stenosis may also result in chronic renal insufficiency. The physician must be aware of the clinical scenarios in which renal artery stenosis may occur, methods of diagnosis, and indications for intervention.

Medical therapy for critical limb ischemia and the diabetic foot: an update.

Critical limb ischemia is the most severe manifestation of chronic peripheral artery disease (PAD). The goal of medical care is to provide symptomatic relief in patients who are unsuitable for percutaneous or surgical revascularization and to reduce systemic cardiovascular risk. PAD is a common manifestation of systemic atherosclerosis and is associated with significant morbidity and mortality. PAD represents a marker for premature cardiovascular events. Patients with PAD, even in the absence of a history of myocardial infarction or ischemic stroke, have approximately the same relative risk of death from cardiovascular causes as do patients with a history of coronary or cerebrovascular disease alone. The PARTNERS study demonstrated that patients with PAD were less likely to receive appropriate treatment for their atherosclerotic risk factors than those who were being treated for coronary artery disease. The long term prognosis of patients with PAD is significantly worse than for patients with coronary artery disease alone. Newer therapies are being investigated to treat patients with critical limb ischemia who are unsuitable candidates for revascularization, and these will be discussed briefly.

Adenosine elicits an eNOS-independent reduction in arterial blood pressure in conscious mice that involves adenosine A2A receptors.

AIMS: Adenosine plays an important role in the regulation of heart rate (HR) and vascular reactivity. However, the mechanisms underlying the acute effect of adenosine on arterial blood pressure in conscious mice are unclear. Therefore, this study investigated the effect of the nucleoside on mean arterial blood pressure (MAP) and HR in conscious mice. METHODS: Chronic indwelling catheters were placed in C57Bl/6J (WT) and endothelial nitric oxide synthase knockout (eNOS(-/-)) mice for continuous measurements of MAP and HR. Using PCR and myograph analysis, involvement of adenosine receptors was investigated in human and mouse renal blood vessels. RESULTS: Bolus infusion of 0.5 mg kg(-1) adenosine elicited significant transient decreases in MAP (99.3 ± 2.3 to 70.4 ± 4.5 mmHg) and HR (603.2 ± 18.3 to 364.3 ± 49.2 min(-1)), which were inhibited by the A(2A) receptor antagonist ZM 241385. Activation of adenosine A(2A) receptors with CGS 21680 (0.02 mg kg(-1)) caused a significant reduction in MAP from 99.6 ± 1.2 to 73.1 ± 3.6 mmHg accompanied by tachycardia (610.5 ± 9.3 to 677.5 ± 9.5 min(-1)). The reduction in MAP observed after adenosine or CGS 21680 administrations was not significantly different in WT and eNOS(-/-) mice. In isolated human and mouse intrarenal arteries, adenosine caused a relaxation dependent on A(2A) adenosine receptor activation. A(2A) receptors were present in both human and mouse arteries whereas A(1) and A(2B) receptors were only present in mouse arteries. CONCLUSION: In conclusion, acute adenosine administration and selective stimulation of adenosine A(2A) receptors results in an immediate, transient eNOS-independent reduction in MAP. A(2A) receptor activation causes relaxation of human and mouse arteries.