Soluble intercellular adhesion molecule-1, soluble vascular adhesion molecule-1, and the development of symptomatic peripheral arterial disease in men.
ABSTRACT Elevated levels of soluble cellular adhesion molecules have been linked to the development of occlusive coronary events in otherwise healthy individuals. It is not certain, however, whether similar relationships exist for the development of early systemic atherosclerosis.
In a prospective, nested case-control study conducted among 14 916 middle-aged men, we evaluated the relationship between baseline levels of soluble intercellular adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and the subsequent development of symptomatic peripheral arterial disease (PAD) during a 9-year follow-up period. Median levels of sICAM-1 but not sVCAM-1 were significantly higher at baseline among men who developed PAD than among those who did not (285.2 versus 267.8 ng/mL [P=0.005] for sICAM-1 and 701.0 versus 709.3 ng/mL [P=0.8] for sVCAM-1). In analyses adjusted for age and smoking, the odds ratio in the highest compared with the lowest quartile of sICAM-1 was 3.9 (95% CI 1.7 to 8.6; P(trend)=0.001). After additional adjustment for lipid and nonlipid risk factors, including C-reactive protein, elevated sICAM-1 remained significantly associated with subsequent PAD (OR 3.5, 95% CI 1.4 to 8.5, P(trend)=0.008). Whereas a monotonic dose-response relationship was evident over the full spectrum of ICAM-1 levels, elevated sVCAM-1 was not associated with future PAD in either age- and smoking-adjusted or fully adjusted models.
Elevated levels of sICAM-1 are independently associated with the development of accelerated atherosclerosis among otherwise healthy men even in the absence of acute coronary occlusion.
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ABSTRACT: Peripheral arterial disease (PAD) continues to grow in global prevalence and consumes an increasing amount of resources in the United States health care system. Overall rates of intervention for PAD have been rising steadily in recent years. Changing demographics, evolution of technologies, and an expanding database of outcomes studies are primary forces influencing clinical decision making in PAD. The management of PAD is multidisciplinary, involving primary care physicians and vascular specialists with varying expertise in diagnostic and treatment modalities. PAD represents a broad spectrum of disease from asymptomatic through severe limb ischemia. The Society for Vascular Surgery Lower Extremity Practice Guidelines committee reviewed the evidence supporting clinical care in the treatment of asymptomatic PAD and intermittent claudication (IC). The committee made specific practice recommendations using the GRADE (Grades of Recommendation Assessment, Development and Evaluation) system. There are limited Level I data available for many of the critical questions in the field, demonstrating the urgent need for comparative effectiveness research in PAD. Emphasis is placed on risk factor modification, medical therapies, and broader use of exercise programs to improve cardiovascular health and functional performance. Screening for PAD appears of unproven benefit at present. Revascularization for IC is an appropriate therapy for selected patients with disabling symptoms, after a careful risk-benefit analysis. Treatment should be individualized based on comorbid conditions, degree of functional impairment, and anatomic factors. Invasive treatments for IC should provide predictable functional improvements with reasonable durability. A minimum threshold of a >50% likelihood of sustained efficacy for at least 2 years is suggested as a benchmark. Anatomic patency (freedom from restenosis) is considered a prerequisite for sustained efficacy of revascularization in IC. Endovascular approaches are favored for most candidates with aortoiliac disease and for selected patients with femoropopliteal disease in whom anatomic durability is expected to meet this minimum threshold. Conversely, caution is warranted in the use of in-terventions for IC in anatomic settings where durability is limited (extensive calcification, small-caliber arteries, diffuse infrainguinal disease, poor runoff). Surgical bypass may be a preferred strategy in good-risk patients with these disease patterns or in those with prior endovascular failures. Common femoral artery disease should be treated surgically, and saphenous vein is the preferred conduit for infrainguinal bypass grafting. Patients who undergo invasive treatments for IC should be monitored regularly in a surveillance program to record subjective improvements, assess risk factors, optimize compliance with cardioprotective medications, and monitor hemodynamic and patency status. (J Vasc Surg 2015;-:1-40.) DEVELOPMENT OF THE GUIDELINES DOCUMENT The Society for Vascular Surgery (SVS) Lower Extrem-ity Guidelines Committee began the process by developing a detailed outline of the diagnostic and management choices for peripheral arterial disease (PAD) by stage of dis-ease. Given the broad scope of the field, the committee determined that this document should focus on the evalu-ation and management of asymptomatic disease and inter-mittent claudication (IC). Separate practice guidelines for critical limb ischemia (CLI) will be established in a future document. The committee developed sets of key questions and, with the input of a methodologist, condensed these into topics that framed systematic evidence reviews. The quantity and quality of evidence available was also anJournal of Vascular Surgery 01/2015; 61(3). DOI:10.1016/j.jvs.2014.12.009 · 2.98 Impact Factor
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ABSTRACT: The knowledge on the level of systemic inflammation in peripheral artery disease (PAD) is less well established than that in coronary artery disease (CAD). Systemic inflammation frequently coincides with atherosclerosis, but also with various traits of the metabolic syndrome (MetS). The individual contribution of CAD, PAD, and the MetS to inflammation is not known.Atherosclerosis 04/2015; 239(2). DOI:10.1016/j.atherosclerosis.2015.01.021 · 3.97 Impact Factor
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ABSTRACT: VCAM-1 and ICAM-1 are two important members of the immunoglobulin gene superfamily of adhesion molecules, and their potential role as biomarkers of diagnosis, severity and prognosis of cardiovascular disease has been investigated in a number of clinical studies. The aim of the present study was to determine the relationship between circulating ICAM-1 and VCAM-1 levels and aortic stiffness in patients referred for echocardiographic examination. Aortic distensibility was determined by echocardiography using systolic and diastolic aortic diameters in 63 consecutive patients referred for echocardiography. Venous samples were collected in the morning after a 12-hour overnight fast, and serum concentrations of ICAM-1 and VCAM-1 were measured using commercial enzyme immunoassay kits. Data of a total of 63 participants (mean age 55.6 ± 10.5 years, 31 male) were included in the study. Circulating levels of adhesion molecules were VCAM-1: 12.604 ± 3.904 ng/ml and ICAM-1: 45.417 ± 31.429 ng/ml. We were unable to demonstrate any correlation between indices of aortic stiffness and VCAM-1 and ICAM-1 levels. The role of soluble adhesion molecules in cardiovascular disease has not been fully established and clinical studies show inconsistent results. Our results indicate that levels of circulating adhesion molecules cannot be used as markers of aortic stiffness in patients.03/2015; 26(1):21-4. DOI:10.5830/CVJA-2014-060